page_title
stringlengths 1
91
| page_text
stringlengths 0
34.2k
|
|---|---|
Melioidosis | Melioidosis is an infectious disease caused by a gram-negative bacterium called Burkholderia pseudomallei. Most people exposed to B. pseudomallei experience no symptoms; however, those who do experience symptoms have signs and symptoms that range from mild such as fever and skin changes, to severe with pneumonia, abscesses, and septic shock that could cause death. Approximately 10% of people with melioidosis develop symptoms that last longer than two months, termed "chronic melioidosis".Humans are infected with B. pseudomallei by contact with contaminated soil or water. The bacteria enter the body through wounds, inhalation, or ingestion. Person-to-person or animal-to-human transmission is extremely rare. The infection is constantly present in Southeast Asia particularly in northeast Thailand and northern Australia. In temperate countries such as Europe and the United States, melioidosis cases are usually imported from countries where melioidosis is endemic. The signs and symptoms of melioidosis resemble tuberculosis and misdiagnosis is common. Diagnosis is usually confirmed by the growth of B. pseudomallei from an infected persons blood or other bodily fluid such as pus, sputum, and urine. Those with melioidosis are treated first with an "intensive phase" course of intravenous antibiotics (most commonly ceftazidime) followed by a several-months treatment course of co-trimoxazole. In countries with the advanced healthcare system, approximately 10% of people with melioidosis die from the disease. In less developed countries, the death rate could reach 40%.Efforts to prevent melioidosis include: wearing protective gear while handling contaminated water or soil, practising hand hygiene, drinking boiled water, and avoiding direct contact with soil, water, or heavy rain. There is little evidence in supporting the use of melioidosis prophylaxis in humans. The antibiotic co-trimoxazole is used as a preventative only for individuals at high risk for getting the disease after being exposed to the bacteria in laboratory settings. One study conducted in 2018 determined that the drug could be useful in preventing melioidosis in high-risk renal failure patients undergoing haemodylysis. There is no approved vaccine for melioidosis.Approximately 165,000 people are infected by melioidosis per year, resulting in about 89,000 deaths, based on a mathematical model published in 2016. Diabetes is a major risk factor for melioidosis; over half of melioidosis cases are in people with diabetes. Increased rainfall and severe weather events such as thunderstorm are associated with an increased number of melioidosis cases in endemic areas.
Signs and symptoms
Acute
Most people exposed to B. pseudomallei experience no symptoms. The mean incubation period of acute melioidosis is 9 days (range 1–21 days). Nevertheless, symptoms of melioidosis can appear in 24 hours for those who experienced near drowning in water. Those affected present with symptoms of sepsis (predominantly fever) with or without pneumonia, or localised abscess or other focus of infection. The presence of non-specific signs and symptoms has caused melioidosis to be nicknamed "the great mimicker".Diabetes mellitus is one of the most important risk factors in developing melioidosis. The disease should be considered in anyone who has spent time in endemic areas who develops a fever, pneumonia, or abscesses in their liver, spleen, prostate, or parotid gland. The clinical manifestation of the disease can range from simple skin changes such as abscesses or ulcerations to severe organ problems. The commonest organs affected are liver, spleen, lungs, prostate, and kidneys. Among the most common features are bacteremia (in 40 to 60% of cases), pneumonia (50%), and septic shock (20%).
People with only pneumonia may have a prominent cough with sputum and shortness of breath. However, those with septic shock together with pneumonia may have minimal coughing. Results of a chest X-ray can range from diffuse nodular infiltrates in those with septic shock to progressive consolidation located most commonly in the upper lobes for those with pneumonia only. Pleural effusion and empyema are more common for melioidosis affecting lower lobes of the lungs. In 10% of cases, people develop secondary pneumonia caused by other bacteria after the primary infection. In northern Australia, 60% of the infected children presented with only skin lesions, while 20% presented with pneumonia.Depending on the course of infection, other severe manifestations develop. Approximately 1 to 5% of those infected develop inflammation of the brain and brain covering or brain abscess; 14 to 28% develop pyelonephritis, kidney abscess or prostatic abscesses; 0 to 30% develop neck or salivary gland abscesses; 10 to 33% develop liver, spleen, or paraintestinal abscesses; and 4 to 14% develop septic arthritis and osteomyelitis. Rare manifestations include lymph node disease resembling tuberculosis, mediastinal masses, pericardial effusion, mycotic aneurysm, and inflammation of the pancreas. In Australia, up to 20% of infected males develop prostatic abscess which may manifests clinically as pain during urination, difficulty in passing urine, and urinary retention requiring catheterisation. Rectal examination may find enlarged prostate. In Thailand, 30% of the infected children develop parotid abscesses. Encephalomyelitis not only happens in those with risk factors, but can also occur in healthy people without risk factors. Those with melioidosis encephomyelitis tend to have normal computed tomography (CT) scans but increased T2 signal by magnetic resonance imaging (MRI), extending to the brain stem and spinal cord. Clinical signs include: unilateral upper motor neuron limb weakness, cerebellar signs, and cranial nerve palsies (VI, VII nerve palsies and bulbar palsy). Some cases presented with flaccid paralysis alone. In northern Australia, all melioidosis with encephalomyelitis cases had elevated white cells in the cerebrospinal fluid (CSF), mostly mononuclear cells with elevated CSF protein.
Chronic
Chronic melioidosis is usually defined by symptoms lasting greater than two months and occurs in about 10% of patients. Clinical presentations include fever, weight loss, productive cough with or without bloody sputum which may mimic tuberculosis. Additionally, long-standing abscesses at multiple body sites may also present. Tuberculosis should be considered for lymph nodes enlargement at the root of the lung. Additionally, pneumonia caused by melioidosis rarely causes scarring and calcification of the lungs, unlike tuberculosis.
Latent
The potential for prolonged incubation was recognized in US servicemen involved in the Vietnam War, and was referred to as the "Vietnam time-bomb". Initially, it was thought that the longest period between presumed exposure and clinical presentation is 62 years in a prisoner of war in Burma-Thailand-Malaysia. However, subsequent genotyping of the bacteria isolate from the Vietnam veteran showed that the isolate may not come from Southeast Asia, but from South America. This reinstates another report that put the longest latency period for melioidosis as 29 years. Patients with latent melioidosis may be symptom-free for decades. Less than 5% of all melioidosis cases have activation after a period of latency. Various comorbidities such as diabetes, renal failure, and alcoholism can predispose to reactivation of melioidosis.
Cause
Bacteria
Melioidosis is caused by gram-negative, motile, saprophytic bacteria named Burkholderia pseudomallei. The bacteria are usually opportunistic, facultative intracellular pathogens. It is also aerobic and oxidase test positive. A granule at the centre of the bacterium makes it resemble a "safety pin" when Gram stained. The bacteria emit a strong soil smell after 24 to 48 hours of growth in culture, however smelling for the identification of the bacteria is not recommended for routine laboratory practice. One of the factors causing B. pseudomalleis resistance to various kinds of antibiotics is because of its production of a glycocalyx polysaccharide capsule. It is generally resistant to gentamicin and colistin but sensitive to co-amoxiclav. B. pseudomallei is a biosafety level 3 pathogen which requires specialized laboratory handling. In humans and animals, another similar organism named Burkholderia mallei is the causative agent of the disease glanders. B. pseudomallei can be differentiated from another closely related, but less pathogenic species B. thailandensis by its ability to assimilate arabinose. B. pseudomallei is highly adaptable to various host environments ranging from inside mycorrhizal fungi spores to amoeba. Its adaptability may give it a survival advantage in the human body.The genome of B. pseudomallei consists of two replicons: chromosome 1 encodes housekeeping functions of the bacteria such as cell wall synthesis, mobility, and metabolism; chromosome 2 encodes functions that allow the bacteria to adapt to various environments. Horizontal gene transfer has resulted in highly variable genomes in B. pseudomallei. Australia has been suggested as the origin for B. pseudomallei because of the high genetic variability of the bacteria found in this region. Bacteria that was introduced to Central and South America in the 17th to 19th centuries seem to have a common ancestor from Africa. B. mallei is a clone of B. pseudomallei that has lost substantial portions of its genome as it adapted to live exclusively in mammals. This makes the B. mallei genome much smaller than B. pseudomallei.
Transmission
B. pseudomallei is normally found in soil and surface water, and is most abundant at soil depths of 10 to 90 cm. It has been found in soils, ponds, streams, pools, stagnant water, and rice paddy fields. B. pseudomallei can survive in nutrient-poor conditions such as distilled water, desert soil, and nutrient-depleted soil for more than 16 years. It can also survive in antiseptic and detergent solutions, acidic environments (pH 4.5 for 70 days), and in environments at temperatures ranging from 24 °C (75.2 °F) to 32 °C (89.6 °F). However, the bacteria may be killed by the presence of ultraviolet light.Bacteria can enter the body through wounds, inhalation, and ingestion of contaminated soil or water. Person-to-person transmission is extremely rare. Melioidosis is a recognised disease in animals including pigs, cats, dogs, goats, sheep, horses and others. Cattle, water buffalo, and crocodiles are considered to be relatively resistant to melioidosis despite their constant exposure to mud. Birds are also considered resistant to melioidosis although several cases had been reported in Australia and aquatic birds. Transmission from animals to humans is rare.Inadequate chlorination of water supply has been associated with B. pseudomallei outbreak in Northern and Western Australia. The were also several cases of where bacteria have also been found in unchlorinated water supply in rural Thailand. Based on the whole genome sequencing of the bacteria, the variety of the bacteria B. pseudomallei in Papua New Guinea is narrow due to limited movements of the indigenous people. This findings supports the hypothesis that humans play an important role in bacterial transmission.
Pathogenesis
B. pseudomallei has the ability to infect various types of cells and to evade human immune responses. Bacteria first enter at a break in the skin or mucous membrane and replicate in the epithelial cells. From there, they use flagellar motility to spread and infect various cell types. In the bloodstream, the bacteria can infect both phagocytes and non-phagocytes. B. pseudomallei use their flagella to move near host cells, then attach to the cells using various adhesion proteins, including the type IV pilus protein PilA as well as adhesion proteins BoaA and BoaB. Additionally, adhesion of the bacteria partially depends on the presence of the host protein Protease-activated receptor-1 which is present on the surface of endothelial cells, platelets, and monocytes. Once bound, the bacteria enter host cells through endocytosis, ending up inside an endocytic vesicle. As the vesicle acidifies, B. pseudomallei uses its Type 3 secretion system (T3SS) to inject effector proteins into the host cell, disrupting the vesicle and allowing the bacteria to escape into the host cytoplasm. Within the host cytoplasm, the bacteria evade being killed by the host autophagy using various T3SS effector proteins. The bacteria replicate in the host cytoplasm.Inside the host cell, the bacteria move by inducing the polymerization of the host actin behind them, propelling the bacteria forward. This actin-mediated motility is accomplished with the autotransporter BimA which interacts with actin at the tail-end of the bacterium. The bacteria that has BimABm allele has higher possibility of causing neurological melioidosis, thus higher chance of death and residual disability to the host when compared to the bacteria that has BimABp variant. Propelled by actin, the bacteria push against the host membrane, creating protrusions that extend into neighbouring cells. These protrusions cause neighboring cells to fuse, leading to the formation of multinucleated giant cells (MNGCs). When MNGCs lyse, they form plaques (a central clear area with a ring of fused cells) that provide shelter for the bacteria for further replication or latent infection. This same process in infected neurons can allow bacteria to travel through nerve roots in the spinal cord and brain, leading to inflammation of the brain and spinal cord. In addition to spreading from cell to cell, the bacteria can also spread through the bloodstream, causing sepsis. The bacteria can survive in antigen-presenting cells and dendritic cells. Thus, these cells act as vehicles that transport the bacteria into the lymphatic system, causing widespread dissemination of the bacteria in the human body.While B. pseudomallei can survive in phagocytic cells, these cells can kill B. pseudomallei by several mechanisms. Macrophages activated by interferon gamma (IFN) have improved the killing of B. pseudomallei via the production of inducible nitric oxide synthase. Acidification of the endosome and degradation of the bacteria is also possible, however, the bacterial capsule and LPS makes B. pseudomallei resistant to lysosomal degradation. Once B. pseudomallei escapes into the host cytosol it can be recognized by pattern recognition receptors such as NOD-like receptors, triggering the formation of the inflammasome and activation of caspase 1, which induces death of the host cell by pyroptosis and further activation of the immune system. Several systemic host defenses also contribute to the immune response. B. pseudomallei triggers both the complement system and coagulation cascade, however the thick bacterial capsule prevent the action of the complement membrane attack complex.Additional elements of the immune system are activated by the host toll-like receptors such as TLR2, TLR4, and TLR5 that recognize the conserved pieces of the bacteria such as LPS and flagella. This activation results in the production of cytokines such as Interleukin 1 beta (IL-1β) and Interleukin 18 (IL-18). IL-18 increases IFN production through natural killer cells while IL-1beta reduces the IFN production. These immune molecules drive the recruitment of other immune cells such as neutrophils, dendritic cells, B cells, and T cells to the site of infection. T cells seem to be particularly important for controlling B. pseudomallei; T cell numbers are increased in survivors, and low T cell numbers are associated with a high risk of death from melioidosis. Despite this, HIV infection is not a risk factor for melioidosis. Although macrophages show deregulated cytokine responses in individuals with HIV infection, bacterial internalization and intracellular killing are still effective. People infected with B. pseudomallei may develop antibodies against the bacteria, and people that live in endemic areas tend to have antibodies in their blood that recognize B. pseudomallei. However, the effectiveness of these antibodies at preventing melioidosis is unclear.B. pseudomallei can remain latent in the human body for up to 29 years until it is reactivated during human immunosuppression or stress response. However, the site of bacteria during latent infection and the mechanism by which they avoid immune recognition for years are both unclear. Amongst mechanisms suggested are: residing in the nucleus of the cell to prevent being digested, entering a stage of slower growth, antibiotic resistance, and genetic adaption to the host environment. Granulomas (containing neutrophils, macrophages, lymphocytes, and multinucleated giant cells) formed at the infection site in melioidosis have been associated with latent infection in humans.
Diagnosis
Culture
Bacterial culture has 60% sensitivity in diagnosing melioidosis. B. pseudomallei is never part of human flora. Therefore, any growth of the bacteria is diagnostic of melioidosis. Other samples such as throat, rectal swabs, pus from abscesses, and sputum can also be used for culture. However, culture from CSF is difficult because in one case series, only 29% of the neuromelioidosis cases are culture positive. When bacteria do not grow from people strongly suspected of having melioidosis, repeated cultures should be taken as subsequent cultures can become positive. B. pseudomallei can be grown on any blood agar, MacConkey agar, and agar containing antibiotics such as Ashdowns medium (containing gentamicin), and Ashdowns broth (containing colistin) for better isolation of B. pseudomallei from other types of bacteria. Agar plates for melioidosis should be incubated at 37 °C (98.6 °F) in air and inspected daily for four days. On the agar plates, B. pseudomallei forms creamy, non-haemolytic, colonies after 2 days of incubation. After 4 days of incubation, colonies appear dry and wrinkled. Colonies of B. pseudomallei that are grown on Francis medium (a modification of Ashdown medium with gentamicin concentration increased to 8 mg/L and neutral red indicator replaced with 0.2% bromocresol purple) are yellow. For laboratories located outside endemic areas, Burkholderia cepacia selective agar can be used if Ashdowns medium is not available. It is important not misinterpret the bacterial growth as Pseudomonas or Bacillus spp. Other biochemical screening tools can also be used for detecting B. pseudomallei, including the API 20NE or 20E biochemical kit combined with Gram stain, oxidase test, typical growth characteristics, and resistance to certain antibiotics of the bacteria. API 20NE biochemical kit is 99% sensitive in identifying B. pseudomallei.Molecular methods such as 16S rDNA sequencing, multiplex polymerase chain reaction (PCR), and real-time PCR can also be used to identify B. pseudomallei in culture. Other bacterial genes such as fliC genes encoding flagellin, rpsU gene encoding for ribosomal protein, and TTS genes encoding Type III secretion systems has also been employed for detection. Another method of gene detection namely multiple cross displacement amplification for the bacterial TTS1 gene detection produces results within an hour.
Hematological and biochemical tests
General blood tests in people with melioidosis show low white blood cell counts (indicates infection), raised liver enzymes, increased bilirubin levels (indicates liver dysfunction), and raised urea and creatinine levels (indicates kidney dysfunction). Low blood glucose and acidosis predicts a poorer prognosis in those with melioidosis. However, other tests such as C-reactive protein and procalcitonin levels are not reliable in predicting the severity of melioidosis infection.
Serological tests
Serological tests such as indirect haemagglutination assay (IHA) have been used to detect the presence of antibodies against B. pseudomallei. However, different groups of people have widely different levels of antibodies, so interpretation of these tests depends on location. In Australia, less than 5% of people have B. pseudomallei antibodies, so the presence of even relatively low amounts of antibody is unusual and could suggest melioidosis. In Thailand, many people have antibodies against B. pseudomallei so the diagnosis of melioidosis should not be reliant entirely on the serological tests done in endemic areas. Indirect immunofluorescent test (IFAT) uses either B. pseudomallei or B. thailandensis antigens to look for the total number of antibodies in human serum. Using IFAT is labour intensive and is not used in large scale investigations.Antigen detect tests allow rapid detection of melioidosis. Examples of antigen detection tests are: latex agglutination test and ELISA. Latex agglutination uses antibodies coated on latex beads to detect B. pseudomallei antigens in solid or liquid media, although not all the assays can detect different species of Burkholderia. Latex agglutination is useful in screening for suspected B. pseudomallei colonies. IgG and IgM ELISAs has been used to detect lipopolysaccharide (LPS) antigens of B. pseudomallei, but plagued with low sensitivity. Commercial ELISA kits for melioidosis no longer available in the market due to low sensitivity to human antibodies detection. Nevertheless, antigen detection tests may be useful in severely ill patients because the bacterial load is high enough for detection. Other methods of antigen detection such as direct immunofluorescence, antibody-sandwich ELISAs, and lateral flow immunoassays using monoclonal antibody.
Microscopy
By microscopy, B. pseudomallei is seen as gram-negative and rod-shaped, with a bipolar staining similar in appearance to a safety pin. Bacteria can sometimes be seen directly in clinical samples from infected people; however, identification by light microscopy is neither specific nor sensitive. Immunofluorescence microscopy is highly specific for detecting bacteria directly from clinical specimens, but has less than 50% sensitivity.
Imaging
Various imaging modalities can also help with the diagnosis of melioidosis. In acute melioidosis with the spreading of the bacteria through the bloodstream, the chest X-ray shows multifocal nodular lesions. It may also show merging nodules or cavitations. For those with acute melioidosis without the spread to the bloodstream, chest x-ray most commonly shows upper lobe consolidation or cavitations. In chronic melioidosis, the slowly progressing of upper lobe consolidation of the lungs resembles tuberculosis. For abscesses located in other parts of the body apart from the lungs, especially in the liver and spleen, CT scan has higher sensitivity when compared with an ultrasound scan. In liver and splenic abscesses, an ultrasound scan shows "target-like" lesions while CT scan shows "honeycomb sign" (abscess with loculations separated by thin septa) in liver abscesses. For melioidosis involving the brain, MRI have higher sensitivity than a CT scan in diagnosing the lesion. MRI shows ring-enhancing lesions for brain melioidosis.
Prevention
Melioidosis is a notifiable disease in Australia which enables the country to monitor disease burden and contain outbreaks. On the other hand, melioidosis is only a notifiable condition in Thailand since June 2016. However, until recently, the official notification system in Thailand has significantly underestimated the incidence of culture-positive melioidosis and its mortality. Nevertheless, Australia also embarked on awareness campaigns to increase the communitys understanding of the disease. In the United Kingdom, where reporting by laboratories is mandatory, 41.3% of cases imported since 2010 were not notified. In the United States, lab workers can handle clinical specimens of B. pseudomallei under BSL-2 conditions, while mass production of such organisms requires BSL-3 precautions. On the other hand, in other endemic areas where the B. pseudomallei samples were handled less stringently, there has been no confirmed laboratory-acquired infection reported. This phenomenon may show that the risk of infection with B. pseudomallei is less than a typical biohazard type 3 agent. There are also several cases of hospital-acquired infection of melioidosis. Therefore, healthcare providers are recommended to practice hand hygiene and universal precautions.Large-scale water chlorination has been successful at reducing B. pseudomallei in the water in Australia. In middle to low-income countries, water should be boiled before consumption. In high income countries, water could be treated with ultraviolet light for those at risk of contracting melioidosis. Those who are at high risk of contact with the bacteria should wear protective gear (such as boots and gloves) during work. Those staying in endemic areas should avoid direct contact with soil, and outdoor exposure to heavy rain or dust clouds. Bottled water or boiled water are preferred as drinking water. A study conducted from 2014 to 2018, however showed no significant differences on whether behavioural changes can reduce the risk of contracting melioidosis. Modification of behavioural changes or more frequent interventions may be needed to ensure a definite reduction in risk of getting melioidosis.
Antibiotic prophylaxis
Administering cotrimoxazole three times a week throughout a wet season for dialysis patients has no obvious benefit of preventing melioidosis. Besides, high cost and side effects of this drug limits its use to only those with high risk of getting melioidosis. After exposure to B. pseudomallei (particularly following a laboratory accident, penetrating injuries, exposure of mouth and eyes to contaminated materials or aerosols), treatment with antibiotics is only given when in highly selected individuals after weighing the risk of adverse effects of the drugs against the benefits from contracting melioidosis. Cotrimoxazole can be used in this context. Alternatively, co-amoxiclav and doxycycline can be used for those who are intolerant to co-trimoxazole. Low-risk individuals would receive frequent monitoring instead.
Vaccination
Several vaccine candidates have been tested in animal models. Nevertheless, no vaccine candidates have been tried in humans. Major hurdles of the vaccines are limited efficacy in animal models, establishing the best method of vaccine administration in humans and logistical and financial issues in establishing human trials in endemic areas.
Treatment
The treatment of melioidosis is divided into two stages: an intravenous intensive phase and an eradication phase to prevent recurrence. The choice of antibiotics depends upon the susceptibility of the bacteria to various antibiotics. B. pesudomallei are generally susceptible to ceftazidime, meropenem, imipenem, and co-amoxiclav. These drugs generally kill bacteria. B. pseudomallei is also susceptible to doyxcycline, chloramphenicol, and co-trimoxazole. These drugs generally inhibit the growth of the bacteria. However, the bacteria are resistant to penicillin, ampicillin, 1st and 2nd generation cephalosporin, gentamicin, streptomycin, tobramycin, macrolides, and polymyxins. On the other hand, 86% of the B. pseudomallei isolates from the region of Sarawak, Malaysia are susceptible to gentamicin and this has not been found elsewhere in other parts of the world.Prior to 1989, the standard treatment for acute melioidosis was a three-drug combination of chloramphenicol, co-trimoxazole and doxycycline; this regimen is associated with a mortality rate of 80% and is no longer used unless no other alternatives are available. All three drugs are bacteriostatic (they stop the bacterium from growing, but do not kill it) and the action of co-trimoxazole antagonizes both chloramphenicol and doxycycline.
Intensive phase
Intravenous ceftaz |
Melioidosis | idime is the current drug of choice for treatment of acute melioidosis and should be administered for at least 10 to 14 days. Meropenem, imipenem and the cefoperazone-sulbactam combination (Sulperazone) are also effective. Intravenous amoxicillin-clavulanate (co-amoxiclav) may be used if none of the above four drugs is available; co-amoxiclav prevents death from melioidosis as well as ceftazidime. Co-amoxiclav is also used if patient has allergy towards sulfonamide, unable to tolerate co-trimaxazole, in pregnant patients or in children. High dose of co-amoxiclav (20 mg/kg for amoxicillin and 5 mg/kg for clavulanate) is recommended to prevent treatment failures. Intravenous antibiotics are given for a minimum of 10 to 14 days. The median fever clearance time in melioidosis is 9 days. The treatment duration is in accordance with Darwin melioidosis treatment guidelines where there is low rate of recrudescence and relapse.Meropenem is the preferred antibiotic therapy for neurological melioidosis and those with septic shock admitted into intensive care units. Co-trimoxazole is recommended in addition to ceftazidime for neurological melioidosis, osteomyelitis, septic arthritis, skin and gastrointestinal infection, and deeply seated abscess. For deep-seated infections such as abscesses of internal organs, osteomyelitis, septic arthritis, and neurological melioidosis, the duration of antibiotics given should be longer (up to 4 to 8 weeks). The time taken for the fever to be resolved can be more than 10 days in those with deep-seated infection. According to the 2020 Revised Royal Darwin Hospital Guideline, the dosage for intravenous ceftazidime is 2g 6-hourly in adults (50 mg/kg up to 2g in children less than 15 years old). The dosage for meropenem is 1g 8-hourly in adults (25 mg/kg up to 1g in children). Acquired resistance to ceftazidime, carbapenems, and co-amoxiclav is rare in the intensive phase but resistance to cotrimoxazole during eradication therapy is technically difficult to assess. There are no differences between using cefoperazone/sulbactam or ceftazidime to treat melioidosis as both shows similar death rates and disease progression following treatment. However, data are lacking to recommend cefoperazone/sulbactam usage. For those with kidney impairment, the dosage of ceftazidime, meropenem, and co-trimoxazole should be lowered. Once the clinical condition improved, meropenem can be switched back to ceftazidime.
Eradication phase
Following the treatment of the acute disease, eradication treatment with co-trimoxazole is the drug of choice and should be used for 3 months (12 weeks) as all-cause mortality was lower in 12 weeks group when compared to those receiving treatment for 20 weeks. For those with neurological melioidosis and osteomyelitis, drugs should be given for more than 6 months. Co-amoxiclav and doxycycline are drugs of second choice. Co-trimoxazole should not be used in those with glucose-6-phosphate dehydrogenase deficiency as it can cause haemolytic anemia. However, in Thailand, usage of co-trimoxazole does not accompany G6PD screening. Other side effects such as rash, hyperkalemia, renal dysfunction, and gastrointestinal symptoms should prompt the reduction of co-trimoxazole doses. Chloramphenicol is no longer routinely recommended for this purpose. Co-amoxiclav is an alternative for patients unable to take co-trimoxazole and doxycycline (e.g. pregnant women and children under the age of 12), but is not as effective and has a higher relapse rate. Single-agent treatment with fluoroquinolone (e.g., ciprofloxacin) or doxycycline for the oral eradication phase is ineffective.In Australia, co-trimoxazole is used with children and pregnant mothers after the first 12 weeks of pregnancy. Meanwhile, in Thailand, co-amoxiclav is the drug of choice for children and pregnant women. B. pseudomallei rarely acquires resistance when co-amoxiclav is used. The dosing regimen for co-trimoxazole (trimethoprim/sulfamethoxazole) in eradication phase is 6/30 mg/kg, up to maximum 240/1200 mg in children, 240/1200 mg in adults weighing 40 to 60 kg, and 320/1600 mg in adults weighing more than 60 kg, taken orally every 12 hours. In both Thailand and Australia, co-trimoxazole is taken together with folic acid (0.1 mg/kg up to 5 mg in children). There are also cases where melioidosis is successfully treated with co-trimoxazole for 3 months without going through intensive therapy provided that there is only skin manifestations without the involvement of internal organs or sepsis. Resistance to cotrimoxazole is rare in Asia. Besides that, it is difficult to determine the resistance reliably because resistance to cotrimoxazole is defined when minimum inhibitory concentration (MIC) of more than 4 mg/L is required to completely inhibit the growth of 80% of the bacteria (80% inhibition point). Interpretation of 80% inhibition point is subjective and prone to human error. In 2021, European Committee on Antimicrobial Susceptibility Testing (EUCAST) released a new guideline on interpreting the susceptibility of B pseudomallei towards various antibiotics on disc susceptibility testing. The new guideline includes "S" for susceptible organism, "I" for susceptible organism only after increased exposure (when dosage or concentration of the drug increases) and "R" for resistant organism.
Surgery
Surgical drainage is indicated for single, large abscesses in the liver, muscle, and prostate. However, for multiple abscesses in the liver, spleen, and kidney, surgical drainage may not be possible or necessary. For septic arthritis, arthrotomy washout and drainage are required. Surgical debridement may be necessary. For those with mycotic aneurysm, urgent surgery is required for prosthetic vascular grafts. Lifelong therapy with co-trimoxazole may be needed for those with prosthetic vascular grafts according to a review of case reports in 2005. Other abscesses rarely need to be drained because most resolve with antibiotic treatment. Prostate abscess may require routine imaging. Antibiotics treatment for prostatic abscess may be enough except for abscesses more than 10 to 15 mm where surgical drainage is required.
Others
Several immunomodulating therapies are suggested to boost the human body immune function against the bacteria because the pathogenesis of melioidosis is thought to be contributed by defects in neutrophils. The Royal Darwin Hospital 2014 guidelines recommended granulocyte colony-stimulating factor (G-CSF) as immunomodulating therapy for those with septic shock at 300 ug daily as soon as the bacteriological laboratory flag the culture as possibly Burkholderia pseudomallei. The main contraindication of starting (G-CSF) is a heart event. The G-CSF is continued for ten days depends on clinical response or a contraindication develops such as white cell count greater than >50,000 X106/litre.Anti-PDI (programmed cell death) agents could be useful in melioidosis treatment especially for those with septic shock. This is because Burkholderia pseudomallei bacteria increases the expression of PDI-1 that regulates and inhibits the formation of T-cells that are essential for fighting against melioidosis.
Prognosis
In well-resourced settings, where the disease can be detected and treated early, the risk of death is 10%. In resource-poor settings, the risk of death from the disease is more than 40%.Recurrent melioidosis can occur either due to re-infection or relapse after the completion of eradication therapy. Re-infection is due to a new strain of B. pseudomallei bacteria. Meanwhile, relapse is due to failure to clear infections after the eradication therapy. Recurrent melioidosis is rare since 2014 due to improved antibiotic therapy and prolongation of the intensive phase of therapy as evident in Darwin Prospective Melioidosis Study. On the other hand, recrudescence are those who present with symptoms during the eradication therapy. Recrudescence rates may be improved by ensuring adherence to a full course of eradication therapy e.g. by reducing self-discharge against medical advice.Underlying medical conditions such as diabetes mellitus, chronic kidney disease, and cancer can worsen the long-term survival and disability of those who recover from infection. One of the complications of melioidosis is encephalomyelitis. It can cause quadriparesis (muscle weakness in all the limbs), partial flaccid paraparesis (muscle weakness of both legs), or foot drop. For those with previous melioidosis-associated bone and joint infections, complications such as sinus tract infection, bone and joint deformities with limited range of motion can occur.
Epidemiology
Melioidosis is an understudied disease that remains endemic in developing countries. In 2015, the International Melioidosis Society was formed to raise awareness of the disease. In 2016, a statistical model was developed which predicted that the number is 165,000 cases per year with 138,000 of those occurring in East and South Asia and the Pacific. In approximately half of those cases (54% or 89,000), people will die. Under-reporting is a common problem as only 1,300 cases were reported worldwide since 2010, which is less than 1% of the projected incidence based on the modelling. Lack of laboratory diagnostic capabilities and lack of disease awareness amongst health care providers also causes under diagnosis. Even if bacterial cultures show positive result for B. pesudomallei, they can be discarded as contaminants especially in laboratories in non-endemic areas. In 2015, it was estimated that the yearly disability-adjusted life year (DALY) was 84.3 per 100,000 people. As of 2022, melioidosis is not included in the WHO list of neglected tropical diseases.
Geography
Melioidosis is endemic in parts of southeast Asia (including Thailand, Laos, Singapore, Brunei, Malaysia, Myanmar and Vietnam), southern China, Taiwan northern Australia. India, and South America. Since 1991, a total of 583 cases were reported in India. Most Indian cases are located in Karnataka and Tamil Nadu. Fifty-one cases of melioidosis were reported in Bangladesh from 1961–2017. Nonetheless, lack of awareness and resources gives rise to under diagnosis of the disease in the country. The true burden of melioidosis in Africa and Middle East remain unknown due to low amount of data. Several melioidosis cases were reported over the years. Although 24 African countries and three Middle Eastern countries predicted to be endemic with melioidosis, however not a single case was reported from these specific countries. In the United States, two historical cases (1950 and 1971) and four recent cases (2010, 2011, 2013, 2020) have been reported amongst people that did not travel overseas. Despite extensive investigations, the source of melioidosis was never confirmed. One possible explanation is that importation of medicinal plant products or exotic reptiles could have resulted in the introduction of melioidosis in the United States. In 2021, there was a melioidosis outbreak in several states in the United States due to usage of contaminated aromatherapy spray imported from India. There are also cases of infection through imported tropical fishes in home aquariums.
In Europe, more than half of the melioidosis cases are imported from Thailand.
Age, risk factors
Melioidosis is found in all age groups. For Australia and Thailand, the median age of infection is at 50 years; 5 to 10% of the patients are under 15 years. The single most important risk factor for developing melioidosis is diabetes mellitus, followed by hazardous alcohol use, chronic kidney disease, and chronic lung disease. More than 50% of people with melioidosis have diabetes; diabetics have a 12-fold increased risk of contracting melioidosis. Diabetes decreases the ability of macrophages to fight the bacteria and reduced the T helper cell production. Excessive release of Tumor necrosis factor alpha and Interleukin 12 by mononuclear cells increases the risk of septic shock. Other risk factors include thalassaemia, occupational exposure (e.g. rice paddy farmers), recreational exposure to soil, water, being male, age greater than 45 years, and prolonged steroid use/immunosuppression. However, 8% of children and 20% of adults with melioidosis have no risk factors. HIV infection does not appear to predispose to melioidosis, although several other co-infections have been reported. Infant cases have been reported possibly due to mother-to-child transmission, community-acquired infection, or healthcare-associated infection. Those who are well may also be infected with B. pseudomallei. For example, 25% of children started producing antibodies against B. pseudomallei between 6 months to 4 years of staying in endemic areas although they did not experience any melioidosis symptoms; suggesting they were exposed to it over this time. This means that many people without symptoms will test positive in serology tests in endemic areas. In Thailand, the seropositivity rate exceeds 50%, while in Australia the seropositivity rate is only 5%. The disease is clearly associated with increased rainfall, with the number of cases rising following increased precipitation. Severe rainfall increases the concentration of the bacteria in the topsoil, thus increasing thus of transmitting the bacteria through the air. A recent CDC Advisory indicated that the recent detection of the organism in the environment in Mississippi following the occurrence of two indigenous cases of melioidosis, confirms that parts of the southern USA should now be regarded as melioidosis-endemic.
History
Pathologist Alfred Whitmore and his assistant Krishnaswami first reported melioidosis among beggars and morphine addicts at autopsy in Rangoon, present-day Myanmar, in a report published in 1912. Whitmore was able to grow the organism in culture and its showed similarity with B. mallei, another bacteria that was known causing glanders in animals. Therefore, he named the new organism Bacillus pseudomallei. He did no further work on the organism. Arthur Conan Doyle may have read Whitmores report before writing a short story that involved the fictitious tropical disease "Tapanuli fever" in a Sherlock Holmes story titled "The Adventure of the Dying Detective" published in 1913. In the same year, melioidosis outbreak occurred inside the Institute for Medical Research (IMR), Kuala Lumpur, Malaya after its laboratory animals such as guinea pigs and rabbits were infected. William Fletcher and Ambrose Thomas Stanton, doctors who worked at the IMR, were the next ones to study the organism. They were unable identify the organism that caused the outbreak. It was only in 1917, when Fletcher isolated an organism similar to Whitmores bacillus from a Tamil rubber estate worker, the presence of the new species of bacteria was confirmed. The term "melioidosis" was first coined in 1921. The name melioidosis is derived from the Greek melis (μηλις) meaning "a distemper of asses" with the suffixes -oid meaning "similar to" and -osis meaning "a condition", that is, a condition similar to glanders. B pseudomallei is similar in clinical presentation and genome make-up with B. mallei but is distinguished from it due to epidemiological and zoonotic characteristics.The first human case of melioidosis in South Asia was reported in Sri Lanka in 1927. In 1932, Thomas and Fletcher collected 83 cases of melioidosis from literature. In this case series, there were only two survivals. Since then, more case series of melioidosis were reported. Thomas and Fletcher also pioneered the use of serological methods in diagnosing the disease. Thomas and Fletcher incorrectly believed that melioidosis infection came from human contact with rodents. However, observations on the disease noted that humans usually got it after exposure to mud or contaminated water. Besides, the organism was never grown from rats. This led to a search of the bacteria in the environment. In 1936, the first animal (pig) case of melioidosis in Africa was reported in Madagascar. In 1937, water was first identified as the habitat of B. pseudomallei. The first case of Australian melioidosis was described in an outbreak in sheep in 1949 at North Queensland. This was followed by the first case of human melioidosis at Townsville in 1950. Initially, the discovery of melioidosis in Australia had led to a debate on when and how the disease spread from Southeast Asia to a new distant environment. However, this hypothesis was later disproved in 2017 when whole genome sequencing of B. pseudomallei over 30 countries collected over 79 years suggested Australia as the early reservoir for melioidosis. In 1955, first case of local human melioidosis was reported in Thailand. During the Vietnam War from 1967 to 1973, 343 American soldiers were reported with melioidosis, with about 50 cases transmitted through inhalation. An outbreak of melioidosis at the Paris Zoo in the 1970s (known as Laffaire du jardin des plantes) was thought to have originated from an imported panda or horses from Iran. It is unclear how imported melioidosis is able to persist in a completely new environment. Eventually, the outbreak terminated by itself after a period of time. It was only during the 1980s, Infectious Disease Association of Thailand started took notice of this disease. First conference on melioidosis was held in 1985 in Thailand. It was during this meeting that collaboration between Sappasitprasong Hospital, Thailand, and Wellcome-Mahido-Oxford Tropical Medicine Research Programme was established. Such collaboration made Thailand a world leader in clinical and epidemiology research on melioidosis.In 1989, several studies conducted in Thailand demonstrated ceftazidime as an effective antibiotic against melioidosis. Ceftazidime had been shown to reduce the risk of death of melioidosis from 74% to 37%. In 1990, a non-virulent arabinose-positive B. pseudomallei was found by Vanaporn Wuthiekanun. The organism was later reclassified into a new species called B. thailandensis. This species has become a useful tool in the laboratory for the studies of the pathogenesis of B. pseudomallei. B. pseudomallei was previously classified as part of the genus Pseudomonas. In 1992, the pathogen was formally named B. pseudomallei. In 1994, First International Symposium on melioidosis was held in Kuala Lumpur where 80 delegates attended. Papers were presented and later published as a book. Subsequent congresses were held in Thailand, Australia, and Singapore once every three years. In 2002, B. pseudomallei was classified as a "Category B agent". In 2004, the complete genome of B. pseudomallei was published. In 2012, B pseudomallei was classified as a "Tier 1 select agent" by the U.S. Centers for Disease Control. In 2014, co-trimoxazole was established as the only oral eradication therapy rather than combination therapy of co-trimoxazole with doxycycline. In 2016, a statistical model was developed to predict the occurrence of global melioidosis per year.
Synonyms
Pseudoglanders
Whitmores disease (after Captain Alfred Whitmore, who first described the disease)
Nightcliff gardeners disease (Nightcliff is a suburb of Darwin, Australia where melioidosis is endemic)
Paddy-field disease
Morphia injectors septicaemia
Biological warfare
Interest in melioidosis has been expressed because it has the potential to be developed as a biological weapon. Another similar bacterium, Burkholderia mallei was used by the Germans in World War I to infect livestock shipped to Allied countries. Deliberate infection of human prisoners of war and animals using B. mallei were carried out in Chinas Pingfang District by the Japanese during World War II. The Soviet Union reportedly used B. mallei during the Soviet–Afghan War in 1982 and 1984. B. pseudomallei, like B. mallei, was studied by both the US and Soviet Union as a potential biological warfare agent, but never weaponized. Other countries such as Iran, Iraq, North Korea, and Syria may have investigated the properties of B. pseudomallei for biological weapons. The bacterium is readily available in the environment. It can also be aerosolized and transmitted via inhalation. However, the B. pseudomallei has never been used in biological warfare. The actual risk of the deliberate release of B. pseudomallei or B. mallei is unknown.
References
This article was adapted from the following source under a [ ] license (2022) (reviewer reports):
Siang Ching Raymond Chieng (14 August 2022). "Melioidosis" (PDF). WikiJournal of Medicine. 9 (1): 4. doi:10.15347/WJM/2022.004. ISSN 2002-4436. Wikidata Q100400594.
External links
Resource Center for melioidosis
CDC Disease Info melioidosisBurkholderia pseudomallei genomes and related information at PATRIC, a Bioinformatics Resource Center funded by NIAID |
Avoidant personality disorder | Avoidant personality disorder (AvPD) is a Cluster C personality disorder characterized by excessive social anxiety and inhibition, fear of intimacy (despite an intense desire for it), severe feelings of inadequacy and inferiority, and an overreliance on avoidance of feared stimuli (e.g. self-imposed social isolation) as a maladaptive coping method. Those affected typically display a pattern of extreme sensitivity to negative evaluation and rejection, a belief that one is socially inept or personally unappealing to others, and avoidance of social interaction despite a strong desire for it. It affects an approximately equal number of men and women.People with AvPD often avoid social interaction for fear of being ridiculed, humiliated, rejected, or disliked. They typically avoid becoming involved with others unless they are certain they will not be rejected, and may also pre-emptively abandon relationships due to a real or imagined fear that they are at risk of being rejected by the other party.Childhood emotional neglect (in particular, the rejection of a child by one or both parents) and peer group rejection are associated with an increased risk for its development; however, it is possible for AvPD to occur without any notable history of abuse or neglect.
Signs and symptoms
Avoidant individuals are preoccupied with their own shortcomings and form relationships with others only if they believe they will not be rejected. They often view themselves with contempt, while showing a decreased ability to identify traits within themselves that are generally considered as positive within their societies. Loss and social rejection are so painful that these individuals will choose to be alone rather than risk trying to connect with others.
Some with this disorder fantasize about idealized, accepting and affectionate relationships because of their desire to belong. They often feel themselves unworthy of the relationships they desire, and shame themselves from ever attempting to begin them. If they do manage to form relationships, it is also common for them to pre-emptively abandon them out of fear of the relationship failing.Individuals with the disorder tend to describe themselves as uneasy, anxious, lonely, unwanted and isolated from others. They often choose jobs of isolation in which they do not have to interact with others regularly. Avoidant individuals also avoid performing activities in public spaces for fear of embarrassing themselves in front of others.
Symptoms include:
Extreme shyness or anxiety in social situations, though the person feels a strong desire for close relationships
Heightened attachment-related anxiety, which may include a fear of abandonment
Substance use disorders
Comorbidity
AvPD is reported to be especially prevalent in people with anxiety disorders, although estimates of comorbidity vary widely due to differences in (among others) diagnostic instruments. Research suggests that approximately 10–50% of people who have panic disorder with agoraphobia have avoidant personality disorder, as well as about 20–40% of people who have social anxiety disorder. In addition to this, AvPD is more prevalent in people who have comorbid social anxiety disorder and generalised anxiety disorder than in those who have only one of the aforementioned conditions.Some studies report prevalence rates of up to 45% among people with generalized anxiety disorder and up to 56% of those with obsessive–compulsive disorder. Posttraumatic stress disorder is also commonly comorbid with avoidant personality disorder.Avoidants are prone to self-loathing and, in certain cases, self-harm. Substance use disorders are also common in individuals with AvPD—particularly in regard to alcohol, benzodiazepines, and opioids—and may significantly affect a patients prognosis.Earlier theorists proposed a personality disorder with a combination of features from borderline personality disorder and avoidant personality disorder, called "avoidant-borderline mixed personality" (AvPD/BPD).
Causes
Causes of AvPD are not clearly defined, but appear to be influenced by a combination of social, genetic and psychological factors. The disorder may be related to temperamental factors that are inherited.Specifically, various anxiety disorders in childhood and adolescence have been associated with a temperament characterized by behavioral inhibition, including features of being shy, fearful and withdrawn in new situations. These inherited characteristics may give an individual a genetic predisposition towards AvPD.Childhood emotional neglect and peer group rejection are both associated with an increased risk for the development of AvPD. Some researchers believe a combination of high-sensory-processing sensitivity coupled with adverse childhood experiences may heighten the risk of an individual developing AvPD.
Subtypes
Millon
Psychologist Theodore Millon notes that because most patients present a mixed picture of symptoms, their personality disorder tends to be a blend of a major personality disorder type with one or more secondary personality disorder types. He identified four adult subtypes of avoidant personality disorder.
Others
In 1993, Lynn E. Alden and Martha J. Capreol proposed two other subtypes of avoidant personality disorder:
Diagnosis
ICD
The World Health Organizations ICD-10 lists avoidant personality disorder as anxious (avoidant) personality disorder (F60.6).
It is characterized by the presence of at least four of the following:
persistent and pervasive feelings of tension and apprehension;
belief that one is socially inept, personally unappealing, or inferior to others;
excessive preoccupation with being criticized or rejected in social situations;
unwillingness to become involved with people unless certain of being liked;
restrictions in lifestyle because of need to have physical security;
avoidance of social or occupational activities that involve significant interpersonal contact because of fear of criticism, disapproval, or rejection.Associated features may include hypersensitivity to rejection and criticism.
It is a requirement of ICD-10 that all personality disorder diagnoses also satisfy a set of general personality disorder criteria.
DSM
The Diagnostic and Statistical Manual of Mental Disorders (DSM) of the American Psychiatric Association also has an avoidant personality disorder diagnosis (301.82). It refers to a widespread pattern of inhibition around people, feeling inadequate and being very sensitive to negative evaluation. Symptoms begin by early adulthood and occur in a range of situations.
Four of the following seven specific symptoms should be present:
Avoids occupational activities that involve significant interpersonal contact, because of fears of criticism, disapproval, or rejection
is unwilling to get involved with people unless certain of being liked
shows restraint within intimate relationships because of the fear of being shamed or ridiculed
is preoccupied with being criticized or rejected in social situations
is inhibited in new interpersonal situations because of feelings of inadequacy
views self as socially inept, personally unappealing, or inferior to others
is unusually reluctant to take personal risk or to engage in any new activities because they may prove embarrassing
Differential diagnosis
In contrast to social anxiety disorder, a diagnosis of avoidant personality disorder (AvPD) also requires that the general criteria for a personality disorder be met.
According to the DSM-5, avoidant personality disorder must be differentiated from similar personality disorders such as dependent, paranoid, schizoid, and schizotypal. But these can also occur together; this is particularly likely for AvPD and dependent personality disorder. Thus, if criteria for more than one personality disorder are met, all can be diagnosed.There is also an overlap between avoidant and schizoid personality traits (see Schizoid avoidant behavior) and AvPD may have a relationship to the schizophrenia spectrum.Avoidant personality disorder must also be differentiated from the autism spectrum, specifically Asperger syndrome.
Treatment
Treatment of avoidant personality disorder can employ various techniques, such as social skills training, psychotherapy, cognitive therapy, and exposure treatment to gradually increase social contacts, group therapy for practicing social skills, and sometimes drug therapy.A key issue in treatment is gaining and keeping the patients trust since people with an avoidant personality disorder will often start to avoid treatment sessions if they distrust the therapist or fear rejection. The primary purpose of both individual therapy and social skills group training is for individuals with an avoidant personality disorder to begin challenging their exaggerated negative beliefs about themselves.Significant improvement in the symptoms of personality disorders is possible, with the help of treatment and individual effort.
Prognosis
Being a personality disorder, which is usually chronic and has long-lasting mental conditions, an avoidant personality disorder may not improve with time without treatment. Given that it is a poorly studied personality disorder and in light of prevalence rates, societal costs, and the current state of research, AvPD qualifies as a neglected disorder.
Controversy
There is debate as to whether avoidant personality disorder (AvPD) is distinct from social anxiety disorder. Both have similar diagnostic criteria and may share a similar causation, subjective experience, course, treatment and identical underlying personality features, such as shyness.It is contended by some that they are merely different conceptualizations of the same disorder, where avoidant personality disorder may represent the more severe form. In particular, those with AvPD experience not only more severe social phobia symptoms, but are also more depressed and more functionally impaired than patients with generalized social phobia alone. But they show no differences in social skills or performance on an impromptu speech. Another difference is that social phobia is the fear of social circumstances whereas AvPD is better described as an aversion to intimacy in relationships.
Epidemiology
Data from the 2001–02 National Epidemiologic Survey on Alcohol and Related Conditions indicates a prevalence of 2.36% in the American general population. It appears to occur with equal frequency in males and females. In one study, it was seen in 14.7% of psychiatric outpatients.
History
The avoidant personality has been described in several sources as far back as the early 1900s, although it was not so named for some time. Swiss psychiatrist Eugen Bleuler described patients who exhibited signs of avoidant personality disorder in his 1911 work Dementia Praecox: Or the Group of Schizophrenias. Avoidant and schizoid patterns were frequently confused or referred to synonymously until Kretschmer (1921), in providing the first relatively complete description, developed a distinction.
See also
Attachment theory
Avoidance coping
Counterphobic attitude
Experiential avoidance
Inferiority complex
Sensory processing sensitivitySocial:
Hermit
Hikikomori
Loner
Recluse
Solitude
Taijin kyofusho
References
== External links == |
Pigment dispersion syndrome | Pigment dispersion syndrome (PDS) is an eye disorder that can lead to a form of glaucoma known as pigmentary glaucoma. It takes place when pigment cells slough off from the back of the iris and float around in the aqueous humor. Over time, these pigment cells can accumulate in the anterior chamber in such a way that they begin to clog the trabecular meshwork (the major site of aqueous humour drainage), which can in turn prevent the aqueous humour from draining and therefore increases the pressure inside the eye. A common finding in PDS are central, vertical corneal endothelial pigment deposits, known as Krukenberg spindle. With PDS, the intraocular pressure tends to spike at times and then can return to normal. Exercise has been shown to contribute to spikes in pressure as well. When the pressure is great enough to cause damage to the optic nerve, this is called pigmentary glaucoma. As with all types of glaucoma, when damage happens to the optic nerve fibers, the vision loss that occurs is irreversible and painless.
Risk factors
This condition is rare, but occurs most often in Caucasians, particularly men, and the age of onset is relatively low: mid 20s to 40s. As the crystalline lens hardens with age, the lens zonules pull away from the iris and the syndrome lessens and stops. The main risk factor is nearsightedness. Genetic factors may also play a part in the transition from syndrome to the glaucoma condition.
Diagnosis
Diagnosis for pigment dispersion syndrome is made with characteristic slit lamp and gonioscopy findings.
Management
There is no cure, but pigmentary glaucoma can be managed with eye drops or treated with simple surgeries. If caught early and monitored, chances of glaucoma are greatly reduced.
A 2016 Cochrane Review sought to determine the effectiveness of YAG laser iridotomy versus no laser iridotomy for pigment dispersion syndrome and pigmentary glaucoma, in 195 participants, across five studies. No clear benefits in preventing loss of visual field were found for eyes treated with peripheral laser iridotomy. There was weak evidence suggesting that laser iridotomy could be more effective in lowering intraocular pressure in eyes versus no treatment.
References
== External links == |
Fibroma | Fibromas are benign tumors that are composed of fibrous or connective tissue. They can grow in all organs, arising from mesenchyme tissue. The term "fibroblastic" or "fibromatous" is used to describe tumors of the fibrous connective tissue. When the term fibroma is used without modifier, it is usually considered benign, with the term fibrosarcoma reserved for malignant tumors.
Types
Hard fibroma
The hard fibroma (fibroma durum) consists of many fibres and few cells, e.g. in skin it is called dermatofibroma (fibroma simplex or nodulus cutaneous). A special form is the keloid, which derives from hyperplastic growth of scars.
Soft fibroma
The soft fibroma (fibroma molle) or fibroma with a shaft (acrochordon, skin tag, fibroma pendulans) consist of many loosely connected cells and less fibroid tissue. It mostly appears at the neck, armpits or groin. The photo shows a soft fibroma of the eyelid.
Other types of fibroma
The fibroma cavernosum or angiofibroma, consists of many often dilated vessels, it is a vasoactive tumor occurring almost exclusively in adolescent males.
The cystic fibroma (fibroma cysticum) has central softening or dilated lymphatic vessels.
The myxofibroma (fibroma myxomatodes) is produced by liquefaction of the underlying soft tissue.
The cemento-ossifying fibroma is hard and fibrous, most frequently seen in the jaw or mouth, sometimes in connection with a fracture or another type of injury.
Other fibromas: chondromyxoid fibroma, desmoplasmic fibroma, nonossifying fibroma, ossifying fibroma, nuchal fibroma, collagenous fibroma, fibroma of tendon sheath, perifollicular fibroma, pleomorphic fibroma, uterine fibroma, Gardner fibroma, etc.
The neurofibroma is a benign nerve-sheath tumor in the peripheral nervous system.
Ovarian fibroma
It appears in the sex cord-stromal tumour group of ovarian neoplasms. Ovary fibromas are most frequent during middle age, and rare in children.
Upon gross pathological inspection, ovary fibromas are firm and white or tan.
Variants with edema are especially likely to be associated with Meigs syndrome.
On microscopic examination, there are intersecting bundles of spindle cells producing collagen.
There may be thecomatous areas (fibrothecoma). The presence of an ovarian fibroma can cause ovarian torsion in some cases.
Treatment
Benign fibromas may, but need not, be removed. Removal is usually a brief outpatient procedure or using cryotherapy in which the lesion is deep frozen (-196 degrees Celsius using liquid nitrogen) and thawed for two or more cycles, with full recovery within 3 to 4 weeks. The cryotherapy treatment needs no anesthetics and is painless. Another simple treatment is snip removal after injecting local anesthetic.
See also
Acrochordon (skin tags)
Fibrous lesions
References
== External links == |
Bizarre parosteal osteochondromatous proliferation | Bizarre parosteal osteochondromatous proliferation (BPOP), also known as Noras lesion, is a type of non-cancerous bone tumor belonging to the group of cartilage tumors. It is generally seen in the tubular bones of the hands and feet, where it presents with a rapidly enlarging painless lump in a finger or toe.It is composed of bone, cartilage and spindle cells. Some people report previous trauma.Diagnosis is by medical imaging. Treatment is by surgical excision. Up to 50% recur after surgery.It is rare, and occurs more often in the 20s and 30s. Combined with subungal exostosis, it accounts for less than 5% of cartilage tumors. Males and females are affected equally. The condition was first described by Frederick E. Nora in 1983.
Signs and symptoms
BPOP generally presents with a 1–3 cm painless lump in a finger or more frequently a toe. Growth can be rapid.
Mechanism
It is composed of bone, cartilage and spindle cells. A small number of people have reported previous trauma.
Diagnosis
Medical imaging usually shows a well-defined wide-based bony growth on the surface of bone.
Differential diagnosis
BPOP is distinct from subungal exostosis. Conditions that may appear similar to BPOP include: myositis ossficans, ostechondroma, surface osteosarcoma and granulomatous infection.
Treatment
Treatment is by surgical excision.
Outcomes
Up to 50% recur after surgery.
Epidemiology
BPOP is rare. It is most often seen in people in their 20s and 30s. Combined with subungal exostosis, it accounts for less than 5% of cartilage tumors. Males and females are affected equally.
History
Bizarre parosteal osteochondromatous proliferation was first described by Frederick E. Nora in 1983. Generally in the US, it has been thought of as a mouthful and hence it is sometimes referred to as Noras lesion.
Other animals
In 1998 a report of a similar lesion to BPOP was reported in a wallaby.
== References == |
Stomatitis | Stomatitis is inflammation of the mouth and lips. It refers to any inflammatory process affecting the mucous membranes of the mouth and lips, with or without oral ulceration.In its widest meaning, stomatitis can have a multitude of different causes and appearances. Common causes include infections, nutritional deficiencies, allergic reactions, radiotherapy, and many others.
When inflammation of the gums and the mouth generally presents itself, sometimes the term gingivostomatitis is used, though this is also sometimes used as a synonym for herpetic gingivostomatitis.
The term is derived from the Greek stoma (στόμα), meaning "mouth", and the suffix -itis (-ῖτις), meaning "inflammation".
Causes
Nutritional deficiency
Malnutrition (improper dietary intake) or malabsorption (poor absorption of nutrients into the body) can lead to nutritional deficiency states, several of which can lead to stomatitis. For example, deficiencies of iron, vitamin B2 (riboflavin),: 490 vitamin B3 (niacin), vitamin B6 (pyridoxine), vitamin B9 (folic acid) or vitamin B12 (cobalamine) may all manifest as stomatitis. Iron is necessary for the upregulation of transcriptional elements for cell replication and repair. Lack of iron can cause genetic downregulation of these elements, leading to ineffective repair and regeneration of epithelial cells, especially in the mouth and lips. Many disorders which cause malabsorption can cause deficiencies, which in turn causes stomatitis. Examples include tropical sprue.: 49
Aphthous stomatitis
Aphthous stomatitis (canker sores) is the recurrent appearance of mouth ulcers in otherwise healthy individuals. The cause is not completely understood, but it is thought that the condition represents a T cell mediated immune response which is triggered by a variety of factors. The individual ulcers (aphthae) recur periodically and heal completely, although in the more severe forms, new ulcers may appear in other parts of the mouth before the old ones have finished healing. Aphthous stomatitis is one of the most common diseases of the oral mucosa, and is thought to affect about 20% of the general population to some degree. The symptoms range from a minor nuisance to being disabling in their impact on eating, swallowing, and talking, and the severe forms can cause people to lose weight. There is no cure for aphthous stomatitis, and therapies are aimed at alleviating the pain, reducing the inflammation and promoting healing of the ulcers, but there is little evidence of efficacy for any treatment that has been used.
Angular stomatitis
Inflammation of the corners (angles) of the lips is termed angular stomatitis or angular cheilitis. In children a frequent cause is repeated lip-licking, and in adults it may be a sign of underlying iron deficiency anemia, or vitamin B deficiencies (e.g., B2-riboflavin, B9-folate, or B12-cobalamin, which in turn may be evidence of poor diets or malnutrition such as celiac disease).
Also, angular cheilitis can be caused by a patients jaws at rest being overclosed due to edentulousness or tooth wear, causing the jaws to come to rest closer together than if the complete/unaffected dentition were present. This causes skin folds around the angle of the mouth which are kept moist by saliva, which in turn favours infection; mostly by Candida albicans or similar species. Treatment usually involves the administration of topical nystatin or similar antifungal agents. Another treatment can be to correct the jaw relationship with dental treatment (e.g., dentures or occlusal adjustment).
Denture-related stomatitis
This is a common condition present in denture wearers. It appears as reddened but painless mucosa beneath the denture. 90% of cases are associated with Candida species, and it is the most common form of oral candidiasis. Treatment is by antifungal medication and improved dental hygiene, such as not wearing the denture during sleep.
Allergic contact stomatitis
Allergic contact stomatitis (also termed "allergic gingivostomatitis" or "allergic contact gingivostomatitis") is a type IV (delayed) hypersensitivity reaction that occurs in susceptible atopic individuals when allergens penetrate the skin or mucosa.Allergens, which may be different for different individuals, combine with epithelial-derived proteins, forming haptens which bind with Langerhans cells in the mucosa, which in turn present the antigen on their surface to T lymphocytes, sensitizing them to that antigen and causing them to produce many specific clones. The second time that specific antigen is encountered, an inflammatory reaction is triggered at the site of exposure. Allergic contact stomatitis is less common than allergic contact dermatitis because the mouth is coated in saliva, which washes away antigens and acts as a barrier. The oral mucosa is also more vascular (has a better blood supply) than skin, meaning that any antigens are more quickly removed from the area by the circulation. Finally, there is substantially less keratin in oral mucosa, meaning that there is less likelihood that haptens will form.Allergic contact stomatitis appears as non-specific inflammation, so it may be mistaken for chronic physical irritation. There may be burning or soreness of the mouth and ulceration. Chronic exposure to the allergen may result in a lichenoid lesion. Plasma cell gingivitis may also occur, which may be accompanied by glossitis and cheilitis.
Allergens that may cause allergic contact stomatitis in some individuals include cinnamaldehyde, Balsam of Peru, peppermint, mercury, gold, pyrophosphates, zinc citrate, free acrylic monomer, nickel, fluoride, and sodium lauryl sulfate. These allergens may originate from many sources, including various foods and drink, chewing gum, toothpaste, mouthwash, dental floss, dental fillings, dentures, orthodontic bands or wires, and many other sources. If the substance containing the allergen comes into contact with the lips, allergic contact cheilitis can occur, together with allergic contact stomatitis.
The diagnosis is confirmed by patch test, and management is by avoidance of exposure to the allergen.
Migratory stomatitis
Migratory stomatitis (or geographic stomatitis) is an atypical presentation of a condition which normally presents on the tongue, termed geographic tongue. Geographic tongue is so named because there are atrophic, erythematous areas of depapillation that migrate over time, giving a map-like appearance.
In migratory stomatitis, other mucosal sites in the mouth, such as the ventral surface (undersurface) of the tongue, buccal mucosa, labial mucosa, soft palate, or floor of mouth may be afflicted with identical lesions, usually in addition to the tongue. Apart from not being restricted to the tongue, migratory stomatitis is an identical condition in every regard to geographic tongue. Another synonym for geographic tongue which uses the term stomatitis is "stomatitis areata migrans".
Herpetic gingivostomatitis
This is inflammation of the mouth caused by herpes simplex virus.
Irradiation and chemotherapy
Stomatitis may also be caused by chemotherapy, or radiation therapy of the oropharyngeal area. The term mucositis is sometimes used synonymously with stomatitis, however the former usually refers to mucosal reactions to radiotherapy or chemotherapy, and may occur anywhere in the gastrointestinal tract and not just in the mouth.
Necrotizing ulcerative gingivostomatitis
The term necrotizing ulcerative gingivostomatitis is sometimes used as a synonym of the necrotizing periodontal disease more commonly termed necrotizing ulcerative gingivitis, or a more severe form (also termed necrotizing stomatitis). The term necrotizing gingivostomatitis is also sometimes used.
Stomatitis nicotina
Also called smokers palatal keratosis,: 176 this condition may occur in smokers, especially pipe smokers. The palate appears dry and cracked, and white from keratosis. The minor salivary glands appear as small, red and swollen bumps. It is not a premalignant condition, and the appearance reverses if the smoking is stopped.: 176
Chronic ulcerative stomatitis
Chronic ulcerative stomatitis is a condition with specific immunopathologic features, which was first described in 1990. It is characterized by erosions and ulcerations which relapse and remit. Lesions are located on the buccal mucosa (inside of the cheeks) or on the gingiva (gums). The condition resembles oral lichen planus when biopsied.
The diagnosis is made by microscopic examination of biopsy tissue: direct immunofluorescence can reveal the presence of antinuclear antibodies specifically directed against the ΔNp63α form of the p63 protein, which is normally expressed within the basal layer of stratified epithelium. Treatment with hydroxychloroquine can be effective.
Plasma cell gingivostomatitis
Terms such as plasma cell gingivostomatitis, atypical gingivostomatitis and idiopathic gingivostomatitis are sometimes a synonym for plasma cell gingivitis, or specifically to refer to a severe form of plasma cell gingivitis.
Other forms of stomatitis
Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome—occurs in children.
Uremic stomatitis—a rare form of stomatitis that occurs with kidney failure.
Pyostomatitis vegetans
Bovine papular stomatitis
References
== External links == |
Paratyphoid fever | Paratyphoid fever, also known simply as paratyphoid, is a bacterial infection caused by one of the three types of Salmonella enterica. Symptoms usually begin 6–30 days after exposure and are the same as those of typhoid fever. Often, a gradual onset of a high fever occurs over several days. Weakness, loss of appetite, and headaches also commonly occur. Some people develop a skin rash with rose-colored spots. Without treatment, symptoms may last weeks or months. Other people may carry the bacteria without being affected; however, they are still able to spread the disease to others. Typhoid and paratyphoid are of similar severity. Paratyphoid and typhoid fever are types of enteric fever.Paratyphoid is caused by the bacterium Salmonella enterica of the serotypes Paratyphi A, Paratyphi B, or Paratyphi C growing in the intestines and blood. They are usually spread by eating or drinking food or water contaminated with the feces of an infected person. They may occur when a person who prepares food is infected. Risk factors include poor sanitation as is found among poor crowded populations. Occasionally, they may be transmitted by sex. Humans are the only animals infected. Diagnosis may be based on symptoms and confirmed by either culturing the bacteria or detecting the bacterial DNA in the blood, stool, or bone marrow. Culturing the bacteria can be difficult. Bone-marrow testing is the most accurate. Symptoms are similar to that of many other infectious diseases. Typhus is a different disease.While no vaccine is available specifically for paratyphoid, the typhoid vaccine may provide some benefit. Prevention includes drinking clean water, better sanitation, and better handwashing. Treatment of the disease is with antibiotics such as azithromycin. Resistance to a number of other previously effective antibiotics is common.Paratyphoid affects about six million people a year. It is most common in parts of Asia and rare in the developed world. Most cases are due to Paratyphi A rather than Paratyphi B or C. In 2015, paratyphoid fever resulted in about 29,200 deaths, down from 63,000 deaths in 1990. The risk of death is between 10 and 15% without treatment, while with treatment, it may be less than 1%.
Signs and symptoms
Paratyphoid fever resembles typhoid fever. Infection is characterized by a sustained fever, headache, abdominal pain, malaise, anorexia, a nonproductive cough (in early stage of illness), a relative bradycardia (slow heart rate), and hepatosplenomegaly (an enlargement of the liver and spleen). About 30% of Caucasians develop rosy spots on the central body. In adults, constipation is more common than diarrhea.Only 20 to 40% of people initially have abdominal pain. Nonspecific symptoms such as chills, sweating, headache, loss of appetite, cough, weakness, sore throat, dizziness, and muscle pains are frequently present before the onset of fever. Some very rare symptoms are psychosis (mental disorder), confusion, and seizures.
Cause
Paratyphoid fever is caused by any of three serovars of Salmonella enterica subsp. enterica: S. Paratyphi A, S. Paratyphi B (invalid alias S. schottmuelleri), S. Paratyphi C (invalid alias S. hirschfeldii).
Transmission
They are usually spread by eating or drinking food or water contaminated with the feces of an infected person. They may occur when a person who prepares food is infected. Risk factors include poor sanitation as is found among poor crowded populations. Occasionally, they may be transmitted by sex. Humans are the only animals infected.
Paratyphoid B
Paratyphoid B is more frequent in Europe. It can present as a typhoid-like illness, as a severe gastroenteritis or with features of both. Herpes labialis, rare in true typhoid fever, is frequently seen in paratyphoid B. Rarely a subdural empyema can occur. Diagnosis is with isolation of the agent in blood or stool and demonstration of antibodies antiBH in the Widal test. The disease responds well to chloramphenicol or co-trimoxazole.
Paratyphoid C
Paratyphoid C is a rare infection, generally seen in the Far East. It presents as a septicaemia with metastatic abscesses. Cholecystitis is possible in the course of the disease. Antibodies to paratyphoid C are not usually tested and the diagnosis is made with blood cultures. Chloramphenicol therapy is generally effective.
Carriers
Humans and, occasionally, domestic animals are the carriers of paratyphoid fever. Members of the same family can be transient or permanent carriers. In most parts of the world, short-term fecal carriers are more common than urinary carriers. The chronic urinary carrier state occurs in those who have schistosomiasis (parasitic blood fluke).Continuing to shed Salmonella Paratyphi is possible for up to one year, and during this phase, a person is considered to be a carrier. The chronic carrier state may follow acute illness, or mild or even subclinical infections. Chronic carriers are most often women who were infected in their middle age.
Pathophysiology
After ingestion, if the immune system is unable to stop the infection, the bacteria multiply and then spread to the bloodstream, after which the first signs of disease are observed in the form of fever. They penetrate further to the bone marrow, liver, and bile ducts, from which bacteria are excreted into the bowel contents. In the second phase of the disease, the bacteria penetrate the immune tissue of the small intestine, and the initial symptoms of small-bowel movements begin.
Diagnosis
Prevention
Providing basic sanitation and safe drinking water and food are the keys for controlling the disease. In developed countries, enteric fever rates decreased in the past when treatment of municipal water was introduced, human feces were excluded from food production, and pasteurization of dairy products began. In addition, children and adults should be carefully educated about personal hygiene. This would include careful handwashing after defecation and sexual contact, before preparing or eating food, and especially the sanitary disposal of feces. Food handlers should be educated in personal hygiene prior to handling food or utensils and equipment. Infected individuals should be advised to avoid food preparation. Sexually active people should be educated about the risks of sexual practices that permit fecal-oral contact.Those who travel to countries with poor sanitation should receive a live attenuated typhoid vaccine—Ty21a (Vivotif), which, in addition to the protection against typhoid fever, may provide some protection against paratyphoid fever caused by the S. enterica serotypes A and B. In particular, a reanalysis of data from a trial conducted in Chile showed the Ty21a vaccine was 49% effective (95% CI: 8–73%) in preventing paratyphoid fever caused by the serotype B. Evidence from a study of international travelers in Israel also indicates the vaccine may prevent a fraction of infections by the serotype A, although no trial confirms this. This cross-protection by a typhoid vaccine is most likely due to O antigens shared between different S. enterica serotypes.Exclusion from work and social activities should be considered for symptomatic, and asymptomatic people who are food handlers, healthcare/daycare staff who are involved in patient care and/or child care, children attending unsanitary daycare centers, and older children who are unable to implement good standards of personal hygiene. The exclusion applies until two consecutive stool specimens are taken from the infected patient and are reported negative.
Treatments
Control requires treatment of antibiotics and vaccines prescribed by a doctor. Major control treatments for paratyphoid fever include ciprofloxacin for 10 days, ceftriaxone/cefotaxime for 14 days, or aziththromycin.
Prognosis
Those diagnosed with Type A of the bacterial strain rarely die from it except in rare cases of severe intestinal complications. With proper testing and diagnosis, the mortality rate falls to less than 1%. Antibiotics such as azithromycin are particularly effective in treating the disease.
Epidemiology
Factors outside the household, such as unclean food from street vendors and flooding, help distribute the disease from person to person.
Because of poverty and poor hygiene and insanitary conditions, the disease is more common in less-industrialized countries, principally owing to the problem of unsafe drinking water, inadequate sewage disposal, and flooding. Occasionally causing epidemics, paratyphoid fever is found in large parts of Asia, Africa, and Central and South America. Many of those infected get the disease in Asian countries. About 16 million cases occur a year, which result in about 25,000 deaths worldwide.
References
Further reading
"Typhoid and Paratyphoid Fever." Communicable Disease Management Protocol. November 2001 https://www.gov.mb.ca/health/publichealth/cdc/protocol/typhoid.pdf.
"Typhoid and Paratyphoid Fever." Public Health Notifiable Disease Management Guidelines. Disease Control and Prevention. Alberta Health and Wellness: June 2013 https://web.archive.org/web/20130925214850/http://www.health.alberta.ca/documents/Guidelines-Paratyphoid-Fever-2013.pdf |
Ulnar nerve entrapment | Ulnar nerve entrapment is a condition where the ulnar nerve becomes physically trapped or pinched, resulting in pain, numbness, or weakness, primarily affecting the little finger and ring finger of the hand. Entrapment may occur at any point from the spine at cervical vertebra C7 to the wrist; the most common point of entrapment is in the elbow (Cubital tunnel syndrome). Prevention is mostly through correct posture and avoiding repetitive or constant strain (e.g. "cell phone elbow"). Treatment is usually conservative, including medication, activity modification, and exercise, but may sometimes include surgery. Prognosis is generally good, with mild to moderate symptoms often resolving spontaneously.
Signs and symptoms
In general, ulnar neuropathy will result in symptoms in a specific anatomic distribution, affecting the little finger, the ulnar half of the ring finger, and the intrinsic muscles of the hand.
The specific symptoms experienced in the characteristic distribution depend on the specific location of ulnar nerve impingement. Symptoms of ulnar neuropathy may be motor, sensory, or both depending on the location of injury. Motor symptoms consistent of muscle weakness; sensory symptoms or paresthesias consist of numbness or tingling in the areas innervated by the ulnar nerve.Proximal impingement is associated with mixed symptoms, as the proximal nerve consists of mixed sensory and motor innervation.
Distal impingement is associated with variable symptoms, as the ulnar nerve separates near the hand into distinct motor and sensory branches.
In cubital tunnel syndrome (a proximal impingement), sensory and motor symptoms tend to occur in a certain sequence. Initially, there may be numbness of the small and ulnar fourth finger which may be transient. If the impingement is not corrected, the numbness may become constant and progress to hand weakness. A characteristic resting hand position of "ulnar claw," where the small and ring fingers curl up, occurs late in the disease and is a sign of severe neuropathy.
By contrast, in Guyons canal syndrome (distal impingement) motor symptoms and claw hand may be more pronounced, a phenomenon known as the ulnar paradox. Also, the back of the hand will have normal sensation.
Diagnosis
The distinct innervation of the hand usually enables diagnosis of an ulnar nerve impingement by symptoms alone. Ulnar nerve damage that causes paralysis to these muscles will result in a characteristic ulnar claw position of the hand at rest. Clinical tests such as the card test for Froments sign, can be easily performed for assessment of ulnar nerve. However, a complete diagnosis should identify the source of the impingement, and radiographic imaging may be necessary to determine or rule-out an underlying cause.Imaging studies, such as ultrasound or MRI, may reveal anatomic abnormalities or masses responsible for the impingement. Additionally, imaging may show secondary signs of nerve damage that further confirm the diagnosis of impingement. Signs of nerve damage include flattening of the nerve, swelling of the nerve proximal to site of injury, abnormal appearance of nerve, or characteristic changes to the muscles innervated by the nerve.
Differential diagnoses
Symptoms of ulnar neuropathy or neuritis do not necessarily indicate an actual physical impingement of the nerve; any injury to the ulnar nerve may result in identical symptoms. In addition, other functional disturbances may result in irritation to the nerve and are not true "impingement". For example, anterior dislocation and "snapping" of ulnar nerve across the medial epicondyle of the elbow joint can result in ulnar neuropathy.Entrapment of other major sensory nerves of the upper extremities result in deficits in other patterns of distribution. Entrapment of the median nerve causes carpal tunnel syndrome, which is characterized by numbness in the thumb, index, middle, and half of the ring finger. Compression of the radial nerve causes numbness of the back of the hand and thumb, and is much rarer.A simple way of differentiating between significant median and ulnar nerve injury is by testing for weakness in flexing and extending certain fingers of the hand. Median nerve injuries are associated with difficulty flexing the index and middle finger when attempting to make a fist. However, with an ulnar nerve lesion, the pinky and ring finger cannot be unflexed when attempting to extend the fingers.Some people are affected by multiple nerve compressions, which can complicate diagnosis.
Classification
Ulnar nerve entrapment is classified by location of entrapment. The ulnar nerve passes through several small spaces as it courses through the medial side of the upper extremity, and at these points the nerve is vulnerable to compression or entrapment—a so-called "pinched nerve". The nerve is particularly vulnerable to injury when there has been a disruption in the normal anatomy. The most common site of ulnar nerve entrapment is at the elbow, followed by the wrist.Causes or structures which have been reported to cause ulnar nerve entrapment include:
Problems originating at the neck: thoracic outlet syndrome, cervical spine pathology, compression by anterior scalene muscles
Problems originating in the chest: compression by pectoralis minor muscles
Brachial plexus abnormalities
Elbow: fractures, growth plate injuries, cubital tunnel syndrome, flexorpronator aponeurosis, arcade of Struthers
Forearm: tight flexor carpi ulnaris muscles
Wrist: fractures, ulnar tunnel syndrome, hypothenar hammer syndrome
Artery aneurysms or thrombosis
Other: Infections, tumors, diabetes, hypothyroidism, rheumatism, and alcoholism
Cubital tunnel syndrome
The most common location of ulnar nerve impingement at the elbow is within the cubital tunnel, and is known as cubital tunnel syndrome. The tunnel is formed by the medial epicondyle of the humerus, the olecranon process of the ulna and the tendinous arch joining the humeral and ulnar heads of the flexor carpi ulnaris muscle. While most cases of injury are minor and resolve spontaneously with time, chronic compression or repetitive trauma may cause more persistent problems. Commonly cited scenarios include:
Sleeping with the arm folded behind neck, elbows bent.
Pressing the elbows upon the arms of a chair while typing.
Resting or bracing the elbow on the arm rest of a vehicle.
Bench pressing.
Intense exercising and strain involving the elbow.Compression of the ulnar nerve at the medial elbow may occasionally be caused by an epitrocheloanconeus muscle, an anatomical variant.
Ulnar tunnel syndrome
Ulnar nerve impingement along an anatomical space in the wrist called the ulnar canal is known as ulnar tunnel syndrome. Recognized causes of ulnar nerve impingement at this location include local trauma, fractures, ganglion cysts, and classically avid cyclists who experience repetitive trauma against bicycle handlebars. This form of ulnar neuropathy comprises two work-related syndromes: so-called "hypothenar hammer syndrome," seen in workers who repetitively use a hammer, and "occupational neuritis" due to hard, repetitive compression against a desk surface.
Prevention
Cubital tunnel syndrome may be prevented or reduced by maintaining good posture and proper use of the elbow and arms, such as wearing an arm splint while sleeping to maintain the arm is in a straight position instead of keeping the elbow tightly bent. A recent example of this is popularization of the concept of cell phone elbow and game hand.
Treatment
The most effective treatment for cubital tunnel syndrome is surgical decompression. The most safe and effective operation is in-situ decompression +/- medial epicondylectomy.For pain symptoms, medications such as NSAID, amitriptyline, or vitamin B6 supplementation may help although there is no evidence to support this claim.Mild symptoms may first be treated non-operatively, with the following:
Elbow joint immobilization in extension at night +/- during the day
Neural flossing/gliding exercises
Strengthening/stretching exercises
Activity modification (e.g. avoidance of pressure on the elbows)It is important to identify positions and activities that aggravate symptoms and to find ways to avoid them. For example, if the person experiences symptoms when holding a telephone up to the head, then the use of a telephone headset will provide immediate symptomatic relief and reduce the likelihood of further damage and inflammation to the nerve. For cubital tunnel syndrome, it is recommended to avoid repetitive elbow flexion and also avoiding prolonged elbow flexion during sleep, as this position puts stress of the ulnar nerve.Cubital tunnel decompression surgery involves an incision posteromedial to the medial epicondyle which helps avoid the medial antebrachial cutaneous nerve branches. The ulnar nerve is identified and released from its fascia proximally and distally up to the flexor carpi ulnaris heads. After release, flexion and extension of the arm are performed to ensure there is no subluxation of the ulnar nerve.
Prognosis
Following surgery, on average, 85% of patients report an improvement in their symptomsMost patients diagnosed with cubital tunnel syndrome have advanced disease (atrophy, static numbness, weakness) that might reflect permanent nerve damage that will not recover after surgery. When diagnosed prior to atrophy, weakness or static numbness, the disease can be arrested with treatment. Mild and intermittent symptoms often resolve spontaneously.
Epidemiology
People with diabetes mellitus are at higher risk for any kind of peripheral neuropathy, including ulnar nerve entrapments.Cubital tunnel syndrome is more common in people who spend long periods of time with their elbows bent, such as when holding a telephone to the head. Flexing the elbow while the arm is pressed against a hard surface, such as leaning against the edge of a table, is a significant risk factor. The use of vibrating tools at work or other causes of repetitive activities increase the risk, including throwing a baseball.Damage to or deformity of the elbow joint increases the risk of cubital tunnel syndrome. Additionally, people who have other nerve entrapments elsewhere in the arm and shoulder are at higher risk for ulnar nerve entrapment. There is some evidence that soft tissue compression of the nerve pathway in the shoulder by a bra strap over many years can cause symptoms of ulnar neuropathy, especially in very large-breasted women.
See also
Cervical Vertebrae
Ulnar neuropathy
References
== External links == |
Epidermolysis bullosa acquisita | Epidermolysis bullosa acquisita, also known as acquired epidermolysis bullosa, is a longterm autoimmune blistering skin disease. It generally presents with fragile skin that blisters and becomes red with or without trauma. Marked scarring is left with thin skin, milia and nail changes. It typically begins around age 50-years.It is caused by antibodies to type VII collagen within anchoring fibril structures located at the dermoepidermal junction in skin. Damaged skin may become infected.Diagnosis is by observing the persistence of the condition, direct immunofluorescence, and detecting autoantibodies against type VII collagen. It can appear similar to porphyria cutanea tarda, pemphigoid, pemphigus, dermatitis herpetiformis, or blistering drug eruption. The condition is longterm and has no cure. A good response may be seen with corticosteroids, either alone or combined with azathioprine or dapsone.It is rare, with around 0.08 to 0.5 new cases per million people per year, and it affects males and females equally.
Signs and symptoms
It generally presents with fragile skin that blisters and becomes red with or without trauma. Marked scarring is left with thin skin, milia and nail changes. It typically begins around age 50-years.
Cause
It is caused by antibodies to type VII collagen within anchoring fibril structures located at the dermoepidermal junction in skin.
Diagnosis
Diagnosis is by observing the persistence of the condition, direct immunofluorescence, and detecting autoantibodies against type VII collagen. It can appear similar to porphyria cutanea tarda, pemphigoid, pemphigus, dermatitis herpetiformis, or blistering drug eruption.
Treatment
The condition is longterm and has no cure. A good response may be seen with corticosteroids, either alone or combined with azathioprine or dapsone.
Epidemiology
It is rare, with around 0.08 to 0.5 new cases per million people per year, and it affects males and females equally.
See also
List of cutaneous conditions
List of target antigens in pemphigoid
List of immunofluorescence findings for autoimmune bullous conditions
List of human leukocyte antigen alleles associated with cutaneous conditions
References
== External links == |
Vascular myelopathy | Vascular myelopathy (vascular disease of the spinal cord) refers to an abnormality of the spinal cord in regard to its blood supply. The blood supply is complicated and supplied by two major vessel groups: the posterior spinal arteries and the anterior spinal arteries—of which the Artery of Adamkiewicz is the largest. Both the posterior and anterior spinal arteries run the entire length of the spinal cord and receive anastomotic (conjoined) vessels in many places. The anterior spinal artery has a less efficient supply of blood and is therefore more susceptible to vascular disease. Whilst atherosclerosis of spinal arteries is rare, necrosis (death of tissue) in the anterior artery can be caused by disease in vessels originating from the segmental arteries such as atheroma (arterial wall swelling) or aortic dissection (a tear in the aorta).
Spinal cord infarction
Anterior spinal artery syndrome
Anterior spinal artery syndrome is necrosis of tissue in the anterior spinal artery or its branches. It is characterised by pain which radiates at onset and sudden quadraplegia (paralysis of all four limbs) or paraplegia (paralysis of the lower body). Within days, flaccid limbs become spastic and hyporeflexia (underactive nerve responses) turns into hyperreflexia (overactive nerve responses) and extensor plantar nerve responses. Sensory loss to pain and temperature also occurs up to the level of damage on the spinal cord, as damage to different areas will affect different parts of the body.In diagnosis, other causes of abrupt paralysis should be excluded such as cord compression, transverse myelitis (inflammation of the spinal cord) and Guillain–Barré syndrome. A specific cause of the infarction should be looked for, such as diabetes, polyarteritis nodosa (inflammatory damage of vessels) or systemic lupus erythematosus. Neurosyphilis is also a known cause. Other causes include:
Treatment is supportive and aims to relieve symptoms. The prognosis is dependent upon individual circumstances and factors.
Posterior spinal artery syndrome
Posterior spinal artery syndrome is much rarer than its anterior counterpart as the white matter structures that are present are much less vulnerable to ischemia since they have a better blood supply. When posterior spinal artery syndrome does occur, dorsal columns are damaged and ischemia may spread into the posterior horns. Clinically the syndrome presents as a loss of tendon reflexes and loss of joint position sense
Transient ischemic attack
Transient ischemic attacks (TIAs) rarely affect the spinal cord and usually affect the brain; however, cases have been documented in these areas. Spinal arteriovenous malformations are the main cause and are represented later in this article. However, TIAs can result from emboli in calcific aortic disease and aortic coarctation.
Spinal arteriovenous malformations
Spinal arteriovenous malformations (AVMs, or angiomatous malformations) are congenital (from birth) abnormalities of blood vessels. Arteries that directly communicate with veins bypass the capillary network (which has not yet developed) and thus creates a shunt. AVMs appear as a mass of convoluted, dilated vessels. In regards to the spinal cord, they are usually located in the thoracolumbar region (between the thoracic and lumbar regions, 60% of the time), as opposed to the upper thoracic (20%) and cervical regions (approximately 15%). Cervical malformations arise from the anterior spinal artery and lie within the cord, whereas thoracolumbar malformations can be internal, external or encompass both areas of the cord.Malformations can be recognised as part of an acute illness or gradual onset disease. In diseases such as subarachnoid hemorrhage, signs and symptoms include headache, neck stiffness and back and leg pain. Extradural, subdural and intramedullary hematomas are all signs of acute cord compression. Gradual onset diseases are more common (85-90% of all diseases leading to a diagnosis of malformation) and are usually due to an increased venous pressure. Other factors such as thrombosis or arachnoiditis can be involved. A bruit (unusual blood sounds) may be heard overlying the spinal arteriovenous malformation. Very occasionally, nevus (moles) or angiolipomas are found.Myelography is used to confirm the diagnosis of AVMs and it shows snake-like vessels on the cords surface. If the myelogram is positive, angiography is required to show the extent of malformation and the exact site of the shunt. Magnetic resonance imaging (MRI) may show the appropriate area. If AVMs are left untreated, 50% of patients with gradual symptoms will be unable to walk within 3 years of onset. Surgical occlusion has been shown to halt the progression and may improve any gait or incontinence.
See also
Foix–Alajouanine syndrome
Chronic cerebrospinal venous insufficiency
Peripheral vascular disease
References
== External links == |
Morvans syndrome | Morvans syndrome is a rare, life-threatening autoimmune disease named after the nineteenth century French physician Augustin Marie Morvan. "La chorée fibrillaire" was first coined by Morvan in 1890 when describing patients with multiple, irregular contractions of the long muscles, cramping, weakness, pruritus, hyperhidrosis, insomnia, and delirium.
It normally presents with a slow insidious onset over months to years.
Approximately 90% of cases spontaneously go into remission, while the other 10% of cases lead to death.In 1890, Morvan described a patient with myokymia (muscle twitching) associated with muscle pain, excessive sweating, and disordered sleep.
This rare disorder is characterized by severe insomnia, amounting to no less than complete lack of sleep (agrypnia) for weeks or months in a row, and associated with autonomic alterations consisting of profuse perspiration with characteristic skin miliaria (also known as sweat rash), tachycardia, increased body temperature, and hypertension. Patients display a remarkable hallucinatory behavior, and peculiar motor disturbances, which Morvan reported under the term “fibrillary chorea” but which are best described in modern terms as neuromyotonic discharges.The association of the disease with thymoma, tumour, autoimmune diseases, and autoantibodies suggests an autoimmune or paraneoplastic aetiology. Besides an immune-mediated etiology, it is also believed to occur in gold, mercury, or manganese poisoning.
Signs and symptoms
In one of the few reported cases, the subject presented with muscle weakness and fatigue, muscle twitching, excessive sweating and salivation, small joint pain, itching and weight loss. The subject also developed confusional episodes with spatial and temporal disorientation, visual and auditory hallucinations, complex behavior during sleep and progressive nocturnal insomnia associated with diurnal drowsiness. There was also severe constipation, urinary incontinence, and excessive lacrimation. When left alone, the subject would slowly lapse into a stuporous state with dreamlike episodes characterized by complex and quasi-purposeful gestures and movements (enacted dreams). Marked hyperhidrosis and excessive salivation were evident. Neurological examination disclosed diffuse muscle twitching and spontaneous and reflex myoclonus, slight muscle atrophy in the limbs, absence of tendon reflexes in the lower limbs and diffuse erythema especially on the trunk with scratching lesions of the skin.
Compulsive behaviours, stereotypies and reduplicative paramnesias can be part of the CNS spectrum.
Insomnia
In all of the reported cases, the need for sleep was severely reduced and in some cases not necessary. The duration of sleep in one case decreased to about 2–4 hours per 24-hour period. Clinical features pertaining to insomnia include daytime drowsiness associated with a loss of ability to sleep, intermingled with confusional oneiric status, and the emergence of atypical REM sleep from wakefulness. The polysomnogram (PSG) picture of this disease is characterized by an inability to generate physiological sleep (key features are the suppression of the hallmarks of stage 2 non-REM sleep: spindles and K complexes) and by the emergence of REM sleep without atonia. The involvement of the thalamus and connected limbic structures in the pathology indicate the prominent role that the limbic thalamus plays in the pathophysiology of sleep. In a case documented in 1974, PSG findings documented the sustained absence of all sleep rhythms for up to a period of 4 months.Electroencephalography (EEG) in one case was dominated by "wakefulness" and “subwakefulness” states alternating or intermingled with short (< 1 min) atypical REM sleep phases, characterized by a loss of muscle atonia. The “subwakefulness” state was characterized by 4–6 Hz theta activity intermingled with fast activity and desynchronized lower voltage theta activity, behaviourally associated with sleep-like somatic and autonomic behavior. The subject was said to have “agrypnia excitata”, which consists of severe total insomnia of long duration associated with decreased vigilance, mental confusion, hallucinations, motor agitation, and complex motor behavior mimicking dreams, and autonomic activation. CNS and autonomic symptoms were caused by impaired corticolimbic control of the subcortical structures regulating the sleep-wake and autonomic functions.
Neuromyotonia
Neuromyotonia refers to muscle twitching and cramping at rest that is exacerbated with exercise. It is caused by sustained or repetitive spontaneous muscle activity of peripheral nerve origin. Myokymia, or spontaneous rippling and twitching movements of muscles, is a visible component of neuromyotonia. Electromyography (EMG) discloses spontaneous, repetitive motor unit or single fiber discharges firing in irregular rhythmic bursts at high intraburst frequencies. Some of the muscles exhibiting twitching include the bilateral gastrocnemii, quadriceps femoris, biceps brachii, and right masseter. In vivo electrophysiological studies suggest at least some dysfunction of the muscle cell membrane. In the examined muscles, no abnormal insertional activity or fibrillation potentials were noted. Nerve conduction studies were normal.
Other symptoms
Breathing difficulties can occur, resulting from neuromyotonic activity of the laryngeal muscles. Laryngeal spasm possibly resulting from neuromyotonia has been described previously, and this highlights that, in patients with unexplained laryngospasm, neuromytonia should be added to the list of differential diagnoses.Studies have shown subtly decreased metabolism on positron emission tomography (PET) and single photon emission computed tomography (SPECT) in the left inferior frontal and left temporal lobes. and or basal ganglia hypermetabolism. Ancillary laboratory tests including MRI and brain biopsy have confirmed temporal lobe involvement. Cranial MRI shows increased signal in the hippocampus.Cerebral spinal fluid (CSF) shows normal protein, glucose, white blood cell, and immunoglobulin G (IgG) levels, but there are weak oligoclonal bands, which are absent in the blood serum. Marked changes in circadian serum levels of neurohormones and increased levels of peripheral neurotransmitters were also observed. The absence of morphological alterations of the brain pathology, the suggestion of diffusion of IgG into the thalamus and striatum, more marked than in the cortex (consistent with effects on the thalamolimbic system) the oligoclonal bands in the CSF and the amelioration after PE all strongly support an antibody-mediated basis for the condition. Raised CSF IgG concentrations and oligoclonal bands have been reported in patients with psychosis. Anti-acetylcholine receptors (anti-AChR) antibodies have also been detected in patients with thymoma, but without clinical manifestations of myasthenia gravis. There have also been reports of non-paraneoplastic limbic encephalitis associated with raised serum VGKC suggesting that these antibodies may give rise to a spectrum of neurological disease presenting with symptoms arising peripherally, centrally, or both. Yet, in two cases, oligoclonal bands were absent in the CSF and serum, and CSF immunoglobulin profiles were unremarkable.
Comorbid conditions
In one case, a patient was diagnosed with both Morvans syndrome and pulmonary hyalinizing granulomas (PHG). PHG are rare fibrosing lesions of the lung, which have central whorled deposits of lamellar collagen. How these two diseases relate to one another is still unclear.Thymoma, prostate adenoma, and in situ carcinoma of the sigmoid colon have also been found in patients with Morvans Syndrome.
Mechanism
Antibodies against voltage-gated potassium channels (VGKC), which are detectable in about 40% of patients with acquired neuromytonia, have been implicated in Morvans pathophysiology. Raised serum levels of antibodies to VGKCs have been reported in three patients with Morvans Syndrome. Binding of serum from a patient with Morvans Syndrome to the hippocampus in a similar pattern of antibodies to known VGKC suggest that these antibodies can also cause CNS dysfunction. Additional antibodies against neuromuscular junction channels and receptors have also been described. Experimental evidence exists that these anti-VGKC antibodies cause nerve hyperexcitability by suppression of voltage gated K+ outward currents, whereas other, yet undefined humoral factors have been implicated in anti-VGKC antibody negative neuromyotonia. It is believed that antibodies to the Shaker-type K+ channels (the Kv1 family) are the type of potassium channel most strongly associated with acquired neuromyotonia and Morvans Syndrome.Whether VGKC antibodies play a pathogenic role in the encephalopathy as they do in the peripheral nervous system is as yet unclear. It has been suggested that the VGKC antibodies may cross the blood–brain barrier and act centrally, binding predominantly to thalamic and striatal neurons causing encephalopathic and autonomic features.
Diagnosis
Differential diagnosis
The symptoms of Morvans Syndrome have been noted to bear a striking similarity to limbic encephalitis (LE). These include the CNS symptoms consisting of insomnia, hallucinations, and disorientation, as well as dementia and psychosis. Both entities can be paraneoplastic and associated with thymoma. Recently, VGKC antibodies were found in patients with LE, strengthening the hypothesis that LE and Morvans Syndrome may be closely connected. Varying symptoms may be used to determine which of the two diseases the subject has. Amnesia, seizures, and mesial temporal lobe structural abnormalities are features of LE, whereas myokymia, hyperhydrosis, and insomnia favor Morvans Syndrome.
Treatment
In most of the reported cases, the treatment options were very similar. Plasmapheresis alone or in combination with steroids, sometimes also with thymectomy and azathioprine, have been the most frequently used therapeutic approach in treating Morvans Syndrome. However, this does not always work, as failed response to steroids and to subsequently added plasmapheresis have been reported. Intravenous immunoglobulin was effective in one case.In one case, the dramatic response to high-dose oral prednisolone together with pulse methylprednisolone with almost complete disappearance of the symptoms within a short period should induce consideration of corticosteroids.In another case, the subject was treated with haloperidol (6 mg/day) with some improvement in the psychomotor agitation and hallucinations, but even high doses of carbamazepine given to the subject failed to improve the spontaneous muscle activity. Plasma Exchange (PE) was initiated, and after the third such session, the itching, sweating, mental disturbances, and complex nocturnal behavior improved and these symptoms completely disappeared after the sixth session, with improvement in insomnia and reduced muscle twitching. However, one month after the sixth PE session, there was a progressive worsening of insomnia and diurnal drowsiness, which promptly disappeared after another two PE sessions.In one case, high dose steroid treatment resulted in a transient improvement, but aggressive immuno-suppressive therapy with cyclophosphamide was necessary to control the disease and result in a dramatic clinical improvement.In another case, the subject was treated with prednisolone (1 mg/kg body weight) with carbamazepine, propranolol, and amitriptyline. After two weeks, improvement with decreased stiffness and spontaneous muscle activity and improved sleep was observed. After another 7–10 days, the abnormal sleep behavior disappeared completely.In another case, symptomatic improvement with plasmapheresis, thymectomy, and chronic immunosuppression provide further support for an autoimmune or paraneoplastic basis.Although thymectomy is believed to be a key element in the proposed treatment, there is a reported case of Morvans Syndrome presenting itself post-thymectomy.
Epidemiology
There are only about 14 reported cases of Morvans syndrome in the English literature. With only a limited number of reported cases, the complete spectrum of the central nervous system (CNS) symptomatology has not been well established. The natural history of Morvans is highly variable. Two cases have been reported to remit spontaneously. Others have required a combination of plasmapheresis and long term immunosuppression, although in one of these cases the patient died shortly after receiving plasma exchange (PE). Other fatalities without remission have been described by, amongst others, Morvan himself.
References
== External links == |
Calcific tendinitis | Calcific tendinitis is a common condition where calcium deposits form in a tendon, sometimes causing pain at the affected site. Deposits can occur in several places in the body, but are by far most common in the rotator cuff of the shoulder. Around 80% of those with deposits experience symptoms, typically chronic pain during certain shoulder movements, or sharp acute pain that worsens at night. Calcific tendinitis is typically diagnosed by physical exam and X-ray imaging. The disease often resolves completely on its own, but is typically treated with non-steroidal anti-inflammatory drugs to relieve pain, rest and physical therapy to promote healing, and in some cases various procedures to breakdown and/or remove the calcium deposits.
Adults aged 30–50 are most commonly affected by calcific tendinitis. It is twice as common in women as men, and is not associated with exercise. Calcifications in the rotator cuff were first described by Ernest Codman in 1934. The name, "calcifying tendinitis" was coined by Henry Plenk in 1952.
Signs and symptoms
Up to 20% of those with calcific tendinitis have no symptoms. For those with symptoms, the symptoms vary based on the phase of the disease. In the initial "formative phase" when the calcium deposits are being formed, people rarely experience any symptoms. Those that do have symptoms tend to have intermittent shoulder pain, particularly during forward should flexion (i.e. lifting the arm in front of the body). In the "resorptive phase" when the calcium deposit is breaking down, many experience severe acute pain that worsens at night. Those affected tend to hold the shoulder rotated inwards to alleviate pain, and have difficulty lying on the affected shoulder. Some people experience heat and redness at the affected shoulder, as well as a limited range of motion.
Cause
Calcific tendinitis is caused by deposits of calcium phosphate crystals in the tendons of the shoulder. These deposits are most frequently found in the supraspinatus tendon (63% of the time), and less frequently in the infraspinatus tendon (7%), subacromial bursa (7%), subscapularis tendon (3%), or in both the supraspinatus and subscapularis tendons at the same time (20%).The development of calcific tendinitis is often divided into three stages. First, in the "precalcific stage", something causes tendon cells to transform into other cells that can act as sites for calcium deposition. This is followed by the two-part "calcific stage"; first calcium is deposited (the formative phase), then the body begins to break down the calcium deposit (the resporptive phase). Finally, in the "postcalcific stage" the calcium deposits are replaced with new tissue and the tendon completely heals.The cause of the calcium deposits remains unclear, although several theories have been put forward. Some theories involve the differentiation of tendon cells into other cells, namely cartilages or bone cells. Others associate the condition with cell death due to aging, wear, or lack of oxygen in the tissue; however, the disease is uncommon in the very old, not associated with exercise, and tends to resolve completely even if untreated.
Diagnosis
Calcific tendinitis is typically diagnosed by physical examination and X-ray imaging. During the formative phase, X-ray images typically reveal calcium deposits with uniform density and a clear margin. In the more painful resorptive phase, deposits instead appear cloudy and with unclear margins. By arthroscopy, formative stage deposits appear crystalline and chalk-like, while resorptive stage deposits appear smooth resembling toothpaste. Ultrasound is also used to locate and assess calcium deposits. In the formative stage, deposits are hyperechoic and arc-shaped; in the resorptive stage deposits are less echogenic and appear fragmented.
Treatment
The first line of treatment for calcific tendinitis is typically nonsteroidal anti-inflammatory drugs to relieve pain, rest for the affected joint, and sometimes physical therapy to avoid joint stiffness. For those with severe pain direct injections of steroids to the affected site are often effective for pain relief, but may interfere with reabsorption of the calcium deposit. For those whose pain doesnt improve with medication and rest, the deposit can be dissolved and removed with techniques called "ultrasound-guided needling", "barbotage", and "US-PICT" (for "ultrasound percutaneous injection in calcific tenditis"). In each, ultrasound is used to locate the deposit and guide a needle to the affected site. There saline and lidocaine are injected to dissolve the deposit, then removed to wash it away. Another common treatment is extracorporeal shockwave therapy, where pulses of sound are used to break up the deposit and promote healing. There is little standardization of energy levels, duration, and time interval of treatment; though most studies report positive outcomes with low- to medium-energy waves (below 0.28 mJ/mm2).
Surgery
Surgery is only recommended once 6 months of conservative, non-operative treatment has failed to reduce symptoms. Surgery is arthroscopic and involves calcification removal with or without acromioplasty of the shoulder. Additionally, debate remains over whether a complete removal of the deposits is necessary, or if equal pain relief can be obtained from a partial removal of calcium deposits.Removing the deposits either with open shoulder surgery or arthroscopic surgery are both difficult operations, but with high success rates (around 90%). About 10% require re-operation. If the deposit is large, then frequently the patient will require a rotator cuff repair to fix the defect left in the tendon when the deposit is removed or to reattach the tendon to the bone if the deposit was at the tendon insertion into the bone.
Outcomes
Nearly all people with calcific tendinitis recover completely with time or treatment. Treatment helps alleviate pain, but long-term follow-up studies have shown that people recover with or without treatment.
Epidemiology
Calcific tendinitis typically occurs in adults aged 30 to 50, and is rare in those older than 70. It is twice as common in women as men.Risk factors that increase the chance of developing calcific tendinitis include; hormonal disorders, like diabetes and hypothyroidism, autoimmune disorders, like rheumatoid arthritis, and metabolic disorders that also cause kidney stones, gallstones, and gout. Occupations that consist of repetitive overhead lifting, such as athletes or construction workers, do not seem to significantly increase the likelihood of developing calcific tendinitis.
History
Calcifications in the rotator cuff tendon were first described by Ernest Codman in his 1934 book The Shoulder. In 1952, in his study on x-ray therapy for people with such calcifications, Henry Plenk coined the term "calcifying tendinitis".
References
External links
eMedicine on Calcific Tendonitis
Extracorporeal shock wave therapy (subscription required) |
Post-kala-azar dermal leishmaniasis | Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL); it is characterised by a macular, maculopapular, and nodular rash in a patient who has recovered from VL and who is otherwise well. The rash usually starts around the mouth from where it spreads to other parts of the body depending on severity.
Post-kala-azar dermal leishmaniasis (also known as "Post-kala-azar dermatosis") found mainly on the face, arms, and upper part of the trunk. It occurs years (in the Indian variation) or a few months(in the African strain) after the successful treatment of visceral leishmaniasis.
It is mainly seen in Sudan and India where it follows treated VL in 50% and 5-10% of cases, respectively. Thus, it is largely restricted to areas where Leishmania donovani is the causative parasite. The interval at which PKDL follows VL is 0–6 months in Sudan and 2–3 years in India. PKDL probably has an important role in interepidemic periods of VL, acting as a reservoir for parasites.
PKDL was first identified by Sir Upendranath Brahmachari, who initially called it dermal leishmanoid. He published his observations in the Indian Medical Gazette in 1922.
Mechanism
The cause of PKDL is uncertain. Possibilities may include use of antimonial drugs, sunburn, reinfection with kala-azar, memory T cell responses failing in certain organs; and genetic susceptibility.There is increasing evidence that the pathogenesis is largely immunologically mediated; high concentrations of interleukin 10 in the peripheral blood of VL patients predict the development of PKDL. During VL, interferon gamma is not produced by peripheral blood mononuclear cells (PBMC). After treatment of VL, PBMCs start producing interferon gamma, which coincides with the appearance of PKDL lesions due to interferon-gamma-producing cells causing skin inflammation as a reaction to persisting parasites in the skin.
Diagnosis
PKDL is difficult to diagnose.Diagnosis is mainly clinical, but parasites can be seen by microscopy in smears with limited sensitivity. PCR and monoclonal antibodies may detect parasites in more than 80% of cases. Serological tests and the leishmanin skin test are of limited value.
Treatment
Treatment is always needed in Indian PKDL; in Sudan, most cases are self-limited but severe and chronic cases are treated. Sodium stibogluconate is given at 20 mg/kg for 2 months in Sudan and for 4 months in India. Liposomal amphotericine B seems effective. Although research has brought many new insights in pathogenesis and management of PKDL, several issues in particular in relation to control remain unsolved and deserve urgent attention.Miltefosine is the only available oral medication available for VL and PKDL. While the drug works for short-term treatment of VL, PKDL would require a longer treatment of more than 28 days with this drug. Miltefosine is not recommended for use as a monotherapy to treat PKDL.
Society and culture
People with PKDL are a reservoir of leishmaniasis. To eliminate leishmaniasis from a population, people with PKDL must get treatment.The government of India has an kala-azar elimination program ongoing which entered a consolidation phase in 2017.
See also
List of cutaneous conditions
== References == |
Fordyce spots | Fordyce spots (also termed Fordyce granules) are visible sebaceous glands that are present in most individuals. They appear on the genitals and/or on the face and in the mouth. They appear as small, painless, raised, pale, red or white spots or bumps 1 to 3 mm in diameter that may appear on the scrotum, shaft of the penis or on the labia, as well as the inner surface (retromolar mucosa) and vermilion border of the lips of the face. They are not associated with any disease or illness, nor are they infectious but rather they represent a natural occurrence on the body. No treatment is therefore required. Persons with this condition sometimes consult a dermatologist because they are worried they may have a sexually transmitted disease (especially genital warts) or some form of cancer.Some diseases may appear similar to Fordyce spots such as sexually transmitted diseases.
Description
On the shaft of the penis, Fordyce spots are more visible when the skin is stretched, and may only be noticeable during an erection. The spots can also appear on the skin of the scrotum.Oral Fordyce granules appear as rice-like granules, white or yellow-white in color. They are painless papules (small bumps), about 1–3 mm in greatest dimension. The most common site is along the line between the vermilion border and the oral mucosa of the upper lip, or on the buccal mucosa (inside the cheeks) in the commissural region, often bilaterally. They may also occur on the mandibular retromolar pad and tonsillar areas, but any oral surface may be involved. There is no surrounding mucosal change. Some patients will have hundreds of granules while most have only one or two.Occasionally, several adjacent glands will coalesce into a larger cauliflower-like cluster similar to sebaceous hyperplasia of the skin. In such an instance, it may be difficult to determine whether or not to diagnose the lesion as sebaceous hyperplasia or sebaceous adenoma. The distinction may be moot because both entities have the same treatment, although the adenoma has a greater growth potential. Sebaceous carcinoma of the oral cavity has been reported, presumably arising from Fordyce granules or hyperplastic foci of sebaceous glands.In some persons with Fordyce spots, the glands express a thick, chalky discharge when squeezed.
Causes
Normally, sebaceous glands are only found in association with a hair follicle.They appear to be more obvious in people with oily skin types, with some rheumatic disorders, and in hereditary nonpolyposis colorectal cancer. In the latter, the most common site for Fordyce spots is the lower gingiva (gums) and vestibular mucosa.
Diagnosis
Large numbers of lobules coalescing into a definitely elevated mass may be called benign sebaceous hyperplasia, and occasional small keratin-filled pseudocysts may be seen and must be differentiated from epidermoid cyst or dermoid cyst with sebaceous adnexa. The pathologist must be careful to differentiate such lesions from salivary neoplasms with sebaceous cells, such as sebaceous lymphadenoma and sebaceous carcinoma.
Oral Fordyce granules are usually not biopsied because they are readily diagnosed clinically, but they are often seen as incidental findings of mucosal biopsies of the buccal, labial and retromolar mucosa. The granules are similar to normal sebaceous glands of the skin but lack hair follicles and almost always lack a ductal communication with the surface. The glands are located just beneath the overlying epithelium and often produce a local elevation of the epithelium. Individual sebaceous cells are large, with central dark nuclei and abundant foamy cytoplasm.
Classification
Sebaceous glands are normal structures of the skin but may also be found ectopically in the mouth, where they are referred to as oral Fordyce granules or ectopic sebaceous glands.
On the foreskin they are called Tysons glands, not to be confused with hirsuties coronae glandis.When they appear on the penis, they are also called penile sebaceous glands.
Treatment
Most doctors consider this a normal physiological phenomenon and advise against treatment.
Prognosis
Fordyce spots are completely benign and require no treatment. They occur in 70 to 80 percent of adults. Often their presence is considered normal anatomic variance rather than a true medical condition.
Epidemiology
This variation of normal anatomy is seen in the majority of adults. It is estimated about 80% of people have oral Fordyce spots, but seldom are granules found in large numbers. They are not usually visible in children, and tend to appear at about age 3, then increasing during puberty and become more obvious in later adulthood. They are more prominent in males.
History
They are named after an American dermatologist, John Addison Fordyce.
References
External links
DermAtlas: Fordyce spots
Fordyce spots |
Linear focal elastosis | Linear focal elastosis or elastotic striae is a skin condition that presents with asymptomatic, palpable or atrophic, yellow lines of the middle and lower back, thighs, arms and breasts.
See also
Skin lesion
References
== External links == |
Phalanx bone | The phalanges (singular: phalanx ) are digital bones in the hands and feet of most vertebrates. In primates, the thumbs and big toes have two phalanges while the other digits have three phalanges. The phalanges are classed as long bones.
Structure
The phalanges are the bones that make up the fingers of the hand and the toes of the foot. There are 56 phalanges in the human body, with fourteen on each hand and foot. Three phalanges are present on each finger and toe, with the exception of the thumb and large toe, which possess only two. The middle and far phalanges of the fourth and fifth toes are often fused together (symphalangism). The phalanges of the hand are commonly known as the finger bones. The phalanges of the foot differ from the hand in that they are often shorter and more compressed, especially in the proximal phalanges, those closest to the torso.A phalanx is named according to whether it is proximal, middle, or distal and its associated finger or toe. The proximal phalanges are those that are closest to the hand or foot. In the hand, the prominent, knobby ends of the phalanges are known as knuckles. The proximal phalanges join with the metacarpals of the hand or metatarsals of the foot at the metacarpophalangeal joint or metatarsophalangeal joint. The intermediate phalanx is not only intermediate in location, but usually also in size. The thumb and large toe do not possess a middle phalanx. The distal phalanges are the bones at the tips of the fingers or toes. The proximal, intermediate, and distal phalanges articulate with one another through interphalangeal joints of hand and interphalangeal joints of the foot.: 708–711 : 708–711
Bone anatomy
Each phalanx consists of a central part, called the body, and two extremities.
The body is flat on either side, concave on the palmar surface, and convex on the dorsal surface. Its sides are marked with rough areas giving attachment to fibrous sheaths of flexor tendons. It tapers from above downwards.
The proximal extremities of the bones of the first row present oval, concave articular surfaces, broader from side to side than from front to back. The proximal extremity of each of the bones of the second and third rows presents a double concavity separated by a median ridge.
The distal extremities are smaller than the proximal, and each ends in two condyles (knuckles) separated by a shallow groove; the articular surface extends farther on the palmar than on the dorsal surface, a condition best marked in the bones of the first row.In the foot, the proximal phalanges have a body that is compressed from side to side, convex above, and concave below. The base is concave, and the head presents a trochlear surface for articulation with the second phalanx. The middle are remarkably small and short, but rather broader than the proximal. The distal phalanges, as compared with the distal phalanges of the finger, are smaller and are flattened from above downward; each presents a broad base for articulation with the corresponding bone of the second row, and an expanded distal extremity for the support of the nail and end of the toe.
Distal phalanx
In the hand, the distal phalanges are flat on their palmar surface, small, and with a roughened, elevated surface of horseshoe form on the palmar surface, supporting the finger pulp.: 6b. 3. The Phalanges of the Hand The flat, wide expansions found at the tips of the distal phalanges are called apical tufts. They support the fingertip pads and nails. The phalanx of the thumb has a pronounced insertion for the flexor pollicis longus (asymmetric towards the radial side), an ungual fossa, and a pair of unequal ungual spines (the ulnar being more prominent). This asymmetry is necessary to ensure that the thumb pulp is always facing the pulps of the other digits, an osteological configuration which provides the maximum contact surface with held objects.In the foot, the distal phalanges are flat on their dorsal surface. It is largest proximally and tapers to the distal end. The proximal part of the phalanx presents a broad base for articulation with the middle phalanx, and an expanded distal extremity for the support of the nail and end of the toe.: 6b. 3. The Phalanges of the Foot The phalanx ends in a crescent-shaped rough cap of bone epiphysis — the apical tuft (or ungual tuberosity/process) which covers a larger portion of the phalanx on the volar side than on the dorsal side. Two lateral ungual spines project proximally from the apical tuft. Near the base of the shaft are two lateral tubercles. Between these a V-shaped ridge extending proximally serves for the insertion of the flexor pollicis longus. Another ridge at the base serves for the insertion of the extensor aponeurosis. The flexor insertion is sided by two fossae — the ungual fossa distally and the proximopalmar fossa proximally.
Development
The number of phalanges in animals is often expressed as a "phalangeal formula" that indicates the numbers of phalanges in digits, beginning from the innermost medial or proximal. For example, humans have a 2-3-3-3-3 formula for the hand, meaning that the thumb has two phalanges, whilst the other fingers each have three.
In the distal phalanges of the hand the centres for the bodies appear at the distal extremities of the phalanges, instead of at the middle of the bodies, as in the other phalanges. Moreover, of all the bones of the hand, the distal phalanges are the first to ossify.: 6b. 3. The Phalanges of the Hand
Function
The distal phalanges of ungulates carry and shape nails and claws and these in primates are referred to as the ungual phalanges.
History of phalanges
Etymology
The term phalanx or phalanges refers to an ancient Greek army formation in which soldiers stand side by side, several rows deep, like an arrangement of fingers or toes.
In animals
Most land mammals including humans have a 2-3-3-3-3 formula in both the hands (or paws) and feet. Primitive reptiles usually had the formula 2-3-4-4-5, and this pattern, with some modification, remained in many later reptiles and in the mammal-like reptiles. The phalangeal formula in the flippers of cetaceans (marine mammals) varies widely due to hyperphalangy (the increase in number of phalanx bones in the digits). In humpback whales, for example, the phalangeal formula is 0/2/7/7/3; in pilot whales the formula is 1/10/7/2/1.In vertebrates, proximal phalanges have a similar placement in the corresponding limbs, be they paw, wing or fin. In many species, they are the longest and thickest phalanx ("finger" bone). The middle phalanx also a corresponding place in their limbs, whether they be paw, wing, hoof or fin.
The distal phalanges are cone-shaped in most mammals, including most primates, but relatively wide and flat in humans.
Primates
The morphology of the distal phalanges of human thumbs closely reflects an adaptation for a refined precision grip with pad-to-pad contact. This has traditionally been associated with the advent of stone tool-making. However, the intrinsic hand proportions of australopiths and the resemblance between human hands and the short hands of Miocene apes, suggest that human hand proportions are largely plesiomorphic (as found in ancestral species) — in contrast to the derived elongated hand pattern and poorly developed thumb musculature of other extant hominoids.In Neanderthals, the apical tufts were expanded and more robust than in modern and early upper Paleolithic humans. A proposal that Neanderthal distal phalanges was an adaptation to colder climate (than in Africa) is not supported by a recent comparison showing that in hominins, cold-adapted populations possessed smaller apical tufts than do warm-adapted populations.
In non-human, living primates the apical tufts vary in size, but they are never larger than in humans. Enlarged apical tufts, to the extent they actually reflect expanded digital pulps, may have played a significant role in enhancing friction between the hand and held objects during Neolithic toolmaking.Among non-human primates phylogenesis and style of locomotion appear to play a role in apical tuft size. Suspensory primates and New World monkeys have the smallest apical tufts, while terrestrial quadrupeds and Strepsirrhines have the largest.
A study of the fingertip morphology of four small-bodied New World monkey species, indicated a correlation between increasing small-branch foraging and reduced flexor and extensor tubercles in distal phalanges and broadened distal parts of distal phalanges, coupled with expanded apical pads and developed epidermal ridges. This suggests that widened distal phalanges were developed in arboreal primates, rather than in quadrupedal terrestrial primates.
Cetaceans
Whales exhibit hyperphalangy. Hyperphalangy is an increase in the number of phalanges beyond the plesiomorphic mammal condition of three phalanges-per-digit. Hyperphalangy was present among extinct marine reptiles -- ichthyosaurs, plesiosaurs, and mosasaurs -- but not other marine mammals, leaving whales as the only marine mammals to develop this characteristic. The evolutionary process continued over time, and a very derived form of hyperphalangy, with six or more phalanges per digit, evolved convergently in rorqual whales and oceanic dolphins, and was likely associated with another wave of signaling within the interdigital tissues.
Other mammals
In ungulates (hoofed mammals) the forelimb is optimized for speed and endurance by a combination of length of stride and rapid step; the proximal forelimb segments are short with large muscles, while the distal segments are elongated with less musculature. In two of the major groups of ungulates, odd-toed and even-toed ungulates, what remain of the "hands" — the metacarpal and phalangeal bones — are elongated to the extent that they serve little use beyond locomotion. The giraffe, the largest even-toed ungulate, has large terminal phalanges and fused metacarpal bones able to absorb the stress from running.The sloth spends its life hanging upside-down from branches, and has highly specialized third and fourth digits for the purpose. They have short and squat proximal phalanges with much longer terminal phalanges. They have vestigial second and fifth metacarpals, and their palm extends to the distal interphalangeal joints. The arboreal specialization of these terminal phalanges makes it impossible for the sloth to walk on the ground where the animal has to drag its body with its claws.
Additional images
See also
Hand
Foot
References
External links
MedTerms.com Medical Dictionary |
Irregular sleep–wake rhythm | Irregular sleep–wake rhythm (ISWD) is a rare form of circadian rhythm sleep disorder. It is characterized by numerous naps throughout the 24-hour period, no main nighttime sleep episode, and irregularity from day to day. Affected individuals have no pattern of when they are awake or asleep, may have poor quality sleep, and often may be very sleepy while they are awake.
The total time asleep per 24 hours is normal for the persons age. The disorder is serious—an invisible disability. It can create social, familial, and work problems, making it hard for a person to maintain relationships and responsibilities, and may make a person home-bound and isolated.
Causes
ISWD has various causes, including neurological disorders such as dementia (particularly Alzheimers Disease), brain damage, or intellectual disabilities. It is thought that those affected have a weak circadian clock. The risk for the disorder increases with age, but only due to increased prevalence of co-morbid medical disorders.
Diagnosis
A sleep diary should be kept to aid in diagnosis and for chronicling the sleep schedule during treatment. Other ways to monitor the sleep schedule are actigraphy or use of a Continuous Positive Airway Pressure (CPAP) machine that can log sleeping times
The following are possible warning signs:
sleeping off and on in a series of naps during the day and at night, with no regular pattern but with normal total sleep time,
difficulty getting restorative sleep, and
excessive daytime sleepiness.Because of the changes in sleep/wake time, and because this is a rare disorder, initially it can seem like another circadian rhythm sleep disorder such as non-24-hour sleep–wake disorder or like insomnia.
Initial visit with sleep physician
A physician specializing in sleep medicine may ask patients about their medical history; for example: neurological problems, prescription or non-prescription medications taken, alcohol use, family history, and any other sleep problems. A thorough medical and neurological exam is indicated. The patient will be asked to complete a sleep diary, recording natural sleep and wake up times, over several weeks. Sleep rating with the Epworth Sleepiness Scale may be used.
Medical testing
A neurological condition or another medical problem may be suspected, in which case, blood tests, a CT scan or an MRI may be used. An overnight sleep study is usually not needed to detect this disorder, but may be indicated if other sleep disorders, such as sleep apnea and periodic limb movement disorder, seem likely. The overnight sleep study is called polysomnography. It charts brain waves, heart beat, muscle activity, and breathing during sleep. It also records arm and leg movement. It will show if there are other sleep disorders that are causing or increasing the problems with ISWD.
Management
Treatment for irregular sleep–wake rhythm tries to enable the body clock in the brain, such that a normal long sleep period at night can be achieved. Education about sleep hygiene is important, and counseling can be helpful. Melatonin, vitamin B12, sleep aids, wake aids, and other medications may also be used. Exposure to light during the daytime and activities occurring at regular times each day may help to restore a normal rhythm.The management of this disorder may vary for different subgroups of patients. Affected individuals with dementia should not be prescribed sleep-promoting medications (sedatives) for ISWD due to the increased prevalence of adverse effects in this group outweighing the possible benefits.
Research
There is currently a great deal of active research on various aspects of circadian rhythm; this often occurs at major universities in conjunction with sleep research clinics at major hospitals. An example is the program with Harvard Medical School and Brigham and Womens Hospital. This research includes programs that are staffed by researchers from various departments at the university, including psychiatry, neurology, chemistry, biology. Other major sleep research centers are in Tel Aviv in Israel, Munich in Germany and in Japan.A wide variety of sleep disorders are actively being researched. Measuring body temperature or melatonin levels may be used. Some hospitals do blood tests for melatonin levels. Saliva tests for melatonin are now available for online purchase; its metabolites can also be tested in urine.
Nomenclature
The current formally correct name of the disorder is Circadian Rhythm Sleep Disorder: Irregular Sleep Wake Rhythm Type. This disorder has been referred to by many other terms, including: Irregular Sleep Wake Pattern, irregular sleep wake syndrome, Irregular Sleep Wake Rhythm (ISWRD), Irregular Sleep Wake Cycle, Irregular Sleep Wake Schedule and Irregular Sleep Wake Disorder (ISWD). Sometimes the words sleep and wake are hyphenated (sleep-wake), sometimes joined with an en dash (sleep–wake) and sometimes open (sleep wake). Sometimes the words are capitalized and sometimes they are not.
See also
Advanced sleep phase syndrome
Chronobiology
Circadian rhythm
Delayed sleep phase disorder
References
== External links == |
Fistula | A fistula (plural: fistulas or fistulae ; from Latin fistula, "tube, pipe") in anatomy is an abnormal connection between two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other hollow organs. Types of fistula can be described by their location. Anal fistulas connect between the anal canal and the perianal skin. Anovaginal or rectovaginal fistulas occur when a hole develops between the anus or rectum and the vagina. Colovaginal fistulas occur between the colon and the vagina. Urinary tract fistulas are abnormal openings within the urinary tract or an abnormal connection between the urinary tract and another organ such as between the bladder and the uterus in a vesicouterine fistula, between the bladder and the vagina in a vesicovaginal fistula, and between the urethra and the vagina in urethrovaginal fistula. When occurring between two parts of the intestine, it is known as an enteroenteral fistula, between the small intestine and the skin as an enterocutaneous fistula, and between the colon and the skin as a colocutaneous fistula.Fistulas can result from an infection or inflammation, injury or surgery. Fistulas are sometimes surgically created as part of a treatment, for example arteriovenous fistulas for hemodialysis.Treatment for fistula varies depending on the cause and extent of the fistula, but often involves surgical intervention combined with antibiotic therapy. In some cases the fistula is temporarily covered using a fibrin glue or plug. Catheters may be required to drain a fistula.Globally, every year between 50,000 and 100,000 women are affected by fistula relating to childbirth. In botany, the term is most common in its adjectival forms, where it is used in binomial names to refer to species that are distinguished by hollow or tubular structures. Monarda fistulosa, for example, has tubular flowers. The term was first used in the 14th century.
Definition
A fistula is an abnormal connection between vessels or organs that do not usually connect. It can be due to a disease or trauma, or purposely surgically created.
Classification
Various types of fistulas include:
Blind: Only one open end; may also be called sinus tracts.
Complete: Both internal and external openings.
Incomplete: An external skin opening that does not connect to any internal organ.Although most fistulas are in forms of a tube, some can also have multiple branches.
Location
Types of fistula can be described by their location. Anal fistulas connect between the epithelialized surface of the anal canal and the perianal skin. Anovaginal or rectovaginal fistulas occur when a hole develops between the anus or rectum and the vagina. Colovaginal fistulas occur between the colon and the vagina. Urinary tract fistulas are abnormal openings within the urinary tract or an abnormal connection between the urinary tract and another organ such as between the bladder and the uterus in a vesicouterine fistula, between the bladder and the vagina in a vesicovaginal fistula, and between the urethra and the vagina in urethrovaginal fistula. When occurring between two parts of the intestine, it is known as an enteroenteral fistula, between the small intestine and the skin as an enterocutaneous fistula, and between the small intestine and the colon as a colocutaneous fistula.The following list is sorted by the International Statistical Classification of Diseases and Related Health Problems.
H: Diseases of the eye, adnexa, ear, and mastoid process
(H04.6) Lacrimal fistula
(H05.81) Carotid cavernous fistula
(H70.1) Mastoid fistula
Craniosinus fistula: between the intracranial space and a paranasal sinus
(H83.1) Labyrinthine fistula
Perilymph fistula: tear between the membranes between the middle and inner ears
Preauricular fistula
Preauricular fistula: usually on the top of the cristae helicis of the ears
I: Diseases of the circulatory system
(I25.4) Coronary arteriovenous fistula, acquired
(I28.0) Arteriovenous fistula of pulmonary vessels
Pulmonary arteriovenous fistula: between an artery and vein of the lungs, resulting in shunting of blood. This results in improperly oxygenated blood.
(I67.1) Cerebral arteriovenous fistula, acquired
(I77.0) Arteriovenous fistula, acquired
(I77.2) Fistula of artery
J: Diseases of the respiratory system
(J86.0) Pyothorax with fistula
(J95.0) Tracheoesophageal fistula, between the trachea and the esophagus. This may be congenital or acquired, for example as a complication of a tracheostomy.
K: Diseases of the digestive system
(K11.4) Salivary gland fistula
(K31.6) Fistula of stomach and duodenum
(K31.6) Gastrocolic fistula
(K31.6) Gastrojejunocolic fistula – after a Billroth II a fistula forms between the transverse colon and the upper jejunum (which, post Billroth II, is attached to the remainder of the stomach). Fecal matter passes improperly from the colon to the stomach and causes halitosis.
Enterocutaneous fistula: between the intestine and the skin surface, namely from the duodenum or the jejunum or the ileum. This definition excludes the fistulas arising from the colon or the appendix.
Gastric fistula: from the stomach to the skin surface
(K38.3) Fistula of appendix
(K60) Anal and rectal fissures and fistulas
(K60.3) Anal fistula
(K60.5) Anorectal fistula (fecal fistula, fistula-in-ano): connecting the rectum or other anorectal area to the skin surface. This results in abnormal discharge of feces through an opening other than the anus.
(K63.2) Fistula of intestine
Enteroenteral fistula: between two parts of the intestine
(K82.3) Fistula of gallbladder
(K83.3) Fistula of bile duct
Biliary fistula: connecting the bile ducts to the skin surface, often caused by gallbladder surgery
Pancreatic fistula: between the pancreas and the exterior via the abdominal wall
M: Diseases of the musculoskeletal system and connective tissue
(M25.1) Fistula of joint
N: Diseases of the urogenital system
(N32.1) Vesicointestinal fistula
(N36.0) Urethral fistula
Innora:between the prostatic utricle and the outside of the body
(N64.0) Fistula of nipple
(N82) Fistulae involving female genital tract / Obstetric fistula
(N82.0) Vesicovaginal fistula: between the bladder and the vagina
(N82.1) Other female urinary-genital tract fistulae
Cervical fistula: abnormal opening in the cervix
(N82.2) Fistula of vagina to small intestine
Enterovaginal fistula: between the intestine and the vagina
(N82.3) Fistula of vagina to large intestine
Rectovaginal: between the rectum and the vagina
(N82.4) Other female intestinal-genital tract fistulae
(N82.5) Female genital tract-skin fistulae
(N82.8) Other female genital tract fistulae
(N82.9) Female genital tract fistula, unspecified
Q: Congenital malformations, deformations and chromosomal abnormalities
(Q18.0) Sinus, fistula and cyst of branchial cleft
Congenital preauricular fistula: A small pit in front of the ear. Also known as an ear pit or preauricular sinus.
(Q26.6) Portal vein-hepatic artery fistula
(Q38.0) Congenital fistula of lip
(Q38.4) Congenital fistula of salivary gland
(Q42.0) Congenital absence, atresia and stenosis of rectum with fistula
(Q42.2) Congenital absence, atresia and stenosis of anus with fistula
(Q43.6) Congenital fistula of rectum and anus
(Q51.7) Congenital fistulae between uterus and digestive and urinary tracts
(Q52.2) Congenital rectovaginal fistula
T: External causes
(T14.5) Traumatic arteriovenous fistula
(T81.8) Persistent postoperative fistula
Causes
Disease: Infections including an anorectal abscess and inflammatory diseases including Crohns disease and ulcerative colitis can result in fistulas. Fistulas to the anus may occur in hidradenitis suppurativa. In women, fistulas can also occur following pelvic infection and inflammation.
Surgical and medical treatment: Complications from gallbladder surgery can lead to biliary fistulas. As well as being congenital or resulting from trauma, arteriovenous fistulas are created purposefully for hemodialysis. Radiation therapy to the pelvis can lead to vesicovaginal fistulas. Persistent gastrocutenaous fistulas can develop after gastrostomy.
Trauma: Prolonged childbirth can lead to fistulas in women, in whom abnormal connections may occur between the bladder and vagina, or the rectum and vagina. An obstetric fistula develops when blood supply to the tissues of the vagina and the bladder (and/or rectum) is cut off during prolonged obstructed labor. The tissues die and a hole forms through which urine and/or feces pass uncontrollably. Vesicovaginal and rectovaginal fistulas may also be caused by rape, in particular gang rape, and rape with foreign objects, as evidenced by the abnormally high number of women in conflict areas who have developed fistulae. In 2003, thousands of women in eastern Congo presented themselves for treatment of traumatic fistulas caused by systematic, violent gang rape, often also with sharp objects that occurred during the countrys five years of war. So many cases have been reported that the destruction of the vagina is considered a war injury and recorded by doctors as a crime of combat. Head trauma can lead to perilymph fistulas, whereas trauma to other parts of the body can cause arteriovenous fistulas.
Treatment
Treatment for fistula varies depending on the cause and extent of the fistula, but often involves surgical intervention combined with antibiotic therapy. In some cases the fistula is temporarily covered, using a fibrin glue or plug. Catheters may be required to drain a fistula.Surgery is often required to assure adequate drainage of the fistula (so that pus may escape without forming an abscess). Various surgical procedures are used, most commonly fistulotomy, placement of a seton (a cord that is passed through the path of the fistula to keep it open for draining), or an endorectal flap procedure (where healthy tissue is pulled over the internal side of the fistula to keep feces or other material from reinfecting the channel).Management involves treating any underlying causative condition. For example, surgical treatment of fistulae in Crohns disease can be effective, but if the Crohns disease itself is not treated, the rate of recurrence of the fistula is very high (well above 50%).
Therapeutic use
In people with kidney failure, requiring dialysis, a cimino fistula is often deliberately created in the arm by means of a short day surgery in order to permit easier withdrawal of blood for hemodialysis.As a radical treatment for portal hypertension, surgical creation of a portacaval fistula produces an anastomosis between the hepatic portal vein and the inferior vena cava across the omental foramen (of Winslow). This spares the portal venous system from high pressure which can cause esophageal varices, caput medusae, and hemorrhoids.
Epidemiology
Globally, every year between 50,000 and 100,000 women are affected by fistula relating to childbirth.
Botany
In botany, the term is most common in its adjectival forms, where it is used in binomial names to refer to species that are distinguished by hollow or tubular structures. Monarda fistulosa, for example, has tubular flowers; Eutrochium fistulosum has a tubular stem; Allium fistulosum has hollow or tubular leaves, and Acacia seyal subsp. fistula is the subspecies with hollow spines.
Society and culture
The term was first used in the 14th century.
See also
Obstetric fistula
Alexis St. Martin
Stoma (medicine)
References
== External links == |
Papillary thyroid cancer | Papillary thyroid cancer or papillary thyroid carcinoma is the most common type of thyroid cancer, representing 75 percent to 85 percent of all thyroid cancer cases. It occurs more frequently in women and presents in the 20–55 year age group. It is also the predominant cancer type in children with thyroid cancer, and in patients with thyroid cancer who have had previous radiation to the head and neck. It is often well-differentiated, slow-growing, and localized, although it can metastasize.
Diagnosis
Papillary thyroid carcinoma is usually discovered on routine examination as an asymptomatic thyroid nodule that appears as a neck mass. In some instances, the mass may have produced local symptoms. This mass is normally referred to a fine needle aspiration biopsy (FNA) for investigation. FNA accuracy is very high and it is a process widely used in these cases. Other investigation methods include ultrasound imaging and nuclear scan. The ultrasound is a useful test to distinguish solid from cystic lesions and to identify calcifications. The thyroid ultrasound is also very effective to discover microcarcinomas, which refer to very small carcinomas (<1 cm).
Papillary thyroid carcinomas are also discovered when a hard nodule is found in multinodular goiter, when enlarged cervical lymph nodes are detected, or when there are unidentified metastatic lesions elsewhere in the body. Expanding lesions found in the thyroid gland, especially if they are painful, should be examined as they may indicate the presence of papillary thyroid carcinoma. Other clinical signs that could indicate papillary thyroid are fixation to the trachea, a firm neck mass, damage to recurrent laryngeal or cervical sympathetic nerves. Five percent of the population can have thyroid nodules, and the majority will be benign.Appropriate workup includes an ultrasound of the neck, followed by lab studies. Patients will usually meet with both an endocrinologist and a surgeon (head and neck surgeon or endocrine surgeon).
Markers
Thyroglobulin can be used as a tumor marker for well-differentiated papillary thyroid cancer. HBME-1 staining may be useful for differentiating papillary carcinomas from follicular carcinomas; in papillary lesions it tends to be positive.Reduced expression of ATP5E is significantly associated with the diagnosis of papillary thyroid cancer and may serve as an early tumor marker of the disease. Serum microRNAs have shown good diagnostic performance for distinguishing patients with papillary thyroid cancer from patients with benign thyroid nodules and healthy controls, and are suggested as novel and minimally invasive diagnostic approach in clinical practice.
Pathology
Papillary thyroid cancer gets its name from the papillae among its cells, visible on microscopy. Features include:
Characteristic Orphan Annie eye nuclear clearings (nuclei with uniform staining, which appear empty due to powdery chromatin and marginal micronucleoli) and psammoma bodies on light microscopy. The former is useful in identifying the follicular variant of papillary thyroid carcinomas.
Lymphatic spread is more common than hematogenous spread
Multifocality is common
The so-called lateral aberrant thyroid is usually a lymph node metastasis from a papillary thyroid carcinoma.
Papillary microcarcinoma is a subset of papillary thyroid cancer defined as measuring less than or equal to 1 cm. The highest incidence of papillary thyroid microcarcinoma in an autopsy series was reported by Harach et al. in 1985, who found 36 of 101 consecutive autopsies to have an incidental microcarcinoma. Michael Pakdaman et al. report the highest incidence in a retrospective surgical series at 49.9 percent of 860 cases. Management strategies for incidental papillary microcarcinoma on ultrasound (and confirmed on FNAB) range from total thyroidectomy with radioactive iodine ablation to observation alone. Harach et al. suggest using the term "occult papillary tumor" to avoid giving patients distress over having cancer. It was Woolner et al. who first arbitrarily coined the term "occult papillary carcinoma" in 1960, to describe papillary carcinomas ≤ 1.5 cm in diameter.Several variants are recognized, although classic papillary thyroid carcinoma is the most frequent: microscopic-follicular variant, diffuse-sclerosing variant, tall-cell variant, columnar-cell variant, hobnail variant, and others. The encapsulated-follicular variant, specifically when noninvasive, has been newly reclassified as the noninvasive follicular thyroid neoplasm with papillary-like nuclear features.Although papillary carcinoma has a propensity to invade lymphatics, it is less likely to invade blood vessels.
These kinds of tumors are most commonly unencapsulated, and they have a high tendency to metastasize locally to lymph nodes, which may produce cystic structures near the thyroid that are difficult to diagnose because of the paucity of malignant tissue. Furthermore, papillary tumors may metastasize to the lungs and produce a few nodules or the lung fields may exhibit a snowflake appearance throughout.
Other characteristics of the papillary carcinoma is that E.M. shows increased mitochondria, increased RER, as well as increased apical microvilli. Moreover, papillary carcinomas have an indolent growth, and 40 percent of cases spread out of the capsule.
Associated mutations
Mutations associated with papillary thyroid cancer are mainly two forms of chromosomal translocation and one form of point mutation. These alterations lead to activation of a common carcinogenic pathway—the MAPK/ERK pathway.
Chromosomal translocations involving the RET proto-oncogene (encoding a tyrosine kinase receptor that plays essential roles in the development of neuroendocrine cells) located on chromosome 10q11 occur in approximately a fifth of papillary thyroid cancers. The fusion oncoproteins generated are termed RET/PTC proteins (ret/papillary thyroid carcinoma), and constitutively activate RET and the downstream MAPK/ERK pathway. The frequency of ret/PTC translocations is significantly higher in papillary cancers arising in children and after radiation exposure. The gene NTRK1 (encoding the TrkA receptor), located on chromosome 1q, is similarly translocated in approximately 5 percent to 10 percent of papillary thyroid cancers.Approximately a third to a half of papillary thyroid carcinomas harbor point mutations in the BRAF oncogene, also activating the MAPK/ERK pathway. In those cases the BRAF mutations found were V600E mutation. After performing a multivariate analysis, it was found that the absence of tumor capsule was the only parameter associated (P=0.0005) with BRAF V600E mutation. According to recent studies, papillary cancers carrying the common V600E mutation tend to have a more aggressive long-term course. BRAF mutations are frequent in papillary carcinoma and in undifferentiated cancers that have developed from papillary tumors.
Many more changes in gene expression are currently being investigated. Previous studies demonstrated the dysregulation of different microRNAs in thyroid cancer. For example, downregulation of miR-369-3p and consequent upregulation of its target TSPAN13 appear to be involved in the pathophysiology of PTC.Mitochondrial mutations: MtDNA(mitochondrial) haplogroups, characterized by unique sets of non pathological mtDNA polymorphisms can modulate the pathogenesis of different diseases in specific populations because of its influence on the expression of genes related to ROS production and OXPHOS coupling efficiency and the regulation of apoptosis. In Asian populations, haplogroup D4a is associated with an increased risk of thyroid cancer while in European populations, Haplogroup K is considered to be protective of Thyroid cancer.
Treatment
Surgery remains the mainstay of treatment for papillary thyroid cancer. The Revised 2009 American Thyroid Association guidelines for papillary thyroid cancer state that the initial procedure should be near-total or total thyroidectomy. Thyroid lobectomy alone may be sufficient treatment for small (<1 cm), low-risk, unifocal, intrathyroidal papillary carcinomas in the absence of prior head and neck irradiation or radiologically or clinically involved cervical nodal metastasis.
Minimal disease (diameter up to 1.0 centimeters) - hemithyroidectomy (or unilateral lobectomy) and isthmectomy may be sufficient. There is some discussion whether this is still preferable over total thyroidectomy for this group of patients.
Gross disease (diameter over 1.0 centimeters) - total thyroidectomy, and central compartment lymph node removal is the therapy of choice. Additional lateral neck nodes can be removed at the same time if an ultrasound guided FNA and thyroglobulin TG cancer washing was positive on the pre-operative neck node ultrasound evaluation.Arguments for total thyroidectomy are:
Reduced risk of recurrence, if central compartment nodes are removed at the original surgery.
30-85% of papillary carcinoma is multifocal disease. Hemithyroidectomy may leave disease in the other lobe. However, multifocal disease in the remnant lobe may not necessarily become clinically significant or serve as a detriment to patient survival.
Ease of monitoring with thyroglobulin (sensitivity for picking up recurrence is increased in presence of total thyroidectomy, and ablation of the remnant normal thyroid by low dose radioiodine 131 after following a low iodine diet (LID).
Ease of detection of metastatic disease by thyroid and neck node ultrasound.
Post-operative complications at high-volume thyroid surgery centers with experienced surgeons are comparable to that of hemithyroidectomy.Arguments for hemithyroidectomy:
Most patients have low-risk cancer with an excellent prognosis, with similar survival outcomes in low-risk patients who undergo total thyroidectomy versus hemithyroidectomy.
Less likelihood of patient requiring lifelong thyroid hormone replacement after surgery.Thyroid total body scans are less reliable at finding recurrence than TG and ultrasound.
Papillary tumors tend to be more aggressive in patients over age 45. In such cases, it might be required to perform a more extensive resection including portions of the trachea. Also, the sternocleidomastoid muscle, jugular vein, and accessory nerve are to be removed if such procedure allows apparently complete tumor resection. If a significant amount of residual tumor is left in the neck, external radiotherapy has been indicated and has proven useful especially in those cases when the residual tumor does not take up radioiodine.
After surgical thyroid removal, the patient waits around 4–6 weeks to then have radioiodine therapy. This therapy is intended to both detect and destroy any metastasis and residual tissue in the thyroid. The treatment may be repeated 6–12 months after initial treatment of metastatic disease where disease recurs or has not fully responded.Patients are administered hormone replacement levothyroxine for life after surgery, especially after total thyroidectomy. Chemotherapy with cisplatin or doxorubicin has proven limited efficacy, however, it could be helpful for patients with bone metastases to improve their quality of life. Patients are also prescribed levothyroxine and radioiodine after surgery. Levothyroxine influences growth and maturation of tissues and it is involved in normal growth, metabolism, and development. In case of metastases, patients are prescribed antineoplastic agents which inhibit cell growth and proliferation and help in palliating symptoms in progressive disease.
After successful treatment, 35 percent of the patients may experience a recurrence within a 40-year span. Also, patients may experience a high incidence of nodule metastasis, with 35 percent cases of cervical node metastases. Approximately 20 percent of patients will develop multiple tumors within the thyroid gland.There is ongoing discussion regarding the best management regarding the optimal surgical procedure for papillary thyroid cancer. Prognosis of patients with papillary thyroid cancer is found to be dependent on the patients age, the size of the tumor, presence of metastatic disease, and the presence of tumor invasion into adjacent tissues near the thyroid gland. Recent studies have examined a more conservative approach to surgery and have demonstrated that hemithyroidectomy may be acceptable for patients with low-risk papillary thyroid cancer with tumor size 1 cm to 4 cm with no presence of invasion to tissues surrounding the thyroid or metastasis. Studies examining large databases of patients with papillary thyroid cancer have concluded that there is no survival advantage for patients with stage I papillary thyroid cancer size 1–4 cm receiving total thyroidectomy versus hemithyroidectomy. In light of this data, choosing the optimal course of surgical and medical management of papillary thyroid cancer should involve shared decision making from patient, endocrinologists, and surgeons.
Prognosis
Depending on source, the overall 5-year survival rate for papillary thyroid cancer is 96 percent or 97 percent, with a 10-year survival rate of 93 percent.For a more specific prognosis for individual cases, there are at minimum 13 known scoring systems for prognosis; among the more often used are:
AGES - Age, Grade, Extent of disease, Size
AMES - Age, Metastasis, Extent of disease, Size
MACIS - Metastasis, Age at presentation, Completeness of surgical resection, Invasion (extrathyroidal), Size (this is a modification of the AGES system). It is probably the most reliable staging method available. Also known as the MAICS system.
TNM staging - Tumor, node, metastasis. Remarkable about the TNM staging for (differentiated) thyroid carcinoma is that the scoring is different according to age.
MACIS
The MACIS system of estimating the prognosis of papillary thyroid cancer was developed by Clive S. Grant at the Mayo Clinic, and was based on careful evaluation of a large group of patients. It is probably the most reliable staging method available.It assigns scores to the main factors involved, and uses the sum of this score to calculate the prognosis:
Most patients fall into the low-risk category (MACIS score less than 6.0) and are cured of the cancer at the time of surgery.Children with multiple lung metastases and/or a miliary aspect still have an excellent long-term prognosis if given adequate treatment.
Stage
Based on overall cancer staging into stages I to IV, papillary thyroid cancer has a 5-year survival rate of 100 percent for stages I and II, 93 percent for stage III and 51 percent for stage IV.
Epidemiology
According to Surveillance, Epidemiology, and End Results (SEER), the incidence of papillary cancer has increased from 4.8 to 14.9 per 100,000 from 1975 to 2012. Females are more likely to get papillary cancer when compared to males with incidence ratio of 2.5 to 1 where most of the cancers are diagnosed between 40 and 50 years old in females. However, death rates from papillary cancer remains static from 2003 to 2012 at 0.5 per 100,000 men and women. There was an increased incidence of papillary cancer from 1910 to 1960 due to the use of ionising radiation in treating childhood head and neck cancers. The incidence decreased after radiation therapy was abandoned. Environmental exposures to radiation such as atomic bombings of Hiroshima and Nagasaki and Chernobyl disaster also causes an increase in childhood papillary thyroid cancer at 5 to 20 years after the exposure to radiation. Family history of thyroid cancer syndrome such as familial adenomatous polyposis, Carney complex, Multiple endocrine neoplasia type 2 (MEN-2), Werner syndrome, and Cowden syndrome increases the risk of getting papillary cancer.
References
External links
Thyroid cancer at DMOZ
Cancer Management Handbook: Thyroid and Parathyroid Cancers
Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. (January 2016). "2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer". Thyroid. 26 (1): 1–133. doi:10.1089/thy.2015.0020. PMC 4739132. PMID 26462967. |
WAGR syndrome | WAGR syndrome (also known as WAGR complex, Wilms tumour-aniridia syndrome, aniridia-Wilms tumour syndrome) is a rare genetic syndrome in which affected children are predisposed to develop Wilms tumour (a tumour of the kidneys), Aniridia (absence of the coloured part of the eye, the iris), Genitourinary anomalies, and mental Retardation. The G is sometimes instead given as "gonadoblastoma," since the genitourinary anomalies can include tumours of the gonads (testes or ovaries).Some WAGR syndrome patients show severe childhood obesity and hyperphagia; the acronym WAGRO (O for obesity) has been used to describe this category and may be associated with the coinciding loss of BDNF a gene that is also on chromosome 11.The condition, first described by Miller et al. in 1964 in its association with other congenital malformations, results from a deletion on chromosome 11 resulting in the loss of several genes. As such, it is one of the best studied examples of a condition caused by loss of neighbouring (contiguous) genes.It is possible for those with WAGR syndrome to develop Wilms tumor, a rare form of kidney cancer.
Signs and symptoms
Newborn children with WAGR syndrome are soon noted to have aniridia. The clinical suspicion for WAGR may be increased with the presence of other genital anomalies, though genitourinary anomalies are not always present, particularly in girls.In older children, clinical diagnosis of the syndrome can be made when aniridia and one of the other features are present. While aniridia is rarely absent in WAGR syndrome, cases have been reported without it. Chromosomal analysis is necessary for definitive diagnosis. Other common eye defects include cataracts and ptosis. About 50% of people develop Wilms tumour.
Pathophysiology
WAGR syndrome is caused by a mutation on chromosome 11 in the 11p13 region. Specifically, several genes in this area are deleted, including the PAX6 ocular development gene and the Wilms tumour gene (WT1). Abnormalities in WT1 may also cause genitourinary anomalies. Mutations in the PAX6 gene have recently been shown to not only cause ocular abnormalities, but also problems in the brain and pancreas.The gene for brain-derived neurotrophic factor (BDNF), located on 11p14.1, has been proposed as a candidate gene for the obesity and excessive eating in a subset of WAGR patients. This strengthens the case for a role for BDNF in energy balance.
Diagnosis
Diagnosis for WAGR syndrome can be made by confirming microdeletion of 11p13 utilizing FISH (fluorescent in situ hybridization), the primary method of choice for diagnosis. FISH which will demonstrate a lack of a fluorescent signal coordinating to the specific location of the gene.
Treatment
Children with WAGR syndrome receive regular (3-4 yearly) kidney surveillance for Wilms tumour until at least the age of 6–8 years and thereafter remain under some follow-up because of the risk of late onset nephropathy (40% of patients with WAGR Syndrome over the age of 12 years). Females with WAGR syndrome may have streak ovaries, which can increase the risk for gonadoblastoma. Malformations of the vagina and/or uterus may also be present.
See also
Denys–Drash syndrome
References
External links
DECIPHER database entry for WAGR syndrome |
Costello syndrome | Costello syndrome, also called faciocutaneoskeletal syndrome or FCS syndrome, is a rare genetic disorder that affects many parts of the body. It is characterized by delayed development and intellectual disabilities, distinctive facial features, unusually flexible joints, and loose folds of extra skin, especially on the hands and feet.: 571 Heart abnormalities are common, including a very fast heartbeat (tachycardia), structural heart defects, and overgrowth of the heart muscle (hypertrophic cardiomyopathy). Infants with Costello syndrome may be large at birth, but grow more slowly than other children and have difficulty feeding. Later in life, people with this condition have relatively short stature and many have reduced levels of growth hormones. It is a RASopathy.Beginning in early childhood, people with specific mutations on the Costello syndrome gene variant have an increased risk of developing certain cancerous and noncancerous tumors. Small growths called papillomas are the most common noncancerous tumors seen with this condition. They usually develop around the nose and mouth. The most frequent cancerous tumor associated with Costello syndrome is a soft tissue tumor called a rhabdomyosarcoma. Other cancers also have been reported in children and adolescents with this disorder, including a tumor that arises in developing nerve cells (neuroblastoma) and a form of bladder cancer (transitional cell carcinoma).
Costello syndrome was discovered by Jack Costello, a New Zealand paediatrician, in 1977. He is credited with first reporting the syndrome in the Australian Paediatric Journal, Volume 13, No.2 in 1977.
Signs and symptoms
Genetics
Costello syndrome is caused by any of at least five different mutations in the HRAS gene on chromosome 11. This gene provides instructions for making a protein, H-Ras, that helps control cell growth and division. Mutations that cause Costello syndrome lead to the production of an H-Ras protein that is permanently active. Instead of triggering cell growth in response to particular signals from outside the cell, the overactive protein directs cells to grow and divide constantly. This unchecked cell division may predispose those affected to the development of benign and malignant tumors. It remains unclear how mutations in HRAS cause other features of Costello syndrome, but many of the signs and symptoms may result from cell overgrowth and abnormal cell division.HRAS is a proto-oncogene in which somatic mutations in healthy people can contribute to cancer. Whereas children with Costello syndrome typically have a mutation in HRAS in every cell of their bodies, an otherwise healthy person with a tumor caused in part by HRAS mutation will only have mutant HRAS within the tumor. The test for the mutation in cancer tumors can also be used to test children for Costello syndrome.Costello syndrome is inherited in an autosomal dominant manner, which means one copy of the altered gene is sufficient to cause the disorder. Almost all cases have resulted from new mutations, and occur in people with no history of the disorder in their family. This condition is rare; as of 20 April 2007, 200 to 300 cases have been reported worldwide.
Diagnosis
Costello Syndrome can be difficult for doctors to immediately clinically diagnose, as there are similar conditions that resemble this syndrome. A physician will start by assessing the childs height, the size of the head, and birth weight.Full genome and Exome next generation DNA testing is the primary diagnostic tool for Costello Syndrome.
Treatments
At the 2005 American Society of Human Genetics meeting, Francis Collins gave a presentation about a treatment he devised for children affected by Progeria. He discussed how farnesyltransferase inhibitors (FTIs) affects H-Ras. After his presentation, members of the Costello Syndrome Family Network discussed the possibility of FTIs helping children with Costello syndrome. Mark Kieran, who presented at the 1st International Costello Syndrome Research Symposium in 2007, agreed that FTIs might help children with Costello syndrome. He discussed with Costello advocates what he had learned in establishing and running the Progeria clinical trial with an FTI, to help them consider next steps.Another medication that affects H-Ras is Lovastatin, which is planned as a treatment for neurofibromatosis type I. When this was reported in mainstream news, the Costello Syndrome Professional Advisory Board was asked about its use in Costello Syndrome. Research into the effects of Lovastatin was linked with Alcino Silva, who presented his findings at the 2007 symposium. Silva also believed that the medication he was studying could help children with Costello syndrome with cognition.A third medication that might help children with Costello syndrome is a MEK inhibitor that helps inhibit the pathway closer to the cell nucleus.
Research
Spanish researchers reported the development of a Costello mouse, with the G12V mutation, in early 2008. Although the G12V mutation is rare among children with Costello syndrome, and the G12V mouse does not appear to develop tumors as expected, information about the mouse models heart may be transferable to humans.
Italian and Japanese researchers published their development of a Costello zebrafish in late 2008, also with the G12V mutation. The advent of animal models may accelerate identification of treatment options.
Historical
That genetic mutations in HRAS cause Costello syndrome was first reported in 2005. These mutations, along with mutations that cause cardiofaciocutaneous syndrome, found soon after, surprised geneticists and changed how genetic syndromes can be grouped. Before this, geneticists looked for new mutations in genes with mutations that caused syndromes similar to the unknown syndrome. For example, researchers looked at and around the most common Noonan syndrome mutation, PTPN11, but did not find anything related to Costello syndrome or cardiofaciocutaneous syndrome. The first mutation that is now identified as one of the Costello syndrome alleles was found unexpectedly when Japanese researchers used the DNA of children with Costello syndrome as a control, looking for another Noonan gene
Geneticists realized that the syndromes they were grouping together clinically according to their signs and symptoms were related in a way they had never realized: the mutations that cause Costello syndrome, Noonan syndrome and cardiofaciocutaneous syndromes are linked by their cellular function, not by being on or close to a gene with a known mutation. The cellular function that links them is a common signalling pathway that brings information from outside the cell to the nucleus. This pathway is called the Ras-MAP-kinase signal transduction pathway (Ras-MAPK Pathway).
References
Some text in this article was originally taken from http://ghr.nlm.nih.gov/condition=costellosyndrome, a public domain source
External links
GeneReviews: Costello Syndrome
GeneReviews: Daisys battle with Costello Syndrome |
Skew deviation | Skew deviation is an unusual ocular deviation (strabismus), wherein the eyes move upward (hypertropia) in opposite directions. Skew deviation is caused by abnormal prenuclear vestibular input to the ocular motor nuclei, most commonly due to brainstem or cerebellar stroke. Other causes include multiple sclerosis and head trauma. Skew deviation is usually characterized by torticollis (head tilting) and binocular torsion. The exact pathophysiology of skew deviation remains incompletely understood. Skew deviation appears to be a perturbation of the ocular tilt reaction, which is itself is most likely a vestigial righting response used to keep fish and other lateral-eyed animals properly oriented.There are three types of skew deviations:Type 1: Upward deviation of both eyes; sound-induced vestibular symptoms; both eyes show counterclockwise rotary upward rotation
Type 2: Hypertropia in one eye; dorsolateral medullary infarctions; excyclotropia in the ipsilateral eye; hypertropia in the contralateral eye
Type 3: Simultaneous hypertropia one eye and hypotropia in the other eye; upper brainstem lesion
References
Further reading
Adams, Raymond D.; Victor, Maurice; Ropper, Allan H. (1997). Principles of Neurology (6 ed.). New York: McGraw Hill, Health Professions Division. ISBN 978-0-07-067439-4. |
Blistering distal dactylitis | Blistering distal dactylitis is a cutaneous condition characterized by tense superficial bullae occurring on a tender erythematous base over the volar fat pad of the phalanx of a finger or thumb.: 262 The most common organism responsible for this is Beta-hemolytic Streptococci.
See also
List of cutaneous conditions
== References == |
Mitral regurgitation | Mitral regurgitation (MR), also known as mitral insufficiency or mitral incompetence, is a form of valvular heart disease in which the mitral valve is insufficient and does not close properly when the heart pumps out blood. It is the abnormal leaking of blood backwards – regurgitation from the left ventricle, through the mitral valve, into the left atrium, when the left ventricle contracts. Mitral regurgitation is the most common form of valvular heart disease.
Definition
Mitral regurgitation, also known as mitral insufficiency or mitral incompetence, is the backward flow of blood from the left ventricle, through the mitral valve, and into the left atrium, when the left ventricle contracts, resulting in a systolic murmur radiating to the left armpit.
Signs and symptoms
Mitral regurgitation may be present for many years before any symptoms appear. The symptoms associated with MR are dependent on which phase of the disease process the individual is in. Individuals with acute MR are typically severely symptomatic and will have the signs and symptoms of acute decompensated congestive heart failure (i.e. shortness of breath, pulmonary edema, orthopnea, and paroxysmal nocturnal dyspnea). In acute cases, a murmur and tachycardia may be the only distinctive signs.Individuals with chronic compensated MR may be asymptomatic for long periods of time, with a normal exercise tolerance and no evidence of heart failure. Over time, however, there may be decompensation and patients can develop volume overload (congestive heart failure). Symptoms of entry into a decompensated phase may include fatigue, shortness of breath particularly on exertion, and leg swelling. Also, there may be development of an irregular heart rhythm known as atrial fibrillation.Findings on clinical examination depend on the severity and duration of MR. The mitral component of the first heart sound is usually soft and with a laterally displaced apex beat, often with heave. The first heart sound is followed by a high-pitched holosystolic murmur at the apex, radiating to the back or clavicular area. Its duration is, as the name suggests, the whole of systole. The loudness of the murmur does not correlate well with the severity of regurgitation. It may be followed by a loud, palpable P2, heard best when lying on the left side. A third heart sound is commonly heard.Patients with mitral valve prolapse may have a holosystolic murmur or often a mid-to-late systolic click and a late systolic murmur. Cases with a late systolic regurgitant murmur may still be associated with significant hemodynamic consequences.Mitral regurgitation as a result of papillary muscle damage or rupture may be a complication of a heart attack and lead to cardiogenic shock.
Cause
The mitral valve apparatus comprises two valve leaflets, the mitral annulus, which forms a ring around the valve leaflets, and the papillary muscles, which tether the valve leaflets to the left ventricle and prevent them from prolapsing into the left atrium. The chordae tendineae is also present and connects the valve leaflets to the papillary muscles. Dysfunction of any of these portions of the mitral valve apparatus can cause regurgitation.The most common cause of MR in developing countries is mitral valve prolapse. It is the most common cause of primary mitral regurgitation in the United States, causing about 50% of cases. Myxomatous degeneration of the mitral valve is more common in women as well as with advancing age, which causes a stretching of the leaflets of the valve and the chordae tendineae. Such elongation prevents the valve leaflets from fully coming together when the valve closes, causing the valve leaflets to prolapse into the left atrium, thereby causing MR.Ischemic heart disease causes MR by the combination of ischemic dysfunction of the papillary muscles, and the dilatation of the left ventricle. This can lead to the subsequent displacement of the papillary muscles and the dilatation of the mitral valve annulus.Rheumatic fever (RF), Marfans syndrome and the Ehlers–Danlos syndromes are other typical causes. Mitral valve stenosis (MVS) can sometimes be a cause of mitral regurgitation (MR) in the sense that a stenotic valve (calcified and with restricted range of movement) allows backflow (regurgitation) if it is too stiff and misshapen to close completely. Most MVS is caused by RF, so one can say that MVS is sometimes the proximal cause of MI/MR (that is, stenotic MI/MR) and that RF is often the distal cause of MVS, MI/MR, or both. MR and mitral valve prolapse are also common in Ehlers–Danlos syndromes.Secondary mitral regurgitation is due to the dilatation of the left ventricle that causes stretching of the mitral valve annulus and displacement of the papillary muscles. This dilatation of the left ventricle can be due to any cause of dilated cardiomyopathy including aortic insufficiency, nonischemic dilated cardiomyopathy, and noncompaction cardiomyopathy. Because the papillary muscles, chordae, and valve leaflets are usually normal in such conditions, it is also called functional mitral regurgitation.Acute MR is most often caused by endocarditis, mainly S. aureus. Rupture or dysfunction of the papillary muscle are also common causes in acute cases, dysfunction, which can include mitral valve prolapse.
Pathophysiology
The pathophysiology of MR can be broken into three phases of the disease process: the acute phase, the chronic compensated phase, and the chronic decompensated phase.
Acute phase
Acute MR (as may occur due to the sudden rupture of the chordae tendinae or papillary muscle) causes a sudden volume overload of both the left atrium and the left ventricle. The left ventricle develops volume overload because with every contraction it now has to pump out not only the volume of blood that goes into the aorta (the forward cardiac output or forward stroke volume) but also the blood that regurgitates into the left atrium (the regurgitant volume). The combination of the forward stroke volume and the regurgitant volume is known as the total stroke volume of the left ventricle.In the acute setting, the stroke volume of the left ventricle is increased (increased ejection fraction); this happens because of more complete emptying of the heart. However, as it progresses the LV volume increases and the contractile function deteriorates, thus leading to dysfunctional LV and a decrease in ejection fraction. The increase in stroke volume is explained by the Frank–Starling mechanism, in which increased ventricular pre-load stretches the myocardium such that contractions are more forceful.The regurgitant volume causes a volume overload and a pressure overload of the left atrium and the left ventricle. The increased pressures in the left side of the heart may inhibit drainage of blood from the lungs via the pulmonary veins and lead to pulmonary congestion.
Chronic phase
Compensated
If the MR develops slowly over months to years or if the acute phase cannot be managed with medical therapy, the individual will enter the chronic compensated phase of the disease. In this phase, the left ventricle develops eccentric hypertrophy in order to better manage the larger than normal stroke volume. The eccentric hypertrophy and the increased diastolic volume combine to increase the stroke volume (to levels well above normal) so that the forward stroke volume (forward cardiac output) approaches the normal levels.In the left atrium, the volume overload causes enlargement of the left atrium, allowing the filling pressure in the left atrium to decrease. This improves the drainage from the pulmonary veins, and signs and symptoms of pulmonary congestion will decrease.These changes in the left ventricle and left atrium improve the low forward cardiac output state and the pulmonary congestion that occur in the acute phase of the disease. Individuals in the chronic compensated phase may be asymptomatic and have normal exercise tolerances.
Decompensated
An individual may be in the compensated phase of MR for years, but will eventually develop left ventricular dysfunction, the hallmark for the chronic decompensated phase of MR. It is currently unclear what causes an individual to enter the decompensated phase of this disease. However, the decompensated phase is characterized by calcium overload within the cardiac myocytes.In this phase, the ventricular myocardium is no longer able to contract adequately to compensate for the volume overload of mitral regurgitation, and the stroke volume of the left ventricle will decrease. The decreased stroke volume causes a decreased forward cardiac output and an increase in the end-systolic volume. The increased end-systolic volume translates to increased filling pressures of the left ventricle and increased pulmonary venous congestion. The individual may again have symptoms of congestive heart failure.The left ventricle begins to dilate during this phase. This causes a dilatation of the mitral valve annulus, which may worsen the degree of MR. The dilated left ventricle causes an increase in the wall stress of the cardiac chamber as well.While the ejection fraction is less in the chronic decompensated phase than in the acute phase or the chronic compensated phase, it may still be in the normal range (i.e.: > 50 percent), and may not decrease until late in the disease course. A decreased ejection fraction in an individual with MR and no other cardiac abnormality should alert the physician that the disease may be in its decompensated phase.
Diagnosis
There are many diagnostic tests that have abnormal results in the presence of MR. These tests suggest the diagnosis of MR and may indicate to the physician that further testing is warranted. For instance, the electrocardiogram (ECG) in long-standing MR may show evidence of left atrial enlargement and left ventricular dilatation. Atrial fibrillation may also be noted on the ECG in individuals with chronic mitral regurgitation. The ECG may not show any of these findings in the setting of acute MR.
The quantification of MR usually employs imaging studies such as echocardiography or magnetic resonance angiography of the heart.
Chest X-ray
The chest X-ray in individuals with chronic MR is characterized by enlargement of the left atrium and the left ventricle, and then maybe calcification of the mitral valve.
Echocardiogram
An echocardiogram is commonly used to confirm the diagnosis of MR. Color doppler flow on the transthoracic echocardiogram (TTE) will reveal a jet of blood flowing from the left ventricle into the left atrium during ventricular systole. Also, it may detect a dilated left atrium and ventricle and decreased left ventricular function. A transesophageal echocardiogram can give clearer images if needed as the back of the heart can also be viewed.
Electrocardiography
P mitrale is a broad, bifid notched P wave in several or many leads with a prominent late negative component to the P wave in lead V1, and may be seen in MR, but also in mitral stenosis, and, potentially, any cause of overload of the left atrium.
Quantification of mitral regurgitation
The degree of severity of MR can be quantified by the regurgitant fraction, which is the percentage of the left ventricular stroke volume that regurgitates into the left atrium.
regurgitant fraction =
V
m
i
t
r
a
l
−
V
a
o
r
t
i
c
V
m
i
t
r
a
l
×
100
%
{\displaystyle {\frac {V_{mitral}-V_{aortic}}{V_{mitral}}}\times 100\%}
where Vmitral and Vaortic are, respectively, the volumes of blood that flow forward through the mitral valve and aortic valve during a cardiac cycle.
Methods that have been used to assess the regurgitant fraction in mitral regurgitation include echocardiography, cardiac catheterization, fast CT scan, and cardiac MRI.The echocardiographic technique to measure the regurgitant fraction is to determine the forward flow through the mitral valve (from the left atrium to the left ventricle) during ventricular diastole, and comparing it with the flow out of the left ventricle through the aortic valve in ventricular systole. This method assumes that the aortic valve does not have aortic insufficiency.Another way to quantify the degree of MR is to determine the area of the regurgitant flow at the level of the valve. This is known as the regurgitant orifice area and correlates with the size of the defect in the mitral valve. One particular echocardiographic technique used to measure the orifice area is measurement of the proximal isovelocity surface area (PISA). The flaw of using PISA to determine the mitral valve regurgitant orifice area is that it measures the flow at one moment in time in the cardiac cycle, which may not reflect the average performance of the regurgitant jet.
Treatment
The treatment of MR depends on the acuteness of the disease and whether there are associated signs of hemodynamic compromise. In general, medical therapy is non-curative and is used for mild-to-moderate regurgitation or in patients unable to tolerate surgery.In acute MR secondary to a mechanical defect in the heart (i.e., rupture of a papillary muscle or chordae tendineae), the treatment of choice is mitral valve surgery. If the patient is hypotensive prior to the surgical procedure, an intra-aortic balloon pump may be placed in order to improve perfusion of the organs and to decrease the degree of MR.
Medicine
If the individual with acute MR is normotensive, vasodilators may be of use to decrease the afterload seen by the left ventricle and thereby decrease the regurgitant fraction. The vasodilator most commonly used is nitroprusside.Individuals with chronic MR can be treated with vasodilators as well to decrease afterload. In the chronic state, the most commonly used agents are ACE inhibitors and hydralazine. Studies have shown that the use of ACE inhibitors and hydralazine can delay surgical treatment of MR. The current guidelines for treatment of MR limit the use of vasodilators to individuals with hypertension, however. Any hypertension is treated aggressively, e.g. by diuretics and a low sodium diet. In both hypertensive and normotensive cases, digoxin and antiarrhythmics are also indicated. Also, chronic anticoagulation is given where there is concomitant mitral valve prolapse or atrial fibrillation.
Surgery
Surgery is curative of mitral valve regurgitation. There are two surgical options for the treatment of MR: mitral valve replacement and mitral valve repair. Mitral valve repair is preferred to mitral valve replacement where a repair is feasible as bioprosthetic replacement valves have a limited lifespan of 10 to 15 years, whereas synthetic replacement valves require ongoing use of blood thinners to reduce the risk of stroke. There are two general categories of approaches to mitral valve repair: resection of the prolapsed valvular segment (sometimes referred to as the "Carpentier" approach) and installation of artificial chordae to "anchor" the prolapsed segment to the papillary muscle (sometimes referred to as the "David" approach). With the resection approach, any prolapsing tissue is resected, in effect removing the hole through which the blood is leaking. In the artificial chordae approach, ePTFE (expanded polytetrafluoroethylene, or Gore-Tex) sutures are used to replace the broken or stretched chordae tendonae, bringing the natural tissue back into the physiological position, thus restoring the natural anatomy of the valve. With both techniques, an annuloplasty ring is typically secured to the annulus, or opening of the mitral valve, to provide additional structural support. In some cases, the "double orifice" (or Alfieri) technique for mitral valve repair, the opening of the mitral valve is sewn closed in the middle, leaving the two ends still able to open. This ensures that the mitral valve closes when the left ventricle pumps blood, yet allows the mitral valve to open at the two ends to fill the left ventricle with blood before it pumps. In general, mitral valve surgery requires "open-heart" surgery in which the heart is arrested and the patient is placed on a heart-lung machine (cardiopulmonary bypass). This allows the complex surgery to proceed in a still environment.Due to the physiological stress associated with open-heart surgery, elderly and very sick patients may be subject to increased risk, and may not be candidates for this type of surgery. As a consequence, there are attempts to identify means of correcting MR on a beating heart. The Alfieri technique for instance, has been replicated using a percutaneous catheter technique, which installs a "MitraClip" device to hold the middle of the mitral valve closed.Indications for surgery for chronic MR include signs of left ventricular dysfunction with ejection fraction less than 60%, severe pulmonary hypertension with pulmonary artery systolic pressure greater than 50 mmHg at rest or 60 mmHg during activity, and new-onset atrial fibrillation.
Epidemiology
Significant mitral valve regurgitation has a prevalence of approximately 2% of the population, affecting males and females equally. It is one of the two most common valvular heart diseases in the elderly, and the commonest type of valvular heart disease in low and middle income countries.In a study of 595 male elite football players aged 18–38 and 47 sedentary non-athletes, mitral regurgitation was found in 20% football players and 15% in control group. Football players with mitral regurgitation were found to have larger mitral annulus diameter compared to athletes without regurgitation, and left atrium diameter was larger in athletes with MR.
See also
Tricuspid regurgitation
Aortic regurgitation
Pulmonary insufficiency
References
== External links == |
Pyridoxine-dependent epilepsy | Pyridoxine-dependent epilepsy (PDE) is a rare genetic disorder characterized by intractable seizures in the prenatal and neonatal period. The disorder was first recognized in the 1950s, with the first description provided by Hunt et al. in 1954. More recently, pathogenic variants within the ALDH7A1 gene have been identified to cause PDE.
Genetics
PDE is inherited in an autosomal recessive manner and is estimated to affect around 1 in 400,000 to 700,000 births, though one study conducted in Germany estimated a prevalence of 1 in 20,000 births. The ALDH7A1 gene encodes for the enzyme antiquitin or α-aminoadipic semialdehyde dehydrogenase, which is involved with the catabolism of lysine.
Treatment
Patients with PDE do not respond to anticonvulsant medications, but seizures rapidly cease with therapeutic intravenous doses of vitamin B6 and remission from seizures are often maintained on daily therapeutic doses of vitamin B6. An optimal dose has not yet been established, but doses of 50–100 mg/day or 15–30 mg/kg/day have been proposed. Importantly, excessive doses of vitamin B6 can result in irreversible neurological damage, and therefore several guidelines recommend between 200 mg (neonates) and 500 mg per day as the maximal daily dose.Despite remission of seizure activity with vitamin B6 supplementation, intellectual disability is frequently seen in patients with PDE. Because the affected enzyme antiquitin is involved in the cerebral lysine degradation pathway, lysine restriction as an additional treatment modality has recently been explored. Studies have been published which demonstrate potential for improved biomarkers, development, and behavior in patients treated with lysine restriction in addition to pyridoxine supplementation. In trial, lysine restriction of 70–100 mg/kg/day in children less than 1 year of age, 45–80 mg/kg/day in children between 1–7 years of age, and 20–45 mg/kg/day in children older than 7 years of age were prescribed. Despite the potential of additional benefit from lysine restriction, vitamin B6 supplementation remains the main-stay of treatment given lack of studies thus far demonstrating the safety and efficacy of lysine restriction for this purpose.
Monitoring
Plasma and cerebrospinal fluid levels of pipecolic acid are frequently elevated in patients with PDE, though it is a non-specific biomarker. α-aminodipic semialdehyde is elevated in urine and plasma and is a more specific biomarker for PDE. Improvements in these biomarkers have been reported with the implementation of a lysine-restricted diet. Initial studies evaluating the safety and efficacy of lysine restriction evaluated developmental and cognitive outcomes by age-appropriate tests and parental observations.
References
External links
GeneReview/NCBI/NIH/UW entry on Pyridoxine-Dependent Seizures
Pyridoxine-dependent epilepsy. Genetics Home Reference. June 17, 2013. |
Hypotension | Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the diastolic blood pressure (the bottom number), which are the maximum and minimum blood pressures, respectively. A systolic blood pressure of less than 90 millimeters of mercury (mmHg) or diastolic of less than 60 mmHg is generally considered to be hypotension. Different numbers apply to children. However, in practice, blood pressure is considered too low only if noticeable symptoms are present. Primary symptoms generally include dizziness and lightheadedness. Other symptoms include fatigue, shortness of breath, headaches, shakiness, increased thirst, irregular heartbeat, chest pain, confusion.Hypotension is the opposite of hypertension, which is high blood pressure. It is best understood as a physiological state rather than a disease. Severely low blood pressure can deprive the brain and other vital organs of oxygen and nutrients, leading to a life-threatening condition called shock. Shock is classified based on the underlying cause, including hypovolemic shock, cardiogenic shock, distributive shock, and obstructive shock.Hypotension can be caused by strenuous exercise, excessive heat, low blood volume (hypovolemia), hormonal changes, widening of blood vessels, anemia, vitamin B12 deficiency, anaphylaxis, heart problems, or endocrine problems. Some medications can also lead to hypotension. There are also syndromes that can cause hypotension in patients including orthostatic hypotension, vasovagal syncope, and other rarer conditions.For many people, excessively low blood pressure can cause dizziness and fainting or indicate serious heart, endocrine or neurological disorders.For some people who exercise and are in top physical condition, low blood pressure could be normal. A single session of exercise can induce hypotension and water-based exercise can induce a hypotensive response.Treatment of hypotension may include the use of intravenous fluids or vasopressors. When using vasopressors, trying to achieve a mean arterial pressure (MAP) of greater than 70 mmHg does not appear to result in better outcomes than trying to achieve a MAP of greater than 65 mmHg in adults.
Signs and symptoms
The primary symptoms of hypotension are lightheadedness or dizziness.If the blood pressure is sufficiently low, fainting (syncope) may occur.Low blood pressure is sometimes associated with certain symptoms, many of which are related to causes rather than effects of hypotension:
Causes
Low blood pressure can be caused by low blood volume, hormonal changes, widening of blood vessels, medicine side effects, severe dehydration, anemia, vitamin B12 deficiency, anaphylaxis, heart problems or endocrine problems.Reduced blood volume, hypovolemia, is the most common cause of hypotension. This can result from hemorrhage; insufficient fluid intake, as in starvation; or excessive fluid losses from diarrhea or vomiting. Hypovolemia can be induced by excessive use of diuretics. Low blood pressure may also be attributed to heat stroke which can be indicated by absence of perspiration, light headedness and dark colored urine.Other medications can produce hypotension by different mechanisms. Chronic use of alpha blockers or beta blockers can lead to hypotension. Beta blockers can cause hypotension both by slowing the heart rate and by decreasing the pumping ability of the heart muscle.Decreased cardiac output despite normal blood volume, due to severe congestive heart failure, large myocardial infarction, heart valve problems, or extremely low heart rate (bradycardia), often produces hypotension and can rapidly progress to cardiogenic shock. Arrhythmias often result in hypotension by this mechanism.Excessive vasodilation, or insufficient constriction of the blood vessels (mostly arterioles), causes hypotension. This can be due to decreased sympathetic nervous system output or to increased parasympathetic activity occurring as a consequence of injury to the brain or spinal cord. Dysautonomia, an intrinsic abnormality in autonomic system functioning, can also lead to hypotension. Excessive vasodilation can also result from sepsis, acidosis, or medications, such as nitrate preparations, calcium channel blockers, or AT1 receptor antagonists (Angiotensin II acts on AT1 receptors). Many anesthetic agents and techniques, including spinal anesthesia and most inhalational agents, produce significant vasodilation.Lower blood pressure is a side effect of certain herbal medicines, which can also interact with several medications. An example is the theobromine in Theobroma cacao, which lowers blood pressure through its actions as both a vasodilator and a diuretic, and has been used to treat high blood pressure.
Syndromes
Orthostatic hypotension
Orthostatic hypotension, also called postural hypotension, is a common form of low blood pressure. It occurs after a change in body position, typically when a person stands up from either a seated or lying position. It is usually transient and represents a delay in the normal compensatory ability of the autonomic nervous system. It is commonly seen in hypovolemia and as a result of various medications. In addition to blood pressure-lowering medications, many psychiatric medications, in particular antidepressants, can have this side effect. Simple blood pressure and heart rate measurements while lying, seated, and standing (with a two-minute delay in between each position change) can confirm the presence of orthostatic hypotension. Taking these measurements is known as orthostatic vitals. Orthostatic hypotension is indicated if there is a drop of 20 mmHg in systolic pressure (and a 10 mmHg drop in diastolic pressure in some facilities) and a 20 beats per minute increase in heart rate.
Vasovagal syncope
Vasovagal syncope is a form of dysautonomia characterized by an inappropriate drop in blood pressure while in the upright position. Vasovagal syncope occurs as a result of increased activity of the vagus nerve, the mainstay of the parasympathetic nervous system. Patients will feel sudden, unprovoked lightheadedness, sweating, changes in vision, and finally a loss of consciousness. Consciousness will often return rapidly once patient is lying down and the blood pressure returns to normal.
Other
Another, but rarer form, is postprandial hypotension, a drastic decline in blood pressure that occurs 30 to 75 minutes after eating substantial meals. When a great deal of blood is diverted to the intestines (a kind of "splanchnic blood pooling") to facilitate digestion and absorption, the body must increase cardiac output and peripheral vasoconstriction to maintain enough blood pressure to perfuse vital organs, such as the brain. Postprandial hypotension is believed to be caused by the autonomic nervous system not compensating appropriately, because of aging or a specific disorder.Hypotension is a feature of Flammer syndrome, which is characterized by cold hands and feet and predisposes to normal tension glaucoma.Hypotension can be a symptom of relative energy deficiency in sport, sometimes known as the female athlete triad, although it can also affect men.
Pathophysiology
Blood pressure is continuously regulated by the autonomic nervous system, using an elaborate network of receptors, nerves, and hormones to balance the effects of the sympathetic nervous system, which tends to raise blood pressure, and the parasympathetic nervous system, which lowers it. The vast and rapid compensation abilities of the autonomic nervous system allow normal individuals to maintain an acceptable blood pressure over a wide range of activities and in many disease states. Even small alterations in these networks can lead to hypotension.
Diagnosis
For most adults, the optimal blood pressure is below 120/80 mmHg. If the systolic blood pressure is <90 mmHg or the diastolic blood pressure is <60 mmHg, it would be classified as hypotension. However, occasional blood pressure readings below 90/60 mmHg are not infrequent in the general population, and, in the absence of some pathological cause, hypotension appears to be a relatively benign condition in most people. The diagnosis of hypotension is usually made by measuring blood pressure, either non-invasively with a sphygmomanometer or invasively with an arterial catheter (mostly in an intensive care setting). Another way to diagnose low blood pressure is by using the mean arterial pressure (MAP) measured using an arterial catheter or by continuous, non-invasive hemodynamic monitoring which measures intra-operative blood pressure beat-by-beat throughout surgery. A MAP <65 mmHg is considered hypotension. Intra-operative hypotension <65 mmHg can lead to an increased risk of acute kidney injury, myocardial injury or post-operative stroke. While an incidental finding of hypotension during a routine blood pressure measurement may not be particularly worrying, a substantial drop in blood pressure following standing, exercise or eating can be asssociated with symptoms and may have implications for future health. A drop in blood pressure after standing, termed postural or othostatic hypotension, is defined as a decrease in supine-to-standing BP >20 mm Hg systolic or >10 mm Hg diastolic within 3 minutes of standing. Orthostatic hypotension is associated with increased risk of future cardiovascular events and mortality. Orthostatic vitals are frequently measured to assist with the diagnosis of orthostatic hypotension, and may involve the use of a tilt table test to evaluate vasovagal syncope.
Treatment
The treatment for hypotension depends on its cause. Chronic hypotension rarely exists as more than a symptom. Asymptomatic hypotension in healthy people usually does not require treatment. Adding electrolytes to a diet can relieve symptoms of mild hypotension. A morning dose of caffeine can also be effective. In mild cases, where the patient is still responsive, laying the person in dorsal decubitus (lying on the back) position and lifting the legs increases venous return, thus making more blood available to critical organs in the chest and head. The Trendelenburg position, though used historically, is no longer recommended.Hypotensive shock treatment always follows the first four following steps. Outcomes, in terms of mortality, are directly linked to the speed that hypotension is corrected. Still-debated methods are in parentheses, as are benchmarks for evaluating progress in correcting hypotension. A study on septic shock provided the delineation of these general principles. However, since it focuses on hypotension due to infection, it is not applicable to all forms of severe hypotension.
Volume resuscitation (usually with crystalloid or blood products)
Blood pressure support with a vasopressor (all seem equivalent with respect to risk of death, with norepinephrine possibly better than dopamine). Trying to achieve a mean arterial pressure (MAP) of greater than 70 mmHg does not appear to result in better outcomes than trying to achieve a MAP of greater than 65 mmHg in adults.
Ensure adequate tissue perfusion (maintain SvO2 >70 with use of blood or dobutamine)
Address the underlying problem (i.e., antibiotic for infection, stent or CABG (coronary artery bypass graft surgery) for infarction, steroids for adrenal insufficiency, etc...)The best way to determine if a person will benefit from fluids is by doing a passive leg raise followed by measuring the output from the heart.
Medication
Chronic hypotension sometimes requires the use of medications. Some medications that are commonly used include Fludrocortisone, Erythropoietin, and Sympathomimetics such as Midodrine and Noradrenaline and precursor (L-DOPS).
Fludrocortisone is the first-line therapy (in the absence of heart failure) for patients with chronic hypotension or resistant orthostatic hypotension. It works by increasing the intravascular volume.
Midodrine is a therapy used for severe orthostatic hypotension, and works by increasing peripheral vascular resistance.
Noradrenaline and its precursor L-DOPS are used for primary autonomic dysfunction by increasing vascular tone.
Erythropoietin is given to patients with neurogenic orthostatic hypotension and it works through increasing vascular volume and viscosity.
Pediatrics
The definition of hypotension changes in the pediatric population depending on the childs age as seen in the table below.
The clinical history provided by the caretaker is the most important part in determining the cause of hypotension in pediatric patients. Symptoms for children with hypotension include increased sleepiness, not using the restroom as much (or at all), having difficulty breathing or breathing rapidly, or syncope. The treatment for hypotension in pediatric patients is similar to the treatment in adults by following the four first steps listed above (see Treatment). Children are more likely to undergo intubation during the treatment of hypotension because their oxygen levels drop more rapidly than adults. The closing of fetal shunts following birth can create instability in the "transitional circulation" of the fetus, and often creates a state of hypotension following birth; while many infants can overcome this hypotension through the closing of shunts, a mean blood pressure (MBP) of lower than 30 mmHg is correlated with severe cerebral injury and can be experienced by premature infants who have poor shunt closure.
Etymology
Hypotension, from Ancient Greek hypo-, meaning "under" or "less" + English tension, meaning "strain" or "tightness". This refers to the under-constriction of the blood vessels and arteries which leads to low blood pressure.
See also
Hypertension
References
External links
Curlie.org: Hypotension |
Attenuated familial adenomatous polyposis | Attenuated familial adenomatous polyposis is a form of familial adenomatous polyposis, a cancer syndrome. It is a pre-malignant disease that can develop into colorectal cancer. A patient will have fewer than a hundred polyps located typically in right side of the colon. Cancer might develop as early as the age of five, though typically presents later than classical FAP.
See also
Familial adenomatous polyposis
Birt–Hogg–Dubé syndrome
Cowden syndrome
Cronkhite–Canada syndrome
Juvenile polyposis
MUTYH
Peutz–Jeghers syndrome
References
== External links == |
Coccidioidomycosis | Coccidioidomycosis (, kok-SID-ee-oy-doh-my-KOH-sis), commonly known as cocci, Valley fever, as well as California fever, desert rheumatism, or San Joaquin Valley fever, is a mammalian fungal disease caused by Coccidioides immitis or Coccidioides posadasii. Coccidioidomycosis is endemic in certain parts of the United States in Arizona, California, Nevada, New Mexico, Texas, Utah, and northern Mexico.C. immitis is a dimorphic saprophytic fungus that grows as a mycelium in the soil and produces a spherule form in the host organism. It resides in the soil in certain parts of the southwestern United States, most notably in California and Arizona. It is also commonly found in northern Mexico, and parts of Central and South America. C. immitis is dormant during long dry spells, then develops as a mold with long filaments that break off into airborne spores when it rains. The spores, known as arthroconidia, are swept into the air by disruption of the soil, such as during construction, farming, low-wind or singular dust events, or an earthquake. Windstorms may also cause epidemics far from endemic areas. In December 1977, a windstorm in an endemic area around Arvin, California led to several hundred cases, including deaths, in non-endemic areas hundreds of miles away.Coccidioidomycosis is a common cause of community-acquired pneumonia in the endemic areas of the United States. Infections usually occur due to inhalation of the arthroconidial spores after soil disruption. The disease is not contagious. In some cases the infection may recur or become chronic.
It was reported in 2022 that valley fever had been increasing in Californias Central Valley for years (1,000 cases in Kern county in 2014, 3,000 in 2021); experts said that cases could rise across the American west as the climate crisis makes the landscape drier and hotter.
Classification
After Coccidioides infection, coccidioidomycosis begins with Valley fever, which is its initial acute form. Valley fever may progress to the chronic form and then to disseminated coccidioidomycosis. Therefore, coccidioidomycosis may be divided into the following types:
Acute coccidioidomycosis, sometimes described in literature as primary pulmonary coccidioidomycosis
Chronic coccidioidomycosis
Disseminated coccidioidomycosis, which includes primary cutaneous coccidioidomycosisValley fever is not a contagious disease.
Signs and symptoms
An estimated 60% of people infected with the fungi responsible for coccidioidomycosis have minimal to no symptoms, while 40% will have a range of possible clinical symptoms. Of those who do develop symptoms, the primary infection is most often respiratory, with symptoms resembling bronchitis or pneumonia that resolve over a matter of a few weeks. In endemic regions, coccidioidomycosis is responsible for 20% of cases of community-acquired pneumonia. Notable coccidioidomycosis signs and symptoms include a profound feeling of tiredness, loss of smell and taste, fever, cough, headaches, rash, muscle pain, and joint pain. Fatigue can persist for many months after initial infection. The classic triad of coccidioidomycosis known as "desert rheumatism" includes the combination of fever, joint pains, and erythema nodosum.A minority (3–5%) of infected individuals do not recover from the initial acute infection and develop a chronic infection. This can take the form of chronic lung infection or widespread disseminated infection (affecting the tissues lining the brain, soft tissues, joints, and bone). Chronic infection is responsible for most of the morbidity and mortality. Chronic fibrocavitary disease is manifested by cough (sometimes productive of mucus), fevers, night sweats and weight loss. Osteomyelitis, including involvement of the spine, and meningitis may occur months to years after initial infection. Severe lung disease may develop in HIV-infected persons.
Complications
Serious complications may occur in patients who have weakened immune systems, including severe pneumonia with respiratory failure and bronchopleural fistulas requiring resection, lung nodules, and possible disseminated form, where the infection spreads throughout the body. The disseminated form of coccidioidomycosis can devastate the body, causing skin ulcers, abscesses, bone lesions, swollen joints with severe pain, heart inflammation, urinary tract problems, and inflammation of the brains lining, which can lead to death.
Cause
Rain starts the cycle of initial growth of the fungus underneath the soil. In soil (and in agar media), Coccidioides exist in filament form. It forms hyphae in both horizontal and vertical directions. Over a prolonged dry period, cells within hyphae degenerate to form alternating barrel-shaped cells (arthroconidia) which are light in weight and carried by air currents. This happens when the soil is disturbed, often by clearing trees, construction or farming. As the population grows, so do all these activities, causing a potential cascade effect. The more land that is cleared and the more arid the soil, the riper the environment for Coccidioides. These spores can be easily inhaled unknowingly. On reaching alveoli they enlarge in size to become spherules, and internal septations develop. This division of cells is made possible by the optimal temperature inside the body. Septations develop and form endospores within the spherule. Rupture of spherules release these endospores, which in turn repeat the cycle and spread the infection to adjacent tissues within the body of the infected individual. Nodules can form in lungs surrounding these spherules. When they rupture, they release their contents into bronchi, forming thin-walled cavities. These cavities can cause symptoms including characteristic chest pain, coughing up blood, and persistent cough. In individuals with a weakened immune system, the infection can spread through the blood. The fungus can also, rarely, enter the body through a break in the skin and cause infection.
Diagnosis
Coccidioidomycosis diagnosis relies on a combination of an infected persons signs and symptoms, findings on radiographic imaging, and laboratory results.
The disease is commonly misdiagnosed as bacterial community-acquired pneumonia. The fungal infection can be demonstrated by microscopic detection of diagnostic cells in body fluids, exudates, sputum and biopsy tissue by methods of Papanicolaou or Grocotts methenamine silver staining. These stains can demonstrate spherules and surrounding inflammation.With specific nucleotide primers, C. immitis DNA can be amplified by polymerase chain reaction (PCR). It can also be detected in culture by morphological identification or by using molecular probes that hybridize with C. immitis RNA. C. immitis and C. posadasii cannot be distinguished on cytology or by symptoms, but only by DNA PCR.An indirect demonstration of fungal infection can be achieved also by serologic analysis detecting fungal antigen or host IgM or IgG antibody produced against the fungus. The available tests include the tube-precipitin (TP) assays, complement fixation assays, and enzyme immunoassays. TP antibody is not found in cerebrospinal fluid (CSF). TP antibody is specific and is used as a confirmatory test, whereas ELISA is sensitive and thus used for initial testing.If the meninges are affected, CSF will show abnormally low glucose levels, an increased level of protein, and lymphocytic pleocytosis. Rarely, CSF eosinophilia is present.
Imaging
Chest X-rays rarely demonstrate nodules or cavities in the lungs, but these images commonly demonstrate lung opacification, pleural effusions, or enlargement of lymph nodes associated with the lungs. Computed tomography scans of the chest are more sensitive than chest X-rays to detect these changes.
Prevention
Preventing Valley fever is challenging because it is difficult to avoid breathing in the fungus should it be present; however, the public health effect of the disease is essential to understand in areas where the fungus is endemic. Enhancing surveillance of coccidioidomycosis is key to preparedness in the medical field in addition to improving diagnostics for early infections. Currently there are no completely effective preventive measures available for people who live or travel through Valley fever-endemic areas. Recommended preventive measures include avoiding airborne dust or dirt, but this does not guarantee protection against infection. People in certain occupations may be advised to wear face masks. The use of air filtration indoors is also helpful, in addition to keeping skin injuries clean and covered to avoid skin infection.In 1998–2011, there were 111,117 cases of coccidioidomycosis in the U.S. that were logged into the National Notifiable Diseases Surveillance System (NNDSS). Since many U.S. states do not require reporting of coccidioidomycosis, the actual numbers may be higher. The United States Centers for Disease Control and Prevention (CDC) called the disease a "silent epidemic" and acknowledged that there is no proven anticoccidioidal vaccine available. A 2001 cost-effectiveness analysis indicated that a potential vaccine could improve health as well as reducing total health care expenditures among infants, teens, and immigrant adults, and more modestly improve health but increase total health care expenditures in older age groups.Raising both surveillance and awareness of the disease while medical researchers are developing a human vaccine can positively contribute towards prevention efforts. Research demonstrates that patients from endemic areas who are aware of the disease are most likely to request diagnostic testing for coccidioidomycosis. Presently, Meridian Bioscience manufactures the so-called EIA test to diagnose the Valley fever, which however is known for producing a fair quantity of false positives. Currently, recommended prevention measures can include type-of-exposure-based respirator protection for persons engaged in agriculture, construction and others working outdoors in endemic areas. Dust control measures such as planting grass and wetting the soil, and also limiting exposure to dust storms are advisable for residential areas in endemic regions.
Treatment
Significant disease develops in fewer than 5% of those infected and typically occurs in those with a weakened immune system. Mild asymptomatic cases often do not require any treatment. Those with severe symptoms may benefit from antifungal therapy, which requires 3–6 months or more of treatment depending on the response to the treatment. There is a lack of prospective studies that examine optimal antifungal therapy for coccidioidomycosis.On the whole, oral fluconazole and intravenous amphotericin B are used in progressive or disseminated disease, or in immunocompromised individuals. Amphotericin B was originally the only available treatment, but alternatives, including itraconazole and ketoconazole, became available for milder disease. Fluconazole is the preferred medication for coccidioidal meningitis, due to its penetration into CSF. Intrathecal or intraventricular amphotericin B therapy is used if infection persists after fluconazole treatment. Itraconazole is used for cases that involve treatment of infected persons bones and joints. The antifungal medications posaconazole and voriconazole have also been used to treat coccidioidomycosis. Because the symptoms of coccidioidomycosis are similar to the common flu, pneumonia, and other respiratory diseases, it is important for public health professionals to be aware of the rise of coccidioidomycosis and the specifics of diagnosis. Greyhound dogs often get coccidioidomycosis; their treatment regimen involves 6–12 months of ketoconazole taken with food.A particular severe case of meningitis caused by valley fever initially received several incorrect diagnoses such as sinus infections and cluster headaches. The patient became unable to work during diagnosis and original search for treatments. Eventually the right treatment was found—albeit with severe side effects—requiring four pills a day and medication administered directly into the brain every 16 weeks.
Toxicity
Conventional amphotericin B desoxycholate (AmB: used since the 1950s as a primary agent) is known to be associated with increased drug-induced nephrotoxicity impairing kidney function. Other formulations have been developed such as lipid-soluble formulations to mitigate side-effects such as direct proximal and distal tubular cytotoxicity. These include liposomal amphotericin B, amphotericin B lipid complex such as Abelcet (brand) amphotericin B phospholipid complex also as AmBisome Intravenous, or Amphotec Intravenous (Generic; Amphotericin B Cholesteryl Sul), and amphotericin B colloidal dispersion, all shown to exhibit a decrease in nephrotoxicity. The latter was not as effective in one study as amphotericin B desoxycholate which had a 50% murine (rat and mouse) morbidity rate versus zero for the AmB colloidal dispersion.The cost of the nephrotoxic AmB deoxycholate, in 2015, for a patient of 70 kilograms (150 lb) at 1 mg/kg/day dosage, was approximately US$63.80, compared to $1318.80 for 5 mg/kg/day of the less toxic liposomal AmB.
Epidemiology
Coccidioidomycosis is endemic to the western hemisphere between 40°N and 40°S. The ecological niches are characterized by hot summers and mild winters with an annual rainfall of 10–50 cm.
The species are found in alkaline sandy soil, typically 10–30 cm below the surface. In harmony with the mycelium life cycle, incidence increases with periods of dryness after a rainy season; this phenomenon, termed "grow and blow", refers to growth of the fungus in wet weather, producing spores which are spread by the wind during succeeding dry weather. While the majority of cases are observed in the endemic region, cases reported outside the area are generally visitors, who contact the infection and return to their native areas before becoming symptomatic.
North America
In the United States, C. immitis is endemic to southern and central California with the highest presence in the San Joaquin Valley. C. posadassi is most prevalent in Arizona, although it can be found in a wider region spanning from Utah, New Mexico, Texas, and Nevada. An estimated 150,000 infections occur annually, with 25,000 new infections occurring every year. The incidence of coccidioidomycosis in the United States in 2011 (42.6 per 100,000) was almost ten times higher than the incidence reported in 1998 (5.3 per 100,000). In area where it is most prevalent, the infection rate is 2-4%.Incidence varies widely across the west and southwest. In Arizona, for instance, in 2007, there were 3,450 cases in Maricopa County, which in 2007 had an estimated population of 3,880,181 for an incidence of approximately 1 in 1,125. In contrast, though southern New Mexico is considered an endemic region, there were 35 cases in the entire state in 2008 and 23 in 2007, in a region that had an estimated 2008 population of 1,984,356, for an incidence of approximately 1 in 56,695.
Infection rates vary greatly by county, and although population density is important, so are other factors that have not been proven yet. Greater construction activity may disturb spores in the soil. In addition, the effect of altitude on fungi growth and morphology has not been studied, and altitude can range from sea level to 10,000 feet or higher across California, Arizona, Utah and New Mexico.In California from 2000 to 2007, there were 16,970 reported cases (5.9 per 100,000 people) and 752 deaths of the 8,657 people hospitalized. The highest incidence was in the San Joaquin Valley with 76% of the 16,970 cases (12,855) occurring in the area. Following the 1994 Northridge earthquake, there was a sudden increase of cases in the areas affected by the quake, at a pace of over 10 times baseline.There was an outbreak in the summer of 2001 in Colorado, away from where the disease was considered endemic. A group of archeologists visited Dinosaur National Monument, and eight members of the crew, along with two National Park Service workers were diagnosed with Valley fever.California state prisons, beginning in 1919, have been particularly affected by coccidioidomycosis. In 2005 and 2006, the Pleasant Valley State Prison near Coalinga and Avenal State Prison near Avenal on the western side of the San Joaquin Valley had the highest incidence in 2005, of at least 3,000 per 100,000. The receiver appointed in Plata v. Schwarzenegger issued an order in May 2013 requiring relocation of vulnerable populations in those prisons.
The incidence rate has been increasing, with rates as high as 7% during 2006–2010. The cost of care and treatment is $23 million in California prisons. A lawsuit was filed against the state in 2014 on behalf of 58 inmates stating that the Avenal and Pleasant valley state prisons did not take necessary steps to prevent infections.
Population risk factors
There are several populations that have a higher risk for contracting coccidioidomycosis and developing the advanced disseminated version of the disease. Populations with exposure to the airborne arthroconidia working in agriculture and construction have a higher risk. Outbreaks have also been linked to earthquakes, windstorms and military training exercises where the ground is disturbed. Historically, an infection is more likely to occur in males than females, although this could be attributed to occupation rather than being sex-specific. Women who are pregnant and immediately postpartum are at a high risk of infection and dissemination. There is also an association between stage of pregnancy and severity of the disease, with third trimester women being more likely to develop dissemination. Presumably this is related to highly elevated hormonal levels, which stimulate growth and maturation of spherules and subsequent release of endospores. Certain ethnic populations are more susceptible to disseminated coccidioidomycosis. The risk of dissemination is 175 times greater in Filipinos and 10 times greater in African Americans than non-Hispanic whites. Individuals with a weakened immune system are also more susceptible to the disease. In particular, individuals with HIV and diseases that impair T-cell function. Individuals with pre-existing conditions such as diabetes are also at a higher risk. Age also affects the severity of the disease, with more than one-third of deaths being in the 65-84 age group.
History
The first case of what was later named coccidioidomycosis was described in 1892 in Buenos Aires by Alejandro Posadas, a medical intern at the Hospital de Clínicas "José de San Martín". Posadas established an infectious character of the disease after being able to transfer it in laboratory conditions to lab animals. In the U.S., Dr. E. Rixford, a physician from a San Francisco hospital, and T. C. Gilchrist, a pathologist at Johns Hopkins Medical School, became early pioneers of clinical studies of the infection. They decided that the causative organism was a Coccidia-type protozoan and named it Coccidioides immitis (resembling Coccidia, not mild).Dr. William Ophüls, a professor at Stanford University Hospital (San Francisco), discovered that the causative agent of the disease that was at first called Coccidioides infection and later coccidioidomycosis was a fungal pathogen, and coccidioidomycosis was also distinguished from Histoplasmosis and Blastomycosis. Further, Coccidioides immitis was identified as the culprit of respiratory disorders previously called San Joaquin Valley fever, desert fever, and Valley fever, and a serum precipitin test was developed by Charles E. Smith that was able to detect an acute form of the infection. In retrospect, Smith played a major role in both medical research and raising awareness about coccidioidomycosis, especially when he became dean of the School of Public Health at the University of California at Berkeley in 1951.
Coccidioides immitis was considered by the United States during the 1950s and 1960s as a potential biological weapon. The strain selected for investigation was designated with the military symbol OC, and initial expectations were for its deployment as a human incapacitant. Medical research suggested that OC might have had some lethal effects on the populace, and Coccidioides immitis started to be classified by the authorities as a threat to public health. However, Coccidioides immitis was never weaponized to the publics knowledge, and most of the military research in the mid-1960s was concentrated on developing a human vaccine. Currently, it is not on the U.S. Department of Health and Human Services or Centers for Disease Control and Preventions list of select agents and toxins.
In 2002, Coccidioides posadasii was identified as genetically distinct from Coccidioides immitis despite their morphologic similarities and can also cause coccidioidomycosis.
Research
As of 2013, there is no vaccine available to prevent infection with Coccidioides immitis or Coccidioides posadasii, but efforts to develop such a vaccine are underway.
Other animals
Valley fever is not contagious.
In dogs, the most common symptom of coccidioidomycosis is a chronic cough, which can be dry or moist. Other symptoms include fever (in approximately 50% of cases), weight loss, anorexia, lethargy, and depression. The disease can disseminate throughout the dogs body, most commonly causing osteomyelitis (infection of the bone), which leads to lameness. Dissemination can cause other symptoms, depending on which organs are infected. If the fungus infects the heart or pericardium, it can cause heart failure and death.In cats, symptoms may include skin lesions, fever, and loss of appetite, with skin lesions being the most common.Other species in which Valley fever has been found include livestock such as cattle and horses; llamas; marine mammals, including sea otters; zoo animals such as monkeys and apes, kangaroos, tigers, etc.; and wildlife native to the geographic area where the fungus is found, such as cougars, skunks, and javelinas.
Additional images
In Popular Culture
Everything in Between, a 2022 Australian feature film, contains references to coccidioidomycosis.
See also
Coccidioides
Coccidioides immitis
Coccidioides posadasii
Zygomycosis
Medical geology
List of cutaneous conditions
Thunderhead, a 1998 novel by Douglas Preston and Lincoln Child which uses the fungus and illness as a central plot point.
References
Further reading
Twarog M, Thompson GR (2015). "Coccidioidomycosis: Recent Updates". Seminars in Respiratory and Critical Care Medicine. 36 (5): 746–755. doi:10.1055/s-0035-1562900. PMID 26398540. (Review).
Stockamp NW, Thompson GR (2016). "Coccidioidomycosis". Infectious Disease Clinics of North America. 30 (1): 229–246. doi:10.1016/j.idc.2015.10.008. PMID 26739609. (Review).
External links
U.S. Centers for Disease Control and Prevention page on coccidioidomycosis
Medline Plus Entry for coccidioidomycosis |
Filippi syndrome | Filippi syndrome, also known as Syndactyly Type I with Microcephaly and Mental Retardation, is a very rare autosomal recessive genetic disease. Only a very limited number of cases have been reported to date. Filippi Syndrome is associated with diverse symptoms of varying severity across affected individuals, for example malformation of digits, craniofacial abnormalities, intellectual disability, and growth retardation. The diagnosis of Filippi Syndrome can be done through clinical observation, radiography, and genetic testing. Filippi Syndrome cannot be cured directly as of 2022, hence the main focus of treatments is on tackling the symptoms observed on affected individuals. It was first reported in 1985.
Signs and symptoms
The symptoms of Filippi Syndrome can be congenital (apparent as an infant). The occurrence and severity of such symptoms are variable across affected individuals. The progression of symptoms over ones lifetime has not been thoroughly studied due to the small number of people with Filippi Syndrome globally.
Malformations of digits
Malformations of digits are expressed among people with Filippi Syndrome. One of the most common malformations is the webbing or fusion of digits, which is termed syndactyly. In particular, syndactyly of the third and fourth fingers or the second, third and fourth toes is termed "syndactyly type 1". The degree of syndactyly may differ across affected individuals, with some exhibiting syndactyly of soft tissues and skin only, and more severe cases exhibiting syndactyly of digital bones.Other malformations of digits include clinodactyly (curving) of the fifth fingers and brachydactyly (abnormal shortening) of digits. Brachydactyly is believed to be largely due to abnormalities arising from the bones inside the hands and feet, specifically the metacarpals and metatarsals.
Craniofacial abnormalities
Furthermore, most people with Filippi Syndrome exhibit craniofacial abnormalities. Craniofacial abnormalities are birth defects observed at the head or face region of affected individuals. Some of the craniofacial abnormalities present in people with Filippi Syndrome include microcephaly (having a skull that is smaller than normal), prominent/ elevated nasal bridge, hypertelorism (having ones pair of eyes further apart from each other than normal), and underdeveloped nasal alae (underdeveloped tissues surrounding the nostril). Less common craniofacial abnormalities include having a broad forehead, thin vermilion border (having a thin upper lip), and frontal hirsutism (having a hairy forehead).
Mental retardation
People with Filippi Syndrome may also demonstrate varying degrees of intellectual disability. Affected individuals may experience defective speech development, aphasia (experiencing difficulty in finding the appropriate words to use), vision impairment, and an inability to speak.
Growth retardation
Another characteristic symptom of people with Filippi Syndrome is the occurrence of growth retardation, which is also referred to as growth delay. Such growth delays may be either prenatal or postnatal, meaning that they can occur both before and after birth. In particular, delayed bone maturation can be observed in patients with Filippi Syndrome.
Other symptoms
People with Filippi Syndrome may exhibit some other physical abnormalities. Examples of such abnormalities include dwarfism (having a severely short stature), dislocated elbows, decreased joint mobility, muscular hypotonia (having weak muscle tone), and involuntary muscle stiffness.They may also exhibit abnormal conditions at their skin and teeth. Moreover, a portion of affected males may demonstrate cryptorchidism (a condition in which the testes fail to descend into the scrotum).
Causes
Filippi syndrome is a genetic disease with an autosomal recessive inheritance pattern at the Cytoskeleton Associated Protein 2 Like (CKAP2L) gene.
Inheritance pattern
An autosomal recessive inheritance pattern means that the disease trait is exhibited on an individual only when both copies of the disease gene in the individual demonstrate a specific pathogenic mutation. This happens when the individual inherits one copy of the mutated gene from each of their parents. In the case of Filippi Syndrome, both copies of the CKAP2L gene of an individual have to be mutated in order for them to demonstrate symptoms of the disorder.
CKAP2L gene
The CKAP2L gene is the human ortholog of the mouse CKAP2I (Radmis) gene. It contains 10 exons and is located on chromosome 2q14.1. It is a protein-coding gene that is associated with microtubules and some cellular structures involved in mitosis. The CKAP2L gene is essential for the proper formation of mitotic spindles during mitosis and the progression of the cell cycle of human cells. The expression pattern of the CKAP2L gene can explain the occurrence of syndactyly in Filippi Syndrome.
Mutations
Multiple mutations at the CKAP2L gene can cause Filippi Syndrome. Some of these mutations include a 1-base pair duplication in exon 4, a 2-base pair insertion in exon 2, a 1-base pair deletion in exon 4, and a 329-base pair deletion in exon 4 of the gene. The above mutations cause a frameshift in the gene. A frameshift mutation refers to a condition in which the reading frame of the gene is disrupted by the insertion or deletion of base pairs from the gene (if the number of inserted or deleted base pairs is not divisible by three). This frameshift mutation ultimately results in a premature termination codon (the formation of a termination codon at a position more "forward" than normal). Other mutations include a base pair transition in the start codon, which is the starting site of translation of the gene. A transition mutation occurring at this codon disrupts the codon sequence and abolishes the site. This prevents the cell from carrying out translation of the gene.
Diagnosis
The diagnosis of Filippi Syndrome is mostly done postnatally. Initial diagnosis of the disease relies on clinical observation of symptoms, including different degrees of syndactyly and craniofacial abnormalities, exhibited by affected individuals. Diagnosis can also be done through radiography, which checks for malformation of digits.Confirmation of diagnosis requires the use of genetic testing. Specifically, it can be done through detecting mutations in the CKAP2L gene, of which a total of eight causative variants having been identified.Genetic testing of Filippi Syndrome makes use of three major techniques:
Whole Exome Sequencing, which focuses on sequencing the exons in the region of the genome coding for proteins.
Next-generation Sequencing, which is a high-throughput genomic sequence analysis method that make use of flow cytometry, and is able to analyze gigabases of sequences in one instrument run.
Array Based Techniques, which makes use of microarray applications to determine chromosomal abnormalities with greater precision compare to the conventional karyotyping tests.
Treatment
Currently, Filippi Syndrome has no direct cure. It is treated according to observed symptoms on affected individuals.
Syndactyly release surgery
Syndactyly exhibit varying degrees of severity in individuals. Hence not all affected individuals with this condition must undergo surgical intervention. For example, syndactyly that occurs at the proximal end of the digits may have limited effect on the normal functioning of the hand and foot, and correction through surgery is optional.Simple syndactyly is the condition of cutaneous fusion between two digits, and can be treated by surgically rebuilding the hourglass shape web space between digits. During surgery, incision is first carried out to separate the fused fingers. It is followed by reconstruction of the web spaces side walls using dorsal advancement flaps or skin grafts obtained from the affected individuals groin. After reconstruction, additional fingerpulp flaps are required for rebuilding of the nailfold between the nail bed and the surrounding skin if there is the occurrence of syndactyly at the tip of the fingers.Treatment for complex syndactyly, which refers to the bony fusion between two digits, has a higher degree of complexity. It involves the reconstruction of web space as well as highly specific surgical procedures with accordance to different types of bony fusion. It may also require separation and relocation of the flexor digitorum profundus or tendon-diverted transplantation if the structure of the tendons in the fused digits are also affected by syndactyly.Professionals usually advice that affected individuals receive surgical treatment during the first two years of life to avoid hindrance to motor ability development.
Craniofacial surgery
Craniofacial abnormalities can be corrected through surgical methods.
Affected individuals with severe hypertelorism may undergo orbital osteotomy. The two major osteotomy methods are box osteotomy and facial bipartition, which operate from different osteotomy sites but follow the same general procedures. During surgery, part of the bone, and sometimes excessive skin, are selectively removed from the central area of the nasofrontal region, such that this part of the skull can close in and correct hypertelorism. In addition, bone grafts are placed to provide support to the eyeballs and protect them from displacement.Underdeveloped nasal alae can be corrected by orofacial reconstruction. This procedure recreates the nasal alae with the use of cartilage grafts, which are cartilage taken from the patients ear, septum or rib. Afterwards, nasolabial flaps are placed to sustain the shape of the nose, specifically the alar groove.
Speech therapy
Patients who are affected by speech impairments can be treated by speech therapy.Speech disability can be a manifestation of various physical or psychological causes. Symptomatic treatment of it is carried out after diagnostic tests such as video fluoroscopic barium study ("cookie swallow" test) or fiber-optic endoscopic evaluation. Despite the diversity in speech therapy techniques, most treatment plans follow the same progression:
Identification of defective features
Assistance with producing simple sounds; physical contact may be required to aid with motor speech disorders
Refrainment of assistance that allows patient to develop self-correction ability
Increase in length of syllables or speech
Self-evaluation of progress and provide explanation on the cause of improvementsFor post-treatment monitoring, computer-based speech therapy that makes use of instructional software can provide computer-led practices as aftercare and quantify performances outside of conventional treatments.
Epidemiology
Filippi syndrome is rare, with an estimated prevalence of less than one in a million. It has around thirty cases recorded in medical literature.The number of affected males recorded is more than twice the number of affected females. However, this is insufficient to conclude that male are at a higher risk due to the small number of reported cases. However, the CDC says less than 25 cases have been reported, the National Organization for Rare Disorders says about 18 cases have been reported, while the National Center for Advancing Translational Sciences says 30 cases have been reported in literature.
== References == |
Endometrial stromal tumour | Endometrial stromal tumours are a type of mesenchymal tumor of the main body of the uterus. Types include endometrial stromal nodule, the distinct low and high-grade endometrial stromal sarcomas, and undifferentiated uterine sarcoma.
== References == |
Aerosinusitis | Aerosinusitis, also called barosinusitis, sinus squeeze or sinus barotrauma is a painful inflammation and sometimes bleeding of the membrane of the paranasal sinus cavities, normally the frontal sinus. It is caused by a difference in air pressures inside and outside the cavities.
Presentation
Typically, sinus barotrauma is preceded by an upper respiratory tract infection or allergy. The affected person has a sudden sharp facial pain or headache during descent, which increases as the aircraft approaches ground level. The pain can ultimately become disabling unless the ambient pressure is reversed.
The pressure difference causes the mucosal lining of the sinuses to become swollen and submucosal bleeding follows with further difficulties ventilating the sinus, especially if the orifices are involved. Ultimately fluid or blood will fill the space.
In most cases of sinus barotrauma, localized pain to the frontal area is the predominant symptom. This is due to pain originating from the frontal sinus, it being above the brow bones. Less common is pain referred to the temporal, occipital, or retrobulbar region. Epistaxis or serosanguineous secretion from the nose may occur. Neurological symptoms may affect the adjacent fifth cranial nerve and especially the infraorbital nerve.
Pathology
The pathology of sinus barotrauma is directly related to Boyles law, which states that the volume of a gas is inversely proportional to the pressure on it, when temperature is constant (P1 × V1 = P2 × V2). Two types of acute barotrauma are observed: squeeze and reverse squeeze.
On ascent, the air in the paranasal sinuses will expand according to Boyles law, contracting during descent. Normally, the sinuses drain into the nasal cavity through small ostia, which permit mucociliary clearance and ventilation that equilibrates pressure. However, when the opening is obstructed due to inflammation, polyps, mucosal thickening, anatomical abnormalities, or other lesions, pressure equilibration is impossible. Squeeze is produced on descent when trapped air in the sinuses contracts and produces negative pressure. The pressure differentials are directed to the center of the sinuses producing mucosal edema, transudation, and mucosal-or submucosal-hematoma, leading to further occlusion of the sinus ostium. The sinus will fill with fluid or blood unless the pressure differential is neutralized.If the outlet is blocked during ascent, the situation is reversed and "reverse squeeze" appears. Pressure inside the sinus increases, affecting the walls of the sinus and producing pain or epistaxis.
Location
The majority of episodes of sinus barotrauma occur in the frontal sinuses with pain localized over the frontal area. Possible explanations for this might be the relatively long and delicate nasofrontal duct that connects the narrow frontal recess with the frontal sinuses.
Barotrauma located in the maxillary, ethmoidal, or sphenoid sinuses is observed less frequently and appears when the ostia are blocked; the majority of cases are probably caused by an acute upper respiratory tract infection. The magnitude of the pressure difference needed to produce a barotrauma probably shows great individual variation and is related to the size of the sinus ostium and the rate of ambient pressure change. Due to this, even commercial flying may produce severe cases of barotraumas, although most of the cases are observed in high performance aircraft with lower pressurized cabins.
Diagnosis
Most cases occur in scuba divers and fliers, and is easily diagnosed when presented to physicians immediately after exposure. On the other hand, the problem may remain undiagnosed when the history fails to relate the symptoms to exposure to environmental pressure changes or if the focus is on other etiologies.
Grades
Weissman defined three grades of sinus barotraumas according to symptomatology.
Grade I includes cases with mild transient sinus discomfort without changes visible on X-ray.
Grade II is characterized by severe pain for up to 24 h, with some mucosal thickening on X-ray.
Patients with grade III have severe pain lasting for more than 24 h and X-ray shows severe mucosal thickening or opacification of the affected sinus; epistaxis or subsequent sinusitis may be observed.
Treatment
Mild cases of barotrauma are readily treated by topical decongestants and painkillers. In severe cases or cases resistant to local treatment, functional endoscopic sinus surgery is indicated in order to re-establish drainage and ventilation of the sinuses. This treatment has shown good results in aviators who have recurrent sinus barotrauma. Computer-aided surgery has re-established the drainage of affected sinuses, especially with regard to the sphenoid sinuses. When the sphenoids were entered endoscopically, mucosal petechia and hematoma were clearly seen.
History
Sinus barotrauma or aerosinusitis has been known since the early development of aviation medicine. However, it was during World War II that the subject first received serious attention and the pathogenesis of the disease was understood to be due to exposure to high altitude flights. Rapid altitude changes with accompanying changes in ambient pressure exposed the aircrews to an increasing number of episodes of sinus barotrauma.
Referred pain from barosinusitis to the maxilla consists about one-fifth of in-flight barodontalgia (i.e., pain in the oral cavity caused by barometric pressure change) cases. Although the environment of fighter pilots produces the most stressful barometric changes, commercial flying has changed the picture of the disease.
See also
Barodontalgia – Tooth pain caused by ambient pressure change
Barotrauma – Injury caused by pressure
References
== External links == |
Chiari malformation | Chiari malformation (CM) is a structural defect in the cerebellum, characterized by a downward displacement of one or both cerebellar tonsils through the foramen magnum (the opening at the base of the skull). CMs can cause headaches, difficulty swallowing, vomiting, dizziness, neck pain, unsteady gait, poor hand coordination, numbness and tingling of the hands and feet, and speech problems. Less often, people may experience ringing or buzzing in the ears, weakness, slow heart rhythm, or fast heart rhythm, curvature of the spine (scoliosis) related to spinal cord impairment, abnormal breathing, such as central sleep apnea, characterized by periods of breathing cessation during sleep, and, in severe cases, paralysis.This can sometimes lead to non-communicating hydrocephalus as a result of obstruction of cerebrospinal fluid (CSF) outflow. The cerebrospinal fluid outflow is caused by phase difference in outflow and influx of blood in the vasculature of the brain. The malformation is named for Austrian pathologist Hans Chiari. A type II CM is also known as an Arnold–Chiari malformation in honor of Chiari and German pathologist Julius Arnold.
Signs and symptoms
Findings are due to brain stem and lower cranial nerve dysfunction. Onset of symptoms are less likely to be present during adulthood in most patients. Younger children generally have a substantially different presentation of clinical symptoms from older children. Younger children are more likely to have a more rapid neurological degeneration with profound brain stem dysfunction over several days.
Neurogenic dysphagia: Difficulty swallowing. Seen by poor feeding in patient.
Cyanosis: Bluish discoloration of skin while feeding.
Weak crying
Facial weakness
Aspiration
Headaches aggravated by Valsalva maneuvers, such as yawning, laughing, crying, coughing, sneezing or straining, bending over, or getting up suddenly
Tinnitus (ringing in the ears)
Lhermittes sign (electrical sensation that runs down the back and into the limbs)
Vertigo (dizziness)
Nausea
Schmahmann syndrome
Nystagmus (irregular eye movements; typically, so-called "downbeat nystagmus")
Facial pain
Muscle weakness
Impaired gag reflex
Dysphagia (difficulty swallowing)
Restless leg syndrome
Sleep apnea
Sleep disorders
Impaired coordination
Severe cases may develop all the symptoms and signs of a bulbar palsy
Paralysis due to pressure at the cervico-medullary junction may progress in a so-called "clockwise" fashion, affecting the right arm, then the right leg, then the left leg, and finally the left arm; or the opposite way around.
Papilledema on fundoscopic exam due to Increased intracranial pressure
Pupillary dilation
Dysautonomia: tachycardia (rapid heart), syncope (fainting), polydipsia (extreme thirst), chronic fatigue
Apnea: Sudden pause of breathing, usually during sleep.
Opisthotonos: Spasm of the head which causes head to arch backwards. More common in infants than adults.
StridorThe blockage of cerebrospinal fluid (CSF) flow may also cause a syrinx to form, eventually leading to syringomyelia. Central cord symptoms such as hand weakness, dissociated sensory loss, and, in severe cases, paralysis may occur.
Syringomyelia
Syringomyelia is a chronic progressive degenerative disorder characterized by a fluid-filled cyst located in the spinal cord. Its symptoms include pain, weakness, numbness, and stiffness in the back, shoulders, arms or legs. Other symptoms include headaches, the inability to feel changes in the temperature, sweating, sexual dysfunction, and loss of bowel and bladder control. It is usually seen in the cervical region but can extend into the medulla oblongata and pons or it can reach downward into the thoracic or lumbar segments. Syringomyelia is often associated with type I Chiari malformation and is commonly seen between the C-4 and C-6 levels. The exact development of syringomyelia is unknown but many theories suggest that the herniated tonsils in type I Chiari malformations cause a "plug" to form, which does not allow an outlet of CSF from the brain to the spinal canal. Syringomyelia is present in 25% of patients with type I Chiari malformations.
Pathophysiology
The most widely accepted pathophysiological mechanism by which Chiari type I malformations occur is by a reduction or lack of development of the posterior fossa as a result of congenital or acquired disorders. Congenital causes include hydrocephalus, craniosynostosis (especially of the lambdoid suture), hyperostosis (such as craniometaphyseal dysplasia, osteopetrosis, erythroid hyperplasia), X-linked vitamin D-resistant rickets, and neurofibromatosis type I. Acquired disorders include space occupying lesions due to one of several potential causes ranging from brain tumors to hematomas.
Traumatic brain injury may cause delayed acquired Chiari malformation, but the pathophysiology of this is unknown. Additionally, ectopia may be present but asymptomatic until a whiplash injury causes it to become symptomatic.Some neurological experts believe that Chiari malformation type I is developed as a result of Filum Disease, an abnormal traction of the spinal cord caused by an excessively tense Filum terminale. This theory was first introduced by Dr. Miguel B. Royo Salvador in 1993.
Diagnosis
Diagnosis is made through a combination of patient history, neurological examination, and medical imaging. Magnetic resonance imaging (MRI) is considered the preferred imaging modality for Chiari malformation. The MRI visualizes neural tissue such as the cerebellar tonsils and spinal cord as well as bone and other soft tissues. CT and CT myelography are other options and were used prior to the advent of MRI, unfortunately the resolution of CT based modalities do not characterize syringomyelia and other neural abnormalities as well.By convention, the cerebellar tonsil position is measured relative to the basion-opisthion line, using sagittal T1 MRI images or sagittal CT images. The selected cutoff distance for abnormal tonsil position is somewhat arbitrary, as not every person will be symptomatic at a certain amount of tonsil displacement, and the probability of symptoms and syrinx increases with greater displacement; however, greater than 5 mm is the most frequently cited cutoff number, though some consider 3–5 mm to be "borderline,"; pathological signs and syrinx may occur beyond that distance. One study showed little difference in cerebellar tonsil position between standard recumbent MRI and upright MRI for patients without a history of whiplash injury. Neuroradiological investigation is used to first rule out any intracranial condition that could be responsible for tonsillar herniation. Neuroradiological diagnostics evaluate the severity of crowding of the neural structures within the posterior cranial fossa and their pressure against the foramen magnum. Chiari 1.5 is a term used when both brainstem and tonsillar herniation through the foramen magnum are present.The diagnosis of a Chiari II malformation can be made prenatally, through ultrasound.
Classification
In the late 19th century, Austrian pathologist Hans Chiari described seemingly related anomalies of the hindbrain, the so-called Chiari malformations I, II and III. Later, other investigators added a fourth (Chiari IV) malformation. The scale of severity is rated I – IV, with IV being the most severe. Types III and IV are very rare. Since Dr. Chiaris original descriptions Chiari 0, 1.5, 3.5, and 5 have been described in the medical literature.
Types of Chiari malformation
Other conditions sometimes causally associated with Chiari malformation include hydrocephalus, syringomyelia, spinal curvature, tethered spinal cord syndrome, and connective tissue disorders such as Ehlers-Danlos syndrome and Marfan syndrome.
Chiari malformation is the most frequently used term for this set of conditions. The use of the term "Arnold–Chiari malformation" has fallen somewhat out of favor over time, although it is used to refer to the type II malformation. Current sources use "Chiari malformation" to describe its four specific types, reserving the term "Arnold-Chiari" for type II only. Some sources still use "Arnold-Chiari" for all four types.Chiari malformation or Arnold–Chiari malformation should not be confused with Budd-Chiari syndrome, a hepatic condition also named for Hans Chiari.
In Pseudo-Chiari Malformation, leaking of CSF may cause displacement of the cerebellar tonsils and similar symptoms sufficient to be mistaken for a Chiari I malformation.
Treatment
While there is no current cure, the treatments for Chiari malformation are surgery and management of symptoms, based on the occurrence of clinical symptoms rather than the radiological findings. The presence of a syrinx is known to give specific signs and symptoms that vary from dysesthetic sensations to algothermal dissociation to spasticity and paresis. These are important indications that decompressive surgery is needed for patients with Chiari Malformation Type II. Type II patients have severe brain stem damage and rapidly diminishing neurological response.Decompressive surgery involves removing the lamina of the first and sometimes the second or third cervical vertebrae and part of the occipital bone of the skull to relieve pressure. The flow of spinal fluid may be augmented by a shunt. Since this surgery usually involves the opening of the dura mater and the expansion of the space beneath, a dural graft is usually applied to cover the expanded posterior fossa.A small number of neurological surgeons believe that detethering the spinal cord as an alternate approach relieves the compression of the brain against the skull opening (foramen magnum), obviating the need for decompression surgery and associated trauma. However, this approach is significantly less documented in the medical literature, with reports on only a handful of patients. The alternative spinal surgery is also not without risk.Complications of decompression surgery can arise. They include bleeding, damage to structures in the brain and spinal canal, meningitis, CSF fistulas, occipito-cervical instability and pseudomeningeocele. Rare post-operative complications include hydrocephalus and brain stem compression by retroflexion of odontoid. Also, an extended CVD created by a wide opening and big duroplasty can cause a cerebellar "slump". This complication needs to be corrected by cranioplasty.In certain cases, irreducible compression of the brainstem occurs from in front (anteriorly or ventral) resulting in a smaller posterior fossa and associated Chiari malformation. In these cases, an anterior decompression is required. The most commonly used approach is to operate through the mouth (transoral) to remove the bone compressing the brainstem, typically the odontoid. This results in decompressing the brainstem and therefore gives more room for the cerebellum, thus decompressing the Chiari malformation. Arnold Menzes, MD, is the neurosurgeon who pioneered this approach in the 1970s at the University of Iowa. Between 1984 and 2008 (the MR imaging era), 298 patients with irreducible ventral compression of the brainstem and Chiari type 1 malformation underwent a transoral approach for ventral cervicomedullary decompression at the University of Iowa. The results have been excellent resulting in improved brainstem function and resolution of the Chiari malformation in the majority of patients.
Epidemiology
Congenital Chiari I malformation, defined as tonsilar herniations of 3 to 5 mm or greater, was previously believed to be in the range of one per 1000 births, but is likely much higher. Women are three times more likely than men to have a congenital Chiari malformation. Type II malformations are more prevalent in people of Celtic descent. A study using upright MRI found cerebellar tonsillar ectopia in 23% of adults with headache from motor-vehicle-accident head trauma. Upright MRI was more than twice as sensitive as standard MRI, likely because gravity affects cerebellar position.Cases of congenital Chiari malformation may be explained by evolutionary and genetic factors. Typically, an infants brain weighs around 400g at birth and triples to 1100-1400g by age 11. At the same time the cranium triples in volume from 500 cm3 to 1500 cm3 to accommodate the growing brain. During human evolution, the skull underwent numerous changes to accommodate the growing brain. The evolutionary changes included increased size and shape of the skull, decreased basal angle and basicranial length. These modifications resulted in significant reduction of the size of the posterior fossa in modern humans. In normal adults, the posterior fossa comprises 27% of the total intracranial space, while in adults with Chiari Type I, it is only 21%. H. neanderthalensis had platycephalic (flattened) skulls. Some cases of Chiari are associated with platybasia (flattening of the skull base).
History
The history of Chiari malformation is described below and categorized by the year:
1883: Cleland was the first to describe Chiari II or Arnold–Chiari malformation on his report of a child with spina bifida, hydrocephalus, and anatomical alterations of the cerebellum and brainstem.
1891: Hans Chiari, a Viennese pathologist, described the case of a 17-year-old female with elongation of the tonsils into cone shaped projections which accompany the medulla and are crammed into the spinal canal.
1907: Schwalbe and Gredig, pupils of German pathologist Julius Arnold, described four cases of meningomyelocele and alterations in the brainstem and cerebellum, and gave the name "Arnold-Chiari" to these malformations.
1932: Van Houweninge Graftdijk was the first to report the surgical treatment of Chiari malformations. All patients died from surgery or postoperative complications.
1935: Russell and Donald suggested that decompression of the spinal cord at the foramen magnum might facilitate the CSF circulation.
1940: Gustafson and Oldberg diagnosed Chiari malformation with syringomyelia.
1974: Bloch et al. described the tonsils position to be classified between 7 mm and 8 mm below cerebellum.
1985: Aboulezz used MRI for discovery of extension
Society and culture
The condition was brought to the mainstream on the series CSI: Crime Scene Investigation in the tenth-season episode "Internal Combustion" on February 4, 2010.
Chiari malformation was briefly mentioned on the medical drama House M.D. in the fifth-season episode "House Divided", It was the focus of the sixth-season episode "The Choice." It is also the focus of Private Practice Season 4 episode 4, where a pregnant woman is diagnosed with it. It was the a cause of death on the reality television series Dr. G: Medical Examiner in the sixth-season episode "Bruised and Battered". It was also mentioned in the medical drama A Gifted Man, in the first-season episode "In Case of Separation Anxiety".
It is also featured in the 3rd and 4th episode of the 7th season of the series Rizzoli & Isles where Dr. Maura Isles is diagnosed with the condition.
Notable people
Rosanne Cash – U.S. singer-songwriter; daughter of Johnny Cash
Julia Clukey – U.S. luge competitor for Team USA in 2010 Vancouver Winter Olympics
Joanna David – British television and stage actress
J. B. Holmes – U.S. professional golfer
Marissa Irwin – U.S. fashion model with Chiari secondary to Ehlers-Danlos syndrome
Bobby Jones – U.S. World Golf Hall of Fame golfer and founder of the Augusta National Golf Club
Allysa Seely – U.S. Gold Medalist at the 2016 Summer Paralympics in the paratriathlon
Leah Shapiro – U.S. drummer for the band Black Rebel Motorcycle Club
Michelle Stilwell – Canadian wheelchair racer and politician
Rachid Taha – Algerian singer
Sabre Norris – Australian skateboarder and surfer
See also
Hypermobility spectrum disorder
== References == |
Stasis dermatitis | Stasis dermatitis refers to the skin changes that occur in the leg as a result of "stasis" or blood pooling from insufficient venous return; the alternative name of varicose eczema comes from a common cause of this being varicose veins.Insufficient venous return results in increased pressure in the capillaries with the result that both fluid and cells may "leak" out of the capillaries. This results in red cells breaking down, with iron containing hemosiderin possibly contributing to the pathology of this entity.
Symptoms
Stasis dermatitis may be characterized by:
Skin that appears thin, brown and tissue-like, with possible skin lesions (macule or patches), red spots, superficial skin irritation and/or darkening and/or thickening of the skin at the ankles or legs
Weak skin may ulcerate in some areas and legs, ankles, or other areas may become swollen
Open sores, ulcers
Itching and/or leg pains
Sometimes pain may persist from swollen tissues and may feel like "stabbing" or "needle pricks"If skin continues to deteriorate and breaks down, a venous ulcer (also known as a stasis ulcer) may form. Without proper wound care, open cracks predispose patients for the entry of a bacterial infection, causing cellulitis in the leg.
Diagnosis
Stasis dermatitis is diagnosed clinically by assessing the appearance of red plaques on the lower legs and the inner side of the ankle. Stasis dermatitis can resemble a number of other conditions, such as cellulitis and contact dermatitis, and at times needs the use of a duplex ultrasound to confirm the diagnosis or if clinical diagnosis alone is not sufficient.
Treatment
Treatment may consist of topical applications of steroid based creams and the use of compression stockings or intermittent pneumatic compression pumps, to help force the underlying buildup of fluids back out of the lower leg.Compression therapy should consist of moderate pressures and works best for ambulating patients.
Ultimately, treating the underlying venous reflux is necessary to treat Stasis dermatitis. Invasive surgical procedures like saphenofemoral junction ligation with stripping were the norm for treatment in the past. However, less invasive methods are now more widely used. These newer methods include endovenous thermal ablation, ambulatory phlebotomy, and ultrasound foam sclerotherapy.
Complications
If stasis dermatitis goes untreated, the patient is at risk of developing venous ulcers and Acroangiodermatitis.
See also
Sinus pericranii
List of cutaneous conditions
References
== External links == |
Cystocele | A cystocele, also known as a prolapsed bladder, is a medical condition in which a womans bladder bulges into her vagina. Some may have no symptoms. Others may have trouble starting urination, urinary incontinence, or frequent urination. Complications may include recurrent urinary tract infections and urinary retention. Cystocele and a prolapsed urethra often occur together and is called a cystourethrocele. Cystocele can negatively affect quality of life.Causes include childbirth, constipation, chronic cough, heavy lifting, hysterectomy, genetics, and being overweight. The underlying mechanism involves weakening of muscles and connective tissue between the bladder and vagina. Diagnosis is often based on symptoms and examination.If the cystocele causes few symptoms, avoiding heavy lifting or straining may be all that is recommended. In those with more significant symptoms a vaginal pessary, pelvic muscle exercises, or surgery may be recommended. The type of surgery typically done is known as a colporrhaphy. The condition becomes more common with age. About a third of women over the age of 50 are affected to some degree.
Signs and symptoms
The symptoms of a cystocele may include:
a vaginal bulge
the feeling that something is falling out of the vagina
the sensation of pelvic heaviness or fullness
difficulty starting a urine stream
a feeling of incomplete urination
frequent or urgent urination
fecal incontinence
frequent urinary tract infections
back and pelvic pain
fatigue
painful sexual intercourse
bleedingA bladder that has dropped from its normal position and into the vagina can cause some forms of incontinence and incomplete emptying of the bladder.
Complications
Complications may include urinary retention, recurring urinary tract infections and incontinence. The anterior vaginal wall may actually protrude though the vaginal introitus (opening). This can interfere with sexual activity. Recurrent urinary tract infections are common for those who have urinary retention. In addition, though cystocele can be treated, some treatments may not alleviate troubling symptoms, and further treatment may need to be performed. Cystocele may affect the quality of life, women who have cystocele tend to avoid leaving their home and avoid social situations. The resulting incontinence puts women at risk of being placed in a nursing home or long-term care facility.
Cause
A cystocele occurs when the muscles, fascia, tendons and connective tissues between a womans bladder and vagina weaken, or detach. The type of cystocele that can develop can be due to one, two or three vaginal wall attachment failures: the midline defect, the paravaginal defect, and the transverse defect. The midline defect is a cystocele caused by the overstretching of the vaginal wall; the paravaginal defect is the separation of the vaginal connective tissue at the arcus tendineus fascia pelvis; the transverse defect is when the pubocervical fascia becomes detached from the top (apex) of the vagina. There is some pelvic prolapse in 40–60% of women who have given birth. Muscle injuries have been identified in women with cystocele. These injuries are more likely to occur in women who have given birth than those who have not. These muscular injuries result in less support to the anterior vaginal wall.Some women with connective tissue disorders are predisposed to developing anterior vaginal wall collapse. Up to one third of women with Marfan syndrome have a history of vaginal wall collapse. Ehlers-Danlos syndrome in women is associated with a rate of 3 out of 4.
Risk factors
Risk factors for developing a cystocele are:
Connective tissue disorders predispose women to developing cystocele and other pelvic organ prolapse. The tissues tensile strength of the vaginal wall decreases when the structure of the collagen fibers change and become weaker.
Diagnosis
There are two types of cystocele. The first is distension. This is thought to be due to the overstretching of the vaginal wall and is most often associated with aging, menopause and vaginal delivery. It can be observed when the rugae are less visible or even absent. The second type is displacement. Displacement is the detachment or abnormal elongation of supportive tissue.The initial assessment of cystocele can include a pelvic exam to evaluate leakage of urine when the women is asked to bear down or give a strong cough (Valsalva maneuver), and the anterior vaginal wall measured and evaluated for the appearance of a cystocele. If a woman has difficulty emptying her bladder, the clinician may measure the amount of urine left in the womans bladder after she urinates called the postvoid residual. This is measured by ultrasound. A voiding cystourethrogram is a test that involves taking x-rays of the bladder during urination. This x-ray shows the shape of the bladder and lets the doctor see any problems that might block the normal flow of urine. A urine culture and sensitivity test will assess the presence of a urinary tract infection that may be related to urinary retention. Other tests may be needed to find or rule out problems in other parts of the urinary system. Differential diagnosis will be improved by identifying possible inflammation of the Skenes glands and Bartholin glands.
Grading
A number of scales exist to grade the severity of a cystocele.The pelvic organ prolapse quantification (POP-Q) assessment, developed in 1996, quantifies the descent of the cystocele into the vagina. The POP-Q provides reliable description of the support of the anterior, posterior and apical vaginal wall. It uses objective and precise measurements to the reference point, the hymen. Cystocele and prolapse of the vagina from other causes is staged using POP-Q criteria can range from good support (no descent into the vagina) reported as a POP-Q stage 0 or I to a POP-Q score of IV which includes prolapse beyond the hymen. It also used to quantifies the movement of other structures into the vaginal lumen and their descent.The Baden–Walker Halfway Scoring System is used as the second most used system and assigns the classifications as mild (grade 1) when the bladder droops only a short way into the vagina; (grade 2) cystocele, the bladder sinks far enough to reach the opening of the vagina; and (grade 3) when the bladder bulges out through the opening of the vagina.
Classifications
Cystocele can be further described as being apical, medial, lateral, or mediolateral.Apical cystocele is located upper third of the vagina. The structures involved are the endopelvic fascia and ligaments. The cardinal ligaments and the uterosacral ligaments suspend the upper vaginal-dome. The cystocele in this region of the vagina is thought to be due to a cardinal ligament defect.Medial cystocele forms in the mid-vagina and is related to a defect in the suspension provided by to a sagittal suspension system defect in the uterosacral ligaments and pubocervical fascia. The pubocervical fascia may thin or tear and create the cystocele. An aid in diagnosis is the creation of a shiny spot on the epithelium of the vagina. This defect can be assessed by MRI.Lateral cystocele forms when both the pelviperineal muscle and its ligamentous–fascial develop a defect. The ligamentous– fascial creates a hammock-like suspension and support for the lateral sides of the vagina. Defects in this lateral support system results in a lack of bladder support. Cystocele that develops laterally is associated with an anatomic imbalance between anterior vaginal wall and the arcus tendineus fasciae pelvis – the essential ligament structure.
Prevention
Cystocele may be mild enough not to result in symptoms that are troubling to a woman. In this case, steps to prevent it from worsening include:
smoking cessation
losing weight
pelvic floor strengthening
treatment of a chronic cough
maintaining healthy bowel habits
eating high fiber foods
avoiding constipation and straining
Treatment
Treatment options range from no treatment for a mild cystocele to surgery for a more extensive cystocele. If a cystocele is not bothersome, the clinician may only recommend avoiding heavy lifting or straining that could cause the cystocele to worsen. If symptoms are moderately bothersome, the doctor may recommend a pessary, a device placed in the vagina to hold the bladder in place and to block protrusion. Treatment can consist of a combination of non-surgical and surgical management. Treatment choice is also related to age, desire to have children, severity of impairment, desire to continue sexual intercourse and other diseases that a woman may have.
Non-surgical
Cystocele is often treated by non-surgical means:
Pessary – This is a removable device inserted into the vagina to support the anterior vaginal wall. Pessaries come in many different shapes and sizes. There are sometimes complications with the use of a pessary.
Pelvic floor muscle therapy – Pelvic floor exercises to strengthen vaginal support can be of benefit. Specialized physical therapy can be prescribed to help strengthen the pelvic floor muscles.
Dietary changes – Ingesting high fiber foods will aid in promoting bowel movements.
Estrogen – intravaginal administration helps to prevent pelvic muscle atrophy
Surgery
The surgery to repair the anterior vaginal wall may be combined with other procedures that will repair the other points of pelvic organ support such as anterior-posterior repair and anterior colporrhaphy. Treatment of cystocele often accompanies the more invasive hysterectomy. Since the failure rate in cystocele repair remains high, additional surgery may be needed. Women who have surgery to repair a cystocele have a 17% of needing another operation within the next ten years.The surgical treatment of cystocele will depend on the cause of the defect and whether it occurs at the top (apex), middle, or lower part of the anterior vaginal wall. The type of surgery will also depend on the type of damage that exists between supporting structures and the vaginal wall. One of the most common surgical repairs is colporrhaphy. This surgical procedure consists of making a longitudinal folding of the vaginal tissue, suturing it into place and creating a stronger point of resistance to the intruding bladder wall. Surgical mesh is sometimes used to strengthen the anterior vaginal wall. It has a 10–50% failure rate. In some cases a surgeon may choose to use surgical mesh to strengthen the repair.During surgery, the repair of the vaginal wall consists of folding over and then suturing the existing tissue between the vagina and bladder to strengthen it. This tightens the layers of tissue to promote the replacement of the pelvic organs into their normal place. The surgery also provides more support for the bladder. This surgery is done by a surgeon specializing in gynecology and is performed in a hospital. Anesthesia varies according to the needs of each woman. Recovery may take four to six weeks. Other surgical treatment may be performed to treat cystocele. Support for the vaginal wall is accomplished with the paravaginal defect repair. This is a surgery, usually laproscopic, that is done to the ligaments and fascia through the abdomen. The lateral ligaments and supportive structures are repaired, sometimes shortened to provide additional support to the vaginal wall.Sacrocolpopexy is a procedure that stabilizes the vaginal vault (the uppermost portion of the vagina) and is often chosen as the treatment for cystocele, especially if previous surgeries were not successful. The procedure consists of attaching the vaginal vault to the sacrum. It has a success rate of 90%. Some women choose not to have surgery to close the vagina. This surgery, called colpocleisis, treats cystocele by closing the vaginal opening. This can be an option for women who no longer want to have vaginal intercourse.If an enterocele/sigmoidocele, or prolapse of the rectum/colon, is also present, the surgical treatment will take this concurrent condition into account while planning and performing the repairs. Estrogen that is administered vaginally before surgical repair can strengthen the vaginal tissue providing a more successful outcome when mesh or sutures are used for the repair. Vaginal thickness increases after estrogen therapy. Another review on the surgical management of cystocele describes a more successful treatment that more strongly attaches the ligaments and fascia to the vagina to lift and stabilize it.Post surgical complications can develop. The complications following surgical treatment of cystocele are:
After surgery, a woman is instructed to restrict her activities and monitor herself for signs of infection such as an elevated temperature, discharge with a foul odor and consistent pain. Clinicians may recommend that sneezing, coughing, and constipation are to be avoided. Splinting the abdomen while coughing provides support to an incised area and decreases pain on coughing. This is accomplished by applying gentle pressure to the surgical site for bracing during a cough.Recurrent surgery on the pelvic organs may not be due to a failure of the surgery to correct the cystocele. Subsequent surgeries can be directly or indirectly relating to the primary surgery. Prolapse can occur at a different site in the vagina. Further surgery after the initial repair can be to treat complications of mesh displacement, pain, or bleeding. Further surgery may be needed to treat incontinence.One goal of surgical treatment is to restore the vagina and other pelvic organs to their anatomically normal positions. This may not be the outcome that is most important to the woman being treated who may only want relief of symptoms and an improvement in her quality of life. The International Urogynecological Association (IUGA) has recommended that the data collected regarding the success of cystocele and pelvic organ repairs include the presence or absence of symptoms, satisfaction and Quality of Life. Other measures of a successful outcome should include perioperative data, such as operative time and hospital stay. Standardized Healthcare Quality of Life should be part of the measure of a successful resolution of cystocele. Data regarding short- and long-term complications is included in the recommendations of the IUGA to better assess the risk–benefit ratio of each procedure. Current investigations into the superiority of using biological grafting versus native tissue or surgical mesh indicates that using grafts provides better results.
Epidemiology
A large study found a rate of 29% over the lifetime of a woman. Other studies indicate a recurrence rate as low as 3%.In the US, greater than 200,000 surgeries are performed each year for pelvic organ prolapse and 81% of these are to correct cystocele. Cystocele occurs most frequently compared to the prolapse of other pelvic organs and structure. Cystocele is found to be three times as common as vaginal vault prolapse and twice as often as posterior vaginal wall defects. The incidence of cystocele is around 9 per 100 women-years. The highest incidence of symptoms occurs between ages of 70 and 79 years. Based on population growth statistics, the number of women with prolapse will increase by a minimum of 46% by the year 2050 in the US. Surgery to correct prolapse after hysterectomy is 3.6 per 1,000 women-years.
History
Notable is the mention of cystocele in many older cultures and locations. In 1500 B.C. Egyptians wrote about the "falling of the womb". In 400 B.C. a Greek physician documented his observations and treatments:
"After the patient had been tied to a ladder-like frame, she was tipped upward so that her head was toward the bottom of the frame. The frame was then moved upward and downward more or less rapidly for approximately 3–5 min. As the patient was in an inverted position, it was thought that the prolapsing organs of the genital tract would be returned to their normal position by the force of gravity and the shaking motion."Hippocrates had his own theories regarding the cause of prolapse. He thought that recent childbirth, wet feet, sexual excesses, exertion, and fatigue may have contributed to the condition. Polybus, Hippocratess son-in-law, wrote: "a prolapsed uterus was treated by using local astringent lotions, a natural sponge packed into the vagina, or placement of half a pomegranate in the vagina." In 350 A.D., another practitioner named Soranus described his treatments which stated that the pomegranate should be dipped into vinegar before insertion. Success could be enhanced if the woman was on bed rest and reduced intake of fluid and food. If the treatment was still not successful, the womans legs were tied together for three days.In 1521, Berengario da Carpi performed the first surgical treatment for prolapse. This was to tie a rope around the prolapse, tighten it for two days until it was no longer viable and cut it off. Wine, aloe, and honey were then applied to the stump.In the 1700s, a Swiss gynecologist, Peyer, published a description of a cystocele. He was able to describe and document both cystocele and uterine prolapse. In 1730, Halder associated cystocele with childbirth. During this same time, efforts began to standardize the terminology that is still familiar today. In the 1800s, the surgical advancements of anesthesia, suturing, suturing materials and acceptance of Joseph Listers theories of antisepsis improved outcomes for women with cystocele. The first surgical techniques were practiced on female cadavers. In 1823, Geradin proposed that an incision and resection may provide treatment. In 1830, the first dissection of the vagina was performed by Dieffenbach on a living woman. In 1834, Mendé proposed that dissecting and repair of the edges of the tissues could be done. In 1859, Huguier proposed the amputation of the cervix was going to solve the problem for elongation.In 1866, a method of correcting a cystocele was proposed that resembled current procedures. Sim subsequently developed another procedure that did not require the full-thickness dissection of the vaginal wall. In 1888, another method of treating anterior vaginal wall Manchester combined an anterior vaginal wall repair with an amputation of the cervix and a perineorrhaphy. In 1909, White noted the high rate of recurrence of cystocele repair. At this time it was proposed that reattaching the vagina to support structures was more successful and resulted in less recurrence. This same proposal was proposed again in 1976 but further studies indicated that the recurrence rate was not better.In 1888, treatments were tried that entered the abdomen to make reattachments. Some did not agree with this and suggested an approach through the inguinal canal. In 1898, further abdominal approaches were proposed. No further advances have been noted until 1961 when reattachment of the anterior vaginal wall to Coopers ligament began to be used. Unfortunately, posterior vaginal wall prolapse occurred in some patients even though the anterior repair was successful.In 1955, using mesh to support pelvic structures came into use. In 1970, tissue from pigs began to be used to strengthen the anterior vaginal wall in surgery. Beginning in 1976, improvement in suturing began along with the surgical removal of the vagina being used to treat prolapse of the bladder. In 1991, assumptions about the detailed anatomy of the pelvic support structures began to be questioned regarding the existence of some pelvic structures and the non-existence of others. More recently, the use of stem cells, robot-assisted laparoscopic surgery are being used to treat cystocele.
See also
Hysterectomy
Fecal incontinence
Sigmoidocele
Urethropexy
References
Further reading
Using splinting to support and diminish pain while coughing, Craven and Hirnles Fundamentals of Nursing: Human Health and Function, 6th edition
External links
Cystocele, Pelvic Organ Prolapse |
Distal intestinal obstruction syndrome | Distal intestinal obstruction syndrome (DIOS) involves obstruction of the distal part of the small intestines by thickened intestinal content and occurs in about 20% of mainly adult individuals with cystic fibrosis. DIOS was previously known as meconium ileus equivalent, a name which highlights its similarity to the intestinal obstruction seen in newborn infants with cystic fibrosis. DIOS tends to occur in older individuals with pancreatic insufficiency. Individuals with DIOS may be predisposed to bowel obstruction, though it is a separate entity than true constipation.
Signs and symptoms
Signs and symptoms of DIOS include a sudden onset of crampy abdominal pain, vomiting, and a palpable mass (often in the right lower quadrant) in the abdomen. The characteristic abdominal pain is typically located in the center or right lower quadrant of the abdomen. X-rays of the abdomen may reveal stool in the colon and air-fluid levels in the small intestines.
Diagnosis
A complete history and physical examination can be suggestive, especially if a palpable mass in the right lower quadrant of the abdomen is present (though this can be present in the absence of DIOS). Ultrasound and computed tomography (CT) imaging of the abdomen can confirm the diagnosis by demonstrating dilated loops of intestine with material in the intestinal lumen with bubbles. Air-fluid levels may be seen in those affected by DIOS.
Classification
DIOS is sometimes classified by the degree of obstruction as incomplete or complete DIOS.
Differential diagnosis
Additional diagnoses which may present with similar symptoms to DIOS include severe constipation, appendicitis, and intussusception.
Management
Differentiation of DIOS from constipation is generally performed by unit specializing in the treatment of cystic fibrosis. Adequate hydration and an aggressive regimen of laxatives are essential for treatment and prevention of DIOS. Osmotic laxatives such as polyethylene glycol are preferred. Individuals prone to DIOS tend to be at risk for repeated episodes and often require maintenance therapy with pancreatic enzyme replacement, hydration and laxatives (if the symptoms are also mild). Oral contrast instillation into the colon/ileum under radiological control has been found to reduce the need for surgical intervention.
References
External links
http://www.cfmedicine.com/htmldocs/CFText/dios.htm
http://www.rbht.nhs.uk/healthprofessionals/clinical-departments/cystic-fibrosis/clinical-guidelines/nutritional-and-gastrointestinal-care/constipation-and-distal-intestinal-obstructive-syndrome/ |
Scoliosis | Scoliosis is a condition in which a persons spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not typically cause problems, but more severe cases can affect breathing and movement. Pain is usually present in adults, and can worsen with age.The cause of most cases is unknown, but it is believed to involve a combination of genetic and environmental factors. Risk factors include other affected family members. It can also occur due to another condition such as muscle spasms, cerebral palsy, Marfan syndrome, and tumors such as neurofibromatosis. Diagnosis is confirmed with X-rays. Scoliosis is typically classified as either structural in which the curve is fixed, or functional in which the underlying spine is normal.Treatment depends on the degree of curve, location, and cause. Minor curves may simply be watched periodically. Treatments may include bracing, specific exercises, posture checking, and surgery. The brace must be fitted to the person and used daily until growing stops. Specific exercises, such as exercises that focus on the core, may be used to try to decrease the risk of worsening. They may be done alone or along with other treatments such as bracing. Evidence that chiropractic manipulation, dietary supplements, or exercises can prevent the condition from worsening is weak. However, exercise is still recommended due to its other health benefits.Scoliosis occurs in about 3% of people. It most commonly develops between the ages of ten and twenty. Females typically are more severely affected than males with a ratio of 4:1. The term is from Ancient Greek: σκολίωσις, romanized: skoliosis which means "a bending".
Signs and symptoms
Symptoms associated with scoliosis can include:
Pain in the back, shoulders, neck, ribs and buttock pain nearest the bottom of the back
Respiratory or cardiac problems in severe cases
Constipation due to curvature causing "tightening" of the stomach, intestines, etc.
Limited mobility secondary to pain or functional limitation in adults mostly when twisting the torso.The signs of scoliosis can include:
Uneven musculature on one side of the spine
Rib prominence or a prominent shoulder blade, caused by rotation of the rib cage in thoracic scoliosis
Uneven hips, arms, or leg lengths
Slow nerve action
Uneven posture
Heart and lung problems in severe cases
Calcium deposits in the cartilage endplate and sometimes in the disc itself
Course
People who have reached skeletal maturity are less likely to have a worsening case. Some severe cases of scoliosis can lead to diminishing lung capacity, pressure exerted on the heart, and restricted physical activities.Recent longitudinal studies reveal that the most common form of the condition, late-onset idiopathic scoliosis, causes little physical impairment other than back pain and cosmetic concerns, even when untreated, with mortality rates similar to the general population. Older beliefs that untreated idiopathic scoliosis necessarily progresses into severe (cardiopulmonary) disability by old age have been refuted by later studies.
Causes
The many causes of scoliosis include neuromuscular problems and inherited diseases or conditions caused by the environment.An estimated 65% of scoliosis cases are idiopathic, about 15% are congenital, and about 10% are secondary to a neuromuscular disease.About 38% of variance in scoliosis risk is due to genetic factors, and 62% is due to the environment. The genetics are likely complex, however, given the inconsistent inheritance and discordance among monozygotic twins. The specific genes that contribute to development of scoliosis have not been conclusively identified. At least one gene, CHD7, has been associated with the idiopathic form of scoliosis.
Several candidate gene studies have found associations between idiopathic scoliosis and genes mediating bone formation, bone metabolism, and connective tissue structure. Several genome-wide studies have identified a number of loci as significantly linked to idiopathic scoliosis. In 2006, idiopathic scoliosis was linked with three microsatellite polymorphisms in the MATN1 gene (encoding for matrilin 1, cartilage matrix protein). Fifty-three single nucleotide polymorphism markers in the DNA that are significantly associated with adolescent idiopathic scoliosis were identified through a genome-wide association study.Adolescent idiopathic scoliosis has no clear causal agent, and is generally believed to be multifactorial; leading to "progressive functional limitations" for individuals. Research suggests that Posterior Spinal Fusion (PSF) can be used to correct the more severe deformities caused by adolescent idiopathic scoliosis. Such procedures can result in a return to physical activity in about 6 months, which is very promising, although minimal back pain is still to be expected in the most severe cases. The prevalence of scoliosis is 1% to 2% among adolescents, but the likelihood of progression among adolescents with a Cobb angle less than 20° is about 10% to 20%.Congenital scoliosis can be attributed to a malformation of the spine during weeks three to six in utero due to a failure of formation, a failure of segmentation, or a combination of stimuli. Incomplete and abnormal segmentation results in an abnormally shaped vertebra, at times fused to a normal vertebra or unilaterally fused vertebrae, leading to the abnormal lateral curvature of the spine.
Resulting from other conditions
Secondary scoliosis due to neuropathic and myopathic conditions can lead to a loss of muscular support for the spinal column so that the spinal column is pulled in abnormal directions. Some conditions which may cause secondary scoliosis include muscular dystrophy, spinal muscular atrophy, poliomyelitis, cerebral palsy, spinal cord trauma, and myotonia. Scoliosis often presents itself, or worsens, during an adolescents growth spurt and is more often diagnosed in females than males.Scoliosis associated with known syndromes is often subclassified as "syndromic scoliosis". Scoliosis can be associated with amniotic band syndrome, Arnold–Chiari malformation, Charcot–Marie–Tooth disease, cerebral palsy, congenital diaphragmatic hernia, connective tissue disorders, muscular dystrophy, familial dysautonomia, CHARGE syndrome, Ehlers–Danlos syndrome (hyperflexibility, "floppy baby" syndrome, and other variants of the condition), fragile X syndrome, Friedreichs ataxia, hemihypertrophy, Loeys–Dietz syndrome, Marfan syndrome, nail–patella syndrome, neurofibromatosis, osteogenesis imperfecta, Prader–Willi syndrome, proteus syndrome, spina bifida, spinal muscular atrophy, syringomyelia, and pectus carinatum.Another form of secondary scoliosis is degenerative scoliosis, also known as de novo scoliosis, which develops later in life secondary to degenerative (may or may not be associated with aging) changes. This is a type of deformity that starts and progresses because of the collapse of the vertebral column in an asymmetrical manner. As bones start to become weaker and the ligaments and discs located in the spine become worn as a result of age-related changes, the spine begins to curve.
Diagnosis
People who initially present with scoliosis undergo a physical examination to determine whether the deformity has an underlying cause and to exclude the possibility of the underlying condition more serious than simple scoliosis.The persons gait is assessed, with an exam for signs of other abnormalities (e.g., spina bifida as evidenced by a dimple, hairy patch, lipoma, or hemangioma). A thorough neurological examination is also performed, the skin for café au lait spots, indicative of neurofibromatosis, the feet for cavovarus deformity, abdominal reflexes and muscle tone for spasticity.When a person can cooperate, they are asked to bend forward as far as possible. This is known as the Adams forward bend test and is often performed on school students. If a prominence is noted, then scoliosis is a possibility and an X-ray may be done to confirm the diagnosis.
As an alternative, a scoliometer may be used to diagnose the condition.When scoliosis is suspected, weight-bearing, full-spine AP/coronal (front-back view) and lateral/sagittal (side view) X-rays are usually taken to assess the scoliosis curves and the kyphosis and lordosis, as these can also be affected in individuals with scoliosis. Full-length standing spine X-rays are the standard method for evaluating the severity and progression of scoliosis, and whether it is congenital or idiopathic in nature. In growing individuals, serial radiographs are obtained at 3- to 12-month intervals to follow curve progression, and, in some instances, MRI investigation is warranted to look at the spinal cord. An average scoliosis patient has been in contact with around 50-300mGy of radiation due to these radiographs during this time period. The standard method for assessing the curvature quantitatively is measuring the Cobb angle, which is the angle between two lines, drawn perpendicular to the upper endplate of the uppermost vertebra involved and the lower endplate of the lowest vertebra involved. For people with two curves, Cobb angles are followed for both curves. In some people, lateral-bending X-rays are obtained to assess the flexibility of the curves or the primary and compensatory curves.Congenital and idiopathic scoliosis that develops before the age of 10 is referred to as early-onset scoliosis. Progressive idiopathic early-onset scoliosis can be a life-threatening condition with negative effects on pulmonary function. Scoliosis that develops after 10 is referred to as adolescent idiopathic scoliosis. Screening adolescents without symptoms for scoliosis is of unclear benefit.
Definition
Scoliosis is defined as a three-dimensional deviation in the axis of a persons spine. Most instances, including The Scoliosis Research Society, define scoliosis as a Cobb angle of more than 10° to the right or left as the examiner faces the person, i.e. in the coronal plane.Scoliosis has been described as a biomechanical deformity, the progression of which depends on asymmetric forces otherwise known as the Hueter-Volkmann Law.
Management
Scoliosis curves do not straighten out on their own. Many children have slight curves that do not need treatment. In these cases, the children grow up to lead normal body posture by itself, even though their small curves never go away. If the patient has a larger curve and they are still growing, it is important to monitor the curve for change by periodic examination and standing x-rays as needed. The rise in spinal abnormalities require examination by an orthopaedic surgeon to determine if active treatment is needed.The traditional medical management of scoliosis is complex and is determined by the severity of the curvature and skeletal maturity, which together help predict the likelihood of progression.
The conventional options for children and adolescents are:
Observation
Bracing
Surgery
Physical Therapy. Evidence suggests use of scoliosis specific exercises might prevent the progression of the curve along with possible bracing and surgery avoidance.For adults, treatment usually focuses on relieving any pain:
Pain medication
Posture checking
Bracing
SurgeryTreatment for idiopathic scoliosis also depends upon the severity of the curvature, the spines potential for further growth, and the risk that the curvature will progress. Mild scoliosis (less than 30° deviation) and moderate scoliosis (30–45°) can typically be treated conservatively with bracing in conjunction with scoliosis-specific exercises. Severe curvatures that rapidly progress may require surgery with spinal rod placement and spinal fusion. In all cases, early intervention offers the best results.A specific type of physical therapy may be useful. Evidence to support their use however is weak. Low quality evidence suggests scoliosis-specific exercises (SSE) may be more effective than electrostimulation. Evidence for the Schroth method is insufficient to support its use. Significant improvement in function, vertebral angles and trunk asymmetries have been recorded following the implementation of Schroth method in terms of conservative management of scoliosis. Some other forms of exercises interventions have been lately used in the clinical practice for therapeutic management of scoliosis such as global postural reeducation and the Klapp method.
Bracing
Bracing is normally done when the person has bone growth remaining and is, in general, implemented to hold the curve and prevent it from progressing to the point where surgery is recommended. In some cases with juveniles, bracing has reduced curves significantly, going from a 40° (of the curve, mentioned in length above) out of the brace to 18°. Braces are sometimes prescribed for adults to relieve pain related to scoliosis. Bracing involves fitting the person with a device that covers the torso; in some cases, it extends to the neck (example being the Milwaukee Brace).
The most commonly used brace is a TLSO, such as a Boston brace, a corset-like an appliance that fits from armpits to hips and is custom-made from fiberglass or plastic. It is typically recommended to be worn 22–23 hours a day, and applies pressure on the curves in the spine. The effectiveness of the brace depends on not only brace design and orthotist skill, but also peoples compliance and amount of wear per day.
An alternative form of brace is a nighttime only brace, that are worn only at night whilst the child sleeps, which overcorrect the deformity. Whilst nighttime braces are more convenient for children and families, it is unknown if the effectiveness of the brace is as good as conventional braces, therefore the UK government have funded a large clinical trial to resolve this uncertainty; called the BASIS study. The BASIS study is ongoing throughout the UK in all of the leading UK childrens hospitals that treat scoliosis, with families encouraged to take part.
Indications for bracing: people who are still growing who present with Cobb angles less than 20° should be closely monitored. People who are still growing who present with Cobb angles of 20 to 29° should be braced according to the risk of progression by considering age, Cobb angle increase over a six-month period, Risser sign, and clinical presentation. People who are still growing who present with Cobb angles greater than 30° should be braced. However, these are guidelines and not every person will fit into this table.
For example, a person who is still growing with a 17° Cobb angle and significant thoracic rotation or flatback could be considered for nighttime bracing. On the opposite end of the growth spectrum, a 29° Cobb angle and a Risser sign three or four might not need to be braced because the potential for progression is reduced. The Scoliosis Research Societys recommendations for bracing include curves progressing to larger than 25°, curves presenting between 30 and 45°, Risser sign 0, 1, or 2 (an X-ray measurement of a pelvic growth area), and less than six months from the onset of menses in girls.Scoliosis braces are usually comfortable, especially when well designed and well fitted, also after the 7- to 10-day break-in period. A well fitted and functioning scoliosis brace provides comfort when it is supporting the deformity and redirecting the body into a more corrected and normal physiological position.Evidence supports that bracing prevents worsening of disease, but whether it changes quality of life, appearance, or back pain is unclear.
Surgery
Surgery is usually recommended by orthopedists for curves with a high likelihood of progression (i.e., greater than 45 to 50° of magnitude), curves that would be cosmetically unacceptable as an adult, curves in people with spina bifida and cerebral palsy that interfere with sitting and care, and curves that affect physiological functions such as breathing.Surgery is indicated by the Society on Scoliosis Orthopaedic and Rehabilitation Treatment (SOSORT) at 45 to 50° and by the Scoliosis Research Society (SRS) at a Cobb angle of 45°. SOSORT uses the 45 to 50° threshold as a result of the well-documented, plus or minus 5° measurement error that can occur while measuring Cobb angles.Surgeons who are specialized in spine surgery perform surgery for scoliosis. To completely straighten a scoliotic spine is usually impossible, but for the most part, significant corrections are achieved.The two main types of surgery are:
Anterior fusion: This surgical approach is through an incision at the side of the chest wall.
Posterior fusion: This surgical approach is through an incision on the back and involves the use of metal instrumentation to correct the curve.One or both of these surgical procedures may be needed. The surgery may be done in one or two stages and, on average, takes four to eight hours.
A new tethering procedure (anterior vertebral body tethering) may be appropriate for some patients.
Prognosis
A 50-year follow-up study published in the Journal of the American Medical Association (2003) asserted the lifelong physical health, including cardiopulmonary and neurological functions, and mental health of people with idiopathic scoliosis are comparable to those of the general population. Scoliosis that interferes with normal systemic functions is "exceptional" and "rare", and "untreated [scoliosis] people had similar death rates and were just as functional and likely to lead productive lives 50 years after diagnosis as people with normal spines." In an earlier University of Iowa follow-up study, 91% of people with idiopathic scoliosis displayed normal pulmonary function, and their life expectancy was 2% less than that of the general population. Later (2006-) studies corroborate these findings, adding that they are "reassuring for the adult patient who has adolescent onset idiopathic scoliosis in approximately the 50–70° range." These modern landmark studies supersede earlier studies (e.g. Mankin-Graham-Schauk 1964) that did implicate moderate idiopathic scoliosis in impaired pulmonary function.Generally, the prognosis of scoliosis depends on the likelihood of progression. The general rules of progression are larger curves carry a higher risk of progression than smaller curves, and thoracic and double primary curves carry a higher risk of progression than single lumbar or thoracolumbar curves. In addition, people not having yet reached skeletal maturity have a higher likelihood of progression (i.e., if the person has not yet completed the adolescent growth spurt).
Epidemiology
Scoliosis affects 2–3% of the United States population, which is equivalent to about five to nine million cases. A scoliosis spinal column curve of 10° or less affects 1.5% to 3% of individuals. The age of onset is usually between 10 years and 15 years (can occur at a younger age) in children and adolescents, making up to 85% of those diagnosed. This is seen to be due to rapid growth spurts occurring at puberty when spinal development is most relenting to genetic and environmental influences. Because female adolescents undergo growth spurts before postural musculoskeletal maturity, scoliosis is more prevalent among females.Although fewer cases are present today using Cobb angle analysis for diagnosis, scoliosis remains a prevailing condition, appearing in otherwise healthy children. Despite the fact that scoliosis is a disfigurement of the spine, it has been shown to influence the pneumonic function, balance while standing and stride execution of kids with scoliosis. The impacts of backpack carriage on these three side effects have been broadly researched. Incidence of idiopathic scoliosis (IS) stops after puberty when skeletal maturity is reached, however, further curvature may proceed during late adulthood due to vertebral osteoporosis and weakened musculature.
History
Ever since the condition was discovered by the Greek physician Hippocrates, a cure has been sought. Treatments such as bracing and the insertion of rods into the spine were employed during the 1900s. In the mid-20th century, new treatments and improved screening methods have been developed to reduce the progression of scoliosis in patients and alleviate their associated pain. School children were during this period believed to develop poor posture as a result of working at their desks, and many were diagnosed with scoliosis. It was also considered to be caused by tuberculosis or poliomyelitis, diseases that were successfully managed using vaccines and antibiotics.The American orthopaedic surgeon Alfred Shands Jr. discovered that two percent of patients had non-disease related scoliosis, later termed idiopathic scoliosis, or the "cancer of orthopaedic surgery". These patients were treated with questionable remedies. A theory at the time—now discredited—was that the condition needed to be detected early to halt its progression, and so some schools made screening for scoliosis mandatory. Measurements of shoulder height, leg length and spinal curvature were made, and the ability to bend forwards, along with body posture, was tested, but students were sometimes misdiagnosed because of their poor posture.An early treatment was the Milwaukee brace, a rigid contraption of metal rods attached to a plastic or leather girdle, designed to straighten the spine. Because of the constant pressure applied to the spine, the brace was uncomfortable. It caused jaw and muscle pain, skin irritation, as well as low self-esteem.
Surgery
In 1962, the American orthopaedic surgeon Paul Harrington introduced a metal spinal system of instrumentation that assisted with straightening the spine, as well as holding it rigid while fusion took place. The now obsolete Harrington rod operated on a ratchet system, attached by hooks to the spine at the top and bottom of the curvature that when cranked would distract—or straighten—the curve. The Harrington rod obviates the need for prolonged casting, allowing patients greater mobility in the postoperative period and significantly reducing the quality of life burden of fusion surgery. The Harrington rod was the precursor to most modern spinal instrumentation systems. A major shortcoming was that it failed to produce a posture wherein the skull would be in proper alignment with the pelvis, and it did not address rotational deformity. As the person aged, there would be increased wear and tear, early onset arthritis, disc degeneration, muscular stiffness, and acute pain. "Flatback" became the medical name for a related complication, especially for those who had lumbar scoliosis.In the 1960s, the gold standard for idiopathic scoliosis was a posterior approach using a single Harrington rod. Post-operative recovery involved bed rest, casts, and braces. Poor results became apparent over time.In the 1970s, an improved technique was developed using two rods and wires attached at each level of the spine. This segmented instrumentation system allowed patients to become mobile soon after surgery.In the 1980s, Cotrel-Dubousset instrumentation improved fixation and addressed sagittal imbalance and rotational defects unresolved by the Harrington rod system. This technique used multiple hooks with rods to give stronger fixation in three dimensions, usually eliminating the need for postoperative bracing.
Evolution
There are links between human spinal morphology, bipedality, and scoliosis which suggest an evolutionary basis for the condition. Scoliosis has not been found in chimpanzees or gorillas. Thus, it has been hypothesized that scoliosis may actually be related to humans morphological differences from these apes. Other apes have a shorter and less mobile lower spine than humans. Some of the lumbar vertebrae in Pan are "captured", meaning that they are held fast between the ilium bones of the pelvis. Compared to humans, Old World monkeys have far larger erector spinae muscles, which are the muscles which hold the spine steady. These factors make the lumbar spine of most primates less flexible and far less likely to deviate than those of humans. While this may explicitly relate only to lumbar scolioses, small imbalances in the lumbar spine could precipitate thoracic problems as well.Scoliosis may be a byproduct of strong selection for bipedalism. For a bipedal stance, a highly mobile, elongated lower spine is very beneficial. For instance, the human spine takes on an S-shaped curve with lumbar lordosis, which allows for better balance and support of an upright trunk. Selection for bipedality was likely strong enough to justify the maintenance of such a disorder. Bipedality is hypothesized to have emerged for a variety of different reasons, many of which would have certainly conferred fitness advantages. It may increase viewing distance, which can be beneficial in hunting and foraging as well as protection from predators or other humans; it makes long-distance travel more efficient for foraging or hunting; and it facilitates terrestrial feeding from grasses, trees, and bushes. Given the many benefits of bipedality which depends on a particularly formed spine, it is likely that selection for bipedalism played a large role in the development of the spine as we see it today, in spite of the potential for "scoliotic deviations". According to the fossil record, scoliosis may have been more prevalent among earlier hominids such as Australopithecus and Homo erectus, when bipedality was first emerging. Their fossils indicate that there may have been selected over time for a slight reduction in lumbar length to what we see today, favouring a spine that could efficiently support bipedality with a lower risk of scoliosis.
Society and culture
The cost of scoliosis involves both monetary losses and lifestyle limitations that increase with severity. Respiratory deficiencies may also arise from thoracic deformities and cause abnormal breathing. This directly affects exercise and work capacity, decreasing the overall quality of life.In the health care system of the United States, the average hospital cost for cases involving surgical procedures was $30,000 to $60,000 per person in 2010. As of 2006, the cost of bracing has been published as up to $5,000 during rapid growth periods, when braces must be consistently replaced across multiple follow-ups.
Research
Genetic testing for adolescent idiopathic scoliosis, which became available in 2009 and is still under investigation, attempts to gauge the likelihood of curve progression.
See also
References
External links
Scoliosis at Curlie
Early Onset Scoliosis is the abnormal, side-to-side curve of the spine in children under five years old, often including children with congenital scoliosis (present at birth, with spine abnormalities) and infantile scoliosis (birth to three years).
Questions and Answers about Scoliosis in Children and Adolescents – US National Institute of Arthritis and Musculoskeletal and Skin Diseases |
Expressive language disorder | Expressive language disorder is a communication disorder in which there are difficulties with verbal and written expression. It is a specific language impairment characterized by an ability to use expressive spoken language that is markedly below the appropriate level for the mental age, but with a language comprehension that is within normal limits. There can be problems with vocabulary, producing complex sentences, and remembering words, and there may or may not be abnormalities in articulation.Careful diagnosis is also important because "atypical language development can be a secondary characteristic of other physical and developmental problems that may first manifest as language problems".
Models of language production
Willem Levelt outlined the currently accepted theory of speech production. Words are produced after the concept waiting to be produced is conceptualized, related words are selected, encoded and the sound waves of speech are produced.
Association with language networks
There is also a lot of debate about whether specific language impairments, such as expressive language disorder, are caused by deficits in grammar or by a deficit in processing language information. However, an alternative hypothesis to the cause of SLIs has been posited, called the Procedural Deficit Hypothesis. The Procedural Deficit Hypothesis opines that we can explain language impairments due to abnormal development of brain structures that are involved in procedural memory, our memories that remember how to perform different cognitive and motor tasks. The procedural memory system is associated with basal-ganglia circuits in the frontal lobe and further investigation of this particular hypothesis could aid in the development of a clinical neurological picture of what the underlying causes of SLI are.
Scientific studies of speech and language
Some of the earliest neuroscientific discoveries were related to the discovery that damage to certain areas of the brain related to impairments in language, such as the discovery of Wernickes area and Brocas area. Lesions in these parts of the brain impair language comprehension and language production, respectively. Paul Broca was the first to note that the left hemisphere of the brain appeared to be localized for language function, particularly for right handed patients. Modern neuroscientific research has verified this, though language may be lateralizaed to the right hemisphere in some right-handed individuals.
Developmental verbal dyspraxia
In 1990, it was reported that the several generations of the KE family had developmental verbal dyspraxia and orofacial praxis that were inherited in a typical autosomal dominant pattern. Further analysis traced this inheritance pattern back to mutations in the FOXP2 genes. These studies have allowed scientists to begin to investigate how changes to one gene can alter human communication.
FOXP2 is the first gene that has been identified that is specifically linked to speech and language production. Mutant alleles of the normal FOXP2 gene have been found to be the cause of severe speech impairments.
Specific language impairment
Neuroimaging techniques, such as structural and functional MRI, found no significant differences between individuals with SLI and normal controls. However, more subtle and sophisticated techniques, such as voxel-based morphometry studies have allowed researchers to identify bilateral abnormalities in neural volume in areas of the brain associated with motor functions, such as the caudate nucleus, in the affected members of the KE family when compared to the unaffected family members. This volume reduction showed a high correlation between reduced volume and tests of oral praxis, supporting the idea that odd development of the caudate nucleus is related to the problems in motor control observed in the KE family.Due to the vague nature of the diagnosis of expressive language disorder, there is little specific scientific research that we can currently locate. A larger body of research exists around neuroscientific studies with children diagnosed with a specific language impairment (SLI). fMRI studies have shown that children with SLI have a significantly smaller left hemispheric pars triangularis (Brocas area) and asymmetry of dominance of language structures, as opposed to the more typical left hemisphere dominance. Scientists are beginning to elucidate differences in activation patterns in children with SLIs using neuroimaging techniques to capture brain activity while performing different cognitive tasks. A major observation is lack of left hemisphere lateralization in major language structures such as the inferior frontal gyrus-opercularis, inferior frontal gyrus-triangularis, supramarginal gyrus and superior temporal gyrus. The same study reported hypoactivation and hyper activation of other brain regions - the supramarginal junction and anterior insula, respectively. Other in-depth imaging studies report finding previously undiagnosed lesions in the brains of children with well-characterized developmental language development. Together, these findings strongly suggest that language impairments are the result of an underlying neurological defect in an area of the brain related to language.
Studies looking at long-term outcomes for individuals with specific language impairments such as expressive language disorder track these individuals from childhood to adulthood. As Whitehouse and his colleagues suggest, "When childhood language problems persist into adulthood, they can have far reaching consequences in terms of academic, social and vocational outcomes." These researchers found that children diagnosed with an SLI would have persistent problems with language and are more likely to pursue vocational training rather than university, thereby avoiding professions requiring high levels of literacy. A lower socioeconomic status was also noted by adults who were diagnosed with an SLI as a child. Whitehouse also reported that these adults had more difficulties in establishing friendships, most likely due to a decreased ability to express themselves socially.
Current educational interventions for students with an SLI
Specific language impairments are often secondary characteristics of other disorders such as autism spectrum disorder and attention deficit hyperactivity disorder. In these cases, issues with speech and language are often not treated specifically, but rather attention is given to the primary complaint. Due to the high correlation of an SLI with other disorders, it is difficult to tell the difference between "pure SLI" or language impairments due to the presence of another disorder.
See also
Auditory processing disorder
Speech-Language Pathology
Mixed receptive-expressive language disorder
References
Further reading
Bacon C, Rappold GA (November 2012). "The distinct and overlapping phenotypic spectra of FOXP1 and FOXP2 in cognitive disorders". Hum. Genet. 131 (11): 1687–98. doi:10.1007/s00439-012-1193-z. PMC 3470686. PMID 22736078.
Bearzotti F, Tavano A, Fabbro F (June 2007). "Development of orofacial praxis of children from 4 to 8 years of age". Percept mot Skills. 104 (3 Pt 2): 1355–66. doi:10.2466/pms.104.4.1355-1366. PMID 17879670. S2CID 11775613.
Caulfield MB, Fischel JE, DeBaryshe BD, Whitehurst GJ (April 1989). "Behavioral correlates of developmental expressive language disorder". J Abnorm Child Psychol. 17 (2): 187–201. doi:10.1007/bf00913793. PMID 2745899. S2CID 7560818.
Pinel P, Fauchereau F, Moreno A, et al. (January 2012). "Genetic variants of FOXP2 and KIAA0319/TTRAP/THEM2 locus are associated with altered brain activation in distinct language-related regions". J. Neurosci. 32 (3): 817–25. doi:10.1523/JNEUROSCI.5996-10.2012. PMC 6621137. PMID 22262880.
== External links == |
Acral nevus | An acral nevus is a cutaneous condition of the palms, soles, fingers, or toes (peripheral body parts), characterized by a skin lesion that is usually macular or only slightly elevated, and may display a uniform brown or dark brown color, often with linear striations.: 1726 Acral nevi may occur in all ethnic groups, but are more common in dark-skinned people. The acral nevus is a benign skin lesion that can occur at any age, but is generally noticed between 10 and 30 years of age. Both children and adults may be observed with this skin lesion. The prevalence of acral nevi increases directly with degree of skin pigmentation. In a study, palmar or plantar nevi were detected in 42.0% of black (50 of 119) vs 23.0% of whites (79 of 343). Palmar or plantar nevi of 6 mm diameter or larger were detected in 3.4% of blacks (4 of 119) vs 0.6% of whites.They are brown to dark brown in color and have linear streaks of darker pigmentation. Size is usually 7 mm or less, oval or spindle shaped, and well-demarcated. They become stable after an initial growth phase, and the number of lesions also decreases; a new lesion in middle-aged or elderly people should raise suspicion of acral lentiginous melanoma.
Additional image
See also
Acral lentiginous melanoma
List of cutaneous conditions
References
== External links == |
Sialectasis | Sialectasis (also termed sialectasia, or siadochiectasis) is cystic dilation of the ducts of salivary glands. It may be caused by salivary duct strictures or stones (sialolithiasis). It can also rarely be congenital.
See also
Bronchiectasis
== References == |
Retrobulbar bleeding | Retrobulbar bleeding, also known as retrobulbar hemorrhage, is when bleeding occurs behind the eye. Symptoms may include pain, bruising around the eye, the eye bulging outwards, vomiting, and vision loss.Retrobulbar bleeding can occur as a result of trauma to the eye, surgery to the eye, blood thinners, or an arteriovenous malformation.In those with significant symptoms lateral canthotomy with cantholysis is indicated. This is recommended to be carried out within two hours. The condition is rare.
== References == |
Dermatographic urticaria | Dermatographic urticaria is a skin disorder and one of the most common types of urticaria, affecting 2–5% of the population.
Signs and symptoms
The condition manifests as an allergic-like reaction, causing a warm red wheal to appear on the skin. As it is often the result of scratches, involving contact with other materials, it can be confused with an allergic reaction, when in fact it is the act of being scratched that causes a wheal to appear. These wheals are a subset of urticaria (hives), and appear within minutes, in some cases accompanied by itching. The first outbreak of urticaria can lead to other reactions on body parts not directly stimulated, scraped, or scratched. In a normal case, the swelling will decrease without treatment within 15–30 minutes, but, in extreme cases, itchy red welts may last anywhere from a few hours to days.
Causes
Symptoms are thought to be the result of histamine being released by mast cells on the surface of the skin. Despite the lack of antigens, histamine causes the skin to swell in affected areas. If the membrane that surrounds the mast cells is too weak it will easily and rapidly break down under physical pressure, which then causes an allergic-like reaction.Symptoms can be caused or induced by:
The underlying cause of dermographism is not known, and it can last for many years without relief. The condition may subside and be effectively cured; however, it is often a lifelong ailment. It is not a life-threatening disease, and it is not contagious.Dermographism may occur in mastocytosis (systemic mast cell proliferation).
Diagnosis
This condition is diagnosed by a health care provider writing or drawing on the patients skin with a tongue depressor or other implement, to see whether a red wheal appears soon afterwards.
Treatment
Dermographism can be treated by substances which prevent histamine from causing the reaction (i.e. an antihistamine). These may need to be given as a combination of H1 antagonists, or possibly with an H2-receptor antagonist such as cimetidine.
Over-the-counter vitamin C, 1000 mg daily, increases histamine degradation and removal.Refraining from taking hot baths or showers may help if the condition is generalized (i.e. all over), as well as possibly for localized cases (i.e. in a specific area). If taking hot showers helps, it may be a condition called shower eczema. If it affects mainly the head, it may be psoriasis. In rare cases, allergy tests may uncover substances the patient is allergic to.While cromoglycate, which prevents histamine from being released from mast cells, is used topically in rhinitis and asthma, it is not effective orally for treating chronic urticaria.
See also
Triple response of Lewis
References
== External links == |
Lumbar vertebrae | The lumbar vertebrae are, in human anatomy, the five vertebrae between the rib cage and the pelvis. They are the largest segments of the vertebral column and are characterized by the absence of the foramen transversarium within the transverse process (since it is only found in the cervical region) and by the absence of facets on the sides of the body (as found only in the thoracic region). They are designated L1 to L5, starting at the top. The lumbar vertebrae help support the weight of the body, and permit movement.
Human anatomy
General characteristics
The adjacent figure depicts the general characteristics of the first through fourth lumbar vertebrae. The fifth vertebra contains certain peculiarities, which are detailed below.
As with other vertebrae, each lumbar vertebra consists of a vertebral body and a vertebral arch. The vertebral arch, consisting of a pair of pedicles and a pair of laminae, encloses the vertebral foramen (opening) and supports seven processes.
Body
The vertebral body of each lumbar vertebra is kidney shaped, wider from side to side than from front to back, and a little thicker in front than in back. It is flattened or slightly concave above and below, concave behind, and deeply constricted in front and at the sides.
Arch
The pedicles are very strong, directed backward from the upper part of the vertebral body; consequently, the inferior vertebral notches are of considerable depth. The pedicles change in morphology from the upper lumbar to the lower lumbar. They increase in sagittal width from 9 mm to up to 18 mm at L5. They increase in angulation in the axial plane from 10 degrees to 20 degrees by L5. The pedicle is sometimes used as a portal of entrance into the vertebral body for fixation with pedicle screws or for placement of bone cement as with kyphoplasty or vertebroplasty.
The laminae are broad, short, and strong. They form the posterior portion of the vertebral arch. In the upper lumbar region the lamina are taller than wide but in the lower lumbar vertebra the lamina are wider than tall. The lamina connects the spinous process to the pedicles.
The vertebral foramen within the arch is triangular, larger than the thoracic vertebrae, but smaller than in the cervical vertebrae.
Processes
The spinous process is thick, broad, and somewhat quadrilateral; it projects backward and ends in a rough, uneven border, thickest below where it is occasionally notched.The superior and inferior articular processes are well-defined, projecting respectively upward and downward from the junctions of pedicles and laminae. The facets on the superior processes are concave, and look backward and medialward; those on the inferior are convex, and are directed forward and lateralward. The former are wider apart than the latter since in the articulated column, the inferior articular processes are embraced by the superior processes of the subjacent vertebra.The transverse processes are long and slender. They are horizontal in the upper three lumbar vertebrae and incline a little upward in the lower two. In the upper three vertebrae they arise from the junctions of the pedicles and laminae, but in the lower two they are set farther forward and spring from the pedicles and posterior parts of the vertebral bodies. They are situated in front of the articular processes instead of behind them as in the thoracic vertebrae, and are homologous with the ribs.Three portions or tubercles can be noticed in a transverse process of a lower lumbar vertebrae: the lateral or costiform process, the mammillary process, and the accessory process. The costiform is lateral, the mammillary is superior (cranial), and the accessory is inferior (caudal). The mammillary is connected in the lumbar region with the back part of the superior articular process. The accessory process is situated at the back part of the base of the transverse process. The tallest and thickest costiform process is usually that of L5.
First and fifth lumbar vertebrae
The first lumbar vertebra is level with the anterior end of the ninth rib. This level is also called the important transpyloric plane, since the pylorus of the stomach is at this level. Other important structures are also located at this level, they include; fundus of the gall bladder, celiac trunk, superior mesenteric artery, termination of spinal cord, beginning of filum terminale, renal vessels, middle suprarenal arteries, and hila of kidneys.
The fifth lumbar vertebra is characterized by its body being much deeper in front than behind, which accords with the prominence of the sacrovertebral articulation; by the smaller size of its spinous process; by the wide interval between the inferior articular processes, and by the thickness of its transverse processes, which spring from the body as well as from the pedicles.
The fifth lumbar vertebra is by far the most common site of spondylolysis and spondylolisthesis.Most individuals have five lumbar vertebrae, while some have four or six. Lumbar disorders that normally affect L5 will affect L4 or L6 in these latter individuals.
Segmental movements
The range of segmental movements in a single segment is difficult to measure clinically, not only because of variations between individuals, but also because it is age and sex dependent. Furthermore, flexion and extension in the lumbal spine is the product of a combination of rotation and translation in the sagittal plane between each vertebra.Ranges of segmental movements in the lumbar spine (White and Punjabi, 1990) are (in degrees):
Congenital anomalies
Congenital vertebral anomalies can cause compression of the spinal cord by deforming the vertebral canal or causing instability.
Other animals
African apes have three and four lumbar vertebrae, (bonobos have longer spines with an additional vertebra) and humans normally five. This difference, and because the lumbar spines of the extinct Nacholapithecus (a Miocene hominoid with six lumbar vertebrae and no tail) are similar to those of early Australopithecus and early Homo, it is assumed that the Chimpanzee-human last common ancestor also had a long vertebral column with a long lumbar region and that the reduction in the number of lumbar vertebrae evolved independently in each ape clade.
The limited number of lumbar vertebrae in chimpanzees and gorillas result in an inability to lordose (curve) their lumbar spines, in contrast to the spines of Old World monkeys and Nacholapithecus and Proconsul, which suggests that the last common ancestor was not "short-backed" as previously believed.
Additional images
MRI
Illustrations
See also
Bertolottis syndrome
Spinal disc herniation
Lumbar spinal stenosis
Degenerative disc disease
References
This article incorporates text in the public domain from page 104 of the 20th edition of Grays Anatomy (1918)
External links
"Lower Back Pain Condition, Treatment and Exercise". SpineUniverse. Retrieved February 15, 2017.
"Virtual Spine — Online Learning Resource". Toronto Western Hospital Department of Anesthesia and Pain Management. Retrieved February 15, 2017. |
Infantile myofibromatosis | Infantile myofibromatosis (IMF) is a rare tumor found in 1 in 150,000 to 1 in 400,000 live births. It is nonetheless the most common tumor derived from fibrous connective tissue that occurs primarily in infants and young children. IMF tumors are benign in the sense that they do not metastasize to distant tissues although when occurring in the viscera, i.e. internal organs, carry guarded to poor prognoses and can be life-threatening, particularly in newborns and young infants.IMF tumors occur in three clinical patterns: 1) solitary IMF tumors (also called myofibromas) which often regress spontaneously and rarely cause serious issues; 2) multiple tumors (no viscera involvement) which consists of numerous (i.e. dozens to >100) IMF lesions most of which are located in the skin, subcutaneous tissues, and non-visceral but not visceral organs, may regress spontaneously, and rarely cause serious issues; and 3) multiple tumors (with viscera involvement) (also called generalized myofibromatosis) which rarely regress spontaneously and consist of numerous IMF lesions in non-visceral tissues plus one or more visceral tumors that may be life-threatening.A minority of infantile myofibromatosis tumors present in individuals with a strong family history of the disease. These familial cases are associated with mutations in either the PDGFRB or NOTCH3 gene. However, most IMF cases have no family history of the disease but nonetheless have PDGFRB gene mutations in their tumor cells; these mutations are similar to those occurring in the familial PDGFRB gene mutations. Regardless of these genetic variations, all IMF tumors consist of bland-appearing, benign (i.e. non-malignant) myofibroblasts, i.e. cells that blend a variable set of features seen in fibroblasts, the most common cell type in connective tissue, with a variable set of features seen in smooth muscle cells.Treatment of IMF tumors depends upon the tumor numbers, locations, and genetic abnormalities found in each individual and often include more than one therapeutic regimen. Individuals with solitary tumors are usually treated by observation with the expectation that many of these tumors will regress spontaneiously. Single tumors located in vital areas (e.g. intracranial tumors) and tumors that do not regress over suitable observation periods are often treated by surgical removal. Multiple tumors (with viscera involvement) and surgically inaccessible life-threatening IMF tumors have been treated with one or a combination of chemotherapy drugs, radiation therapy or, in tumors with certain PDGFRB gene mutations, drugs directed specifically against this mutated genes protein product.
Presentation
IMF tumors are usually painless, well-encapsulated, rubbery to hard, and freely movable-to-fixed masses. They may be evident at birth in up to 60% of cases but generally go undetected until they are diagnosed in the first year of life, uncommonly in older infants and young (<10 years/old) children, or rarely in older children and adults (one individual was diagnosed with IMF at 85 years of age). The tumors may be flesh-colored papules or nodules; plaques (i.e. flat-topped papules that are equal to or greater than 10 mm in largest diameter); pedunculated, calcified masses; or ulcerated, necrotic masses. Most of these tumors are <1 cm in diameter but can be much larger, e.g. 5.2 cm in diameter. At least 9 IMF cases described in the English literature were diagnosed in fetuses based on the findings of fetal spectrogram and/or magnetic resonance imaging. IMF tumors in the viscera or deep tissues may present with serious or life-threatening signs and symptoms of organ and/or deep tissue damage due to these tumors space-filling and pressuring effects.Some individuals with IMF present with a family history of IMF tumors. To date (2021), 20 families have been reported to carry various germline (i.e. inherited) mutations in one of their two PDGFRB genes. All of these mutations were gain of function mutations (i.e. the mutant genes product is overactive) and inherited in an autosomal dominant manner with incomplete penetrance. Among 36 identified familial carriers of these mutant genes, 4 had no history of IMF, 3 had developed a solitary IMF, 29 had developed multiple tumors (no viscera involvement) or multiple tumors (with viscera involvement) IMF, and 2 had died. Most of these individuals were diagnosed with IMF in their infancy or early childhood. Subsequent studies have found that up to 70% of individuals with IMF and no family history of the disease also carry mutations in one of their two PDGFRB genes in the cells of their tumor tissues. These mutations are somatic mutations (i.e. non-inherited mutations developing only after conception) that are identical or similar to those seen in familial cases. The familial and non-familial mutated PDGFRB genes produce highly overactive platelet-derived growth factor receptor beta (i.e. PDGFβ receptor) proteins that contribute to the development and/or progression of IMF.A mutation in one of the two NOTCH3 genes has been reported to occur in a single family with autosomal dominant inheritance of IMF: 9 of this familys members had IMF plus the mutation while 7 of its members did not have IMF or the mutation. Since the mutated NOTCH3 gene in this family produces an overactive neurogenic locus notch homolog protein 3 product that in cell culture studies increases the expression of the PDGFRB genes product, the PDGFβ receptor, this NOTCH3 mutation may promote the development and/or progression of IMF in a manner similar to PDGFRB mutant genes, i.e. by increasing the number and therefore overall activity of the PDGFβ receptor. Further studies are needed to define NOTCH3 gene mutations frequency of occurrence in, and contribution to the development of, IMF.
Solitary IMF tumors
Solitary IMF tumors represent 50 to 74% of all IMF cases. These tumors commonly present with a mass that infiltrates the surrounding tissue in the head and neck areas (e.g. in the ethmoid sinus/maxillary sinus, infratemporal fossa, tongue, hard palate, behind an ear, or temporal bone); less commonly in other sites such as the scapula/axilla area, lower back, or soft tissue/bone in the lower leg; and also less commonly in visceral organs such as the pancreas, spleen, lung, or heart. Solitary IMF tumors often (i.e. 25 to 61% of cases in different studies) regress spontaneously.
Multiple tumors (no viscera involvement)
Multiple tumors (no viscera involvement) typically occur as dozens to hundreds of mostly small tumors located in various areas such as the skin, muscles, and frontal eye socket, These tumors do not involve visceral organs, often take a benign course, and may regress spontaneously.
Multiple tumors (with viscera involvement)
Multiple tumors (with viscera involvement) typically occur as dozens to hundreds of tumors located in the same sites as multiple tumors (no viscera involvement) but also occur in one or more visceral organs such as those in the gastrointestinal tract and upper respiratory tract and/or the heart, liver, cerebellum, rectum, parietal cortex of brain, and lung. This form of IMF, particularly in cases with tumors involving the gastrointestinal tract, heart, and/or lung, has a far higher morbidity and mortality than the other forms with death occurring in infants during the first weeks to 4 months of life in 30–70% of cases Death is typically due to a tumors compression of vital organs or tissues (e.g. blood vessels). However, there are uncommon cases of multiple tumors (with viscera involvement) that were not associated with serious symptoms, were observed without treatment, and over time showed spontaneous regressions of all or almost all of their tumors.
Pathology
Microscopic histopathologic analyses of IMF tumor tissues commonly show repeated patterns of a central zone consisting of spindle-shaped cells lining capillaries and round-to-oval cells arranged around prominent "antler-shaped" vascular spaces all of which are surrounded by a peripheral zone of clustered smooth muscle-like cells. The relative proportions of the two zones can vary within different areas of a tumor and between tumors. Immunohistochemical analyses indicate that the spindle-shaped cells strongly express smooth muscle actin, calponin, and, less commonly, desmin proteins.
Gene abnormalities
Familial IMF
Twenty families with inherited IMF have been shown to have mutations in one of their two PDGFRB genes. The PDGFRB gene is located in band 32 on the long (or "q") arm of chromosome 5. Of the 20 families with PDGFRB gene mutations, 15 carried a p.Arg561Cys mutation. This mutation substitutes the amino acid Arg, i.e. arginine, for the amino acid cystine at the 561st amino acid position as numbered starting at the N-terminus of the genes product protein, the PDGFβ receptor. Four of the remaining families carried either a p.Pro560Leu (Pro=proline, Leu=leucine); p.Arg561Ser (Ser=serine); p. Lys567Glu (Lys=lysine, Glu=glutamate); or p.Pro660Thr (Thr=threonine) mutation in this protein. The NOTCH3 gene (located in band 13.12 on the short (or "p") arm of chromosome 19) mutation in the carrier family was p. Leu1519Pro. The p.Arg561Cys, p.Pro560Leu, p.Arg561Ser, and p. Lys567Glu mutations are regarded as contributing to the development and/or progression of IMF while the p.Pro660Thr PDGFRB gene mutation and the p. Leu1519Pro NOTCH3 p. Leu1519Pro gene mutation require further study to determine more clearly their clinical significances.
Non-familial IMF
Somatic PDGFRB gene mutations have been found in 29% of individuals with solitary IMF tumors and 68% of individuals with multiple tumors (with viscera involvement) plus multiple tumors (no visceral involvement) IMF. In about 50% of these cases, these somatic mutations were the same as those found in familial IMF with the remaining cases having mutations in other sites of the gene. These other somatic mutation sites included 2 cases of p.Asp850Val (Asp=aspartate, Val=valine), 2 case of p.Asn666Lys (Asn=asparagine, Lys=lysine), and concurrent double mutations p.Arg561Cyt plus Asp666Lys in one case and p.Trp566Arg (Trp=tryptophan) plus AspN666Lys in another case. Three cases had more complex mutations involving multiple gene sites with two of them having the p.Asn666Lys mutation gene in combination with other mutations.
PDGFRB gene
The PDGFRB gene product, the PDGFβ receptor, is normally highly expressed in fibroblasts and other cells of mesenchymal origin including vascular smooth muscle cells. When activated, the PDGFβ receptors tyrosine kinase stimulates cell signaling proteins such as phosphatidylinositol-3 kinase, STAT proteins, phospholipase Cγ, and GRB2 which in turn promote their parent cells to grow, proliferate, and survive for abnormally prolonged times. The PDGFβ receptor gene is a proto-oncogene, i.e. a normal gene that when mutated could form a cancer-causing oncoprotein. Studies show that the PDGFRB mutant proteins in IMF are constitutively overactive and that the tyrosine kinase inhibitor imatinib blocks the activity of the p.Arg561Cys and p.Asn666Lys mutants as well as the p.Arg561Cyt plus Asp666Lys and p.Trp566Arg plus AspN666Lys double mutants but not the p.Asp850Val mutant. Two other tyrosine kinase inhibitors, dasatinib and ponatinib, do inhibit the p.Asp850Val mutants tyrosine kinase activity. Limited initial studies suggest that these inhibitors are useful in treating severe cases of IMF.
Diagnosis
Based on their clinical presentation and gross appearance IMF tumors can be confused with a wide range of benign and malignant papular, nodular, and tumorous lesions particular in cases which involve multiple tumors. However, the presence of two zone histopathology, family history of disease, and presence of the above cited PDGFRB gene mutations are almost always definitive indicators of IMF. IMF and the classic form of mesoblastic nephroma have been suggested to be the same disease because of their very similar histopathology. However, mesoblastic nephroma tumor cells, unlike IMF tumor cells, express cyclin D1 and Beta-catenin proteins and therefore likely have a very different cellular origin than IMF tumors. Infantile digital fibromatosis, a tumor that develops primarily in the fingers and toes, had been regarded as a type of IMF. However its tumors have a distinctly different clinical presentation and histopathology than IMF. The World Health Organization (2020) redefined infantile digital fibromatosis as a benign tumor in the in the category of benign fibroblastic and myofibroblastic tumors and therefore different than IMF.
Treatment and prognosis
There are no controlled studies to define the optimal treatment(s) for IMF. The following give the currently widely used and recommended treatments along with the result of these treatments for the three categories of the IMF tumors.
Solitary IMF tumors
Solitary IMF tumors typically grow slowly, produce few or no symptoms, and often regress spontaneously within 18 to 24 months of diagnosis. A watchful waiting strategy is commonly used for these tumors. Visceral solitary IMF tumors that cause significant tissue injury, are located in vital areas, and/or are life-threatening have been treated by surgical excision or, if surgery is deemed inappropriate, are treated with drugs and/or radiation therapy as indicated in the following section on multiple tumors (with visceral involvement). Surgical excision has also be used if the diagnosis of the tumor is in doubt. In rare cases, aggressive IMF tumors have recurred after regressing and required further observation and/or treatment. Overall, the prognosis in almost all cases of solitary IMF is good to excellent.
Multiple tumors (no viscera involvement)
Multiple tumors (no viscera involvement) also may regress spontaneously and carry a good to excellent prognosis even when they invade local tissues. However, neonates presenting with multiple IMF tumors should undergo a through examination including medical imaging tests to determine the extent of their disease, particularly with respect to determining if a visceral tumor(s) is present and therefore that the proper diagnosis is multiple tumors (with viscera involvement). The treatment of multiple tumors (no viscera involvement) is similar to that used for solitary IMF tumors.
Multiple tumors (with viscera involvement)
Individuals with multiple tumors (with viscera involvement) have numerous tumors one or more of which are located in and often injure a vital internal organ and may be life-threatening. Cases in which one of the tumors is in a vital organ and seriously symptomatic have been successfully treated with surgical resection. Cases where surgical resection of a single symptomatic tumor is not a good option and cases with multiple visceral tumors are treated by non-surgical methods. These tumors typically respond to conventional systemic chemotherapy with reductions in their sizes; these responses are usually observed only after several weeks of therapy. Chemotherapy regimes that have successfully treated these cases include low dosage: vincristine plus dactinomycin; vinblastine plus methotrexate; vinblastine plus the glucocorticoid, prednisolone; vincristine plus actinomycin D plus the glucocorticoid, prednisone; and vincristine plus dactinomycin plus cyclophosphamide. A cytokine, interferon alpha, has also been used as a single-drug treatment in at least one of these cases. Multiple tumors (with viscera involvement) have also been treated with surgical resection in combination with these drugs and/or with radiation therapy alone or combined with these drugs.Recently, tyrosine kinase inhibitors have been used to treat PDGFRB-associated IMF cases. Imatinib or imatinib plus a second tyrosine kinase inhibitor, sorafenib, have successful treated several cases and chemotherapy plus imatinib have successfully treated a few cases of life-threatening IMF. Studies suggest that: 1) the tyrosine kinase inhibitor should be selected based on the PDGFRB oncoproteins sensitivity to it (e.g. dasatinib or ponatinib should be used to treat patients with the imatinib-resistant p.Asp850Val PDGFRB gene mutation.); 2) imatinib should be the initial choice and dasatinib or ponatinib be used for cases failing to respond to imatinib in cases where the PDGFRB gene mutation has not been defined; and 3) the inhibitors precise dosages for use in newborns and infants are not well-defined, have serious side-affects, and therefore should only be considered for refractory, life-threatening IMF tumors.
See also
Skin lesion
List of cutaneous conditions
mesoblastic nephroma
References
== External links == |
Lichen sclerosus | Lichen sclerosus (LS) is a chronic, inflammatory skin disease of unknown cause which can affect any body part of any person but has a strong preference for the genitals (penis, vulva) and is also known as balanitis xerotica obliterans (BXO) when it affects the penis. Lichen sclerosus is not contagious. There is a well-documented increase of skin cancer risk in LS, potentially improvable with treatment. LS in adult age women is normally incurable, but improvable with treatment, and often gets progressively worse if not treated properly. Most males with mild or intermediate disease restricted to prepuce or glans can be cured by either medical or surgical treatment.
Signs and symptoms
LS can occur without symptoms. White patches on the LS body area, itching, pain, dyspareunia (in genital LS), easier bruising, cracking, tearing and peeling, and hyperkeratosis are common symptoms in both men and women. In women, the condition most commonly occurs on the vulva and around the anus with ivory-white elevations that may be flat and glistening.In males, the disease may take the form of whitish patches on the foreskin and its narrowing (preputial stenosis), forming an "indurated ring", which can make retraction more difficult or impossible (phimosis). In addition there can be lesions, white patches or reddening on the glans. In contrast to women, anal involvement is less frequent. Meatal stenosis, making it more difficult or even impossible to urinate, may also occur.On the non-genital skin, the disease may manifest as porcelain-white spots with small visible plugs inside the orifices of hair follicles or sweat glands on the surface. Thinning of the skin may also occur.
Psychological effect
Distress due to the discomfort and pain of lichen sclerosus is normal, as are concerns with self-esteem and sex. Counseling can help.According to the National Vulvodynia Association, which also supports women with lichen sclerosus, vulvo-vaginal conditions can cause feelings of isolation, hopelessness, low self-image, and much more. Some women are unable to continue working or have sexual relations and may be limited in other physical activities. Depression, anxiety, and even anger are all normal responses to the ongoing pain LS patients experience.
Pathophysiology
Although it is not clear what causes LS, several theories have been postulated. Lichen sclerosus is not contagious; it cannot be caught from another person.Several risk factors have been proposed, including autoimmune diseases, infections and genetic predisposition. There is evidence that LS can be associated with thyroid disease.
Genetic
Lichen sclerosus may have a genetic component. A high correlation of lichen sclerosus has been reported between twins and between family members.
Autoimmunity
Autoimmunity is a process in which the body fails to recognize itself and therefore attacks its own cells and tissue. Specific antibodies have been found in LS. Furthermore, there seems to be a higher prevalence of other autoimmune diseases such as diabetes mellitus type 1, vitiligo, alopecia areata, and thyroid disease.
Infection
Both bacterial as well as viral pathogens have been implicated in the etiology of LS. A disease that is similar to LS, acrodermatitis chronica atrophicans is caused by the spirochete Borrelia burgdorferi. Viral involvement of HPV and hepatitis C are also suspected.
A link with Lyme disease is shown by the presence of Borrelia burgdorferi in LSA biopsy tissue.
Hormones
Since LS in females is primarily found in women with a low estrogen state (prepubertal and postmenopausal women), hormonal influences were postulated. To date though, very little evidence has been found to support this theory.
Local skin changes
Some findings suggest that LS can be initiated through scarring or radiation, although these findings were sporadic and very uncommon.
Diagnosis
The disease often goes undiagnosed for several years, as it is sometimes not recognized and misdiagnosed as thrush or other problems and not correctly diagnosed until the patient is referred to a specialist when the problem does not clear up.A biopsy of the affected skin can be done to confirm diagnosis. When a biopsy is done, hyperkeratosis, atrophic epidermis, sclerosis of dermis and lymphocyte activity in dermis are histological findings associated with LS. The biopsies are also checked for signs of dysplasia.It has been noted that clinical diagnosis of BXO can be "almost unmistakable," though there are other dermatologic conditions such as lichen planus, localized scleroderma, leukoplakia, vitiligo, and the cutaneous rash of Lyme disease can have a similar appearance.
Treatment
Main treatment
There is no definitive cure for LS. Behavior change is part of treatment. The patient should minimize or preferably stop scratching LS-affected skin. Any scratching, stress or damage to the skin can worsen the disease. Scratching has been theorized to increase cancer risks. Furthermore, the patient should wear comfortable clothes and avoid tight clothing, as it is a major factor in the severity of symptoms in some cases.Topically applied corticosteroids to the LS-affected skin are the first-line treatment for lichen sclerosus in women and men, with strong evidence showing that they are "safe and effective" when appropriately applied, even over long courses of treatment, rarely causing serious adverse effects. They improve or suppress all symptoms for some time, which highly varies across patients, until it is required to use them again. Methylprednisolone aceponate has been used as a safe and effective corticosteroid for mild and moderate cases. For severe cases, it has been theorized that mometasone furoate might be safer and more effective than clobetasol. Recent studies have shown that topical calcineurin inhibitors such as tacrolimus can have an effect similar to corticosteroids, but its effects on cancer risks in LS are not conclusively known. Based on limited evidence, a 2011 Cochrane review concluded that clobetasol propionate, mometasone furoate, and pimecrolimus (calcineurin inhibitor) all are effective therapies in treating genital lichen sclerosus. However, randomized-controlled trials are needed to further identify the optimal potency and regimen of topical corticosteroids and assess the duration of remission and/or the prevention of flares patients experience with these topical therapies.Continuous usage of appropriate doses of topical corticosteroids is required to ensure symptoms stay relieved over the patients life time. If continuously used, corticosteroids have been suggested to minimize the risk of cancer in various studies. In a prospective longitudinal cohort study of 507 women throughout 6 years, cancer occurred for 4.7% of patients who were only "partially compliant" with corticosteroid treatment, while it occurred in 0% of cases where they were "fully compliant". In a second study, of 129 patients, cancer occurred in 11% of patients, none of which were fully compliant with corticosteroid treatment. Both these studies however also said that a corticosteroid as powerful as clobetasol is not necessary in most cases. In a prospective study of 83 patients, throughout 20 years, 8 patients developed cancer. 6 already had cancer at presentation and had not had treatment, while the other 2 were not taking corticosteroids often enough. In all three studies, every single cancer case observed occurred in patients who werent taking corticosteroids as often as the study recommended.Continuous, abundant usage of emollients topically applied to the LS-affected skin is recommended to improve symptoms. They can supplement but not replace corticosteroid therapy. They can be used much more frequently than corticosteroids due to the extreme rarity of serious adverse effects. Appropriate lubrication should be used every time before and during sex in genital LS in order to avoid pain and worsening the disease. Some oils such as olive oil and coconut oil can be used to accomplish both the emollient and sexual lubrication function.In males, it has been reported that circumcision can have positive effects, but does not necessarily prevent further flares of the disease and does not protect against the possibility of cancer. Circumcision does not prevent or cure LS; in fact, "balanitis xerotica obliterans" in men was first reported as a condition affecting a set of circumcised men, by Stühmer in 1928.
Other treatments
Carbon dioxide laser treatment is safe and effective, and it improves symptoms over a long time, but it does not lower cancer risks.
Platelet-rich plasma was reported to be effective in one study, producing large improvements in the patients quality of life, with an average IGA improvement of 2.04 and DLQI improvement of 7.73.
Prognosis
The disease can last for a considerably long time. Occasionally, "spontaneous cure" may ensue, particularly in young girls.
Lichen sclerosus is associated with a higher risk of cancer. Skin that has been scarred as a result of lichen sclerosus is more likely to develop skin cancer. Women with lichen sclerosus may develop vulvar carcinoma. Lichen sclerosus is associated with 3–7% of all cases of vulvar squamous cell carcinoma. In women, it has been reported that 33.6 times higher vulvar cancer risk is associated with LS. A study in men reported that "The reported incidence of penile carcinoma in patients with BXO is 2.6–5.8%".
Epidemiology
There is a bimodal age distribution in the incidence of LS in women. It occurs in females with an average age of diagnosis of 7.6 years in girls and 60 years old in women. The average age of diagnosis in boys is 9–11 years old.In men, the most common age of incidence is 21–30.
History
In 1875, Weir reported what was possible vulvar or oral LS as "ichthyosis." In 1885, Breisky described kraurosis vulvae. In 1887, Hallopeau described a series of extragenital cases of LS. In 1892, Darier formally described the classic histopathology of LS. In 1900 the concept was formed that scleroderma and LS are closely related, which continues to this day. In 1901, pediatric LS was described. From 1913 to present, the concept that scleroderma is not closely related to LS also was formed. In 1920, Taussig established vulvectomy as the treatment of choice for kraurosis vulvae, a premalignant condition. In 1927, Kyrle defined LS ("white spot disease") as an entity sui generis. In 1928, Stühmer described balanitis xerotica obliterans as a postcircumcision phenomenon. In 1936, retinoids (vitamin A) were used in LS. In 1945, testosterone was used in genital LS. In 1961, the use of corticosteroids started. Jeffcoate presented an argument against vulvectomy for simple LS. In 1971, progesterone was used in LS. Wallace defined clinical factors and the epidemiology of LS. In 1976, Friedrich defined LS as a dystrophic, not an atrophic condition; "et atrophicus" was dropped. The International Society for Study of Vulvar Disease classification system established that "kraurosis" and "leukoplakia" were no longer to be used. In 1980, fluorinated and superpotent steroids were first used in LS. In 1981, studies into HLA serotypes and LS were published. In 1984, etretinate and acetretin were used in LS. In 1987, LS was linked with Borrelia infection.Lichen sclerosus et atrophicus was first described in 1887 by François Henri Hallopeau. Since not all cases of lichen sclerosus exhibit atrophic tissue, et atrophicus was dropped in 1976 by the International Society for the Study of Vulvovaginal Disease (ISSVD), officially proclaiming the name lichen sclerosus.
See also
Lichen planus
List of cutaneous conditions
List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer
List of human leukocyte antigen alleles associated with cutaneous conditions
References
External links
NIAMS – Questions and Answers About Lichen Sclerosus
NIAMS – Fast Facts About Lichen Sclerosus
dermnetnz.org
better medicine
Medscape Reference Author: Jeffrey Meffert, MD; Chief Editor: Dirk M Elston, MDMedical pictures
http://www.dermlectures.com/LecturesWMV.cfm?lectureID=88
https://web.archive.org/web/20070927210529/http://dermis.multimedica.de/dermisroot/de/34088/diagnose.htm
https://web.archive.org/web/20071008130921/http://dermnetnz.org/immune/ls-imgs.html |
Frontal lobe disorder | Frontal lobe disorder, also frontal lobe syndrome, is an impairment of the frontal lobe that occurs due to disease or frontal lobe injury. The frontal lobe of the brain plays a key role in executive functions such as motivation, planning, social behaviour, and speech production. Frontal lobe syndrome can be caused by a range of conditions including head trauma, tumours, neurodegenerative diseases, Neurodevelopmental disorders, neurosurgery and cerebrovascular disease. Frontal lobe impairment can be detected by recognition of typical signs and symptoms, use of simple screening tests, and specialist neurological testing.
Signs and symptoms
The signs and symptoms of frontal lobe disorder can be indicated by dysexecutive syndrome which consists of a number of symptoms which tend to occur together. Broadly speaking, these symptoms fall into three main categories; cognitive (movement and speech), emotional or behavioral. Although many of these symptoms regularly co-occur, it is common to encounter patients who have several, but not all of these symptoms. This is one reason why some researchers are beginning to argue that dysexecutive syndrome is not the best term to describe these various symptoms. The fact that many of the dysexecutive syndrome symptoms can occur alone has led some researchers to suggest that the symptoms should not be labelled as a "syndrome" as such. Some of the latest imaging research on frontal cortex areas suggests that executive functions may be more discrete than was previously thought.
Signs/symptoms can be divided as follows:
Causes
The causes of frontal lobe disorders can be closed head injury. An example of this can be from an accident, which can cause damage to the orbitofrontal cortex area of the brain.Cerebrovascular disease may cause a stroke in the frontal lobe. Tumours such as meningiomas may present with a frontal lobe syndrome. Frontal lobe impairment is also a feature of Alzheimers disease, and frontotemporal dementia.
Pathogenesis
The pathogenesis of frontal lobe disorders entails various pathologies, some are as follows:
Anatomy and functions
The frontal lobe contains the precentral gyrus and prefrontal cortex and, by some conventions, the orbitofrontal cortex. These three areas are represented in both the left and the right cerebral hemispheres. The precentral gyrus or primary motor cortex is concerned with the planning, initiation and control of fine motor movements dorsolateral to each hemisphere. The dorsolateral part of the frontal lobe is concerned with planning, strategy formation, and other executive functions. The prefrontal cortex in the left hemisphere is involved with verbal memory while the prefrontal cortex in the right hemisphere is involved in spatial memory. The left frontal operculum region of the prefrontal cortex, or Brocas area, is responsible for expressive language, i.e. language production. The orbitofrontal cortex is concerned with response inhibition, impulse control, and social behaviour.
Diagnosis
The diagnosis of frontal lobe disorder can be divided into the following three categories:
Clinical historyFrontal lobe disorders may be recognized through a sudden and dramatic change in a persons personality, for example with loss of social awareness, disinhibition, emotional instability, irritability or impulsiveness. Alternatively, the disorder may become apparent because of mood changes such as depression, anxiety or apathy.
ExaminationOn mental state examination a person with frontal lobe damage may show speech problems, with reduced verbal fluency. Typically the person is lacking in insight and judgment, but does not have marked cognitive abnormalities or memory impairment (as measured for example by the mini-mental state examination). With more severe impairment there may be echolalia or mutism. Neurological examination may show primitive reflexes (also known as frontal release signs) such as the grasp reflex. Akinesia (lack of spontaneous movement) will be present in more severe and advanced cases.
Further investigationA range of neuropsychological tests are available for clarifying the nature and extent of frontal lobe dysfunction. For example, concept formation and ability to shift mental sets can be measured with the Wisconsin Card Sorting Test, planning can be assessed with the Mazes subtest of the WISC. Frontotemporal dementia shows up as atrophy of the frontal cortex on MRI. Frontal impairment due to head injuries, tumours or cerebrovascular disease will also appear on brain imaging.
Treatment
In terms of treatment for frontal lobe disorder, there is none, general supportive care is given, also some level of supervision could be needed. The prognosis will depend on the cause of the disorder, of course. A possible complication is that individuals with severe injuries may be disabled, such that, a caregiver may be unrecognizable to the person. Another aspect of treatment of frontal lobe disorder is speech therapy. This type of therapy might help individuals with symptoms that are associated with aphasia and dysarthria.
History
Phineas Gage, who sustained a severe frontal lobe injury in 1848, has been called a case of dysexecutive syndrome. Gages psychological changes are almost always exaggerated – of the symptoms listed, the only ones Gage can be said to have exhibited are "anger and frustration", slight memory impairment, and "difficulty in planning".
See also
Attention
Cognitive neuropsychology
Dysexecutive syndrome
Executive functions
Frontal lobe
Gourmand syndrome
Klüver–Bucy syndrome
Phineas Gage
Working memory
References
Further reading
Paradiso, S (1999). "Frontal lobe syndrome reassessed: comparison of patients with lateral or medial frontal brain damage". Journal of Neurology, Neurosurgery, and Psychiatry. 67 (5): 664–7. doi:10.1136/jnnp.67.5.664. PMC 1736625. PMID 10519877.
Paradiso, Sergio; Chemerinski, Eran; Yazici, Kazim M.; Tartaro, Armando; Robinson, Robert G. (1999-11-01). "Frontal lobe syndrome reassessed: comparison of patients with lateral or medial frontal brain damage". Journal of Neurology, Neurosurgery & Psychiatry. 67 (5): 664–667. doi:10.1136/jnnp.67.5.664. ISSN 1468-330X. PMC 1736625. PMID 10519877.
== External links == |
Android fat distribution | Android fat distribution describes the distribution of human adipose tissue mainly around the trunk and upper body, in areas such as the abdomen, chest, shoulder and nape of the neck. This pattern may lead to an "apple”-shaped body or central obesity, and is more common in males than in females. Thus, the android fat distribution of men is about 48.6%, which is 10.3% higher than that of premenopausal women. In other cases, an ovoid shape forms, which does not differentiate between men and women. Generally, during early adulthood, females tend to have a more peripheral fat distribution such that their fat is evenly distributed over their body. However, it has been found that as females age, bear children and approach menopause, this distribution shifts towards the android pattern of fat distribution, resulting in a 42.1% increase in android body fat distribution in postmenopausal women. This could potentially provide evolutionary advantages such as lowering a womans center of gravity making her more stable when carrying offspring.Android fat distribution is contrasted with gynoid fat distribution, whereby fat around the hips, thighs, and bottom results in a “pear”-shaped body.
Jean Vague, a physician from Marseilles, France, was one of the first individuals to bring to attention the increased risk of developing certain diseases (e.g., diabetes and gout) in individuals with an android distribution compared to a gynoid distribution. There are other health consequences beyond these, including psychological consequences.
Biology
Android fat is readily mobilized by deficits in energy balance. It is stored in different depots to gynoid fat.Android fat cells are mostly visceral - they are large, deposited deep under the skin and are highly metabolically active. The hormones they secrete have direct access to the liver. The presence of fat in the trunk and upper body in males is facilitated by testosterone. Testosterone circulation causes fat cells to deposit around the abdominal and gluteofemoral region, whereas in women oestrogen circulation leads to fat deposits around areas such as thighs, breasts and buttocks. Therefore, measuring a persons oestrogen to testosterone ratio can reveal their predicted gynoid to android fat distribution. Android fat develops as a back-up source of energy when the male body is experiencing an imbalance, whereas gynoid fat develops after puberty, in order to better prepare the body for supporting a potential infant.
50% of the variance in abdominal fat mass observed in humans is due to genetic factors The cellular characteristics of adipose tissue in android and [gynoid] obese women are different. Android type have larger fat (hypertrophy) cells whereas gynoid type have increased number of fat cells (hyperplasia). This allows for hypertrophic obesity and hyperplastic obesity. Two different receptors, alpha and beta fat cell receptors, vary in their ability to facilitate or inhibit fat mobilization. Alpha-receptors are predominately in the lower body thus more abundant in gynoid patterns and Beta-receptors are predominantly in the upper body and so more abundant in android patterns.
Causes
Hormonal disorders or fluctuations can lead to the formation of a lot of visceral fat and a protruding abdomen. Medications such as protease inhibitors that are used to treat HIV and AIDS also form visceral fat. Android fat can be controlled with proper diet and exercise. A poor diet with lack of exercise is likely to increase android fat level.
Health consequences
Differences in body fat distribution are found to be associated with high blood pressure, high triglyceride, lower high-density lipoprotein (HDL) cholesterol levels and high fasting and post-oral glucose insulin levels The android, or male pattern, fat distribution has been associated with a higher incidence of coronary artery disease, in addition to an increase in resistance to insulin in both obese children and adolescents. Studies have also related central abdominal obesity (indicated via increased waist–hip ratio) with increases in peripheral fasting insulin levels.Android fat is also associated with a change in pressor response in circulation. Specifically, in response to stress in a subject with central obesity the cardiac output dependent pressor response is shifted toward a generalised rise in peripheral resistance with an associated decrease in cardiac output.There are differences in android and gynoid fat distribution among individuals, which relates to various health issues among individuals. Android body fat distribution is related to high cardiovascular disease and mortality rate. People with android obesity have higher hematocrit and red blood cell count and higher blood viscosity than people with gynoid obesity. Blood pressure is also higher in those with android obesity which leads to cardiovascular disease.Women who are infertile and have polycystic ovary syndrome show high amounts of android fat tissue. In contrast, patients with anorexia nervosa have increased gynoid fat percentage Women normally have small amounts of androgen, however when the amount is too high they develop male psychological characteristics and male physical characteristics of muscle mass, structure and function and an android adipose tissue distribution. Women who have high amounts of androgen and thus an increase tendency for android fat distribution are in the lowest quintiles of levels of sex-hormone-binding globulin and more are at high risks of ill health associated with android fat High levels of android fat have been associated with obesity and diseases caused by insulin insensitivity, such as diabetes. Insulin responsiveness is dependent on adipose cell size. The larger the adipose cell size the less sensitive the insulin. Diabetes is more likely to occur in obese women with android fat distribution and hypertrophic fat cells. It is not just general obesity that is a consequence of android fat distribution but also other health consequences. There are connections between high android fat distributions and the severity of diseases such as acute pancreatitis - where the higher the levels of android fat are, the more severe the pancreatitis can be.
An increase in android fat distribution is positively correlated with foot pain and disability associated with foot pain. Foot pain is reported to be the second most common musculoskeletal symptom in children who are obese. Even adults who are overweight and obese report foot pain to be a common problem.
Psychological consequences
Body fat can impact on an individual mentally, for example high levels of android fat have been linked to poor mental wellbeing, including anxiety, depression and body confidence issues. On the reverse, psychological aspects can impact on body fat distribution too, for example women classed as being more extraverted tend to have less android body fat.
Waist–hip ratio
See gynoid fat distribution
Central obesity is measured as increase by waist circumference or waist–hip ratio. Increase in waist circumference > 102 cm (40 in.) in males and > 88 cm (35 in.) in females. However increase in abdominal circumference may be due to increasing in subcutaneous or visceral fat, and it is the visceral fat which increases the risk of coronary diseases. The visceral fat can be estimated with the help of MRI and CT scan.
In females, measures of Waist to Hip ratio have been observed as an evolutionary sign of attractiveness and reproductive success. A females waist being smaller than her hips by a ratio of 0.7 is considered most attractive as it indicated readiness to give birth to offspring, and overall health to ensure survival of offspring. Waist to hip ratio is determined by an individuals proportions of android fat and gynoid fat. A small waist to hip ratio indicates less android fat, high waist to hip ratios indicate high levels of android fat.As WHR is associated with a womans pregnancy rate, it has been found that a high waist-to-hip ratio can impair pregnancy, thus a health consequence of high android fat levels is its interference with the success of pregnancy and in-vitro fertilisation. Body fat distribution is also related to the sex ratio of offspring. Women with large waists (a high WHR) tend to have an android fat distribution caused by a specific hormone profile, that is, having higher levels of androgens. This leads to such women having more sons.
Liposuction
Liposuction is a medical procedure used to remove fat from the body, common areas being around the abdomen, thighs and buttocks. Liposuction does not improve an individuals health or insulin sensitivity and is therefore considered a cosmetic surgery. liposuction improves quality of life in everyday activities and issues regarding ones psychological state or social life after liposuction are less serious. It has been found that abdominal exercise alone cannot reduce android fat around the trunk and abdomen so liposuction is often a short term solution.
As liposuction can lower a persons waist–hip ratio by removing fat from locations where android fat accumulates, it can give the appearance of a more attractive body shape, and imitate an indication of reproductive health. Another method of reducing android fat is Laparoscopic Adjustable Gastric Banding which has been found to significantly reduce overall android fat percentages in obese individuals.
Individual differences
Cultural differences
Cultural differences in the distribution of android fat have been observed in several studies. Compared to Europeans, South Asian individuals living in the UK have greater abdominal fat. Asian Indians living in the USA have high levels of body fat in contrast to their muscle mass and BMI
Newborn babies in India also show similar differences in their body fat distribution.
There is a difference in waist-to-hip ratio (WHRs) between Indian people and Africans living in South Africa such that Indians have greater WHRs compared to African people.A difference in body fat distribution was observed between men and women living in Denmark (this includes both android fat distribution and gynoid fat distribution), of those aged between 35 and 65 years, men showed greater body fat mass than women. Men showed a total body fat mass increase of 6.9 kg and women showed a total body fat mass increase of 4.5 kg between the ages of 35 and 65.
These observed differences could be due to a difference in muscularity.
Australian Aborigines who live a hunter gatherer lifestyle, have been noted to have high levels of obesity (with an android fat distribution) when they switch to a Westernized lifestyle. This is because in comparison to their previous lifestyle where they would engage in strenuous physical activity daily and have meals that are low in fat and high in fiber, the Westernized lifestyle has less physical activity and the diet includes high levels of carbohydrates and fats.
Age related changes
Android fat distributions change across life course. The main changes in women are associated with menopause. Premenopausal women tend to show a more gynoid fat distribution than post-menopausal women - this is associated with a drop in oestrogen levels. An android fat distribution becomes more common post-menopause, where oestrogen is at its lowest levels. Older men show android fat distributions more often than younger men which may be due to lifestyle changes, or hormonal changes related to age.
Older adults have a greater waist-to-hip ratio than young adults which indicates high levels of android fat in older adults. Computed tomography studies show that older adults have a two-fold increase in visceral fat compared to young adults. These changes in android fat distribution in older adults occurs in the absence of any clinical diseases.
== References == |
Myxoid liposarcoma | A myxoid liposarcoma is a malignant adipose tissue neoplasm of myxoid appearance histologically.
Myxoid liposarcomas are the second-most common type of liposarcoma, representing 30–40% of all liposarcomas in the limbs, occurring most commonly in the legs, particularly the thigh, followed by the buttocks, retroperitoneum, trunk, ankle, proximal limb girdle, head and neck, and wrist. They occur in the intermuscular fascial planes or deep-seated areas. They present as a large, slow-growing, painless mass.The neoplastic cells in these neoplasms contain chromosomal translocations which create one of two fusion genes: the FUS-DDIT3 in ~90% and the EWSR1-DDIT3 fusion gene in up to 10% of myxoid liposarcoma cases. The FUS-DDIT3 fusion gene forms by a merger of part of the FUS FET gene family gene normally located at band 11.2 on the short (or "p") arm of chromosome 16 with part of the DDIT3 ETS transcription factor family gene normally located at band 13.3 on the long (or "q") arm of chromosome 12. This fusion gene is notated as t(12;16)(q13;p11). Preclinical studies, i.e. laboratory studies, suggest that the FUS-DDIT3 fusion gene may act as an oncogene to promote the development of myxoid liposarmas. The EWSR1-DDIT3 fusion gene forms by a merger of the EWSR1 FET gene family gene located at band 12.2 on the q arm of chromosome 22 with part of the DDIT3 gene. This fusion gene is notated as t(12;22)(q13;12).
Additional images
See also
Lipoma
Trabectedin
References
External links
Myxoid liposarcoma: a rare soft-tissue tumor with a misleading benign appearance
Efficacy of first-line doxorubicin and ifosfamide in myxoid liposarcoma. 2012 |
Muscular dystrophy | Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affected, the degree of weakness, how fast they worsen, and when symptoms begin. Some types are also associated with problems in other organs.Over 30 different disorders are classified as muscular dystrophies. Of those, Duchenne muscular dystrophy (DMD) accounts for approximately 50% of cases and affects males beginning around the age of four. Other relatively common muscular dystrophies include Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy, whereas limb–girdle muscular dystrophy and congenital muscular dystrophy are themselves groups of several – usually ultrarare – genetic disorders.
Muscular dystrophies are caused by mutations in genes, usually those involved in making muscle proteins. These mutations are either inherited from parents or may occur spontaneously during early development. Muscular dystrophies may be X-linked recessive, autosomal recessive, or autosomal dominant. Diagnosis often involves blood tests and genetic testing.There is no cure for any disorder from the muscular dystrophy group. Several drugs designed to address the root cause are under development, including gene therapy (Microdystrophin), and antisense drugs (Ataluren, Eteplirsen etc.). Other medications used include corticosteroids (Deflazacort), calcium channel blockers (Diltiazem) to slow skeletal and cardiac muscle degeneration, anticonvulsants to control seizures and some muscle activity, and immunosuppressants (Vamorolone) to delay damage to dying muscle cells. Physical therapy, braces, and corrective surgery may help with some symptoms while assisted ventilation may be required in those with weakness of breathing muscles.Outcomes depend on the specific type of disorder. Many affected people will eventually become unable to walk and Duchenne muscular dystrophy in particular is associated with shortened life expectancy.
Muscular dystrophy was first described in the 1830s by Charles Bell. The word "dystrophy" comes from the Greek dys, meaning "no, un-" and troph- meaning "nourish".
Signs and symptoms
The signs and symptoms consistent with muscular dystrophy are:
Causes
The majority of muscular dystrophies are inherited; the different muscular dystrophies follow various inheritance patterns (X-linked, autosomal recessive or autosomal dominant). In a small percentage of patients, the disorder may have been caused by a de novo (spontaneous) mutation.
Diagnosis
The diagnosis of muscular dystrophy is based on the results of muscle biopsy, increased creatine phosphokinase (CpK3), electromyography, and genetic testing. A physical examination and the patients medical history will help the doctor determine the type of muscular dystrophy. Specific muscle groups are affected by different types of muscular dystrophy.
Classification
Management
Currently, there is no cure for muscular dystrophy. In terms of management, physical therapy, occupational therapy, orthotic intervention (e.g., ankle-foot orthosis), speech therapy, and respiratory therapy may be helpful. Low intensity corticosteroids such as prednisone, and deflazacort may help to maintain muscle tone. Orthoses (orthopedic appliances used for support) and corrective orthopedic surgery may be needed to improve the quality of life in some cases. The cardiac problems that occur with Emery–Dreifuss muscular dystrophy (EDMD) and myotonic muscular dystrophy may require a pacemaker. The myotonia (delayed relaxation of a muscle after a strong contraction) occurring in myotonic muscular dystrophy may be treated with medications such as quinine.Occupational therapy assists the individual with MD to engage in activities of daily living (such as self-feeding and self-care activities) and leisure activities at the most independent level possible. This may be achieved with use of adaptive equipment or the use of energy-conservation techniques. Occupational therapy may implement changes to a persons environment, both at home or work, to increase the individuals function and accessibility; furthermore, it addresses psychosocial changes and cognitive decline which may accompany MD, and provides support and education about the disease to the family and individual.
Prognosis
Prognosis depends on the individual form of muscular dystrophy. Some dystrophies cause progressive weakness and loss of muscle function, which may result in severe physical disability and a life-threatening deterioration of respiratory muscles or heart. Other dystrophies do not affect life expectancy and only cause relatively mild impairment.
History
In the 1860s, descriptions of boys who grew progressively weaker, lost the ability to walk, and died at an early age became more prominent in medical journals. In the following decade, French neurologist Guillaume Duchenne gave a comprehensive account of the most common and severe form of the disease, which now carries his name – Duchenne MD.
Society and culture
In 1966 in the US and Canada, Jerry Lewis and the Muscular Dystrophy Association (MDA) began the annual Labor Day telecast The Jerry Lewis Telethon, significant in raising awareness of muscular dystrophy in North America. Disability rights advocates, however, have criticized the telethon for portraying those living with the disease as deserving pity rather than respect.On December 18, 2001, the MD CARE Act was signed into law in the US; it amends the Public Health Service Act to provide research for the various muscular dystrophies. This law also established the Muscular Dystrophy Coordinating Committee to help focus research efforts through a coherent research strategy.
See also
References
Further reading
De Los Angeles Beytía, Maria; Vry, Julia; Kirschner, Janbernd (2012). "Drug treatment of Duchenne musculardystrophy: available evidence and perspectives". Acta Myologica. 31 (1): 4–8. PMC 3440798. PMID 22655510.
Bertini, Enrico; DAmico, Adele; Gualandi, Francesca; Petrini, Stefania (December 2011). "Congenital Muscular Dystrophies: A Brief Review". Seminars in Pediatric Neurology. 18 (4): 277–288. doi:10.1016/j.spen.2011.10.010. PMC 3332154. PMID 22172424.
External links
Muscular dystrophies at Curlie |
Heart failure with preserved ejection fraction | Heart failure with preserved ejection fraction (HFpEF) is a form of heart failure in which the ejection fraction – the percentage of the volume of blood ejected from the left ventricle with each heartbeat divided by the volume of blood when the left ventricle is maximally filled – is normal, defined as greater than 50%; this may be measured by echocardiography or cardiac catheterization. Approximately half of people with heart failure have preserved ejection fraction, while the other half have a reduction in ejection fraction, called heart failure with reduced ejection fraction (HFrEF).Risk factors for HFpEF include hypertension, hyperlipidemia, diabetes, smoking, and obstructive sleep apnea.
HFpEF is characterized by abnormal diastolic function: there is an increase in the stiffness of the left ventricle, which causes a decrease in left ventricular relaxation during diastole, with resultant increased pressure and/or impaired filling. There is an increased risk for atrial fibrillation and pulmonary hypertension.
There is controversy regarding the relationship between diastolic heart failure and HFpEF.
Signs and symptoms
Clinical manifestations of HFpEF are similar to those observed in HFrEF and include shortness of breath including exercise induced dyspnea, paroxysmal nocturnal dyspnea and orthopnea, exercise intolerance, fatigue, elevated jugular venous pressure, and edema.Patients with HFpEF poorly tolerate stress, particularly hemodynamic alterations of ventricular loading or increased diastolic pressures. Often there is a more dramatic elevation in systolic blood pressure in HFpEF than is typical of HFrEF.
Risk factors
Diverse mechanisms contribute to the development of HFpEF, many of which are under-investigated and remain obscure. Despite this, there are clear risk factors that contribute to the development of HFpEF.Hypertension, obesity, metabolic syndrome, and sedentary lifestyle have been identified as important risk factors for diverse types of heart disease including HFpEF. There is mechanistic and epidemiological evidence for a link between insulin resistance and HFpEF.This pro-inflammatory state may also induce changes in the vascular endothelium of the heart. Specifically, by reducing availability of nitric oxide, an important vasodilator and regulator of protein kinase G activity. As protein kinase G activity diminishes, cardiomyocytes undergo hypertrophic changes. Endothelial cells also are responsible for the production of E-selectin, which recruits lymphocytes into the tissue beneath the endothelium that subsequently release transforming growth factor beta, encouraging fibrosis and thus ventricular stiffening. Cardiac macrophages are thought to play an important role in the development of fibrosis as they are increased in HFpEF and release pro-fibrotic cytokines, such as IL-10. Further investigation of the role of inflammation in HFpEF is needed.
Hypertension
Conditions, such as hypertension, that encourage increased left ventricular afterload can lead to structural changes in the heart on a gross, as well as a microscopic level. It is thought that increased pressure, in concert with a pro-inflammatory state (insulin resistance, obesity), encourage ventricular stiffening and remodeling that lead to poor cardiac output seen in HFpEF. There changes are a result of left ventricular muscle hypertrophy caused by the high pressure, leading to the left ventricle becoming stiff.
Ischemia
Ischemia, or inadequate oxygenation of the myocardium, is observed in a high proportion of HFpEF patients. This ischemia may be secondary to coronary artery disease, or a result of the previously described changes in microvasculature.
Ischemia can result in impaired relaxation of the heart; when myocytes fail to relax appropriately, myosin cross bridges remain intact and generate tension throughout diastole and thus increase stress on the heart. This is termed partial persistent systole. Ischemia may manifest in distinct ways, either as a result of increasing tissue oxygen demand, or diminished ability of the heart to supply oxygen to the tissue. The former is the result of stress, such as exercise, while the latter is the result of reduced coronary flow.
Aging
Cardiac senescence, or cellular deterioration that occurs as part of normal aging, closely resembles the manifestations of HFpEF. Specifically, loss of cardiac reserve, diminished vascular compliance, and diastolic dysfunction are characteristic of both processes. It has been suggested that HFpEF merely represents an acceleration of a normal aging process.
Senile systemic amyloidosis, resulting from accumulation of aggregated wild-type transthyretin as part of the degenerative aging process, is emerging as an important and underdiagnosed contributor to HFpEF with age.
Other
Any condition or process that leads to stiffening of the left ventricle can lead to diastolic dysfunction. Other causes of left ventricular stiffening include:
Aortic stenosis of any cause where the ventricular muscle becomes hypertrophied, and thence stiff, as a result of the increased pressure load placed on it by the stenosis.
Diabetes
Age – elderly patients mainly if they have hypertension.Causes of isolated right ventricular diastolic failure are uncommon. These causes include:
Constrictive pericarditis
Restrictive cardiomyopathy, which includes Amyloidosis (most common restrictive), Sarcoidosis and fibrosis.
Pathophysiology
Gross structural abnormalities
Structural changes that occur with HFpEF are often radically different from those associated with heart failure with reduced ejection fraction (HFrEF). Many patients experience increased thickening of the ventricular wall in comparison to chamber size, termed concentric hypertrophy. This leads to increased left ventricular mass and is typically accompanied by a normal, or slightly reduced, end diastolic filling volume. Conversely, HFrEF is typically associated with eccentric hypertrophy, characterized by an increase in cardiac chamber size without an accompanying increase in wall thickness. This leads to a corresponding increase in left ventricular end diastolic volume.
Cellular abnormalities
Cellular changes generally underlie alterations in cardiac structure. In HFpEF cardiomyocytes have been demonstrated to show increased diameter without an increase in length; this is consistent with observed concentric ventricular hypertrophy and increased left ventricular mass. HFrEF cardiomyocytes exhibit the opposite morphology; increased length without increased cellular diameter. This too is consistent with eccentric hypertrophy seen in this condition.Changes in the extracellular environment are of significant importance in heart disease. Particularly, regulation of genes that alter fibrosis contribute to the development and progression of HFrEF. This regulation is dynamic and involves changes in fibrillar collagens through increased deposition as well as inhibition of enzymes that break down extracellular matrix components (matrix metalloproteinases, collagenases). While early stage HFrEF is associated with a significant disruption of extracellular matrix proteins initially, as it progresses fibrotic replacement of myocardium may occur, leading to scarring and increased interstitial collagen. Fibrotic changes in HFpEF are more variable. Though there is typically an increased amount of collagen observed in these patients it is usually not dramatically different from healthy individuals.
Diastolic dysfunction
Diastolic alterations in HFpEF are the predominating factor in impaired cardiac function and subsequent clinical presentation. Diastolic dysfunction is multifaceted, and a given patient may express diverse combinations of the following: incomplete myocardial relaxation, impaired rate of ventricular filling, increased left atrial pressure in filling, increased passive stiffness and decreased distensibility of the ventricle, limited ability to exploit the Frank-Starling mechanism with increased output demands, increased diastolic left heart or pulmonary venous pressure.Diastolic failure appears when the ventricle cannot be filled properly because it cannot relax because its wall is thick or rigid. This situation presents usually a concentric hypertrophy. In contrast, systolic heart failure has usually an eccentric hypertrophy.Diastolic failure is characterized by an elevated diastolic pressure in the left ventricle, despite an essentially normal/physiologic end diastolic volume (EDV). Histological evidence supporting diastolic dysfunction demonstrates ventricular hypertrophy, increased interstitial collagen deposition and infiltration of the myocardium. These influences collectively lead to a decrease in distensibility and elasticity (ability to stretch) of the myocardium. As a consequence, cardiac output becomes diminished. When the left ventricular diastolic pressure is elevated, venous pressure in lungs must also become elevated too: left ventricular stiffness makes it more difficult for blood to enter it from the left atrium. As a result, pressure rises in the atrium and is transmitted back to the pulmonary venous system, thereby increasing its hydrostatic pressure and promoting pulmonary edema.
It may be misguided to classify the volume-overloaded heart as having diastolic dysfunction if it is behaving in a stiff and non-compliant manner. The term diastolic dysfunction should not be applied to the dilated heart. Dilated ("remodeled") hearts have increased volume relative to the amount of diastolic pressure, and therefore have increased (not decreased) distensibility. The term diastolic dysfunction is sometimes erroneously applied in this circumstance, when increased fluid volume retention causes the heart to be over-filled (High output cardiac failure).Although the term diastolic heart failure is often used when there are signs and symptoms of heart failure with normal left ventricular systolic function, this is not always appropriate. Diastolic function is determined by the relative end diastolic volume in relation to end diastolic pressure, and is therefore independent of left ventricular systolic function. A leftward shift of the end-diastolic pressure-volume relationship (i.e. decreased left ventricular distensibility) can occur both in those with normal and those with decreased left ventricular systolic function. Likewise, heart failure may occur in those with dilated left ventricular and normal systolic function. This is often seen in valvular heart disease and high-output heart failure. Neither of these situations constitutes a diastolic heart failure.Stiffening of the left ventricle contributes heart failure with preserved ejection fraction, a condition that can be prevented with exercise.In diastolic heart failure, the volume of blood contained in the ventricles during diastole is lower than it should be, and the pressure of the blood within the chambers is elevated.
Diastole
During diastole, the ventricular pressure falls from the peak reached at the end of systole. When this pressure falls below the atrial pressure, atrio-ventricular valves open (mitral valve at left side and tricuspid valve at right side) and the blood passes from the atria into the ventricles. First, ventricles are filled by a pressure gradient but near the end, atria contract (atrial kick) and force more blood to pass into ventricles. Atrial contraction is responsible for around 20% of the total filling blood volume. (In atrial fibrillation, this additional 20% filling volume is lost and the patient may experience systolic heart failure symptoms). Complete left ventricular filling is essential to maintain maximum cardiac output. Left ventricular filling is dependent upon ventricular relaxation and compliance, mitral valve area, atrio-ventricular gradient, atrial contraction and end-systolic volume. Diastole has four phases: isovolumetric relaxation, rapid filling, diastasis and atrial contraction. All of these phases can be evaluated by Doppler echocardiography.
Non-diastolic dysfunction
Though HFpEF is characterized by a normal ejection fraction, this parameter is a rather poor index of the hearts contractile function. Some studies have shown that metrics of load independent contractility (such as left ventricular stiffness) reveal diminished systolic function in HFpEF patients compared to healthy controls, and are corroborated by tissue Doppler findings that reveal changes in longitudinal contraction and motion abnormalities. While these systolic impairments may be minimal at rest, they become more exaggerated with increased demand, as seen in exercise.
Pulmonary hypertension and right ventricular dysfunction
Most HFpEF patients exhibit pulmonary hypertension which is significantly associated with increased morbidity and mortality. Left atrial and pulmonary venous pressure increases in HFpEF due to diastolic insufficiency thus increasing pulmonary artery pressure. In patients with advanced HFpEF changes in the pulmonary vasculature may develop, leading to pre-capillary pulmonary hypertension. Right ventricular dysfunction is also common in HFpEF patients, occurring in 20-35% of patients. This right ventricular dysfunction is more common in patients with more advanced HFpEF as well as those with pulmonary hypertension and lower ejection fractions.
Heart rate
Cardiac output is dependent on stroke volume and heart rate. A significant portion (55-77%) of HFpEF patients are unable to increase heart rate to compensate for increased output demand (as in the setting of exercise); this is termed chronotropic incompetence. Combined with the characteristic deficit in stroke volume observed in HFpEF patients, many individuals display poor exercise tolerance.
Dyssynchrony
Non-simultaneous contraction of the left and right ventricle, dyssychrony, is present in up to 58% of HFpEF patients. However, dyssynchrony is also common in HFrEF and its role in HFpEF in particular remains obscure. While therapies for dyssynchrony, such as biventricular pacing provide benefits to HFrEF patients, no benefit is appreciable in HFpEF patients at this time.
Systemic abnormalities
Patients with HFpEF, in addition to cardiac abnormalities, display changes in (endothelial) microvascular function, skeletal muscle metabolism and in fat distribution and character throughout the body. The importance of these changes is demonstrated in that stable, non-decompensated patients seem to benefit from exercise; specifically increased VO2 max and exercise tolerance. However, this benefit appears to be derived from changes in muscle and vasculature as opposed to directly on the heart, which displays minimal change in output following exercise training.
Diagnosis
HFpEF is typically diagnosed with echocardiography. Techniques such as catheterization are invasive procedures and thus reserved for patients with co-morbid conditions or those who are suspected to have HFpEF but lack clear non-invasive findings. Catheterization does represent are more definitive diagnostic assessment as pressure and volume measurements are taken simultaneously and directly. In either technique, the heart is evaluated for left ventricular diastolic function. Important parameters include, rate of isovolumic relaxation, rate of ventricular filling, and stiffness.Frequently patients are subjected to stress echocardiography, which involves the above assessment of diastolic function during exercise. This is undertaken because perturbations in diastole are exaggerated during the increased demands of exercise. Exercise requires increased left ventricular filling and subsequent output. Typically the heart responds by increasing heart rate and relaxation time. However, in patients with HFpEF both responses are diminished due to increased ventricular stiffness. Testing during this demanding state may reveal abnormalities that are not as discernible at rest.Diastolic dysfunction must be differentiated from diastolic heart failure. Diastolic dysfunction can be found in elderly and apparently quite healthy patients. If diastolic dysfunction describes an abnormal mechanical property, diastolic heart failure describes a clinical syndrome. Mathematics describing the relationship between the ratio of Systole to Diastole in accepted terms of End Systolic Volume to End Diastolic Volume implies many mathematical solutions to forward and backward heart failure.Criteria for diagnosis of diastolic dysfunction or diastolic heart failure remain imprecise. This has made it difficult to conduct valid clinical trials of treatments for diastolic heart failure. The problem is compounded by the fact that systolic and diastolic heart failure commonly coexist when patients present with many ischemic and nonischemic etiologies of heart failure. Narrowly defined, diastolic failure has often been defined as "heart failure with normal systolic function" (i.e. left ventricular ejection fraction of 60% or more). Chagasic heart disease may represent an optimal academic model of diastolic heart failure that spares systolic function.A patient is said to have diastolic dysfunction if he has signs and symptoms of heart failure but the left ventricular ejection fraction is normal. A second approach is to use an elevated BNP level in the presence of normal ejection fraction to diagnose diastolic heart failure. Concordance of both volumetric and biochemical measurements and markers lends to even stronger terminology regarding scientific/mathematical expression of diastolic heart failure. These are both probably too broad a definition for diastolic heart failure, and this group of patients is more precisely described as having heart failure with normal systolic function. Echocardiography can be used to diagnose diastolic dysfunction but is a limited modality unless it is supplemented by stress imaging. MUGA imaging is an earlier mathematical attempt to distinguish systolic from diastolic heart failure.No single echocardiographic parameter can confirm a diagnosis of diastolic heart failure. Multiple echocardiographic parameters have been proposed as sufficiently sensitive and specific, including mitral inflow velocity patterns, pulmonary vein flow patterns, E/A reversal, tissue Doppler measurements, and M-mode echo measurements (i.e. of left atrial size). Algorithms have also been developed which combine multiple echocardiographic parameters to diagnose diastolic heart failure.There are four basic Echocardiographic patterns of diastolic heart failure, which are graded I to IV:
The mildest form is called an "abnormal relaxation pattern", or grade I diastolic dysfunction. On the mitral inflow Doppler echocardiogram, there is reversal of the normal E/A ratio. This pattern may develop normally with age in some patients, and many grade I patients will not have any clinical signs or symptoms of heart failure.
Grade II diastolic dysfunction is called "pseudonormal filling dynamics". This is considered moderate diastolic dysfunction and is associated with elevated left atrial filling pressures. These patients more commonly have symptoms of heart failure, and many have left atrial enlargement due to the elevated pressures in the left heart.Grade III and IV diastolic dysfunction are called "restrictive filling dynamics". These are both severe forms of diastolic dysfunction, and patients tend to have advanced heart failure symptoms:
Class III diastolic dysfunction patients will demonstrate reversal of their diastolic abnormalities on echocardiogram when they perform the Valsalva maneuver. This is referred to as "reversible restrictive diastolic dysfunction".
Class IV diastolic dysfunction patients will not demonstrate reversibility of their echocardiogram abnormalities, and are therefore said to have "fixed restrictive diastolic dysfunction".The presence of either class III and IV diastolic dysfunction is associated with a significantly worse prognosis. These patients will have left atrial enlargement, and many will have a reduced left ventricular ejection fraction that indicates a combination of systolic and diastolic dysfunction.Imaged volumetric definition of systolic heart performance is commonly accepted as ejection fraction. Volumetric definition of the heart in systole was first described by Adolph Fick as cardiac output. Fick may be readily and inexpensively inverted to cardiac output and ejection fraction to mathematically describe diastole. Decline of ejection fraction paired with decline of E/A ratio seems a stronger argument in support of a mathematical definition of diastolic heart failure.Another parameter to assess diastolic function is the E/E ratio, which is the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E). Diastolic dysfunction is assumed when the E/E ratio exceed 15.Newer echocardiographic techniques such as speckle tracking for strain measurement, particularly for the left atrium, are becoming increasingly utilised for the diagnosis of HFpEF.
Treatment
Despite increasing incidence of HFpEF effective inroads to therapeutics have been largely unsuccessful. Currently, recommendations for treatment are directed at symptom relief and co-morbid conditions. Frequently this involves administration of diuretics to relieve complications associated with volume overload, such as leg swelling and high blood pressure.Commonly encountered conditions that must be treated for and have independent recommendations for standard of care include atrial fibrillation, coronary artery disease, hypertension, and hyperlipidemia. There are particular factors unique to HFpEF that must be accounted for with therapy. Unfortunately, currently available randomized clinical trials addressing the therapeutic adventure for these conditions in HFpEF present conflicting or limited evidence.Specific aspects of therapeutics should be avoided in HFpEF to prevent the deterioration of the condition. Considerations that are generalizable to heart failure include avoidance of a fast heart rate, elevations in blood pressure, development of ischemia, and atrial fibrillation. More specific to HFpEF include avoidance of preload reduction. As patients display normal ejection fraction but reduced cardiac output they are especially sensitive to changes in preloading and may rapidly display signs of output failure. This means administration of diuretics and vasodilators must be monitored carefully.HFrEF and HFpEF represent distinct entities in terms of development and effective therapeutic management. Specifically cardiac resynchronization, administration of beta blockers and angiotensin converting enzyme inhibitors are applied to good effect in HFrEF but are largely ineffective at reducing morbidity and mortality in HFpEF. Many of these therapies are effective in reducing the extent of cardiac dilation and increasing ejection fraction in HFrEF patients. It is unsurprising they fail to effect improvement in HFpEF patients, given their un-dilated phenotype and relative normal ejection fraction. Understanding and targeting mechanisms unique to HFpEF are thus essential to the development of therapeutics.Randomized studies on HFpEF patients have shown that exercise improves left ventricular diastolic function, the hearts ability to relax, and is associated with improved aerobic exercise capacity. The benefit patients seem to derive from exercise does not seem to be a direct cardiac effect but rather is due to changes in peripheral vasculature and skeletal muscle, which show abnormalities in HFpEF patients.Patients should be regularly assessed to determine progression of the condition, response to interventions, and need for alteration of therapy. Ability to perform daily tasks, hemodynamic status, kidney function, electrolyte balance, and serum natriuretic peptide levels are important parameters. Behavioral management is important in these patients and it is recommended that individuals with HFpEF avoid alcohol, smoking, and high sodium intake.
Pharmacologic therapy
Indications
Management of HFpEF is primarily dependent on the treatment of symptoms and exacerbating conditions. The role of specific treatments for diastolic dysfunction per se is as yet unclear.
Benefit
Currently treatment with ACE inhibitors, calcium channel blockers, beta blockers, and angiotensin receptor blockers are employed but do not have a proven benefit in HFpEF patients. Additionally, use of diuretics or other therapies that can alter loading conditions or blood pressure should be used with caution. It is not recommended that patients be treated with phosphodiesterase-5-inhibitors or digoxin.
Agents
Mineralocorticoid receptor antagonists
An antimineralocorticoid is currently recommended for patients with HFpEF who show elevated brain natriuretic peptide levels. Spironolactone is the first member of this medication class and the most frequently employed. Care should be taken to monitor serum potassium levels as well as kidney function, specifically glomerular filtration rate during treatment.
Beta blockers
Beta blockers play a rather obscure role in HFpEF treatment though there is suggestion of a beneficial role in patient management. Evidence from a meta-analysis demonstrated significant reductions in all cause mortality with beta-blocker therapy, though overall effects were driven largely by small, older trials of patients post-myocardial infarction. Some evidence suggests that vasodilating beta blockers, such as nebivolol, can provide a benefit for patients with heart failure regardless of ejection fraction. Additionally, because of the chronotropic perturbation and diminished LV filling seen in HFpEF the bradycardic effect of beta blockers may enable improved filling, reduce myocardial oxygen demand, and lower blood pressure. However, this effect also can contribute to diminished response to exercise demands and can result in an excessive reduction in heart rate.Beta-blockers are the first-line therapy: they lower the heart rate and thus give more time for ventricles to fill. They may also improve survival.
Angiotensin converting enzyme (ACE) inhibitors
Likewise, treatment with angiotensin converting enzyme inhibitors, such as enalapril, ramipril, and many others, may be of benefit due to their effect on preventing ventricular remodeling but under control to avoid hypotension.
ACE inhibitors do not appear to improve morbidity or mortality associated with HFpEF alone. However, they are important in the management of hypertension, a significant player in the pathophysiology of HFpEF.
Angiotensin II receptor blockers (ARBs)
ARB treatment results in an improvement in diastolic dysfunction and hypertension that is comparable to other anti-hypertensive medication.
Calcium channel blockers
There is some evidence that calcium channel blockers may be of benefit in reducing ventricular stiffness. In some cases, (verapamil has the benefit lowering the heart rate).
Diuretics
Diuretics can be useful if significant congestion develops, but patients must be monitored because they frequently develop low blood pressure.
Experimental
The use of a self-expanding device that attaches to the external surface of the left ventricle has been suggested, yet still awaits FDA approval. When the heart muscle squeezes, energy is loaded into the device, which absorbs the energy and releases it to the left ventricle in the diastolic phase. This helps retain muscle elasticity.
Prognosis
The progression of HFpEF and its clinical course is poorly understood in comparison to HFrEF. Despite this, patients with HFrEF and HFpEF appear to have comparable outcomes in terms of hospitalization and mortality. Causes of death in patients vary substantially. However, among patients in more advanced heart failure (NYHA classes II-IV), cardiovascular death, including heart attacks and sudden cardiac death, was the predominant cause in population-based studies.Until recently, it was generally assumed that the prognosis for individuals with diastolic dysfunction and associated intermittent pulmonary edema was better than those with systolic dysfunction. In fact, in two studies appearing in the New England Journal of Medicine in 2006, evidence was presented to suggest that the prognosis in diastolic dysfunction is the same as that in systolic dysfunction.
References
Bibliography
Estafanous FG (2001). Cardiac anesthesia. Principles and clinical practice (2nd ed.). Lippincott Williams & Wilkins. ISBN 978-0781721950.{{cite book}}: CS1 maint: ref duplicates default (link)
Fuster V, ORouke RA (2001). Hursts The Heart (10 (International edition) ed.). McGraw-Hill. pp. 658–60. ISBN 978-0-07-116296-8.
== External links == |
Personality disorder | Personality disorders (PD) are a class of mental disorders characterized by enduring maladaptive patterns of behavior, cognition, and inner experience, exhibited across many contexts and deviating from those accepted by the individuals culture. These patterns develop early, are inflexible, and are associated with significant distress or disability. The definitions vary by source and remain a matter of controversy. Official criteria for diagnosing personality disorders are listed in the sixth chapter of the International Classification of Diseases (ICD) and in the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders (DSM).
Personality, defined psychologically, is the set of enduring behavioral and mental traits that distinguish individual humans. Hence, personality disorders are defined by experiences and behaviors that deviate from social norms and expectations. Those diagnosed with a personality disorder may experience difficulties in cognition, emotiveness, interpersonal functioning, or impulse control. For psychiatric patients, the prevalence of personality disorders is estimated between 40 and 60%, The behavior patterns of personality disorders are typically recognized by adolescence, the beginning of adulthood or sometimes even childhood and often have a pervasive negative impact on the quality of life.Treatment for personality disorders is primarily psychotherapeutic. Evidence-based psychotherapies for personality disorders include cognitive behavioral therapy, and dialectical behavior therapy especially for borderline personality disorder. A variety of psychoanalytic approaches are also used.Personality disorders are associated with considerable stigma in popular and clinical discourse alike. Despite various methodological schemas designed to categorize personality disorders, many issues occur with classifying a personality disorder because the theory and diagnosis of such disorders occur within prevailing cultural expectations; thus, their validity is contested by some experts on the basis of inevitable subjectivity. They argue that the theory and diagnosis of personality disorders are based strictly on social, or even sociopolitical and economic considerations.
Classification and symptoms
The two latest editions of the major systems of classification are
the International Classification of Diseases (11th revision, ICD-11) published by the World Health Organization
the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition, DSM-5) by the American Psychiatric Association.The ICD is a collection of alpha-numerical codes which have been assigned to all known clinical states, and provides uniform terminology for medical records, billing, statistics and research. The DSM defines psychiatric diagnoses based on research and expert consensus. Both have deliberately aligned their diagnoses to some extent, but some differences remain. For example, the ICD-10 included narcissistic personality disorder in the group of other specific personality disorders, while DSM-5 does not include enduring personality change after catastrophic experience. The ICD-10 classified the DSM-5 schizotypal personality disorder as a form of schizophrenia rather than as a personality disorder. There are accepted diagnostic issues and controversies with regard to distinguishing particular personality disorder categories from each other. Dissociative identity disorder, previously known as multiple personality as well as multiple personality disorder, has always been classified as a dissociative disorder and never was regarded as a personality disorder.
DSM-5
The most recent fifth edition of the Diagnostic and Statistical Manual of Mental Disorders stresses that a personality disorder is an enduring and inflexible pattern of long duration leading to significant distress or impairment and is not due to use of substances or another medical condition. The DSM-5 lists personality disorders in the same way as other mental disorders, rather than on a separate axis, as previously.DSM-5 lists ten specific personality disorders: paranoid, schizoid, schizotypal, antisocial, borderline, histrionic, narcissistic, avoidant, dependent and obsessive–compulsive personality disorder.
The DSM-5 also contains three diagnoses for personality patterns not matching these ten disorders, but nevertheless exhibit characteristics of a personality disorder:
Personality change due to another medical condition – personality disturbance due to the direct effects of a medical condition.
Other specified personality disorder – general criteria for a personality disorder are met but fails to meet the criteria for a specific disorder, with the reason given.
Unspecified personality disorder – general criteria for a personality disorder are met but the personality disorder is not included in the DSM-5 classification.These specific personality disorders are grouped into the following three clusters based on descriptive similarities:
Cluster A (odd or eccentric disorders)
Cluster A personality disorders are often associated with schizophrenia: in particular, schizotypal personality disorder shares some of its hallmark symptoms with schizophrenia, e.g., acute discomfort in close relationships, cognitive or perceptual distortions, and eccentricities of behavior. However, people diagnosed with odd-eccentric personality disorders tend to have a greater grasp on reality than those with schizophrenia. People with these disorders can be paranoid and have difficulty being understood by others, as they often have odd or eccentric modes of speaking and an unwillingness and inability to form and maintain close relationships. Though their perceptions may be unusual, these anomalies are distinguished from delusions or hallucinations as people with these would be diagnosed with other conditions. Significant evidence suggests a small proportion of people with Cluster A personality disorders, especially schizotypal personality disorder, have the potential to develop schizophrenia and other psychotic disorders. These disorders also have a higher probability of occurring among individuals whose first-degree relatives have either schizophrenia or a Cluster A personality disorder.
Paranoid personality disorder: characterized by a pattern of irrational suspicion and mistrust of others, interpreting motivations as malevolent.
Schizoid personality disorder: lack of interest and detachment from social relationships, apathy, and restricted emotional expression.
Schizotypal personality disorder: pattern of extreme discomfort interacting socially, and distorted cognition and perceptions.
Cluster B (dramatic, emotional or erratic disorders)
Cluster B personality disorders are characterized by impulsive, self-destructive, emotional behavior and sometimes incomprehensible interactions with others.
Antisocial personality disorder: pervasive pattern of disregard for and violation of the rights of others, lack of empathy, bloated self-image, manipulative and impulsive behavior.
Borderline personality disorder: pervasive pattern of abrupt emotional outbursts, altered empathy, instability in relationships, self-image, identity, behavior and affect, often leading to self-harm and impulsivity.
Histrionic personality disorder: pervasive pattern of attention-seeking behavior, excessive emotions, and egocentrism.
Narcissistic personality disorder: pervasive pattern of superior grandiosity, need for admiration, and a perceived or real lack of empathy. In a more severe expression, narcissistic personality disorder may show evidence of paranoia, aggression, psychopathy, and sadistic personality disorder, which is known as malignant narcissism.
Cluster C (anxious or fearful disorders)
Avoidant personality disorder: pervasive feelings of social inhibition and inadequacy, extreme sensitivity to negative evaluation.
Dependent personality disorder: pervasive psychological need to be cared for by other people.
Obsessive–compulsive personality disorder: characterized by rigid conformity to rules, perfectionism, and control to the point of satisfaction and exclusion of leisurely activities and friendships (distinct from obsessive–compulsive disorder).
DSM-5 general criteria
Both the DSM-5 and the ICD-11 diagnostic systems provide a definition and six criteria for a general personality disorder. These criteria should be met by all personality disorder cases before a more specific diagnosis can be made.
In DSM-5, any personality disorder diagnosis must meet the following criteria:
An enduring pattern of inner experience and behavior that deviates markedly from the expectations of the individuals culture. This pattern is manifested in two (or more) of the following areas:
Cognition (i.e., ways of perceiving and interpreting self, other people, and events).
Affectivity (i.e., the range, intensity, lability, and appropriateness of emotional response).
Interpersonal functioning.
Impulse control.
The enduring pattern is inflexible and pervasive across a broad range of personal and social situations.
The enduring pattern leads to clinically significant distress or impairment in social, occupational, or other important areas of functioning.
The pattern is stable and of long duration, and its onset can be traced back at least to adolescence or early adulthood.
The enduring pattern is not better explained as a manifestation or consequence of another mental disorder.
The enduring pattern is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition (e.g., head trauma).
ICD-11
The ICD-11 personality disorder section differs substantially compared to the previous edition ICD-10. All distinct PDs have been merged into one: Personality disorder (6D10), which can be coded as Mild (6D10.0), Moderate (6D10.1), Severe (6D10.2), or severity unspecified (6D10.Z). There is also an additional category called Personality difficulty (QE50.7), which can be used to describe personality traits that are problematic, but do not meet the diagnostic criteria for a PD. A personality disorder or difficulty can be specified by one or more Prominent personality traits or patterns (6D11). The ICD-11 uses five trait domains: (1) Negative affectivity (6D11.0); (2) Detachment (6D11.1), (3) Dissociality (6D11.2), (4) Disinhibition (6D11.3), and (5) Anankastia (6D11.4). Listed directly underneath is Borderline pattern (6D11.5), a category similar to Borderline personality disorder. This is not a trait in itself, but a combination of the five traits in certain severity.
In the ICD-11, any personality disorder must meet all of the following criteria:
An enduring disturbance characterized by problems in functioning of aspects of the self (e.g., identity, self-worth, accuracy of self-view, self-direction), and/or interpersonal dysfunction (e.g., ability to develop and maintain close and mutually satisfying relationships, ability to understand others perspectives and to manage conflict in relationships).
The disturbance has persisted over an extended period of time (e.g., lasting 2 years or more).
The disturbance is manifest in patterns of cognition, emotional experience, emotional expression, and behaviour that are maladaptive (e.g., inflexible or poorly regulated).
The disturbance is manifest across a range of personal and social situations (i.e., is not limited to specific relationships or social roles), though it may be consistently evoked by particular types of circumstances and not others.
The symptoms are not due to the direct effects of a medication or substance, including withdrawal effects, and are not better accounted for by another mental disorder, a Disease of the Nervous System, or another medical condition.
The disturbance is associated with substantial distress or significant impairment in personal, family, social, educational, occupational or other important areas of functioning.
Personality Disorder should not be diagnosed if the patterns of behaviour characterizing the personality disturbance are developmentally appropriate (e.g., problems related to establishing an independent self-identity during adolescence) or can be explained primarily by social or cultural factors, including socio-political conflict.
ICD-10
The ICD-10 lists these general guideline criteria:
Markedly disharmonious attitudes and behavior, generally involving several areas of functioning, e.g. affectivity, arousal, impulse control, ways of perceiving and thinking, and style of relating to others;
The abnormal behavior pattern is enduring, of long standing, and not limited to episodes of mental illness;
The abnormal behavior pattern is pervasive and clearly maladaptive to a broad range of personal and social situations;
The above manifestations always appear during childhood or adolescence and continue into adulthood;
The disorder leads to considerable personal distress but this may only become apparent late in its course;
The disorder is usually, but not invariably, associated with significant problems in occupational and social performance.The ICD adds: "For different cultures it may be necessary to develop specific sets of criteria with regard to social norms, rules and obligations."Chapter V in the ICD-10 contains the mental and behavioral disorders and includes categories of personality disorder and enduring personality changes. They are defined as ingrained patterns indicated by inflexible and disabling responses that significantly differ from how the average person in the culture perceives, thinks, and feels, particularly in relating to others.The specific personality disorders are: paranoid, schizoid, schizotypal, dissocial, emotionally unstable (borderline type and impulsive type), histrionic, narcissistic, anankastic, anxious (avoidant) and dependent.Besides the ten specific PD, there are the following categories:
Other specific personality disorders (involves PD characterized as eccentric, haltlose, immature, narcissistic, passive–aggressive, or psychoneurotic.)
Personality disorder, unspecified (includes "character neurosis" and "pathological personality").
Mixed and other personality disorders (defined as conditions that are often troublesome but do not demonstrate the specific pattern of symptoms in the named disorders).
Enduring personality changes, not attributable to brain damage and disease (this is for conditions that seem to arise in adults without a diagnosis of personality disorder, following catastrophic or prolonged stress or other psychiatric illness).
Other personality types and Millons description
Some types of personality disorder were in previous versions of the diagnostic manuals but have been deleted. Examples include sadistic personality disorder (pervasive pattern of cruel, demeaning, and aggressive behavior) and self-defeating personality disorder or masochistic personality disorder (characterized by behavior consequently undermining the persons pleasure and goals). They were listed in the DSM-III-R appendix as "Proposed diagnostic categories needing further study" without specific criteria. Psychologist Theodore Millon, a researcher on personality disorders, and other researchers consider some relegated diagnoses to be equally valid disorders, and may also propose other personality disorders or subtypes, including mixtures of aspects of different categories of the officially accepted diagnoses. Millon proposed the following description of personality disorders:
Additional factors
In addition to classifying by category and cluster, it is possible to classify personality disorders using additional factors such as severity, impact on social functioning, and attribution.
Severity
This involves both the notion of personality difficulty as a measure of subthreshold scores for personality disorder using standard interviews and the evidence that those with the most severe personality disorders demonstrate a “ripple effect” of personality disturbance across the whole range of mental disorders. In addition to subthreshold (personality difficulty) and single cluster (simple personality disorder), this also derives complex or diffuse personality disorder (two or more clusters of personality disorder present) and can also derive severe personality disorder for those of greatest risk.
There are several advantages to classifying personality disorder by severity:
It not only allows for but also takes advantage of the tendency for personality disorders to be comorbid with each other.
It represents the influence of personality disorder on clinical outcome more satisfactorily than the simple dichotomous system of no personality disorder versus personality disorder.
This system accommodates the new diagnosis of severe personality disorder, particularly "dangerous and severe personality disorder" (DSPD).
Effect on social functioning
Social function is affected by many other aspects of mental functioning apart from that of personality. However, whenever there is persistently impaired social functioning in conditions in which it would normally not be expected, the evidence suggests that this is more likely to be created by personality abnormality than by other clinical variables. The Personality Assessment Schedule gives social function priority in creating a hierarchy in which the personality disorder creating the greater social dysfunction is given primacy over others in a subsequent description of personality disorder.
Attribution
Many who have a personality disorder do not recognize any abnormality and defend valiantly their continued occupancy of their personality role. This group have been termed the Type R, or treatment-resisting personality disorders, as opposed to the Type S or treatment-seeking ones, who are keen on altering their personality disorders and sometimes clamor for treatment. The classification of 68 personality disordered patients on the caseload of an assertive community team using a simple scale showed a 3 to 1 ratio between Type R and Type S personality disorders with Cluster C personality disorders being significantly more likely to be Type S, and paranoid and schizoid (Cluster A) personality disorders significantly more likely to be Type R than others.Psychoanalytic theory has been used to explain treatment-resistant tendencies as egosyntonic (i.e. the patterns are consistent with the ego integrity of the individual) and are therefore perceived to be appropriate by that individual. In addition, This behavior can result in maladaptive coping skills and may lead to personal problems that induce extreme anxiety, distress, or depression and result in impaired psychosocial functioning.
Presentation
Comorbidity
There is a considerable personality disorder diagnostic co-occurrence. Patients who meet the DSM-IV-TR diagnostic criteria for one personality disorder are likely to meet the diagnostic criteria for another. Diagnostic categories provide clear, vivid descriptions of discrete personality types but the personality structure of actual patients might be more accurately described by a constellation of maladaptive personality traits.
Sites used DSM-III-R criterion sets. Data obtained for purposes of informing the development of the DSM-IV-TR personality disorder diagnostic criteria.
Abbreviations used: PPD – Paranoid Personality Disorder, SzPD – Schizoid Personality Disorder, StPD – Schizotypal Personality Disorder, ASPD – Antisocial Personality Disorder, BPD – Borderline Personality Disorder, HPD – Histrionic Personality Disorder, NPD – Narcissistic Personality Disorder, AvPD – Avoidant Personality Disorder, DPD – Dependent Personality Disorder, OCPD – Obsessive–Compulsive Personality Disorder, PAPD – Passive–Aggressive Personality Disorder.
The disorders in each of the three clusters may share with each other underlying common vulnerability factors involving cognition, affect and impulse control, and behavioral maintenance or inhibition, respectively. But they may also have a spectrum relationship to certain syndromal mental disorders:
Paranoid, schizoid or schizotypal personality disorders may be observed to be premorbid antecedents of delusional disorders or schizophrenia.
Borderline personality disorder is seen in association with mood and anxiety disorders, with impulse-control disorders, eating disorders, ADHD, or a substance use disorder.
Avoidant personality disorder is seen with social anxiety disorder.
Impact on functioning
It is generally assumed that all personality disorders are linked to impaired functioning and a reduced quality of life (QoL) because that is a basic diagnostic requirement. But research shows that this may be true only for some types of personality disorder.
In several studies, higher levels of disability and lower QoL were predicted by avoidant, dependent, schizoid, paranoid, schizotypal and antisocial personality disorders. This link is particularly strong for avoidant, schizotypal and borderline PD. However, obsessive–compulsive PD was not related to a reduced QoL or increased impairment. A prospective study reported that all PD were associated with significant impairment 15 years later, except for obsessive compulsive and narcissistic personality disorder.One study investigated some aspects of "life success" (status, wealth and successful intimate relationships). It showed somewhat poor functioning for schizotypal, antisocial, borderline and dependent PD, schizoid PD had the lowest scores regarding these variables. Paranoid, histrionic and avoidant PD were average. Narcissistic and obsessive–compulsive PD, however, had high functioning and appeared to contribute rather positively to these aspects of life success.There is also a direct relationship between the number of diagnostic criteria and quality of life. For each additional personality disorder criterion that a person meets there is an even reduction in quality of life.
Issues
In the workplace
Depending on the diagnosis, severity and individual, and the job itself, personality disorders can be associated with difficulty coping with work or the workplace—potentially leading to problems with others by interfering with interpersonal relationships. Indirect effects also play a role; for example, impaired educational progress or complications outside of work, such as substance abuse and co-morbid mental disorders, can be problematic. However, personality disorders can also bring about above-average work abilities by increasing competitive drive or causing the individual with the condition to exploit his or her co-workers.In 2005 and again in 2009, psychologists Belinda Board and Katarina Fritzon at the University of Surrey, UK, interviewed and gave personality tests to high-level British executives and compared their profiles with those of criminal psychiatric patients at Broadmoor Hospital in the UK. They found that three out of eleven personality disorders were actually more common in executives than in the disturbed criminals:
Histrionic personality disorder: including superficial charm, insincerity, egocentricity and manipulation
Narcissistic personality disorder: including grandiosity, self-focused lack of empathy for others, exploitativeness and independence.
Obsessive–compulsive personality disorder: including perfectionism, excessive devotion to work, rigidity, stubbornness and dictatorial tendencies.According to leadership academic Manfred F.R. Kets de Vries, it seems almost inevitable that some personality disorders will be present in a senior management team.
In children
Early stages and preliminary forms of personality disorders need a multi-dimensional and early treatment approach. Personality development disorder is considered to be a childhood risk factor or early stage of a later personality disorder in adulthood.
In addition, in Robert F. Kruegers review of their research indicates that some children and adolescents do experience clinically significant syndromes that resemble adult personality disorders, and that these syndromes have meaningful correlates and are consequential. Much of this research has been framed by the adult personality disorder constructs from Axis II of the Diagnostic and Statistical Manual. Hence, they are less likely to encounter the first risk they described at the outset of their review: clinicians and researchers are not simply avoiding use of the PD construct in youth. However, they may encounter the second risk they described: under-appreciation of the developmental context in which these syndromes occur. That is, although PD constructs show continuity over time, they are probabilistic predictors; not all youths who exhibit PD symptomatology become adult PD cases.
Versus normal personality
The issue of the relationship between normal personality and personality disorders is one of the important issues in personality and clinical psychology. The personality disorders classification (DSM-5 and ICD-10) follows a categorical approach that views personality disorders as discrete entities that are distinct from each other and from normal personality. In contrast, the dimensional approach is an alternative approach that personality disorders represent maladaptive extensions of the same traits that describe normal personality.
Thomas Widiger and his collaborators have contributed to this debate significantly. He discussed the constraints of the categorical approach and argued for the dimensional approach to the personality disorders. Specifically, he proposed the Five Factor Model of personality as an alternative to the classification of personality disorders. For example, this view specifies that Borderline Personality Disorder can be understood as a combination of emotional lability (i.e., high neuroticism), impulsivity (i.e., low conscientiousness), and hostility (i.e., low agreeableness). Many studies across cultures have explored the relationship between personality disorders and the Five Factor Model. This research has demonstrated that personality disorders largely correlate in expected ways with measures of the Five Factor Model and has set the stage for including the Five Factor Model within DSM-5.In clinical practice, individuals are generally diagnosed by an interview with a psychiatrist based on a mental status examination, which may take into account observations by relatives and others. One tool of diagnosing personality disorders is a process involving interviews with scoring systems. The patient is asked to answer questions, and depending on their answers, the trained interviewer tries to code what their responses were. This process is fairly time-consuming.
Abbreviations used: PPD – Paranoid Personality Disorder, SzPD – Schizoid Personality Disorder, StPD – Schizotypal Personality Disorder, ASPD – Antisocial Personality Disorder, BPD – Borderline Personality Disorder, HPD – Histrionic Personality Disorder, NPD – Narcissistic Personality Disorder, AvPD – Avoidant Personality Disorder, DPD – Dependent Personality Disorder, OCPD – Obsessive–Compulsive Personality Disorder, PAPD – Passive–Aggressive Personality Disorder, DpPD – Depressive Personality Disorder, SDPD – Self-Defeating Personality Disorder, SaPD – Sadistic Personality Disorder, and n/a – not available.
As of 2002, there were over fifty published studies relating the five factor model (FFM) to personality disorders. Since that time, quite a number of additional studies have expanded on this research base and provided further empirical support for understanding the DSM personality disorders in terms of the FFM domains. In her seminal review of the personality disorder literature published in 2007, Lee Anna Clark asserted that "the five-factor model of personality is widely accepted as representing the higher-order structure of both normal and abnormal personality traits".The five factor model has been shown to significantly predict all 10 personality disorder symptoms and outperform the Minnesota Multiphasic Personality Inventory (MMPI) in the prediction of borderline, avoidant, and dependent personality disorder symptoms.Research results examining the relationships between the FFM and each of the ten DSM personality disorder diagnostic categories are widely available. For example, in a study published in 2003 titled "The five-factor model and personality disorder empirical literature: A meta-analytic review", the authors analyzed data from 15 other studies to determine how personality disorders are different and similar, respectively, with regard to underlying personality traits. In terms of how personality disorders differ, the results showed that each disorder displays a FFM profile that is meaningful and predictable given its unique diagnostic criteria. With regard to their similarities, the findings revealed that the most prominent and consistent personality dimensions underlying a large number of the personality disorders are positive associations with neuroticism and negative associations with agreeableness.
Openness to experience
At least three aspects of openness to experience are relevant to understanding personality disorders: cognitive distortions, lack of insight (means the ability to recognize ones own mental illness here) and impulsivity. Problems related to high openness that can cause problems with social or professional functioning are excessive fantasising, peculiar thinking, diffuse identity, unstable goals and nonconformity with the demands of the society.High openness is characteristic to schizotypal personality disorder (odd and fragmented thinking), narcissistic personality disorder (excessive self-valuation) and paranoid personality disorder (sensitivity to external hostility). Lack of insight (shows low openness) is characteristic to all personality disorders and could help explain the persistence of maladaptive behavioral patterns.The problems associated with low openness are difficulties adapting to change, low tolerance for different worldviews or lifestyles, emotional flattening, alexithymia and a narrow range of interests. Rigidity is the most obvious aspect of (low) openness among personality disorders and that shows lack of knowledge of ones emotional experiences. It is most characteristic of obsessive–compulsive personality disorder; the opposite of it known as impulsivity (here: an aspect of openness that shows a tendency to behave unusually or autistically) is characteristic of schizotypal and borderline personality disorders.
Causes
Currently, there are no definitive proven causes for personality disorders. However, there are numerous possible causes and known risk factors supported by scientific research that vary depending on the disorder, the individual, and the circumstance. Overall, findings show that genetic disposition and life experiences, such as trauma and abuse, play a key role in the development of personality disorders.
Child abuse
Child abuse and neglect consistently show up as risk factors to the development of personality disorders in adulthood. A study looked at retrospective reports of abuse of participants that had demonstrated psychopathology throughout their life and were later found to have past experience with abuse. In a study of 793 mothers and children, researchers asked mothers if they had screamed at their children, and told them that they did not love them or threatened to send them away. Children who had experienced such verbal abuse were three times as likely as other children (who did not experience such verbal abuse) to have borderline, narcissistic, obsessive–compulsive or paranoid personality disorders in adulthood. The sexually abused group demonstrated the most consistently elevated patterns of psychopathology. Officially verified physical abuse showed an extremely strong correlation with the development of antisocial and impulsive behavior. On the other hand, cases of abuse of the neglectful type that created childhood pathology were found to be subject to partial remission in adulthood.
Socioeconomic status
Socioeconomic status has also been looked at as a potential cause for personality disorders. There is a strong association with low parental/neighborhood socioeconomic status and personality disorder symptoms. In a 2015 publication from Bonn, Germany, which compared parental socioeconomic status and a childs personality, it was seen that children who were from higher socioeconomic backgrounds were more altruistic, less risk seeking, and had overall higher IQs. These traits correlate with a low risk of developing personality disorders later on in life. In a study looking at female children who were detained for disciplinary actions found that psychological problems were most negatively associated with socioeconomic problems. Furthermore, social disorganization was found to be inversely correlated with personality disorder symptoms.
Parenting
Evidence shows personality disorders may begin with parental personality issues. These cause the child to have their own difficulties in adulthood, such as difficulties reaching higher education, obtaining jobs, and securing dependable relationships. By either genetic or modeling mechanisms, children can pick up these traits. Additionally, poor parenting appears to have symptom elevating effects on personality disorders. More specifically, lack of maternal bonding has also been correlated with |
Personality disorder | personality disorders. In a study comparing 100 healthy individuals to 100 borderline personality disorder patients, analysis showed that BPD patients were significantly more likely not to have been breastfed as a baby (42.4% in BPD vs. 9.2% in healthy controls). These researchers suggested this act may be essential in fostering maternal relationships. Additionally, findings suggest personality disorders show a negative correlation with two attachment variables: maternal availability and dependability. When left unfostered, other attachment and interpersonal problems occur later in life ultimately leading to development of personality disorders.
Genetics
Currently, genetic research for the understanding of the development of personality disorders is severely lacking. However, there are a few possible risk factors currently in discovery. Researchers are currently looking into genetic mechanisms for traits such as aggression, fear and anxiety, which are associated with diagnosed individuals. More research is being conducted into disorder specific mechanisms.
Neurobiological correlates - hippocampus, amygdala
Research shows that several brain regions are altered in personality disorders, particularly: hippocampus up to 18% smaller, a smaller amygdala, malfunctions in the striatum-nucleus accumbens and the cingulum neural pathways connecting them and taking care of the feedback loops on what to do with all the incoming information from the multiple senses; so what comes out is anti-social - not according to what is the social norm, socially acceptable and appropriate.
Management
Specific approaches
There are many different forms (modalities) of treatment used for personality disorders:
Individual psychotherapy has been a mainstay of treatment. There are long-term and short-term (brief) forms.
Family therapy, including couples therapy.
Group therapy for personality dysfunction is probably the second most used.
Psychological-education may be used as an addition.
Self-help groups may provide resources for personality disorders.
Psychiatric medications for treating symptoms of personality dysfunction or co-occurring conditions.
Milieu therapy, a kind of group-based residential approach, has a history of use in treating personality disorders, including therapeutic communities.
The practice of mindfulness that includes developing the ability to be nonjudgmentally aware of unpleasant emotions appears to be a promising clinical tool for managing different types of personality disorders.There are different specific theories or schools of therapy within many of these modalities. They may, for example, emphasize psychodynamic techniques, or cognitive or behavioral techniques. In clinical practice, many therapists use an eclectic approach, taking elements of different schools as and when they seem to fit to an individual client. There is also often a focus on common themes that seem to be beneficial regardless of techniques, including attributes of the therapist (e.g. trustworthiness, competence, caring), processes afforded to the client (e.g. ability to express and confide difficulties and emotions), and the match between the two (e.g. aiming for mutual respect, trust and boundaries).
Challenges
The management and treatment of personality disorders can be a challenging and controversial area, for by definition the difficulties have been enduring and affect multiple areas of functioning. This often involves interpersonal issues, and there can be difficulties in seeking and obtaining help from organizations in the first place, as well as with establishing and maintaining a specific therapeutic relationship. On the one hand, an individual may not consider themselves to have a mental health problem, while on the other, community mental health services may view individuals with personality disorders as too complex or difficult, and may directly or indirectly exclude individuals with such diagnoses or associated behaviors. The disruptiveness that people with personality disorders can create in an organisation makes these, arguably, the most challenging conditions to manage.
Apart from all these issues, an individual may not consider their personality to be disordered or the cause of problems. This perspective may be caused by the patients ignorance or lack of insight into their own condition, an ego-syntonic perception of the problems with their personality that prevents them from experiencing it as being in conflict with their goals and self-image, or by the simple fact that there is no distinct or objective boundary between normal and abnormal personalities. There is substantial social stigma and discrimination related to the diagnosis.
The term personality disorder encompasses a wide range of issues, each with a different level of severity or impairment; thus, personality disorders can require fundamentally different approaches and understandings. To illustrate the scope of the matter, consider that while some disorders or individuals are characterized by continual social withdrawal and the shunning of relationships, others may cause fluctuations in forwardness. The extremes are worse still: at one extreme lie self-harm and self-neglect, while at another extreme some individuals may commit violence and crime. There can be other factors such as problematic substance use or dependency or behavioral addictions.
Therapists in this area can become disheartened by lack of initial progress, or by apparent progress that then leads to setbacks. Clients may be perceived as negative, rejecting, demanding, aggressive or manipulative. This has been looked at in terms of both therapist and client; in terms of social skills, coping efforts, defense mechanisms, or deliberate strategies; and in terms of moral judgments or the need to consider underlying motivations for specific behaviors or conflicts. The vulnerabilities of a client, and indeed a therapist, may become lost behind actual or apparent strength and resilience. It is commonly stated that there is always a need to maintain appropriate professional personal boundaries, while allowing for emotional expression and therapeutic relationships. However, there can be difficulty acknowledging the different worlds and views that both the client and therapist may live with. A therapist may assume that the kinds of relationships and ways of interacting that make them feel safe and comfortable have the same effect on clients. As an example of one extreme, people who may have been exposed to hostility, deceptiveness, rejection, aggression or abuse in their lives, may in some cases be made confused, intimidated or suspicious by presentations of warmth, intimacy or positivity. On the other hand, reassurance, openness and clear communication are usually helpful and needed. It can take several months of sessions, and perhaps several stops and starts, to begin to develop a trusting relationship that can meaningfully address a clients issues.
Epidemiology
The prevalence of personality disorder in the general community was largely unknown until surveys starting from the 1990s. In 2008 the median rate of diagnosable PD was estimated at 10.6%, based on six major studies across three nations. This rate of around one in ten, especially as associated with high use of cocaine, is described as a major public health concern requiring attention by researchers and clinicians.The prevalence of individual personality disorders ranges from about 2% to 8% for the more common varieties, such as obsessive-compulsive, schizotypal, antisocial, borderline, and histrionic, to 0.5–1% for the least common, such as narcissistic and avoidant.A screening survey across 13 countries by the World Health Organization using DSM-IV criteria, reported in 2009 a prevalence estimate of around 6% for personality disorders. The rate sometimes varied with demographic and socioeconomic factors, and functional impairment was partly explained by co-occurring mental disorders. In the US, screening data from the National Comorbidity Survey Replication between 2001 and 2003, combined with interviews of a subset of respondents, indicated a population prevalence of around 9% for personality disorders in total. Functional disability associated with the diagnoses appeared to be largely due to co-occurring mental disorders (Axis I in the DSM). This statistic has been supported by other studies in the US, with overall global prevalence statistics ranging from 9% to 11%.A UK national epidemiological study (based on DSM-IV screening criteria), reclassified into levels of severity rather than just diagnosis, reported in 2010 that the majority of people show some personality difficulties in one way or another (short of threshold for diagnosis), while the prevalence of the most complex and severe cases (including meeting criteria for multiple diagnoses in different clusters) was estimated at 1.3%. Even low levels of personality symptoms were associated with functional problems, but the most severely in need of services was a much smaller group.Personality disorders (especially Cluster A) are found more commonly among homeless people.There are some sex differences in the frequency of personality disorders which are shown in the table below.: 206 The known prevalence of some personality disorders, especially borderline PD and antisocial PD are affected by diagnostic bias. This is due to many factors including disproportionately high research towards borderline PD and antisocial PD, alongside social and gender stereotypes, and the relationship between diagnosis rates and prevalence rates. Since the removal of depressive PD, self-defeating PD, sadistic PD and passive-aggressive PD from the DSM-5, studies analysing their prevalence and demographics have been limited.
History
Diagnostic and Statistical Manual history
Before the 20th century
Personality disorder is a term with a distinctly modern meaning, owing in part to its clinical usage and the institutional character of modern psychiatry. The currently accepted meaning must be understood in the context of historical changing classification systems such as DSM-IV and its predecessors. Although highly anachronistic, and ignoring radical differences in the character of subjectivity and social relations, some have suggested similarities to other concepts going back to at least the ancient Greeks.: 35 For example, the Greek philosopher Theophrastus described 29 character types that he saw as deviations from the norm, and similar views have been found in Asian, Arabic and Celtic cultures. A long-standing influence in the Western world was Galens concept of personality types, which he linked to the four humours proposed by Hippocrates.
Such views lasted into the eighteenth century, when experiments began to question the supposed biologically based humours and temperaments. Psychological concepts of character and self became widespread. In the nineteenth century, personality referred to a persons conscious awareness of their behavior, a disorder of which could be linked to altered states such as dissociation. This sense of the term has been compared to the use of the term multiple personality disorder in the first versions of the DSM.Physicians in the early nineteenth century started to diagnose forms of insanity involving disturbed emotions and behaviors but seemingly without significant intellectual impairment or delusions or hallucinations. Philippe Pinel referred to this as manie sans délire – mania without delusions – and described a number of cases mainly involving excessive or inexplicable anger or rage. James Cowles Prichard advanced a similar concept he called moral insanity, which would be used to diagnose patients for some decades. Moral in this sense referred to affect (emotion or mood) rather than ethics, but it was arguably based in part on religious, social and moral beliefs, with a pessimism about medical intervention so social control should take precedence. These categories were much different and broader than later definitions of personality disorder, while also being developed by some into a more specific meaning of moral degeneracy akin to later ideas about psychopaths. Separately, Richard von Krafft-Ebing popularized the terms sadism and masochism, as well as homosexuality, as psychiatric issues.
The German psychiatrist Koch sought to make the moral insanity concept more scientific, and in 1891 suggested the phrase psychopathic inferiority, theorized to be a congenital disorder. This referred to continual and rigid patterns of misconduct or dysfunction in the absence of apparent "mental retardation" or illness, supposedly without a moral judgment. Described as deeply rooted in his Christian faith, his work established the concept of personality disorder as used today.
20th century
In the early 20th century, another German psychiatrist, Emil Kraepelin, included a chapter on psychopathic inferiority in his influential work on clinical psychiatry for students and physicians. He suggested six types – excitable, unstable, eccentric, liar, swindler and quarrelsome. The categories were essentially defined by the most disordered criminal offenders observed, distinguished between criminals by impulse, professional criminals, and morbid vagabonds who wandered through life. Kraepelin also described three paranoid (meaning then delusional) disorders, resembling later concepts of schizophrenia, delusional disorder and paranoid personality disorder. A diagnostic term for the latter concept would be included in the DSM from 1952, and from 1980 the DSM would also include schizoid, schizotypal; interpretations of earlier (1921) theories of Ernst Kretschmer led to a distinction between these and another type later included in the DSM, avoidant personality disorder.
In 1933 Russian psychiatrist Pyotr Borisovich Gannushkin published his book Manifestations of Psychopathies: Statics, Dynamics, Systematic Aspects, which was one of the first attempts to develop a detailed typology of psychopathies. Regarding maladaptation, ubiquity, and stability as the three main symptoms of behavioral pathology, he distinguished nine clusters of psychopaths: cycloids (including constitutionally depressive, constitutionally excitable, cyclothymics, and emotionally labile), asthenics (including psychasthenics), schizoids (including dreamers), paranoiacs (including fanatics), epileptoids, hysterical personalities (including pathological liars), unstable psychopaths, antisocial psychopaths, and constitutionally stupid. Some elements of Gannushkins typology were later incorporated into the theory developed by a Russian adolescent psychiatrist, Andrey Yevgenyevich Lichko, who was also interested in psychopathies along with their milder forms, the so-called accentuations of character.In 1939, psychiatrist David Henderson published a theory of psychopathic states that contributed to popularly linking the term to anti-social behavior. Hervey M. Cleckleys 1941 text, The Mask of Sanity, based on his personal categorization of similarities he noted in some prisoners, marked the start of the modern clinical conception of psychopathy and its popularist usage.Towards the mid 20th century, psychoanalytic theories were coming to the fore based on work from the turn of the century being popularized by Sigmund Freud and others. This included the concept of character disorders, which were seen as enduring problems linked not to specific symptoms but to pervasive internal conflicts or derailments of normal childhood development. These were often understood as weaknesses of character or willful deviance, and were distinguished from neurosis or psychosis. The term borderline stems from a belief some individuals were functioning on the edge of those two categories, and a number of the other personality disorder categories were also heavily influenced by this approach, including dependent, obsessive–compulsive and histrionic, the latter starting off as a conversion symptom of hysteria particularly associated with women, then a hysterical personality, then renamed histrionic personality disorder in later versions of the DSM. A passive aggressive style was defined clinically by Colonel William Menninger during World War II in the context of mens reactions to military compliance, which would later be referenced as a personality disorder in the DSM. Otto Kernberg was influential with regard to the concepts of borderline and narcissistic personalities later incorporated in 1980 as disorders into the DSM.
Meanwhile, a more general personality psychology had been developing in academia and to some extent clinically. Gordon Allport published theories of personality traits from the 1920s—and Henry Murray advanced a theory called personology, which influenced a later key advocate of personality disorders, Theodore Millon. Tests were developing or being applied for personality evaluation, including projective tests such as the Rorschach test, as well as questionnaires such as the Minnesota Multiphasic Personality Inventory. Around mid-century, Hans Eysenck was analysing traits and personality types, and psychiatrist Kurt Schneider was popularising a clinical use in place of the previously more usual terms character, temperament or constitution.
American psychiatrists officially recognized concepts of enduring personality disturbances in the first Diagnostic and Statistical Manual of Mental Disorders in the 1950s, which relied heavily on psychoanalytic concepts. Somewhat more neutral language was employed in the DSM-II in 1968, though the terms and descriptions had only a slight resemblance to current definitions. The DSM-III published in 1980 made some major changes, notably putting all personality disorders onto a second separate axis along with "mental retardation", intended to signify more enduring patterns, distinct from what were considered axis one mental disorders. Inadequate and asthenic personality disorder categories were deleted, and others were expanded into more types, or changed from being personality disorders to regular disorders. Sociopathic personality disorder, which had been the term for psychopathy, was renamed Antisocial Personality Disorder. Most categories were given more specific operationalized definitions, with standard criteria psychiatrists could agree on to conduct research and diagnose patients. In the DSM-III revision, self-defeating personality disorder and sadistic personality disorder were included as provisional diagnoses requiring further study. They were dropped in the DSM-IV, though a proposed depressive personality disorder was added; in addition, the official diagnosis of passive–aggressive personality disorder was dropped, tentatively renamed negativistic personality disorder.International differences have been noted in how attitudes have developed towards the diagnosis of personality disorder. Kurt Schneider argued they were abnormal varieties of psychic life and therefore not necessarily the domain of psychiatry, a view said to still have influence in Germany today. British psychiatrists have also been reluctant to address such disorders or consider them on par with other mental disorders, which has been attributed partly to resource pressures within the National Health Service, as well as to negative medical attitudes towards behaviors associated with personality disorders. In the US, the prevailing healthcare system and psychanalytic tradition has been said to provide a rationale for private therapists to diagnose some personality disorders more broadly and provide ongoing treatment for them.
See also
Depressive personality disorder
Borderline personality disorder
References
Further reading
Marshall, W. & Serin, R. (1997) Personality Disorders. In Sm.M. Turner & R. Hersen (Eds.) Adult Psychopathology and Diagnosis. New York: Wiley. 508–41
Murphy, N. & McVey, D. (2010) Treating Severe Personality Disorder: Creating Robust Services for Clients with Complex Mental Health Needs. London: Routledge
Millon, Theodore (and Roger D. Davis, contributor) – Disorders of Personality: DSM IV and Beyond – 2nd ed. – New York, John Wiley and Sons, 1995 ISBN 0-471-01186-X
Yudofsky, Stuart C. (2005). Fatal Flaws: Navigating Destructive Relationships With People With Disorders of Personality and Character (1st ed.). Washington, DC. ISBN 978-1-58562-214-6.
External links
Personality Disorders Foundation
National Mental Health Association personality disorder fact sheet
Personality Disorders information leaflet from The Royal College of Psychiatrists |
Phobia | A phobia is an anxiety disorder defined by a persistent and excessive fear of an object or situation. Phobias typically result in a rapid onset of fear and are usually present for more than six months. Those affected go to great lengths to avoid the situation or object, to a degree greater than the actual danger posed. If the object or situation cannot be avoided, they experience significant distress. Other symptoms can include fainting, which may occur in blood or injury phobia, and panic attacks, often found in agoraphobia. Around 75% of those with phobias have multiple phobias.Phobias can be divided into specific phobias, social anxiety disorder, and agoraphobia. Specific phobias are further divided to include certain animals, natural environment, blood or injury, and particular situations. The most common are fear of spiders, fear of snakes, and fear of heights. Specific phobias may be caused by a negative experience with the object or situation in early childhood. Social phobia is when a person fears a situation due to worries about others judging them. Agoraphobia is a fear of a situation due to perceived difficulty or inability to escape.It is recommended that specific phobias be treated with exposure therapy, in which the person is introduced to the situation or object in question until the fear resolves. Medications are not helpful for specific phobias. Social phobia and agoraphobia may be treated with counseling, medications, or a combination of both. Medications used include antidepressants, benzodiazepines, or beta-blockers.Specific phobias affect about 6–8% of people in the Western world and 2–4% in Asia, Africa, and Latin America in a given year. Social phobia affects about 7% of people in the United States and 0.5–2.5% of people in the rest of the world. Agoraphobia affects about 1.7% of people. Women are affected by phobias about twice as often as men. The typical onset of a phobia is around 10–17, and rates are lower with increasing age. Those with phobias are more likely to attempt suicide.
Classification
Fear is an emotional response to a current perceived danger. This differs from anxiety which is a response in preparation of a future threat. Fear and anxiety often can overlap but this distinction can help identify subtle differences between disorders, as well as differentiate between a response that would be expected given a persons developmental stage and culture.
ICD-11
The International Classification of Diseases (11th version: ICD-11) is a globally used diagnostic tool for epidemiology, health management and clinical purposes maintained by the World Health Organization (WHO). The ICD classifies phobic disorders under the category of mental, behavioural or neurodevelopmental disorders. The ICD-10 differentiates between Phobic anxiety disorders, such as Agoraphobia, and Other anxiety disorders, such as Generalized anxiety disorder. The ICD-11 merges both groups together as Anxiety or fear-related disorders.
DSM-V
Most phobias are classified into three categories. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), such phobias are considered subtypes of anxiety disorder. The categories are:
Specific phobias: Fear of particular objects or situations that results in anxiety and avoidance. May lead to panic attacks if exposed to feared stimulus or in anticipation of encounter. A specific phobia may be further subdivided into five categories: animal, natural environment, situational, blood-injection-injury, and other.
Agoraphobia: a generalized fear of leaving home or a small familiar safe area and of possible panic attacks that might follow. Various specific phobias may also cause it, such as fear of open spaces, social embarrassment (social agoraphobia), fear of contamination (fear of germs, possibly complicated by obsessive–compulsive disorder) or PTSD (post-traumatic stress disorder) related to a trauma that occurred outdoors.
Social anxiety disorder (SAD), also known as social phobia, is when the situation is feared out of a worrying about others judging them. Performance only is a subtype of social anxiety disorder Phobias vary in severity among individuals. Some individuals can avoid the subject and experience relatively mild anxiety over that fear. Others experience full-fledged panic attacks with all the associated impairing symptoms. Most individuals understand that their fear is irrational but cannot override their panic response. These individuals often report dizziness, loss of bladder or bowel control, tachypnea, feelings of pain, and shortness of breath.
Causes
There are multiple theories about how phobias develop and likely occur due to a combination of environmental and genetic factors. The degree to whether environment or genetic influences have a more significant role varies by condition, with social anxiety disorder and agoraphobia having around a 50% heritability rate.
Environmental
Rachman proposed three pathways for the development of phobias: direct or classical conditioning (exposure to phobic stimulus), vicarious acquisition (seeing others experience phobic stimulus), and informational/instructional acquisition (learning about phobic stimulus from others).
Classical conditioning
Much of the progress in understanding the acquisition of fear responses in phobias can be attributed to classical conditioning (Pavlovian model). When an aversive stimulus and a neutral one are paired together, for instance, when an electric shock is given in a specific room, the subject can start to fear not only the shock but the room as well. In behavioral terms, the room is a conditioned stimulus (CS). When paired with an aversive unconditioned stimulus (UCS) (the shock), it creates a conditioned response (CR) (fear for the room) (CS+UCS=CR). For example, in case of the fear of heights (acrophobia), the CS is heights. Such as a balcony on the top floors of a high rise building. The UCS can originate from an aversive or traumatizing event in the persons life, such as almost falling from a great height. The original fear of nearly falling is associated with being high, leading to a fear of heights. In other words, the CS (heights) associated with the aversive UCS (almost falling) leads to the CR (fear).
Though historically influential in the theory of fear acquisition, this direct conditioning model is not the only proposed way to acquire a phobia. This theory in fact has limitations as not everyone that has experienced a traumatic event develops a phobia and vice versa.
Vicarious conditioning
Vicarious fear acquisition is learning to fear something, not by a subjects own experience of fear, but by watching others, oftentimes a parent (observational learning). For instance, when a child sees a parent reacting fearfully to an animal, the child can also become afraid of the animal. Through observational learning, humans can learn to fear potentially dangerous objects—a reaction observed in other primates. A study on non-human primates, showed that the primates learned to fear snakes at a fast rate after watching parents fearful reactions. An increase in fearful behaviours was observed as the non-human primates observed their parents fearful reactions. Although observational learning has proven effective in creating reactions of fear and phobias, it has also been shown that by physically experiencing an event, increases the chance of fearful and phobic behaviours. In some cases, physically experiencing an event may increase the fear and phobia more than observing a fearful reaction of another human or non-human primate.
Informational/Instructional acquisition
Informational/instructional fear acquisition is learning to fear something by getting information. For instance, fearing electrical wire after hearing that touching it causes an electric shock.A conditioned fear response to an object or situation is not always a phobia. There must also be symptoms of impairment and avoidance. Impairment is defined as an inability to complete routine tasks, whether occupational, academic, or social. For example, an occupational impairment can result from acrophobia, from not taking a job solely because of its location on the top floor of a building, or socially not participating in an event at a theme park. The avoidance aspect is defined as behaviour that results in the omission of an aversive event that would otherwise occur, intending to prevent anxiety.
Genetic
With the completion of the Human Genome Project in 2003, much research has been completed looking at specific genes that may cause or contribute to medical conditions. Candidate genes were the focus of most of these studies until the past decade, when the cost and ability to perform genome-wide analyses became more available. The GLRB gene was identified as a possible target for agoraphobia. An area still in development is reviewing epigenetic components or the interaction of the environment on genes through methylation. A number of genes are being examined through this epigenetic lens which may be linked with social anxiety disorder, including MAOA, CRHR1, and OXTR. Each phobia related disorder has some degree of genetic susceptibility. Those with specific phobias are more likely to have first degree relatives with the same specific phobia. Similarly, social anxiety disorder is found two to six times more frequently in those with first degree relatives that have it versus those that do not. Agoraphobia is believed to have the strongest genetic association.
Mechanism
Limbic system
Beneath the lateral fissure in the cerebral cortex, the insula, or insular cortex, of the brain has been identified as part of the limbic system, along with the cingulated gyrus, hippocampus, corpus callosum, and other nearby cortices. This system has been found to play a role in emotion processing, and the insula, in particular, may contribute to maintaining autonomic functions. Studies by Critchley et al. indicate the insula as being involved in the experience of emotion by detecting and interpreting threatening stimuli. Similar studies monitoring insula activity have shown a correlation between increased insular activation and anxiety.In the frontal lobes, other cortices involved with phobia and fear are the anterior cingulate cortex and the medial prefrontal cortex. In the processing of emotional stimuli, studies on phobic reactions to facial expressions have indicated that these areas are involved in the processing and responding to negative stimuli. The ventromedial prefrontal cortex has been said to influence the amygdala by monitoring its reaction to emotional stimuli or even fearful memories. Most specifically, the medial prefrontal cortex is active during the extinction of fear and is responsible for long-term extinction. Stimulation of this area decreases conditioned fear responses, so its role may be in inhibiting the amygdala and its reaction to fearful stimuli.The hippocampus is a horseshoe-shaped structure that plays an essential part in the brains limbic system. This is because it forms memories and connects them with emotions and the senses. When dealing with fear, the hippocampus receives impulses from the amygdala that allow it to connect the fear with a certain sense, such as a smell or sound.
Amygdala
The amygdala is an almond-shaped mass of nuclei located deep in the brains medial temporal lobe. It processes the events associated with fear and is linked to social phobia and other anxiety disorders. The amygdalas ability to respond to fearful stimuli occurs through fear conditioning. Like classical conditioning, the amygdala learns to associate a conditioned stimulus with a negative or avoidant stimulus, creating a conditioned fear response often seen in phobic individuals. The amygdala is responsible for recognizing certain stimuli or cues as dangerous and plays a role in the storage of threatening stimuli to memory. The basolateral nuclei (or basolateral amygdala) and the hippocampus interact with the amygdala in-memory storage. This connection suggests why memories are often remembered more vividly if they have emotional significance.In addition to memory, the amygdala also triggers the secretion of hormones that affect fear and aggression. When the fear or aggression response is initiated, the amygdala releases hormones into the body to put the human body into an "alert" state, which prepares the individual to move, run, fight, etc. This defensive "alert" state and response are known as the fight-or-flight response.However, inside the brain, this stress response can be observed in the hypothalamic-pituitary-adrenal axis (HPA). This circuit incorporates the process of receiving stimuli, interpreting them, and releasing certain hormones into the bloodstream. The parvocellular neurosecretory neurons of the hypothalamus release corticotropin-releasing hormone (CRH), which is sent to the anterior pituitary. Here the pituitary releases adrenocorticotropic hormone (ACTH), which ultimately stimulates the release of cortisol. In relation to anxiety, the amygdala activates this circuit, while the hippocampus is responsible for suppressing it. Glucocorticoid receptors in the hippocampus monitor the amount of cortisol in the system and through negative feedback can tell the hypothalamus to stop releasing CRH.Studies on mice engineered to have high concentrations of CRH showed higher levels of anxiety, while those engineered to have no or low amounts of CRH receptors were less anxious. In people with phobias, therefore, high amounts of cortisol may be present, or there may be low levels of glucocorticoid receptors or even serotonin (5-HT).
Disruption by damage
For the areas in the brain involved in emotion—most specifically fear— the processing and response to emotional stimuli can be altered when one of these regions is damaged. Damage to the cortical areas involved in the limbic system, such as the cingulate cortex or frontal lobes, has resulted in extreme emotion changes. Other types of damage include Klüver–Bucy syndrome and Urbach–Wiethe disease. In Klüver–Bucy syndrome, a temporal lobectomy, or removal of the temporal lobes, results in changes involving fear and aggression. Specifically, the removal of these lobes results in decreased fear, confirming its role in fear recognition and response. Damage to both side (Bilateral damage) of the medial temporal lobes is known as Urbach–Wiethe disease. It presents with similar symptoms of decreased fear and aggression but with the addition of the inability to recognize emotional expressions, especially angry or fearful faces.The amygdalas role in learned fear includes interactions with other brain regions in the neural circuit of fear. While damage in the amygdala can inhibit its ability to recognize fearful stimuli, other areas such as the ventromedial prefrontal cortex and the basolateral nuclei of the amygdala can affect the regions ability to not only become conditioned to fearful stimuli but to extinguish them eventually. Through receiving stimulus info, the basolateral nuclei undergo synaptic changes that allow the amygdala to develop a conditioned response to fearful stimuli. Damage to this area, therefore, have been shown to disrupt the acquisition of learned responses to fear. Likewise, damage in the ventromedial prefrontal cortex (the area responsible for monitoring the amygdala) has been shown to slow down the speed of extinguishing a learned fear response and how effective the extinction is. This suggests there is a pathway or circuit among the amygdala and nearby cortical areas that process emotional stimuli and influence emotional expression, all of which can be disrupted when damage occurs.
Diagnosis
It is recommended that the terms distress and impairment take into account the context of the persons environment during diagnosis. The DSM-IV-TR states that if a feared stimulus, whether it be an object or a situation, is absent entirely in an environment, a diagnosis cannot be made. An example of this situation would be an individual who has a fear of mice but lives in an area without mice. Even though the concept of mice causes marked distress and impairment within the individual, because the individual does not usually encounter mice, no actual distress or impairment is ever experienced. It is recommended that proximity to, and ability to escape from, the stimulus also be considered. As the phobic person approaches a feared stimulus, anxiety levels increase, and the degree to which the person perceives they might escape from the stimulus affects the intensity of fear in instances such as riding an elevator (e.g. anxiety increases at the midway point between floors and decreases when the floor is reached and the doors open). The DSM-V has been updated to reflect that an individual may have changed their daily activities around the feared stimulus in such a way that they may avoid it altogether. The person may still meet criteria for the diagnosis if they continue to avoid or refuse to participate in activities they would involve possible exposure to the phobic stimulus.
Specific phobias
A specific phobia is a marked and persistent fear of an object or situation. Specific phobias may also include fear of losing control, panicking, and fainting from an encounter with the phobia. Specific phobias are defined concerning objects or situations, whereas social phobias emphasize social fear and the evaluations that might accompany them.
The DSM breaks specific phobias into five subtypes: animal, natural environment, blood-injection-injury, situational and other. In children, blood-injection-injury phobia, animal phobias, and natural environment phobias usually develop between the ages of 7 and 9 reflective of normal development. Additionally, specific phobias are most prevalent in children between the ages 10 and 13. Situational phobias are typically found in older children and adults.
Treatments
There are various methods used to treat phobias. These methods include systematic desensitization, progressive relaxation, virtual reality, modeling, medication, and hypnotherapy. Over the past several decades, psychologists and other researchers have developed effective behavioral, pharmacological, and technological interventions for the treatment of phobia.
Therapy
Cognitive behavioral therapy (CBT) can be beneficial by allowing the person to challenge dysfunctional thoughts or beliefs by being mindful of their feelings to recognize that their fear is irrational. CBT may occur in a group setting. Gradual desensitization treatment and CBT are often successful, provided the person is willing to endure some discomfort. In one clinical trial, 90% of people no longer had a phobic reaction after successful CBT treatment.Evidence supports that eye movement desensitization and reprocessing (EMDR) is effective in treating some phobias. Its effectiveness in treating complex or trauma-related phobias has not been empirically established. Primarily used to treat post-traumatic stress disorder, EMDR has been demonstrated to ease phobia symptoms following a specific trauma, such as a fear of dogs following a dog bite.
Systematic desensitization
Systematic desensitization is a process in which people seeking help slowly become accustomed to their phobia, and ultimately overcome it. Traditional systematic desensitization involves a person being exposed to the object they are afraid of over time so that the fear and discomfort do not become overwhelming. This controlled exposure to the anxiety-provoking stimulus is key to the effectiveness of exposure therapy in the treatment of specific phobias. It has been shown that humor is an excellent alternative when traditional systematic desensitization is ineffective. Humor systematic desensitization involves a series of treatment activities that elicit humor with the feared object. Previously learned progressive muscle relaxation procedures can be used as the activities become more difficult. Progressive muscle relaxation helps people relax before and during exposure to the feared stimulus.
Virtual reality therapy is another technique that helps phobic people confront a feared object. It uses virtual reality to generate scenes that may not have been possible or ethical in the physical world. It is equally as effective as traditional exposure therapy and offers additional advantages. These include controlling the scenes and having the phobic person endure more exposure than they might handle in reality.
Medications
Medications are a treatment option often utilized in combination with CBT or if CBT was not tolerated or effective. Medications can help regulate apprehension and fear of a particular fearful object or situation. There are various medication options available for both social anxiety disorder and agoraphobia. The use of medications for specific phobias, besides the limited role of benzodiazepines, do not currently have established guidelines due to minimal supporting evidence.
Antidepressants
Antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors (MAOIs) may be helpful in some cases. SSRIs / SNRIs act on serotonin, a neurotransmitter in the brain. Because of serotonins positive impacts mood, an antidepressant may be offered and prescribed as a treatment option. For social anxiety, the SSRIs sertraline, paroxetine, fluvoxamine, and the SNRI venlafaxine have FDA approval. Similar medications may be offered for agoraphobia.
Benzodiazepines
Sedatives such as benzodiazepines (clonazepam, alprazolam) are another therapeutic option, which can help people relax by reducing the amount of anxiety they feel. Benzodiazepines may be useful in the acute treatment of severe symptoms, but the risk-benefit ratio usually goes against their long-term use in phobic disorders. This class of medication has recently been shown as effective if used with negative behaviours such as excessive alcohol use. Despite this positive finding, benzodiazepines are used with caution due to side effects and risk of developing dependence or withdrawal symptoms. In specific phobia for example if the phobic stimulus is one that is not regularly encountered such as flying a short course may be provided.
Beta-blockers
Beta blockers (propranolol) are another therapeutic option, particularly for those with the performance only subtype of social anxiety disorder. They may stop the stimulating effects of adrenaline, such as sweating, increased heart rate, elevated blood pressure, tremors, and the feeling of a pounding heart. By taking beta-blockers before a phobic event, these symptoms are decreased, making the event less frightening. Beta-blockers are not effective for generalized social anxiety disorder.
Hypnotherapy
Hypnotherapy can be used alone and in conjunction with systematic desensitization to treat phobias. Through hypnotherapy, the underlying cause of the phobia may be uncovered. The phobia may be caused by a past event that the person does not remember, a phenomenon known as repression. The mind represses traumatic memories from the conscious mind until the person is ready to deal with them.
Hypnotherapy may also eliminate the conditioned responses that occur during different situations. People are first placed into a hypnotic trance, an extremely relaxed state in which the unconscious can be retrieved. This state makes people more open to suggestion, which helps bring about desired change. Consciously addressing old memories helps individuals understand the event and see it less threateningly.
Prognosis
Outcomes vary widely among the phobic anxiety disorders. There is a possibility that remission occurs without intervention but relapses are common. Response to treatment as well as remission and relapse rates are impacted by the severity of an individuals disorder as well as how long they have been experiencing symptoms. For example, in social anxiety disorder (social phobia) a majority of individuals will experience remission within the first couple of years of symptom onset without specific treatment. On the other hand, in Agoraphobia as few as 10% of individuals are seen to reach complete remission without treatment. A study looking at the 2 year remission rates for anxiety disorders found that those with multiple anxieties were less likely to experience remission.
Specific phobia
The majority of those that develop a specific phobia first experience symptoms in childhood. Often individuals will experience symptoms periodically with periods of remission before complete remission occurs. However, specific phobias that continue into adulthood are likely to experience a more chronic course. Specific phobias in older adults has been linked with a decrease in quality of life. Those with specific phobias are at an increased risk of suicide. Greater impairment is found in those that have multiple phobias. Response to treatment is relatively high but many do not seek treatment due to lack of access, ability to avoid phobia, or unwilling to face feared object for repeated CBT sessions.
Comorbidities
Many of those with a phobia often have more than one phobia. There are also a number of psychological and physiological disorders that tend to occur or coexist at higher rates among this population. As with all anxiety disorders the most common psychiatric condition to occur with a phobia is major depressive disorder. Additionally bipolar disorder, substance dependence disorder, obsessive-compulsive disorder, and post traumatic stress disorder have also been found to occur in those with phobias at higher rates.
Epidemiology
Phobias are a common form of anxiety disorder, and distributions are heterogeneous by age and gender. An American study by the National Institute of Mental Health (NIMH) found that between 8.7 percent and 18.1 percent of Americans have phobias, making it the most common mental illness among women in all age groups and the second most common illness among men older than 25. Between 4 percent and 10 percent of all children experience specific phobias during their lives, and social phobias occur in one percent to three percent of children.A Swedish study found that females have a higher number of cases per year than males (26.5 percent for females and 12.4 percent for males). Among adults, 21.2 percent of women and 10.9 percent of men have a single specific phobia, while multiple phobias occur in 5.4 percent of females and 1.5 percent of males. Women are nearly four times as likely as men to have a fear of animals (12.1 percent in women and 3.3 percent in men) — a higher dimorphic than with all specific or generalized phobias or social phobias. Social phobias are more common in girls than boys, while situational phobia occurs in 17.4 percent of women and 8.5 percent of men.
Society and culture
Terminology
The word phobia comes from the Greek: φόβος (phóbos), meaning "aversion", "fear" or "morbid fear". The regular system for naming specific phobias uses prefixes based on a Greek word for the object of the fear, plus the suffix -phobia. Benjamin Rushs 1786 satyrical text, On the different Species of Phobia, established the terms dictionary sense of specific morbid fears. However, many phobias are irregularly named with Latin prefixes, such as apiphobia instead of melissaphobia (fear of bees) or aviphobia instead of ornithophobia (fear of birds). Creating these terms is something of a word game. Such fears are psychological rather than physiological in origin, and few of these terms are found in medical literature. In ancient Greek mythology Phobos was the twin brother of Deimos (terror).
The word phobia may also refer to conditions other than true phobias. For example, the term hydrophobia is an old name for rabies, since an aversion to water is one of that diseases symptoms. A specific phobia to water is called aquaphobia instead. A hydrophobe is a chemical compound that repels water. Similarly, photophobia usually refers to a physical complaint (aversion to light due to inflamed eyes or excessively dilated pupils), rather than an irrational fear of light.
Non-medical, deterrent and political use
Several terms with the suffix -phobia are used non-clinically to imply irrational fear or hatred. Examples include:
Chemophobia – Irrational fear or hatred of chemistry and synthetic chemicals.
Xenophobia – Irrational fear or hatred of strangers or the unknown, sometimes used to describe nationalistic political beliefs and movements.
Homophobia – Irrational fear or hatred of homosexuality or people who identify or perceived as being lesbian, gay, bisexual or transgender (LGBT).
Islamophobia – Irrational fear or hatred of Islam
Hinduphobia – Irrational fear or hatred of Hinduism or Sanatan Dharma
Biphobia – Irrational fear or hatred of bisexual people
Transphobia – Irrational fear or hatred of transgender peopleUsually, these kinds of "phobias" are described as fear, dislike, disapproval, prejudice, hatred, discrimination, or hostility towards the object of the "phobia". It is a form of hyperbole.
Popular Culture
A number of films and TV shows have portrayed individuals with a variety of phobic disorders.
Movies
Benchwarmers – Howie Goodman (Nick Swardson), portrayed as being agoraphobic and heliophobic.
Television Shows
Monk – Adrian Monk (Tony Shalhoub) is a former homicide detective and a consultant for the San Francisco Police Department. He has an extreme case of OCD and is well known for his various fears and ph |
Phobia | obias, including (but certainly not limited to) heights, snakes, crowds, glaciers, rodeos, wind, and milk.
Shameless (American TV Series) – Sheila Jackson (Joan Cusack) has agoraphobia and mysophobia (fear of germs).
Research directions
Before the development of pharmacotherapy, the treatment of phobias and mental health disorders relied solely on therapy such as CBT. Although therapy can be incredibly effective for many, it does not always achieve the desired effect. Interventional psychiatry is an additional branch in medicine that has expanded treatment options, and further research continues to explore effectiveness and applications. Electroconvulsive Therapy (ECT) and Transcranial Magnetic Stimulation (TMS) are two examples of device-based interventions widely utilized. In terms of use in treating phobias and anxiety disorders as a whole, TMS is being explored as an augmentation option for those who do not have the desired response to other therapeutic options or side effects from medications. A majority of research has been conducted exploring the use of TMS in PTSD and generalized anxiety disorder. A meta‐analysis conducted in 2019 found only two clinical trials for the use of TMS in specific phobias, one of which explored anxiety and avoidance rates in individuals with acrophobia. Although the study found decreased rates in both anxiety and avoidance after two TMS sessions because of the limited number of studies and small sample size, few conclusions can be made. D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist, is an additional investigational approach to augmentation specific phobias that a meta-analysis suggested had better outcomes and less symptom severity when utilized before initiating CBT.
See also
Childhood phobia
List of phobias
References
External links
Media related to Phobias at Wikimedia Commons
Social Anxiety at Curlie |
Gonorrhea | Gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium Neisseria gonorrhoeae. Infection may involve the genitals, mouth, or rectum. Infected men may experience pain or burning with urination, discharge from the penis, or testicular pain. Infected women may experience burning with urination, vaginal discharge, vaginal bleeding between periods, or pelvic pain. Complications in women include pelvic inflammatory disease and in men include inflammation of the epididymis. Many of those infected, however, have no symptoms. If untreated, gonorrhea can spread to joints or heart valves.Gonorrhea is spread through sexual contact with an infected person. This includes oral, anal, and vaginal sex. It can also spread from a mother to a child during birth. Diagnosis is by testing the urine, urethra in males, or cervix in females. Testing all women who are sexually active and less than 25 years of age each year as well as those with new sexual partners is recommended; the same recommendation applies in men who have sex with men (MSM).Gonorrhea can be prevented with the use of condoms, having sex with only one person who is uninfected, and by not having sex. Treatment is usually with ceftriaxone by injection and azithromycin by mouth. Resistance has developed to many previously used antibiotics and higher doses of ceftriaxone are occasionally required. Retesting is recommended three months after treatment. Sexual partners from the last two months should also be treated.Gonorrhea affects about 0.8% of women and 0.6% of men. An estimated 33 to 106 million new cases occur each year, out of the 498 million new cases of curable STI – which also includes syphilis, chlamydia, and trichomoniasis. Infections in women most commonly occur when they are young adults. In 2015, it caused about 700 deaths. Descriptions of the disease date back to before the Common Era within the Old Testament. The current name was first used by the Greek physician Galen before 200 AD who referred to it as "an unwanted discharge of semen".
Signs and symptoms
Gonorrhea infections of mucosal membranes can cause swelling, itching, pain, and the formation of pus. The time from exposure to symptoms is usually between two and 14 days, with most symptoms appearing between four and six days after infection, if they appear at all. Both men and women with infections of the throat may experience a sore throat, though such infection does not produce symptoms in 90% of cases. Other symptoms may include swollen lymph nodes around the neck. Either sex can become infected in the eyes or rectum if these tissues are exposed to the bacterium.
Women
Half of women with gonorrhea are asymptomatic but the other half experience vaginal discharge, lower abdominal pain, or pain with sexual intercourse associated with inflammation of the uterine cervix. Common medical complications of untreated gonorrhea in women include pelvic inflammatory disease which can cause scars to the fallopian tubes and result in later ectopic pregnancy among those women who become pregnant.
Men
Most infected men with symptoms have inflammation of the penile urethra associated with a burning sensation during urination and discharge from the penis. In men, discharge with or without burning occurs in half of all cases and is the most common symptom of the infection. This pain is caused by a narrowing and stiffening of the urethral lumen. The most common medical complication of gonorrhea in men is inflammation of the epididymis. Gonorrhea is also associated with increased risk of prostate cancer.
Infants
If not treated, gonococcal ophthalmia neonatorum will develop in 28% of infants born to women with gonorrhea.
Spread
If left untreated, gonorrhea can spread from the original site of infection and infect and damage the joints, skin, and other organs. Indications of this can include fever, skin rashes, sores, and joint pain and swelling. In advanced cases, gonorrhea may cause a general feeling of tiredness similar to other infections. It is also possible for an individual to have an allergic reaction to the bacteria, in which case any appearing symptoms will be greatly intensified. Very rarely it may settle in the heart, causing endocarditis, or in the spinal column, causing meningitis. Both are more likely among individuals with suppressed immune systems, however.
Cause
Gonorrhea is caused by the bacterium Neisseria gonorrhoeae. Previous infection does not confer immunity – a person who has been infected can become infected again by exposure to someone who is infected. Infected persons may be able to infect others repeatedly without having any signs or symptoms of their own.
Spread
The infection is usually spread from one person to another through vaginal, oral, or anal sex. Men have a 20% risk of getting the infection from a single act of vaginal intercourse with an infected woman. The risk for men who have sex with men (MSM) is higher. Insertive MSM may get a penile infection from anal intercourse, while receptive MSM may get anorectal gonorrhea. Women have a 60–80% risk of getting the infection from a single act of vaginal intercourse with an infected man.A mother may transmit gonorrhea to her newborn during childbirth; when affecting the infants eyes, it is referred to as ophthalmia neonatorum. It may be able to spread through the objects contaminated with body fluid from an infected person. The bacteria typically does not survive long outside the body, typically dying within minutes to hours.
Risk factors
It is discovered that sexually active women younger than 25 and men who have sex with men are at increased risk of getting gonorrhea.Other risk factors include:
Having a new sex partner
Having a sex partner who has other partners
Having more than one sex partner
Having had gonorrhea or another sexually transmitted infection
Complications
Medically it has been said that Untreated gonorrhea can lead to major complications, such as:
Infertility in women. Gonorrhea can spread into the uterus and fallopian tubes, causing pelvic inflammatory disease (PID). PID can result in scarring of the tubes, greater risk of pregnancy complications and infertility. PID requires immediate treatment.
Infertility in men. Gonorrhea can cause a small, coiled tube in the rear portion of the testicles where the sperm ducts are located (epididymis) to become inflamed (epididymitis). Untreated epididymitis can lead to infertility.
Infection that spreads to the joints and other areas of the body. The bacterium that causes gonorrhea can spread through the bloodstream and infect other parts of the body, including the joints. Fever, rash, skin sores, joint pain, swelling and stiffness are possible results.
Increased risk of HIV/AIDS. Having gonorrhea increases the susceptibility to infection with human immunodeficiency virus (HIV), the virus that leads to AIDS. People who have both gonorrhea and HIV (untreated by anti-retroviral therapy) are able to pass both diseases more readily to their partners.
Complications in babies. Babies who contract gonorrhea from their mothers during birth can develop blindness, sores on the scalp and infections.
Diagnosis
Traditionally, gonorrhea was diagnosed with Gram stain and culture; however, newer polymerase chain reaction (PCR)-based testing methods are becoming more common. In those failing initial treatment, culture should be done to determine sensitivity to antibiotics.Tests that use PCR (aka nucleic acid amplification) to identify genes unique to N. gonorrhoeae are recommended for screening and diagnosis of gonorrhea infection. These PCR-based tests require a sample of urine, urethral swabs, or cervical/vaginal swabs. Culture (growing colonies of bacteria in order to isolate and identify them) and Gram-stain (staining of bacterial cell walls to reveal morphology) can also be used to detect the presence of N. gonorrhoeae in all specimen types except urine.If Gram-negative, oxidase-positive diplococci are visualized on direct Gram stain of urethral pus (male genital infection), no further testing is needed to establish the diagnosis of gonorrhea infection. However, in the case of female infection direct Gram stain of cervical swabs is not useful because the N. gonorrhoeae organisms are less concentrated in these samples. The chances of false positives are increased as Gram-negative diplococci native to the normal vaginal flora cannot be distinguished from N. gonorrhoeae. Thus, cervical swabs must be cultured under the conditions described above. If oxidase positive, Gram-negative diplococci are isolated from a culture of a cervical/vaginal swab specimen, then the diagnosis is made. Culture is especially useful for diagnosis of infections of the throat, rectum, eyes, blood, or joints—areas where PCR-based tests are not well established in all labs. Culture is also useful for antimicrobial sensitivity testing, treatment failure, and epidemiological purposes (outbreaks, surveillance).In patients who may have disseminated gonococcal infection (DGI), all possible mucosal sites should be cultured (e.g., pharynx, cervix, urethra, rectum). Three sets of blood cultures should also be obtained. Synovial fluid should be collected in cases of septic arthritis.All people testing positive for gonorrhea should be tested for other sexually transmitted diseases such as chlamydia, syphilis, and human immunodeficiency virus. Studies have found co-infection with chlamydia ranging from 46 to 54% in young people with gonorrhea. Among persons in the United States between 14 and 39 years of age, 46% of people with gonorrheal infection also have chlamydial infection. For this reason, gonorrhea and chlamydia testing are often combined. People diagnosed with gonorrhea infection have a fivefold increase risk of HIV transmission. Additionally, infected persons who are HIV positive are more likely to shed and transmit HIV to uninfected partners during an episode of gonorrhea.
Screening
The United States Preventive Services Task Force (USPSTF) recommends screening for gonorrhea in women at increased risk of infection, which includes all sexually active women younger than 25 years. Extragenital gonorrhea and chlamydia are highest in men who have sex with men (MSM). Additionally, the USPSTF also recommends routine screening in people who have previously tested positive for gonorrhea or have multiple sexual partners and individuals who use condoms inconsistently, provide sexual favors for money, or have sex while under the influence of alcohol or drugs.Screening for gonorrhea in women who are (or intend to become) pregnant, and who are found to be at high risk for sexually transmitted diseases, is recommended as part of prenatal care in the United States.
Prevention
As with most sexually transmitted diseases, the risk of infection can be reduced significantly by the correct use of condoms, not having sex, or can be removed almost entirely by limiting sexual activities to a mutually monogamous relationship with an uninfected person.Those previously infected are encouraged to return for follow up care to make sure that the infection has been eliminated. In addition to the use of phone contact, the use of email and text messaging have been found to improve the re-testing for infection.Newborn babies coming through the birth canal are given erythromycin ointment in the eyes to prevent blindness from infection. The underlying gonorrhea should be treated; if this is done then usually a good prognosis will follow.
Treatment
Antibiotics
Antibiotics are used to treat gonorrhea infections. As of 2016, both ceftriaxone by injection and azithromycin by mouth are most effective. However, due to increasing rates of antibiotic resistance, local susceptibility patterns must be taken into account when deciding on treatment. Ertapenem is a potential effective alternative treatment for ceftriaxone-resistant gonorrhea.Adults may have eyes infected with gonorrhoea and require proper personal hygiene and medications. Addition of topical antibiotics have not been shown to improve cure rates compared to oral antibiotics alone in treatment of eye infected gonorrhea. For newborns, erythromycin ointment is recommended as a preventative measure for gonococcal infant conjunctivitis.Infections of the throat can be especially problematic, as antibiotics have difficulty becoming sufficiently concentrated there to destroy the bacteria. This is amplified by the fact that pharyngeal gonorrhoea is mostly asymptomatic, and gonococci and commensal Neisseria species can coexist for long time periods in the pharynx and share anti-microbial resistance genes. Accordingly, an enhanced focus on early detection (i.e., screening of high-risk populations, such as men who have sex with men, PCR testing should be considered) and appropriate treatment of pharyngeal gonorrhoea is important.
Sexual partners
It is recommended that sexual partners be tested and potentially treated. One option for treating sexual partners of people infected is patient-delivered partner therapy (PDPT), which involves providing prescriptions or medications to the person to take to his/her partner without the health care providers first examining him/her.The United States Centers for Disease Control and Prevention (CDC) currently recommend that individuals who have been diagnosed and treated for gonorrhea avoid sexual contact with others until at least one week past the final day of treatment in order to prevent the spread of the bacterium.
Antibiotic resistance
Many antibiotics that were once effective including penicillin, tetracycline, and fluoroquinolones are no longer recommended because of high rates of resistance. Resistance to cefixime has reached a level such that it is no longer recommended as a first-line agent in the United States, and if it is used a person should be tested again after a week to determine whether the infection still persists. Public health officials are concerned that an emerging pattern of resistance may predict a global epidemic. In 2016, the WHO published new guidelines for treatment, stating "There is an urgent need to update treatment recommendations for gonococcal infections to respond to changing antimicrobial resistance (AMR) patterns of N. gonorrhoeae. High-level resistance to previously recommended quinolones is widespread and decreased susceptibility to the extended-spectrum (third-generation) cephalosporins, another recommended first-line treatment in the 2003 guidelines, is increasing and several countries have reported treatment failures."
Prognosis
Gonorrhea if left untreated may last for weeks or months with higher risks of complications. One of the complications of gonorrhea is systemic dissemination resulting in skin pustules or petechia, septic arthritis, meningitis, or endocarditis. This occurs in between 0.6 and 3% of infected women and 0.4 and 0.7% of infected men.In men, inflammation of the epididymis, prostate gland, and urethra can result from untreated gonorrhea. In women, the most common result of untreated gonorrhea is pelvic inflammatory disease. Other complications include inflammation of the tissue surrounding the liver, a rare complication associated with Fitz-Hugh–Curtis syndrome; septic arthritis in the fingers, wrists, toes, and ankles; septic abortion; chorioamnionitis during pregnancy; neonatal or adult blindness from conjunctivitis; and infertility. Men who have had a gonorrhea infection have an increased risk of getting prostate cancer.
Epidemiology
About 88 million cases of gonorrhea occur each year, out of the 448 million new cases of curable STI each year – that also includes syphilis, chlamydia and trichomoniasis. The prevalence was highest in the African region, the Americas, and Western Pacific, and lowest in Europe. In 2013, it caused about 3,200 deaths, up from 2,300 in 1990.In the United Kingdom, 196 per 100,000 males 20 to 24 years old and 133 per 100,000 females 16 to 19 years old were diagnosed in 2005. In 2013, the CDC estimated that more than 820,000 people in the United States get a new gonorrheal infection each year. Fewer than half of these infections are reported to CDC. In 2011, 321,849 cases of gonorrhea were reported to the CDC. After the implementation of a national gonorrhea control program in the mid-1970s, the national gonorrhea rate declined from 1975 to 1997. After a small increase in 1998, the gonorrhea rate has decreased slightly since 1999. In 2004, the rate of reported gonorrheal infections was 113. 5 per 100,000 persons.In the US, it is the second-most-common bacterial sexually transmitted infections; chlamydia remains first. According to the CDC African Americans are most affected by gonorrhea, accounting for 69% of all gonorrhea cases in 2010.The World Health Organization warned in 2017 of the spread of untreatable strains of gonorrhea, following analysis of at least three cases in Japan, France and Spain, which survived all antibiotic treatment.
History
Some scholars translate the biblical terms zav (for a male) and zavah (for a female) as gonorrhea.It has been suggested that mercury was used as a treatment for gonorrhea. Surgeons tools on board the recovered English warship the Mary Rose included a syringe that, according to some, was used to inject the mercury via the urinary meatus into crewmen with gonorrhea. The name "the clap", in reference to the disease, is recorded as early as the sixteenth century, referring to a medieval red-light district in Paris, Les Clapiers. Translating to "The rabbit holes", it was so named for the small huts in which prostitutes worked.In 1854, Dr. Wilhelm Gollmann addressed gonorrhea in his book, Homeopathic Guide to all Diseases Urinary and Sexual Organs. He noted that the disease was common in prostitutes and homosexuals in large cities. Gollmann recommended the following as cures: aconite to cure "shooting pains with soreness and inflammation;" mercury "for stitching pain with purulent discharge;" nux vomica and sulphur "when the symptoms are complicated with hemorrhoids and stricture of the rectum. Other remedies include argentum, aurum (gold), belladonna, calcarea, ignatia, phosphorus, and sepia.Silver nitrate was one of the widely used drugs in the 19th century. However, it became replaced by Protargol. Arthur Eichengrün invented this type of colloidal silver, which was marketed by Bayer from 1897 onward. The silver-based treatment was used until the first antibiotics came into use in the 1940s.The exact time of onset of gonorrhea as prevalent disease or epidemic cannot be accurately determined from the historical record. One of the first reliable notations occurs in the Acts of the (English) Parliament. In 1161, this body passed a law to reduce the spread of "... the perilous infirmity of burning". The symptoms described are consistent with, but not diagnostic of, gonorrhea. A similar decree was passed by Louis IX in France in 1256, replacing regulation with banishment. Similar symptoms were noted at the siege of Acre by Crusaders.
Coincidental to, or dependent on, the appearance of a gonorrhea epidemic, several changes occurred in European medieval society. Cities hired public health doctors to treat affected patients without right of refusal. Pope Boniface rescinded the requirement that physicians complete studies for the lower orders of the Catholic priesthood.Medieval public health physicians in the employ of their cities were required to treat prostitutes infected with the "burning", as well as lepers and other epidemic patients. After Pope Boniface completely secularized the practice of medicine, physicians were more willing to treat a sexually transmitted disease.
Research
A vaccine for gonorrhea has been developed that is effective in mice. It will not be available for human use until further studies have demonstrated that it is both safe and effective in the human population. Development of a vaccine has been complicated by the ongoing evolution of resistant strains and antigenic variation (the ability of N. gonorrhoeae to disguise itself with different surface markers to evade the immune system).As N. gonorrhoeae is closely related to N. meningitidis and they have 80–90% homology in their genetic sequences some cross-protection by meningococcal vaccines is plausible. A study published in 2017 showed that MeNZB group B meningococcal vaccine provided a partial protection against gonorrhea. The vaccine efficiency was calculated to be 31%.
References
External links
Gonorrhea at Curlie
"Gonorrhea – CDC Fact Sheet" |
Wolff–Parkinson–White syndrome | Wolff–Parkinson–White syndrome (WPWS) is a disorder due to a specific type of problem with the electrical system of the heart. About 60% of people with the electrical problem developed symptoms, which may include an abnormally fast heartbeat, palpitations, shortness of breath, lightheadedness, or syncope. Rarely, cardiac arrest may occur. The most common type of irregular heartbeat that occurs is known as paroxysmal supraventricular tachycardia.The cause of WPW is typically unknown and is likely due to a combination of chance and genetic factors. A small number of cases are due to a mutation of the PRKAG2 gene which may be inherited from a persons parents in an autosomal dominant fashion. The underlying mechanism involves an accessory electrical conduction pathway between the atria and the ventricles. It is associated with other conditions such as Ebstein anomaly and hypokalemic periodic paralysis. The diagnosis of WPW occurs with a combination of palpitations and when an electrocardiogram (ECG) show a short PR interval and a delta wave. It is a type of pre-excitation syndrome.WPW syndrome may be monitored or treated with either medications or an ablation (destroying the tissues) such as with radiofrequency catheter ablation. It affects between 0.1 and 0.3% in the population. The risk of death in those without symptoms is about 0.5% per year in children and 0.1% per year in adults. In some cases, non-invasive monitoring may help to more carefully risk stratify patients into a lower risk category. In those without symptoms ongoing observation may be reasonable. In those with WPW complicated by atrial fibrillation, cardioversion or the medication procainamide may be used. The condition is named after Louis Wolff, John Parkinson, and Paul Dudley White who described the ECG findings in 1930.
Signs and symptoms
People with WPW are usually asymptomatic when not having a fast heart rate. However, individuals may experience palpitations, dizziness, shortness of breath, or infrequently syncope (fainting or near fainting) during episodes of supraventricular tachycardia. WPW is also associated with a very small risk of sudden death due to more dangerous heart rhythm disturbances.
Pathophysiology
Electrical activity in the normal human heart begins when a cardiac action potential arises in the sinoatrial (SA) node, which is located in the right atrium. From there, the electrical stimulus is transmitted via internodal pathways to the atrioventricular (AV) node. After a brief delay at the AV node, the stimulus travels through the bundle of His to the left and right bundle branches and then to the Purkinje fibers and the endocardium at the apex of the heart, then finally to the ventricular myocardium.The AV node serves an important function as a "gatekeeper", limiting the electrical activity that reaches the ventricles. In situations where the atria generate excessively rapid electrical activity (such as atrial fibrillation or atrial flutter), the AV node limits the number of signals conducted to the ventricles. For example, if the atria are electrically activated at 300 beats per minute, half those electrical impulses may be blocked by the AV node, so that the ventricles are stimulated at only 150 beats per minute – resulting in a pulse of 150 beats per minute. Another important property of the AV node is that it slows down individual electrical impulses. This is manifested on the electrocardiogram as the PR interval (the time from electrical activation of the atria to electrical activation of the ventricles), which is usually shortened to less than 120 milliseconds in duration.Individuals with WPW have an accessory pathway that communicates between the atria and the ventricles, in addition to the AV node. This accessory pathway is known as the bundle of Kent. This accessory pathway does not share the rate-slowing properties of the AV node and may conduct electrical activity at a significantly higher rate than the AV node. For instance, in the example above, if an individual had an atrial rate of 300 beats per minute, the accessory bundle may conduct all the electrical impulses from the atria to the ventricles, causing the ventricles to contract at 300 beats per minute. Extremely rapid heart rates such as this may result in hemodynamic instability or cardiogenic shock. In some cases, the combination of an accessory pathway and abnormal heart rhythms can trigger ventricular fibrillation, a leading cause of sudden cardiac death.WPW may be associated with PRKAG2, a protein kinase enzyme encoded by the PRKAG2 gene.
Bundle of Kent
The bundle of Kent is an abnormal extra or accessory conduction pathway between the atria and ventricles that is present in a small percentage (between 0.1 and 0.3%) of the general population. This pathway may communicate between the left atrium and the left ventricle, in which case it is termed a "type A pre-excitation", or between the right atrium and the right ventricle, in which case it is termed a "type B pre-excitation" in old, currently abandoned classification. Problems arise when this pathway creates an electrical circuit that bypasses the AV node. The AV node is capable of slowing the rate of conduction of electrical impulses to the ventricles, whereas the bundle of Kent lacks this capability. When an aberrant electrical connection is made via the bundle of Kent, tachydysrhythmias may therefore result.
Diagnosis
WPW is commonly diagnosed on the basis of the electrocardiogram in an asymptomatic individual. In this case, it is manifested as a delta wave, which is a slurred upstroke in the QRS complex that is associated with a short PR interval. The short PR interval and slurring of the QRS complex are reflective of the impulse making it to the ventricles early (via the accessory pathway) without the usual delay experienced in the AV node.If a person with WPW experiences episodes of atrial fibrillation, the ECG shows a rapid polymorphic wide-complex tachycardia (without torsades de pointes). This combination of atrial fibrillation and WPW is considered dangerous, and most antiarrhythmic drugs are contraindicated.When an individual is in normal sinus rhythm, the ECG characteristics of WPW are a short PR interval (less than 120 milliseconds in duration), widened QRS complex (greater than 120 milliseconds in duration) with slurred upstroke of the QRS complex, and secondary repolarization changes (reflected in ST segment-T wave changes).In individuals with WPW, electrical activity that is initiated in the SA node travels through the accessory pathway, as well as through the AV node to activate the ventricles via both pathways. Since the accessory pathway does not have the impulse slowing properties of the AV node, the electrical impulse first activates the ventricles via the accessory pathway, and immediately afterwards via the AV node. This gives the short PR interval and slurred upstroke of the QRS complex known as the delta wave.In case of type A pre-excitation (left atrioventricular connections), a positive R wave is seen in V1 ("positive delta") on the precordial leads of the electrocardiogram, while in type B pre-excitation (right atrioventricular connections), a predominantly negative delta wave is seen in lead V1 ("negative delta").People with WPW may have more than one accessory pathway – in some cases, as many as eight abnormal pathways have been found. This has been seen in individuals with Ebsteins anomaly.Wolff–Parkinson–White syndrome is sometimes associated with Lebers hereditary optic neuropathy, a form of mitochondrial disease.
Risk stratification
WPW carries a small risk of sudden death, presumably due to rapidly conducted atrial fibrillation causing ventricular fibrillation. While the overall risk is approximately 2.4 per 1000 person years, the risk in an individual is dependent on the properties of the accessory pathway causing pre-excitation.A higher risk accessory pathway may be suggested by a history of syncope, but risk stratification is best performed by assessing how frequently a pathway can conduct impulse to the ventricles, usually via programmed electrical stimulation (PES) in the cardiac electrophysiology laboratory. This is an invasive but generally low-risk procedure during which the atria are stimulated to try to induce tachycardia. If a tachycardia involving the accessory pathway can be triggered, the cardiologist can then assess how rapidly the accessory pathway is able to conduct. The faster it can conduct, the higher the likelihood the accessory pathway can conduct fast enough to trigger a lethal tachycardia.High-risk features that may be present during PES include an effective refractory period of the accessory pathway less than 250 ms, multiple pathways, septal location of pathway, and inducibility of supraventricular tachycardia (AVRT, atrial fibrillation). Individuals with any of these high-risk features are generally considered at increased risk for SCD or symptomatic tachycardia, and should be treated accordingly (i.e.: catheter ablation).It is unclear whether invasive risk stratification (with PES) is necessary in the asymptomatic individual. While some groups advocate PES for risk stratification in all individuals under 35 years old, others only offer it to individuals who have history suggestive of a tachydysrhythmia, since the incidence of sudden cardiac death is so low (less than 0.6% in some reports).Other methods of risk stratification include observing the ventricular rate during spontaneous atrial fibrillation on a 12-lead ECG. RR intervals of less than 250 ms suggest a higher risk pathway. During exercise testing, abrupt loss of pre-excitation as heart rate increases also suggest a lower risk pathway. However, this approach is hampered by the normal improvement in AV node conduction during exercise which can also mask pre-excitation despite ongoing conduction down the accessory pathway.
Treatment
According to the ACLS protocol, people with WPW who are experiencing rapid abnormal heart rhythms (tachydysrhythmias) may require synchronized electrical cardioversion if they are demonstrating severe signs or symptoms (for example, low blood pressure or lethargy with altered mental status). If they are relatively stable, medication may be used.
Medications
WPW pattern with hemodynamically stability and orthodromic AVRT leading to a regular narrow complex tachycardia may be managed similarly to other regular narrow complex supraventricular tachycardias: first with vagal maneuvers followed by a trial of adenosine (first-line therapy). The 2015 ACC/AHA/HRS guidelines recommend beta-blockers or calcium channel blockers as second-line agents, electric cardioversion is reserved for refractory arrhythmias. However, if there is any doubt about the diagnosis of orthodromic AVRT or if aberrant conduction leading to a wide complex QRS is observed, it may be prudent to manage as undifferentiated wide complex tachycardia. People with atrial fibrillation and rapid ventricular response may be treated with amiodarone or procainamide to stabilize their heart rate. Procainamide and cardioversion are accepted treatments for conversion of tachycardia found with WPW. Amiodarone in atrial fibrillation with WPW, is linked to ventricular fibrillation, and thus may be worse than procainamide.AV node blockers should be avoided in atrial fibrillation and atrial flutter with WPW or history of it; this includes adenosine, diltiazem, verapamil, other calcium channel blockers, and beta blockers. They can exacerbate the syndrome by blocking the hearts normal electrical pathway (therefore favoring 1:1 atrial to ventricle conduction through the pre-excitation pathway, potentially leading to unstable ventricular arrhythmias).
Catheter ablation
The definitive treatment of WPW is the destruction of the abnormal electrical pathway by catheter ablation. Two main types of catheter ablation include radiofrequency ablation with heat or cryoablation with cold energy. This procedure is performed by cardiac electrophysiologists and has high success rate in the hands of an experienced electrophysiologist. Findings from 1994 indicate success rates of as high as 95% in people treated with radiofrequency catheter ablation for WPW. If radiofrequency catheter ablation is successfully performed, the condition is generally considered cured. Recurrence rates are typically less than 5% after a successful ablation. Some patients, such as the ones with underlying Ebsteins anomaly and inherited cardiomyopathies, may have multiple accessory pathways.
History
The bundle of Kent is eponymously named for British physiologist Albert Frank Stanley Kent (1863–1958), who described lateral branches in the atrioventricular groove of the monkey heart (erroneously believing these constituted the normal atrioventricular conduction system).In 1915, Frank Norman Wilson (1890–1952) became the first to describe the condition later called Wolff–Parkinson–White syndrome. Alfred M. Wedd (1887–1967) was the next to describe the condition in 1921. Cardiologists Louis Wolff (1898–1972), John Parkinson (1885–1976) and Paul Dudley White (1886–1973) are credited with the definitive description of the disorder in 1930.
Notable cases
LaMarcus Aldridge, American basketball player
Michael Cera, Canadian actor
Nathan Eagleton, former Australian rules football player
Jeff Garlin, American actor, writer, and comedian
Quentin Groves, American football player who died of a heart attack at age 32
Dan Hardy, British UFC welterweight fighter, turned analyst and commentator
Alicia Hoskin, New Zealand Olympic canoeist.
Mitch Hurwitz, American television writer and producer, creator of Arrested Development
Jessie J, British musician
Marilyn Manson, American musician, painter, and actor
Meat Loaf, American musician
Michael Montgomery, American football player
Montel Vontavious Porter, professional wrestler
Michael Rupp, American ice hockey player
See also
Re-entry ventricular arrhythmia
References
External links
Wolff–Parkinson–White syndrome at Curlie
Genetics Home Reference:Wolff-Parkinson-White syndrome (United States National Library of Medicine, Bethesda, Maryland)
Wolff-Parkinson-White Syndrome Clinic, The University of Wisconsin - Madison |
Ventricular septal defect | A ventricular septal defect (VSD) is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart. The extent of the opening may vary from pin size to complete absence of the ventricular septum, creating one common ventricle. The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively innervated with conducting cardiomyocytes.
The membranous portion, which is close to the atrioventricular node, is most commonly affected in adults and older children in the United States. It is also the type that will most commonly require surgical intervention, comprising over 80% of cases.Membranous ventricular septal defects are more common than muscular ventricular septal defects, and are the most common congenital cardiac anomaly.
Signs and symptoms
Ventricular septal defect is usually symptomless at birth. It usually manifests a few weeks after birth.VSD is an acyanotic congenital heart defect, aka a left-to-right shunt, so there are no signs of cyanosis in the early stage. However, uncorrected VSD can increase pulmonary resistance leading to the reversal of the shunt and corresponding cyanosis.
Pansystolic (Holosystolic) murmur along lower left sternal border (depending upon the size of the defect) +/- palpable thrill (palpable turbulence of blood flow). Heart sounds are normal. Larger VSDs may cause a parasternal heave, a displaced apex beat (the palpable heartbeat moves laterally over time, as the heart enlarges). An infant with a large VSD will fail to thrive and become sweaty and tachypnoeic (breathe faster) with feeds.The restrictive ventricular septal defects (smaller defects) are associated with a louder murmur and more palpable thrill (grade IV murmur). Larger defects may eventually be associated with pulmonary hypertension due to the increased blood flow. Over time this may lead to an Eisenmengers syndrome the original VSD operating with a left-to-right shunt, now becomes a right-to-left shunt because of the increased pressures in the pulmonary vascular bed.
Cause
Congenital VSDs are frequently associated with other congenital conditions, such as Down syndrome.A VSD can also form a few days after a myocardial infarction (heart attack) due to mechanical tearing of the septal wall, before scar tissue forms, when macrophages start remodeling the dead heart tissue.
A congenital VSD can result from a disturbance in the morphogenesis of the heart in its embryonic stages. In the fifth week of gestation, the heart undergoes multiple processes of septation and forming a dextral loop. Interfering with the latter leads to insufficient leftward movement of the ventricular outflow tract over the atrioventricular canal, which in turn can result in a VSD or, in the most extreme cases, a double outlet right ventricle with one.A ventricular septal defect arises when the superior part of the interventricular septum, which separates the right and left ventricles of the heart, fails to fully develop. The right ventricle pumps blood to the lungs to get oxygen, while the left ventricle pumps blood to the rest of the body to provide oxygen to tissues. A ventricular septal defect results in the mixing of oxygen-rich blood with oxygen-poor blood, increasing strain on the heart and lungs.
Pathophysiology
During ventricular contraction, or systole, some of the blood from the left ventricle leaks into the right ventricle, passes through the lungs and reenters the left ventricle via the pulmonary veins and left atrium. This has two net effects. First, the circuitous refluxing of blood causes volume overload on the left ventricle. Second, because the left ventricle normally has a much higher systolic pressure (~120 mmHg) than the right ventricle (~20 mmHg), the leakage of blood into the right ventricle therefore elevates right ventricular pressure and volume, causing pulmonary hypertension with its associated symptoms.
In serious cases, the pulmonary arterial pressure can reach levels that equal the systemic pressure. This reverses the left to right shunt, so that blood then flows from the right ventricle into the left ventricle, resulting in cyanosis, as blood is by-passing the lungs for oxygenation.This effect is more noticeable in patients with larger defects, who may present with breathlessness, poor feeding and failure to thrive in infancy. Patients with smaller defects may be asymptomatic. Four different septal defects exist, with perimembranous most common, outlet, atrioventricular, and muscular less commonly.
Diagnosis
A VSD can be detected by cardiac auscultation. Classically, a VSD causes a pathognomonic holo- or pansystolic murmur. Auscultation is generally considered sufficient for detecting a significant VSD. The murmur depends on the abnormal flow of blood from the left ventricle, through the VSD, to the right ventricle. If there is not much difference in pressure between the left and right ventricles, then the flow of blood through the VSD will not be very great and the VSD may be silent. This situation occurs a) in the fetus (when the right and left ventricular pressures are essentially equal), b) for a short time after birth (before the right ventricular pressure has decreased), and c) as a late complication of unrepaired VSD. Confirmation of cardiac auscultation can be obtained by non-invasive cardiac ultrasound (echocardiography). To more accurately measure ventricular pressures, cardiac catheterization, can be performed.
Classification
Although there are several classifications for VSD, the most accepted and unified classification is that of Congenital Heart Surgery Nomenclature and Database Project.
The classification is based on the location of the VSD on the right ventricular surface of the inter ventricular septum and is as follows:
Multiple
Type 1
Type 1 is sub aortic
Type 2
Type 2 also known as perimembranous, paramembranous, conoventricular, membranous septal defect, and subaortic.
Most common variety found in 70%
Type 3
Type 3 also known as inlet (or AV canal type).
Commonly associated with atrioventricular septal defect, found in about 5%
Type 4
Type 4 also known as muscular (trabecular)
Located in the muscular septum, found in 20%. Can be sub classified again based on the location into anterior, apical, posterior and mid
Type: Gerbode
Type: Gerbode also known as left ventricular to right atrial communication
Due to absence of Atrioventricular septum.
Treatment
Most cases do not need treatment and heal during the first years of life. Treatment is either conservative or surgical. Smaller congenital VSDs often close on their own, as the heart grows, and in such cases may be treated conservatively.
Some cases may necessitate surgical intervention, i.e. with the following indications:
Failure of congestive cardiac failure to respond to medications
VSD with pulmonic stenosis
Large VSD with pulmonary hypertension
VSD with aortic regurgitationFor the surgical procedure, a heart-lung machine is required and a median sternotomy is performed. Percutaneous endovascular procedures are less invasive and can be done on a beating heart, but are only suitable for certain patients. Repair of most VSDs is complicated by the fact that the conducting system of the heart is in the immediate vicinity.
Ventricular septum defect in infants is initially treated medically with cardiac glycosides (e.g., digoxin 10-20 μg/kg per day), loop diuretics (e.g., furosemide 1–3 mg/kg per day) and ACE inhibitors (e.g., captopril 0.5–2 mg/kg per day).
Transcatheter closure
A device, known as the Amplatzer muscular VSD occluder, may be used to close certain VSDs. It was initially approved in 2009. It appears to work well and be safe. The cost is also lower than having open heart surgery. The device is placed through a small incision in the groin.The Amplatzer septal occluder was shown to have full closure of the ventricular defect within the 24 hours of placement. It has a low risk of embolism after implantation. Some tricuspid valve regurgitation was shown after the procedure that could possibly be due from the right ventricular disc. There have been some reports that the Amplatzer septal occluder may cause life-threatening erosion of the tissue inside the heart. This occurs in one percent of people implanted with the device and requires immediate open-heart surgery. This erosion occurs due to improper sizing of the device resulting with it being too large for the defect, causing rubbing of the septal tissue and erosion.
Surgery
Surgical closure of a Perimembranous VSD is performed on cardiopulmonary bypass with ischemic arrest. Patients are usually cooled to 28 degrees. Percutaneous Device closure of these defects is rarely performed in the United States because of the reported incidence of both early and late onset complete heart block after device closure, presumably secondary to device trauma to the AV node.
Surgical exposure is achieved through the right atrium. The tricuspid valve septal leaflet is retracted or incised to expose the defect margins.
Several patch materials are available, including native pericardium, bovine pericardium, PTFE (Gore-Tex or Impra), or Dacron.
Suture techniques include horizontal pledgeted mattress sutures, and running polypropylene suture.
Critical attention is necessary to avoid injury to the conduction system located on the left ventricular side of the interventricular septum near the papillary muscle of the conus. Care is taken to avoid injury to the aortic valve with sutures.
Once the repair is complete, the heart is extensively deaired by venting blood through the aortic cardioplegia site, and by infusing Carbon Dioxide into the operative field to displace air.
Intraoperative transesophageal echocardiography is used to confirm secure closure of the VSD, normal function of the aortic and tricuspid valves, good ventricular function, and the elimination of all air from the left side of the heart.
The sternum, fascia and skin are closed, with potential placement of a local anesthetic infusion catheter under the fascia, to enhance postoperative pain control.
Multiple muscular VSDs are a challenge to close, achieving a complete closure can be aided by the use of fluorescein dye.
Epidemiology
VSDs are the most common congenital cardiac abnormalities. They are found in 30-60% of all newborns with a congenital heart defect, or about 2-6 per 1000 births. During heart formation, when the heart begins life as a hollow tube, it begins to partition, forming septa. If this does not occur properly it can lead to an opening being left within the ventricular septum. It is debatable whether all those defects are true heart defects, or if some of them are normal phenomena, since most of the trabecular VSDs close spontaneously. Prospective studies give a prevalence of 2-5 per 100 births of trabecular VSDs that close shortly after birth in 80-90% of the cases.
Famous people who had ventricular septal defect
Madhubala (1933–69), Indian actress. Died at age 36.
See also
Atrial septal defect
Atrioventricular septal defect
Cardiac output
Congenital heart disease
Heart sounds
Pulmonary hypertension
References
== External links == |
Yellow fever | Yellow fever is a viral disease of typically short duration. In most cases, symptoms include fever, chills, loss of appetite, nausea, muscle pains – particularly in the back – and headaches. Symptoms typically improve within five days. In about 15% of people, within a day of improving the fever comes back, abdominal pain occurs, and liver damage begins causing yellow skin. If this occurs, the risk of bleeding and kidney problems is increased.The disease is caused by the yellow fever virus and is spread by the bite of an infected mosquito. It infects only humans, other primates, and several types of mosquitoes. In cities, it is spread primarily by Aedes aegypti, a type of mosquito found throughout the tropics and subtropics. The virus is an RNA virus of the genus Flavivirus. The disease may be difficult to tell apart from other illnesses, especially in the early stages. To confirm a suspected case, blood-sample testing with polymerase chain reaction is required.A safe and effective vaccine against yellow fever exists, and some countries require vaccinations for travelers. Other efforts to prevent infection include reducing the population of the transmitting mosquitoes. In areas where yellow fever is common, early diagnosis of cases and immunization of large parts of the population are important to prevent outbreaks. Once a person is infected, management is symptomatic; no specific measures are effective against the virus. Death occurs in up to half of those who get severe disease.In 2013, yellow fever resulted in about 127,050 severe infections and 45,000 deaths worldwide, with nearly 90 percent of these occurring in Africa. Nearly a billion people live in an area of the world where the disease is common. It is common in tropical areas of the continents of South America and Africa, but not in Asia. Since the 1980s, the number of cases of yellow fever has been increasing. This is believed to be due to fewer people being immune, more people living in cities, people moving frequently, and changing climate increasing the habitat for mosquitoes.The disease originated in Africa and spread to the Americas starting in the 15th century with the European trafficking of enslaved Africans from sub-Saharan Africa. Since the 17th century, several major outbreaks of the disease have occurred in the Americas, Africa, and Europe. In the 18th and 19th centuries, yellow fever was considered one of the most dangerous infectious diseases; numerous epidemics swept through major cities of the US and in other parts of the world.In 1927, yellow fever virus was the first human virus to be isolated.
Signs and symptoms
Yellow fever begins after an incubation period of three to six days. Most cases cause only a mild infection with fever, headache, chills, back pain, fatigue, loss of appetite, muscle pain, nausea, and vomiting. In these cases, the infection lasts only three to six days.But in 15% of cases, people enter a second, toxic phase of the disease characterized by recurring fever, this time accompanied by jaundice due to liver damage, as well as abdominal pain. Bleeding in the mouth, nose, the eyes, and the gastrointestinal tract cause vomit containing blood, hence the Spanish name for yellow fever, vómito negro ("black vomit"). There may also be kidney failure, hiccups, and delirium.Among those who develop jaundice, the fatality rate is 20 to 50%, while the overall fatality rate is about 3 to 7.5%. Severe cases may have a mortality greater than 50%.Surviving the infection provides lifelong immunity, and normally results in no permanent organ damage.
Complication
Yellow fever can lead to death for 20% to 50% of those who develop severe disease. Jaundice, fatigue, heart rhythm problems, seizures and internal bleeding may also appear as complications of yellow fever during recovery time.
Cause
Yellow fever is caused by yellow fever virus, an enveloped RNA virus 40–50 nm in width, the type species and namesake of the family Flaviviridae. It was the first illness shown to be transmissible by filtered human serum and transmitted by mosquitoes, by American doctor Walter Reed around 1900. The positive-sense, single-stranded RNA is around 10,862 nucleotides long and has a single open reading frame encoding a polyprotein.Host proteases cut this polyprotein into three structural (C, prM, E) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5); the enumeration corresponds to the arrangement of the protein coding genes in the genome. Minimal yellow fever virus (YFV) 3UTR region is required for stalling of the host 5-3 exonuclease XRN1. The UTR contains PKS3 pseudoknot structure, which serves as a molecular signal to stall the exonuclease and is the only viral requirement for subgenomic flavivirus RNA (sfRNA) production. The sfRNAs are a result of incomplete degradation of the viral genome by the exonuclease and are important for viral pathogenicity. Yellow fever belongs to the group of hemorrhagic fevers.The viruses infect, amongst others, monocytes, macrophages, Schwann cells, and dendritic cells. They attach to the cell surfaces via specific receptors and are taken up by an endosomal vesicle. Inside the endosome, the decreased pH induces the fusion of the endosomal membrane with the virus envelope. The capsid enters the cytosol, decays, and releases the genome. Receptor binding, as well as membrane fusion, are catalyzed by the protein E, which changes its conformation at low pH, causing a rearrangement of the 90 homodimers to 60 homotrimers.After entering the host cell, the viral genome is replicated in the rough endoplasmic reticulum (ER) and in the so-called vesicle packets. At first, an immature form of the virus particle is produced inside the ER, whose M-protein is not yet cleaved to its mature form, so is denoted as precursor M (prM) and forms a complex with protein E. The immature particles are processed in the Golgi apparatus by the host protein furin, which cleaves prM to M. This releases E from the complex, which can now take its place in the mature, infectious virion.
Transmission
Yellow fever virus is mainly transmitted through the bite of the yellow fever mosquito Aedes aegypti, but other mostly Aedes mosquitoes such as the tiger mosquito (Aedes albopictus) can also serve as a vector for this virus. Like other arboviruses, which are transmitted by mosquitoes, yellow fever virus is taken up by a female mosquito when it ingests the blood of an infected human or another primate. Viruses reach the stomach of the mosquito, and if the virus concentration is high enough, the virions can infect epithelial cells and replicate there. From there, they reach the haemocoel (the blood system of mosquitoes) and from there the salivary glands. When the mosquito next sucks blood, it injects its saliva into the wound, and the virus reaches the bloodstream of the bitten person. Transovarial transmissionial and transstadial transmission of yellow fever virus within A. aegypti, that is, the transmission from a female mosquito to its eggs and then larvae, are indicated. This infection of vectors without a previous blood meal seems to play a role in single, sudden breakouts of the disease.Three epidemiologically different infectious cycles occur in which the virus is transmitted from mosquitoes to humans or other primates. In the "urban cycle", only the yellow fever mosquito A. aegypti is involved. It is well adapted to urban areas, and can also transmit other diseases, including Zika fever, dengue fever, and chikungunya. The urban cycle is responsible for the major outbreaks of yellow fever that occur in Africa. Except for an outbreak in Bolivia in 1999, this urban cycle no longer exists in South America.Besides the urban cycle, both in Africa and South America, a sylvatic cycle (forest or jungle cycle) is present, where Aedes africanus (in Africa) or mosquitoes of the genus Haemagogus and Sabethes (in South America) serve as vectors. In the jungle, the mosquitoes infect mainly nonhuman primates; the disease is mostly asymptomatic in African primates. In South America, the sylvatic cycle is currently the only way humans can become infected, which explains the low incidence of yellow fever cases on the continent. People who become infected in the jungle can carry the virus to urban areas, where A. aegypti acts as a vector. Because of this sylvatic cycle, yellow fever cannot be eradicated except by eradicating the mosquitoes that serve as vectors.In Africa, a third infectious cycle known as "savannah cycle" or intermediate cycle, occurs between the jungle and urban cycles. Different mosquitoes of the genus Aedes are involved. In recent years, this has been the most common form of transmission of yellow fever in Africa.Concern exists about yellow fever spreading to southeast Asia, where its vector A. aegypti already occurs.
Pathogenesis
After transmission from a mosquito, the viruses replicate in the lymph nodes and infect dendritic cells in particular. From there, they reach the liver and infect hepatocytes (probably indirectly via Kupffer cells), which leads to eosinophilic degradation of these cells and to the release of cytokines. Apoptotic masses known as Councilman bodies appear in the cytoplasm of hepatocytes.Fatality may occur when cytokine storm, shock, and multiple organ failure follow.
Diagnosis
Yellow fever is most frequently a clinical diagnosis, based on symptomatology and travel history. Mild cases of the disease can only be confirmed virologically. Since mild cases of yellow fever can also contribute significantly to regional outbreaks, every suspected case of yellow fever (involving symptoms of fever, pain, nausea, and vomiting 6–10 days after leaving the affected area) is treated seriously.If yellow fever is suspected, the virus cannot be confirmed until 6–10 days following the illness. A direct confirmation can be obtained by reverse transcription polymerase chain reaction, where the genome of the virus is amplified. Another direct approach is the isolation of the virus and its growth in cell culture using blood plasma; this can take 1–4 weeks.Serologically, an enzyme-linked immunosorbent assay during the acute phase of the disease using specific IgM against yellow fever or an increase in specific IgG titer (compared to an earlier sample) can confirm yellow fever. Together with clinical symptoms, the detection of IgM or a four-fold increase in IgG titer is considered sufficient indication for yellow fever. As these tests can cross-react with other flaviviruses, such as dengue virus, these indirect methods cannot conclusively prove yellow fever infection.Liver biopsy can verify inflammation and necrosis of hepatocytes and detect viral antigens. Because of the bleeding tendency of yellow fever patients, a biopsy is only advisable post mortem to confirm the cause of death.In a differential diagnosis, infections with yellow fever must be distinguished from other feverish illnesses such as malaria. Other viral hemorrhagic fevers, such as Ebola virus, Lassa virus, Marburg virus, and Junin virus, must be excluded as the cause.
Prevention
Personal prevention of yellow fever includes vaccination and avoidance of mosquito bites in areas where yellow fever is endemic. Institutional measures for prevention of yellow fever include vaccination programmes and measures to control mosquitoes. Programmes for distribution of mosquito nets for use in homes produce reductions in cases of both malaria and yellow fever. Use of EPA-registered insect repellent is recommended when outdoors. Exposure for even a short time is enough for a potential mosquito bite. Long-sleeved clothing, long pants, and socks are useful for prevention. The application of larvicides to water-storage containers can help eliminate potential mosquito breeding sites. EPA-registered insecticide spray decreases the transmission of yellow fever.
Use insect repellent when outdoors such as those containing DEET, picaridin, ethyl butylacetylaminopropionate (IR3535), or oil of lemon eucalyptus on exposed skin.
Mosquitoes may bite through thin clothing, so spraying clothes with repellent containing permethrin or another EPA-registered repellent gives extra protection. Clothing treated with permethrin is commercially available. Mosquito repellents containing permethrin are not approved for application directly to the skin.
The peak biting times for many mosquito species are dusk to dawn. However, A. aegypti, one of the mosquitoes that transmits yellow fever virus, feeds during the daytime. Staying in accommodations with screened or air-conditioned rooms, particularly during peak biting times, also reduces the risk of mosquito bites.
Vaccination
Vaccination is recommended for those traveling to affected areas, because non-native people tend to develop more severe illness when infected. Protection begins by the 10th day after vaccine administration in 95% of people, and had been reported to last for at least 10 years. The World Health Organization (WHO) now states that a single dose of vaccine is sufficient to confer lifelong immunity against yellow fever disease. The attenuated live vaccine stem 17D was developed in 1937 by Max Theiler. The WHO recommends routine vaccination for people living in affected areas between the 9th and 12th month after birth.Up to one in four people experience fever, aches, and local soreness and redness at the site of injection. In rare cases (less than one in 200,000 to 300,000), the vaccination can cause yellow fever vaccine-associated viscerotropic disease, which is fatal in 60% of cases. It is probably due to the genetic morphology of the immune system. Another possible side effect is an infection of the nervous system, which occurs in one in 200,000 to 300,000 cases, causing yellow fever vaccine-associated neurotropic disease, which can lead to meningoencephalitis and is fatal in less than 5% of cases.The Yellow Fever Initiative, launched by the WHO in 2006, vaccinated more than 105 million people in 14 countries in West Africa. No outbreaks were reported during 2015. The campaign was supported by the GAVI alliance and governmental organizations in Europe and Africa. According to the WHO, mass vaccination cannot eliminate yellow fever because of the vast number of infected mosquitoes in urban areas of the target countries, but it will significantly reduce the number of people infected.Demand for yellow fever vaccine has continued to increase due to the growing number of countries implementing yellow fever vaccination as part of their routine immunization programmes. Recent upsurges in yellow fever outbreaks in Angola (2015), the Democratic Republic of Congo (2016), Uganda (2016), and more recently in Nigeria and Brazil in 2017 have further increased demand, while straining global vaccine supply. Therefore, to vaccinate susceptible populations in preventive mass immunization campaigns during outbreaks, fractional dosing of the vaccine is being considered as a dose-sparing strategy to maximize limited vaccine supplies. Fractional dose yellow fever vaccination refers to administration of a reduced volume of vaccine dose, which has been reconstituted as per manufacturer recommendations. The first practical use of fractional dose yellow fever vaccination was in response to a large yellow fever outbreak in the Democratic Republic of the Congo in mid-2016.In March 2017, the WHO launched a vaccination campaign in Brazil with 3.5 million doses from an emergency stockpile. In March 2017 the WHO recommended vaccination for travellers to certain parts of Brazil. In March 2018, Brazil shifted its policy and announced it planned to vaccinate all 77.5 million currently unvaccinated citizens by April 2019.
Compulsory vaccination
Some countries in Asia are considered to be potentially in danger of yellow fever epidemics, as both mosquitoes with the capability to transmit yellow fever as well as susceptible monkeys are present. The disease does not yet occur in Asia. To prevent introduction of the virus, some countries demand previous vaccination of foreign visitors who have passed through yellow fever areas. Vaccination has to be proved by a vaccination certificate, which is valid 10 days after the vaccination and lasts for 10 years. Although the WHO on 17 May 2013 advised that subsequent booster vaccinations are unnecessary, an older (than 10 years) certificate may not be acceptable at all border posts in all affected countries. A list of the countries that require yellow fever vaccination is published by the WHO. If the vaccination cannot be given for some reason, dispensation may be possible. In this case, an exemption certificate issued by a WHO-approved vaccination center is required. Although 32 of 44 countries where yellow fever occurs endemically do have vaccination programmes, in many of these countries, less than 50% of their population is vaccinated.
Vector control
Control of the yellow fever mosquito A. aegypti is of major importance, especially because the same mosquito can also transmit dengue fever and chikungunya disease. A. aegypti breeds preferentially in water, for example, in installations by inhabitants of areas with precarious drinking water supplies, or in domestic refuse, especially tires, cans, and plastic bottles. These conditions are common in urban areas in developing countries.Two main strategies are employed to reduce A. aegypti populations. One approach is to kill the developing larvae. Measures are taken to reduce the water accumulations in which the larvae develop. Larvicides are used, along with larvae-eating fish and copepods, which reduce the number of larvae. For many years, copepods of the genus Mesocyclops have been used in Vietnam for preventing dengue fever. This eradicated the mosquito vector in several areas. Similar efforts may prove effective against yellow fever. Pyriproxyfen is recommended as a chemical larvicide, mainly because it is safe for humans and effective in small doses.The second strategy is to reduce populations of the adult yellow fever mosquito. Lethal ovitraps can reduce Aedes populations, using lesser amounts of pesticide because it targets the pest directly. Curtains and lids of water tanks can be sprayed with insecticides, but application inside houses is not recommended by the WHO. Insecticide-treated mosquito nets are effective, just as they are against the Anopheles mosquito that carries malaria.
Treatment
As with other Flavivirus infections, no cure is known for yellow fever. Hospitalization is advisable and intensive care may be necessary because of rapid deterioration in some cases. Certain acute treatment methods lack efficacy: passive immunization after the emergence of symptoms is probably without effect; ribavirin and other antiviral drugs, as well as treatment with interferons, are ineffective in yellow fever patients. Symptomatic treatment includes rehydration and pain relief with drugs such as paracetamol (acetaminophen). Acetylsalicylic acid (aspirin). However, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are often avoided because of an increased risk of gastrointestinal bleeding due to their anticoagulant effects.
Epidemiology
Yellow fever is common in tropical and subtropical areas of South America and Africa. Worldwide, about 600 million people live in endemic areas. The WHO estimates 200,000 cases of yellow fever worldwide each year. About 15% of people infected with yellow fever progress to a severe form of the illness, and up to half of those will die, as there is no cure for yellow fever.
Africa
An estimated 90% of yellow fever infections occur on the African continent. In 2016, a large outbreak originated in Angola and spread to neighboring countries before being contained by a massive vaccination campaign. In March and April 2016, 11 imported cases of the Angola genotype in unvaccinated Chinese nationals were reported in China, the first appearance of the disease in Asia in recorded history.Phylogenetic analysis has identified seven genotypes of yellow fever viruses, and they are assumed to be differently adapted to humans and to the vector A. aegypti. Five genotypes (Angola, Central/East Africa, East Africa, West Africa I, and West Africa II) occur only in Africa. West Africa genotype I is found in Nigeria and the surrounding region. West Africa genotype I appears to be especially infectious, as it is often associated with major outbreaks. The three genotypes found outside of Nigeria and Angola occur in areas where outbreaks are rare. Two outbreaks, in Kenya (1992–1993) and Sudan (2003 and 2005), involved the East African genotype, which had remained undetected in the previous 40 years.
South America
In South America, two genotypes have been identified (South American genotypes I and II). Based on phylogenetic analysis these two genotypes appear to have originated in West Africa and were first introduced into Brazil. The date of introduction of the predecessor African genotype which gave rise to the South American genotypes appears to be 1822 (95% confidence interval 1701 to 1911). The historical record shows an outbreak of yellow fever occurred in Recife, Brazil, between 1685 and 1690. The disease seems to have disappeared, with the next outbreak occurring in 1849. It was likely introduced with the trafficking of slaves through the slave trade from Africa. Genotype I has been divided into five subclades, A through E.In late 2016, a large outbreak began in Minas Gerais state of Brazil that was characterized as a sylvan or jungle epizootic. It began as an outbreak in brown howler monkeys, which serve as a sentinel species for yellow fever, that then spread to men working in the jungle. No cases had been transmitted between humans by the A. aegypti mosquito, which can sustain urban outbreaks that can spread rapidly. In April 2017, the sylvan outbreak continued moving toward the Brazilian coast, where most people were unvaccinated. By the end of May the outbreak appeared to be declining after more than 3,000 suspected cases, 758 confirmed and 264 deaths confirmed to be yellow fever. The Health Ministry launched a vaccination campaign and was concerned about spread during the Carnival season in February and March. The CDC issued a Level 2 alert (practice enhanced precautions.)A Bayesian analysis of genotypes I and II has shown that genotype I accounts for virtually all the current infections in Brazil, Colombia, Venezuela, and Trinidad and Tobago, while genotype II accounted for all cases in Peru. Genotype I originated in the northern Brazilian region around 1908 (95% highest posterior density interval [HPD]: 1870–1936). Genotype II originated in Peru in 1920 (95% HPD: 1867–1958). The estimated rate of mutation for both genotypes was about 5 × 10−4 substitutions/site/year, similar to that of other RNA viruses.
Asia
The main vector (A. aegypti) also occurs in tropical and subtropical regions of Asia, the Pacific, and Australia, but yellow fever has never occurred there, until jet travel introduced 11 cases from the 2016 Angola and DR Congo yellow fever outbreak in Africa. Proposed explanations include:
That the strains of the mosquito in the east are less able to transmit yellow fever virus.
That immunity is present in the populations because of other diseases caused by related viruses (for example, dengue).
That the disease was never introduced because the shipping trade was insufficient.But none is considered satisfactory. Another proposal is the absence of a slave trade to Asia on the scale of that to the Americas. The trans-Atlantic slave trade probably introduced yellow fever into the Western Hemisphere from Africa.
History
Early history
The evolutionary origins of yellow fever most likely lie in Africa, with transmission of the disease from nonhuman primates to humans. The virus is thought to have originated in East or Central Africa and spread from there to West Africa. As it was endemic in Africa, local populations had developed some immunity to it. When an outbreak of yellow fever would occur in an African community where colonists resided, most Europeans died, while the indigenous Africans usually developed nonlethal symptoms resembling influenza. This phenomenon, in which certain populations develop immunity to yellow fever due to prolonged exposure in their childhood, is known as acquired immunity. The virus, as well as the vector A. aegypti, were probably transferred to North and South America with the trafficking of slaves from Africa, part of the Columbian exchange following European exploration and colonization.The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados. An outbreak was recorded by Spanish colonists in 1648 in the Yucatán Peninsula, where the indigenous Mayan people called the illness xekik ("blood vomit"). In 1685, Brazil suffered its first epidemic in Recife. The first mention of the disease by the name "yellow fever" occurred in 1744.
(John Mitchell) (1805) (Mitchells account of the Yellow Fever in Virginia in 1741–2) Archived 2017-02-23 at the Wayback Machine, The Philadelphia Medical Museum, 1 (1) : 1–20.
(John Mitchell) (1814) "Account of the Yellow fever which prevailed in Virginia in the years 1737, 1741, and 1742, in a letter to the late Cadwallader Colden, Esq. of New York, from the late John Mitchell, M.D.F.R.S. of Virginia," Archived 2017-02-23 at the Wayback Machine American Medical and Philosophical Register, 4 : 181–215. The term "yellow fever" appears on p. 186. On p. 188, Mitchell mentions "… the distemper was what is generally called yellow fever in America". However, on pages 191–192, he states "… I shall consider the cause of the yellowness which is so remarkable in this distemper, as to have given it the name of the Yellow Fever."However, Dr. Mitchell misdiagnosed the disease that he observed and treated, and the disease was probably Weils disease or hepatitis. McNeill argues that the environmental and ecological disruption caused by the introduction of sugar plantations created the conditions for mosquito and viral reproduction, and subsequent outbreaks of yellow fever. Deforestation reduced populations of insectivorous birds and other creatures that fed on mosquitoes and their eggs.
In Colonial times and during the Napoleonic Wars, the West Indies were known as a particularly dangerous posting for soldiers due to yellow fever being endemic in the area. The mortality rate in British garrisons in Jamaica was seven times that of garrisons in Canada, mostly because of yellow fever and other tropical diseases. Both English and French forces posted there were seriously affected by the "yellow jack". Wanting to regain control of the lucrative sugar trade in Saint-Domingue (Hispaniola), and with an eye on regaining Frances New World empire, Napoleon sent an army under the command of his brother-in-law General Charles Leclerc to Saint-Domingue to seize control after a slave revolt. The historian J. R. McNeill asserts that yellow fever accounted for about 35,000 to 45,000 casualties of these forces during the fighting. Only one third of the French troops survived for withdrawal and return to France. Napoleon gave up on the island and his plans for North America, selling the Louisiana Purchase to the US in 1803. In 1804, Haiti proclaimed its independence as the second republic in the Western Hemisphere. Considerable debate exists over whether the number of deaths caused by disease in the Haitian Revolution was exaggerated.Although yellow fever is most prevalent in tropical-like climates, the northern United States were not exempted from the fever. The first outbreak in English-speaking North America occurred in New York City in 1668. English colonists in Philadelphia and the French in the Mississippi River Valley recorded major outbreaks in 1669, as well as additional yellow fever epidemics in Philadelphia, Baltimore, and New York City in the 18th and 19th centuries. The disease traveled along steamboat routes from New Orleans, causing some 100,000–150,000 deaths in total. The yellow fever epidemic of 1793 in Philadelphia, which was then the capital of the United States, resulted in the deaths of several thousand people, more than 9% of the population. One of these deaths was James Hutchinson, a physician helping to treat the population of the city. The national government fled the city to Trenton, New Jersey, including President George Washington.
The southern city of New Orleans was plagued with major epidemics during the 19th century, most notably in 1833 and 1853. A major epidemic occurred |
Yellow fever | in both New Orleans and Shreveport, Louisiana in 1873. Its residents called the disease "yellow jack". Urban epidemics continued in the United States until 1905, with the last outbreak affecting New Orleans.At least 25 major outbreaks took place in the Americas during the 18th and 19th centuries, including particularly serious ones in Cartagena, Chile, in 1741; Cuba in 1762 and 1900; Santo Domingo in 1803; and Memphis, Tennessee, in 1878.In the early nineteenth century, the prevalence of yellow fever in the Caribbean "led to serious health problems" and alarmed the United States Navy as numerous deaths and sickness curtailed naval operations and destroyed morale. One episode began in April 1822 when the frigate USS Macedonian left Boston and became part of Commodore James Biddles West India Squadron. Unbeknownst to all, they were about to embark on a cruise to disaster and their assignment "would prove a cruise through hell". Secretary of the Navy Smith Thompson had assigned the squadron to guard United States merchant shipping and suppress piracy. During their time on deployment from 26 May to 3 August 1822, 76 of the Macedonians officers and men died, including John Cadle, surgeon USN. Seventy-four of these deaths were attributed to yellow fever. Biddle reported that another 52 of his crew were on sick-list. In their report to the secretary of the Navy, Biddle and Surgeons Mate Charles Chase stated the cause as "fever". As a consequence of this loss, Biddle noted that his squadron was forced to return to Norfolk Navy Yard early. Upon arrival, the Macedonians crew were provided medical care and quarantined at Craney Island, Virginia.
In 1853, Cloutierville, Louisiana, had a late-summer outbreak of yellow fever that quickly killed 68 of the 91 inhabitants. A local doctor concluded that some unspecified infectious agent had arrived in a package from New Orleans. In 1854, 650 residents of Savannah, Georgia, died from yellow fever. In 1858, St. Matthews German Evangelical Lutheran Church in Charleston, South Carolina, had 308 yellow fever deaths, reducing the congregation by half. A ship carrying persons infected with the virus arrived in Hampton Roads in southeastern Virginia in June 1855. The disease spread quickly through the community, eventually killing over 3,000 people, mostly residents of Norfolk and Portsmouth. In 1873, Shreveport, Louisiana, lost 759 citizens in an 80-day period to a yellow fever epidemic, with over 400 additional victims eventually succumbing. The total death toll from August through November was approximately 1,200.In 1878, about 20,000 people died in a widespread epidemic in the Mississippi River Valley. That year, Memphis had an unusually large amount of rain, which led to an increase in the mosquito population. The result was a huge epidemic of yellow fever. The steamship John D. Porter took people fleeing Memphis northward in hopes of escaping the disease, but passengers were not allowed to disembark due to concerns of spreading yellow fever. The ship roamed the Mississippi River for the next two months before unloading her passengers.Major outbreaks have also occurred in southern Europe. Gibraltar lost many lives to outbreaks in 1804, 1814, and 1828. Barcelona suffered the loss of several thousand citizens during an outbreak in 1821. The Duke de Richelieu deployed 30,000 French troops to the border between France and Spain in the Pyrenees Mountains, to establish a cordon sanitaire in order to prevent the epidemic from spreading from Spain into France.
Causes and transmission
Ezekiel Stone Wiggins, known as the Ottawa Prophet, proposed that the cause of a yellow fever epidemic in Jacksonville, Florida, in 1888, was astrological.
The planets were in the same line as the sun and earth and this produced, besides Cyclones, Earthquakes, etc., a denser atmosphere holding more carbon and creating microbes. Mars had an uncommonly dense atmosphere, but its inhabitants were probably protected from the fever by their newly discovered canals, which were perhaps made to absorb carbon and prevent the disease.
In 1848, Josiah C. Nott suggested that yellow fever was spread by insects such as moths or mosquitoes, basing his ideas on the pattern of transmission of the disease. Carlos Finlay, a Cuban doctor and scientist, proposed in 1881 that yellow fever might be transmitted by previously infected mosquitoes rather than by direct contact from person to person, as had long been believed. Since the losses from yellow fever in the Spanish–American War in the 1890s were extremely high, Army doctors began research experiments with a team led by Walter Reed, and composed of doctors James Carroll, Aristides Agramonte, and Jesse William Lazear. They successfully proved Finlays "mosquito hypothesis". Yellow fever was the first virus shown to be transmitted by mosquitoes. The physician William Gorgas applied these insights and eradicated yellow fever from Havana. He also campaigned against yellow fever during the construction of the Panama Canal. A previous effort of canal building by the French had failed in part due to mortality from the high incidence of yellow fever and malaria, which killed many workers.Although Reed has received much of the credit in United States history books for "beating" yellow fever, he had fully credited Finlay with the discovery of the yellow fever vector, and how it might be controlled. Reed often cited Finlays papers in his own articles, and also credited him for the discovery in his personal correspondence. The acceptance of Finlays work was one of the most important and far-reaching effects of the U.S. Army Yellow Fever Commission of 1900. Applying methods first suggested by Finlay, the United States government and Army eradicated yellow fever in Cuba and later in Panama, allowing completion of the Panama Canal. While Reed built on the research of Finlay, historian François Delaporte notes that yellow fever research was a contentious issue. Scientists, including Finlay and Reed, became successful by building on the work of less prominent scientists, without always giving them the credit they were due. Reeds research was essential in the fight against yellow fever. He is also credited for using the first type of medical consent form during his experiments in Cuba, an attempt to ensure that participants knew they were taking a risk by being part of testing.Like Cuba and Panama, Brazil also led a highly successful sanitation campaign against mosquitoes and yellow fever. Beginning in 1903, the campaign led by Oswaldo Cruz, then director general of public health, resulted not only in eradicating the disease but also in reshaping the physical landscape of Brazilian cities such as Rio de Janeiro. During rainy seasons, Rio de Janeiro had regularly suffered floods, as water from the bay surrounding the city overflowed into Rios narrow streets. Coupled with the poor drainage systems found throughout Rio, this created swampy conditions in the citys neighborhoods. Pools of stagnant water stood year-long in city streets and proved to be a fertile ground for disease-carrying mosquitoes. Thus, under Cruzs direction, public health units known as "mosquito inspectors" fiercely worked to combat yellow fever throughout Rio by spraying, exterminating rats, improving drainage, and destroying unsanitary housing. Ultimately, the citys sanitation and renovation campaigns reshaped Rio de Janeiros neighborhoods. Its poor residents were pushed from city centers to Rios suburbs, or to towns found in the outskirts of the city. In later years, Rios most impoverished inhabitants would come to reside in favelas.
During 1920–1923, the Rockefeller Foundations International Health Board undertook an expensive and successful yellow fever eradication campaign in Mexico. The IHB gained the respect of Mexicos federal government because of the success. The eradication of yellow fever strengthened the relationship between the US and Mexico, which had not been very good in the years prior. The eradication of yellow fever was also a major step toward better global health.In 1927, scientists isolated the yellow fever virus in West Africa. Following this, two vaccines were developed in the 1930s. Max Theiler led the completion of the 17D yellow fever vaccine in 1937, for which he was subsequently awarded the Nobel Prize in Physiology or Medicine. That vaccine, 17D, is still in use, although newer vaccines, based on vero cells, are in development (as of 2018).
Current status
Using vector control and strict vaccination programs, the urban cycle of yellow fever was nearly eradicated from South America. Since 1943, only a single urban outbreak in Santa Cruz de la Sierra, Bolivia, has occurred. Since the 1980s, however, the number of yellow fever cases has been increasing again, and A. aegypti has returned to the urban centers of South America. This is partly due to limitations on available insecticides, as well as habitat dislocations caused by climate change. It is also because the vector control program was abandoned. Although no new urban cycle has yet been established, scientists believe this could happen again at any point. An outbreak in Paraguay in 2008 was thought to be urban in nature, but this ultimately proved not to be the case.In Africa, virus eradication programs have mostly relied upon vaccination. These programs have largely been unsuccessful because they were unable to break the sylvatic cycle involving wild primates. With few countries establishing regular vaccination programs, measures to fight yellow fever have been neglected, making the future spread of the virus more likely.
Research
In the hamster model of yellow fever, early administration of the antiviral ribavirin is an effective treatment of many pathological features of the disease. Ribavirin treatment during the first five days after virus infection improved survival rates, reduced tissue damage in the liver and spleen, prevented hepatocellular steatosis, and normalised levels of alanine aminotransferase, a liver damage marker. The mechanism of action of ribavirin in reducing liver pathology in yellow fever virus infection may be similar to its activity in treatment of hepatitis C, a related virus. Because ribavirin had failed to improve survival in a virulent rhesus model of yellow fever infection, it had been previously discounted as a possible therapy. Infection was reduced in mosquitoes with the wMel strain of Wolbachia.Yellow fever has been researched by several countries as a potential biological weapon.
Notes
References
Further reading
External links
Yellow fever at Curlie
Finlay CJ (January 2012). "The Mosquito Hypothetically Considered as the Transmitting Agent of Yellow Fever". MEDICC Review. 14 (1): 56–59. doi:10.37757/MR2012V14.N1.10. PMID 34503309.
"U.S. Army Yellow Fever Commission." Claude Moore Health Sciences Library, University of Virginia
"Yellow fever virus". NCBI Taxonomy Browser. 11089. |
Animal bite | An animal bite is a wound, usually a puncture or laceration, caused by the teeth. An animal bite usually results in a break in the skin but also includes contusions from the excessive pressure on body tissue from the bite. The contusions can occur without a break in the skin. Bites can be provoked or unprovoked. Other bite attacks may be apparently unprovoked. Biting is a physical action not only describing an attack but it is a normal response in an animal as it eats, carries objects, softens and prepares food for its young, removes ectoparasites from its body surface, removes plant seeds attached to its fur or hair, scratching itself, and grooming other animals. Animal bites often result in serious infections and mortality. Animal bites not only include injuries from the teeth of reptiles, mammals, but fish, and amphibians. Arthropods can also bite and leave injuries.
Signs and symptoms
Bite wounds can cause a number of signs and symptoms
Generalized tissue damage due to tearing and scratching
Serious hemorrhage if major blood vessels are pierced
Infection by bacteria or other pathogens, including rabies
Introduction of venom into the wound by venomous animals such as some snakes
Introduction of other irritants into the wound, causing inflammation and itching
Classification
Bites are usually classified by the type of animal causing the wound.
Many different animals are known to bite humans.
Vertebrates
Companion animals, including dogs, cats, rats, ferrets, and parrots, may bite humans.
Wildlife may sometimes bite humans. The bites of various mammals such as bats, skunks, wolves, raccoons, etc. may transmit rabies, which is almost always fatal if left untreated.
Human bites are themselves capable of doing great flesh damage, but are particularly known for spreading communicable diseasesInvoluntary biting injuries due to closed-fist injuries from fists striking teeth (referred to as reverse bite injuries) are a common consequence of fist fights. These have been termed "fight bites". Injuries in which the knuckle joints or tendons of the hand are bitten into tend to be the most serious.
Teething infants are known to bite objects to relieve pressure on their growing teeth, and may inadvertently bite peoples hands or arms while doing so. Young children may also bite people out of anger or misbehaviour, although this is usually corrected early in the childs life.
Reverse bite injury
A reverse bite injury (also called a clenched fist injury, closed fist injury, or fight bite) results when a person punches another person in the face, and the skin (and sometimes tendons) of their knuckles are cut against the teeth of the person they are punching. The proximity of the wound is often located over the metacarpophalangeal joint resulting in tendon injury.The medical treatment of this injury is similar to those of a human bite, but may also involve damage of the underlying tendons.These injuries should be managed as other human bites: wound irrigation and antibiotics are essential as human saliva can contain a number of bacteria. The nature of these injuries is such that even if the injury is optimally managed, poor outcomes may still occur.
Arthropods
The bites of arthropods have some of the most serious health consequences known. Mosquito bites transmit serious disease and result in millions of deaths and illnesses in the world. Ticks also transmit many diseases such as Lyme disease.
Spider bite
Insect bites and stings
Flea bites are responsible for the transmission of plague.
Mosquito bites are responsible for the transmission of dengue fever and malaria.
Leech bite
Mechanism
Trauma
A natural consequence of a bite is tissue trauma at the site. Trauma may consist of scratching, tearing, punture or laceration of the skin, hematoma (bruising), embedding of foreign objects, for example a tooth or hair, damage to or severing of underlying structures such as connective tissue or muscle, amputations, and the ripping off of skin and hair. If major blood vessels are damaged, severe blood loss can occur.
Infection
Pathogen organisms can be introduced into the bite. Some of the pathogens can originate from the mouth of the biter, the substrate onto which the injured person or animal can fall or from the naturally occurring microorganisms that are present on the skin or hair of the animal. The advent of antibiotics improved the outcome of bite wound infections.
Rabies
Animal bites where skin has been penetrated, most commonly by dogs and bats, transmit rabies to humans. Rabies from other animals is rare. If the animal is caught alive or dead with its head preserved, the head can be analyzed to detect the disease. Signs of rabies include foaming at the mouth, growling, self-mutilation, jerky behavior, red eyes, and hydrophobia.
If the animal cannot be captured, preventative rabies treatment is recommended in many places. Several countries are known not to have native rabies, see the Wikipedia page for prevalence of rabies.
Treatment
The first step in treatment includes washing the bite wound. If there is a low risk of infection the wound may be sutured. Debridement and drainage of bite wounds was practiced in the pre-antibiotic era, but high rates of infection still occurred. A 2019 Cochrane systematic review aimed to evaluate the healing and infection rates in bite wounds based on if/when they were stitched closed. The review authors looked for studies that compared stitching wounds closed straight away, leaving them open for a short time or not stitching them at all. Due to a lack of high-certainty evidence, the review authors concluded that more robust randomised controlled trials were needed to fully answer this question.
Antibiotics
Antibiotics to prevent infection are recommended for dog and cat bites of the hand, and human bites if they are more than superficial. They are also recommended in those who have poor immune function. Evidence for antibiotics to prevent infection in bites in other areas is not clear.The first choice is amoxicillin with clavulanic acid, and if the person is penicillin-allergic, doxycycline and metronidazole. The antistaphylococcal penicillins (e.g., cloxacillin, nafcillin, flucloxacillin) and the macrolides (e.g., erythromycin, clarithromycin) are not used for empirical therapy, because they do not cover Pasteurella species.
Vaccinations
Rabies prevention is generally available in North America and the Northern European states.
Tetanus toxoid treatment is recommended in those whose vaccinations are not up to date and have a bite that punctures the skin. Tetanus immune globulin is indicated in people with more than 10 years since prior vaccination. Tetanus boosters (Td) should be given every ten years.
TT = tetanus toxoid; TIG: tetanus immune globulin
Mosquito bites
Antihistamines are effective treatment for the symptoms from bites. Many diseases such as malaria and dengue are transmitted by mosquitoes.
Epidemiology
Human bites are the third most frequent type of bite after dog and cat bites. Dog bites are commonplace, with children the most commonly bitten and the face and scalp the most common target. About 4.7 million dog bites are reported annually in the United States. The US estimated annual count of animal bites is 250,000 human bites, 1 to 2 million dog bites, 400,000 cat bites, and 45,000 bites from snakes. Bites from skunks, horses, squirrels, rats, rabbits, pigs, and monkeys may be up to 1 percent of bite injuries. Pet ferrets attacks that were unprovoked have caused serious facial injuries. Non-domesticated animals though assumed to be more common especially as a cause of rabies infection, make up less than one percent of reported bite wounds. When a person is bitten, it is more likely to occur on the right arm, most likely due to defensive reactions when the person uses their dominant arm. Estimates are that three-quarters of bites are located on the arms or legs of humans. Bites to the face of humans constitute only 10 percent of the total. Two-thirds of bite injuries in humans are suffered by children aged ten and younger.Up to three-fourths of dog bites happen to those younger than 20 years-old. In the United States, the costs associated with dog bites are estimated to be more than $1 billion annually. The age groups that suffer most from dog bites are children 5 to 9 years-old. Often, bites go unreported and no medical treatment given - these bites go unreported. As many as one percent of pediatric emergency room visits are for treatment for animal bites. This is more frequent during the summer months. Up to five percent of children receiving emergency care for dog bites are then admitted to the hospital. Bites typically occur in the late afternoon and early evening. Girls are bitten more frequently by cats than they are by dogs. Boys are bitten by dogs two times more often than girls are bitten by dogs.
History
The bites of humans are recorded during the biblical era. Reports of secondary infection occurring after a human bite in children have been noted in the United States since at least 1910. Morbidity and mortality rates improved with the use of antibiotics.
See also
Bite force quotient
Wilderness first aid
Dog bite
Dog bite prevention
References
== External links == |
Absence seizure | Absence seizures are one of several kinds of generalized seizures. These seizures are sometimes referred to as petit mal seizures (from the French for "little illness", a term dating from the late 18th century). Absence seizures are characterized by a brief loss and return of consciousness, generally not followed by a period of lethargy (i.e. without a notable postictal state). Absence seizure is very common in children. It affects both sides of the brain.
Epidemiology
Absence seizures affect between 0.7 and 4.6 per 100,000 in the general population and 6% to 8% in children younger than 15 years. Childhood absence seizures account for 10% to 17% of all absence seizures. Onset is between 4 and 10 years and peaks at 5 to 7 years. It is more common in girls than in boys.
Etiology
An absence seizure is specifically caused by multifactorial inheritance. The voltage-gated T-type calcium channel is regulated by GABRG2, GABRG3, and CACNA1A2 genes. Inheritance of these genes is involved in etiology of absence seizure. The factors that trigger an absence seizure are lack of sleep and compliance, drinking alcohol, and benzodiazepine withdrawal, and use of medication that reduces the threshold of seizure such as Isoniazid, antipsychotics.
Signs and symptoms
The clinical manifestations of absence seizures vary significantly among patients. Impairment of consciousness is the essential symptom, and may be the only clinical symptom, but this can be combined with other manifestations. The hallmark of the absence seizures is abrupt and sudden-onset impairment of consciousness, interruption of ongoing activities, a blank stare, possibly a brief upward rotation of the eyes. If the patient is speaking, speech is slowed or interrupted; if walking, they stand transfixed; if eating, the food will stop on its way to the mouth. Usually, the patient will be unresponsive when addressed. In some cases, attacks are aborted when the patient is called. The attack lasts from a few seconds to half a minute and evaporates as rapidly as it commenced. Absence seizures generally are not followed by a period of disorientation or lethargy (postictal state), in contrast to the majority of seizure disorders.
Absence with impairment of consciousness only as per the above description.
Absence with mild clonic components. Here the onset of the attack is indistinguishable from the above, but clonic components may occur in the eyelids, at the corner of the mouth, or in other muscle groups which may vary in severity from almost imperceptible movements to generalised myoclonic jerks. Objects held in the hand may be dropped.
Absence with atonic components. Here there may be a diminution in tone of muscles subserving posture as well as in the limbs leading to dropping of the head, occasionally slumping of the trunk, dropping of the arms, and relaxation of the grip. Rarely tone is sufficiently diminished to cause this person to fall.
Absence with tonic components. Here during the attack tonic muscular contraction may occur, leading to increase in muscle tone which may affect the extensor muscles or the flexor muscles symmetrically or asymmetrically. If the patient is standing, the head may be drawn backward and the trunk may arch. This may lead to retropulsion, which may cause eyelids to twitch rapidly; eyes may jerk upwards or the patients head may rock back and forth slowly, as if nodding. The head may tonically draw to one or another side.
Absence with automatisms. Purposeful or quasi-purposeful movements occurring in the absence of awareness during an absence attack are frequent and may range from lip licking and swallowing to clothes fumbling or aimless walking. If spoken to, the patient may grunt, and when touched or tickled may rub the site. Automatisms are quite elaborate and may consist of combinations of the above described movements or may be so simple as to be missed by casual observation.
Absence with autonomic components. These may be pallor, and less frequently flushing, sweating, dilatation of pupils and incontinence of urine.Mixed forms of absence frequently occur.
These seizures can happen a few times a day or in some cases, hundreds of times a day, to the point that the person cannot concentrate in school or in other situations requiring sustained, concentrated attention.
Risk factors
Typical absences are easily induced by hyperventilation (over-breathing) in more than 90% of people with typical absences. This is a reliable test for the diagnosis of absence seizures: a patient suspected of typical absences should be asked to hyperventilate for three minutes, counting breaths. During hyperventilation, the oxygen and carbon dioxide level will become abnormal. This results in weakening of electrical signal which leads to a reduction in the seizure threshold. Intermittent photic stimulation may precipitate or facilitate absence seizures; eyelid myoclonia is a common clinical feature.A specific mechanism difference exists in absence seizures in that T-type Ca++ channels are believed to be involved. Ethosuximide is specific for these channels and thus it is not effective for treating other types of seizures. Valproate and gabapentin (among others) have multiple mechanisms of action including blockade of T-type Ca++ channels, and are useful in treating multiple seizure types. Gabapentin can aggravate absence seizures.
Pathophysiology
The corticothalamic cortical circuit plays an important role in the pathophysiology of absence seizure. Some of the neurons are important in their occurrence. They are
Cortical glutamatergic neurons
Thalamic relay neurons
Neurons of thalamic nucleus reticularisAbnormal oscillatory rhythms develop in the thalamic nucleus reticularis. This causes inhibition of GABAergic neurotransmission and excitation of glutamate neurotransmission. Abnormal oscillatory spikes are produced by the low threshold T-type calcium channel. This explains how inheritance of gene code for T-type calcium channel leads to an absence seizure. Antiepileptic drugs such as Gabapentin, Tiagabine and Vigabatrin cause inhibition of GABA results in exacerbation of absence seizures.
Diagnosis
The primary diagnostic test for absence seizures is electroencephalography (EEG). However, brain scans such as by an MRI can help rule out other diseases, such as a stroke or a brain tumor.During EEG, hyperventilation can be used to provoke these seizures. Ambulatory EEG monitoring over 24 hours can quantify the number of seizures per day and their most likely times of occurrence.Absence seizures are brief (usually less than 20 seconds) generalized epileptic seizures of sudden onset and termination. When someone experiences an absence seizure they are often unaware of their episode. Those most susceptible to this are children, and the first episode usually occurs between 4–12 years old. It is very rare that someone older will experience their first absence seizure. Episodes of absence seizures can often be mistaken for inattentiveness when misdiagnosed, and can occur 50–100 times a day. They can be so difficult to detect that some people may go months or years before being given a proper diagnosis. There are no known before or after effects of absence seizures.Absence seizures have two essential components:
Clinical - the impairment of consciousness (absence)
EEG - the EEG shows generalized spike-and-slow wave dischargesAbsence seizures are broadly divided into typical and atypical types:
Typical absence seizures usually occur in the context of idiopathic generalised epilepsies and an EEG shows fast >2.5 Hz generalised spike-wave discharges. The prefix "typical" is to differentiate them from atypical absences rather than to characterise them as "classical" or characteristic of any particular syndrome.
Atypical absence seizures:
Occur only in the context of mainly severe symptomatic or cryptogenic epilepsies of children with learning difficulties who also have frequent seizures of other types, such as atonic, tonic and myoclonic.
Have slower onset and termination and changes in tone are more pronounced.
Have particular ictal characteristics: EEG is of slow (less than 2.5 Hz) spike and slow wave. The discharge is heterogeneous, often asymmetrical and may include irregular spike and slow wave complexes, fast and other paroxysmal activity. Background interictal EEG is usually abnormal.
Syndromes
Absence seizure syndromes are childhood absence epilepsy, epilepsy with myoclonic absences, juvenile absence epilepsy and juvenile myoclonic epilepsy. Other proposed syndromes are Jeavons syndrome (eyelid myoclonia with absences), and genetic generalised epilepsy with phantom absences.
Absence seizures are also known to occur to patients with porphyria and can be triggered by stress or other porphyrin-inducing factors.
Treatment
Treatment of patients with absence seizures only is mainly with ethosuximide or valproic acid, which are of equal efficacy controlling absences in around 75% of patients. Lamotrigine monotherapy is less effective, controlling absences in around 50% of patients. This summary has been recently confirmed by Glauser et al. (2010), who studied the effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug dosages were incrementally increased until the child was free of seizures, the maximal allowable dose was reached, or a criterion indicating treatment failure was met. The primary outcome was freedom from treatment failure after 16 weeks of therapy; the secondary outcome was attentional dysfunction. After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar and were higher than the rate for lamotrigine. There were no significant differences between the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide.
If monotherapy fails or unacceptable adverse reactions appear, replacement of one by another of the three antiepileptic drugs is the alternative. Adding small doses of lamotrigine to sodium valproate may be the best combination in resistant cases.
Although ethosuximide is effective in treating only absence seizures, valproic acid is effective in treating multiple seizure types including tonic-clonic seizure and partial seizure, suggesting it is a better choice if a patient is exhibiting multiple types of seizures.
Similarly, lamotrigine treats multiple seizure types including partial seizures and generalized seizures, therefore it is also an option for patients with multiple seizure types. Clonazepam (Klonopin, Rivotril) is effective in the short term but is not generally recommended for treatment of absence seizure because of the rapid development of tolerance and high frequency of side effects. If medication is not effective in treating absence seizures, surgical treatment such as deep brain stimulation can reduce seizure episodes.
Prevention
Medication alone cannot prevent absence seizure. It need to be supplemented by life-style changes such as exercise, stress reduction, good sleep hygiene, and healthy diet. Research shows that patient with ketogenic diet have 50% reduction in seizure episodes and 34% of patients become seizure free.
Medications that should not be used
Carbamazepine, vigabatrin, and tiagabine are contraindicated in the treatment of absence seizures, irrespective of cause and severity. This is based on clinical and experimental evidence. In particular, the GABA agonists vigabatrin and tiagabine are used to induce, not to treat, absence seizures and absence status epilepticus. Similarly, oxcarbazepine, phenytoin, phenobarbital, gabapentin, and pregabalin should not be used in the treatment of absence seizures because these medications may worsen absence seizures.
Data limitations
In the treatment of absence seizures there is often insufficient evidence for which of the available medications has the best combination of safety and efficacy for a particular patient. Nor is it easily known how long a medication must be continued before an off-medication trial should be conducted to determine whether the patient has outgrown the absence seizures, as is often the case in children.
To date there have been no published results of any large, double-blind, placebo-controlled studies comparing the efficacy and safety of these or any other medications for absence seizures. A 2019 Cochrane review found that ethosuximide was the best mono-therapy for children and adolescents but noted that if absence seizures co-exist with tonic-clonic seizures then valproate should be preferred.
References
External links
Mechanisms of absence seizures (Scholarpedia)
Thalamocortical oscillations (Scholarpedia)
Absence (a comic about an affected persons experiences) |
Meckels diverticulum | A Meckels diverticulum, a true congenital diverticulum, is a slight bulge in the small intestine present at birth and a vestigial remnant of the omphalomesenteric duct (also called the vitelline duct or yolk stalk). It is the most common malformation of the gastrointestinal tract and is present in approximately 2% of the population, with males more frequently experiencing symptoms.
Meckels diverticulum was first explained by Fabricius Hildanus in the sixteenth century and later named after Johann Friedrich Meckel, who described the embryological origin of this type of diverticulum in 1809.
Signs and symptoms
The majority of people with a Meckels diverticulum are asymptomatic. An asymptomatic Meckels diverticulum is called a silent Meckels diverticulum. If symptoms do occur, they typically appear before the age of two years. The most common presenting symptom is painless rectal bleeding such as melaena-like black offensive stools, followed by intestinal obstruction, volvulus and intussusception. Occasionally, Meckels diverticulitis may present with all the features of acute appendicitis. Also, severe pain in the epigastric region is experienced by the person along with bloating in the epigastric and umbilical regions. At times, the symptoms are so painful that they may cause sleepless nights with acute pain felt in the foregut region, specifically in the epigastric and umbilical regions. In some cases, bleeding occurs without warning and may stop spontaneously. The symptoms can be extremely painful, often mistaken as just stomach pain resulting from not eating or constipation. Rarely, a Meckels diverticulum containing ectopic pancreatic tissue can present with abdominal pain and increased serum amylase levels, mimicking acute pancreatitis.
Complications
The lifetime risk for a person with Meckels diverticulum to develop certain complications is about 4–6%. Gastrointestinal bleeding, peritonitis or intestinal obstruction may occur in 15–30% of symptomatic people (Table 1). Only 6.4% of all complications require surgical treatment, and untreated Meckels diverticulum has a mortality rate of 2.5–15%.Table 1 – Complications of Meckels Diverticulum:
Bleeding
Bleeding of the diverticulum is most common in young children, especially in males who are less than 2 years of age. Symptoms may include bright red blood in stools (hematochezia), weakness, abdominal tenderness or pain, and even anaemia in some cases.Bleeding may be caused by:
Ectopic gastric or pancreatic mucosa:Where diverticulum contains embryonic remnants of mucosa of other tissue types.
Secretion of gastric acid or alkaline pancreatic juice from the ectopic mucosa leads to ulceration in the adjacent ileal mucosa i.e. peptic or pancreatic ulcer.
Pain, bleeding or perforation of the bowel at the diverticulum may result.
Mechanical stimulation may also cause erosion and ulceration.Gastrointestinal bleeding may be self-limiting but chronic bleeding may lead to iron deficiency anaemia.The appearance of stools may indicate the nature of the bleeding:
Tarry stools: Alteration of blood produced by slow bowel transit due to minor bleeding in upper gastrointestinal tract
Bright red blood stools: Brisk bleeding
Stools with blood streak: Anal fissure
"Currant jelly" stools: Ischaemia of the intestine leads to copious mucus production and may indicate that one part of the bowel invaginates into another intussusception.
Diverticulitis
Inflammation of the diverticulum can mimic symptoms of appendicitis, i.e., periumbilical tenderness and intermittent crampy abdominal pain. Perforation of the inflamed diverticulum can result in peritonitis. Diverticulitis can also cause adhesions, leading to intestinal obstruction.Diverticulitis may result from:
Association with the mesodiverticular band attaching to the diverticulum tip where torsion has occurred, causing inflammation and ischaemia.
Peptic ulceration resulting from ectopic gastric mucosa of the diverticulum
Following perforation by trauma or ingested foreign material e.g. stalk of vegetable, seeds or fish/chicken bone that become lodged in Meckels diverticulum.
Luminal obstruction due to tumors, enterolith, foreign body, causing stasis or bacterial infection.
Association with acute appendicitis
Intestinal obstruction
Symptoms: Vomiting, abdominal pain and severe or complete constipation.
The vitelline vessels remnant that connects the diverticulum to the umbilicus may form a fibrous or twisting band (volvulus), trapping the small intestine and causing obstruction. Localised periumbilical pain may be experienced in the right lower quadrant (like appendicitis).
"Incarceration": when a Meckels diverticulum is constricted in an inguinal hernia, forming a Littré hernia that obstructs the intestine.
Chronic diverticulitis causing stricture
Strangulation of the diverticulum in the obturator foramen.
Tumors e.g. carcinoma: direct spread of an adenocarcinoma arising in the diverticulum may lead to obstruction
Lithiasis, stones that are formed in Meckels diverticulum can:Extrude into the terminal ileum, leading to obstruction
Induce local inflammation and intussusception.The diverticulum itself or tumour within it may cause intussusception. For example, from the ileum to the colon, causing obstruction. Symptoms of this include "currant jelly" stools and a palpable lump in the lower abdomen. This occurs when the diverticulum inverts into the lumen of the ileum, due to either:An active peristaltic mechanism of the diverticulum that attempts to remove irritating factors
A passive process such as the transit of food
Umbilical anomalies
Anomalies between the diverticulum and umbilicus may include the presence of fibrous cord, cyst, fistula, or sinus, leading to:
Infection or excoriation of periumbilical skin, resulting in a discharging sinus
Recurrent infection and healing of sinus
Abscess formation in the abdominal wall
Fibrous cord increases the risk of volvulus formation and internal herniation
Neoplasm
Tumors in Meckels diverticulum may cause bleeding, acute abdominal pain, gastrointestinal obstruction, perforation or intussusception.
Benign tumors:Leiomyoma
Lipoma
Vascular and neuromuscular hamartomaMalignant tumors:Carcinoids: most common, 44%
Mesenchymal tumors: Leiomyosarcoma, peripheral nerve sheath and gastrointestinal stromal tumors, 35%
Adenocarcinoma, 16%
Desmoplastic small round cell tumor
Other complications
A diverticulum inside a Meckels diverticulum (daughter diverticula)
Stones and phytobezoar (a bezoar of vegetable fibers) in Meckels diverticulum
Vesicodiverticular fistula
Pathophysiology
The omphalomesenteric duct (omphaloenteric duct, vitelline duct, or yolk stalk) normally connects the embryonic midgut to the yolk sac ventrally, providing nutrients to the midgut during embryonic development. The vitelline duct narrows progressively and disappears between the 5th and 8th weeks of gestation.In Meckels diverticulum, the proximal part of vitelline duct fails to regress and involute, which remains as a remnant of variable length and location. The solitary diverticulum lies on the antimesenteric border of the ileum (opposite to the mesenteric attachment) and extends into the umbilical cord of the embryo. The left and right vitelline arteries originate from the primitive dorsal aorta, and travel with the vitelline duct. The right becomes the superior mesenteric artery that supplies a terminal branch to the diverticulum, while the left involutes. Having its own blood supply, Meckels diverticulum is susceptible to obstruction or infection.
Meckels diverticulum is located in the distal ileum, usually within 60–100 cm (2 feet) of the ileocecal valve. This blind segment or small pouch is about 3–6 cm (2 inch) long and may have a greater lumen diameter than that of the ileum. It runs antimesenterically and has its own blood supply. It is a remnant of the connection from the yolk sac to the small intestine present during embryonic development. It is a true diverticulum, consisting of all 3 layers of the bowel wall which are mucosa, submucosa and muscularis propria.As the vitelline duct is made up of pluripotent cell lining, Meckels diverticulum may harbor abnormal tissues, containing embryonic remnants of other tissue types. Jejunal, duodenal mucosa or Brunners tissue were each found in 2% of ectopic cases. Heterotopic rests of gastric mucosa and pancreatic tissue are seen in 60% and 6% of cases respectively. Heterotopic means the displacement of an organ from its normal anatomic location. Inflammation of this Meckels diverticulum may mimic appendicitis. Therefore, during appendectomy, ileum should be checked for the presence of Meckels diverticulum, if it is found to be present it should be removed along with appendix.A memory aid is the rule of 2s:
2% (of the population)
2 feet (proximal to the ileocecal valve)
2 inches (in length)
2 types of common ectopic tissue (gastric and pancreatic)
2 years is the most common age at clinical presentation
2:1 male:female ratioHowever, the exact values for the above criteria range from 0.2–5 (for example, prevalence is probably 0.2–4%).It can also be present as an indirect hernia, typically on the right side, where it is known as a "Hernia of Littré". A case report of strangulated umbilical hernia with Meckels diverticulum has also been published in the literature. Furthermore, it can be attached to the umbilical region by the vitelline ligament, with the possibility of vitelline cysts, or even a patent vitelline canal forming a vitelline fistula when the umbilical cord is cut. Torsions of intestine around the intestinal stalk may also occur, leading to obstruction, ischemia, and necrosis.
Diagnosis
A technetium-99m (99mTc) pertechnetate scan, also called Meckel scan or nuclear scintigraphy scan, is the investigation of choice to diagnose Meckels diverticula in children. This scan detects gastric mucosa; since approximately 50% of symptomatic Meckels diverticula have ectopic gastric or pancreatic cells contained within them, this is displayed as a spot on the scan distant from the stomach itself. In children, this scan is highly accurate and noninvasive, with 95% specificity and 85% sensitivity; however, in adults the test is only 9% specific and 62% sensitive.
Patients with these misplaced gastric cells may experience peptic ulcers as a consequence. Therefore, other tests such as colonoscopy and screenings for bleeding disorders should be performed, and angiography can assist in determining the location and severity of bleeding. Colonoscopy might be helpful to rule out other sources of bleeding but it is not used as an identification tool. Angiography might identify brisk bleeding in patients with Meckels diverticulum.Ultrasonography could demonstrate omphaloenteric duct remnants or cysts. Computed tomography (CT scan) might be a useful tool to demonstrate a blind ended and inflamed structure in the mid-abdominal cavity, which is not an appendix.In asymptomatic patients, Meckels diverticulum is often diagnosed as an incidental finding during laparoscopy or laparotomy.
Treatment
Treatment is surgical, potentially with a laparoscopic resection. In patients with bleeding, strangulation of bowel, bowel perforation or bowel obstruction, treatment involves surgical resection of both the Meckels diverticulum itself along with the adjacent bowel segment, and this procedure is called a "small bowel resection". In patients without any of the aforementioned complications, treatment involves surgical resection of the Meckels diverticulum only, and this procedure is called a simple diverticulectomy.With regards to asymptomatic Meckels diverticulum, some recommend that a search for Meckels diverticulum should be conducted in every case of appendectomy/laparotomy done for acute abdomen, and if found, Meckels diverticulectomy or resection should be performed to avoid secondary complications arising from it.
Epidemiology
Meckels diverticulum occurs in about 2% of the population. Prevalence in males is 3–5 times higher than in females. Only 2% of cases are symptomatic, which usually presents among children at the age of 2.Most cases of Meckels diverticulum are diagnosed when complications manifest or incidentally in unrelated conditions such as laparotomy, laparoscopy or contrast study of the small intestine. Classic presentation in adults includes intestinal obstruction and inflammation of the diverticulum (diverticulitis). Painless rectal bleeding most commonly occurs in toddlers.Inflammation in the ileal diverticulum has symptoms that mimic appendicitis, therefore its diagnosis is of clinical importance. Detailed knowledge of the pathophysiological properties is essential in dealing with the life-threatening complications of Meckels diverticulum.
References
External links
Meckels Diverticulum at eMedicine |
Foreign body in alimentary tract | One of the most common locations for a foreign body is the alimentary tract. It is possible for foreign bodies to enter the from the mouth, or from the rectum.The objects most commonly swallowed by children are coins. Meat impaction, resulting in esophageal food bolus obstruction is more common in adults. Swallowed objects are more likely to lodge in the esophagus or stomach than in the pharynx or duodenum.
Diagnosis
If the person who swallowed the foreign body is doing well, usually an x-ray image will be taken which will show any metal objects, and this will be repeated a few days later to confirm that the object has passed all the way through the digestive system. Also it needs to be confirmed that the object is not stuck in the airways, in the bronchial tree.
Treatment
Most objects that are swallowed will, if they have passed the pharynx, pass all the way through the gastrointestinal tract unaided. However, sometimes an object becomes arrested (usually in the terminal ileum or the rectum) or a sharp object penetrates the bowel wall. If the foreign body causes problems like pain, vomiting or bleeding it must be removed.Swallowed batteries can be associated with additional damage, with mercury poisoning (from mercury batteries) and lead poisoning (from lead batteries) presenting important risks.While swallowed coins typically traverse the alimentary tract without further incident, care must be taken to monitor patients, as reaction of the metals in the coin with gastric acid and other digestive juices may produce various toxic compounds if the coin remains within the alimentary tract for a prolonged period of time.Endoscopic foreign body retrieval is the first-line treatment for removal of a foreign body from the alimentary tract.Glucagon has been used to treat esophageal foreign bodies, with the intent that it relaxes the smooth muscle of the lower esophageal spincter to allow the foreign body to pass into the stomach. However, evidence does not support a benefit of treatment with glucagon, and its use may result in side effects.
See also
101 Things Removed from the Human Body, 2003 British documentary detailing unusual foreign objects located and removed from patients
Bezoar
Rectal foreign body
References
== External links == |
Adhesive capsulitis of the shoulder | Adhesive capsulitis, also known as frozen shoulder, is a condition associated with shoulder pain and stiffness. It is a common shoulder ailment that is marked by pain and a loss of range of motion, particularly in external rotation. There is a loss of the ability to move the shoulder, both voluntarily and by others, in multiple directions. The shoulder itself, however, does not generally hurt significantly when touched. Muscle loss around the shoulder may also occur. Onset is gradual over weeks to months. Complications can include fracture of the humerus or biceps tendon rupture.The cause in most cases is unknown. The condition can also occur after injury or surgery to the shoulder. Risk factors include diabetes and thyroid disease. The underlying mechanism involves inflammation and scarring. The diagnosis is generally based on a persons symptoms and a physical exam. The diagnosis may be supported by an MRI. Adhesive capsulitis has been linked to diabetes and hypothyroidism, according to research. Adhesive capsulitis was five times more common in diabetic patients than in the control group, according to a meta-analysis published in 2016.The condition often resolves itself over time without intervention but this may take several years. While a number of treatments, such as NSAIDs, physical therapy, steroids, and injecting the shoulder at high pressure, may be tried, it is unclear what is best. Surgery may be suggested for those who do not get better after a few months. About 4% of people are affected. It is more common in people 40–60 years of age and in women.
Signs and symptoms
Symptoms include shoulder pain and limited range of motion although these symptoms are common in many shoulder conditions. An important symptom of adhesive capsulitis is the severity of stiffness that often makes it nearly impossible to carry out simple arm movements. Pain due to frozen shoulder is usually dull or aching and may be worse at night and with any motion.The symptoms of primary frozen shoulder have been described as having three or four stages. Sometimes a prodromal stage is described that can be present up to three months prior to the shoulder freezing. During this stage people describe sharp pain at end ranges of motion, achy pain at rest, and sleep disturbances.
Stage one: The "freezing" or painful stage, which may last from six weeks to nine months, and in which the patient has a slow onset of pain. As the pain worsens, the shoulder loses motion.
Stage two: The "frozen" or adhesive stage is marked by a slow improvement in pain but the stiffness remains. This stage generally lasts from four to twelve months.
Stage three: The "thawing" or recovery, when shoulder motion slowly returns toward normal. This generally lasts from 5 to 26 months.Physical exam findings include restricted range of motion in all planes of movement in both active and passive range of motion. This contrasts with conditions such as shoulder impingement syndrome or rotator cuff tendinitis in which the active range of motion is restricted but passive range of motion is normal. Some exam maneuvers of the shoulder may be impossible due to pain.
Causes
The causes of adhesive capsulitis are incompletely understood; however, there are several factors associated with higher risk. Risk factors for secondary adhesive capsulitis include injury or surgery leading to prolonged immobility. Risk factors for primary, or idiopathic adhesive capsulitis include many systemic diseases, such as diabetes mellitus, stroke, lung disease, connective tissue diseases, thyroid disease, heart disease, autoimmune disease, and Dupuytrens contracture. Both type 1 diabetes and type 2 diabetes are risk factors for the condition.
Primary
Primary adhesive capsulitis, also known as idiopathic adhesive capsulitis, occurs with no known trigger. It is more likely to develop in the non-dominant arm.
Secondary
Adhesive capsulitis is called secondary when it develops after an injury or surgery to the shoulder.
Pathophysiology
The underlying pathophysiology is incompletely understood, but is generally accepted to have both inflammatory and fibrotic components. The hardening of the shoulder joint capsule is central to the disease process. This is the result of scar tissue (adhesions) around the joint capsule. There also may be a reduction in synovial fluid, which normally helps the shoulder joint, a ball and socket joint, move by lubricating the gap between the humerus and the socket in the shoulder blade. In the painful stage (stage I), there is evidence of inflammatory cytokines in the joint fluid. Later stages are characterized by dense collagenous tissue in the joint capsule.Under the microscope, the appearance of the affected shoulder joint capsule tissue is similar to the appearance of the tissue that restricts finger movement in Dupuytrens contracture.
Diagnosis
Adhesive capsulitis can be diagnosed by history and physical exam. It is often a diagnosis of exclusion, as other causes of shoulder pain and stiffness must first be ruled out. On physical exam, adhesive capsulitis can be diagnosed if limits of the active range of motion are the same or similar to the limits to the passive range of motion. The movement that is most severely inhibited is external rotation of the shoulder.Imaging studies are not required for diagnosis, but may be used to rule out other causes of pain. Radiographs will often be normal, but imaging features of adhesive capsulitis can be seen on ultrasound or non-contrast MRI. Ultrasound and MRI can help in diagnosis by assessing the coracohumeral ligament, with a width of greater than 3 mm being 60% sensitive and 95% specific for the diagnosis. Shoulders with adhesive capsulitis also characteristically fibrose and thicken at the axillary pouch and "rotator interval", best seen as a dark signal on T1 sequences with edema and inflammation on T2 sequences. A finding on ultrasound associated with adhesive capsulitis is hypoechoic material surrounding the long head of the biceps tendon at the rotator interval, reflecting fibrosis. In the painful stage, such hypoechoic material may demonstrate increased vascularity with Doppler ultrasound.Grey-scale ultrasound can play a key role in timely diagnosis of adhesive capsulitis due to its high sensitivity and specificity. It is also widely available, convenient, and cost efficient. Thickening in the coracohumeral ligament, inferior capsule/ axillary recess capsule, and rotator interval abnormality, as well as restriction in range of motion in the shoulder can be detected using ultrasound. The range of motion is prohibited due to scapulohumeral rhythm changes occurring in the shoulder joint. The altered scapular kinematics can restrict anterior and posterior tilting, downward rotation and depression as well as external rotation. All of these restrictions lead the scapula to be excessively upwardly rotated. The restriction of the scapular posterior tilt is due to tightness in the lower serratus anterior, anterior capsule and the pectoralis minor. Downward rotation and depression are restricted due to the tightness of the rhomboids, upper trapezius and the superior capsule. Respective sensitivity values were 64.4, 82.1, 82.6, and 94.3, and respective specificity levels were 88.9, 95.7, 93.9, and 90.9.
Management
Management of this disorder focuses on restoring joint movement and reducing shoulder pain, involving medications, occupational therapy, physical therapy, or surgery. Treatment may continue for months; there is no strong evidence to favor any particular approach. The main treatment for adhesive capsulitis is a trial of conservative therapies, including analgesia, exercise, physiotherapy, oral nonsteroidal anti-inflammation drugs, and intra-articular corticosteroid injections.Medications such as NSAIDs can be used for pain control. Corticosteroids are used in some cases either through local injection or systemically. In the short term, intra-articular corticosteroid injections were more effective in pain alleviation. Unfortunately, this pain reduction was not long-lasting. In both the short and long term, intra-articular corticosteroid injections improved passive range of motion (ROM). Oral steroids may provide short-term benefits in range of movement and pain but have side effects such as hyperglycemia. Steroid injections compared to physical therapy have a similar effect in improving shoulder function and decreasing pain. The benefits of steroid injections appear to be short-term. The results of this study imply that using an IA corticosteroid early in individuals with frozen shoulder who have had it for less than a year had a better prognosis. To increase the chances of recovery, this treatment should be combined with a home exercise program. Oral corticosteroids should not be used consistently to treat adhesive capsulitis because of the dangers associated with long-term use and the lack of long-term benefit.The role for occupational therapy (OT) in adhesive capsulitis is dependent on restrictions on daily activities, pain, and limitations the person is experiencing; an occupational therapist usually makes an initial evaluation. Pain and limited joint mobility are primary complaints that impact a persons daily life. OT will usually start by using a preparatory method, like physical agent modalities to be used as part of a comprehensive occupational therapy program. The occupational therapist may teach strengthening exercises and provide a home exercise program. The goal of OT would be for the client to resume meaningful functional daily activities.The role for physical therapy in adhesive capsulitis is not settled. Physical therapy is used as an initial treatment in adhesive capsulitis with the use of range of motion (ROM) exercises and manual therapy techniques to restore range and function. A low-dose corticosteroid injection and home exercise programs in those with symptoms for less than 6 months may be useful. There may be some benefit with manual therapy and stretching as part of a rehabilitation program, but, due to the time required, such use should be carefully considered. Physical therapists may utilize joint mobilization directly at the glenohumeral joint to decrease pain, increase function, and increase range of motion as another form of treatment. There are some studies that have shown that intensive passive stretching can promote healing. Additional interventions include modalities such as ultrasound, shortwave diathermy, laser therapy and electrical stimulation. Another osteopathic technique used to treat the shoulder is called the Spencer technique. Mobilization techniques and other therapeutic modalities are most commonly used by physical therapists; however, there is not strong evidence that these methods can change the course of the disease.If these measures are unsuccessful, more aggressive interventions such as surgery can be trialed. Manipulation of the shoulder under general anesthesia to break up the adhesions is sometimes used. Hydrodilatation or distension arthrography is controversial. However, some studies show that arthrographic distension may play a positive role in reducing pain and improve range of movement and function. Surgery to cut the adhesions (capsular release) may be indicated in prolonged and severe cases; the procedure is usually performed by arthroscopy. Surgical evaluation of other problems with the shoulder, e.g., subacromial bursitis or rotator cuff tear, may be needed. Resistant adhesive capsulitis may respond to open release surgery. This technique allows the surgeon to find and correct the underlying cause of restricted glenohumeral movement such as contracture of coracohumeral ligament and rotator interval. Physical therapy may achieve improved results after surgical procedure and postoperative rehabilitation.Physical therapy is an effective procedure that provides essential exercises to improve range of motion. Patients who receive the proper training from an authorized physiotherapist can perform these exercises independently at home. The physiotherapy treatment for frozen shoulder will include manual therapy to mobilize the affected joints and release their muscles. "Pendulum stretch", "finger walk", "towel stretch", "armpit stretch" and "crossbody reach" are some essential mobility exercises specifically designed to improve the shoulder mobility of patients with frozen shoulders. There are also limited case reports of therapy utilizing vibration platforms obtaining fast results, not as a post-operative aid, but instead of surgery.Acupuncture has been found to decrease pain levels and improve shoulder function and range of motion, particularly in shoulder flexion. Acupuncture combined with shoulder exercises was found to be more effective than shoulder exercise alone. However, further studies with longer follow-up times are needed to assess mid- and long term benefits.
Prognosis
Most cases of adhesive capsulitis are self limiting, but may take 1 to 3 years to fully resolve. Pain and stiffness may not completely resolve in 20 to 50 per cent of affected people.
Epidemiology
Adhesive capsulitis newly affects approximately 0.75% to 5.0% percent of people a year. Rates are higher in people with diabetes (10–46%). Following breast surgery, some known complications include loss of shoulder range of motion (ROM) and reduced functional mobility in the involved arm. Occurrence is rare in children and people under 40. with the highest prevalence between 40 and 70 years of age. The condition is more common in women than in men (70% of patients are women aged 40–60). People with diabetes, stroke, lung disease, rheumatoid arthritis, or heart disease are at a higher risk for frozen shoulder. Symptoms in people with diabetes may be more protracted than in the non-diabetic population.
See also
Calcific tendinitis
Milwaukee shoulder syndrome
References
== External links == |
Takayasus arteritis | Takayasus arteritis (TA), also known as aortic arch syndrome, nonspecific aortoarteritis, and pulseless disease, is a form of large vessel granulomatous vasculitis with massive intimal fibrosis and vascular narrowing, most commonly affecting young or middle-aged women of Asian descent, though anyone can be affected. It mainly affects the aorta (the main blood vessel leaving the heart) and its branches, as well as the pulmonary arteries. Females are about 8–9 times more likely to be affected than males.Those with the disease often notice symptoms between 15 and 30 years of age. In the Western world, atherosclerosis is a more frequent cause of obstruction of the aortic arch vessels than Takayasus arteritis. Takayasus arteritis is similar to other forms of vasculitis, including giant cell arteritis which typically affects older individuals. Due to obstruction of the main branches of the aorta, including the left common carotid artery, the brachiocephalic artery, and the left subclavian artery, Takayasus arteritis can present as pulseless upper extremities (arms, hands, and wrists with weak or absent pulses on the physical examination) which may be why it is also commonly referred to as the "pulseless disease." Involvement of renal arteries may lead to a presentation of renovascular hypertension.
Sign and symptoms
Some people develop an initial "inflammatory phase" characterized by systemic illness with signs and symptoms of malaise, fever, night sweats, weight loss, joint pain, fatigue, and fainting. Fainting may result from subclavian steal syndrome or carotid sinus hypersensitivity. There is also often anemia and marked elevation of the ESR or C-reactive protein (nonspecific markers of inflammation). The initial "inflammatory phase" is often followed by a secondary "pulseless phase". The "pulseless phase" is characterized by vascular insufficiency from intimal narrowing of the vessels manifesting as arm or leg claudication, renal artery stenosis causing hypertension, and neurological manifestations due to decreased blood flow to the brain.Of note is the function of renal artery stenosis in the causation of high blood pressure: Normally perfused kidneys produce a proportionate amount of a substance called renin. Stenosis of the renal arteries causes hypoperfusion (decreased blood flow) of the juxtaglomerular apparatus, resulting in exaggerated secretion of renin, and high blood levels of aldosterone, eventually leading to water and salt retention and high blood pressure. The neurological symptoms of the disease vary depending on the degree; the nature of the blood vessel obstruction; and can range from lightheadedness to seizures (in severe cases). One rare, important feature of the Takayasus arteritis is ocular involvement in form of visual field defects, vision loss, or retinal hemorrhage. Some individuals with Takayasus arteritis may present with only late vascular changes, without a preceding systemic illness. In the late stage, weakness of the arterial walls may give rise to localized aneurysms. As with all aneurysms, the possibility of rupture and vascular bleeding is existent and requires monitoring. In view of the chronic process and good collateral development, Raynauds phenomenon or digital gangrene are very rare in Takayasu arteritis. A rare complication of this condition are coronary artery aneurysms.
Laser Doppler imaging by near-infrared digital holography can reveal characteristic blood flow waveforms in the central artery and vein of the retina in patients with vascular insufficiency who may exhibit a smooth systo-diastolic pulse in the central retinal artery. This technique enables non invasive functional microangiography by high-contrast measurement of endoluminal blood flow profiles in vessels in the posterior segment of the eye with a spatial resolution comparable to state-of-the-art indocyanine green angiography.
Pathophysiology
Although the cause of Takayasu arteritis is unknown, the condition is characterized by segmental and patchy granulomatous inflammation of the aorta and its major derivative branches. This inflammation leads to arterial stenosis, thrombosis, and aneurysms. There is irregular fibrosis of the blood vessels due to chronic vasculitis, leading to sometimes massive intimal fibrosis (fibrosis of the inner section of the blood vessels). Prominent narrowing due to inflammation, granuloma, and fibrosis is often seen in arterial studies such as magnetic resonance angiography (MRA), computed tomography angiography (CTA), or arterial angiography (DSA).
Genetics
The genetic contribution to the pathogenesis of Takayasus arteritis is supported by the genetic association with HLA-B∗52. A 2013 large collaborative study uncovered multiple additional susceptibility loci for this disease, increasing its number of genetic loci to five risk loci across the genome. About 200,000 genetic variants were genotyped in two ethnically divergent Takayasus arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. The study identified and confirmed two independent susceptibility loci within the HLA region (r2 < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10-16) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10-9; and rs189754752, OR = 2.47, p = 4.22 × 10-9). In addition, a genetic association was identified and confirmed between Takayasus arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10-12). The risk allele at this locus results in increased mRNA expression of FCGR2A. In addition, a genetic association between IL12B and Takayasu arteritis was established (rs56167332, OR = 1.54, p = 2.18 × 10-8). A fifth genetic locus for the disease in an intergenic region on chromosome 21q22 downstream of PSMG1 was revealed (P=4.39X10-7). A recent genome-wide association study (GWAS) identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10(-9)), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10(-8)), and the intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10(-10)). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 × 10(-8)). In addition, this study identified additional candidate susceptibility genes with suggestive levels of association (P < 1 × 10(-5)) including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B.Another gene associated with this condition is MLX (Max-like protein X)
Diagnosis
Diagnosis is based on the demonstration of vascular lesions in large and middle-sized vessels on angiography, CT scan, magnetic resonance angiography or FDG PET. Seeing abnormal diffuse arterial wall thickening, the macaroni sign, with ultrasound is highly suggestive of the condition. FDG PET can help in diagnosis of active inflammation not just in patients with active Takayasu arteritis prior to treatment but also in addition in relapsing patients receiving immunosuppressive agents.Contrast angiography has been the gold standard. The earliest detectable lesion is a local narrowing or irregularity of the lumen. This may develop into stenosis and occlusion. The characteristic finding is the presence of "skip lesions," where stenosis or aneurysms alternate with normal vessels. Angiography provides information on vessel anatomy and patency but does not provide information on the degree of inflammation in the wall.The age at onset helps to differentiate Takayasus arteritis from other types of large vessel vasculitis. For example, Takaysus arteritis has an age of onset of <40 years, while giant cell arteritis has an age of onset >60 years.Takayasu arteritis is not associated with ANCA, rheumatoid factor, ANA, and anticardiolipin antibodies.
Treatments
Most people with Takayasu’s arteritis respond to steroids such as prednisone. The usual starting dose is approximately 1 milligram per kilogram of body weight per day (for most people, this is approximately 60 milligrams a day). Because of the significant side effects of long-term high-dose prednisone use, the starting dose is tapered over several weeks to a dose that controls symptoms while limiting the side effects of steroids.Promising results are achieved with mycophenolate and tocilizumab. If treatment is not kept to a high standard, long-term damage or death can occur.Patients who do not respond to steroids may require revascularization, either via vascular bypass or angioplasty and stenting. Outcomes following revascularization vary depending on the severity of the underlying disease.
History
The first case of Takayasu’s arteritis was described in 1908 by Japanese ophthalmologist Mikito Takayasu at the Annual Meeting of the Japan Ophthalmology Society. Takayasu described a peculiar "wreathlike" appearance of the blood vessels in the back of the eye (retina). Two Japanese physicians at the same meeting (Drs. Onishi and Kagoshima) reported similar eye findings in individuals whose wrist pulses were absent.It is now known that the blood vessel malformations that occur in the retina are an angiogenic response to the arterial narrowings in the neck and that the absence of pulses noted in some people occurs because of narrowings of the blood vessels to the arms. The eye findings described by Takayasu are rarely seen in patients from North America and British Columbia.
References
BibliographyVinayakumar, Desabandhu; Sulaiman, Sherief; Bastian, Cicy; Rajasekharan, Sandeep (April 2017). "Transradial retrograde percutaneous transluminal angioplasty with stenting of long segment occlusion of subclavian artery". Journal of Cardiology Cases. 15 (4): 119–121. doi:10.1016/j.jccase.2016.12.002. PMC 6135029. PMID 30279756.
== External links == |
Depression in childhood and adolescence | Depression is a mental disorder characterized by prolonged unhappiness or irritability, accompanied by a constellation of somatic and cognitive signs and symptoms such as fatigue, apathy, sleep problems, loss of appetite, loss of engagement; low self-regard or worthlessness; difficulty concentrating or indecisiveness; or recurrent thoughts of death or suicide. Depression in childhood and adolescence is similar to adult major depressive disorder, although young sufferers may exhibit increased irritability or behavioral dyscontrol instead of the more common sad, empty, or hopeless feelings seen with adults. Children who are under stress, experiencing loss, or have other underlying disorders are at a higher risk for depression. Childhood depression is often comorbid with mental disorders outside of other mood disorders; most commonly anxiety disorder and conduct disorder. Depression also tends to run in families. In a 2016 Cochrane review cognitive behavior therapy (CBT), third wave CBT and interpersonal therapy demonstrated small positive benefits in the prevention of depression. Psychologists have developed different treatments to assist children and adolescents suffering from depression, though the legitimacy of the diagnosis of childhood depression as a psychiatric disorder, as well as the efficacy of various methods of assessment and treatment, remains controversial.
Base rates and prevalence
About 8% of children and adolescents suffer from depression. In 2016, 51 percent of students (teens) who visited a counseling center reported having anxiety, followed by depression (41 percent), relationship concerns (34 percent) and suicidal ideation (20.5 percent). Many students reported experiencing multiple conditions at once. Research suggests that the prevalence of children with Major Depressive Disorder in Western cultures ranges from 1.9% to 3.4% among primary school children. Amongst teenagers, up to 9% meet criteria for depression in a given moment and approximately 20% experience depression sometime during adolescence. Studies have also found that among children diagnosed with a depressive episode, there is a 70% rate of recurrence within five years. Furthermore, 50% of children with depression will have a recurrence at least once during their adulthood. While there is no gender difference in depression rates up until age 15, after that age the rate among women doubles compared to men. However, in terms of recurrence rates and symptom severity there is no gender difference. In an attempt to explain these findings, one theory asserts that preadolescent women on average have more risk factors for depression when compared to men. These risk factors then combine with the typical stresses and challenges of adolescent development to trigger the onset of depression. Depression in youth and adolescence is associated with a wide array of outcomes that can come later in life for the affected individual. Some of these outcomes include poor physical and mental health, trouble functioning socially, and suicide.
Suicidal intent
Like their adult counterparts, children and adolescent depression sufferers are at an increased risk of attempting or committing suicide. Suicide is the third leading cause of death among 15-to-19-year-olds. Adolescent males may be at an even higher risk of suicidal behavior when also presenting with a conduct disorder. In the 1990s, the National Institute of Mental Health (NIMH) found that up to 7% of adolescents who develop major depressive disorder may commit suicide as young adults. Such statistics demonstrate the importance of interventions by family and friends, the importance of early diagnosis, and treatment by medical staff, in order to prevent suicide amongst at-risk youth. However, some data showed an opposite conclusion. Most depression symptoms are reported more frequently by females; such as sadness (reported by 85.1% of women and 54.3% of men) and crying (approximately 63.4% of women and 42.9% of men). Women have a higher probability to experience depression than men with the prevalences of 19.2% and 13.5% respectively.
Risk factor
Risk factors for adolescent depression include female sex, a family history of depression, a personal history of trauma, family conflict, minority sexual orientation, or having a chronic medical illness. There tends to be higher prevalence rates and more severe symptoms in adolescent girls when compared to adolescent boys. These higher rates are also applicable in older adolescents when compared to younger adolescents. This may be due to hormonal fluctuations may that make adolescent women to be more vulnerable to depression. The fact that increased prevalence of depression correlates with hormonal changes in women, particularly during puberty, suggests that female hormones may be a trigger for depression. The gender gap in depression between adolescent men and women is mostly due to young womens lower levels of positive thinking, need for approval, and self-focusing negative conditions. Frequent exposure to victimization or bullying was related to high risks of depression, ideation and suicide attempts compared to those not involved in bullying. Nicotine dependence is also associated with depression, anxiety, and poor dieting, mostly in young men. Although causal direction has not been established, involvement in any sex or drug use is cause for concern. Children who develop major depression are more likely to have a family history of the disorder (often a parent who experienced depression at an early age) than patients with adolescent- or adult-onset depression. Adolescents with depression are also likely to have a family history of depression, though the correlation is not as high as it is for children.
Comorbidity
There is also a substantial comorbidity rate with depression in children with anxiety disorder, conduct disorder, and impaired social functioning. Particularly, there is a high comorbidity rate with anxiety, ranging from 15.9% to 75%. Conduct disorders also have a significant comorbidity with depression in children and adolescents with a rate of 23% in one longitudinal study. Beyond other clinical disorders, there is also an association between depression in childhood, poor psychosocial and academic outcomes, as well as a higher risk for substance abuse and suicide.The prevalence of psychiatric comorbidities during adolescence may vary by race and ethnicity.
Social causes
Adolescents are engaged in a search for identity and meaning in their lives. They have also been regarded as a unique group with a wide range of difficulties and problems in their transition to adulthood. Academic pressure, intrapersonal and interpersonal difficulties, death of loved ones, illnesses, and loss of relationships, have shown to be significant stressors in young people. While it is a normal part of development in adolescence to experience distressing and disabling emotions, there is an increasing incidence of mental illness globally. This is due mainly because of the breakdown in traditional social and family structures. Depression is usually a response to life events such as relationship issues, financial problems, physical illness, bereavement, etc. Some people can become depressed for no obvious reason and their suffering is just as real as those reacting from life events. Psychological makeup can also play a role in vulnerability to depression. People who have low self-esteem, constantly view themselves and the world with pessimism, or are readily overwhelmed by stress, may be especially prone to depression. Community surveys find that women are more likely than men to say they are under stress. Other studies suggest that women are more likely than men to become depressed in response to a stressful event. Women are also more likely to experience certain kinds of severe stress such as child sexual abuse, adult sexual assaults, and domestic violence.
Diagnosis
According to the DSM-IV, children must exhibit either a depressed mood or a loss of interest/pleasure in normal activities. These activities may include school, extracurricular activities, or peer interactions. Depressive moods in children can be expressed as being unusually irritable. These expressions may be displayed by "acting out," behaving recklessly, or reacting with anger/hostility. Children who do not have the cognitive or language development to properly express mood states can also exhibit their mood through physical complaints such as showing sad facial expressions (frowning) and poor eye contact. A child must also exhibit four other symptoms in order to be clinically diagnosed. However, according to the Omnigraphics Health References Series: Depression Sourcebook, Third Edition, a more calculated evaluation must be given by a medical or mental health professional such as a physiologist or psychiatrist. Following the bases of symptoms, signs include but are not limited to, an unusual change in sleep habits (for example, trouble sleeping or overly indulged sleeping hours); a significant amount of weight gain/loss by the lack or excessive eating; experiencing aches/pains for no apparent reason that can found; and an inability to concentrate on tasks or activities. If these symptoms are present for a period of two weeks or longer, it is safe to make the assumption that the child, or anybody else for that matter, is falling into major depression.
Assessment
It is recommended by the American Academy of Pediatrics that primary care providers screen children and adolescents for depression with validated screening tools, self-rated, or clinician-administered ones, once per year. However, there is no universally recommended screening tool and the clinician is free to choose from various validated ones based on personal preference. Once the screening tool indicates the potential presence of a depression, a thorough diagnostic assessment is recommended. In early 2016, the USPSTF released an updated recommendation for the screening of adolescents ages 12 to 18 years for major depressive disorder (MDD). Appropriate treatment and follow-up should be provided for adolescents who screen positive.
Correlation between adolescent depression and adulthood obesity
According to research conducted by Laura P. Richardson et al., major depression occurred in 7% of the cohort during early adolescence (11, 13, and 15 years of age) and 27% during late adolescence (18 and 21 years of age). At 26 years of age, 12% of study members were obese. After adjusting for each individuals baseline body mass index (calculated as the weight in kilograms divided by the square of height in meters), depressed late-adolescent girls were at a greater than 2-fold increased risk for obesity in adulthood compared with their non-depressed female peers (relative risk, 2.32; 95% confidence interval, 1.29-3.83). A dose-response relationship between the number of episodes of depression during adolescence and the risk for adult obesity was also observed in female subjects. The association was not observed for late adolescent boys or for early adolescent boys or girls.
Correlation between child depression and adolescent cardiac risks
According to research by RM Carney et al., any history of child depression influences the occurrence of adolescent cardiac risk factors, even if individuals no longer suffer from depression. They are much more likely to develop heart disease as adults.
Distinction from major depressive disorder in adults
While there are many similarities to adult depression, especially in expression of symptoms, there are many differences that create a distinction between the two diagnoses. Research has shown that when a childs age is younger at diagnosis, typically there will be a more noticeable difference in the expression of symptoms from the classic signs in adult depression. One major difference between the symptoms exhibited in adults and in children is that children have higher rates of internalization; therefore, symptoms of child depression are more difficult to recognize. One major cause of this difference is that many of the neurobiological effects in the brain of adults with depression are not fully developed until adulthood. Therefore, in a neurological sense children and adolescents express depression differently.
Treatment
Clinicians often divide treatment into three phases: In the acute phase, which usually lasts six to 12 weeks, the goal is to relieve symptoms. In the continuation phase, which can last for several more months, the goal is to maximize improvements. At this stage, clinicians may make adjustments to the dose of a medication. In the maintenance phase, the aim is to prevent relapse. Sometimes the dose of a drug is lowered at this stage, or psychotherapy carries more of the weight. Unique differences in life experience, temperament, and biology make treatment a complex matter; no single treatment is right for everyone. Psychotherapy and medications are commonly used treatment options. In some research, adolescents showed a preference for psychotherapy rather than antidepressant medication for treatment. For adolescents, cognitive behavioral therapy and interpersonal therapy have been empirically supported as effective treatment options. Studies have shown that a combination of psychotherapy and medication is the most effective treatment. Pediatric massage therapy may have an immediate effect on a childs emotional state at the time of the massage, but sustained effects on depression have not been identified.Treatment programs have been developed that help reduce the symptoms of depression. These treatments focus on immediate symptom reduction by concentrating on teaching children skills pertaining to primary and secondary control. While much research is still needed to confirm this treatment programs efficacy, one study showed it to be effective in children with mild or moderate depressive symptoms.Identification and treatment of concomitant parental depression is associated with improved responses to treatment in adolescents with depression as having a parent with depression may negatively affect a young persons response to therapy as well as their outlook on depression.
Talk therapy
There are a variety of common types of talk therapy. These can assist people to live more fully, help improve good feelings, and have a better life. Effective psychotherapy for children always includes parent involvement, teaching skills that are practiced at home or at school, and measures of progress that are tracked over time. In many types, men are encouraged to open up more emotionally and communicate their personal distress, while women are encouraged to be assertive of their own strengths. Often psychotherapy teaches coping skills while allowing the teens or children to explore feelings and events in a safe environment.Severe depression, low global functioning, higher scores on suicidality scales, co-existing anxiety, distorted thought processes and feelings of hopelessness are characteristics of adolescent depression that are associated with a poor response to psychotherapy. If there is concomitant family conflict then interpersonal therapy is more effective than cognitive therapy.
Talk therapy is one of the best forms of therapy, as the depressed person finds a solace in the one whom he/she is talking to. Through this means, the counselor is able to know and understood fully the mind of the depressed individual. Many people are depressed and simply needs the right person to talk to. This is where the talk therapy comes in as a very helpful solution to those who are in need of it.
Cognitive therapy
Cognitive therapy aims to change harmful ways of thinking and reframe negative thoughts in a more positive way. Aims of cognitive therapy include various steps of patient learning. During cognitive behavioral therapy, children and adolescents with depression work with therapists to learn about their diagnosis, how to identify and reshape negative thought patterns, and how to increase engagement in enjoyable activities. CBT-trained therapists work with individuals, families, and groups. The approach can be used to help anyone irrespective of ability, culture, race, gender, or sexual preference. It can be applied with or without concurrent psychopharmacological medication, depending on the severity or nature of each patients problem. The duration of cognitive-behavioral therapy varies, although it typically is thought of as one of the briefer psychotherapeutic treatments. Especially in research settings, duration of CBT is usually short, between 10 and 20 sessions. In routine clinical practice, duration varies depending on patient comorbidity, defined treatment goals, and the specific conditions of the health care system.
Behavioral therapy
Behavioral therapy helps change harmful ways of acting and gain control over behavior which is causing problems.
Interpersonal therapy
Interpersonal therapy helps one learn to relate better with others, express feelings, and develop better social skills. Interpersonal therapy helps the patient identify and cope through reoccurring conflicts within their relationships. Typically, the therapy will focus on one of the four specific problems, grief, social isolation, conflicts about roles and social expectations, or the effect of a major life change.
Family therapy
The principles of group dynamics are relevant to family therapists who must not only work with individuals, but with entire family systems. Family counseling can help families understand how a childs individual challenges may affect relations with parents and siblings and vice versa.Therapists strive to understand not just what the group members say, but how these ideas are communicated (process). Therapists can help families improve the way they relate and thus enhance their own capacity to deal with the content of their problems by focusing on the process of their discussions. Virginia Satir expanded on the concept of how individuals behave and communicate in groups by describing several family roles that can serve to stabilize expected characteristic behavior patterns in a family. For instance, if one child is considered to be a "rebel child", a sibling may take on the role of the "good child" to alleviate some of the stress in the family. This concept of role reciprocity is helpful in understanding family dynamics because the complementary nature of roles makes behaviors more resistant to change. It is good to understand that most depression in children and adolescents begin right in the home. Parents are advised to treat their children properly and learn to fully understand their child/children, and also give them adequate attention, love, care and quick response to their useful needs. Parents and Guardians should detest ignoring their children or wards and give them attention because neglect can lead to shame, loss of self-confidence, frustration and finally depression.
Antidepressants
As of 2021, the FDA has approved the selective serotonin reuptake inhibitors (SSRIs) fluoxetine and escitalopram for the treatment of depression in adolescents but other SSRIS or serotonin norepinephrine reuptake inhibitors (SNRIs) are often used off label for treatment. Clinicians usually recommend one of these SSRIs as a first line treatment for depression in adolescence. These drugs act on the serotonin system that affects mood, arousal, anxiety, impulses, and aggression. SSRIs also appear to indirectly influence other neurotransmitter systems, including those involving norepinephrine and dopamine. Some possible adverse reactions of SSRIs include headache, gastrointestinal side effects, dry mouth, sedation or insomnia and activation. Activation refers to a state of psychomotor agitation that includes symptoms of insomnia, disinhibition and restlessness that may result in discontinuation of a medication. There is a rare risk of suicidal thoughts or behaviors with SSRIs especially when treatment is started or the dose is increased, with the rate being up to 0.7% as compared to placebo in early meta analyses of SSRIs in the treatment of adolescent depression. This led the FDA to issue a black box warning regarding this risk. Once remission is achieved, the medications are continued for at least 6 to 12 months and then there is consideration of discontinuing them. Early or premature discontinuation of medications, prior to 6 to 12 months of having achieved remission, is associated with an increased risk of relapse of the depression.The combination of psychotherapy with medications has been shown to be more effective for the treatment of depression in adolescence than medications alone.Other medications can be added to SSRIs if a partial response is achieved and further improvement is needed; these agents include lithium, bupropion and atypical antipsychotics. These options are medications that work in different ways. Bupropion (Wellbutrin) works through the neurotransmitters norepinephrine and dopamine, while mirtazapine (Remeron) affects transmission of norepinephrine and serotonin. The drugs venlafaxine (Effexor) and duloxetine (Cymbalta) work in part by simultaneously inhibiting the reuptake of serotonin and norepinephrine. The oldest drugs on the market are not prescribed often, but may be a good option for some women. These include tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). TCAs may cause side effects like dry mouth, constipation, or dizziness. MAOIs can cause sedation, insomnia, dizziness, and weight gain. To avoid the risk of a rapid rise in blood pressure, people taking MAOIs must also avoid eating a substance called tyramine, found in yogurt, aged cheese, pickles, beer, and red wine. Some drug side effects subside with time, while others may lessen when a drug dose is lowered.
Research
Differences in the brains structure and function appear to be present in adolescents with depression though this may depend on age. Younger adolescents, mostly under the age of 18, with depression have shown greater white matter volume within frontal regions of the brain, greater cortical thickness in the anterior cingulate cortex and medial orbitofrontal cortex, as well as greater functional connectivity between cortico-limbic brain regions. Whereas older adolescents, mostly above the age of 18, appear to show lower cortical surface area in regions including the lingual, occipital gyri, as well as medial orbitofrontal and motor cortices. Results such as these have led to the hypothesis that the biological causes of depression may in part be neurodevelopmental, with its biological underpinnings forming early on in brain development.
History
Although antidepressants were used by child and adolescent psychiatrists to treat major depressive disorder, they were not always used in young people with a comorbid conduct disorder because of the risks of overdose in such a population. Tricyclic antidepressant were the predominant antidepressants used at that time in this population. With the advent of selective serotonin re-uptake inhibitors (SSRIs), child and adolescent psychiatrists probably began prescribing more anti-depressants in the comorbid conduct disorder/major depressive group because of the lower risk of serious harm in overdose. This raises the possibility that more effective treatment of these young people might also improve their outcomes in adult life. Although treatment rates are becoming more stable, there is a trend that suggests that little progress has been made in narrowing the mental health treatment gap for adolescent depression. The FDA has also placed a black box warning on using antidepressants, leading doctors to be hesitant on prescribing them to adolescents.
Controversies
Throughout the development and research of this disorder, controversies have emerged over the legitimacy of depression in childhood and adolescence as a diagnosis, the proper measurement and validity of scales to diagnose, and the safety of particular treatments.
Legitimacy as a diagnosis
In early research of depression in children, there was debate as to whether or not children could clinically fit the criteria for major depressive disorder. However, since the 1970s, it has been accepted among the psychological community that depression in children can be clinically significant. The more pertinent controversy in psychology today centers around the clinical significance of sub-threshold mood disorders. This controversy stems from the debate regarding the definition of the specific criteria for a clinically significant depressed mood in relation to the cognitive and behavioral symptoms. Some psychologists argue that the effects of mood disorders in children and adolescents that exist (but do not fully meet the criteria for depression) do not have severe enough risks. Children in this area of severity, they argue, should receive some sort of treatment since the effects could still be severe. However, since there has yet to be enough research or scientific evidence to support that children that fall within the area just shy of a clinical diagnosis require treatment, other psychologists are hesitant to support the dispensation of treatment.
Diagnosis controversy
In order to diagnose a child with depression, different screening measures and reports have been developed to help clinicians make a proper decision. However, the accuracy and effectiveness of certain measures that help psychologists diagnose children have come into question. Due to absence of strong evidence that screening children and adolescents for depression leads to improved mental health outcomes, it has been questioned whether it causes more harm than benefit. Questions have also surfaced about the safety and effectiveness of antidepressant medications.
Measurement reliability
The effectiveness of dimensional child self-report checklists has been criticized. Although literature has documented strong psychometric properties, other studies have shown a poor specificity at the top end of scales, resulting in most children with high scores not meeting the diagnostic criteria for depression. Another issue with reliability of measurement for diagnosis occurs in parent, teacher, and child reports. One study, which observed the similarities between child self-report and parent reports on the childs symptoms of depression, acknowledged that on more subjective symptom reports measures, the agreement was not significant enough to be considered reliable. Two self-report scales demonstrated an erroneous classification of 25% of children in both the depressed and controlled samples. A large concern in the use of self-report scales is the accuracy of the information collected. The main controversy is caused by uncertainty about how the data from these multiple informants can or should be combined to determine whether a child can be diagnosed with depression.
Treatment issues
The controversy over the use of antidepressants began in 2003 when Great Britains Department of Health stated that, based on data collected by the Medicines and Healthcare products Regulatory Agency, paroxetine (an antidepressant) should not be used on patients under the age of 18. Since then, the United States Food and Drug Administration (FDA) has issued a warning describing the increased risk of adverse effects of antidepressants used as treatment in those under the age of 18. The main concern is whether the risks outweigh the benefits of the treatment. In order to decide this, studies often look at the adverse effects caused by the medication in comparison to the overall symptom improvement. While multiple studies have shown an improvement or efficacy rate of over 50%, the concern of severe side effects – such as suicidal ideation or suicidal attempts, worsening of symptoms, or increase in hostility – are still concerns when using antidepressants. However, an analysis of multiple studies argues that while the risk of suicidal ideation or attempt is present, the benefits significantly outweigh the risks. Due to the variability of these studies, it is currently recommended that if antidepressants are chosen as a method of treatment for children or adolescents, the clinician monitor closely for adverse symptoms, since there is still no definitive answer on why they are depressed.
== References == |
Alcoholism | Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word alcoholism, it is not a recognized diagnostic entity. Predominant diagnostic classifications are alcohol use disorder (DSM-5) or alcohol dependence (ICD-11); these are defined in their respective sources.Excessive alcohol use can damage all organ systems, but it particularly affects the brain, heart, liver, pancreas and immune system. Alcoholism can result in mental illness, delirium tremens, Wernicke–Korsakoff syndrome, irregular heartbeat, an impaired immune response, liver cirrhosis and increased cancer risk. Drinking during pregnancy can result in fetal alcohol spectrum disorders. Women are generally more sensitive than men to the harmful effects of alcohol, primarily due to their smaller body weight, lower capacity to metabolize alcohol, and higher proportion of body fat. In a small number of individuals, prolonged, severe alcohol misuse ultimately leads to cognitive impairment and frank dementia.
Environment and genetics are two factors in the risk of development of alcoholism, with about half the risk attributed to each. Stress and associated disorders, including anxiety, are key factors in the development of alcoholism as alcohol consumption can temporarily reduce dysphoria. Someone with a parent or sibling with an alcohol use disorder is three to four times more likely to develop an alcohol use disorder themselves, but only a minority of them do. Environmental factors include social, cultural and behavioral influences. High stress levels and anxiety, as well as alcohols inexpensive cost and easy accessibility, increase the risk. People may continue to drink partly to prevent or improve symptoms of withdrawal. After a person stops drinking alcohol, they may experience a low level of withdrawal lasting for months. Medically, alcoholism is considered both a physical and mental illness. Questionnaires are usually used to detect possible alcoholism. Further information is then collected to confirm the diagnosis.Prevention of alcoholism may be attempted by reducing the experience of stress and anxiety in individuals. It can be attempted by regulating and limiting the sale of alcohol (particularly to minors), taxing alcohol to increase its cost, and providing education and treatment.Treatment of alcoholism may take several forms. Due to medical problems that can occur during withdrawal, alcohol cessation should be controlled carefully. One common method involves the use of benzodiazepine medications, such as diazepam. These can be taken while admitted to a health care institution or individually. The medications acamprosate, disulfiram or naltrexone may also be used to help prevent further drinking. Mental illness or other addictions may complicate treatment. Various forms of individual or group therapy or support groups are used to attempt to keep a person from returning to alcoholism. One support group is Alcoholics Anonymous.The World Health Organization has estimated that as of 2016, there were 380 million people with alcoholism worldwide (5.1% of the population over 15 years of age). As of 2015 in the United States, about 17 million (7%) of adults and 0.7 million (2.8%) of those age 12 to 17 years of age are affected. Alcoholism is most common among males and young adults. Geographically, it is least common in Africa (1.1% of the population) and has the highest rates in Eastern Europe (11%). Alcoholism directly resulted in 139,000 deaths in 2013, up from 112,000 deaths in 1990. A total of 3.3 million deaths (5.9% of all deaths) are believed to be due to alcohol. Alcoholism reduces a persons life expectancy by approximately ten years. Many terms, some slurs and others informal, have been used to refer to people affected by alcoholism; the expressions include tippler, drunkard, dipsomaniac and souse. In 1979, the World Health Organization discouraged the use of alcoholism due to its inexact meaning, preferring alcohol dependence syndrome.
Signs and symptoms
The risk of alcohol dependence begins at low levels of drinking and increases directly with both the volume of alcohol consumed and a pattern of drinking larger amounts on an occasion, to the point of intoxication, which is sometimes called binge drinking.
Long-term misuse
Alcoholism is characterised by an increased tolerance to alcohol – which means that an individual can consume more alcohol – and physical dependence on alcohol, which makes it hard for an individual to control their consumption. The physical dependency caused by alcohol can lead to an affected individual having a very strong urge to drink alcohol. These characteristics play a role in decreasing the ability to stop drinking of an individual with an alcohol use disorder. Alcoholism can have adverse effects on mental health, contributing to psychiatric disorders and increasing the risk of suicide. A depressed mood is a common symptom of heavy alcohol drinkers.
Warning signs
Warning signs of alcoholism include the consumption of increasing amounts of alcohol and frequent intoxication, preoccupation with drinking to the exclusion of other activities, promises to quit drinking and failure to keep those promises, the inability to remember what was said or done while drinking (colloquially known as "blackouts"), personality changes associated with drinking, denial or the making of excuses for drinking, the refusal to admit excessive drinking, dysfunction or other problems at work or school, the loss of interest in personal appearance or hygiene, marital and economic problems, and the complaint of poor health, with loss of appetite, respiratory infections, or increased anxiety.
Physical
Short-term effects
Drinking enough to cause a blood alcohol concentration (BAC) of 0.03–0.12% typically causes an overall improvement in mood and possible euphoria (a "happy" feeling), increased self-confidence and sociability, decreased anxiety, a flushed, red appearance in the face and impaired judgment and fine muscle coordination. A BAC of 0.09% to 0.25% causes lethargy, sedation, balance problems and blurred vision. A BAC of 0.18% to 0.30% causes profound confusion, impaired speech (e.g. slurred speech), staggering, dizziness and vomiting. A BAC from 0.25% to 0.40% causes stupor, unconsciousness, anterograde amnesia, vomiting (death may occur due to inhalation of vomit while unconscious) and respiratory depression (potentially life-threatening). A BAC from 0.35% to 0.80% causes a coma (unconsciousness), life-threatening respiratory depression and possibly fatal alcohol poisoning. With all alcoholic beverages, drinking while driving, operating an aircraft or heavy machinery increases the risk of an accident; many countries have penalties for drunk driving.
Long-term effects
Having more than one drink a day for women or two drinks for men increases the risk of heart disease, high blood pressure, atrial fibrillation, and stroke. Risk is greater with binge drinking, which may also result in violence or accidents. About 3.3 million deaths (5.9% of all deaths) are believed to be due to alcohol each year. Alcoholism reduces a persons life expectancy by around ten years and alcohol use is the third leading cause of early death in the United States. Long-term alcohol misuse can cause a number of physical symptoms, including cirrhosis of the liver, pancreatitis, epilepsy, polyneuropathy, alcoholic dementia, heart disease, nutritional deficiencies, peptic ulcers and sexual dysfunction, and can eventually be fatal. Other physical effects include an increased risk of developing cardiovascular disease, malabsorption, alcoholic liver disease, and several cancers. Damage to the central nervous system and peripheral nervous system can occur from sustained alcohol consumption. A wide range of immunologic defects can result and there may be a generalized skeletal fragility, in addition to a recognized tendency to accidental injury, resulting in a propensity for bone fractures.Women develop long-term complications of alcohol dependence more rapidly than do men, women also have a higher mortality rate from alcoholism than men. Examples of long-term complications include brain, heart, and liver damage and an increased risk of breast cancer. Additionally, heavy drinking over time has been found to have a negative effect on reproductive functioning in women. This results in reproductive dysfunction such as anovulation, decreased ovarian mass, problems or irregularity of the menstrual cycle, and early menopause. Alcoholic ketoacidosis can occur in individuals who chronically misuse alcohol and have a recent history of binge drinking. The amount of alcohol that can be biologically processed and its effects differ between sexes. Equal dosages of alcohol consumed by men and women generally result in women having higher blood alcohol concentrations (BACs), since women generally have a lower weight and higher percentage of body fat and therefore a lower volume of distribution for alcohol than men.
Psychiatric
Long-term misuse of alcohol can cause a wide range of mental health problems. Severe cognitive problems are common; approximately 10% of all dementia cases are related to alcohol consumption, making it the second leading cause of dementia. Excessive alcohol use causes damage to brain function, and psychological health can be increasingly affected over time. Social skills are significantly impaired in people with alcoholism due to the neurotoxic effects of alcohol on the brain, especially the prefrontal cortex area of the brain. The social skills that are impaired by alcohol use disorder include impairments in perceiving facial emotions, prosody, perception problems, and theory of mind deficits; the ability to understand humor is also impaired in people who misuse alcohol. Psychiatric disorders are common in people with alcohol use disorders, with as many as 25% also having severe psychiatric disturbances. The most prevalent psychiatric symptoms are anxiety and depression disorders. Psychiatric symptoms usually initially worsen during alcohol withdrawal, but typically improve or disappear with continued abstinence. Psychosis, confusion, and organic brain syndrome may be caused by alcohol misuse, which can lead to a misdiagnosis such as schizophrenia. Panic disorder can develop or worsen as a direct result of long-term alcohol misuse.The co-occurrence of major depressive disorder and alcoholism is well documented. Among those with comorbid occurrences, a distinction is commonly made between depressive episodes that remit with alcohol abstinence ("substance-induced"), and depressive episodes that are primary and do not remit with abstinence ("independent" episodes). Additional use of other drugs may increase the risk of depression. Psychiatric disorders differ depending on gender. Women who have alcohol-use disorders often have a co-occurring psychiatric diagnosis such as major depression, anxiety, panic disorder, bulimia, post-traumatic stress disorder (PTSD), or borderline personality disorder. Men with alcohol-use disorders more often have a co-occurring diagnosis of narcissistic or antisocial personality disorder, bipolar disorder, schizophrenia, impulse disorders or attention deficit/hyperactivity disorder (ADHD). Women with alcohol use disorder are more likely to experience physical or sexual assault, abuse, and domestic violence than women in the general population, which can lead to higher instances of psychiatric disorders and greater dependence on alcohol.
Social effects
Serious social problems arise from alcohol use disorder; these dilemmas are caused by the pathological changes in the brain and the intoxicating effects of alcohol. Alcohol misuse is associated with an increased risk of committing criminal offences, including child abuse, domestic violence, rape, burglary and assault. Alcoholism is associated with loss of employment, which can lead to financial problems. Drinking at inappropriate times and behavior caused by reduced judgment can lead to legal consequences, such as criminal charges for drunk driving or public disorder, or civil penalties for tortious behavior. An alcoholics behavior and mental impairment while drunk can profoundly affect those surrounding him and lead to isolation from family and friends. This isolation can lead to marital conflict and divorce, or contribute to domestic violence. Alcoholism can also lead to child neglect, with subsequent lasting damage to the emotional development of children of people with alcohol use disorders. For this reason, children of people with alcohol use disorders can develop a number of emotional problems. For example, they can become afraid of their parents, because of their unstable mood behaviors. They may develop shame over their inadequacy to liberate their parents from alcoholism and, as a result of this, may develop self-image problems, which can lead to depression.
Alcohol withdrawal
As with similar substances with a sedative-hypnotic mechanism, such as barbiturates and benzodiazepines, withdrawal from alcohol dependence can be fatal if it is not properly managed. Alcohols primary effect is the increase in stimulation of the GABAA receptor, promoting central nervous system depression. With repeated heavy consumption of alcohol, these receptors are desensitized and reduced in number, resulting in tolerance and physical dependence. When alcohol consumption is stopped too abruptly, the persons nervous system experiences uncontrolled synapse firing. This can result in symptoms that include anxiety, life-threatening seizures, delirium tremens, hallucinations, shakes and possible heart failure. Other neurotransmitter systems are also involved, especially dopamine, NMDA and glutamate.Severe acute withdrawal symptoms such as delirium tremens and seizures rarely occur after 1-week post cessation of alcohol. The acute withdrawal phase can be defined as lasting between one and three weeks. In the period of 3–6 weeks following cessation, anxiety, depression, fatigue, and sleep disturbance are common. Similar post-acute withdrawal symptoms have also been observed in animal models of alcohol dependence and withdrawal.A kindling effect also occurs in people with alcohol use disorders whereby each subsequent withdrawal syndrome is more severe than the previous withdrawal episode; this is due to neuroadaptations which occur as a result of periods of abstinence followed by re-exposure to alcohol. Individuals who have had multiple withdrawal episodes are more likely to develop seizures and experience more severe anxiety during withdrawal from alcohol than alcohol-dependent individuals without a history of past alcohol withdrawal episodes. The kindling effect leads to persistent functional changes in brain neural circuits as well as to gene expression. Kindling also results in the intensification of psychological symptoms of alcohol withdrawal. There are decision tools and questionnaires that help guide physicians in evaluating alcohol withdrawal. For example, the CIWA-Ar objectifies alcohol withdrawal symptoms in order to guide therapy decisions which allows for an efficient interview while at the same time retaining clinical usefulness, validity, and reliability, ensuring proper care for withdrawal patients, who can be in danger of death.
Causes
A complex combination of genetic and environmental factors influences the risk of the development of alcoholism. Genes that influence the metabolism of alcohol also influence the risk of alcoholism, as can a family history of alcoholism. There is compelling evidence that alcohol use at an early age may influence the expression of genes which increase the risk of alcohol dependence. These genetic and epigenetic results are regarded as consistent with large longitudinal population studies finding that the younger the age of drinking onset, the greater the prevalence of lifetime alcohol dependence.Severe childhood trauma is also associated with a general increase in the risk of drug dependency. Lack of peer and family support is associated with an increased risk of alcoholism developing. Genetics and adolescence are associated with an increased sensitivity to the neurotoxic effects of chronic alcohol misuse. Cortical degeneration due to the neurotoxic effects increases impulsive behaviour, which may contribute to the development, persistence and severity of alcohol use disorders. There is evidence that with abstinence, there is a reversal of at least some of the alcohol induced central nervous system damage. The use of cannabis was associated with later problems with alcohol use. Alcohol use was associated with an increased probability of later use of tobacco and illegal drugs such as cannabis.
Availability
Alcohol is the most available, widely consumed, and widely misused recreational drug. Beer alone is the worlds most widely consumed alcoholic beverage; it is the third-most popular drink overall, after water and tea. It is thought by some to be the oldest fermented beverage.
Gender difference
Based on combined data in the US from SAMHSAs 2004–2005 National Surveys on Drug Use & Health, the rate of past-year alcohol dependence or misuse among persons aged 12 or older varied by level of alcohol use: 44.7% of past month heavy drinkers, 18.5% binge drinkers, 3.8% past month non-binge drinkers, and 1.3% of those who did not drink alcohol in the past month met the criteria for alcohol dependence or misuse in the past year. Males had higher rates than females for all measures of drinking in the past month: any alcohol use (57.5% vs. 45%), binge drinking (30.8% vs. 15.1%), and heavy alcohol use (10.5% vs. 3.3%), and males were twice as likely as females to have met the criteria for alcohol dependence or misuse in the past year (10.5% vs. 5.1%).
Genetic variation
There are genetic variations that affect the risk for alcoholism. Some of these variations are more common in individuals with ancestry from certain areas, for example Africa, East Asia, the Middle East and Europe. The variants with strongest effect are in genes that encode the main enzymes of alcohol metabolism, ADH1B and ALDH2. These genetic factors influence the rate at which alcohol and its initial metabolic product, acetaldehyde, are metabolized. They are found at different frequencies in people from different parts of the world. The alcohol dehydrogenase allele ADH1B*2 causes a more rapid metabolism of alcohol to acetaldehyde, and reduces risk for alcoholism; it is most common in individuals from East Asia and the Middle East. The alcohol dehydrogenase allele ADH1B*3 also causes a more rapid metabolism of alcohol. The allele ADH1B*3 is only found in some individuals of African descent and certain Native American tribes. African Americans and Native Americans with this allele have a reduced risk of developing alcoholism. Native Americans, however, have a significantly higher rate of alcoholism than average; risk factors such as cultural environmental effects (e.g. trauma) have been proposed to explain the higher rates. The aldehyde dehydrogenase allele ALDH2*2 greatly reduces the rate at which acetaldehyde, the initial product of alcohol metabolism, is removed by conversion to acetate; it greatly reduces the risk for alcoholism.A genome-wide association study (GWAS) of more than 100,000 human individuals identified variants of the gene KLB, which encodes the transmembrane protein β-Klotho, as highly associated with alcohol consumption. The protein β-Klotho is an essential element in cell surface receptors for hormones involved in modulation of appetites for simple sugars and alcohol. Several large GWAS have found differences in the genetics of alcohol consumption and alcohol dependence, although the two are to some degree related.
DNA damage
Alcohol-induced DNA damage, when not properly repaired, may have a key role in the neurotoxicity induced by alcohol. Metabolic conversion of ethanol to acetaldehyde can occur in the brain and the neurotoxic effects of ethanol appear to be associated with acetaldehyde induced DNA damages including DNA adducts and crosslinks. In addition to acetaldehyde, alcohol metabolism produces potentially genotoxic reactive oxygen species, which have been demonstrated to cause oxidative DNA damage.
Diagnosis
Definition
Misuse, problem use, abuse, and heavy use of alcohol refer to improper use of alcohol, which may cause physical, social, or moral harm to the drinker. The Dietary Guidelines for Americans defines "moderate use" as no more than two alcoholic beverages a day for men and no more than one alcoholic beverage a day for women. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines binge drinking as the amount of alcohol leading to a blood alcohol content (BAC) of 0.08, which, for most adults, would be reached by consuming five drinks for men or four for women over a two-hour period. According to the NIAAA, men may be at risk for alcohol-related problems if their alcohol consumption exceeds 14 standard drinks per week or 4 drinks per day, and women may be at risk if they have more than 7 standard drinks per week or 3 drinks per day. It defines a standard drink as one 12-ounce bottle of beer, one 5-ounce glass of wine, or 1.5 ounces of distilled spirits. Despite this risk, a 2014 report in the National Survey on Drug Use and Health found that only 10% of either "heavy drinkers" or "binge drinkers" defined according to the above criteria also met the criteria for alcohol dependence, while only 1.3% of non-binge drinkers met the criteria. An inference drawn from this study is that evidence-based policy strategies and clinical preventive services may effectively reduce binge drinking without requiring addiction treatment in most cases.
Alcoholism
The term alcoholism is commonly used amongst laypeople, but the word is poorly defined. Despite the imprecision inherent in the term, there have been attempts to define how the word alcoholism should be interpreted when encountered. In 1992, it was defined by the National Council on Alcoholism and Drug Dependence (NCADD) and ASAM as "a primary, chronic disease characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking." MeSH has had an entry for alcoholism since 1999, and references the 1992 definition.The WHO calls alcoholism "a term of long-standing use and variable meaning", and use of the term was disfavored by a 1979 WHO expert committee.
In professional and research contexts, the term alcoholism is not currently favored, but rather alcohol abuse, alcohol dependence, or alcohol use disorder are used. Talbot (1989) observes that alcoholism in the classical disease model follows a progressive course: if a person continues to drink, their condition will worsen. This will lead to harmful consequences in their life, physically, mentally, emotionally and socially. Johnson (1980) explores the emotional progression of the addicts response to alcohol. He looks at this in four phases. The first two are considered "normal" drinking and the last two are viewed as "typical" alcoholic drinking. Johnsons four phases consist of:
Learning the mood swing. A person is introduced to alcohol (in some cultures this can happen at a relatively young age), and the person enjoys the happy feeling it produces. At this stage, there is no emotional cost.
Seeking the mood swing. A person will drink to regain that feeling of euphoria experienced in phase 1; the drinking will increase as more intoxication is required to achieve the same effect. Again at this stage, there are no significant consequences.
At the third stage there are physical and social consequences, i.e., hangovers, family problems, work problems, etc. A person will continue to drink excessively, disregarding the problems.
The fourth stage can be detrimental, as Johnson cites it as a risk for premature death. As a person now drinks to feel normal, they block out the feelings of overwhelming guilt, remorse, anxiety, and shame they experience when sober.
DSM and ICD
In the United States, the Diagnostic and Statistical Manual of Mental Disorders (DSM) is the most common diagnostic guide for substance use disorders, whereas most countries use the International Classification of Diseases (ICD) for diagnostic (and other) purposes. The two manuals use similar but not identical nomenclature to classify alcohol problems.
Social barriers
Attitudes and social stereotypes can create barriers to the detection and treatment of alcohol use disorder. This is more of a barrier for women than men. Fear of stigmatization may lead women to deny that they have a medical condition, to hide their drinking, and to drink alone. This pattern, in turn, leads family, physicians, and others to be less likely to suspect that a woman they know has alcohol use disorder. In contrast, reduced fear of stigma may lead men to admit that they are having a medical condition, to display their drinking publicly, and to drink in groups. This pattern, in turn, leads family, physicians, and others to be more likely to suspect that a man they know is someone with an alcohol use disorder.
Screening
Screening is recommended among those over the age of 18. Several tools may be used to detect a loss of control of alcohol use. These tools are mostly self-reports in questionnaire form. Another common theme is a score or tally that sums up the general severity of alcohol use.The CAGE questionnaire, named for its four questions, is one such example that may be used to screen patients quickly in a doctors office.
Two "yes" responses indicate that the respondent should be investigated further.
The questionnaire asks the following questions:
Have you ever felt you needed to Cut down on your drinking?
Have people Annoyed you by criticizing your drinking?
Have you ever felt Guilty about drinking?
Have you ever felt you needed a drink first thing in the morning (Eye-opener) to steady your nerves or to get rid of a hangover?
The CAGE questionnaire has demonstrated a high effectiveness in detecting alcohol-related problems; however, it has limitations in people with less severe alcohol-related problems, white women and college students.Other tests are sometimes used for the detection of alcohol dependence, such as the Alcohol Dependence Data Questionnaire, which is a more sensitive diagnostic test than the CAGE questionnaire. It helps distinguish a diagnosis of alcohol dependence from one of heavy alcohol use. The Michigan Alcohol Screening Test (MAST) is a screening tool for alcoholism widely used by courts to determine the appropriate sentencing for people convicted of alcohol-related offenses, driving under the influence being the most common. The Alcohol Use Disorders Identification Test (AUDIT), a screening questionnaire developed by the World Health Organization, is unique in that it has been validated in six countries and is used internationally. Like the CAGE questionnaire, it uses a simple set of questions – a high score earning a deeper investigation. The Paddington Alcohol Test (PAT) was designed to screen for alcohol-related problems amongst those attending Accident and Emergency departments. It concords well with the AUDIT questionnaire but is administered in a fifth of the time.
Urine and blood tests
There are reliable tests for the actual use of alcohol, one common test being that of blood alcohol content (BAC). These tests do not differentiate people with alcohol use disorders from people without; however, long-term heavy drinking does have a few recognizable effects on the body, including:
Macrocytosis (enlarged MCV)
Elevated GGT
Moderate elevation of AST and ALT and an AST: ALT ratio of 2:1
High carbohydrate deficient transferrin (CDT)With regard to alcoholism, BAC is useful to judge alcohol tolerance, which in turn is a sign of alcoholism. Electrolyte and acid-base abnormalities including hypokalemia, hypomagnesemia, hyponatremia, hyperuricemia, metabolic acidosis, and respiratory alkalosis are common in people with alcohol use disorders.However, none of these blood tests for biological markers is as sensitive as screening questionnaires.
Prevention
The World Health Organization, the European Union and other regional bodies, national governments and parliaments have formed alcohol policies in order to reduce the harm of alcoholism. Increasing the age at which licit drugs that are susceptible to misuse, such as alcohol, can be purchased, and banning or restricting alcohol beverage advertising are common methods to reduce alcohol use among adolescents and young adults in particular. Credible, evidence-based educational campaigns in the mass media about the consequences of alcohol misuse have been recommended. Guidelines for parents to prevent alcohol misuse amongst adolescents, and for helping young people with mental health problems have also been suggested.
Management
Treatments are varied because there are multiple perspectives of alcoholism. Those who approach alcoholism as a medical condition or disease recommend differing treatments from, for instance, those who approach the condition as one of social choice. Most treatments focus on helping people discontinue their alcohol intake, followed up with life training and/or social support to help them resist a return to alcohol use. Since alcoholism involves multiple factors which encourage a person to continue drinking, they must all be addressed to successfully prevent a relapse. An example of this kind of treatment is detoxification followed by a combination of supportive therapy, attendance at self-help groups, and ongoing development of coping mechanisms. Much of the treatment community for alcoholism supports an abstinence-based zero tolerance approach popularized by the 12 step program of Alcoholics Anonymous; however, some prefer a harm-reduction approach.
Cessation of alcohol intake
Medical treatment for alcohol detoxification usually involves administration of a benzodiazepine, in order to ameliorate alcohol withdrawal syndromes adverse impact. The addition of phenobarbital improves outcomes if benzodiazepine administration lacks the usually efficacy, and phenobarbital alone might be an effective treatment. Propofol also might enhance treatment for individuals showing limited therapeutic response to a benzodiazepine. Individuals who are only at risk of mild to moderate withdrawal symptoms can be treated as outpatients. Individuals at risk of a severe withdrawal syndrome as well as those who have |
Alcoholism | significant or acute comorbid conditions can be treated as inpatients. Direct treatment can be followed by a treatment program for alcohol dependence or alcohol use disorder to attempt to reduce the risk of relapse. Experiences following alcohol withdrawal, such as depressed mood and anxiety, can take weeks or months to abate while other symptoms persist longer due to persisting neuroadaptations.
Psychological
Various forms of group therapy or psychotherapy are often utilized to encourage and support abstinence from alcohol, or to reduce alcohol consumption to levels that are not associated with adverse outcomes. Mutual-aid group-counseling is an approach used to facilitate relapse prevention. Alcoholics Anonymous was one of the earliest organizations formed to provide mutual peer support and it is still the largest. Others include LifeRing Secular Recovery, SMART Recovery, Women for Sobriety, and Secular Organizations for Sobriety.Manualized Twelve Step Facilitation (TSF) interventions (i.e. therapy which encourages active, long-term Alcoholics Anonymous participation) for Alcohol Use Disorder lead to higher abstinence rates, compared to other clinical interventions and to wait-list control groups.
Moderate drinking
Rationing and moderation programs such as Moderation Management and DrinkWise do not mandate complete abstinence. While most people with alcohol use disorders are unable to limit their drinking in this way, some return to moderate drinking. A 2002 US study by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) showed that 17.7% of individuals diagnosed as alcohol dependent more than one year prior returned to low-risk drinking. This group, however, showed fewer initial symptoms of dependency.A follow-up study, using the same subjects that were judged to be in remission in 2001–2002, examined the rates of return to problem drinking in 2004–2005. The study found abstinence from alcohol was the most stable form of remission for recovering alcoholics. There was also a 1973 study showing chronic alcoholics drinking moderately again, but a 1982 follow-up showed that 95% of subjects were not able to maintain drinking in moderation over the long term. Another study was a long-term (60 year) follow-up of two groups of alcoholic men which concluded that "return to controlled drinking rarely persisted for much more than a decade without relapse or evolution into abstinence." Internet based measures appear to be useful at least in the short term.
Medications
In the United States there are four approved medications for alcoholism: acamprosate, two methods of using naltrexone and disulfiram.
Acamprosate may stabilise the brain chemistry that is altered due to alcohol dependence via antagonising the actions of glutamate, a neurotransmitter which is hyperactive in the post-withdrawal phase. By reducing excessive NMDA activity which occurs at the onset of alcohol withdrawal, acamprosate can reduce or prevent alcohol withdrawal related neurotoxicity. Acamprosate reduces the risk of relapse amongst alcohol-dependent persons.
Naltrexone is a competitive antagonist for opioid receptors, effectively blocking the effects of endorphins and opioids. Naltrexone is used to decrease cravings for alcohol and encourage abstinence. Alcohol causes the body to release endorphins, which in turn release dopamine and activate the reward pathways; hence in the body Naltrexone reduces the pleasurable effects from consuming alcohol. Evidence supports a reduced risk of relapse among alcohol-dependent persons and a decrease in excessive drinking. Nalmefene also appears effective and works in a similar manner.
Disulfiram prevents the elimination of acetaldehyde, a chemical the body produces when breaking down ethanol. Acetaldehyde itself is the cause of many hangover symptoms from alcohol use. The overall effect is discomfort when alcohol is ingested: an extremely fast-acting and long-lasting, uncomfortable hangover.Several other drugs are also used and many are under investigation.
Benzodiazepines, while useful in the management of acute alcohol withdrawal, if used long-term can cause a worse outcome in alcoholism. Alcoholics on chronic benzodiazepines have a lower rate of achieving abstinence from alcohol than those not taking benzodiazepines. This class of drugs is commonly prescribed to alcoholics for insomnia or anxiety management. Initiating prescriptions of benzodiazepines or sedative-hypnotics in individuals in recovery has a high rate of relapse with one author reporting more than a quarter of people relapsed after being prescribed sedative-hypnotics. Those who are long-term users of benzodiazepines should not be withdrawn rapidly, as severe anxiety and panic may develop, which are known risk factors for alcohol use disorder relapse. Taper regimes of 6–12 months have been found to be the most successful, with reduced intensity of withdrawal.
Calcium carbimide works in the same way as disulfiram; it has an advantage in that the occasional adverse effects of disulfiram, hepatotoxicity and drowsiness, do not occur with calcium carbimide.
Ondansetron and topiramate are supported by tentative evidence in people with certain genetic patterns. Evidence for ondansetron is stronger in people who have recently started to abuse alcohol. Topiramate is a derivative of the naturally occurring sugar monosaccharide D-fructose. Review articles characterize topiramate as showing "encouraging", "promising", "efficacious", and "insufficient" results in the treatment of alcohol use disorders.Evidence does not support the use of selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), antipsychotics, or gabapentin.
Research
Topiramate, a derivative of the naturally occurring sugar monosaccharide D-fructose, has been found effective in helping alcoholics quit or cut back on the amount they drink. Evidence suggests that topiramate antagonizes excitatory glutamate receptors, inhibits dopamine release, and enhances inhibitory gamma-aminobutyric acid function. A 2008 review of the effectiveness of topiramate concluded that the results of published trials are promising, however as of 2008, data was insufficient to support using topiramate in conjunction with brief weekly compliance counseling as a first-line agent for alcohol dependence. A 2010 review found that topiramate may be superior to existing alcohol pharmacotherapeutic options. Topiramate effectively reduces craving and alcohol withdrawal severity as well as improving quality-of-life-ratings.Baclofen, a GABAB receptor agonist, is under study for the treatment of alcoholism. According to a 2017 Cochrane Systematic Review, there is insufficient evidence to determine the effectiveness or safety for the use of baclofen for withdrawal symptoms in alcoholism. Psilocybin-assisted psychotherapy is under study for the treatment of patients with alcohol use disorder.
Dual addictions and dependencies
Alcoholics may also require treatment for other psychotropic drug addictions and drug dependencies. The most common dual dependence syndrome with alcohol dependence is benzodiazepine dependence, with studies showing 10–20% of alcohol-dependent individuals had problems of dependence and/or misuse problems of benzodiazepine drugs such as diazepam or clonazepam. These drugs are, like alcohol, depressants. Benzodiazepines may be used legally, if they are prescribed by doctors for anxiety problems or other mood disorders, or they may be purchased as illegal drugs. Benzodiazepine use increases cravings for alcohol and the volume of alcohol consumed by problem drinkers. Benzodiazepine dependency requires careful reduction in dosage to avoid benzodiazepine withdrawal syndrome and other health consequences. Dependence on other sedative-hypnotics such as zolpidem and zopiclone as well as opiates and illegal drugs is common in alcoholics. Alcohol itself is a sedative-hypnotic and is cross-tolerant with other sedative-hypnotics such as barbiturates, benzodiazepines and nonbenzodiazepines. Dependence upon and withdrawal from sedative-hypnotics can be medically severe and, as with alcohol withdrawal, there is a risk of psychosis or seizures if not properly managed.
Epidemiology
The World Health Organization estimates that as of 2016 there are 380 million people with alcoholism worldwide (5.1% of the population over 15 years of age). Substance use disorders are a major public health problem facing many countries. "The most common substance of abuse/dependence in patients presenting for treatment is alcohol." In the United Kingdom, the number of dependent drinkers was calculated as over 2.8 million in 2001. About 12% of American adults have had an alcohol dependence problem at some time in their life. In the United States and Western Europe, 10 to 20% of men and 5 to 10% of women at some point in their lives will meet criteria for alcoholism. Estonia had the highest death rate from alcohol in Europe in 2015 at 8.8 per 100,000 population. In the United States, 30% of people admitted to hospital have a problem related to alcohol.Within the medical and scientific communities, there is a broad consensus regarding alcoholism as a disease state. For example, the American Medical Association considers alcohol a drug and states that "drug addiction is a chronic, relapsing brain disease characterized by compulsive drug seeking and use despite often devastating consequences. It results from a complex interplay of biological vulnerability, environmental exposure, and developmental factors (e.g., stage of brain maturity)." Alcoholism has a higher prevalence among men, though, in recent decades, the proportion of female alcoholics has increased. Current evidence indicates that in both men and women, alcoholism is 50–60% genetically determined, leaving 40–50% for environmental influences. Most alcoholics develop alcoholism during adolescence or young adulthood.
Prognosis
Alcoholism often reduces a persons life expectancy by around ten years. The most common cause of death in alcoholics is from cardiovascular complications. There is a high rate of suicide in chronic alcoholics, which increases the longer a person drinks. Approximately 3–15% of alcoholics commit suicide, and research has found that over 50% of all suicides are associated with alcohol or drug dependence. This is believed to be due to alcohol causing physiological distortion of brain chemistry, as well as social isolation. Suicide is also very common in adolescent alcohol abusers, with 25% of suicides in adolescents being related to alcohol abuse. Among those with alcohol dependence after one year, some met the criteria for low-risk drinking, even though only 25.5% of the group received any treatment, with the breakdown as follows: 25% were found to be still dependent, 27.3% were in partial remission (some symptoms persist), 11.8% asymptomatic drinkers (consumption increases chances of relapse) and 35.9% were fully recovered – made up of 17.7% low-risk drinkers plus 18.2% abstainers. In contrast, however, the results of a long-term (60-year) follow-up of two groups of alcoholic men indicated that "return to controlled drinking rarely persisted for much more than a decade without relapse or evolution into abstinence." There was also "return-to-controlled drinking, as reported in short-term studies, is often a mirage."
History
Historically the name dipsomania was coined by German physician C. W. Hufeland in 1819 before it was superseded by alcoholism. That term now has a more specific meaning. The term alcoholism was first used in 1849 by the Swedish physician Magnus Huss to describe the systemic adverse effects of alcohol.Alcohol has a long history of use and misuse throughout recorded history. Biblical, Egyptian and Babylonian sources record the history of abuse and dependence on alcohol. In some ancient cultures alcohol was worshiped and in others, its misuse was condemned. Excessive alcohol misuse and drunkenness were recognized as causing social problems even thousands of years ago. However, the defining of habitual drunkenness as it was then known as and its adverse consequences were not well established medically until the 18th century. In 1647 a Greek monk named Agapios was the first to document that chronic alcohol misuse was associated with toxicity to the nervous system and body which resulted in a range of medical disorders such as seizures, paralysis, and internal bleeding. In the 1910s and 1920s, the effects of alcohol misuse and chronic drunkenness boosted membership of the temperance movement and led to the prohibition of alcohol in many Western countries, nationwide bans on the production, importation, transportation, and sale of alcoholic beverages that generally remained in place until the late 1920s or early 1930s; these policies resulted in the decline of death rates from cirrhosis and alcoholism. In 2005, alcohol dependence and misuse was estimated to cost the US economy approximately 220 billion dollars per year, more than cancer and obesity.
Society and culture
The various health problems associated with long-term alcohol consumption are generally perceived as detrimental to society, for example, money due to lost labor-hours, medical costs due to injuries due to drunkenness and organ damage from long-term use, and secondary treatment costs, such as the costs of rehabilitation facilities and detoxification centers. Alcohol use is a major contributing factor for head injuries, motor vehicle injuries (27%), interpersonal violence (18%), suicides (18%), and epilepsy (13%). Beyond the financial costs that alcohol consumption imposes, there are also significant social costs to both the alcoholic and their family and friends. For instance, alcohol consumption by a pregnant woman can lead to an incurable and damaging condition known as fetal alcohol syndrome, which often results in cognitive deficits, mental health problems, an inability to live independently and an increased risk of criminal behaviour, all of which can cause emotional stress for parents and caregivers. Estimates of the economic costs of alcohol misuse, collected by the World Health Organization, vary from one to six% of a countrys GDP. One Australian estimate pegged alcohols social costs at 24% of all drug misuse costs; a similar Canadian study concluded alcohols share was 41%. One study quantified the cost to the UK of all forms of alcohol misuse in 2001 as £18.5–20 billion. All economic costs in the United States in 2006 have been estimated at $223.5 billion.The idea of hitting rock bottom refers to an experience of stress that can be attributed to alcohol misuse. There is no single definition for this idea, and people may identify their own lowest points in terms of lost jobs, lost relationships, health problems, legal problems, or other consequences of alcohol misuse. The concept is promoted by 12-step recovery groups and researchers using the transtheoretical model of motivation for behavior change. The first use of this slang phrase in the formal medical literature appeared in a 1965 review in the British Medical Journal, which said that some men refused treatment until they "hit rock bottom", but that treatment was generally more successful for "the alcohol addict who has friends and family to support him" than for impoverished and homeless addicts.Stereotypes of alcoholics are often found in fiction and popular culture. The "town drunk" is a stock character in Western popular culture. Stereotypes of drunkenness may be based on racism or xenophobia, as in the fictional depiction of the Irish as heavy drinkers. Studies by social psychologists Stivers and Greeley attempt to document the perceived prevalence of high alcohol consumption amongst the Irish in America. Alcohol consumption is relatively similar between many European cultures, the United States, and Australia. In Asian countries that have a high gross domestic product, there is heightened drinking compared to other Asian countries, but it is nowhere near as high as it is in other countries like the United States. It is also inversely seen, with countries that have very low gross domestic product showing high alcohol consumption. In a study done on Korean immigrants in Canada, they reported alcohol was even an integral part of their meal, and is the only time solo drinking should occur. They also believe alcohol is necessary at any social event as it helps conversations start.Peyote, a psychoactive agent, has even shown promise in treating alcoholism. Alcohol had actually replaced peyote as Native Americans psychoactive agent of choice in rituals when peyote was outlawed.
See also
Notes
References
External links
Alcohol at Curlie |
Chagas disease | Chagas disease, also known as American trypanosomiasis, is a tropical parasitic disease caused by Trypanosoma cruzi. It is spread mostly by insects in the subfamily Triatominae, known as "kissing bugs". The symptoms change over the course of the infection. In the early stage, symptoms are typically either not present or mild, and may include fever, swollen lymph nodes, headaches, or swelling at the site of the bite. After four to eight weeks, untreated individuals enter the chronic phase of disease, which in most cases does not result in further symptoms. Up to 45% of people with chronic infections develop heart disease 10–30 years after the initial illness, which can lead to heart failure. Digestive complications, including an enlarged esophagus or an enlarged colon, may also occur in up to 21% of people, and up to 10% of people may experience nerve damage.T. cruzi is commonly spread to humans and other mammals by the bite of a kissing bug. The disease may also be spread through blood transfusion, organ transplantation, consuming food or drink contaminated with the parasites, and vertical transmission (from a mother to her baby). Diagnosis of early disease is by finding the parasite in the blood using a microscope or detecting its DNA by polymerase chain reaction. Chronic disease is diagnosed by finding antibodies for T. cruzi in the blood.Prevention focuses on eliminating kissing bugs and avoiding their bites. This may involve the use of insecticides or bed-nets. Other preventive efforts include screening blood used for transfusions. As of 2022, a vaccine has not been developed. Early infections are treatable with the medications benznidazole or nifurtimox, which usually cure the disease if given shortly after the person is infected, but become less effective the longer a person has had Chagas disease. When used in chronic disease, medication may delay or prevent the development of end-stage symptoms. Benznidazole and nifurtimox often cause side effects, including skin disorders, digestive system irritation, and neurological symptoms, which can result in treatment being discontinued. As of 2019, new drugs for Chagas disease are under development, and experimental vaccines have been studied in animal models.It is estimated that 6.5 million people, mostly in Mexico, Central America and South America, have Chagas disease as of 2019, resulting in approximately 9,490 annual deaths. Most people with the disease are poor, and most do not realize they are infected. Large-scale population migrations have carried Chagas disease to new regions, which include the United States and many European countries. The disease affects more than 150 types of animals.The disease was first described in 1909 by Brazilian physician Carlos Chagas, after whom it is named. Chagas disease is classified as a neglected tropical disease.
Signs and symptoms
Chagas disease occurs in two stages: an acute stage, which develops one to two weeks after the insect bite, and a chronic stage, which develops over many years. The acute stage is often symptom-free. When present, the symptoms are typically minor and not specific to any particular disease. Signs and symptoms include fever, malaise, headache, and enlargement of the liver, spleen, and lymph nodes. Sometimes, people develop a swollen nodule at the site of infection, which is called "Romañas sign" if it is on the eyelid, or a "chagoma" if it is elsewhere on the skin. In rare cases (less than 1–5%), infected individuals develop severe acute disease, which can involve inflammation of the heart muscle, fluid accumulation around the heart, and inflammation of the brain and surrounding tissues, and may be life-threatening. The acute phase typically lasts four to eight weeks and resolves without treatment.Unless treated with antiparasitic drugs, individuals remain infected with T. cruzi after recovering from the acute phase. Most chronic infections are asymptomatic, which is referred to as indeterminate chronic Chagas disease. However, over decades with the disease, approximately 30–40% of people develop organ dysfunction (determinate chronic Chagas disease), which most often affects the heart or digestive system.The most common long-term manifestation is heart disease, which occurs in 14–45% of people with chronic Chagas disease. People with Chagas heart disease often experience heart palpitations, and sometimes fainting, due to irregular heart function. By electrocardiogram, people with Chagas heart disease most frequently have arrhythmias. As the disease progresses, the hearts ventricles become enlarged (dilated cardiomyopathy), which reduces its ability to pump blood. In many cases the first sign of Chagas heart disease is heart failure, thromboembolism, or chest pain associated with abnormalities in the microvasculature.Also common in chronic Chagas disease is damage to the digestive system, which affects 10–21% of people. Enlargement of the esophagus or colon are the most common digestive issues. Those with enlarged esophagus often experience pain (odynophagia) or trouble swallowing (dysphagia), acid reflux, cough, and weight loss. Individuals with enlarged colon often experience constipation, and may develop severe blockage of the intestine or its blood supply. Up to 10% of chronically infected individuals develop nerve damage that can result in numbness and altered reflexes or movement. While chronic disease typically develops over decades, some individuals with Chagas disease (less than 10%) progress to heart damage directly after acute disease.Signs and symptoms differ for people infected with T. cruzi through less common routes. People infected through ingestion of parasites tend to develop severe disease within three weeks of consumption, with symptoms including fever, vomiting, shortness of breath, cough, and pain in the chest, abdomen, and muscles. Those infected congenitally typically have few to no symptoms, but can have mild non-specific symptoms, or severe symptoms such as jaundice, respiratory distress, and heart problems. People infected through organ transplant or blood transfusion tend to have symptoms similar to those of vector-borne disease, but the symptoms may not manifest for anywhere from a week to five months. Chronically infected individuals who become immunosuppressed due to HIV infection can have particularly severe and distinct disease, most commonly characterized by inflammation in the brain and surrounding tissue or brain abscesses. Symptoms vary widely based on the size and location of brain abscesses, but typically include fever, headaches, seizures, loss of sensation, or other neurological issues that indicate particular sites of nervous system damage. Occasionally, these individuals also experience acute heart inflammation, skin lesions, and disease of the stomach, intestine, or peritoneum.
Cause
Chagas disease is caused by infection with the protozoan parasite T. cruzi, which is typically introduced into humans through the bite of triatomine bugs, also called "kissing bugs". When the insect defecates at the bite site, motile T. cruzi forms called trypomastigotes enter the bloodstream and invade various host cells. Inside a host cell, the parasite transforms into a replicative form called an amastigote, which undergoes several rounds of replication. The replicated amastigotes transform back into trypomastigotes, which burst the host cell and are released into the bloodstream. Trypomastigotes then disseminate throughout the body to various tissues, where they invade cells and replicate. Over many years, cycles of parasite replication and immune response can severely damage these tissues, particularly the heart and digestive tract.
Transmission
T. cruzi can be transmitted by various triatomine bugs in the genera Triatoma, Panstrongylus, and Rhodnius. The primary vectors for human infection are the species of triatomine bugs that inhabit human dwellings, namely Triatoma infestans, Rhodnius prolixus, Triatoma dimidiata and Panstrongylus megistus. These insects are known by a number of local names, including vinchuca in Argentina, Bolivia, Chile and Paraguay, barbeiro (the barber) in Brazil, pito in Colombia, chinche in Central America, and chipo in Venezuela. The bugs tend to feed at night, preferring moist surfaces near the eyes or mouth. A triatomine bug can become infected with T. cruzi when it feeds on an infected host. T. cruzi replicates in the insects intestinal tract and is shed in the bugs feces. When an infected triatomine feeds, it pierces the skin and takes in a blood meal, defecating at the same time to make room for the new meal. The bite is typically painless, but causes itching. Scratching at the bite introduces the T. cruzi-laden feces into the bite wound, initiating infection.In addition to classical vector spread, Chagas disease can be transmitted through consumption of food or drink contaminated with triatomine insects or their feces. Since heating or drying kills the parasites, drinks and especially fruit juices are the most frequent source of infection. This oral route of transmission has been implicated in several outbreaks, where it led to unusually severe symptoms, likely due to infection with a higher parasite load than from the bite of a triatomine bug.T. cruzi can be transmitted independent of the triatomine bug during blood transfusion, following organ transplantation, or across the placenta during pregnancy. Transfusion with the blood of an infected donor infects the recipient 10–25% of the time. To prevent this, blood donations are screened for T. cruzi in many countries with endemic Chagas disease, as well as the United States. Similarly, transplantation of solid organs from an infected donor can transmit T. cruzi to the recipient. This is especially true for heart transplant, which transmits T. cruzi 75–100% of the time, and less so for transplantation of the liver (0–29%) or a kidney (0–19%). An infected mother can pass T. cruzi to her child through the placenta; this occurs in up to 15% of births by infected mothers. As of 2019, 22.5% of new infections occurred through congenital transmission.
Pathophysiology
In the acute phase of the disease, signs and symptoms are caused directly by the replication of T. cruzi and the immune systems response to it. During this phase, T. cruzi can be found in various tissues throughout the body and circulating in the blood. During the initial weeks of infection, parasite replication is brought under control by production of antibodies and activation of the hosts inflammatory response, particularly cells that target intracellular pathogens such as NK cells and macrophages, driven by inflammation-signaling molecules like TNF-α and IFN-γ.During chronic Chagas disease, long-term organ damage develops over years due to continued replication of the parasite and damage from the immune system. Early in the course of the disease, T. cruzi is found frequently in the striated muscle fibers of the heart. As disease progresses, the heart becomes generally enlarged, with substantial regions of cardiac muscle fiber replaced by scar tissue and fat. Areas of active inflammation are scattered throughout the heart, with each housing inflammatory immune cells, typically macrophages and T cells. Late in the disease, parasites are rarely detected in the heart, and may be present at only very low levels.In the heart, colon, and esophagus, chronic disease leads to a massive loss of nerve endings. In the heart, this may contribute to arrythmias and other cardiac dysfunction. In the colon and esophagus, loss of nervous system control is the major driver of organ dysfunction. Loss of nerves impairs the movement of food through the digestive tract, which can lead to blockage of the esophagus or colon and restriction of their blood supply.
Diagnosis
The presence of T. cruzi in the blood is diagnostic of Chagas disease. During the acute phase of infection, it can be detected by microscopic examination of fresh anticoagulated blood, or its buffy coat, for motile parasites; or by preparation of thin and thick blood smears stained with Giemsa, for direct visualization of parasites. Blood smear examination detects parasites in 34–85% of cases. The sensitivity increases if techniques such as microhematocrit centrifugation are used to concentrate the blood. On microscopic examination of stained blood smears, T. cruzi trypomastigotes appear as S or U-shaped organisms with a flagellum connected to the body by an undulating membrane. A nucleus and a smaller structure called a kinetoplast are visible inside the parasites body; the kinetoplast of T. cruzi is relatively large, which helps to distinguish it from other species of trypanosomes that infect humans.Alternatively, T. cruzi DNA can be detected by polymerase chain reaction (PCR). In acute and congenital Chagas disease, PCR is more sensitive than microscopy, and it is more reliable than antibody-based tests for the diagnosis of congenital disease because it is not affected by transfer of antibodies against T. cruzi from a mother to her baby (passive immunity). PCR is also used to monitor T. cruzi levels in organ transplant recipients and immunosuppressed people, which allows infection or reactivation to be detected at an early stage.In chronic Chagas disease, the concentration of parasites in the blood is too low to be reliably detected by microscopy or PCR, so the diagnosis is usually made using serological tests, which detect immunoglobulin G antibodies against T. cruzi in the blood. Two positive serology results, using different test methods, are required to confirm the diagnosis. If the test results are inconclusive, additional testing methods such as Western blot can be used.Various rapid diagnostic tests for Chagas disease are available. These tests are easily transported and can be performed by people without special training. They are useful for screening large numbers of people and testing people who cannot access healthcare facilities, but their sensitivity is relatively low, and it is recommended that a second method is used to confirm a positive result.T. cruzi parasites can be grown from blood samples by blood culture, xenodiagnosis, or by inoculating animals with the persons blood. In the blood culture method, the persons red blood cells are separated from the plasma and added to a specialized growth medium to encourage multiplication of the parasite. It can take up to six months to obtain the result. Xenodiagnosis involves feeding the blood to triatomine insects, then examining their feces for the parasite 30 to 60 days later. These methods are not routinely used, as they are slow and have low sensitivity.
Prevention
Efforts to prevent Chagas disease have largely focused on vector control to limit exposure to triatomine bugs. Insecticide-spraying programs have been the mainstay of vector control, consisting of spraying homes and the surrounding areas with residual insecticides. This was originally done with organochlorine, organophosphate, and carbamate insecticides, which were supplanted in the 1980s with pyrethroids. These programs have drastically reduced transmission in Brazil and Chile, and eliminated major vectors from certain regions: Triatoma infestans from Brazil, Chile, Uruguay, and parts of Peru and Paraguay, as well as Rhodnius prolixus from Central America. Vector control in some regions has been hindered by the development of insecticide resistance among triatomine bugs. In response, vector control programs have implemented alternative insecticides (e.g. fenitrothion and bendiocarb in Argentina and Bolivia), treatment of domesticated animals (which are also fed on by triatomine bugs) with pesticides, pesticide-impregnated paints, and other experimental approaches. In areas with triatomine bugs, transmission of T. cruzi can be prevented by sleeping under bed nets and by housing improvements that prevent triatomine bugs from colonizing houses.Blood transfusion was formerly the second-most common mode of transmission for Chagas disease. T. cruzi can survive in refrigerated stored blood, and can survive freezing and thawing, allowing it to persist in whole blood, packed red blood cells, granulocytes, cryoprecipitate, and platelets. The development and implementation of blood bank screening tests has dramatically reduced the risk of infection during blood transfusion. Nearly all blood donations in Latin American countries undergo Chagas screening. Widespread screening is also common in non-endemic nations with significant populations of immigrants from endemic areas, including the United Kingdom (implemented in 1999), Spain (2005), the United States (2007), France and Sweden (2009), Switzerland (2012), and Belgium (2013). Serological tests, typically ELISAs, are used to detect antibodies against T. cruzi proteins in donor blood.Other modes of transmission have been targeted by Chagas disease prevention programs. Treating T. cruzi-infected mothers during pregnancy reduces the risk of congenital transmission of the infection. To this end, many countries in Latin America have implemented routine screening of pregnant women and infants for T. cruzi infection, and the World Health Organization recommends screening all children born to infected mothers to prevent congenital infection from developing into chronic disease. Similarly to blood transfusions, many countries with endemic Chagas disease screen organs for transplantation with serological tests.There is no vaccine against Chagas disease. Several experimental vaccines have been tested in animals infected with T. cruzi and were able to reduce parasite numbers in the blood and heart, but no vaccine candidates had undergone clinical trials in humans as of 2016.
Management
Chagas disease is managed using antiparasitic drugs to eliminate T. cruzi from the body, and symptomatic treatment to address the effects of the infection. As of 2018, benznidazole and nifurtimox were the antiparasitic drugs of choice for treating Chagas disease, though benznidazole is the only drug available in most of Latin America. For either drug, treatment typically consists of two to three oral doses per day for 60 to 90 days. Antiparasitic treatment is most effective early in the course of infection: it eliminates T. cruzi from 50 to 80% of people in the acute phase, but only 20–60% of those in the chronic phase. Treatment of chronic disease is more effective in children than in adults, and the cure rate for congenital disease approaches 100% if treated in the first year of life. Antiparasitic treatment can also slow the progression of the disease and reduce the possibility of congenital transmission. Elimination of T. cruzi does not cure the cardiac and gastrointestinal damage caused by chronic Chagas disease, so these conditions must be treated separately. Antiparasitic treatment is not recommended for people who have already developed dilated cardiomyopathy.Benznidazole is usually considered the first-line treatment because it has milder adverse effects than nifurtimox, and its efficacy is better understood. Both benznidazole and nifurtimox have common side effects that can result in treatment being discontinued. The most common side effects of benznidazole are skin rash, digestive problems, decreased appetite, weakness, headache, and sleeping problems. These side effects can sometimes be treated with antihistamines or corticosteroids, and are generally reversed when treatment is stopped. However, benzidazole is discontinued in up to 29% of cases. Nifurtimox has more frequent side effects, affecting up to 97.5% of individuals taking the drug. The most common side effects are loss of appetite, weight loss, nausea and vomiting, and various neurological disorders including mood changes, insomnia, paresthesia and peripheral neuropathy. Treatment is discontinued in up to 75% of cases. Both drugs are contraindicated for use in pregnant women and people with liver or kidney failure. As of 2019, resistance to these drugs has been reported.
Complications
In the chronic stage, treatment involves managing the clinical manifestations of the disease. The treatment of Chagas cardiomyopathy is similar to that of other forms of heart disease. Beta blockers and ACE inhibitors may be prescribed, but some people with Chagas disease may not be able to take the standard dose of these drugs because they have low blood pressure or a low heart rate. To manage irregular heartbeats, people may be prescribed anti-arrhythmic drugs such as amiodarone, or have a pacemaker implanted. Blood thinners may be used to prevent thromboembolism and stroke. Chronic heart disease caused by Chagas is a common reason for heart transplantation surgery. Because transplant recipients take immunosuppressive drugs to prevent organ rejection, they are monitored using PCR to detect reactivation of the disease. People with Chagas disease who undergo heart transplantation have higher survival rates than the average heart transplant recipient.Mild gastrointestinal disease may be treated symptomatically, such as by using laxatives for constipation, or taking a prokinetic drug like metoclopramide before meals to relieve esophageal symptoms. Surgery to sever the muscles of the lower esophageal sphincter (cardiomyotomy) may be performed in more severe cases of esophageal disease, and surgical removal of the affected part of the organ may be required for advanced megacolon and megaesophagus.
Epidemiology
In 2019, an estimated 6.5 million people worldwide had Chagas disease, with approximately 173,000 new infections and 9,490 deaths each year. The disease resulted in a global annual economic burden estimated at US$7.2 billion in 2013, 86% of which is borne by endemic countries. Chagas disease results in the loss of over 800,000 disability-adjusted life years each year.The endemic area of Chagas disease stretches from the southern United States to northern Chile and Argentina, with Bolivia (6.1%), Argentina (3.6%), and Paraguay (2.1%) exhibiting the highest prevalence of the disease. Within continental Latin America, Chagas disease is endemic to 21 countries: Argentina, Belize, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, French Guiana, Guatemala, Guyana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Uruguay, and Venezuela. In endemic areas, due largely to vector control efforts and screening of blood donations, annual infections and deaths have fallen by 67% and more than 73% respectively from their peaks in the 1980s to 2010. Transmission by insect vector and blood transfusion has been completely interrupted in Uruguay (1997), Chile (1999), and Brazil (2006), and in Argentina, vectorial transmission had been interrupted in 13 of the 19 endemic provinces as of 2001. During Venezuelas humanitarian crisis, vectorial transmission has begun occurring in areas where it had previously been interrupted, and Chagas disease seroprevalence rates have increased. Transmission rates have also risen in the Gran Chaco region due to insecticide resistance and in the Amazon basin due to oral transmission.While the rate of vector-transmitted Chagas disease has declined throughout most of Latin America, the rate of orally transmitted disease has risen, possibly due to increasing urbanization and deforestation bringing people into closer contact with triatomines and altering the distribution of triatomine species. Orally transmitted Chagas disease is of particular concern in Venezuela, where 16 outbreaks have been recorded between 2007 and 2018.Chagas exists in two different ecological zones: In the Southern Cone region, the main vector lives in and around human homes. In Central America and Mexico, the main vector species lives both inside dwellings and in uninhabited areas. In both zones, Chagas occurs almost exclusively in rural areas, where T. cruzi also circulates in wild and domestic animals. T. cruzi commonly infects more than 100 species of mammals across Latin America including opossums (Didelphis spp.), armadillos, marmosets, bats, various rodents and dogs all of which can be infected by the vectors or orally by eating triatomine bugs and other infected animals. For entomophagous animals this is a common mode. Didelphis spp. are unique in that they do not require the triatomine for transmission, completing the life cycle through their own urine and feces. Veterinary transmission also occurs through vertical transmission through the placenta, blood transfusion and organ transplants.
Non-endemic countries
Though Chagas is traditionally considered a disease of rural Latin America, international migration has dispersed those with the disease to numerous non-endemic countries, primarily in North America and Europe. As of 2020, approximately 300,000 infected people are living in the United States, and in 2018 it was estimated that 30,000 to 40,000 Americans had Chagas cardiomyopathy. The vast majority of cases in the United States occur in immigrants from Latin America, but local transmission is possible. Eleven triatomine species are native to the United States, and some southern states have persistent cycles of disease transmission between insect vectors and animal reservoirs, which include woodrats, possums, raccoons, armadillos and skunks. However, locally acquired infection is very rare: only 28 cases were documented from 1955 to 2015. As of 2013, the cost of treatment in the United States was estimated to be US$900 million annually (global cost $7 billion), which included hospitalization and medical devices such as pacemakers.Chagas disease affects approximately 68,000 to 123,000 people in Europe as of 2019. Spain, which has a high rate of immigration from Latin America, has the highest prevalence of the disease. It is estimated that 50,000 to 70,000 Spanish people are living with Chagas disease, accounting for the majority of European cases. The prevalence varies widely within European countries due to differing immigration patterns. Italy has the second highest prevalence, followed by the Netherlands, the United Kingdom, and Germany.
History
T. cruzi likely circulated in South American mammals long before the arrival of humans on the continent. T. cruzi has been detected in ancient human remains across South America, from a 9000-year-old Chinchorro mummy in the Atacama Desert, to remains of various ages in Minas Gerais, to an 1100-year-old mummy as far north as the Chihuahuan Desert near the Rio Grande. Many early written accounts describe symptoms consistent with Chagas disease, with early descriptions of the disease sometimes attributed to Miguel Diaz Pimenta (1707), Luís Gomes Ferreira (1735), and Theodoro J. H. Langgaard (1842).The formal description of Chagas disease was made by Carlos Chagas in 1909 after examining a two-year-old girl with fever, swollen lymph nodes, and an enlarged spleen and liver. Upon examination of her blood, Chagas saw trypanosomes identical to those he had recently identified from the hindgut of triatomine bugs and named Trypanosoma cruzi in honor of his mentor, Brazilian physician Oswaldo Cruz. He sent infected triatomine bugs to Cruz in Rio de Janeiro, who showed the bite of the infected triatomine could transmit T. cruzi to marmoset monkeys as well. In just two years, 1908 and 1909, Chagas published descriptions of the disease, the organism that caused it, and the insect vector required for infection. Almost immediately thereafter, at the suggestion of Miguel Couto, then professor of the Faculdade de Medicina do Rio de Janeiro, the disease was widely referred to as "Chagas disease". Chagas discovery brought him national and international renown, but in highlighting the inadequacies of the Brazilian governments response to the disease, Chagas attracted criticism to himself and to the disease that bore his name, stifling research on his discovery and likely frustrating his nomination for the Nobel Prize in 1921.In the 1930s, Salvador Mazza rekindled Chagas disease research, describing over a thousand cases in Argentinas Chaco Province. In Argentina, the disease is known as mal de Chagas-Mazza in his honor. Serological tests for Chagas disease were introduced in the 1940s, demonstrating that infection with T. cruzi was widespread across Latin America. This, combined with successes eliminating the malaria vector through insecticide use, spurred the creation of public health campaigns focused on treating houses with insecticides to eradicate triatomine bugs. The 1950s saw the discovery that treating blood with crystal violet could eradicate the parasite, leading to its widespread use in transfusion screening programs in Latin America. Large-scale control programs began to take form in the 1960s, first in São Paulo, then various locations in Argentina, then national-level programs across Latin America. These programs received a major boost in the 1980s with the introduction of pyrethroid insecticides, which did not leave stains |
Chagas disease | or odors after application and were longer-lasting and more cost-effective. Regional bodies dedicated to controlling Chagas disease arose through support of the Pan American Health Organization, with the Initiative of the Southern Cone for the Elimination of Chagas Diseases launching in 1991, followed by the Initiative of the Andean countries (1997), Initiative of the Central American countries (1997), and the Initiative of the Amazon countries (2004).
Research
Treatments
Fexinidazole, an antiparasitic drug approved for treating African trypanosomiasis, has shown activity against Chagas disease in animal models. As of 2019, it is undergoing phase II clinical trials for chronic Chagas disease in Spain. Other drug candidates include GNF6702, a proteasome inhibitor that is effective against Chagas disease in mice and is undergoing preliminary toxicity studies, and AN4169, which has had promising results in animal models.A number of experimental vaccines have been tested in animals. In addition to subunit vaccines, some approaches have involved vaccination with attenuated T. cruzi parasites or organisms that express some of the same antigens as T. cruzi but do not cause human disease, such as Trypanosoma rangeli or Phytomonas serpens. DNA vaccination has also been explored. As of 2019, vaccine research has mainly been limited to small animal models.
Diagnostic tests
As of 2018, standard diagnostic tests for Chagas disease were limited in their ability to measure the effectiveness of antiparasitic treatment, as serological tests may remain positive for years after T. cruzi is eliminated from the body, and PCR may give false-negative results when the parasite concentration in the blood is low. Several potential biomarkers of treatment response are under investigation, such as immunoassays against specific T. cruzi antigens, flow cytometry testing to detect antibodies against different life stages of T. cruzi, and markers of physiological changes caused by the parasite, such as alterations in coagulation and lipid metabolism.Another research area is the use of biomarkers to predict the progression of chronic disease. Serum levels of tumor necrosis factor alpha, brain and atrial natriuretic peptide, and angiotensin-converting enzyme 2 have been studied as indicators of the prognosis of Chagas cardiomyopathy.T. cruzi shed acute-phase antigen (SAPA), which can be detected in blood using ELISA or Western blot, has been used as an indicator of early acute and congenital infection. An assay for T. cruzi antigens in urine has been developed to diagnose congenital disease.
See also
Drugs for Neglected Diseases Initiative
Chagas: Time to Treat campaign
Association for the Promotion of Independent Disease Control in Developing Countries
References
External links
Chagas disease at Curlie
Chagas information at the U.S. Centers for Disease Control
Chagas information from the Drugs for Neglected Diseases initiative
Chagas disease information for travellers from the International Association for Medical Assistance to Travellers |
Behçets disease | Behçets disease (BD) is a type of inflammatory disorder which affects multiple parts of the body. The most common symptoms include painful sores on the mucous membranes of the mouth and other parts of the body, inflammation of parts of the eye, and arthritis. The sores can last from a few days, up to a week or more. Less commonly there may be inflammation of the brain or spinal cord, blood clots, aneurysms, or blindness. Often, the symptoms come and go.The cause is unknown. It is believed to be partly genetic. Behçets is not contagious. Diagnosis is based on at least three episodes of mouth sores in a year together with at least two of the following: genital sores, eye inflammation, skin sores, a positive skin prick test.There is no cure. Treatments may include immunosuppressive medication such as corticosteroids and lifestyle changes. Lidocaine mouthwash may help with the pain. Colchicine may decrease the frequency of attacks.While rare in the United States and Europe, it is more common in the Middle East and Asia. In Turkey, for example, about 2 per 1,000 are affected. Onset is usually in a persons 20s or 40s. The disease was initially described by Turkish dermatologist Hulusi Behçet in 1937.
Signs and symptoms
Skin and mucosa
Nearly all people with Behçets disease present with some form of painful ulcerations inside the mouth. They are a form of aphthous ulcers or non-scarring oral lesions. The oral lesions are similar to those found in inflammatory bowel disease and can be relapsing. Painful genital ulcerations usually develop around the anus, vulva, or scrotum and cause scarring in 75 percent of the patients. Additionally, patients may present with erythema nodosum, cutaneous pustular vasculitis, and lesions similar to pyoderma gangrenosum.
Eyes
Inflammatory eye disease can develop early in the disease course and lead to permanent vision loss in 20 percent of cases. Ocular involvement can be in the form of posterior uveitis, anterior uveitis, or retinal vasculitis. Anterior uveitis presents with painful eyes, conjuctival redness, hypopyon, and decreased visual acuity, while posterior uveitis presents with painless decreased visual acuity and visual field floaters. A rare form of ocular (eye) involvement in this syndrome is retinal vasculitis which presents with painless decrease of vision with the possibility of floaters or visual field defects.Optic nerve involvement in Behçets disease is rare, typically presenting as progressive optic atrophy and visual loss. However, cases of acute optic neuropathy (specifically anterior ischemic optic neuropathy) have also been reported to occur. Optic nerve atrophy has been identified as the most common cause of visual impairment. Behçets disease may result in primary or secondary optic nerve involvement. Papilledema as a result of dural sinus thrombosis and atrophy resulting from retinal disease, have been characterized as secondary causes of optic nerve atrophy in Behçets disease.Signs and symptoms of acute optic neuropathy include painless loss of vision which may affect either one or both eyes, reduced visual acuity, reduced color vision, relative afferent pupillary defect, central scotoma, swollen optic disc, macular edema, or retrobulbar pain. When these symptoms occur with concurrent mucocutaneous ulcerations, they raise suspicion of acute optic neuropathy in Behçets Disease. Progressive optic atrophy may result in decreased visual acuity or color vision. Intracranial hypertension with papilledema may be present.Episcleritis may occur, which causes eye redness and mild pain, without a significant impact on vision.
Bowels
Gastrointestinal (GI) manifestations include abdominal pain, nausea, and diarrhea with or without blood, and they often involve the ileocecal valve. Some patients with BD experience abdominal tenderness, bloating, and general abdominal discomfort. When mild this can resemble irritable bowel syndrome; more severe cases bear similarities to inflammatory bowel diseases such as ulcerative colitis or Crohns.
Lungs
Lung involvement is typically in the form of hemoptysis, pleuritis, cough, or fever, and in severe cases can be life-threatening if the outlet pulmonary artery develops an aneurysm which ruptures causing severe vascular collapse and death from bleeding in the lungs. Nodules, consolidations, cavities and ground glass lesions are common in patients with pulmonary involvement. Pulmonary artery thrombosis may occur.
Joints
Arthritis is seen in up to half of people, and is usually a non-erosive poly or oligoarthritis primarily of the large joints of the lower extremities.
Brain
Central nervous system (CNS) involvement most often occurs as a chronic meningoencephalitis. Lesions tend to occur in the brainstem, the basal ganglia and deep hemispheric white matter and may resemble those of multiple sclerosis (MS). Brainstem atrophy is seen in chronic cases.Neurological involvements range from aseptic meningitis to vascular thrombosis such as dural sinus thrombosis and organic brain syndrome manifesting with confusion, seizures, and memory loss. Sudden hearing loss (sensorineural) is often associated with it. They often appear late in the progression of the disease but are associated with a poor prognosis.
Heart
Pericarditis is a frequent cardiac manifestation. Chronic aortic regurgitation due to aortic root disease may also be seen. Although infrequent, myocardial infarction (heart attack) with angiographically identified acute coronary artery thrombosis has been reported, including one case with a pathologically demonstrable lesion due to arteritis found at autopsy.
Blood vessels
Blood vessel problems are observed in 7–29% of people with arterial lesions representing 15% of vascular lesions. Arterial lesions pose a greater risk. Most common arterial lesions are occlusions or stenosis and aneurysms or pseudoaneurysms.
Cause
The cause is not well-defined, but it is primarily characterized by auto-inflammation of the blood vessels. Although sometimes erroneously referred to as a diagnosis of exclusion, the diagnosis can sometimes be reached by pathologic examination of the affected areas.The primary mechanism of the damage is autoimmune, which by definition is an overactive immune system that targets the patients own body. The involvement of a subset of T cells (Th17) seems to be important. The primary cause is not well known. In fact, no one knows yet why the immune system starts to behave this way in Behçets disease. There does however seem to be a genetic component involved, as first degree relatives of the affected patients are often affected in more than the expected proportion for the general population.Research suggests that previous infections may provoke the autoimmune responses present in Behçets disease. Heat shock proteins (HSPs) are present in some bacteria and serve as a "danger signal" to the immune system. However, some HSPs share a similarity in bacteria and humans. The anti-HSP60 and anti-HSP65 antibodies that target HSPs produced by Streptococci (including S. sanguinis and S. pyogenes) and Mycobacterium tuberculosis can also target human HSPs, leading to immune responses linked to uveitis and various symptoms shown in parenchymal neuro-Behçets disease.An association with the GIMAP ("GTPase of the immunity-associated protein") family of genes on the long arm of chromosome 7 (7q36.1) has been reported. The genes implicated were GIMAP1, GIMAP2 and GIMAP4.
Pathophysiology
Behçets disease is considered more prevalent in the areas surrounding the old silk trading routes in the Middle East and in Central Asia. Thus, it is sometimes known as Silk Road disease. However, this disease is not restricted to people from these regions. A large number of serological studies show a linkage between the disease and HLA-B51. HLA-B51 is more frequently found from the Middle East to South Eastern Siberia, but the incidence of B51 in some studies was 3 fold higher than the normal population. However, B51 tends not to be found in disease when a certain SUMO4 gene variant is involved, and symptoms appear to be milder when HLA-B27 is present. At the current time, a similar infectious origin has not yet been confirmed that leads to Behçets disease, but certain strains of S. sanguinis has been found to have a homologous antigenicity.Vasculitis resulting in occlusion of the vessels supplying the optic nerve may be the cause of acute optic neuropathy and progressive optic atrophy in Behçets disease. Histological evaluation in a reported case of acute optic neuropathy demonstrated substitution of the axonal portion of the optic nerve with fibrous astrocytes without retinal changes. CNS involvement in Behçets disease may lead to intracranial hypertension most commonly due to dural venous sinus thrombosis and subsequent secondary optic atrophy.
Diagnosis
There is no specific pathological testing or technique available for the diagnosis of the disease, although the International Study Group criteria for the disease are highly sensitive and specific, involving clinical criteria and a pathergy test. Behçets disease has a high degree of resemblance to diseases that cause mucocutaneous lesions such as Herpes simplex labialis, and therefore clinical suspicion should be maintained until all the common causes of oral lesions are ruled out from the differential diagnosis.Visual acuity, or color vision loss with concurrent mucocutaneous lesions or systemic Behçets disease symptoms should raise suspicion of optic nerve involvement in Behçets disease and prompt a work-up for Behçets disease if not previously diagnosed in addition to an ocular work-up. Diagnosis of Behçets disease is based on clinical findings including oral and genital ulcers, skin lesions such as erythema nodosum, acne, or folliculitis, ocular inflammatory findings and a pathergy reaction. Inflammatory markers such ESR, and CRP may be elevated. A complete ophthalmic examination may include a slit lamp examination, optical coherence tomography to detect nerve loss, visual field examinations, fundoscopic examination to assess optic disc atrophy and retinal disease, fundoscopic angiography, and visual evoked potentials, which may demonstrate increased latency. Optic nerve enhancement may be identified on Magnetic Resonance Imaging (MRI) in some patients with acute optic neuropathy. However, a normal study does not rule out optic neuropathy. Cerebrospinal fluid (CSF) analysis may demonstrate elevated protein level with or without pleocytosis. Imaging including angiography may be indicated to identify dural venous sinus thrombosis as a cause of intracranial hypertension and optic atrophy.
Diagnostic guidelines
According to the International Study Group guidelines, for a patient to be diagnosed with Behçets disease, the patient must have oral (aphthous) ulcers (any shape, size, or number at least 3 times in any 12 months period) along with 2 out of the following 4 "hallmark" symptoms:
eye inflammation (iritis, uveitis, retinal vasculitis, cells in the vitreous)
genital ulcers (including anal ulcers and spots in the genital region and swollen testicles or epididymitis in men)
pathergy reaction (papule >2 mm dia. 24–48 hrs or more after needle-prick). The pathergy test has a specificity of 95 percent to 100 percent, but the results are often negative in American and European patients
skin lesions (papulo-pustules, folliculitis, erythema nodosum, acne in post-adolescents not on corticosteroids)Despite the inclusive criteria set forth by the International Study Group, there are cases where not all the criteria can be met and therefore a diagnosis cannot readily be made. There is however a set of clinical findings that a physician can rely upon in making a tentative diagnosis of the disease; essentially Behçets disease does not always follow the International Study Group guidelines and so a high degree of suspicion for a patient who presents having any number of the following findings is necessary:
arthritis/arthralgia
cardio-vascular problems of an inflammatory origin
changes of personality, psychoses
deep vein thrombosis
epididymitis
extreme exhaustion - chronic fatigue
inflammatory problems in chest and lungs
mouth ulcers
nervous system symptoms
problems with hearing or balance
stomach or bowel inflammation
superficial thrombophlebitis
any other members of the family with a diagnosis of Behçets disease.
Treatment
Current treatment is aimed at easing the symptoms, reducing inflammation, and controlling the immune system. The quality of the evidence for treating the oral ulcers associated with Behçets disease, however, is poor.High-dose corticosteroid therapy is often used for severe disease manifestations. Anti-TNF therapy such as infliximab has shown promise in treating the uveitis associated with the disease. Another Anti-TNF agent, etanercept, may be useful in people with mainly skin and mucosal symptoms. Apremilast may also be used to treat oral ulcers associated with Behçets disease.Interferon alpha-2a may also be an effective alternative treatment, particularly for the genital and oral ulcers as well as ocular lesions. Azathioprine, when used in combination with interferon alpha-2b also shows promise, and colchicine can be useful for treating some genital ulcers, erythema nodosum, and arthritis. Benzathine‐penicillin may also reduce new arthritic attacks.Thalidomide has also been used due to its immune-modifying effect. Dapsone and rebamipide have been shown, in small studies, to have beneficial results for mucocutaneous lesions.Given its rarity, the optimal treatment for acute optic neuropathy in Behçets disease has not been established. Early identification and treatment are essential. Response to ciclosporin, periocular triamcinolone, and IV methylprednisone followed by oral prednisone has been reported although relapses leading to irreversible visual loss may occur even with treatment. Immunosuppressants such as interferon-alpha and tumour necrosis factor antagonists may improve though not completely reverse symptoms of ocular Behçets disease, which may progress over time despite treatment. When symptoms are limited to the anterior chamber of the eye prognosis is improved. Posterior involvement, particularly optic nerve involvement, is a poor prognostic indicator. Secondary optic nerve atrophy is frequently irreversible. Lumbar puncture or surgical treatment may be required to prevent optic atrophy in cases of intracranial hypertension refractory to treatment with immunomodulators and steroids.IVIG could be a treatment for severe or complicated cases.
Surgery
Surgical treatment of arterial manifestations of BD bears many pitfalls since the obliterative endarteritis of vasa vasorum causes thickening of the medial layer and splitting of elastin fibers. Therefore, anastomotic pseudoaneurysms are likely to form, as well as pseudoaneurysms at the site of the puncture in case of angiography or endovascular treatment; furthermore, early graft occlusion may occur.For these reasons, invasive treatment should not be performed in the acute and active phases of the disease when inflammation is at its peak. The evaluation of diseases activity is usually based on relapsing symptoms, ESR (erythrocyte sedimentation rate), and serum levels of CRP (C‐reactive protein).Endovascular treatment can be an effective and safe alternative to open surgery, with less postoperative complications, faster recovery time, and reduced need for intensive care, while offering patency rates and procedural success rates comparable with those of surgery. This notwithstanding, long‐term results of endovascular treatment in BD are still to be determined.
Epidemiology
The syndrome is rare in the United States, Africa and South America, but is common in the Middle East and Asia, suggesting a possible cause endemic to those areas. A theory suggested that past exposure to lethal infectious agents might have fixed the genetic susceptibility factors to Behçets disease in those area. An estimated 15,000 to 20,000 Americans have been diagnosed with this disease. In the UK, it is estimated to have about 1 case for every 100,000 people. Globally, males are affected more frequently than females.In an epidemiologic study, 56 percent of patients with Behçets disease developed ocular involvement at a mean age of 30. Ocular involvement was the first manifestation of Behçets disease in 8.6 percent of patients. Ocular Behçets disease with involvement of the optic nerve is rarely reported. Among patients with ocular Behçets disease funduscopic findings of optic atrophy, and optic disc paleness have been identified with a frequency of 17.9 percent and 7.4 percent, respectively. Other fundoscopic findings include vascular sheathing (23.7%), retinal hemorrhage (9%), macular edema (11.3%), branch retinal vein occlusion (5.8%), and retinal edema (6.6%). However, optic atrophy was the most significant cause of visual impairment identified in 54 percent of patients with ocular Behçets disease and permanent visual impairment.The prevalence of this disease increases from North to South. It follows a more severe course in patients with an early age of onset particularly in patients with eye and gastrointestinal involvement.
Pregnancy
With Behçets disease as a pre-existing disease in pregnancy or acquired, the pregnancy does not have an adverse effect on the course of Behçets disease and may possibly ameliorate its course. Still, there is a substantial variability in clinical course between patients and even for different pregnancies in the same patient. Also, the other way around, Behçets disease confers an increased risk of pregnancy complications, miscarriage and Cesarean section.Behçets can cause male infertility, either as a result of the condition itself or of a side effect of concomitant medication such as colchicine, which is known to lower sperm count.
History
The first modern formal description of the symptoms was made by H. Planner and F. Remenovsky and published in 1922 in the Archiv für Dermatologie und Syphilis. Behçets disease is named after Hulusi Behçet (1889–1948), the Turkish dermatologist and scientist who first recognized the three main symptoms of the syndrome in one of his patients in 1924 and reported his research on the disease in Journal of Skin and Venereal Diseases in 1936. The name (Morbus Behçet) was formally adopted at the International Congress of Dermatology in Geneva in September 1947. Symptoms of this disease may have been described by Hippocrates in the 5th century BC, in his Epidemion (book 3, case 7).Some sources use the term "Adamantiadess syndrome" or "Adamantiades–Behçet syndrome", for the work done by Benediktos Adamantiades. However, the current World Health Organization/ICD-10 standard is "Behçets disease". In 1991, Saudi Arabian medical researchers described neuro-Behçets disease, a neurological involvement in Behçets disease, considered one of the most devastating manifestations of the disease. The mechanism can be immune-mediated or thrombotic. The term dates back to at least 1990.
References
Further reading
External links
Behçets disease at Curlie
Questions and answers about Behçets disease – US National Institute of Arthritis and Musculoskeletal and Skin Diseases |
Feltys syndrome | Feltys syndrome (FS), also called Felty syndrome, is rare autoimmune disease characterized by the triad of rheumatoid arthritis, enlargement of the spleen and low neutrophil count. The condition is more common in those aged 50–70 years, specifically more prevalent in females than males, and more so in Caucasians than those of African descent. It is a deforming disease that causes many complications for the individual.
Signs and symptoms
The symptoms of Feltys syndrome are similar to those of rheumatoid arthritis. Affected individuals have painful, stiff, and swollen joints, most commonly in the joints of the hands, feet, and arms. In some affected individuals, Feltys syndrome may develop during a period when the symptoms and physical findings associated with rheumatoid arthritis have subsided or are not present; in this case, Feltys syndrome may remain undiagnosed. In more rare instances, the development of Feltys syndrome may precede the development of the symptoms and physical findings associated with rheumatoid arthritis.Feltys syndrome is also characterized by an abnormally enlarged spleen (splenomegaly) and abnormally low levels of certain white blood cells (neutropenia). As a result of neutropenia, affected individuals are increasingly susceptible to certain infections. Keratoconjunctivitis sicca may occur due to secondary Sjögrens syndrome. Individuals with Feltys syndrome may also experience fever, weight loss, and/or fatigue. In some cases, affected individuals may have discoloration (abnormal brown pigmentation) of the skin, particularly of the leg, sores (ulcers) on the lower leg, and/or an abnormally large liver (hepatomegaly). In addition, affected individuals may have abnormally low levels of circulating red blood cells (anemia), a decrease in circulating blood platelets that assist in blood clotting functions (thrombocytopenia), abnormal liver function tests and/or inflammation of the blood vessels (vasculitis).
Complications
Recurrent infection
Enlargement of the spleen causing too few red blood cells and platelets in the bloodstream
Enlarged lymph nodes
Skin hyperpigmentation
Cutaneous ulceration
Causes
The cause of Feltys syndrome is unknown, but it has been found to be more common in those with chronic rheumatoid arthritis. Some patients share the HLA-DR4 serotype. This syndrome is mostly present in people having extra articular manifestations of rheumatoid arthritis. People with this syndrome are at risk of infection because they have a low white blood cell count.
Mechanism
The underlying pathogenesis of Feltys syndrome is not clear.
Rheumatoid Arthritis
Rheumatoid arthritis is an autoimmune disease that is characterized by inflammation of the synovial joints due to attack by the bodys own immune system. In this condition, the white blood cells travel through the bloodstream to the synovial joints and release pro-inflammatory cytokines upon arrival. The result of this chemical release causes the synovial cells to release harmful chemicals in response as well as begin the growth of new blood vessels, forming a pannus. The pannus receives blood supply from the newly formed vessels and grows inward, invading the articular cartilage and bone within the joint. The damage to the once healthy tissue causes inflammation and ultimately fluid build-up in the joint. An accumulation of fluid results and the joints swell, slowly decreasing the space that keeps the bones from touching. If this condition is not treated, the joint space will completely narrow, causing ankylosis. At the advanced stage of ankylosis, joint mobility is completely occluded. Early presentation is commonly seen in the joints of hands and of the feet. As the disease progresses it can be seen in the knees, wrists, hips, and shoulders. This condition can affect and damage several other body systems such as the eyes, heart, lungs, and blood vessels.Rheumatoid arthritis is a condition that cannot be cured but symptoms can be treated using certain medications alone or in conjunction. Due to the increased inflammatory response of the bodys immune system, this condition can cause a reduction in red and white blood cells.
Neutropenia
In Feltys syndrome, chronic activation of neutrophils progresses to neutropenia and unabated infections. Neutropenia is a decreased concentration of neutrophils in the blood. Neutrophils are the most abundant cells among white blood cells and play an important role in the immune system by destroying bacteria via phagocytosis. Inflammatory chemicals draw neutrophils to the area where they congregate and fight infection. A decrease in the number of neutrophils stimulates an autoimmune response which leads to arthritis. The loss and destruction of neutrophils leading to neutropenia are, therefore, inflammation-driven due to the bodys need for an immune response.
Splenomegaly
Splenomegaly is a condition of the spleen causing it to be enlarged. The splenic condition involving Felty syndrome is more specifically noted as inflammatory splenomegaly. The spleen is an important lymphatic organ that is involved in filtration of the blood by discarding old and damaged red blood cells as well as maintaining platelet levels. The spleen is a lymphatic organ, which means it is largely involved in the immune system and immune responses. When the spleen becomes enlarged, it is a strong sign of infection somewhere in the body and can be caused by inflammatory conditions such as rheumatoid arthritis. The increased need for production assistance of white blood cells to affected areas causes hyperfunction of the spleen. This increase in defense activities ultimately causes hypertrophy of the spleen, leading to splenomegaly. The spleen is found in the left upper quadrant (LUQ) of the peritoneal cavity and due to its enlargement, can cause stress on neighboring organs.
Diagnosis
This condition affects less than 1% of patients with rheumatoid arthritis. The presence of three conditions: rheumatoid arthritis, an enlarged spleen (splenomegaly), and an abnormally low white blood cell count are indications that Feltys syndrome is possibly occurring. This condition as a whole is difficult to diagnose due to its complexity given a combination of disorders. It is commonly overlooked or misdiagnosed as other conditions (e.g., leukemia, systemic lupus erythrematosus) because of the rarity and lack of good understanding about it. An acronym can be used to make recognizing this disease somewhat easier:S: SplenomegalyA: AnemiaN: NeutropeniaT: ThrombocytopeniaA: Arthritis (rheumatoid)
Conditions of the blood
A complete blood count (CBC) can be done to diagnose anemia (normochromic, normocytic), thrombocytopenia, and neutropenia. Abnormal liver function tests are commonly used to help in diagnosis as the spleen and liver are strongly affected by one another.
Splenomegaly
If rheumatoid arthritis is present and other symptoms occur that are not commonly found within RA itself, such as a palpable spleen, further testing should be done. A palpable spleen is not always a clinical significance, therefore CT scan, MRI, or ultrasound can be administered in order to help diagnose the condition. According to Poulin et al., dimensional guidelines for diagnosing splenomegaly are as follows:
Moderate if the largest dimension is 11–20 cm
Severe if the largest dimension is greater than 20 cm
Rheumatoid arthritis
RA in patients with Feltys syndrome is chronic (after 10–15 years), and presents with increased severity along with extra articular manifestations. RA can be mistaken for other conditions such as gout if not clinically diagnosed. Diagnosis can be confirmed by use of X-rays or synovial fluid analysis.
Treatment
There is no real treatment for Feltys syndrome, rather the best method in management of the disease is to control the underlying rheumatoid arthritis. Immunosuppressive therapy for RA often improves granulocytopenia and splenomegaly; this finding reflects the fact that Feltys syndrome is an immune-mediated disease. A major challenge in treating FS is recurring infection caused by neutropenia. Therefore, in order to decide upon and begin treatment, the cause and relationship of neutropenia with the overall condition must be well understood. Most of the traditional medications used to treat RA have been used in the treatment of Feltys syndrome. No well-conducted, randomized, controlled trials support the use of any single agent. Most reports on treatment regimens involve small numbers of patients.Splenectomy may improve neutropenia in severe disease.
Use of rituximab and leflunomide have been proposed.
Use of gold therapy has also been described.
Prognosis
Prognosis is dependent on the severity of symptoms and the patients overall health.
History
The condition was named after its discoverer, the American physician Augustus Roi Felty (1895–1964), who in 1924 saw a patient with a rare combination of conditions: chronic arthritis, splenomegaly, and leucopenia. His investigation of the medical literature revealed descriptions of four other cases. His findings prompted him to publish a description of the syndrome, which was subsequently named after him.
See also
Caplans syndrome
Stills disease or Still-Chauffard-Felty syndrome, the juvenile form
References
== External links == |
Severe combined immunodeficiency | Severe combined immunodeficiency (SCID), also known as Swiss-type agammaglobulinemia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in differing clinical presentations. SCID involves defective antibody response due to either direct involvement with B lymphocytes or through improper B lymphocyte activation due to non-functional T-helper cells. Consequently, both "arms" (B cells and T cells) of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is the most severe form of primary immunodeficiencies, and there are now at least nine different known genes in which mutations lead to a form of SCID. It is also known as the bubble boy disease and bubble baby disease because its victims are extremely vulnerable to infectious diseases and some of them, such as David Vetter, have become famous for living in a sterile environment. SCID is the result of an immune system so highly compromised that it is considered almost absent.
SCID patients are usually affected by severe bacterial, viral, or fungal infections early in life and often present with interstitial lung disease, chronic diarrhea, and failure to thrive. Ear infections, recurrent Pneumocystis jirovecii (previously carinii) pneumonia, and profuse oral candidiasis commonly occur. These babies, if untreated, usually die within one year due to severe, recurrent infections unless they have undergone successful hematopoietic stem cell transplantation or gene therapy in clinical trials.
Classification
Diagnosis
Early diagnosis of SCID is usually difficult due to the need for advanced screening techniques. Several symptoms may indicate a possibility of SCID in a child, such as a family history of infant death, chronic coughs, hyperinflated lungs, and persistent infections. A full blood lymphocyte count is often considered a reliable manner of diagnosing SCID, but higher lymphocyte counts in childhood may influence results. Clinical diagnosis based on genetic defects is also a possible diagnostic procedure that has been implemented in the UK.Some SCID can be detected by sequencing fetal DNA if a known history of the disease exists. Otherwise, SCID is not diagnosed until about six months of age, usually indicated by recurrent infections. The delay in detection is because newborns carry their mothers antibodies for the first few weeks of life and SCID babies look normal.
Newborn screening
Several countries test all newborns for SCID as a part of routine newborn screening. All states in the U.S. are performing screening for SCID in newborns using real-time quantitative PCR to measure the concentration of T-cell receptor excision circles. United Kingdom intends to introduce newborn screening for SCID in September 2021.
Treatment
The most common treatment for SCID is bone marrow transplantation, which has been very successful using either a matched related or unrelated donor, or a half-matched donor, who would be either parent. The half-matched type of transplant is called haploidentical. Haploidentical bone marrow transplants require the donor marrow to be depleted of all mature T cells to avoid the occurrence of graft-versus-host disease (GVHD). Consequently, a functional immune system takes longer to develop in a patient who receives a haploidentical bone marrow transplant compared to a patient receiving a matched transplant. The first reported case of successful transplant was a Spanish child patient who was interned in Memorial Sloan Kettering Cancer Center in 1982, in New York City. David Vetter, the original "bubble boy", had one of the first transplantations also, but eventually died because of an unscreened virus, Epstein-Barr (tests were not available at the time), in his newly transplanted bone marrow from his sister, an unmatched bone marrow donor. Today, transplants done in the first three months of life have a high success rate. Physicians have also had some success with in utero transplants done before the child is born and also by using cord blood which is rich in stem cells. In utero transplants allow for the fetus to develop a functional immune system in the sterile environment of the uterus; however complications such as GVHD would be difficult to detect or treat if they were to occur.More recently gene therapy has been attempted as an alternative to the bone marrow transplant. Transduction of the missing gene to hematopoietic stem cells using viral vectors is being tested in ADA SCID and X-linked SCID. In 1990, four-year-old Ashanthi DeSilva became the first patient to undergo successful gene therapy. Researchers collected samples of DeSilvas blood, isolated some of her white blood cells, and used a retrovirus to insert a healthy adenosine deaminase (ADA) gene into them. These cells were then injected back into her body, and began to express a normal enzyme. This, augmented by weekly injections of ADA, corrected her deficiency. However, the concurrent treatment of ADA injections may impair the success of gene therapy, since transduced cells will have no selective advantage to proliferate if untransduced cells can survive in the presence of the injected ADA.
In 2000, a gene therapy "success" resulted in SCID patients with a functional immune system. These trials were stopped when it was discovered that two of ten patients in one trial had developed leukemia resulting from the insertion of the gene-carrying retrovirus near an oncogene. In 2007, four of the ten patients have developed leukemias. Work aimed at improving gene therapy is now focusing on modifying the viral vector to reduce the likelihood of oncogenesis and using zinc-finger nucleases to further target gene insertion. No leukemia cases have yet been seen in trials of ADA-SCID, which does not involve the gamma c gene that may be oncogenic when expressed by a retrovirus.
From the treatments of Ashanthi DeSilva in 1990 which is considered gene therapys first success until 2014 around 60 patients were treated for either ADA-SCID or X-SCID using retroviruses vectors but as previously mentioned the occurrence of cases developing leukemia forced to make changes to improve safety, more recently in 2019 a new method using an altered version of the HIV virus as a lentivirus vector was reported in the treatment of 8 children with X-SCID, and in 2021 the same method was used in 50 children with ADA-SCID obtaining positive results in 48 of them.There are also some non-curative methods for treating SCID. Reverse isolation involves the use of laminar air flow and mechanical barriers (to avoid physical contact with others) to isolate the patient from any harmful pathogens present in the external environment. A non-curative treatment for patients with ADA-SCID is enzyme replacement therapy, in which the patient is injected with polyethyleneglycol-coupled adenosine deaminase (PEG-ADA) which metabolizes the toxic substrates of the ADA enzyme and prevents their accumulation. Treatment with PEG-ADA may be used to restore T cell function in the short term, enough to clear any existing infections before proceeding with curative treatment such as a bone marrow transplant.
Epidemiology
The most commonly quoted figure for the prevalence of SCID is around 1 in 100,000 births, although this is regarded by some to be an underestimate of the true prevalence; some estimates predict that the prevalence rate is as high as 1 in 50,000 live births. A figure of about 1 in 65,000 live births has been reported for Australia.Due to the particular genetic nature of SCID, a higher prevalence may be found in certain regions and associated cultures where higher rates of consanguineous mating occur. A Moroccan study reported that consanguineous parenting was observed in 75% of the families of Moroccan SCID patients.Recent studies indicate that one in every 2,500 children in the Navajo population inherit severe combined immunodeficiency. This condition is a significant cause of illness and death among Navajo children. Ongoing research reveals a similar genetic pattern among the related Apache people.
SCID in animals
SCID mice were and still are used in disease, vaccine, and transplant research; especially as animal models for testing the safety of new vaccines or therapeutic agents in people with weakened immune system.
Recessive gene with clinical signs similar to the human condition, also affects the Arabian horse. In horses, the condition remains a fatal disease, as the animal inevitably succumbs to an opportunistic infection within the first four to six months of life. However, carriers, who themselves are not affected by the disease, can be detected with a DNA test. Thus careful breeding practices can avoid the risk of an affected foal being produced.Another animal with well-characterized SCID pathology is the dog. There are two known forms, an X-linked SCID in Basset Hounds that has similar ontology to X-SCID in humans and an autosomal recessive form seen in one line of Jack Russell Terriers that is similar to SCID in Arabian horses and mice.SCID mice also serve as a useful animal model in the study of the human immune system and its interactions with disease, infections, and cancer. For example, normal strains of mice can be lethally irradiated, killing all rapidly dividing cells. These mice then receive bone marrow transplantation from SCID donors, allowing engraftment of human peripheral blood mononuclear cells (PBMC) to occur. This method can be used to study whether T cell-lacking mice can perform hematopoiesis after receiving human PBMC.
See also
David Vetter
Aisha Chaudhary
List of cutaneous conditions
List of radiographic findings associated with cutaneous conditions
References
Further reading
Buckley RH (2004). "Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution". Annu Rev Immunol. 22: 625–55. doi:10.1146/annurev.immunol.22.012703.104614. PMID 15032591.
Chinen J, Puck JM (2004). "Successes and risks of gene therapy in primary immunodeficiencies". J Allergy Clin Immunol. 113 (4): 595–603, quiz 604. doi:10.1016/j.jaci.2004.01.765. PMID 15100660.
Church AC (2002). "X-linked severe combined immunodeficiency". Hosp Med. 63 (11): 676–80. doi:10.12968/hosp.2002.63.11.1914. PMID 12474613.
Gennery AR, Cant AJ (2001). "Diagnosis of severe combined immunodeficiency". J Clin Pathol. 54 (3): 191–5. doi:10.1136/jcp.54.3.191. PMC 1731376. PMID 11253129.
External links
Learning About Severe Combined Immunodeficiency (SCID) NIH |
Monoclonal gammopathy of undetermined significance | Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia in which plasma cells or other types of antibody-producing cells secrete a myeloma protein, i.e. an abnormal antibody, into the blood; this abnormal protein is usually found during standard laboratory blood or urine tests. MGUS resembles multiple myeloma and similar diseases, but the levels of antibodies are lower, the number of plasma cells (white blood cells that secrete antibodies) in the bone marrow is lower, and it rarely has symptoms or major problems. However, since MGUS can lead to multiple myeloma, which develops at the rate of about 1.5% a year, or other symptomatic conditions, yearly monitoring is recommended.
The progression from MGUS to multiple myeloma usually involves several steps. In rare cases, it may also be related with a slowly progressive symmetric distal sensorimotor neuropathy.
Signs and symptoms
People with monoclonal gammopathy generally do not experience signs or symptoms. Some people may experience a rash or nerve problems, such as numbness or tingling. MGUS is usually detected by chance when the patient has a blood test for another condition or as part of standard screening.
Pathophysiology
Pathologically, the lesion in MGUS is in fact very similar to that in multiple myeloma. There is a predominance of clonal plasma cells in the bone marrow with an abnormal immunophenotype (CD38+ CD56+ CD19−) mixed in with cells of a normal phenotype (CD38+ CD56− CD19+); in MGUS, on average more than 3% of the clonal plasma cells have the normal phenotype, whereas in multiple myeloma, less than 3% of the cells have the normal phenotype.
Diagnosis
MGUS is a common, age-related medical condition characterized by an accumulation of bone marrow plasma cells derived from a single abnormal clone. Patients may be diagnosed with MGUS if they fulfill the following four criteria:
A monoclonal paraprotein band less than 30 g/L (< 3g/dL);
Plasma cells less than 10% on bone marrow examination;
No evidence of bone lesions, anemia, hypercalcemia, or chronic kidney disease related to the paraprotein, and
No evidence of another B-cell proliferative disorder.
Differential diagnosis
Several other illnesses can present with a monoclonal gammopathy, and the monoclonal protein may be the first discovery before a formal diagnosis is made:
Multiple myeloma
Smouldering multiple myeloma
AIDS
Chronic lymphocytic leukemia
Non-Hodgkin lymphoma, particularly Splenic marginal zone lymphoma and Lymphoplasmocytic lymphoma
Hepatitis C
Connective tissue disease such as lupus
Immunosuppression following organ transplantation
Waldenström macroglobulinemia
Guillain–Barré syndrome
Tempi syndrome
POEMS
Management
The protein electrophoresis test should be repeated annually, and if there is any concern for a rise in the level of monoclonal protein, then prompt referral to a hematologist is required. The hematologist, when first evaluating a case of MGUS, will usually perform a skeletal survey (X-rays of the proximal skeleton), check the blood for hypercalcemia and deterioration in renal function, check the urine for Bence Jones protein and perform a bone marrow biopsy. If none of these tests are abnormal, a patient with MGUS is followed up once every 6 months to a year with a blood test (serum protein electrophoresis). Although patients with MGUS have sometimes been reported to have peripheral neuropathy, a debilitating condition which causes bizarre sensory problems to painful sensory problems, no treatment is indicated.
Prognosis
At the Mayo Clinic, MGUS transformed into multiple myeloma or similar lymphoproliferative disorders at the rate of about 1-2% a year, or 17%, 34%, and 39% at 10, 20, and 25 years, respectively, of follow-up—among surviving patients. However, because they were elderly, most patients with MGUS died of something else and did not go on to develop multiple myeloma. When this was taken into account, only 11.2% developed lymphoproliferative disorders.Kyle studied the prevalence of myeloma in the population as a whole (not clinic patients) in Olmsted County, Minnesota. They found that the prevalence of MGUS was 3.2% in people above 50, with a slight male predominance (4.0% vs. 2.7%). Prevalence increased with age: of people over 70 up to 5.3% had MGUS, while in the over-85 age group the prevalence was 7.5%. In the majority of cases (63.5%), the paraprotein level was <1 g/dL, while only a very small group had levels over 2 g/dL. A study of monoclonal protein levels conducted in Ghana showed a prevalence of MGUS of approximately 5.9% in African men over the age of 50.In 2009, prospective data demonstrated that all or almost all cases of multiple myeloma are preceded by MGUS. In addition to multiple myeloma, MGUS may also progress to Waldenströms macroglobulinemia or primary amyloidosis.
See also
Monoclonal gammopathy
Plasma cell dyscrasia
Monoclonal gammopathy of renal significance
References
Further reading
== External links == |
Hydrocele | A hydrocele is an accumulation of serous fluid in a body cavity. A hydrocele testis is the accumulation of fluids around a testicle. It is often caused by fluid collecting within a layer wrapped around the testicle, called the tunica vaginalis, which is derived from peritoneum. Provided there is no hernia present, it goes away without treatment in the first year. Although hydroceles usually develop in males, rare instances have been described in females.Primary hydroceles may develop in adulthood, particularly in the elderly and in hot countries, by slow accumulation of serous fluid. This is presumably caused by impaired reabsorption, which appears to be the explanation for most primary hydroceles, although the reason remains obscure. A hydrocele can also be the result of a plugged inguinal lymphatic system caused by repeated, chronic infection of Wuchereria bancrofti or Brugia malayi, two mosquito-borne parasites of Africa and Southeast Asia, respectively. As such, the condition would be a part of more diffuse sequelae commonly referred to as elephantiasis, which also affects the lymphatic system in other parts of the body.
Presentation
Complications
Among the complications of hydrocele are:
Rupture usually occurs as a result of trauma but may be spontaneous. On rare occasions cure results after the fluid has been absorbed.
Transformation into a haematocele occurs if there is spontaneous bleeding into the sac or as a result of trauma. Acute haemorrhage into the tunica vaginalis sometimes results from testicular trauma and it may be difficult without exploration to decide whether the testis has been ruptured. If the haematocele is not drained, a clotted haematocele usually results.
The sac may calcify. Clotted hydrocele may result from a slow spontaneous ooze of blood into the tunica vaginalis. It is usually painless and by the time the patient seeks help, it may be difficult to be sure that the swelling is not due to a testicular tumour. Indeed, a tumour may present as a haematocele.
Occasionally, severe infection can be introduced by aspiration. Simple aspiration, however, often may be used as a temporary measure in those cases where surgery is contraindicated or must be postponed.
Postherniorrhaphy hydrocele is a relatively rare complication of inguinal hernia repair. It is possibly due to interruption to the lymphatics draining the scrotal contents.
Infection which may lead to pyocele.
Atrophy of testis in long standing cases.Complications are often diagnosed post-operatively, which can be differentiated through duplex ultrasound scanning and are bit observed until 24 to 48 hours for early complications such as drainage, infection, formation of haematocele, rupture, etc., but also for 1 to 6 weeks during follow-up on out-patient basis.
Cause
A hydrocele can be produced in four ways:
by excessive production of fluid within the sac, e.g. secondary hydrocele
through defective absorption of fluid
by interference with lymphatic drainage of scrotal structures as in case of elephantiasis
by connection with a hernia of the peritoneal cavity in the congenital variety, which presents as hydrocele of the cord
Primary hydroceles
The swelling is soft and non-tender, large in size on examination, and the testis cannot usually be felt. The presence of fluid is demonstrated by transillumination. These hydroceles can reach a huge size, containing large amount of fluid, as these are painless and are often ignored. They are otherwise asymptomatic, other than size and weight, causing inconvenience. However the long continued presence of large hydroceles causes atrophy of testis due to compression or by obstructing blood supply. In most cases, the hydrocele, when diagnosed early during complete physical examination, are small and the testis can easily be palpated within a lax hydrocele. However Ultrasound imaging is necessary to visualize the testis if the hydrocele sac is dense to reveal the primary abnormality. But these can become large in cases when left unattended. Hydroceles are usually painless, as are testicular tumors. A common method of diagnosing a hydrocele is by attempting to shine a strong light (transillumination) through the enlarged scrotum. A hydrocele will usually pass light, while a tumor will not (except in the case of a malignancy with reactive hydrocele).
Secondary hydroceles
Secondary hydroceles due to testicular diseases can be the result of cancer, trauma (such as a hernia), or orchitis (inflammation of testis), and can also occur in infants undergoing peritoneal dialysis. A hydrocele is not a cancer but it should be excluded clinically if a presence of a testicular tumor is suspected, however, there are no publications in the world literature that report a hydrocele in association with testicular cancer. Secondary hydrocele is most frequently associated with acute or chronic epididymo-orchitis. It is also seen with torsion of the testis and with some testicular tumors. A secondary hydrocele is usually lax and of moderate size: the underlying testis is palpable. A secondary hydrocele subsides when the primary lesion resolves.
Acute/chronic epididymo-orchitis
Torsion of testis
Testicular tumor
Hematocele
Filarial hydrocele
Post herniorrhaphy
Hydrocele of an hernial sac
Infantile hydroceles
It does not occur only in infants but it occurs in adults also, a hydrocele is usually an expression of a patent processus vaginalis (PPV). The tunica and the processus vaginalis are distended to the inguinal ring but there is no connection with the peritoneal cavity.
Congenital hydroceles
The processus vaginalis is patent and connects with the general peritoneal cavity. The communication is usually too small to allow herniation of intra-abdominal contents. Digital pressure on the hydrocele does not usually empty it, but the hydrocele fluid may drain into the peritoneal cavity when the child is lying down. Ascites or even ascitic tuberculous peritonitis should be considered if the swellings are bilateral.
Encysted hydrocele of the cord
There is a smooth oval swelling near the spermatic cord which is liable to be mistaken for an inguinal hernia. The swelling moves downwards and becomes less mobile if the testis is pulled gently downwards. Rarely, a hydrocele develops in a remnant of the processus vaginalis somewhere along the course of the spermatic cord. This hydrocele also transilluminates, and is known as an encysted hydrocele of the cord. In females, a related region in females, a multicystic hydrocele of the canal of Nuck sometimes presents as a swelling in the groin. It probably results from cystic degeneration of the round ligament. Unlike a hydrocele of the cord, a hydrocele of the canal of Nuck is always at least partially within the inguinal canal.The accuracy of the diagnosis must be ascertained. Great care must be taken to differentiate a hydrocele from a scrotal hernia or tumor of the testicle. Ultrasound imaging can be very useful in these cases. A hernia usually can be reduced, transmits a cough impulse, and is not translucent. A hydrocele cannot be reduced into the inguinal canal and gives no impulse on coughing unless a hernia is also present. In young children a hydrocele is often associated with a complete congenital type of hernial sac.
Diagnosis
A primary hydrocele is described as having the following characteristics:
Transillumination positive
Fluctuation positive
Impulse on coughing negative (positive in congenital hydrocele)
Reducibility absent
Testis cannot be palpated separately. (exception - funicular hydrocele, encysted hydrocele)
Treatment
Most hydroceles appearing in the first year of life seldom require treatment as they resolve without treatment. Hydroceles that persist after the first year or occur later in life require treatment only in selected cases, such as patients who are symptomatic with pain or a pressure sensation, or when the scrotal skin integrity is compromised from chronic irritation; the treatment of choice is surgery and the operation is conducted via an open access technique aiming to excise the hydrocele sac. Anesthesia is required for the operation and general anesthesia is of choice in children, while spinal anesthesia is usually sufficient in adults. Local infiltration anesthesia is not satisfactory because it cannot abolish abdominal pain due to traction on the spermatic cord. In long standing cases, hydrocele fluid may be opalescent with cholesterol and may contain crystals of tyrosine.After aspiration of a primary hydrocele, fluid reaccumulates over the following months and periodic aspiration or operation is needed. For younger patients, operation is usually preferred. Sclerotherapy is an alternative; after aspiration, 6% aqueous phenol (10-20 ml) together with 1% lidocaine for analgesia can be injected, and this often inhibits reaccumulation. These alternative treatments are generally regarded as unsatisfactory treatment because of the high incidence of recurrences and the frequent necessity for repetition of the procedure.
References
External links
Hydrocele at eMedicine |
Fetal alcohol spectrum disorder | Fetal alcohol spectrum disorders (FASDs) are a group of conditions that can occur in a person whose mother drank alcohol during pregnancy. Symptoms can include an abnormal appearance, short height, low body weight, small head size, poor coordination, behavioural problems, learning difficulties, and problems with hearing and sight. Those affected are more likely to have trouble with school, the legal system, alcohol, other drugs, and other areas of high risk. The several forms of the condition (in order of most severe to least severe) are: Fetal Alcohol Syndrome (FAS), Partial Fetal Alcohol Syndrome (pFAS), Alcohol-Related Birth Defects (ARBD),Static Encephalopathy, Alcohol-Related Neurodevelopmental Disorder (ARND) and Neurobehavioral Disorder associated with Prenatal Alcohol Exposure (ND-PAE). Some authorities accept only FAS as a diagnosis, seeing the evidence as inconclusive with respect to other types.Fetal alcohol spectrum disorders are caused by the mothers drinking alcohol while pregnant with the affected person. Surveys from the United States found that about 10% of pregnant women drank alcohol in the past month, and 20% to 30% drank at some point during the pregnancy. 3.6% of pregnant American women met criteria for an alcohol use disorder in a 2001 epidemiological study. The risk of FASD depends on the amount consumed, the frequency of consumption, and the points in pregnancy at which the alcohol is consumed. Other risk factors include the mothers older age, smoking, and poor diet. There is no known safe amount or time to drink alcohol during pregnancy. Although drinking small amounts does not cause facial abnormalities, it may cause behavioral problems. Alcohol crosses the blood–brain barrier and both directly and indirectly affects a developing fetus. Diagnosis is based on the signs and symptoms in the person.Fetal alcohol spectrum disorders are preventable by the mothers avoiding alcohol during pregnancy. For this reason, medical authorities recommend that women completely avoid drinking alcohol during pregnancy and while trying to conceive. Although the condition is permanent, treatment can improve outcomes. Interventions may include parent–child interaction therapy, efforts to modify child behavior, and drugs.FASD is estimated to affect between 1% and 5% of people in the United States and Western Europe. FAS is believed to occur in between 0.2 and 9 per 1,000 live births in the United States. In South Africa, some populations have rates as high as 9%. The negative effects of alcohol during pregnancy have been described since ancient times. The lifetime cost per child with FAS in the United States was $2 million in 2002; however in 2021, Canada revealed that the annual cost for FASD individuals was $9.7 billion (including the costs of the Criminal Justice System, healthcare, and education among others). The term fetal alcohol syndrome was first used in 1973.
Types
FASDs encompass a range of physical and neurodevelopmental problems that can result from prenatal alcohol exposure. The most severe condition is called fetal alcohol syndrome (FAS), which refers to individuals who have a specific set of birth defects and neurodevelopmental disorders characteristic of the diagnosis.Some accept only FAS as a diagnosis, seeing the evidence as inconclusive with respect to other types.
Fetal alcohol syndrome (FAS)
Partial fetal alcohol syndrome (pFAS) refers to individuals with a known, or highly suspected, history of prenatal alcohol exposure who have alcohol-related physical and neurodevelopmental deficits that do not meet the full criteria for FAS. pFAS-subtypes:
Alcohol-related neurodevelopmental disorder (ARND)
Alcohol-related birth defects (ARBD). In addition to FAS, pFAS
Alcohol-Related Neurodevelopmental Disorder (ARND)
Alcohol-Related Birth Defects (ARBD)
Neurobehavioral Disorder Associated With Prenatal Alcohol Exposure (ND-PAE)
Static EncephalopathyThese conditions believed to be related to prenatal alcohol exposure, such as spontaneous abortion and sudden infant death syndrome (SIDS), are also considered to be on the spectrum of related disorders. It is unclear as of 2017 if identifying a FASD-related condition benefits the individual.In 2013, the American Psychiatric Association introduced neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE) into the DSM-V as a "condition for further study" and as a specified condition under, "other specified neurodevelopmental disorders" as a way to better study the behavioral aspects of all FASD disorders. Though similar sounding, ND-PAE is the spectrum-wide term for the psychiatric, behavioral, and neurological symptoms of all FASDs, where as ARND is the specific diagnosis of the non-dysmorphic type of FASD where a majority of the symptoms are witnessed.
Signs and symptoms
The key of FASD can vary between individuals exposed to alcohol during pregnancy. While consensus exists for the definition and diagnosis of FAS, minor variations among the systems lead to differences in definitions and diagnostic cut-off criteria for other diagnoses across the FASD continuum.The central nervous system damage criteria particularly lacks clear consensus. A working knowledge of the key features is helpful in understanding FASD diagnoses and conditions, and each is reviewed with attention to similarities and differences across the four diagnostic systems. More than 400 problems, however, can occur with FASD.
Growth
In terms of FASD, growth deficiency is defined as significantly below average height, weight or both due to prenatal alcohol exposure and can be assessed at any point in the lifespan. Growth measurements must be adjusted for parental height, gestational age (for a premature infant), and other postnatal insults (e.g., poor nutrition), although birth height and weight are the preferred measurements. Deficiencies are documented when height or weight falls at or below the 10th percentile of standardized growth charts appropriate to the population. Prenatal or postnatal presentation of growth deficits can occur, but are most often postnatal.Criteria for FASD are least specific in the Institute of Medicine (IOM) diagnostic system ("low birth weight..., decelerating weight not due to nutrition..., [or] disproportional low weight to height" p. 4 of executive summary), while the CDC and Canadian guidelines use the 10th percentile as a cut-off to determine growth deficiency. The "4-Digit Diagnostic Code" allows for mid-range gradations in growth deficiency (between the 3rd and 10th percentiles) and severe growth deficiency at or below the 3rd percentile. Growth deficiency (at severe, moderate, or mild levels) contributes to diagnoses of FAS and pFAS, but not ARND or static encephalopathy.Growth deficiency is ranked as follows by the "4-Digit Diagnostic Code":
Severe: Height and weight at or below the 3rd percentile.
Moderate: Either height or weight at or below the 3rd percentile, but not both.
Mild: Either height or weight or both between the 3rd and 10th percentiles.
None: Height and weight both above the 10th percentile.In the initial studies that discovered FAS, growth deficiency was a requirement for inclusion in the studies; thus, all the original people with FAS had growth deficiency as an artifact of sampling characteristics used to establish criteria for the syndrome. That is, growth deficiency is a key feature of FASD because growth deficiency was a criterion for inclusion in the study that defined FAS. This suggests growth deficiency may be less critical for understanding the disabilities of FASD than the neurobehavioral sequelae to the brain damage.
Facial features
Several characteristic craniofacial abnormalities are often visible in individuals with FAS. The presence of FAS facial features indicates brain damage, although brain damage may also exist in their absence. FAS facial features (and most other visible, but non-diagnostic, deformities) are believed to be caused mainly during the 10th to 20th week of gestation.Refinements in diagnostic criteria since 1975 have yielded three distinctive and diagnostically significant facial features known to result from prenatal alcohol exposure and distinguishes FAS from other disorders with partially overlapping characteristics. The three FAS facial features are:
A smooth philtrum: The divot or groove between the nose and upper lip flattens with increased prenatal alcohol exposure.
Thin vermilion: The upper lip thins with increased prenatal alcohol exposure.
Small palpebral fissures: Eye width decreases with increased prenatal alcohol exposure.Measurement of FAS facial features uses criteria developed by the University of Washington. The lip and philtrum are measured by a trained physician with the Lip-Philtrum Guide, a five-point Likert scale with representative photographs of lip and philtrum combinations ranging from normal (ranked 1) to severe (ranked 5). Palpebral fissure length (PFL) is measured in millimeters with either calipers or a clear ruler and then compared to a PFL growth chart, also developed by the University of Washington.Ranking FAS facial features is complicated because the three separate facial features can be affected independently by prenatal alcohol. A summary of the criteria follows:
Severe: All three facial features ranked independently as severe (lip ranked at 4 or 5, philtrum ranked at 4 or 5, and PFL two or more standard deviations below average).
Moderate: Two facial features ranked as severe and one feature ranked as moderate (lip or philtrum ranked at 3, or PFL between one and two standard deviations below average).
Mild: A mild ranking of FAS facial features covers a broad range of facial feature combinations:
Two facial features ranked severe and one ranked within normal limits,
One facial feature ranked severe and two ranked moderate, or
One facial feature ranked severe, one ranked moderate and one ranked within normal limits.
None: All three facial features ranked within normal limits.
Central nervous system
Central nervous system (CNS) damage is the primary feature of any FASD diagnosis. Prenatal alcohol exposure, which is classified as a teratogen, can damage the brain across a continuum of gross to subtle impairments, depending on the amount, timing, and frequency of the exposure as well as genetic predispositions of the fetus and mother. While functional abnormalities are the behavioral and cognitive expressions of the FASD disability, CNS damage can be assessed in three areas: structural, neurological, and functional impairments.All four diagnostic systems allow for assessment of CNS damage in these areas, but criteria vary. The IOM system requires structural or neurological impairment for a diagnosis of FAS, but also allows a "complex pattern" of functional anomalies for diagnosing PFAS and ARND. The "4-Digit Diagnostic Code" and CDC guidelines allow for a positive CNS finding in any of the three areas for any FASD diagnosis, but functional anomalies must measure at two standard deviations or worse in three or more functional domains for a diagnosis of FAS, PFAS, and ARND. The "4-Digit Diagnostic Code" also allows for an FASD diagnosis when only two functional domains are measured at two standard deviations or worse. The "4-Digit Diagnostic Code" further elaborates the degree of CNS damage according to four ranks:
Definite: Structural impairments or neurological impairments for FAS or static encephalopathy.
Probable: Significant dysfunction of two standard deviations or worse in three or more functional domains.
Possible: Mild to moderate dysfunction of two standard deviations or worse in one or two functional domains or by judgment of the clinical evaluation team that CNS damage cannot be dismissed.
Unlikely: No evidence of CNS damage.
Structural
Structural abnormalities of the brain are observable, physical damage to the brain or brain structures caused by prenatal alcohol exposure. Structural impairments may include microcephaly (small head size) of two or more standard deviations below the average, or other abnormalities in brain structure (e.g., agenesis of the corpus callosum, cerebellar hypoplasia).Microcephaly is determined by comparing head circumference (often called occipitofrontal circumference, or OFC) to appropriate OFC growth charts. Other structural impairments must be observed through medical imaging techniques by a trained physician. Because imaging procedures are expensive and relatively inaccessible to most people, diagnosis of FAS is not frequently made via structural impairments, except for microcephaly.Evidence of a CNS structural impairment due to prenatal alcohol exposure will result in a diagnosis of FAS, and neurological and functional impairments are highly likely.During the first trimester of pregnancy, alcohol interferes with the migration and organization of brain cells, which can create structural deformities or deficits within the brain. During the third trimester, damage can be caused to the hippocampus, which plays a role in memory, learning, emotion, and encoding visual and auditory information, all of which can create neurological and functional CNS impairments as well.As of 2002, there were 25 reports of autopsies on infants known to have FAS. The first was in 1973, on an infant who died shortly after birth. The examination revealed extensive brain damage, including microcephaly, migration anomalies, callosal dysgenesis, and a massive neuroglial, leptomeningeal heterotopia covering the left hemisphere.In 1977, Dr. Clarren described a second infant whose mother was a binge drinker. The infant died ten days after birth. The autopsy showed severe hydrocephalus, abnormal neuronal migration, and a small corpus callosum (which connects the two brain hemispheres) and cerebellum. FAS has also been linked to brainstem and cerebellar changes, agenesis of the corpus callosum and anterior commissure, neuronal migration errors, absent olfactory bulbs, meningomyelocele, and porencephaly.
Neurological
When structural impairments are not observable or do not exist, neurological impairments are assessed. In the context of FASD, neurological impairments are caused by prenatal alcohol exposure which causes general neurological damage to the central nervous system (CNS), the peripheral nervous system, or the autonomic nervous system. A determination of a neurological problem must be made by a trained physician, and must not be due to a postnatal insult, such as meningitis, concussion, traumatic brain injury, etc.All four diagnostic systems show virtual agreement on their criteria for CNS damage at the neurological level, and evidence of a CNS neurological impairment due to prenatal alcohol exposure will result in a diagnosis of FAS or pFAS, and functional impairments are highly likely.Neurological problems are expressed as either hard signs, or diagnosable disorders, such as epilepsy or other seizure disorders, or soft signs. Soft signs are broader, nonspecific neurological impairments, or symptoms, such as impaired fine motor skills, neurosensory hearing loss, poor gait, clumsiness, and poor hand - eye coordination. Many soft signs have norm-referenced criteria, while others are determined through clinical judgment. "Clinical judgment" is only as good as the clinician, and soft signs should be assessed by either a pediatric neurologist, a pediatric neuropsychologist, or both.
Functional
When structural or neurological impairments are not observed, all four diagnostic systems allow CNS damage due to prenatal alcohol exposure to be assessed in terms of functional impairments. Functional impairments are deficits, problems, delays, or abnormalities due to prenatal alcohol exposure (rather than hereditary causes or postnatal insults) in observable and measurable domains related to daily functioning, often referred to as developmental disabilities. There is no consensus on a specific pattern of functional impairments due to prenatal alcohol exposure and only CDC guidelines label developmental delays as such, so criteria (and FASD diagnoses) vary somewhat across diagnostic systems.
The four diagnostic systems list various CNS domains that can qualify for functional impairment that can determine an FASD diagnosis:
Evidence of a complex pattern of behavior or cognitive abnormalities inconsistent with developmental level in the following CNS domains – Sufficient for a pFAS or ARND diagnosis using IOM guidelinesLearning disabilities, academic achievement, impulse control, social perception, communication, abstraction, math skills, memory, attention, judgment
Performance at two or more standard deviations on standardized testing in three or more of the following CNS domains – Sufficient for an FAS, pFAS or static encephalopathy diagnosis using 4-Digit Diagnostic CodeExecutive functioning, memory, cognition, social/adaptive skills, academic achievement, language, motor skills, attention, activity level
General cognitive deficits (e.g., IQ) at or below the 3rd percentile on standardized testing – Sufficient for an FAS diagnosis using CDC guidelines
Performance at or below the 16th percentile on standardized testing in three or more of the following CNS domains – Sufficient for an FAS diagnosis using CDC guidelinesCognition, executive functioning, motor functioning, attention and hyperactive problems, social skills, sensory processing disorder, social communication, memory, difficulties responding to common parenting practices
Performance at two or more standard deviations on standardized testing in three or more of the following CNS domains – Sufficient for an FAS diagnosis using Canadian guidelines
Cognition, communication, academic achievement, memory, executive functioning, adaptive behavior, motor skills, social skills, social communication
Related signs
Other conditions may commonly co-occur with FAS, stemming from prenatal alcohol exposure. However, these conditions are considered alcohol-related birth defects and not diagnostic criteria for FAS.
Heart: A heart murmur that frequently disappears by one year of age. Ventricular septal defect, atrial septal defect, Tetralogy of Fallot, coarctation of the aorta, and/or cardiac rhythm dysfunction.
Bones: Joint anomalies including abnormal position and function, altered palmar crease patterns, small distal phalanges, and small fifth fingernails.
Kidneys: Horseshoe, aplastic, dysplastic, or hypoplastic kidneys.
Eyes: Strabismus, optic nerve hypoplasia (which may cause light sensitivity, decreased visual acuity, or involuntary eye movements).
Occasional problems: ptosis of the eyelid, microphthalmia, cleft lip with or without a cleft palate, webbed neck, short neck, spina bifida, and hydrocephalus.
Cause
Fetal alcohol spectrum disorder is caused by a woman consuming alcohol while pregnant. Alcohol crosses through the placenta to the unborn child and can interfere with normal development. Alcohol is a teratogen (causes birth defects) and there is no known safe amount of alcohol to consume while pregnant and there is no known safe time during pregnancy to consume alcohol to prevent birth defects such as FASD. Evidence of harm from low levels of alcohol consumption is not clear and since there are not known safe amounts of alcohol, women are suggested to completely abstain from drinking when trying to get pregnant and while pregnant. Small amounts of alcohol may not cause an abnormal appearance, however, small amounts of alcohol consumption while pregnant may cause milder symptoms such as behavioral problems and also increases the risk of miscarriage.Among those women who are alcoholic, an estimated one-third of their children have FAS.
Mechanism
Despite intense research efforts, the exact mechanism for the development of FAS or FASD is unknown. On the contrary, clinical and animal studies have identified a broad spectrum of pathways through which maternal alcohol can negatively affect the outcome of a pregnancy. Clear conclusions with universal validity are difficult to draw, since different ethnic groups show considerable genetic polymorphism for the hepatic enzymes responsible for ethanol detoxification.Genetic examinations have revealed a continuum of long-lasting molecular effects that are not only timing specific but are also dosage specific; with even moderate amounts being able to cause alterations.A human fetus appears to be at triple risk from maternal alcohol consumption:
The placenta allows free entry of ethanol and toxic metabolites like acetaldehyde into the fetal compartment. The so-called placental barrier is practically absent with respect to ethanol.
The developing fetal nervous system appears particularly sensitive to ethanol toxicity. The latter interferes with proliferation, differentiation, neuronal migration, axonic outgrowth, integration, and fine-tuning of the synaptic network. In short, all major processes in the developing central nervous system appear compromised.
Fetal tissues are quite different from adult tissues in function and purpose. For example, the main detoxicating organ in adults is the liver, whereas the fetal liver is incapable of detoxifying ethanol, as the ADH and ALDH enzymes have not yet been brought to expression at this early stage. Up to term, fetal tissues do not have significant capacity for the detoxification of ethanol, and the fetus remains exposed to ethanol in the amniotic fluid for periods far longer than the decay time of ethanol in the maternal circulation. The lack of significant quantities of ADH and ALDH means that fetal tissues have much lower quantities of antioxidant enzymes, like SOD, glutathione transferases, and glutathion peroxidases, resulting in antioxidant protection being much less effective.Additionally, ethanol may alter fetal development by interfering with retinoic acid signaling. Acetaldehyde, the main ethanol metabolite, can compete with retinaldehyde and prevent its oxidation to retinoic acid.
Diagnosis
Because admission of alcohol use during pregnancy can stigmatize birth mothers, many are reluctant to admit to drinking or to provide an accurate report of the quantity they drank. This complicates diagnosis and treatment of the syndrome. As a result, diagnosis of the severity of FASD relies on protocols of observation of the childs physiology and behavior rather than maternal self-reporting.
Presently, four FASD diagnostic systems that diagnose FAS and other FASD conditions have been developed in North America:
The Institute of Medicines guidelines for FAS, the first system to standardize diagnoses of individuals with prenatal alcohol exposure;
The University of Washingtons "The 4-Digit Diagnostic Code", which ranks the four key features of FASD on a Likert scale of one to four and yields 256 descriptive codes that can be categorized into 22 distinct clinical categories, ranging from FAS to no findings;
The Centers for Disease Controls "Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis", which established consensus on the diagnosis FAS in the U.S. but deferred addressing other FASD conditions; and
Canadian guidelines for FASD diagnoses, which established criteria for diagnosing FASD in Canada and harmonized most differences between the IOM and University of Washingtons systems.Each diagnostic system requires that a complete FASD evaluation includes an assessment of the four key features of FASD, described below. A positive finding on all four features is required for a diagnosis of FAS. However, prenatal alcohol exposure and central nervous system damage are the critical elements of the spectrum of FASD, and a positive finding in these two features is sufficient for an FASD diagnosis that is not "full-blown FAS".While the four diagnostic systems essentially agree on criteria for fetal alcohol syndrome (FAS), there are still differences when full criteria for FAS are not met. This has resulted in differing and evolving nomenclature for other conditions across the spectrum of FASD, which may account for such a wide variety of terminology. Most individuals with deficits resulting from prenatal alcohol exposure do not express all features of FAS and fall into other FASD conditions. The Canadian guidelines recommend the assessment and descriptive approach of the "4-Digit Diagnostic Code" for each key feature of FASD and the terminology of the IOM in diagnostic categories, excepting ARBD.Thus, other FASD conditions are partial expressions of FAS. However, these other FASD conditions may create disabilities similar to FAS if the key area of central nervous system damage shows clinical deficits in two or more of ten domains of brain functioning. Essentially, even though growth deficiency and/or FAS facial features may be mild or nonexistent in other FASD conditions, yet clinically significant brain damage of the central nervous system is present. In these other FASD conditions, an individual may be at greater risk for adverse outcomes because brain damage is present without associated visual cues of poor growth or the "FAS face" that might ordinarily trigger an FASD evaluation. Such individuals may be misdiagnosed with primary mental health disorders such as ADHD or oppositional defiance disorder without appreciation that brain damage is the underlying cause of these disorders, which requires a different treatment paradigm than typical mental health disorders. While other FASD conditions may not yet be included as an ICD or DSM-IV-TR diagnosis, they nonetheless pose significant impairment in functional behavior because of underlying brain damage.
Fetal alcohol syndrome
The following criteria must be fully met for an FAS diagnosis:
Growth deficiency: Prenatal or postnatal height or weight (or both) at or below the 10th percentile
FAS facial features: All three FAS facial features present
Central nervous system damage: Clinically significant structural neurological, or functional impairment
Prenatal alcohol exposure: Confirmed or Unknown prenatal alcohol exposureFetal alcohol syndrome (FAS) is the first diagnosable condition of FASD that was discovered. FAS is the only expression of FASD that has garnered consensus among experts to become an official ICD-9 and ICD-10 diagnosis. To make this diagnosis or determine any FASD condition, a multi-disciplinary evaluation is necessary to assess each of the four key features for assessment. Generally, a trained physician will determine growth deficiency and FAS facial features. While a qualified physician may also assess central nervous system structural abnormalities and/or neurological problems, usually central nervous system damage is determined through psychological, speech-language, and occupational therapy assessments to ascertain clinically significant impairments in three or more of the Ten Brain Domains. Prenatal alcohol exposure risk may be assessed by a qualified physician, psychologist, social worker, or chemical health counselor. These professionals work together as a team to assess and interpret data of each key feature for assessment and develop an integrative, multi-disciplinary report to diagnose FAS (or other FASD conditions) in an individual.
Partial FAS
Partial FAS (pFAS) was previously known as atypical FAS in the 1997 edition of the "4-Digit Diagnostic Code". People with pFAS have a confirmed history of prenatal alcohol exposure, but may lack growth deficiency or the complete facial stigmata. Central nervous system damage is present at the same level as FAS. These individuals have the same functional disabilities but "look" less like FAS.The following criteria must be fully met for a diagnosis of Partial FAS:
Growth deficiency: Growth or height may range from normal to deficient
FAS facial features: Two or three FAS facial features present
Central nervous system damage: Clinically significant structural, neurological, or functional impairment in three or more of the Ten Brain Domains
Prenatal alcohol exposure: Confirmed prenatal alcohol exposure
Fetal alcohol effects
Fetal alcohol effects (FAE) is a previous term for alcohol-related neurodevelopmental disorder and alcohol-related birth defects. It was initially used in research studies to describe humans and animals in whom teratogenic effects were seen after confirmed prenatal alcohol exposure (or unknown exposure for humans), but without obvious physical anomalies. Smith (1981) described FAE as an "extremely important concept" to highlight the debilitating effects of brain damage, regardless of the growth or facial features. This term has fallen out of favor with clinicians because it was often regarded by the public as a less severe disability than FAS, when in fact its effects can be just as detrimental.
Alcohol-related neurodevelopmental disorder
Alcohol-related neurodevelopmental disorder (ARND) was initially suggested by the Institute of Medicine to replace the term FAE and focus on central nervous system damage, rather than growth deficiency or FAS facial features. The Canadian guidelines also use this diagnosis and the same criteria. While the "4-Digit Diagnostic Code" includes these criteria for three of its diagnostic categories, it refers to this condition as static encephalopathy. The behavioral effects of ARND are not necessarily unique to alcohol however, so use of the term must be within the context of confirmed prenatal alcohol exposure. ARND may be gaining acceptance over the terms FAE and ARBD to describe FASD conditions with central nervous system abnormalities or behavioral or cognitive abnormalities or both due to prenatal alcohol exposure without regard to growth deficiency or FAS facial features.The following criteria must be fully met for a diagnosis of ARND or static encephalopathy:
Growth deficiency: Growth or height may range from normal to minimally deficient
FAS facial features: Minimal or no FAS facial features present
Central nervous system damage: Clinically significant structural, neurological, or functional impairment in three or more of the Ten Brain Domains
Prenatal alcohol exposure: Confirmed prenatal alcohol exposure;0
Alcohol-related birth defects
Alcohol-related birth defects (ARBD), formerly known as possible fetal alcohol effect (PFAE), was a term proposed as an alternative to FAE and PFAE. The IOM presents ARBD as a list of congenital anomalies that are |
Fetal alcohol spectrum disorder | linked to maternal alcohol use but have no key features of FASD. PFAE and ARBD have fallen out of favor because these anomalies are not necessarily specific to maternal alcohol consumption and are not criteria for diagnosis of FASD. The Canadian guidelines recommend that ARBD should not be used as an umbrella term or diagnostic category for FASD.
Exposure
Prenatal alcohol exposure is determined by interview of the biological mother or other family members knowledgeable of the mothers alcohol use during the pregnancy (if available), prenatal health records (if available), and review of available birth records, court records (if applicable), chemical dependency treatment records (if applicable), chemical biomarkers, or other reliable sources.
Exposure level is assessed as confirmed exposure, unknown exposure, and confirmed absence of exposure by the IOM, CDC and Canadian diagnostic systems. The "4-Digit Diagnostic Code" further distinguishes confirmed exposure as High Risk and Some Risk:
High Risk: Confirmed use of alcohol during pregnancy known to be at high blood alcohol levels (100 mg/dL or greater) delivered at least weekly in early pregnancy.
Some Risk: Confirmed use of alcohol during pregnancy with use less than High Risk or unknown usage patterns.
Unknown Risk: Unknown use of alcohol during pregnancy.
No Risk: Confirmed absence of prenatal alcohol exposure.
Confirmed exposure
Amount, frequency, and timing of prenatal alcohol use can dramatically impact the other three key features of FASD. While consensus exists that alcohol is a teratogen, there is no clear consensus as to what level of exposure is toxic. The CDC guidelines are silent on these elements diagnostically. The IOM and Canadian guidelines explore this further, acknowledging the importance of significant alcohol exposure from regular or heavy episodic alcohol consumption in determining, but offer no standard for diagnosis. Canadian guidelines discuss this lack of clarity and parenthetically point out that "heavy alcohol use" is defined by the National Institute on Alcohol Abuse and Alcoholism as five or more drinks per episode on five or more days during a 30-day period."The 4-Digit Diagnostic Code" ranking system distinguishes between levels of prenatal alcohol exposure as high risk and some risk. It operationalizes high risk exposure as a blood alcohol concentration (BAC) greater than 100 mg/dL delivered at least weekly in early pregnancy. This BAC level is typically reached by a 55 kg female drinking six to eight beers in one sitting.
Unknown exposure
For many adopted or adults and children in foster care, records or other reliable sources may not be available for review. Reporting alcohol use during pregnancy can also be stigmatizing to birth mothers, especially if alcohol use is ongoing. In these cases, all diagnostic systems use an unknown prenatal alcohol exposure designation. A diagnosis of FAS is still possible with an unknown exposure level if other key features of FASD are present at clinical levels.
Confirmed absence of exposure
Confirmed absence of exposure would apply to planned pregnancies in which no alcohol was used or pregnancies of women who do not use alcohol or report no use during the pregnancy. This designation is relatively rare, as most people presenting for an FASD evaluation are at least suspected to have had a prenatal alcohol exposure due to presence of other key features of FASD.
Biomarkers
Evidence is insufficient for the use of chemical biomarkers to detect prenatal alcohol exposure. Biomarkers being studied include fatty acid ethyl esters (FAEE) detected in the meconium (first feces of an infant) and hair. FAEE may be present if chronic alcohol exposure occurs during the 2nd and 3rd trimester since this is when the meconium begins to form. Concentrations of FAEE can be influence by medication use, diet, and individual genetic variations in FAEE metabolism however.
Ten brain domains
A recent effort to standardize assessment of functional CNS damage has been suggested by an experienced FASD diagnostic team in Minnesota. The proposed framework attempts to harmonize IOM, 4-Digit Diagnostic Code, CDC, and Canadian guidelines for measuring CNS damage vis-à-vis FASD evaluations and diagnosis. The standardized approach is referred to as the Ten Brain Domains and encompasses aspects of all four diagnostic systems recommendations for assessing CNS damage due to prenatal alcohol exposure. The framework provides clear definitions of brain dysfunction, specifies empirical data needed for accurate diagnosis, and defines intervention considerations that address the complex nature of FASD with the intention to avoid common secondary disabilities.The proposed Ten Brain Domains include:
Achievement, adaptive behavior, attention, cognition, executive functioning, language, memory, motor skills, multisensory integration or soft neurological problems, social communicationThe Fetal Alcohol Diagnostic Program (FADP) uses unpublished Minnesota state criteria of performance at 1.5 or more standard deviations on standardized testing in three or more of the Ten Brain Domains to determine CNS damage. However, the Ten Brain Domains are easily incorporated into any of the four diagnostic systems CNS damage criteria, as the framework only proposes the domains, rather than the cut-off criteria for FASD.
Differential diagnosis
The CDC reviewed nine syndromes that have overlapping features with FAS; however, none of these syndromes include all three FAS facial features, and none are the result of prenatal alcohol exposure:
Aarskog syndrome
Williams syndrome
Noonan syndrome
Dubowitz syndrome
Brachman-DeLange syndrome
Toluene syndrome
Fetal hydantoin syndrome
Fetal valproate syndrome
Maternal PKU fetal effectsOther disorders that have overlapping behavioral symptoms and/or that might be comorbid to Fetal Alcohol Spectrum Disorder might include:
Attention deficit hyperactive disorder
Autism spectrum disorder
Reactive attachment disorder
Oppositional defiant disorder
Sensory integration dysfunction
Bipolar disorder
DepressionMost people with an FASD have most often been misdiagnosed with ADHD due to the large overlap between their behavioral deficits.
Prevention
The only certain way to prevent FAS is to avoid drinking alcohol during pregnancy. In the United States, the Surgeon General recommended in 1981, and again in 2005, that women abstain from alcohol use while pregnant or while planning a pregnancy, the latter to avoid damage even in the earliest stages (even weeks) of a pregnancy, as the woman may not be aware that she has conceived. The Centers for Disease Control and the American College of Obstetricians and Gynecologists also recommend no alcohol during pregnancy. In the United States, federal legislation has required that warning labels be placed on all alcoholic beverage containers since 1988 under the Alcoholic Beverage Labeling Act.There is some controversy surrounding the "zero-tolerance" approach taken by many countries when it comes to alcohol consumption during pregnancy. The assertion that moderate drinking causes FAS is said to lack strong evidence and, in fact, the practice of equating a responsible level of drinking with potential harm to the fetus may have negative social, legal, and health impacts. In addition, special care should be taken when considering statistics on this disease, as prevalence and causation is often linked with FASD, which is more common and causes less harm, as opposed to FAS.
Treatment
There is no current cure for FASD, but treatment is possible. Early intervention from birth to age 3 has been shown to improve the development of a child born with FASD. Because CNS damage, symptoms, secondary disabilities, and needs vary widely by individual, there is no one treatment type that works for everyone.Between 2017 and 2019 researchers made a breakthrough when they discovered a possible cure using Neural Stem Cells(NSCs) they propose that if applied to a newborn, the damage can be reversed and prevent any lasting effects in the future.
Medication
Psychoactive drugs are frequently tried on those with FASD as many FASD symptoms are mistaken for or overlap with other disorders, most notably ADHD.
Behavioral interventions
Behavioral interventions are based on the learning theory, which is the basis for many parenting and professional strategies and interventions. Along with ordinary parenting styles, such strategies are frequently used by default for treating those with FAS, as the diagnoses oppositional defiance disorder (ODD), conduct disorder, reactive attachment disorder (RAD) often overlap with FAS (along with ADHD), and these are sometimes thought to benefit from behavioral interventions. Frequently, a persons poor academic achievement results in special education services, which also utilizes principles of learning theory, behavior modification, and outcome-based education.
Developmental framework
Many books and handouts on FAS recommend a developmental approach, based on developmental psychology, even though most do not specify it as such and provide little theoretical background. Optimal human development generally occurs in identifiable stages (e.g., Jean Piagets theory of cognitive development, Erik Eriksons stages of psychosocial development, John Bowlbys attachment framework, and other developmental stage theories). FAS interferes with normal development, which may cause stages to be delayed, skipped, or immaturely developed. Over time, an unaffected child can negotiate the increasing demands of life by progressing through stages of development normally, but not so for a child with FAS.By knowing what developmental stages and tasks children follow, treatment and interventions for FAS can be tailored to helping a person meet developmental tasks and demands successfully. If a person is delayed in the adaptive behavior domain, for instance, then interventions would be recommended to target specific delays through additional education and practice (e.g., practiced instruction on tying shoelaces), giving reminders, or making accommodations (e.g., using slip-on shoes) to support the desired functioning level. This approach is an advance over behavioral interventions, because it takes the persons developmental context into account while developing interventions.
Advocacy model
The advocacy model takes the point of view that someone is needed to actively mediate between the environment and the person with FAS. Advocacy activities are conducted by an advocate (for example, a family member, friend, or case manager) and fall into three basic categories. An advocate for FAS: (1) interprets FAS and the disabilities that arise from it and explains it to the environment in which the person operates, (2) engenders change or accommodation on behalf of the person, and (3) assists the person in developing and reaching attainable goals.The advocacy model is often recommended, for example, when developing an Individualized Education Program (IEP) for the persons progress at school.An understanding of the developmental framework would presumably inform and enhance the advocacy model, but advocacy also implies interventions at a systems level as well, such as educating schools, social workers, and so forth on best practices for FAS. However, several organizations devoted to FAS also use the advocacy model at a community practice level as well.
Public health and policy
Treating FAS at the public health and public policy level promotes FAS prevention and diversion of public resources to assist those with FAS. It is related to the advocacy model but promoted at a systems level (rather than with the individual or family), such as developing community education and supports, state or province level prevention efforts (e.g., screening for maternal alcohol use during OB/GYN or prenatal medical care visits), or national awareness programs. Several organizations and state agencies in the U.S. are dedicated to this type of intervention.The US Centers for Disease Control estimates 3 million women in the United States are at risk of having a baby with FASD, and recommended that women of child-bearing age should be on birth control or abstain from drinking alcohol as the safest way to avoid this.
Prognosis
The prognosis of FASD is variable depending on the type, severity, and if treatment is issued.Prognostic disabilities are divided into Primary & Secondary Disabilities:
Primary disabilities
The primary disabilities of FAS are the functional difficulties with which the child is born as a result of CNS damage due to prenatal alcohol exposure.Often, primary disabilities are mistaken as behavior problems, but the underlying CNS damage is the originating source of a functional difficulty, rather than a mental health condition, which is considered a secondary disability. The exact mechanisms for functional problems of primary disabilities are not always fully understood, but animal studies have begun to shed light on some correlates between functional problems and brain structures damaged by prenatal alcohol exposure. Representative examples include:
Learning impairments are associated with impaired dendrites of the hippocampus
Impaired motor development and functioning are associated with reduced size of the cerebellum
Hyperactivity is associated with decreased size of the corpus callosumFunctional difficulties may result from CNS damage in more than one domain, but common functional difficulties by domain include: Note that this is not an exhaustive list of difficulties.
Achievement: Learning disabilities
Adaptive behavior: Poor impulse control, poor personal boundaries, poor anger management, stubbornness, intrusive behavior, too friendly with strangers, poor daily living skills, developmental delays
Attention: Attention-Deficit/Hyperactivity Disorder (ADHD), poor attention or concentration, distractible
Cognition: Intellectual disability, confusion under pressure, poor abstract skills, difficulty distinguishing between fantasy and reality, slower cognitive processing
Executive functioning: Poor judgment, Information-processing disorder, poor at perceiving patterns, poor cause and effect reasoning, inconsistent at linking words to actions, poor generalization ability
Language: Expressive or receptive language disorders, grasp parts but not whole concepts, lack understanding of metaphor, idioms, or sarcasm
Memory: Poor short-term memory, inconsistent memory and knowledge base
Motor skills: Poor handwriting, poor fine motor skills, poor gross motor skills, delayed motor skill development (e.g., riding a bicycle at appropriate age)
Sensory processing and soft neurological problems: sensory processing disorder, sensory defensiveness, undersensitivity to stimulation
Social communication: Intrude into conversations, inability to read nonverbal or social cues, "chatty" but without substance
Secondary disabilities
The secondary disabilities of FAS are those that arise later in life secondary to CNS damage. These disabilities often emerge over time due to a mismatch between the primary disabilities and environmental expectations; secondary disabilities can be ameliorated with early interventions and appropriate supportive services.Six main secondary disabilities were identified in a University of Washington research study of 473 subjects diagnosed with FAS, PFAS (partial fetal alcohol syndrome), and ARND (alcohol-related neurodevelopmental disorder):
Mental health problems: Diagnosed with ADHD, Clinical Depression, or other mental illness, experienced by over 90% of the subjects
Disrupted school experience: Suspended or expelled from school or dropped out of school, experienced by 60% of the subjects (age 12 and older)
Trouble with the law: Charged or convicted with a crime, experienced by 60% of the subjects (age 12 and older)
Confinement: For inpatient psychiatric care, inpatient chemical dependency care, or incarcerated for a crime, experienced by about 50% of the subjects (age 12 and older)
Inappropriate sexual behavior: Sexual advances, sexual touching, or promiscuity, experienced by about 50% of the subjects (age 12 and older)
Alcohol and drug problems: Alcohol use disorder or dependence, experienced by 35% of the subjects (age 12 and older)Two additional secondary disabilities exist for adults:
Dependent living: Group home, living with family or friends, or some sort of assisted living, experienced by 80% of the subjects (age 21 and older)
Problems with employment: Required ongoing job training or coaching, could not keep a job, unemployed, experienced by 80% of the subjects (age 21 and older)
Protective factors and strengths
Eight factors were identified in the same study as universal protective factors that reduced the incidence rate of the secondary disabilities:
Living in a stable and nurturing home for over 73% of life
Being diagnosed with FAS before age six
Never having experienced violence
Remaining in each living situation for at least 2.8 years
Experiencing a "good quality home" (meeting 10 or more defined qualities) from age 8 to 12 years old
Having been found eligible for developmental disability (DD) services
Having basic needs met for at least 13% of life
Having a diagnosis of FAS (rather than another FASD condition)Malbin (2002) has identified the following areas of interests and talents as strengths that often stand out for those with FASD and should be utilized, like any strength, in treatment planning:
Music, playing instruments, composing, singing, art, spelling, reading, computers, mechanics, woodworking, skilled vocations (welding, electrician, etc.), writing, poetry
Participation in non-impact sport or physical fitness activities
Lifespan
One study found that the people with FASD had a significantly shorter life expectancy. With the average life span of 34 years old, a study found that 44% of the deaths were of "external cause", with 15% of deaths being suicides.
Epidemiology
FASD is estimated to affect between 2% and 5% of people in the United States and Western Europe. FAS is believed to occur in between 0.2 and 9 per 1000 live births in the United States. The lifetime costs of an individual with FAS were estimated to be two million USD in 2002. Drinking any quantity during pregnancy, the risk of giving birth to a child with FASD is about 15%, and to a child with FAS about 1.5%. Drinking large quantities, defined as 2 standard drinks a day, or 6 standard drinks in a short time, carries a 4.3% risk of a FAS birth (i.e. one of every 23 heavy-drinking pregnant women will deliver a child with FAS). In a recent count the prevailence of having any FASD disorder was 1 person out of 20, but some people estimate it could be as high as 1 in 7.
Australia
FASD among Australian youth is more common in indigenous Australians. The only states that have registered birth defects in Australian youth are Western Australia, New South Wales, Victoria and South Australia. In Australia, only 12% of Australian health professionals are aware of the diagnostics and symptoms of FASD. In Western Australia, the rate of births resulting in FASD is 0.02 per 1,000 births for non-Indigenous Australians, however among indigenous births the rate is 2.76 per 1,000 births. In Victoria, there have been no registered FASD related births for indigenous Australians, but the rate for the general population in Victoria is 0.01–0.03 per 1000 births. There have been no dedicated FASD clinics within Western Australia, but there are also no nationally supported diagnostic criteria anywhere in Australia. Passive surveillance is a prevention technique used within Australia to assist in monitoring and establishing detectable defects during pregnancy and childhood.
History
From the 1960s to the 1980s, alcohol was commonly used as a tocolytic, a method to stop preterm labor. The method originated with Dr. Fritz Fuchs, the chairman of the department of obstetrics and gynecology at Cornell University Medical College. Doctors recommended a small amount of alcohol to calm the uterus during contractions in early pregnancy or Braxton Hicks contractions. In later stages of pregnancy, the alcohol was administered intravenously and often in large amounts. "Women experienced similar effects as occur with oral ingestion, including intoxication, nausea and vomiting, and potential alcohol poisoning, followed by hangovers when the alcohol was discontinued." Vomiting put the mother at a high risk for aspiration and was "a brutal procedure for all involved". Because the alcohol was being given intravenously, the doctor could continue giving the treatment to the mother long after she had passed out, resulting in her being more intoxicated than would otherwise be possible. Such heavy intoxication is highly likely to contribute to FASD.
Historical references
Admonitions against prenatal alcohol use from ancient Greek, Roman, Talmudic, and possibly Biblical sources indicate a historical awareness of links between alcohol use and fetal development, although sources rarely if ever distinguish maternal alcohol consumption from paternal. For example, Plato writes in his fourth-century B.C. Laws (6.775): "Drinking to excess is a practice that is nowhere seemly [...] nor yet safe. [...] It behooves both bride and bridegroom to be sober [...] in order to ensure, as far as possible, in every case that the child that is begotten may be sprung from the loins of sober parents." Likewise, the sixth-century A.D. Talmud (Kethuboth 60b) cautions, "One who drinks intoxicating liquor will have ungainly children." In such ancient sources, the warnings against alcohol consumption for fetal development are more frequently concerned with conception than pregnancy.
In 1725, British physicians petitioned the House of Commons on the effects of strong drink when consumed by pregnant women saying that such drinking is "too often the cause of weak, feeble, and distempered children, who must be, instead of an advantage and strength, a charge to their country." There are many other such historical references. In Gaelic Scotland, the mother and nurse were not allowed to consume ale during pregnancy and breastfeeding. Claims that alcohol consumption caused idiocy were also part of the Teetotalisms message in the 19th century, but such claims, despite some attempts to offer evidence, were ignored because no mechanism could be advanced.The earliest recorded observation of possible links between maternal alcohol use and fetal damage was made in 1899 by Dr. William Sullivan, a Liverpool prison physician who noted higher rates of stillbirth for 120 alcoholic female prisoners than their sober female relatives; he suggested the causal agent to be alcohol use. This contradicted the predominating belief at the time that heredity caused intellectual disability, poverty, and criminal behavior, which contemporary studies on the subjects usually concluded. A case study by Henry H. Goddard of the Kallikak family—popular in the early 1900s—represents this earlier perspective, though later researchers have suggested that the Kallikaks almost certainly had FAS. General studies and discussions on alcoholism throughout the mid-1900s were typically based on a heredity argument.Prior to fetal alcohol syndrome being specifically identified and named in 1973, only a few studies had noted differences between the children of mothers who used alcohol during pregnancy or breast-feeding and those who did not, and identified alcohol use as a possible contributing factor rather than heredity.
Recognition as a syndrome
Fetal alcohol syndrome was named in 1973 by two dysmorphologists, Drs. Kenneth Lyons Jones and David Weyhe Smith of the University of Washington Medical School in Seattle, United States. They identified a pattern of "craniofacial, limb, and cardiovascular defects associated with prenatal onset growth deficiency and developmental delay" in eight unrelated children of three ethnic groups, all born to mothers who were alcoholics. The pattern of malformations indicated that the damage was prenatal. News of the discovery shocked some, while others were skeptical of the findings.Dr. Paul Lemoine of Nantes, France had already published a study in a French medical journal in 1968 about children with distinctive features whose mothers were alcoholics, and in the U.S., Christy Ulleland and colleagues at the University of Washington Medical School had conducted an 18-month study in 1968–1969 documenting the risk of maternal alcohol consumption among the offspring of 11 alcoholic mothers. The Washington and Nantes findings were confirmed by a research group in Gothenburg, Sweden in 1979. Researchers in France, Sweden, and the United States were struck by how similar these children looked, though they were not related, and how they behaved in the same unfocused and hyperactive manner.Within nine years of the Washington discovery, animal studies, including non-human monkey studies carried out at the University of Washington Primate Center by Dr. Sterling Clarren, had confirmed that alcohol was a teratogen. By 1978, 245 cases of FAS had been reported by medical researchers, and the syndrome began to be described as the most frequent known cause of intellectual disability.While many syndromes are eponymous, i.e. named after the physician first reporting the association of symptoms, Smith named FAS after the causal agent of the symptoms. He reasoned that doing so would encourage prevention, believing that if people knew maternal alcohol consumption caused the syndrome, then abstinence during pregnancy would follow from patient education and public awareness. At the time, nobody was aware of the full range of possible birth defects from FAS or its rate of prevalence.
Over time, as subsequent research and clinical experience suggested that a range of effects (including physical, behavioral, and cognitive) could arise from prenatal alcohol exposure, the term Fetal Alcohol Spectrum Disorder (FASD) was developed to include FAS as well as other conditions resulting from prenatal alcohol exposure. Currently, FAS is the only expression of prenatal alcohol exposure defined by the International Statistical Classification of Diseases and Related Health Problems and assigned ICD-9 and diagnoses.
In fiction
In Aldous Huxleys 1932 novel Brave New World (where all fetuses are gestated in vitro in a factory), lower caste fetuses are created by receiving alcohol transfusions (Bokanovsky Process) to reduce intelligence and height, thus conditioning them for simple, menial tasks. Connections between alcohol and incubating embryos are made multiple times in the novel.The main character of the 2009 film Defendor is implied to have the condition.Tony Loneman, a character in Tommy Oranges novel There There, was born with fetal alcohol syndrome, which he calls "the Drome".
See also
Alcohol and pregnancy
Smoking and pregnancy
Environmental toxicants and fetal development
References
External links
Fetal alcohol spectrum disorder at Curlie
Center for Disease Controls page on Fetal Alcohol Spectrum Disorders (FASDs) |
Childhood obesity | Childhood obesity is a condition where excess body fat negatively affects a childs health or well-being. As methods to determine body fat directly are difficult, the diagnosis of obesity is often based on BMI. Due to the rising prevalence of obesity in children and its many adverse health effects it is being recognized as a serious public health concern. The term overweight rather than obese is often used when discussing childhood obesity, as it is less stigmatizing, although the term overweight can also refer to a different BMI category. The prevalence of childhood obesity is known to differ by sex and gender.
Classification
Body mass index (BMI) is acceptable for determining obesity for children two years of age and older. It is determined by the ratio of weight to height.The normal range for BMI in children vary with age and sex. While a BMI above the 85th percentile is defined as overweight, a BMI greater than or equal to the 95th percentile is defined as obesity by Centers for Disease Control and Prevention. It has published tables for determining this in children.The US Preventive Service Task Force reported that not all children with a high BMI need to lose weight though. High BMI can identify a possible weight problem, but does not differentiate between fat or lean tissue. Additionally, BMI may mistakenly rule out some children who do have excess adipose tissue. It is therefore beneficial to supplement the reliability of a BMI diagnosis with additional screening tools such as adipose tissue or skin fold measurements.
Effects on health
Psychological
The first problems to occur in obese children are usually emotional or psychological. Obese children often experience bullying by their peers. Some are harassed or discriminated against by their own family. Stereotypes abound and may lead to low self-esteem and depression.
Physical
Childhood obesity however can also lead to life-threatening conditions including diabetes, high blood pressure, heart disease, sleep problems, cancer, and other disorders. Some of the other disorders would include liver disease, early puberty or menarche, eating disorders such as anorexia and bulimia, skin infections, and asthma and other respiratory problems.The early physical effects of obesity in adolescence include, almost all of the childs organs being affected, gallstones, hepatitis, sleep apnoea and increased intracranial pressure. Overweight children are also more likely to grow up to be overweight adults. Obesity during adolescence has been found to increase mortality rates during adulthood.A 2008 study has found that children who are obese have carotid arteries which have prematurely aged by as much as thirty years as well as abnormal levels of cholesterol.
Long-term effects
Children who are obese are likely to be obese as adults. Thus, they are more at risk for adult health problems such as heart disease, type 2 diabetes, stroke, several types of cancer, and osteoarthritis. One study showed that children who became obese as early as age 2 were more likely to be obese as adults. According to an article in The New York Times all of these health effects are contributing to a shorter lifespan of five years for these obese children. It is the first time in two centuries that the current generation of children in America may have a shorter lifespan than their parents.
Causes
Childhood obesity can be brought on by a range of factors which often act in combination. "Obesogenic environment" is the medical term set aside for this mixture of elements. The greatest risk factor for child obesity is the obesity of both parents. This may be reflected by the familys environment and genetics. Other reasons may also be due to psychological factors and the childs body type.
A 2010 review stated that childhood obesity likely is the result of the interaction of natural selection favouring those with more parsimonious energy metabolism and todays consumerist society with easy access to energy dense cheap foods and less energy requirements in daily life.Factors include the increase in use of technology, increase in snacks and portion size of meals, and the decrease in the physical activity of children. A study found kids that use electronic devices 3 or more hours a day had between a 17- 44% increased risk of being overweight, or a 10- 61% increased risk of obese (Cespedes 2011).Childhood obesity is common among children from, low-income, African American and Hispanic communities. This is mainly because minority children spend less time playing outside the house and staying active. Some contributors to childhood obesity is that parents would rather have their children stay inside the home because they fear that gang, drug violence, and other dangers might harm them.
Genetics
Childhood obesity is often the result of an interplay between many genetic and environmental factors. Polymorphisms in various genes controlling appetite and metabolism predispose individuals to obesity when sufficient calories are present. Over 200 genes affect weight by determining activity level, food preferences, body type, and metabolism. Having two copies of the allele called FTO increases the likelihood of both obesity and diabetes.As such, obesity is a major feature of a number of rare genetic conditions that often present in childhood:
Prader–Willi syndrome with an incidence between 1 in 12,000 and 1 in 15,000 live births is characterized by hyperphagia and food preoccupations which leads to rapid weight gain in those affected.
Bardet–Biedl syndrome
MOMO syndrome
Leptin receptor mutations
Congenital leptin deficiency
Melanocortin receptor mutationsIn children with early-onset severe obesity (defined by an onset before ten years of age and body mass index over three standard deviations above normal), 7% harbor a single locus mutation.One study found that 80% of the offspring of two obese parents were obese in contrast to less than 10% of the offspring of two parents who were of normal weight. The percentage of obesity that can be attributed to genetics varies from 6% to 85% depending on the population examined.
Family practices
In the recent decades, family practices have significantly changed, and several of these practices greatly contribute to childhood obesity:
With a decreasing number of mothers who breast-feed, more infants become obese children as they grow up and are reared on infant formula instead.
Less children go outside and engage in active play as technology, such as television and video games, keep children indoors.
Rather than walking or biking to a bus-stop or directly to school, more school-age children are driven to school by their parents, reducing physical activity.
As family sizes decrease, the childrens pester power, their ability to force adults to do what they want, increases. This ability enables them to have easier access to calorie-packed foods, such as candy and soda drinks.
The social context around family meal-time plays a role in rates of childhood obesity
Social policies
Different communities and nations have adopted varying social practices and policies that are either beneficial or detrimental to childrens physical health. These social factors include:
the quality of school lunches
the emphasis of schools on physical activity
access to vending machines and fast-food restaurants
prevalence of and access to parks, bike paths, and sidewalks
government subsidies for corn oil and sugar
advertising of fast-food restaurants and candy
prices of healthy and unhealthy foods
access to fresh, healthy, and affordable food
Advertising
Advertising of unhealthy foods correlates with childhood obesity rates. In some nations, advertising of candy, cereal, and fast-food restaurants is illegal or limited on childrens television channels. The media defends itself by blaming the parents for yielding to their childrens demands for unhealthy foods.
Socioeconomic status
It is much more common for young people who come from a racial or ethnic minority, or for those who have a lower socioeconomic status, to be overweight and to engage in less healthy behaviors and sedentary activities.
Prevention
Schools play a large role in preventing childhood obesity by providing a safe and supporting environment with policies and practices that support healthy behaviors. At home, parents can help prevent their children from becoming overweight by changing the way the family eats and exercises together. The best way children learn is by example, so parents should lead by example by living a healthy lifestyle. Screening for obesity is recommended in those over the age of six. Both physical activity and diet can help to reduce the risk of obesity in children from 0 to 5 years old; meanwhile, exclusive physical activity can reduce the risk of obesity for children aged from 6 to 12 years old, and adolescents aged from 13 to 18 years old. The implementation of strategies to improve childcare services such as preschools, nurseries, daycare, and kindergarten on healthy eating, physical activity, and obesity prevention shows little effect on a childs diet, physical activity, and weight status.
Maternal Body Mass Index
Maternal body mass index (BMI) is an important predictor of childhood obesity. Mothers with pre-pregnancy obesity, as defined by BMI ≥30 kg/m2, are known to have children that have higher growth rates and more likely to have obesity.
Dietary
The effects of eating habits on childhood obesity are difficult to determine. A three-year randomized controlled study of 1,704 3rd grade children which provided two healthy meals a day in combination with an exercise program and dietary counsellings failed to show a significant reduction in percentage body fat when compared to a control group. This was partly due to the fact that even though the children believed they were eating less their actual calorie consumption did not decrease with the intervention. At the same time observed energy expenditure remained similar between the groups. This occurred even though dietary fat intake decreased from 34% to 27%. A second study of 5,106 children showed similar results. Even though the children ate an improved diet there was no effect found on BMI. Why these studies did not bring about the desired effect of curbing childhood obesity has been attributed to the interventions not being sufficient enough. Changes were made primarily in the school environment while it is felt that they must occur in the home, the community, and the school simultaneously to have a significant effect.A Cochrane review of a lower fat diet in children (30% or less of total energy) to prevent obesity found the existing evidence of very low to moderate quality, and firm conclusions could not be made.Calorie-rich drinks and foods are readily available to children. Consumption of sugar-laden soft drinks may contribute to childhood obesity. In a study of 548 children over a 19-month period the likelihood of obesity increased 1.6 times for every additional soft drink consumed per day.Calorie-dense, prepared snacks are available in many locations frequented by children. As childhood obesity has become more prevalent, snack vending machines in school settings have been reduced by law in a small number of localities. Some research suggests that the increase in availability of junk foods in schools can account for about one-fifth of the increase in average BMI among adolescents over the last decade. Eating at fast food restaurants is very common among young people with 75% of 7th to 12th grade students consuming fast food in a given week. The fast food industry is also at fault for the rise in childhood obesity. This industry spends about $4.2 billion on advertisements aimed at young children. McDonalds alone has thirteen websites that are viewed by 365,000 children and 294,000 teenagers each month. In addition, fast food restaurants give out toys in childrens meals, which helps to entice children to buy the fast food. According to a 2010 report, 40% of children aged 2 to 11 asked their parents to take them to McDonalds at least once a week, and 15%of preschoolers asked to go every day. To make matters worse, out of 3000 combinations created from popular items on childrens menus at fast food restaurants, only 13 meet the recommended nutritional guidelines for young children. Some literature has found a relationship between fast food consumption and obesity. Including a study which found that fast food restaurants near schools increases the risk of obesity among the student population.Whole milk consumption verses 2% milk consumption in children of one to two years of age had no effect on weight, height, or body fat percentage. Therefore, whole milk continues to be recommended for this age group. However the trend of substituting sweetened drinks for milk has been found to lead to excess weight gain.
Legal
Some jurisdictions use laws and regulations in an effort to steer children and parents towards making healthier food choices. Two examples are calorie count laws and banning soft drinks from sale at vending machines in schools. In the United Kingdom the Obesity Health Alliance has called on whichever party wins the general election to take measures to reduce childhood obesity, for example by banning advertisements for unhealthy foods before 9:00 pm and banning sports sponsorship by manufacturers of unhealthy foods. The failure of the present UK government to cut sugar, fat and salt content in foods has been criticised. Health experts, the health select committee and campaigners described Conservative plans over childhood obesity as, "weak" and "watered down".
Physical activity
Physical inactivity of children has also shown to be a serious cause, and children who fail to engage in regular physical activity are at greater risk of obesity. Researchers studied the physical activity of 133 children over a three-week period using an accelerometer to measure each childs level of physical activity. They discovered the obese children were 35% less active on school days and 65% less active on weekends compared to non-obese children.
Physical inactivity as a child could result in physical inactivity as an adult. In a fitness survey of 6,000 adults, researchers discovered that 25% of those who were considered active at ages 14 to 19 were also active adults, compared to 2% of those who were inactive at ages 14 to 19, who were now said to be active adults. Staying physically inactive leaves unused energy in the body, most of which is stored as fat. Researchers studied 16 men over a 14-day period and fed them 50% more of their energy required every day through fats and carbohydrates. They discovered that carbohydrate overfeeding produced 75–85% excess energy being stored as body fat and fat overfeeding produced 90–95% storage of excess energy as body fat.Many children fail to exercise because they spend long periods of time engaging in sedentary activities such as computer usage, playing video games or watching television. Technology has a large factor on the childrens activeness. Researchers provided a technology questionnaire to 4,561 children, ages 14, 16, and 18. They discovered children were 21.5% more likely to be overweight when watching 4+ hours of TV per day, 4.5% more likely to be overweight when using a computer one or more hours per day, and unaffected by potential weight gain from playing video games. A randomized trial showed that reducing TV viewing and computer use can decrease age-adjusted BMI; reduced calorie intake was thought to be the greatest contributor to the BMI decrease.Technological activities are not the only household influences of childhood obesity. Low-income households can affect a childs tendency to gain weight. Over a three-week period researchers studied the relationship of socioeconomic status (SES) to body composition in 194 children, ages 11–12. They measured weight, waist girth, stretch stature, skinfolds, physical activity, TV viewing, and SES; researchers discovered clear SES inclines to upper class children compared to the lower class children.Childhood inactivity is linked to obesity in the United States with more children being overweight at younger ages. In a 2009 preschool study 89% of a preschoolers day was found to be sedentary while the same study also found that even when outside, 56 percent of activities were still sedentary. One factor believed to contribute to the lack of activity found was little teacher motivation, but when toys, such as balls were made available, the children were more likely to play.
Home environment
Childrens food choices are also influenced by family meals. Researchers provided a household eating questionnaire to 18,177 children, ranging in ages 11–21, and discovered that four out of five parents let their children make their own food decisions. They also discovered that compared to adolescents who ate three or fewer meals per week, those who ate four to five family meals per week were 19% less likely to report poor consumption of vegetables, 22% less likely to report poor consumption of fruits, and 19% less likely to report poor consumption of dairy foods. Adolescents who ate six to seven family meals per week, compared to those who ate three or fewer family meals per week, were 38% less likely to report poor consumption of vegetables, 31% less likely to report poor consumption of fruits, and 27% less likely to report poor consumption of dairy foods. The results of a survey in the UK published in 2010 imply that children raised by their grandparents are more likely to be obese as adults than those raised by their parents. An American study released in 2011 found the more mothers work the more children are more likely to be overweight or obese.
Developmental factors
Various developmental factors may affect rates of obesity. Breast-feeding for example may protect against obesity in later life with the duration of breast-feeding inversely associated with the risk of being overweight later on. A childs body growth pattern may influence the tendency to gain weight. Researchers measured the standard deviation (SD [weight and length]) scores in a cohort study of 848 babies. They found that infants who had an SD score above 0.67 had catch up growth (they were less likely to be overweight) compared to infants who had less than a 0.67 SD score (they were more likely to gain weight). Additionally, breastfeeding for less than 6 months, compared to 6 months or more, has been shown to result in a higher growth rate and higher zBMI at 18, 36, and 72 months of age.A childs weight may be influenced when he/she is only an infant. Researchers also did a cohort study on 19,397 babies, from their birth until age seven and discovered that high weight babies at four months were 1.38 times more likely to be overweight at seven years old compared to normal weight babies. High weight babies at the age of one were 1.17 times more likely to be overweight at age seven compared to normal weight babies.
Medical illness
Cushings syndrome (a condition in which the body contains excess amounts of cortisol) may also influence childhood obesity. Researchers analyzed two isoforms (proteins that have the same purpose as other proteins, but are programmed by different genes) in the cells of 16 adults undergoing abdominal surgery. They discovered that one type of isoform created oxo-reductase activity (the alteration of cortisone to cortisol) and this activity increased 127.5 pmol mg sup when the other type of isoform was treated with cortisol and insulin. The activity of the cortisol and insulin can possibly activate Cushings syndrome.Hypothyroidism is a hormonal cause of obesity, but it does not significantly affect obese people who have it more than obese people who do not have it. In a comparison of 108 obese patients with hypothyroidism to 131 obese patients without hypothyroidism, researchers discovered that those with hypothyroidism had only 0.077 points more on the caloric intake scale than did those without hypothyroidism.
Psychological factors
Researchers surveyed 1,520 children, ages 9–10, with a four-year follow up and discovered a positive correlation between obesity and low self-esteem in the four-year follow up. They also discovered that decreased self-esteem led to 19% of obese children feeling sad, 48% of them feeling bored, and 21% of them feeling nervous. In comparison, 8% of normal weight children felt sad, 42% of them felt bored, and 12% of them felt nervous.Stress can influence a childs eating habits. Researchers tested the stress inventory of 28 college females and discovered that those who were binge eating had a mean of 29.65 points on the perceived stress scale, compared to the control group who had a mean of 15.19 points. This evidence may demonstrate a link between eating and stress.
Feelings of depression can cause a child to overeat. Researchers provided an in-home interview to 9,374 adolescents, in grades seven through 12 and discovered that there was not a direct correlation with children eating in response to depression. Of all the obese adolescents, 8.2% had said to be depressed, compared to 8.9% of the non-obese adolescents who said they were depressed. Antidepressants, however, seem to have very little influence on childhood obesity. Researchers provided a depression questionnaire to 487 overweight/obese subjects and found that 7% of those with low depression symptoms were using antidepressants and had an average BMI score of 44.3, 27% of those with moderate depression symptoms were using antidepressants and had an average BMI score of 44.7, and 31% of those with major depression symptoms were using antidepressants and had an average BMI score of 44.2.Several studies have also explored the connection between Attention-deficit Hyperactivity Disorder (ADHD) and obesity in children. A study in 2005 concluded that within a subgroup of children who were hospitalized for obesity, 57.7% had co-morbid ADHD. This relationship between obesity and ADHD may seem counter-intuitive, as ADHD is typically associated with higher level of energy expenditure, which is thought of as a protective factor against obesity. However, these studies determined that children exhibited more signs of predominantly inattentive-type ADHD rather than combined-type ADHD. It is possible, however, that the symptoms of hyperactivity typically present in individuals with combined-type ADHD are simply masked in obese children with ADHD due to their decreased mobility. The same correlation between obesity and ADHD is also present in adult populations. Existing underlying explanations for the relationship between ADHD and obesity in children include but are not limited to abnormalities in the hypo-dopaminergic pathway, ADHD creating abnormal eating behaviors which leads to obesity, or impulsivity associated with binge eating leading to ADHD in obese patients. A systematic review of the literature on the relationship between obesity and ADHD concluded that all reviewed studies reported ADHD patients were heavier than expected. However, the same systematic review also claimed that all the evidence supporting this connection was still limited and further research is still necessary to learn more about this connection. Given the prevalence rates of both obesity and ADHD in children, understanding the possible relationship between the two is important for public health, particularly when exploring treatment and management options.
Direct intervention for psychological treatment of childhood obesity has become more prevalent in recent years. A meta-analysis of the psychological treatment of obesity in children and adolescents found family-based behavioral treatment (FBT) and Parent-Only Behavior treatment to be the most effective practices in treating obesity in children within a psychological framework.
Management
Obesity in children is treated with dietary changes and physical activity. Dieting and missing meals should; however, be discouraged. The benefit of tracking BMI and providing counselling around weight is minimal.
Lifestyle
Exclusive breast-feeding is recommended in all newborn infants for its nutritional and other beneficial effects. Parents changing the diet and lifestyle of their offspring by offering appropriate food portions, increasing physical activity, and keeping sedentary behaviors at a minimum may also decrease the obesity levels in children.If children were more mobile and less sedentary, the rate of obesity would decrease. Parents should recognize the signs and encourage their children to be more physically active. By walking or riding a bike, instead of using motorised transport or watching television, will reduce sedentary activity.
Medications
There are no medications currently approved for the treatment of obesity in children. The American Academy of Pediatrics recommends medications for obesity be discourage. Orlistat and sibutramine may be helpful in managing moderate obesity in adolescence. Metformin is minimally useful. A Cochrane review in 2016 concluded that medications might reduce BMI and bodyweight to a small extent in obese children and adolescents. This conclusion was based only on low quality evidence.
Surgery
As of 2015 there is not good evidence comparing surgery to lifestyle change for obesity in children, though there are a number of high quality ongoing studies looking at this issue. Bariatric surgical procedures are increasingly used amongst adolescents with severe adolescent obesity to promote weight loss.
Epidemiology
From 1980 to 2013, the prevalence of overweight and obesity in children increased by nearly 50%. Currently 10% of children worldwide are either overweight or obese. In 2014, the World Health Organization established a high-level commission to end childhood obesity.With more than 42 million overweight children around the world, childhood obesity is increasing worldwide. Since 1980, the number of obese children has doubled in all three North American countries, Mexico, the United States, and Canada. Although the rate of childhood obesity in the United States has stopped increasing, the current rate remains high. In 2010, 32.6 percent of 6- to 11-year-olds were overweight, and 18 percent of 6- to 9-year-olds were obese.
Canada
The rate of overweight and obesity among Canadian children has increased dramatically in recent years. In boys, the rate increased from 11% in the 1980s to 30% in the 1990s.
Brazil
The rate of overweight and obesity in Brazilian children increased from 4% in the 1980s to 14% in the 1990s. In 2007 the prevalence of children overweight and childhood obesity was 11.1% and 2.7% in girls, 8.2% and 1.5% in boys, respectively.
United States
The rate of obesity among children and adolescents in the United States has nearly tripled between the early 1980s and 2000. It has however not changed significantly between 2000 and 2006 with the most recent statistics showing a level just over 17 percent. In 2008, the rate of overweight and obese children in the United States was 32%, and had stopped climbing. In 2011, a national cohort study of infants and toddlers found that nearly one-third of US children were overweight or obese at 9 months and 2 years old. In a follow-up study, infant weight status (healthy and obese) was strongly associated with preschool weight status.
Australia
Since the onset of the 21st century, Australia has found that childhood obesity has followed trend with the United States. Information garnered has concluded that the increase has occurred in the lower socioeconomic areas where poor nutritional education has been blamed.
Research
A study of 1800 children aged 2 to 12 in Colac, Australia tested a program of restricted diet (no carbonated drinks or sweets) and increased exercise. Interim results included a 68% increase in after school activity programs, 21% reduction in television viewing, and an average of 1 kg weight reduction compared to a control group.A survey carried out by the American Obesity Association into parental attitudes towards their childrens weight showed the majority of parents think that recess should not be reduced or replaced. Almost 30% said that they were concerned with their childs weight. 35% of parents thought that their childs school was not teaching them enough about childhood obesity, and over 5% thought that childhood obesity was the greatest risk to their childs long-term health.A Northwestern University study indicates that inadequate sleep has a negative impact on a childs performance in school, their emotional and social welfare, and increases their risk of being overweight. This study was the first nationally represented, longitudinal investigation of the correlation between sleep, Body Mass Index (BMI) and overweight status in children between the ages of 3 and 18. The study found that an extra hour of sleep lowered the childrens risk of being overweight from 36% to 30%, while it lessened older childrens risk from 34% to 30%.A 2018 Cochrane review on the impact of physical activity, diet and other behavioral interventions for improving cognition and school achievement in children and adolescents found that school and community-based programs as part of an overall prevention program were beneficial.Obese children and adolescents are more likely to become obese as adults. For example, one study found that approximately 80% of children who were overweight at aged 10–15 years were obese adults at age 25 years. Another study found that 25% of obese adults were overweight as children. The latter study also found that if overweight begins before 8 years of age, obesity in adulthood is likely to be more severe.A study has also found that tackling childhood obesity will not necessarily lead to eating disorders later in life.A review of secular trends in the number of overweight or obese children have come to the conclusion that prevalence had increased during the past two decades in the most industrialised countries, apart from Russia and Poland, and in several low-income countries, especially in urban areas. Prevalence doubled or tripled between the early 1970s and late 1990s in Australia, Brazil, Canada, Chile, Finland, France, Germany, Greece, Japan, the UK, and the USA. By 2010, more than |
Childhood obesity | 40% of children in the North American and eastern Mediterranean WHO regions, 38% in Europe, 27% in the western Pacific, and 22% in southeast Asia were predicted to be overweight or obese. However, that 2006 review pre-dates recent data, which, although still too soon to be certain, suggest that the increase in childhood obesity in the US, the UK, and Sweden might be abating.3–5 A British longitudinal study has found that obesity restricted to childhood has minimal influence on adult outcomes at age 30. The study also found that, while obesity that continues into adulthood has little influence on mens outcomes, it makes women less likely to have ever been employed or to currently have a romantic partner.A 2017 National Bureau of Economic Research paper found that childhood obesity in the United States increases medical costs by $1,354 a year (in 2013 dollars).
See also
International Journal of Pediatric Obesity
Task Force on Childhood Obesity
Classification of childhood obesity
Obesity and the environment
Social influences on fitness behavior
Social stigma of obesity
Sugary drink tax
EPODE International NetworkTransport:
Active mobility
Childrens street culture
Childrens street games
Cycling mobility
Home zone / Play street
Obesity and walking
Student transport
Walking bus
Footnotes
Further reading
Laura Dawes, Childhood Obesity in America: Biography of an Epidemic. Cambridge, MA: Harvard University Press, 2014.
External links
"North American Society for Pediatric Gastroenterology, Hepatology and Nutrition" (PDF). Archived from the original (PDF) on 2016-03-03. Retrieved 2008-08-27. |
Blood transfusion | Blood transfusion is the process of transferring blood products into a persons circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but modern medical practice commonly uses only components of the blood, such as red blood cells, white blood cells, plasma, clotting factors and platelets.
Red blood cells (RBC) contain hemoglobin, and supply the cells of the body with oxygen. White blood cells are not commonly used during transfusion, but they are part of the immune system, and also fight infections. Plasma is the "yellowish" liquid part of blood, which acts as a buffer, and contains proteins and important substances needed for the bodys overall health. Platelets are involved in blood clotting, preventing the body from bleeding. Before these components were known, doctors believed that blood was homogeneous. Because of this scientific misunderstanding, many patients died because of incompatible blood transferred to them.
Medical uses
Red cell transfusion
Historically, red blood cell transfusion was considered when the hemoglobin level fell below 100g/L or hematocrit fell below 30%. Because each unit of blood given carries risks, a trigger level lower than that, at 70 to 80g/L, is now usually used, as it has been shown to have better patient outcomes. The administration of a single unit of blood is the standard for hospitalized people who are not bleeding, with this treatment followed with re-assessment and consideration of symptoms and hemoglobin concentration. Patients with poor oxygen saturation may need more blood. The advisory caution to use blood transfusion only with more severe anemia is in part due to evidence that outcomes are worsened if larger amounts are given. One may consider transfusion for people with symptoms of cardiovascular disease such as chest pain or shortness of breath. In cases where patients have low levels of hemoglobin due to iron deficiency, but are cardiovascularly stable, parenteral iron is a preferred option based on both efficacy and safety. Other blood products are given where appropriate, e.g., to treat clotting deficiencies.
Procedure
Before a blood transfusion is given, there are many steps taken to ensure quality of the blood products, compatibility, and safety to the recipient. In 2012, a national blood policy was in place in 70% of countries and 69% of countries had specific legislation that covers the safety and quality of blood transfusion.
Blood donation
Blood transfusions use as sources of blood either ones own (autologous transfusion), or someone elses (allogeneic or homologous transfusion). The latter is much more common than the former. Using anothers blood must first start with donation of blood. Blood is most commonly donated as whole blood obtained intravenously and mixed with an anticoagulant. In developed countries, donations are usually anonymous to the recipient, but products in a blood bank are always individually traceable through the whole cycle of donation, testing, separation into components, storage, and administration to the recipient. This enables management and investigation of any suspected transfusion related disease transmission or transfusion reaction. In developing countries, the donor is sometimes specifically recruited by or for the recipient, typically a family member, and the donation occurs immediately before the transfusion.
It is unclear whether applying alcohol swab alone or alcohol swab followed by antiseptic is able to reduce contamination of donors blood.
Processing and testing
Donated blood is usually subjected to processing after it is collected, to make it suitable for use in specific patient populations. Collected blood is then separated into blood components by centrifugation: red blood cells, plasma, platelets, albumin protein, clotting factor concentrates, cryoprecipitate, fibrinogen concentrate, and immunoglobulins (antibodies). Red cells, plasma and platelets can also be donated individually via a more complex process called apheresis.
The World Health Organization (WHO) recommends that all donated blood be tested for transfusion-transmissible infections. These include HIV, hepatitis B, hepatitis C, Treponema pallidum (syphilis) and, where relevant, other infections that pose a risk to the safety of the blood supply, such as Trypanosoma cruzi (Chagas disease) and Plasmodium species (malaria). According to the WHO, 25 countries are not able to screen all donated blood for one or more of: HIV, hepatitis B, hepatitis C, or syphilis. One of the main reasons for this is because testing kits are not always available. However the prevalence of transfusion-transmitted infections is much higher in low income countries compared to middle and high income countries.
All donated blood should also be tested for the ABO blood group system and Rh blood group system to ensure that the patient is receiving compatible blood.
In addition, in some countries platelet products are also tested for bacterial infections due to its higher inclination for contamination due to storage at room temperature. Presence of cytomegalovirus (CMV) may also be tested because of the risk to certain immunocompromised recipients if given, such as those with organ transplant or HIV. However, not all blood is tested for CMV because only a certain amount of CMV-negative blood needs to be available to supply patient needs. Other than positivity for CMV, any products tested positive for infections are not used.
Leukocyte reduction is the removal of white blood cells by filtration. Leukoreduced blood products are less likely to cause HLA alloimmunization (development of antibodies against specific blood types), febrile non-hemolytic transfusion reaction, cytomegalovirus infection, and platelet-transfusion refractoriness.
Pathogen Reduction treatment that involves, for example, the addition of riboflavin with subsequent exposure to UV light has been shown to be effective in inactivating pathogens (viruses, bacteria, parasites and white blood cells) in blood products. By inactivating white blood cells in donated blood products, riboflavin and UV light treatment can also replace gamma-irradiation as a method to prevent graft-versus-host disease (TA-GvHD).
Compatibility testing
Before a recipient receives a transfusion, compatibility testing between donor and recipient blood must be done. The first step before a transfusion is given is to type and screen the recipients blood. Typing of recipients blood determines the ABO and Rh status. The sample is then screened for any alloantibodies that may react with donor blood. It takes about 45 minutes to complete (depending on the method used). The blood bank scientist also checks for special requirements of the patient (e.g. need for washed, irradiated or CMV negative blood) and the history of the patient to see if they have previously identified antibodies and any other serological anomalies.
A positive screen warrants an antibody panel/investigation to determine if it is clinically significant. An antibody panel consists of commercially prepared group O red cell suspensions from donors that have been phenotyped for antigens that correspond to commonly encountered and clinically significant alloantibodies. Donor cells may have homozygous (e.g. K+k+), heterozygous (K+k-) expression or no expression of various antigens (K−k−). The phenotypes of all the donor cells being tested are shown in a chart. The patients serum is tested against the various donor cells. Based on the reactions of the patients serum against the donor cells, a pattern will emerge to confirm the presence of one or more antibodies. Not all antibodies are clinically significant (i.e. cause transfusion reactions, HDN, etc.). Once the patient has developed a clinically significant antibody it is vital that the patient receive antigen-negative red blood cells to prevent future transfusion reactions. A direct antiglobulin test (Coombs test) is also performed as part of the antibody investigation.If there is no antibody present, an immediate spin crossmatch or computer-assisted crossmatch is performed where the recipient serum and donor rbc are incubated. In the immediate spin method, two drops of patient serum are tested against a drop of 3–5% suspension of donor cells in a test tube and spun in a serofuge. Agglutination or hemolysis (i.e., positive Coombs test) in the test tube is a positive reaction and the unit should not be transfused.
If an antibody is suspected, potential donor units must first be screened for the corresponding antigen by phenotyping them. Antigen negative units are then tested against the patient plasma using an antiglobulin/indirect crossmatch technique at 37 degrees Celsius to enhance reactivity and make the test easier to read.
In urgent cases where crossmatching cannot be completed, and the risk of dropping hemoglobin outweighs the risk of transfusing uncrossmatched blood, O-negative blood is used, followed by crossmatch as soon as possible. O-negative is also used for children and women of childbearing age. It is preferable for the laboratory to obtain a pre-transfusion sample in these cases so a type and screen can be performed to determine the actual blood group of the patient and to check for alloantibodies.
Compatibility of ABO and Rh system for Red Cell (Erythrocyte) Transfusion
This chart shows possible matches in blood transfusion between donor and receiver using ABO and Rh system.
Adverse effects
In the same way that the safety of pharmaceutical products is overseen by pharmacovigilance, the safety of blood and blood products is overseen by haemovigilance. This is defined by the World Health Organization (WHO) as a system "...to identify and prevent occurrence or recurrence of transfusion related unwanted events, to increase the safety, efficacy and efficiency of blood transfusion, covering all activities of the transfusion chain from donor to recipient." The system should include monitoring, identification, reporting, investigation and analysis of adverse events near-misses and reactions related to transfusion and manufacturing. In the UK this data is collected by an independent organisation called SHOT (Serious Hazards Of Transfusion).Transfusions of blood products are associated with several complications, many of which can be grouped as immunological or infectious. There is controversy on potential quality degradation during storage.
Immunologic reaction
Acute hemolytic reactions are defined according to Serious Hazards of Transfusion (SHOT) as "fever and other symptoms/signs of haemolysis within 24 hours of transfusion; confirmed by one or more of the following: a fall of Hb, rise in lactate dehydrogenase (LDH), positive direct antiglobulin test (DAT), positive crossmatch" This is due to destruction of donor red blood cells by preformed recipient antibodies. Most often this occurs because of clerical errors or improper ABO blood typing and crossmatching resulting in a mismatch in ABO blood type between the donor and the recipient. Symptoms include fever, chills, chest pain, back pain, hemorrhage, increased heart rate, shortness of breath, and rapid drop in blood pressure. When suspected, transfusion should be stopped immediately, and blood sent for tests to evaluate for presence of hemolysis. Treatment is supportive. Kidney injury may occur because of the effects of the hemolytic reaction (pigment nephropathy). The severity of the transfusion reaction is depended upon amount of donors antigen transfused, nature of the donors antigens, the nature and the amount of recipient antibodies.
Delayed hemolytic reactions occur more than 24 hours after a transfusion. They usually occur within 28 days of a transfusion. They can be due to either a low level of antibodies present prior to the start of the transfusion, which are not detectable on pre-transfusion testing; or development of a new antibody against an antigen in the transfused blood. Therefore, delayed haemolytic reaction does not manifest until after 24 hours when enough antibodies are available to cause a reaction. The red blood cells are removed by macrophages from the blood circulation into liver and spleen to be destroyed, which leads to extravascular haemolysis. This process usually mediated by anti-Rh and anti-Kidd antibodies. However, this type of transfusion reaction is less severe when compared to acute haemolytic transfusion reaction.
Febrile nonhemolytic reactions are, along with allergic transfusion reactions, the most common type of blood transfusion reaction and occur because of the release of inflammatory chemical signals released by white blood cells in stored donor blood or attack on donors white blood cells by recipients antibodies. This type of reaction occurs in about 7% of transfusions. Fever is generally short lived and is treated with antipyretics, and transfusions may be finished as long as an acute hemolytic reaction is excluded. This is a reason for the now-widespread use of leukoreduction – the filtration of donor white cells from red cell product units.
Allergic transfusion reactions are caused by IgE anti-allergen antibodies. When antibodies are bound to its antigens, histamine is released from mast cells and basophils. Either IgE antibodies from the donors or recipients side can cause the allergic reaction. It is more common in patients who have allergic conditions such as hay fever. Patient may feel itchy or having hives but the symptoms are usually mild and can be controlled by stopping the transfusion and giving antihistamines.
Anaphylactic reactions are rare life-threatening allergic conditions caused by IgA anti-plasma protein antibodies. For patients who have selective immunoglobulin A deficiency, the reaction is presumed to be caused by IgA antibodies in the donors plasma. The patient may present with symptoms of fever, wheezing, coughing, shortness of breath, and circulatory shock. Urgent treatment with epinephrine is needed.
Post-transfusion purpura is an extremely rare complication that occurs after blood product transfusion and is associated with the presence of antibodies in the patients blood directed against both the donors and recipients platelets HPA (human platelet antigen). Recipients who lack this protein develop sensitization to this protein from prior transfusions or previous pregnancies, can develop thrombocytopenia, bleeding into the skin, and can display purplish discolouration of skin which is known as purpura. Intravenous immunoglobulin (IVIG) is treatment of choice.
Transfusion-related acute lung injury (TRALI) is a syndrome that is similar to acute respiratory distress syndrome (ARDS), which develops during or within 6 hours of transfusion of a plasma-containing blood product. Fever, hypotension, shortness of breath, and tachycardia often occurs in this type of reaction. For a definitive diagnosis to be made, symptoms must occur within 6 hours of transfusion, hypoxemia must be present, there must be radiographic evidence of bilateral infiltrates and there must be no evidence of left atrial hypertension (fluid overload). It occurs in 15% of the transfused patient with mortality rate of 5 to 10%. Recipient risk factors includes: end-stage liver disease, sepsis, haematological malignancies, sepsis, and ventilated patients. Antibodies to human neutrophil antigens (HNA) and human leukocyte antigens (HLA) have been associated with this type of transfusion reaction. Donors antibodies interacting with antigen positive recipient tissue result in release of inflammatory cytokines, resulting in pulmonary capillary leakage. The treatment is supportive.
Transfusion associated circulatory overload (TACO) is a common, yet underdiagnosed, reaction to blood product transfusion consisting of the new onset or exacerbation of three of the following within 6 hours of cessation of transfusion: acute respiratory distress, elevated brain natriuretic peptide (BNP), elevated central venous pressure (CVP), evidence of left heart failure, evidence of positive fluid balance, and/or radiographic evidence of pulmonary edema.
Transfusion-associated graft versus host disease frequently occurs in immunodeficient patients where recipients body failed to eliminate donors T cells. Instead, donors T cells attack the recipients cells. It occurs one week after transfusion. Fever, rash, diarrhoea are often associated with this type of transfusion reaction. Mortality rate is high, with 89.7% of the patients dead after 24 days. Immunosuppressive treatment is the most common way of treatment. Irradiation and leukoreduction of blood products is necessary for high risk patients to prevent T cells from attacking recipient cells.
Infection
The use of greater amount of red blood cells is associated with a high risk of infections. In those who were given red blood only with significant anemia infection rates were 12% while in those who were given red blood at milder levels of anemia infection rates were 17%.On rare occasions, blood products are contaminated with bacteria. This can result in a life-threatening infection known as transfusion-transmitted bacterial infection. The risk of severe bacterial infection is estimated, as of 2002, at about 1 in 50,000 platelet transfusions, and 1 in 500,000 red blood cell transfusions. Blood product contamination, while rare, is still more common than actual infection. The reason platelets are more often contaminated than other blood products is that they are stored at room temperature for short periods of time. Contamination is also more common with longer duration of storage, especially if that means more than 5 days. Sources of contaminants include the donors blood, donors skin, phlebotomists skin, and containers. Contaminating organisms vary greatly, and include skin flora, gut flora, and environmental organisms. There are many strategies in place at blood donation centers and laboratories to reduce the risk of contamination. A definite diagnosis of transfusion-transmitted bacterial infection includes the identification of a positive culture in the recipient (without an alternative diagnosis) as well as the identification of the same organism in the donor blood.
Since the advent of HIV testing of donor blood in the mid/later 1980s, ex. 1985s ELISA, the transmission of HIV during transfusion has dropped dramatically. Prior testing of donor blood only included testing for antibodies to HIV. However, because of latent infection (the "window period" in which an individual is infectious, but has not had time to develop antibodies) many cases of HIV seropositive blood were missed. The development of a nucleic acid test for the HIV-1 RNA has dramatically lowered the rate of donor blood seropositivity to about 1 in 3 million units. As transmittance of HIV does not necessarily mean HIV infection, the latter could still occur at an even lower rate.
The transmission of hepatitis C via transfusion currently stands at a rate of about 1 in 2 million units. As with HIV, this low rate has been attributed to the ability to screen for both antibodies as well as viral RNA nucleic acid testing in donor blood.
Other rare transmissible infections include hepatitis B, syphilis, Chagas disease, cytomegalovirus infections (in immunocompromised recipients), HTLV, and Babesia.
Comparison table
Inefficacy
Transfusion inefficacy or insufficient efficacy of a given unit(s) of blood product, while not itself a "complication" per se, can nonetheless indirectly lead to complications – in addition to causing a transfusion to fully or partly fail to achieve its clinical purpose. This can be especially significant for certain patient groups such as critical-care or neonatals.
For red blood cells (RBC), by far the most commonly transfused product, poor transfusion efficacy can result from units damaged by the so-called storage lesion – a range of biochemical and biomechanical changes that occur during storage. With red cells, this can decrease viability and ability for tissue oxygenation. Although some of the biochemical changes are reversible after the blood is transfused, the biomechanical changes are less so, and rejuvenation products are not yet able to adequately reverse this phenomenon. There has been controversy about whether a given product units age is a factor in transfusion efficacy, specifically about whether "older" blood directly or indirectly increases risks of complications. Studies have not been consistent on answering this question, with some showing that older blood is indeed less effective but with others showing no such difference; these developments are being closely followed by hospital blood bankers – who are the physicians, typically pathologists, who collect and manage inventories of transfusable blood units.
Certain regulatory measures are in place to minimize RBC storage lesion – including a maximum shelf life (currently 42 days), a maximum auto-hemolysis threshold (currently 1% in the US, 0.8% in Europe), and a minimum level of post-transfusion RBC survival in vivo (currently 75% after 24 hours). However, all of these criteria are applied in a universal manner that does not account for differences among units of product. For example, testing for the post-transfusion RBC survival in vivo is done on a sample of healthy volunteers, and then compliance is presumed for all RBC units based on universal (GMP) processing standards (RBC survival by itself does not guarantee efficacy, but it is a necessary prerequisite for cell function, and hence serves as a regulatory proxy). Opinions vary as to the "best" way to determine transfusion efficacy in a patient in vivo. In general, there are not yet any in vitro tests to assess quality or predict efficacy for specific units of RBC blood product prior to their transfusion, though there is exploration of potentially relevant tests based on RBC membrane properties such as erythrocyte deformability and erythrocyte fragility (mechanical).Physicians have adopted a so-called "restrictive protocol" – whereby transfusion is held to a minimum – in part because of the noted uncertainties surrounding storage lesion, in addition to the very high direct and indirect costs of transfusions. However, the restrictive protocol is not an option with some especially vulnerable patients who may require the best possible efforts to rapidly restore tissue oxygenation.
Although transfusions of platelets are far less numerous (relative to RBC), platelet storage lesion and resulting efficacy loss is also a concern.
Other
A known relationship between intra-operative blood transfusion and cancer recurrence has been established in colorectal cancer. In lung cancer intra-operative blood transfusion has been associated with earlier recurrence of cancer, worse survival rates and poorer outcomes after lung resection. Also studies shown to us, failure of the immune system caused by blood transfusion can be categorized as one of the main factors leading to more than 10 different cancer types that are fully associated with blood transfusion and the innate and adaptive immune system. Allogeneic blood transfusion, through five major mechanisms including the lymphocyte-T set, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), natural killer cells (NKCs), and dendritic cells (DCs) can help the recipients defense mechanisms. On the other hand, the role for each of the listed items includes activation of the antitumor CD8+ cytotoxic T lymphocytes (CD8+/CTL), temporal inactivation of Tregs, inactivation of the STAT3 signaling pathway, the use of bacteria to enhance the antitumor immune response and cellular Immunotherapy.
Transfusion-associated volume overload is a common complication simply because blood products have a certain amount of volume. This is especially the case in recipients with underlying cardiac or kidney disease. Red cell transfusions can lead to volume overload when they must be repeated because of insufficient efficacy (see above). Plasma transfusion is especially prone to causing volume overload because large volumes are usually required to give any therapeutic benefit.
It has been proved that blood transfusion produce worse outcomes after cytoreductive surgery and HIPEC.
Hypothermia can occur with transfusions with large quantities of blood products which normally are stored at cold temperatures. Core body temperature can go down as low as 32 °C and can produce physiologic disturbances. Prevention should be done with warming the blood to ambient temperature prior to transfusions.
Transfusions with large amounts of red blood cells, whether due to severe hemorrhaging and/or transfusion inefficacy (see above), can lead to an inclination for bleeding. The mechanism is thought to be due to disseminated intravascular coagulation, along with dilution of recipient platelets and coagulation factors. Close monitoring and transfusions with platelets and plasma is indicated when necessary.
Metabolic alkalosis can occur with massive blood transfusions because of the breakdown of citrate stored in blood into bicarbonate.
Hypocalcemia can also occur with massive blood transfusions because of the complex of citrate with serum calcium. Calcium levels below 0.9 mmol/L should be treated.
Blood doping is often used by athletes, drug addicts or military personnel for reasons such as to increase physical stamina, to fake a drug detection test or simply to remain active and alert during the duty-times respectively. However a lack of knowledge and insufficient experience can turn a blood transfusion into a sudden death. For example, when individuals run the frozen blood sample directly in their veins this cold blood rapidly reaches the heart, where it disturbs the hearts original pace leading to cardiac arrest and sudden death.
Frequency of use
Globally around 85 million units of red blood cells are transfused in a given year.In the United States, blood transfusions were performed nearly 3 million times during hospitalizations in 2011, making it the most common procedure performed. The rate of hospitalizations with a blood transfusion nearly doubled from 1997, from a rate of 40 stays to 95 stays per 10,000 population. It was the most common procedure performed for patients 45 years of age and older in 2011, and among the top five most common for patients between the ages of 1 and 44 years.According to the New York Times: "Changes in medicine have eliminated the need for millions of blood transfusions, which is good news for patients getting procedures like coronary bypasses and other procedures that once required a lot of blood." And, "Blood bank revenue is falling, and the decline may reach $1.5 billion a year this year [2014] from a high of $5 billion in 2008." Job losses will reach as high as 12,000 within the next three to five years, roughly a quarter of the total in the industry, according to the Red Cross.
History
Beginning with William Harveys experiments on the circulation of blood, recorded research into blood transfusion began in the 17th century, with successful experiments in transfusion between animals. However, successive attempts by physicians to transfuse animal blood into humans gave variable, often fatal, results.Pope Innocent VIII is sometimes said to have been given "the worlds first blood transfusion" by his physician Giacomo di San Genesio, who had him drink (by mouth) the blood of three 10-year-old boys. The boys subsequently died. The evidence for this story, however, is unreliable and considered a possible anti-Jewish blood libel.
Early attempts
The Incas
The first reported successful blood transfusions were performed by the Incas as early as the 1500s. Spanish conquistadors witnessed blood transfusions when they arrived in the sixteenth century. The prevalence of type O blood among Indigenous people of the Andean region meant such procedures would have held less risk than blood transfusion attempts among populations with incompatible blood types, which contributed to the failures of early attempts in Europe.
Animal blood
Working at the Royal Society in the 1660s, the physician Richard Lower began examining the effects of changes in blood volume on circulatory function and developed methods for cross-circulatory study in animals, obviating clotting by closed arteriovenous connections. The new instruments he was able to devise enabled him to perform the first reliably documented successful transfusion of blood in front of his distinguished colleagues from the Royal Society.According to Lowers account, "...towards the end of February 1665 [I] selected one dog of medium size, opened its jugular vein, and drew off blood, until its strength was nearly gone. Then, to make up for the great loss of this dog by the blood of a second, I introduced blood from the cervical artery of a fairly large mastiff, which had been fastened alongside the first, until this latter animal showed... it was overfilled... by the inflowing blood." After he "sewed up the jugular veins", the animal recovered "with no sign of discomfort or of displeasure".
Lower had performed the first blood transfusion between animals. He was then "requested by the Honorable [Robert] Boyle... to acquaint the Royal Society with the procedure for the whole experiment", which he did in December 1665 in the Societys Philosophical Transactions.The first blood transfusion from animal to human was administered by Dr. Jean-Baptiste Denys, eminent physician to King Louis XIV of France, on June 15, 1667. He transfused the blood of a sheep into a 15-year-old boy, who survived the |
Blood transfusion | transfusion. Denys performed another transfusion into a labourer, who also survived. Both instances were likely due to the small amount of blood that was actually transfused into these people. This allowed them to withstand the allergic reaction.
Denyss third patient to undergo a blood transfusion was Swedish Baron Gustaf Bonde. He received two transfusions. After the second transfusion Bonde died. In the winter of 1667, Denys performed several transfusions on Antoine Mauroy with calfs blood. On the third account Mauroy died.Six months later in London, Lower performed the first human transfusion of animal blood in Britain, where he "superintended the introduction in [a patients] arm at various times of some ounces of sheeps blood at a meeting of the Royal Society, and without any inconvenience to him." The recipient was Arthur Coga, "the subject of a harmless form of insanity." Sheeps blood was used because of speculation about the value of blood exchange between species; it had been suggested that blood from a gentle lamb might quiet the tempestuous spirit of an agitated person and that the shy might be made outgoing by blood from more sociable creatures. Coga received 20 shillings (equivalent to £183 in 2021) to participate in the experiment.Lower went on to pioneer new devices for the precise control of blood flow and the transfusion of blood; his designs were substantially the same as modern syringes and catheters. Shortly after, Lower moved to London, where his growing practice soon led him to abandon research.These early experiments with animal blood provoked a heated controversy in Britain and France. Finally, in 1668, the Royal Society and the French government both banned the procedure. The Vatican condemned these experiments in 1670. Blood transfusions fell into obscurity for the next 150 years.
Human blood
The science of blood transfusion dates to the first decade of the 20th century, with the discovery of distinct blood types leading to the practice of mixing some blood from the donor and the receiver before the transfusion (an early form of cross-matching).In the early 19th century, British obstetrician Dr. James Blundell made efforts to treat hemorrhage by transfusion of human blood using a syringe. In 1818 following experiments with animals, he performed the first successful transfusion of human blood to treat postpartum hemorrhage. Blundell used the patients husband as a donor, and extracted four ounces of blood from his arm to transfuse into his wife. During the years 1825 and 1830, Blundell performed 10 transfusions, five of which were beneficial, and published his results. He also invented a number of instruments for the transfusion of blood. He made a substantial amount of money from this endeavour, roughly $2 million ($50 million real dollars).In 1840, at St Georges Hospital Medical School in London, Samuel Armstrong Lane, aided by Blundell, performed the first successful whole blood transfusion to treat haemophilia.However, early transfusions were risky and many resulted in the death of the patient. By the late 19th century, blood transfusion was regarded as a risky and dubious procedure, and was largely shunned by the medical establishment.
Work to emulate James Blundell continued in Edinburgh. In 1845 the Edinburgh Journal described the successful transfusion of blood to a woman with severe uterine bleeding. Subsequent transfusions were successful with patients of Professor James Young Simpson after whom the Simpson Memorial Maternity Pavilion in Edinburgh was named.Various isolated reports of successful transfusions emerged towards the end of the 19th century. The largest series of early successful transfusions took place at the Edinburgh Royal Infirmary between 1885 and 1892. Edinburgh later became the home of the first blood donation and blood transfusion services.
20th century
Only in 1901, when the Austrian Karl Landsteiner discovered three human blood groups (O, A, and B), did blood transfusion achieve a scientific basis and become safer.Landsteiner discovered that adverse effects arise from mixing blood from two incompatible individuals. He found that mixing incompatible types triggers an immune response and the red blood-cells clump. The immunological reaction occurs when the receiver of a blood transfusion has antibodies against the donor blood-cells. The destruction of red blood cells releases free hemoglobin into the bloodstream, which can have fatal consequences. Landsteiners work made it possible to determine blood group and allowed blood transfusions to take place much more safely. For his discovery he won the Nobel Prize in Physiology and Medicine in 1930; many other blood groups have been discovered since.George Washington Crile is credited with performing the first surgery using a direct blood transfusion in 1906 at St. Alexis Hospital in Cleveland while a professor of surgery at Case Western Reserve University.Jan Janský also discovered the human blood groups; in 1907 he classified blood into four groups: I, II, III, IV. His nomenclature is still used in Russia and in states of the former USSR, in which blood types O, A, B, and AB are respectively designated I, II, III, and IV.
Dr. William Lorenzo Mosss (1876–1957) Moss-blood typing technique of 1910 was widely used until World War II.William Stewart Halsted, M.D. (1852–1922), an American surgeon, performed one of the first blood transfusions in the United States. He had been called to see his sister after she had given birth. He found her moribund from blood loss, and in a bold move withdrew his own blood, transfused his blood into his sister, and then operated on her to save her life.
Blood banks in WWI
While the first transfusions had to be made directly from donor to receiver before coagulation, it was discovered that by adding anticoagulant and refrigerating the blood it was possible to store it for some days, thus opening the way for the development of blood banks. John Braxton Hicks was the first to experiment with chemical methods to prevent the coagulation of blood at St Marys Hospital, London in the late-19th century. His attempts, using phosphate of soda, however, proved unsuccessful.
The Belgian doctor Albert Hustin performed the first non-direct transfusion on March 27, 1914, though this involved a diluted solution of blood. The Argentine doctor Luis Agote used a much less diluted solution in November of the same year. Both used sodium citrate as an anticoagulant.The First World War (1914-1918) acted as a catalyst for the rapid development of blood banks and transfusion techniques. Canadian doctor and Lieutenant Lawrence Bruce Robertson became instrumental in persuading the Royal Army Medical Corps to adopt the use of blood transfusion at the Casualty Clearing Stations for the wounded. In October 1915, Robertson performed his first wartime transfusion with a syringe to a patient who had multiple shrapnel wounds. He followed this up with four subsequent transfusions in the following months, and his success was reported to Sir Walter Morley Fletcher, director of the Medical Research Committee.
Robertson published his findings in the British Medical Journal in 1916 and, with the help of a few like-minded individuals (including the eminent physician Edward William Archibald (1872–1945), who introduced the citrate anticoagulant method), was able to persuade the British authorities of the merits of blood transfusion. Robertson went on to establish the first blood-transfusion apparatus at a Casualty Clearing Station on the Western Front in the spring of 1917.Oswald Hope Robertson, a medical researcher and U.S. Army officer, was attached to the RAMC in 1917, where he became instrumental in establishing the first blood banks in preparation for the anticipated Third Battle of Ypres. He used sodium citrate as the anticoagulant; blood was extracted from punctures in the vein and was stored in bottles at British and American Casualty Clearing Stations along the Front. Robertson also experimented with preserving separated red blood cells in iced bottles. Geoffrey Keynes, a British surgeon, developed a portable machine that could store blood to enable transfusions to be carried out more easily.
Expansion
The secretary of the British Red Cross, Percy Oliver, established the worlds first blood-donor service in 1921. In that year, Oliver was contacted by Kings College Hospital, where they were in urgent need of a blood donor.
After providing a donor, Oliver set about organizing a system for the voluntary registration of blood donors at clinics around London, with Sir Geoffrey Keynes appointed as a medical adviser. Volunteers were subjected to a series of physical tests to establish their blood group. The London Blood Transfusion Service was free of charge and expanded rapidly in its first few years of operation. By 1925 it was providing services for almost 500 patients; it was incorporated into the structure of the British Red Cross in 1926. Similar systems developed in other cities, including Sheffield, Manchester and Norwich, and the services work began to attract international attention. France, Germany, Austria, Belgium, Australia and Japan established similar services.Alexander Bogdanov founded an academic institution devoted to the science of blood transfusion in Moscow in 1925. Bogdanov was motivated, at least in part, by a search for eternal youth, and remarked with satisfaction on the improvement of his eyesight, suspension of balding, and other positive symptoms after receiving 11 transfusions of whole blood. Bogdanov died in 1928 as a result of one of his experiments, when the blood of a student with malaria and tuberculosis was given to him in a transfusion. Following Bogdanovs lead, Vladimir Shamov and Sergei Yudin in the USSR pioneered the transfusion of cadaveric blood from recently deceased donors. Yudin performed such a transfusion successfully for the first time on March 23, 1930, and reported his first seven clinical transfusions with cadaveric blood at the Fourth Congress of Ukrainian Surgeons at Kharkiv in September. However, this method was never used widely, even in the Soviet Union. Nevertheless, the Soviet Union was the first to establish a network of facilities to collect and store blood for use in transfusions at hospitals.
Frederic Durán-Jordà established one of the earliest blood banks during the Spanish Civil War in 1936. Duran joined the Transfusion Service at the Barcelona Hospital at the start of the conflict, but the hospital was soon overwhelmed by the demand for blood and the paucity of available donors. With support from the Department of Health of the Spanish Republican Army, Duran established a blood bank for the use of wounded soldiers and civilians. The 300–400 mL of extracted blood was mixed with 10% citrate solution in a modified Duran Erlenmeyer flask. The blood was stored in a sterile glass enclosed under pressure at 2 °C. During 30 months of work, the Transfusion Service of Barcelona registered almost 30,000 donors, and processed 9,000 liters of blood.In 1937 Bernard Fantus, director of therapeutics at the Cook County Hospital in Chicago, established the first hospital blood-bank in the United States. In setting up a hospital laboratory that preserved, refrigerated and stored donor blood, Fantus originated the term "blood bank". Within a few years, hospital and community blood-banks were established across the United States.Frederic Durán-Jordà fled to Britain in 1938 and worked with Dr Janet Vaughan at the Royal Postgraduate Medical School at Hammersmith Hospital to establish a system of national blood banks in London. With the outbreak of war appearing imminent in 1938, the War Office created the Army Blood Supply Depot (ABSD) in Bristol, headed by Lionel Whitby and in control of four large blood-depots around the country. British policy through the war was to supply military personnel with blood from centralized depots, in contrast to the approach taken by the Americans and Germans where troops at the front were bled to provide required blood. The British method proved more successful in adequately meeting all requirements, and over 700,000 donors were bled over the course of the war. This system evolved into the National Blood Transfusion Service established in 1946, the first national service to be implemented.
Stories tell of Nazis in Eastern Europe during World War II using captive children as repeated involuntary blood-donors.
Medical advances
A blood-collection program was initiated in the US in 1940 and Edwin Cohn pioneered the process of blood fractionation. He worked out the techniques for isolating the serum albumin fraction of blood plasma, which is essential for maintaining the osmotic pressure in the blood vessels, preventing their collapse.
Gordon R. Ward, writing in the correspondence columns of the British Medical Journal, proposed the use of blood plasma as a substitute for whole blood and for transfusion purposes as early as 1918. At the onset of World War II, liquid plasma was used in Britain. A large project, known as "Blood for Britain", began in August 1940 to collect blood in New York City hospitals for the export of plasma to Britain. A dried plasma package was developed, which reduced breakage and made transportation, packaging, and storage much simpler.
The resulting dried plasma package came in two tin cans containing 400 mL bottles. One bottle contained enough distilled water to reconstitute the dried plasma contained within the other bottle. In about three minutes, the plasma would be ready to use and could stay fresh for around four hours. Dr. Charles R. Drew was appointed medical supervisor, and he was able to transform the test-tube methods into the first successful technique for mass production.
Another important breakthrough came in 1937–40 when Karl Landsteiner (1868–1943), Alex Wiener, Philip Levine, and R.E. Stetson discovered the Rhesus blood group system, which was found to be the cause of the majority of transfusion reactions up to that time. Three years later, the introduction by J.F. Loutit and Patrick L. Mollison of acid–citrate–dextrose (ACD) solution, which reduced the volume of anticoagulant, permitted transfusions of greater volumes of blood and allowed longer-term storage.
Carl Walter and W.P. Murphy Jr. introduced the plastic bag for blood collection in 1950. Replacing breakable glass bottles with durable plastic bags made from PVC allowed for the evolution of a collection system capable of safe and easy preparation of multiple blood components from a single unit of whole blood.
In the field of cancer surgery, the replacement of massive blood-loss became a major problem. The cardiac-arrest rate was high. In 1963 C. Paul Boyan and William S. Howland discovered that the temperature of the blood and the rate of infusion greatly affected survival rates, and introduced blood warming to surgery.Further extending the shelf-life of stored blood up to 42 days was an anticoagulant preservative, CPDA-1, introduced in 1979, which increased the blood supply and facilitated resource-sharing among blood banks.As of 2006 about 15 million units of blood products were transfused per year in the United States. By 2013 the number had declined to about 11 million units, because of the shift towards laparoscopic surgery and other surgical advances and studies that have shown that many transfusions were unnecessary. For example, the standard of care reduced the amount of blood transfused in one case from 750 to 200 mL.
Special populations
Neonate
To ensure the safety of blood transfusion to pediatric patients, hospitals are taking additional precautions to avoid infection and prefer to use specially tested pediatric blood units that are guaranteed negative for Cytomegalovirus. Most guidelines recommend the provision of CMV-negative blood components and not simply leukoreduced components for newborns or low birthweight infants in whom the immune system is not fully developed. These specific requirements place additional restrictions on blood donors who can donate for neonatal use.
Neonatal transfusions typically fall into one of two categories:
"Top-up" transfusions, to replace losses due to investigational losses and correction of anemia.
Exchange (or partial exchange) transfusions are done for removal of bilirubin, removal of antibodies and replacement of red cells (e.g., for anemia secondary to thalassemias and other hemoglobinopathies).
Significant blood loss
A massive transfusion protocol is used when significant blood loss is present such as in major trauma, when more than ten units of blood are needed. Packed red blood cells, fresh frozen plasma, and platelets are generally administered. Typically higher ratios of fresh frozen plasma and platelets are given relative to packed red blood cells.
Unknown blood type
Because blood type O negative is compatible with anyone, it is often overused and in short supply. According to the American Association of Blood Banks, the use of this blood should be restricted to persons with O negative blood, as nothing else is compatible with them, and women who might be pregnant and for whom it would be impossible to do blood group testing before giving them emergency treatment. Whenever possible, the AABB recommends that O negative blood be conserved by using blood type testing to identify a less scarce alternative.
Religious objections
Jehovahs Witnesses may object to blood transfusions because of their belief that blood is sacred.
Research into alternatives
Although there are clinical situations where transfusion with red blood cells is the only clinically appropriate option, clinicians look at whether alternatives are feasible. This can be due to several reasons, such as patient safety, economic burden or scarcity of blood. Guidelines recommend blood transfusions should be reserved for patients with or at risk of cardiovascular instability due to the degree of their anaemia. In these cases parenteral iron is recommended.
Thus far, there are no available oxygen-carrying blood substitutes, which is the typical objective of a blood (RBC) transfusion; however, there are widely available non-blood volume expanders for cases where only volume restoration is required. These are helping doctors and surgeons avoid the risks of disease transmission and immune suppression, address the chronic blood donor shortage, and address the concerns of Jehovahs Witnesses and others who have religious objections to receiving transfused blood.
The research in this area is ongoing. A number of blood substitutes have been explored, but thus far they all have serious limitations. Most attempts to find a suitable alternative to blood thus far have concentrated on cell-free hemoglobin solutions. Blood substitutes could make transfusions more readily available in emergency medicine and in pre-hospital EMS care. If successful, such a blood substitute could save many lives, particularly in trauma where massive blood loss results. Hemopure, a hemoglobin-based therapy, is approved for use in South Africa.
Other uses
Minor blood transfusions are used by a minority of nyaope drug addicts in South Africa to economically share the high the drug induces in a practice colloquially known as Bluetoothing, named after the wireless technology of the same name.
Veterinary use
Veterinarians also administer transfusions to other animals. Various species require different levels of testing to ensure a compatible match. For example, cats have 3 known blood types, cattle have 11, dogs have 13, pigs have 16, and horses have 34. However, in many species (especially horses and dogs), cross matching is not required before the first transfusion, as antibodies against non-self cell surface antigens are not expressed constitutively – i.e. the animal has to be sensitized before it will mount an immune response against the transfused blood.
The rare and experimental practice of inter-species blood transfusions is a form of xenograft.
See also
Anemia
Arnault Tzanck
Blood transfusion in Sri Lanka
Blood type (non-human)
Xenotransfusion
Young blood transfusion, a pseudoscientific practice involving the transfusion of blood taken from young donors to older recipients that is claimed to have health benefits
AIDS
References
Further reading
Tucker, Holly (2012). Blood Work: A Tale of Medicine and Murder in the Scientific Revolution. W. W. Norton & Company. ISBN 978-0393342239.
"Milk as a Substitute for Blood Transfusion", historical account, Scientific American, 13 July 1878, p. 19
External links
Transfusion Evidence Library searchable source of evidence for transfusion medicine.
Blood transfusion societies
American Association of Blood Banks (AABB)
British Blood Transfusion Society (BBTS)
International Society of Blood Transfusion (ISBT)
Books
Blood Groups and Red Cell Antigens Free online book at NCBI Bookshelf ID: NBK2261
Handbook of Transfusion Medicine Free book published in the UK 5th edition
Guidelines
American Association of Blood Banks Clinical Practice Guidelines
Australian National Blood Authority Patient Blood Management Guidelines
British Committee for Standards in Haematology
National Institute for Health and Care Excellence Blood Transfusion Guidance UK Guidance for transfusion.
Canadian Blood Transfusion Guidelines
German Medical Association Guidelines (English), published 2014.
Patient information
Blood Transfusion Leaflets (NHS Blood and Transplant)
Blood Transfusion Leaflets (Welsh Blood Service)
Blood Transfusion Information (Scotland)
Blood Transfusion Information (Australia)
Blood Transfusion Information (American Cancer Society) |
Invasive candidiasis | Invasive candidiasis is an infection (candidiasis) that can be caused by various species of Candida yeast. Unlike Candida infections of the mouth and throat (oral candidiasis) or vagina (Candidal vulvovaginitis), invasive candidiasis is a serious, progressive, and potentially fatal infection that can affect the blood (fungemia), heart, brain, eyes, bones, and other parts of the body.
Signs and symptoms
Symptoms of invasive candidiasis can be confused with other medical conditions, however, the most common symptoms are fever and chills that do not improve with antibiotic treatment. Other symptoms develop as the infection spreads, depending on which parts of the body are involved.
Presentation
Invasive candidiasis can manifest as serious diseases including as fungemia, endocarditis, endophthalmitis, osteomyelitis, and central nervous system infections.
Cause
Invasive candidiasis is caused by 15 of the more than 150 known species of Candida. These species, all confirmed by isolation from patients, are: C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, C. guilliermondii, C. lusitaniae, C. dubliniensis, C. pelliculosa, C. kefyr, C. lipolytica, C. famata, C. inconspicua, C. rugosa, and C. norvegensis. Over the last 20–30 years, C. albicans has been responsible for 95% of infections, with, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei causing the majority of the remaining cases. Recently, C. auris, a species first reported in 2009, has been found to cause invasive candidiasis. C. auris has attracted attention because it can be resistant to the antifungal medications used to treat candidiasis.
Resistance
Resistance to antifungal treatment can arise from species with intrinsic resistance that experience selection pressure or spontaneous induction of resistance in isolates from normally susceptible species. For Candida, the most common is the former, as seen by the emergence of resistant C. glabrata following the introduction of fluconazole and of C. parapsilosis where there was increased use of echinocandins. Insufficient dosing of azoles has also led to the emergence of resistance. Observed rates of echinocandin resistance for C. glabrata are between 2 and 12%. Acquired echinocandin resistance has also been reported for C. albicans, C. tropicalis, C. krusei, C. kefyr, C. lusitaniae, and C. dubliniensis.
Emergent species
Candida auris is an emerging multidrug-resistant yeast that can cause invasive candidiasis and is associated with high mortality. It was first described in 2009. Since then, C. auris infections, specifically fungemia, have been reported from South Korea, India, South Africa, Kuwait, Colombia, Venezuela, Pakistan, the United Kingdom and the United States. The strains isolated in each region are genetically distinct, indicating that this species is emerging in different locations. The reason for this pattern is unknown.
Risk factors
Patients with the following conditions, treatments or situations are at increased risk for invasive candidiasis.
Critical illness
Long-term intensive care unit stay
Abdominal surgery (aggravated by anastomotic leakage or repeat laparotomies)
Immunosuppressive diseases
Acute necrotizing pancreatitis
Malignant hematologic disease
Solid-organ transplantation
Hematopoietic stem cell transplantation
Solid-organ tumors
Neonates (especially low birth weight and preterm infants)
Broad-spectrum antibiotic treatment
Central venous catheter
Internal prosthetic device
Total parenteral nutrition
Hemodialysis
Glucocorticoid use
Chemotherapy
Noninvasive Candida colonization (particularly if multifocal)
Transmission
Invasive candidiasis is a nosocomial infection with the majority of cases associated with hospital stays.
Diagnosis
Because many Candida species are part of the human microbiota, their presence in the mouth, the vagina, sputum, urine, stool, or skin is not definitive evidence for invasive candidiasis.Positive culture of Candida species from normally sterile sites, such as blood, cerebrospinal fluid, pericardium, pericardial fluid, or biopsied tissue, is definitive evidence of invasive candidiasis. Diagnosis by culturing allows subsequent susceptibility testing of causative species. Sensitivity of blood culture is far from ideal, with a sensitivity reported to be between 21 and 71%. Additionally, whereas blood culture can establish a diagnosis during fungemia, the blood may test negative for deep-seated infections because candida may have been successfully cleared from the blood.Diagnosis of invasive candidiasis is supported by histopathologic evidence (for example, yeast cells or hyphae) observed in specimens of affected tissues.Additionally, elevated serum β-glucan can demonstrate invasive candidiasis while a negative test suggests a low likelihood of systemic infection.The emergence of multidrug-resistant C. auris as a cause of invasive candidiasis has necessitated additional testing in some settings. C. auris-caused invasive candidiasis is associated with high mortality. Many C. auris isolates have been found to be resistant to one or more of the three major antifungal classes (azoles, echinocandins, and polyenes) with some resistant to all three classes – severely limiting treatment options. Biochemical-based tests currently used in many laboratories to identify fungi, including API 20C AUX and VITEK-2, cannot differentiate C. auris from related species (for example, C. auris can be identified as C. haemulonii). Therefore, the Centers for Disease Control and Prevention recommends using a diagnostic method based on matrix-assisted laser desorption/ionization-time of flight mass spectrometry or a molecular method based on sequencing the D1-D2 region of the 28s rDNA to identify C. auris in settings where it may be present.
Prevention
Preventive antifungal treatment is supported by studies, but only for specific high-risk groups in intensive care units with conditions that put them at high risk for the disease. For example, one group would be patients recovering from abdominal surgery that may have gastrointestinal perforations or anastomotic leakage. Antifungal prophylaxis can reduce the incidence of fungemia by approximately 50%, but has not been shown to improve survival. A major challenge limiting the number of patients receiving prophylaxis to only those that can potentially benefit, thereby avoiding the creation of selective pressure that can lead to the emergence of resistance.
Treatment
Antifungals are used for treatment with the specific type and dose depending on the patients age, immune status, and specifics of the infection. For most adults, the initial treatment is an echinocandin class antifungal (caspofungin, micafungin, or anidulafungin) given intravenously. Fluconazole, amphotericin B, and other antifungals may also be used. Treatment normally continues for two weeks after resolution of signs and symptoms and Candida yeasts can no longer can be cultured from blood samples. Some forms of invasive candidiasis, such as infections in the bones, joints, heart, or central nervous system, usually need to be treated for a longer period. Retrospective observational studies suggest that prompt presumptive antifungal therapy (based on symptoms or biomarkers) is effective and can reduce mortality.
Epidemiology
Invasive candidiasis is estimated to affect more than 250,000 people and cause more than 50,000 deaths worldwide every year. The CDC estimates that approximately 46,000 cases of healthcare-associated invasive candidiasis occur each year in the US. The estimated mortality attributable to fungemia is 19-40%. However, because the majority of people who develop invasive candidiasis are already sick, it can be difficult to determine if the cause of death is directly attributable to the fungal infection. Fungemia is one of the most common bloodstream infections in the United States. In general, observed incidence rates have been stable or trending higher but declining rates have been achieved with improvements in hygiene and disease management.Deep-seated infections in bones, muscles, joints, eyes, or central nervous system can arise from a bloodstream infection or direct inoculation of Candida may occur, for example, during intestinal surgery.The distribution of Candida species causing invasive candidiasis has changed over the past decades. C. albicans had been the dominant pathogen but now accounts for just half of the isolates. Increasing dominance of C. glabrata in northern Europe, the United States, and Canada has been observed while C. parapsilosis has become more prominent in southern Europe, Asia, and South America. Regional species distribution guides treatment recommendations since the species exhibit different susceptibilities to azole and echinocandin classes of antifungals.The virulence of Candida species differs considerably, with C. parapsilosis and C. krusei being less virulent than C. albicans, C. tropicalis, and C. glabrata. This variation is reflected in mortality rates.
References
Further reading
Pfaller MA, Diekema DJ (2007). "Epidemiology of invasive candidiasis: a persistent public health problem". Clinical Microbiology Reviews. 20 (1): 133–163. doi:10.1128/CMR.00029-06. PMC 1797637. PMID 17223626. (Review).
Yapar N (2014). "Epidemiology and risk factors for invasive candidiasis". Therapeutics and Clinical Risk Management. 10: 95–105. doi:10.2147/TCRM.S40160. PMC 3928396. PMID 24611015. (Review).
External links
Candidiasis (Invasive) in the MSD (Merck) Manual
Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America |
Glycogen storage disease type I | Glycogen storage disease type I (GSD I) is an inherited disease that results in the liver being unable to properly break down stored glycogen. This impairment disrupts the livers ability to break down stored glycogen that is necessary to maintain adequate blood sugar levels. GSD I is divided into two main types, GSD Ia and GSD Ib, which differ in cause, presentation, and treatment. GSD Ia is caused by a deficiency in the enzyme glucose-6-phosphatase, while GSD Ib is caused a deficiency in the enzyme glucose-6-phosphate translocase. Since glycogenolysis is the principal metabolic mechanism by which the liver supplies glucose to the body during periods of fasting, both deficiencies cause severe low blood sugar and, over time, excess glycogen storage in the liver and (in some cases) the kidneys.
GSD I patients typically present with an enlarged liver from non-alcoholic fatty liver disease as the result of this glycogen buildup. Other functions of the liver and kidneys are initially intact in GSD I, but are susceptible to a variety of other problems. Without proper treatment, GSD I gives rise to chronic low blood sugar, which can result in derangements including excessive levels of lactic acid and abnormally high levels of lipids in the bloodstream. Frequent feedings of cornstarch or other carbohydrates are the principal treatment for all forms of GSD I.
GSD Ib also features chronic neutropenia due to a dysfunction in the production of neutrophils in the bone marrow. This immunodeficiency, if untreated, makes GSD Ib patients susceptible to infection. The principal treatment for this feature of GSD Ib is filgrastim; however, patients often still require treatment for frequent infections, and a chronically enlarged spleen is a common side effect. GSD Ib patients often present with inflammatory bowel disease.It is the most common of the glycogen storage diseases. GSD I has an incidence of approximately 1 in 100,000 births in the American population, and approximately 1 in 20,000 births among Ashkenazi Jews. The disease was named after German doctor Edgar von Gierke, who first described it in 1929.
Signs and symptoms
Early research into GSD I identified numerous clinical manifestations falsely thought to be primary features of the genetic disorder. However, continuing research has revealed that these clinical features are the consequences of only one (in GSD Ia) or two (in GSD Ib) fundamental abnormalities:
impairment in the livers ability to convert stored glycogen into glucose through glycogenolysis
in GSD Ib, impairment of the neutrophils ability to take up glucose, resulting in neutrophil dysfunction and neutropeniaThese fundamental abnormalities give rise to a small number of primary clinical manifestations, which are the features considered in diagnosis of GSD I:
Low blood sugar (hypoglycemia), due to impairment of glycogen breakdown (glycogenolysis) causing insufficient fasting blood glucose
hepatomegaly of non-alcoholic fatty liver disease, due to impairment of glycogenolysis causing glycogen accumulation in the liver
in GSD Ib, increased infection risk, due to neutropenia and neutrophil dysfunctionAffected people commonly present with secondary clinical manifestations, linked to one or more of the primary clinical manifestations:
High levels of uric acid in the blood and attendant risk of gout or kidney damage, caused by low serum insulin levels in prolonged hypoglycemia
High levels of lactic acid in the blood, in extreme cases leading to lactic acidosis, caused by prolonged hypoglycemia
hepatic adenomas developing in adulthood and attendant risk of anemia, suspected to be caused by blood glucose dysregulation in the presence of non-alcoholic fatty liver disease
in GSD Ib, inflammatory bowel disease and attendant risk of anemia, caused by neutrophil dysfunction and exacerbated by the increased carbohydrate intake required to prevent hypoglycemiaIn addition, there are several clinical manifestations that often result from the treatment of the primary clinical manifestations:
pancreatic hypertrophy, due to increased carbohydrate intake causing frequent engagement of the insulin response
in GSD Ib, splenomegaly, due to the long-term use of filgrastim to treat neutropenia causing sequestration of blood factors in the spleen
in GSD Ib, an abnormally low number of platelets in the blood may occur, due to long-term use of filgrastim causing sequestration of platelets in the spleen
in GSD Ib, anemia, due to long-term use of filgrastim causing sequestration of hemoglobin in the spleen, potentially exacerbated by uncontrolled inflammatory bowel disease
Hypoglycemia
Low blood sugar (hypoglycemia) is the primary clinical symptom common to both GSD Ia and GSD Ib and most often prompts initial diagnosis of the disease. During fetal development in utero, maternal glucose transferred across the placenta prevents hypoglycemia. However, after birth, the inability to maintain blood glucose from stored glycogen in the liver causes measurable hypoglycemia in no more than 1–2 hours after feedings. Without proper dietary treatment after birth, prolonged hypoglycemia often leads to sudden lactic acidosis that can induce primary respiratory distress in the newborn period, as well as ketoacidosis.Neurological manifestations of hypoglycemia are less severe in GSD I than in other instances. Rather than acute hypoglycemia, GSD I patients experience persistent mild hypoglycemia. The diminished likelihood of neurological manifestations is due to the habituation of the brain to mild hypoglycemia. Given the reduced blood glucose level, the brain adapts to using alternative fuels like lactate. These gradual metabolic adaptations during infancy make severe symptoms like unconsciousness or seizure uncommon before diagnosis.In the early weeks of life, undiagnosed infants with GSD I tolerate persistent hypoglycemia and compensated lactic acidosis between feedings without symptoms. Without consistent carbohydrate feeding, infant blood glucose levels typically measure between 25 and 50 mg/dL (1.4 to 2.8 mmol/L). After weeks to months without treatment with consistent oral carbohydrates, infants will progress to show clear symptoms of hypoglycemia and lactic acidosis. Infants may present with paleness, clamminess, irritability, respiratory distress, and an inability to sleep through the night even in the second year of life. Developmental delay is not an intrinsic effect of GSD I, but is common if the diagnosis is not made in early infancy.
Genetics
GSD I is inherited in an autosomal recessive manner. People with one copy of the faulty gene are carriers of the disease and have no symptoms. As with other autosomal recessive diseases, each child born to two carriers of the disease has a 25% chance of inheriting both copies of the faulty gene and manifesting the disease. Unaffected parents of a child with GSD I can be assumed to be carriers. Prenatal diagnosis has been made by fetal liver biopsy at 18–22 weeks of gestation, but no fetal treatment has been proposed. Prenatal diagnosis is possible with fetal DNA obtained by chorionic villus sampling when a fetus is known to be at risk.The most common forms of GSD I are designated GSD Ia and GSD Ib, the former accounting for over 80% of diagnosed cases and the latter for less than 20%. A few rarer forms have been described.
GSD Ia results from mutations of G6PC, the gene for glucose-6-phosphatase, located on chromosome 17q21.
GSD Ib results from mutations of the gene for SLC37A4 or "G6PT1", the glucose-6-phosphate transporter.
GSD Ic results from mutations of SLC17A3 or SLC37A4.Glucose-6-phosphatase is an enzyme located on the inner membrane of the endoplasmic reticulum. The catalytic unit is associated with a calcium binding protein, and three transport proteins (T1, T2, T3) that facilitate movement of glucose-6-phosphate (G6P), phosphate, and glucose (respectively) into and out of the enzyme.
Pathophysiology
Normal carbohydrate balance and maintenance of blood glucose levels
Glycogen in liver and (to a lesser degree) kidneys serves as a form of stored, rapidly accessible glucose, so that the blood glucose level can be maintained between meals. For about 3 hours after a carbohydrate-containing meal, high insulin levels direct liver cells to take glucose from the blood, to convert it to glucose-6-phosphate (G6P) with the enzyme glucokinase, and to add the G6P molecules to the ends of chains of glycogen (glycogen synthesis). Excess G6P is also shunted into production of triglycerides and exported for storage in adipose tissue as fat.
When digestion of a meal is complete, insulin levels fall, and enzyme systems in the liver cells begin to remove glucose molecules from strands of glycogen in the form of G6P. This process is termed glycogenolysis. The G6P remains within the liver cell unless the phosphate is cleaved by glucose-6-phosphatase. This dephosphorylation reaction produces free glucose and free PO4 anions. The free glucose molecules can be transported out of the liver cells into the blood to maintain an adequate supply of glucose to the brain and other organs of the body. Glycogenolysis can supply the glucose needs of an adult body for 12–18 hours.
When fasting continues for more than a few hours, falling insulin levels permit catabolism of muscle protein and triglycerides from adipose tissue. The products of these processes are amino acids (mainly alanine), free fatty acids, and lactic acid. Free fatty acids from triglycerides are converted to ketones, and to acetyl-CoA. Amino acids and lactic acid are used to synthesize new G6P in liver cells by the process of gluconeogenesis. The last step of normal gluconeogenesis, like the last step of glycogenolysis, is the dephosphorylation of G6P by glucose-6-phosphatase to free glucose and PO4.
Thus glucose-6-phosphatase mediates the final, key, step in both of the two main processes of glucose production during fasting. The effect is amplified because the resulting high levels of glucose-6-phosphate inhibit earlier key steps in both glycogenolysis and gluconeogenesis.
Pathophysiology
The principal metabolic effects of deficiency of glucose-6-phosphatase are hypoglycemia, lactic acidosis, hypertriglyceridemia, and hyperuricemia.
The hypoglycemia of GSD I is termed "fasting", or "post-absorptive", usually about 4 hours after the complete digestion of a meal. This inability to maintain adequate blood glucose levels during fasting results from the combined impairment of both glycogenolysis and gluconeogenesis. Fasting hypoglycemia is often the most significant problem in GSD I, and typically the problem that leads to the diagnosis. Chronic hypoglycemia produces secondary metabolic adaptations, including chronically low insulin levels and high levels of glucagon and cortisol.
Lactic acidosis arises from impairment of gluconeogenesis. Lactic acid is generated both in the liver and muscle and is oxidized by NAD+ to pyruvic acid and then converted via the gluconeogenic pathway to G6P. Accumulation of G6P inhibits conversion of lactate to pyruvate. The lactic acid level rises during fasting as glucose falls. In people with GSD I, it may not fall entirely to normal even when normal glucose levels are restored.
Hypertriglyceridemia resulting from amplified triglyceride production is another indirect effect of impaired gluconeogenesis, amplified by chronically low insulin levels. During fasting, the normal conversion of triglycerides to free fatty acids, ketones, and ultimately acetyl-CoA is impaired. Triglyceride levels in GSD I can reach several times normal and serve as a clinical index of "metabolic control".
Hyperuricemia results from a combination of increased generation and decreased excretion of uric acid, which is generated when increased amounts of G6P are metabolized via the pentose phosphate pathway. It is also a byproduct of purine degradation. Uric acid competes with lactic acid and other organic acids for renal excretion in the urine. In GSD I increased availability of G6P for the pentose phosphate pathway, increased rates of catabolism, and diminished urinary excretion due to high levels of lactic acid all combine to produce uric acid levels several times normal. Although hyperuricemia is asymptomatic for years, kidney and joint damage gradually accrue.
Elevated lactate and lactic acidosis
High levels of lactic acid in the blood are observed in all people with GSD I, due to impaired gluconeogenesis. Baseline elevations generally range from 4 to 10 mol/mL, which will not cause any clinical impact. However, during and after an episode of low blood sugar, lactate levels will abruptly rise to exceed 15 mol/mL, the threshold for lactic acidosis. Symptoms of lactic acidosis include vomiting and hyperpnea, both of which can exacerbate hypoglycemia in the setting of GSD I. In cases of acute lactic acidosis, patients need emergency care to stabilize blood oxygen, and restore blood glucose. Proper identification of lactic acidosis in undiagnosed children presents a challenge, since the first symptoms are typically vomiting and dehydration, both of which mimic childhood infections like gastroenteritis or pneumonia. Moreover, both of these common infections can precipitate more severe hypoglycemia in undiagnosed children, making diagnosis of the underlying cause difficult.
As elevated lactate persists, uric acid, ketoacids, and free fatty acids further increase the anion gap. In adults and children, the high concentrations of lactate cause significant discomfort in the muscles. This discomfort is an amplified form of the burning sensation a runner may feel in the quadriceps after sprinting, which is caused by a brief buildup of lactic acid. Proper control of hypoglycemia in GSD I eliminates the possibility for lactic acidosis.
Elevated urate and complications
High levels of uric acid often present as a consequence of elevated lactic acid in GSD I patients. When lactate levels are elevated, blood-borne lactic acid competes for the same kidney tubular transport mechanism as urate, limiting the rate that urate can be cleared by the kidneys into the urine. If present, increased purine catabolism is an additional contributing factor. Uric acid levels of 6 to 12 mg/dl (530 to 1060 umol/L) are common among GSD I patients, if the disease is not properly treated. In some affected people, the use of the medication allopurinol is necessary to lower blood urate levels. Consequences of hyperuricemia among GSD I patients include the development of kidney stones and the accumulation of uric acid crystals in joints, leading to kidney disease and gout, respectively.
Hyperlipidemia and plasma effects
Elevated triglycerides in GSD I result from low serum insulin in patients with frequent prolonged hypoglycemia. It may also be caused by intracellular accumulation of glucose-6-phosphate with secondary shunting to pyruvate, which is converted into Acetyl-CoA, which is transported to the cytosol where the synthesis of fatty acids and cholesterol occurs. Triglycerides above the 3.4 mmol/L (300 mg/dL) range may produce visible lipemia, and even a mild pseudohyponatremia due to a reduced aqueous fraction of the blood plasma. In GSD I, cholesterol is typically only mildly elevated compared to other lipids.
Hepatomegaly
Impairment in the livers ability to perform gluconeogenesis leads to clinically apparent hepatomegaly. Without this process, the body is unable to liberate glycogen from the liver and convert it into blood glucose, leading to an accumulation of stored glycogen in the liver. Hepatomegaly from the accumulation of stored glycogen in the liver is considered a form of non-alcoholic fatty liver disease. GSD I patients present with a degree of hepatomegaly throughout life, but severity often relates to the consumption of excess dietary carbohydrate. Reductions in the mass of the liver are possible, since most patients retain residual hepatic function that allows for the liberation of stored glycogen at a limited rate.
GSD I patients often present with hepatomegaly from the time of birth. In fetal development, maternal glucose transferred to the fetus prevents hypoglycemia, but the storage of glucose as glycogen in the liver leads to hepatomegaly. There is no evidence that this hepatomegaly presents any risk to proper fetal development.
Hepatomegaly in GSD type I generally occurs without sympathetic enlargement of the spleen. GSD Ib patients may present with splenomegaly, but this is connected to the use of filgrastim to treat neutropenia in this subtype, not comorbid hepatomegaly. Hepatomegaly will persist to some degree throughout life, often causing the abdomen to protrude, and in severe cases may be palpable at or below the navel. In GSD-related non-alcoholic fatty liver disease, hepatic function is usually spared, with liver enzymes and bilirubin remaining within the normal range. However, liver function may be affected by other hepatic complications in adulthood, including the development of hepatic adenomas.
Hepatic adenomas
The specific etiology of hepatic adenomas in GSD I remains unknown, despite ongoing research. The typical GSD I patient presenting with at least one adenoma is an adult, though lesions have been observed in patients as young as fourteen. Adenomas, composed of heterogeneous neoplasms, may occur individually or in multiples. Estimates on the rate of conversion of a hepatocellular adenoma into hepatocellular carcinoma in GSD I range from 0% to 11%, with the latter figure representing more recent research. One reason for the increasing estimate is the growing population of GSD I patients surviving into adulthood, when most adenomas develop.
Treatment standards dictate regular observation of the liver by MRI or CT scan to monitor for structural abnormalities. Hepatic adenomas may be misidentified as focal nodular hyperplasia in diagnostic imaging, though this condition is rare. However, hepatic adenomas in GSD I uniquely involve diffuse Mallory hyaline deposition, which is otherwise commonly observed in focal nodular hyperplasia. Unlike common hepatic adenomas related to oral contraception, hemorrhaging in GSD I patients is rare.
While the reason for the high prevalence of adenomas in GSD I is unclear, research since the 1970s has implicated serum glucagon as a potential driver. In studies, patients that have been put on a dietary regimen to keep blood sugar in a normal range spanning 72 to 108 mg/dL (4.0 to 6.0 mmol/L) have shown a decreased likelihood of developing adenomas. Moreover, patients with well controlled blood glucose have consistently seen a reduction in the size and number of hepatic adenomas, suggesting that adenomas may be caused by imbalances of hepatotropic agents like serum insulin and especially serum glucagon in the liver.
Osteopenia
Patients with GSD I will often develop osteopenia. The specific etiology of low bone mineral density in GSD is not known, though it is strongly associated with poor metabolic control. Osteopenia may be directly caused by hypoglycemia, or the resulting endocrine and metabolic sequelae. Improvements in metabolic control have consistently been shown to prevent or reverse clinically relevant osteopenia in GSD I patients. In cases where osteopenia progresses with age, bone mineral density in the ribs is typically more severe than in the vertebrae. In some cases bone mineral density T-score will drop below -2.5, indicating osteoporosis. There is some evidence that osteopenia may be connected with associated kidney abnormalities in GSD I, particularly glomular hyperfiltration. The condition also seems responsive to calcium supplementation. In many cases bone mineral density can increase and return to the normal range given proper metabolic control and calcium supplementation alone, reversing osteopenia.
Kidney effects
The kidneys are usually 10 to 20% enlarged with stored glycogen. In adults with GSD I, chronic glomerular damage similar to diabetic nephropathy may lead to kidney failure. GSD I may present with various kidney complications. Renal tubular abnormalities related to hyperlactatemia are seen early in life, likely because prolonged lactic acidosis is more likely to occur in childhood. This will often present as Fanconi syndrome with multiple derangements of renal tubular reabsorption, including tubular acidosis with bicarbonate and phosphate wasting. These tubular abnormalities in GSD I are typically detected and monitored by urinary calcium. Long term these derangements can exacerbate uric acid nephropathy, otherwise driven by hyperlactatemia. In adolescence and beyond, glomerular disease may independently develop, initially presenting as glomerular hyperfiltration indicated by elevated urinary eGFR.
Splenomegaly
Enlargement of the spleen (splenomegaly) is common in GSD I and has two primary causes. In GSD Ia, splenomegaly may be caused by a relation between the liver and the spleen which causes either to grow or shrink to match the relative size of the other, to a lessened degree. In GSD Ib, it is a side effect of the use of filgrastim to treat neutropenia.
Bowel effects
Intestinal involvement can cause mild malabsorption with greasy stools (steatorrhea), but usually requires no treatment.
Infection risk
Neutropenia is a distinguishing feature of GSD Ib, absent in GSD Ia. The microbiological cause of neutropenia in GSD Ib is not well understood. Broadly, the problem arises from compromised cellular metabolism in the neutrophil, resulting in accelerated neutrophil apoptosis. The neutropenia in GSD is characterized by both a decrease in absolute neutrophil count and diminished neutrophil function. Neutrophils use a specific G6P metabolic pathway which relies on the presence of G6Pase-β or G6PT to maintain energy homeostasis within the cell. The absence of G6PT in GSD Ib limits this pathway, leading to endoplasmic reticulum stress, oxidative stress within the neutrophil, triggering premature apoptosis. Granulocyte colony-stimulating factor (G-CSF), available as filgrastim, can reduce the risk of infection. In some cases, G-CSF formulated as pegfilgrastim, sold under the trade name Neulasta, may be used as a slow-acting alternative, requiring less frequent dosing.
Thrombocytopenia and blood clotting problems
Impaired platelet aggregation is an uncommon consequence of chronic hypoglycemia, seen in GSD I patients. Research has demonstrated decreased platelet function, characterized by decreased prothrombin consumption, abnormal aggregation reactions, prolonged bleeding time, and low platelet adhesiveness. Severity of platelet dysfunction typically correlates with clinical condition, with the most severe cases correlating with lactic acidosis and severely lipidemia. It may cause clinically significant bleeding, especially epistaxis. Additionally, GSD I patients may present with thrombocytopenia as a consequence of splenomegaly. In the setting of splenomegaly various hematologic factors may be sequestered in the tissues of the spleen as blood is filtered through the organ. This can diminish levels of platelets available in the bloodstream, leading to thrombocytopenia.
Developmental effects
Developmental delay is a potential secondary effect of chronic or recurrent hypoglycemia, but is at least theoretically preventable. Normal neuronal and muscle cells do not express glucose-6-phosphatase, and are thus not impacted by GSD I directly. However, without proper treatment of hypoglycemia, growth failure commonly results from chronically low insulin levels, persistent acidosis, chronic elevation of catabolic hormones, and calorie insufficiency (or malabsorption). The most dramatic developmental delays are often the cause of severe (not just persistent) episodes of hypoglycemia.
Diagnosis
Several different problems may lead to the diagnosis, usually by two years of age:
seizures or other manifestations of severe fasting hypoglycemia
hepatomegaly with abdominal protuberance
hyperventilation and apparent respiratory distress due to metabolic acidosis
episodes of vomiting due to metabolic acidosis, often precipitated by minor illness and accompanied by hypoglycemiaOnce the diagnosis is suspected, the multiplicity of clinical and laboratory features usually makes a strong circumstantial case. If hepatomegaly, fasting hypoglycemia, and poor growth are accompanied by lactic acidosis, hyperuricemia, hypertriglyceridemia, and enlarged kidneys by ultrasound, GSD I is the most likely diagnosis. The differential diagnosis list includes glycogenoses types III and VI, fructose 1,6-bisphosphatase deficiency, and a few other conditions (page 5), but none are likely to produce all of the features of GSD I.
The next step is usually a carefully monitored fast. Hypoglycemia often occurs within six hours. A critical blood specimen obtained at the time of hypoglycemia typically reveals a mild metabolic acidosis, high free fatty acids and beta-hydroxybutyrate, very low insulin levels, and high levels of glucagon, cortisol, and growth hormone. Administration of intramuscular or intravenous glucagon (0.25 to 1 mg, depending on age) or epinephrine produces little rise of blood sugar.
The diagnosis is definitively confirmed by liver biopsy with electron microscopy and assay of glucose-6-phosphatase activity in the tissue and/or specific gene testing, available in recent years.
Treatment
The primary treatment goal is prevention of hypoglycemia and the secondary metabolic derangements by frequent feedings of foods high in glucose or starch (which is readily digested to glucose). To compensate for the inability of the liver to provide sugar, the total amount of dietary carbohydrate should approximate the 24-hour glucose production rate. The diet should contain approximately 65–70% carbohydrate, 10–15% protein, and 20–25% fat. At least a third of the carbohydrates should be supplied through the night, so that a young child goes no more than 3–4 hours without carbohydrate intake.
Once a diagnosis is made, the priority in GSD I treatment is to maintain an adequate blood glucose. Patients aim to maintain a blood glucose above the 72 mg/dL (4.0 mmol/L) cutoff for hypoglycemia. GSD Ib patients have an additional treatment priority relating to neutropenia. Proper management of blood glucose in GSD I is critical in avoiding the more severe effects of high leves of lactic acid and uric acid in the blood, and the development of hepatic adenomas.
In the last 30 years, two methods have been used to achieve this goal in young children: (1) continuous nocturnal gastric infusion of glucose or starch; and (2) night-time feedings of uncooked cornstarch. An elemental formula, glucose polymer, and/or cornstarch can be infused continuously through the night at a rate supplying 0.5–0.6 g/kg/h of glucose for an infant, or 0.3–0.4 for an older child. This method requires a nasogastric or gastrostomy tube and pump. Sudden death from hypoglycemia has occurred due to malfunction or disconnection, and periodic cornstarch feedings are now preferred to continuous infusion.
Cornstarch is an inexpensive way to provide gradually digested glucose. One tablespoon contains nearly 9 g carbohydrate (36 calories). Although it is safer, less expensive, and requires no equipment, this method does require that parents arise every 3–4 hours to administer the cornstarch. A |
Glycogen storage disease type I | typical requirement for a young child is 1.6 g/kg every 4 hours.
Long-term management should eliminate hypoglycemic symptoms and maintain normal growth. Treatment should achieve normal glucose, lactic acid, and electrolyte levels, and only mild elevations of uric acid and triglycerides.
Avoidance of other sugars
Intake of carbohydrates which must be converted to G6P to be utilized (e.g., galactose and fructose) should be minimized. Although elemental formulas are available for infants, many foods contain fructose or galactose in the forms of sucrose or lactose. Adherence becomes a contentious treatment issue after infancy.
Other therapeutic measures
Persistent elevation of uric acid above 6.5 mg/dl warrants treatment with allopurinol to prevent uric acid deposition in kidneys and joints.
Because of the potential for impaired platelet function, coagulation ability should be checked and the metabolic state normalized before surgery. Bleeding time may be normalized with 1–2 days of glucose loading, and improved with ddavp. During surgery, IV fluids should contain 10% dextrose and no lactate.
A patient with GSD, type 1b was treated with a liver transplant at UCSF Medical Center in 1993 that resulted in the resolution of hypoglycemic episodes and the need for the patient to stay away from natural sources of sugar. Other patients have undergone this procedure as well with positive results. Although a liver transplant resulted in the resolution of hypoglycemia it did not however resolve the chronic neutropenia and the risk of infection among patients.
Treatment of acute metabolic acidosis episodes
The most significant acute problem in childhood is a vulnerability to episodes of metabolic acidosis precipitated by minor illnesses. If a vomiting illness persists longer than 2–4 hours, the child should be seen and assessed for dehydration, acidosis, and hypoglycemia. If these are developing, intravenous fluids should be provided at a rate above maintenance. For mild acidosis, an effective fluid is 10% dextrose in ½ normal saline with 20 mEq/L KCl, but if acidosis is severe, 75–100 mEq/L NaHCO3 and 20 mEq/L of K acetate can be substituted for the NaCl and KCl.
Metabolic control
Metabolic control often diminishes during and after puberty, as a result of a patient outgrowing their dietary treatment plan.
Prognosis
Without adequate metabolic treatment, patients with GSD I have died in infancy or childhood of overwhelming hypoglycemia and acidosis. Those who survived were stunted in physical growth and delayed in puberty because of chronically low insulin levels. Intellectual disability resulting from recurrent, severe hypoglycemia is considered preventable with appropriate treatment.
Liver complications have been serious in some patients. Adenomas of the liver can develop in the second decade or later, with a small chance of later malignant transformation to hepatoma or hepatic carcinomas (detectable by alpha-fetoprotein screening). Several children with advanced hepatic complications have improved after liver transplantation.
Additional problems reported in adolescents and adults with GSD I have included hyperuricemic gout, pancreatitis, and chronic kidney failure. Despite hyperlipidemia, atherosclerotic complications are uncommon.
With diagnosis before serious harm occurs, prompt reversal of acidotic episodes, and appropriate long-term treatment, most children will be healthy. With exceptions and qualifications, adult health and life span may also be fairly good, although lack of effective treatment before the mid-1970s means information on long-term efficacy is limited.
Epidemiology
In the United States, GSD I has an incidence of approximately 1 in 50,000 to 100,000 births. None of the glycogenoses are currently detected by standard or extended newborn screening.
The disease is more common in people of Ashkenazi Jewish, Mexican, Chinese, and Japanese descent.
References
Further reading
GeneReview/NIH/UW entry on Glycogen Storage Disease Type I
External links
Media related to Glycogen storage disease type I at Wikimedia Commons |
Wilsons disease | Wilsons disease is a genetic disorder in which excess copper builds up in the body. Symptoms are typically related to the brain and liver. Liver-related symptoms include vomiting, weakness, fluid build up in the abdomen, swelling of the legs, yellowish skin and itchiness. Brain-related symptoms include tremors, muscle stiffness, trouble in speaking, personality changes, anxiety, and psychosis.Wilsons disease is caused by a mutation in the Wilson disease protein (ATP7B) gene. This protein transports excess copper into bile, where it is excreted in waste products. The condition is autosomal recessive; for a person to be affected, they must inherit a mutated copy of the gene from both parents. Diagnosis may be difficult and often involves a combination of blood tests, urine tests and a liver biopsy. Genetic testing may be used to screen family members of those affected.Wilsons disease is typically treated with dietary changes and medication. Dietary changes involve eating a low-copper diet and not using copper cookware. Medications used include chelating agents such as trientine and d-penicillamine and zinc supplements. Complications of Wilsons disease can include liver failure, liver cancer and kidney problems. A liver transplant may be helpful to those for whom other treatments are not effective or if liver failure occurs.Wilsons disease occurs in about 1 in 30,000 people. Symptoms usually begin between the ages of 5 and 35 years. It was first described in 1854 by a German pathologist Friedrich Theodor von Frerichs and is named after British neurologist Samuel Wilson.
Signs and symptoms
The main sites of copper accumulation are the liver and the brain, and consequently liver disease and neuropsychiatric symptoms are the main features that lead to diagnosis. People with liver problems tend to come for medical attention earlier, generally as children or teenagers, than those with neurological and psychiatric symptoms, who tend to be in their twenties or older. Some are identified only because relatives have been diagnosed with Wilsons disease; many of these, when tested, turn out to have been experiencing symptoms of the condition but have not received a diagnosis.
Liver disease
Liver disease may present itself as tiredness, increased bleeding tendency or confusion (due to hepatic encephalopathy) and portal hypertension. The latter, a condition in which the pressure in the portal vein is markedly increased, leads to esophageal varices, blood vessels in the esophagus that may bleed in a life-threatening fashion, as well as enlargement of the spleen (splenomegaly) and accumulation of fluid in the abdominal cavity (ascites). On examination, signs of chronic liver disease such as spider angiomata (small distended blood vessels, usually on the chest) may be observed. Chronic active hepatitis has caused cirrhosis of the liver in most by the time they develop symptoms. While most people with cirrhosis have an increased risk of hepatocellular carcinoma (liver cancer), this risk is relatively very low in Wilsons disease.About 5% of all people are diagnosed only when they develop fulminant acute liver failure, often in the context of a hemolytic anemia (anemia due to the destruction of red blood cells). This leads to abnormalities in protein production (identified by deranged coagulation) and metabolism by the liver. The deranged protein metabolism leads to the accumulation of waste products such as ammonia in the bloodstream. When these irritate the brain, the person develops hepatic encephalopathy (confusion, coma, seizures and finally life-threatening swelling of the brain).
Neuropsychiatric symptoms
About half of the people with Wilsons disease have neurological or psychiatric symptoms. Most initially have mild cognitive deterioration and clumsiness, as well as changes in behavior. Specific neurological symptoms usually then follow, often in the form of parkinsonism (cogwheel rigidity, bradykinesia or slowed movements and a lack of balance are the most common parkinsonian features) with or without a typical hand tremor, masked facial expressions, slurred speech, ataxia (lack of coordination) or dystonia (twisting and repetitive movements of part of the body). Seizures and migraine appear to be more common in Wilsons disease. A characteristic tremor described as "wing-beating tremor" is encountered in many people with Wilsons; this is absent at rest but can be provoked by abducting the arms and flexing the elbows toward the midline.Cognition can also be affected in Wilsons disease. This comes in two, not mutually exclusive, categories: frontal lobe disorder (may present as impulsivity, impaired judgement, promiscuity, apathy and executive dysfunction with poor planning and decision making) and subcortical dementia (may present as slow thinking, memory loss and executive dysfunction, without signs of aphasia, apraxia or agnosia). It is suggested that these cognitive involvements are related and closely linked to psychiatric manifestations of the disease.Psychiatric problems due to Wilsons disease may include behavioral changes, depression, anxiety disorders, and psychosis. Psychiatric symptoms are commonly seen in conjunction with neurological symptoms and are rarely manifested on their own. These symptoms are often poorly defined and can sometimes be attributed to other causes. Because of this, diagnosis of Wilsons disease is rarely made when only psychiatric symptoms are present.
Other organ systems
Medical conditions have been linked with copper accumulation in Wilsons disease:
Eyes: Kayser–Fleischer rings (KF rings), a pathognomonic sign, may be visible in the cornea of the eyes, either directly or on slit lamp examination as deposits of copper form a ring around the cornea. This is due to copper deposition in Descemets membrane. These rings can be either dark brown, golden, or reddish-green, are 1 to 3 mm wide, and appear at the corneal limbus. They do not occur in all people with Wilsons disease. Wilsons disease is also associated with sunflower cataracts exhibited by brown or green pigmentation of the anterior and posterior lens capsule. Neither causes significant visual loss. KF rings occur in approximately 66% of diagnosed cases (more often in those with neurological symptoms rather than with liver problems).
Kidneys: renal tubular acidosis (Type 2), a disorder of bicarbonate handling by the proximal tubules leads to nephrocalcinosis (calcium accumulation in the kidneys), a weakening of bones (due to calcium and phosphate loss), and occasionally aminoaciduria (loss of essential amino acids needed for protein synthesis).
Heart: cardiomyopathy (weakness of the heart muscle) is a rare but recognized problem in Wilsons disease; it may lead to heart failure (fluid accumulation due to decreased pump function) and cardiac arrhythmias (episodes of irregular and/or abnormally fast or slow heart beat).
Hormones: hypoparathyroidism (failure of the parathyroid glands leading to low calcium levels), infertility, and recurrent miscarriage.
Genetics
The Wilsons disease gene (ATP7B) is on chromosome 13 (13q14.3) and is expressed primarily in the liver, kidney, and placenta. The gene codes for a P-type (cation transport enzyme) ATPase that transports copper into bile and incorporates it into ceruloplasmin. Mutations can be detected in 90% of cases. Most (60%) are homozygous for ATP7B mutations (two abnormal copies), and 30% have only one abnormal copy. Ten percent have no detectable mutation.Although 300 mutations of ATP7B have been described, in most populations the cases of Wilsons disease are due to a small number of mutations specific for that population. For instance, in Western populations the H1069Q mutation (replacement of a histidine by a glutamine at position 1069 in the protein) is present in 37–63% of cases, while in China this mutation is very uncommon and R778L (arginine to leucine at 778) is found more often. Relatively little is known about the relative impact of various mutations, although the H1069Q mutation seems to predict later onset and predominantly neurological problems, according to some studies. A comprehensive clinically annotated resource, WilsonGen provides clinical classification for the variants as per the recent ACMG & AMP guidelinesA normal variation in the PRNP gene can modify the course of the disease by delaying the age of onset and affecting the type of symptoms that develop. This gene produces prion protein, which is active in the brain and other tissues and also appears to be involved in transporting copper. A role for the ApoE gene was initially suspected but could not be confirmed.The condition is inherited in an autosomal recessive pattern. In order to inherit it, both of the parents of an individual must carry an affected gene. Most have no family history of the condition. People with only one abnormal gene are called carriers (heterozygotes) and may have mild, but medically insignificant, abnormalities of copper metabolism.Wilsons disease is the most common from a group of hereditary diseases that cause copper overload in the liver. All can cause cirrhosis at a young age. The other members of the group are Indian childhood cirrhosis (ICC), endemic Tyrolean infantile cirrhosis and idiopathic copper toxicosis. These are not related to ATP7B mutations: for example, ICC has been linked to mutations in the KRT8 and the KRT18 gene.
Pathophysiology
Copper is needed by the body for a number of functions, predominantly as a cofactor for a number of enzymes such as ceruloplasmin, cytochrome c oxidase, dopamine β-hydroxylase, superoxide dismutase and tyrosinase.Copper enters the body through the digestive tract. A transporter protein on the cells of the small bowel, copper membrane transporter 1 (Ctr1; SLC31A1), carries copper inside the cells, where some is bound to metallothionein and part is carried by ATOX1 to an organelle known as the trans-Golgi network. Here, in response to rising concentrations of copper, an enzyme called ATP7A (Menkes protein) releases copper into the portal vein to the liver. Liver cells also carry the CMT1 protein, and metallothionein and ATOX1 bind it inside the cell, but here it is ATP7B that links copper to ceruloplasmin and releases it into the bloodstream, as well as removing excess copper by secreting it into bile. Both functions of ATP7B are impaired in Wilsons disease. Copper accumulates in the liver tissue; ceruloplasmin is still secreted, but in a form that lacks copper (termed apoceruloplasmin) and is rapidly degraded in the bloodstream.When the amount of copper in the liver overwhelms the proteins that normally bind it, it causes oxidative damage through a process known as Fenton chemistry; this damage eventually leads to chronic active hepatitis, fibrosis (deposition of connective tissue) and cirrhosis. The liver also releases copper into the bloodstream that is not bound to ceruloplasmin. This free copper precipitates throughout the body but particularly in the kidneys, eyes and brain. In the brain, most copper is deposited in the basal ganglia, particularly in the putamen and globus pallidus (together called the lenticular nucleus); these areas normally participate in the coordination of movement as well as playing a significant role in neurocognitive processes such as the processing of stimuli and mood regulation. Damage to these areas, again by Fenton chemistry, produces the neuropsychiatric symptoms seen in Wilsons disease.It is not clear why Wilsons disease causes hemolysis, but various lines of evidence suggest that a high level of free (non-ceruloplasmin bound) copper has a direct effect on either oxidation of hemoglobin, inhibition of energy-supplying enzymes in the red blood cell, or direct damage to the cell membrane.
Diagnosis
Wilsons disease may be suspected on the basis of any of the symptoms mentioned above, or when a close relative has been found to have Wilsons. Most have slightly abnormal liver function tests such as a raised aspartate transaminase, alanine transaminase and bilirubin level. If the liver damage is significant, albumin may be decreased due to an inability of damaged liver cells to produce this protein; likewise, the prothrombin time (a test of coagulation) may be prolonged as the liver is unable to produce proteins known as clotting factors. Alkaline phosphatase levels are relatively low in those with Wilsons-related acute liver failure. If there are neurological symptoms, magnetic resonance imaging (MRI) of the brain is usually performed; this shows hyperintensities in the part of the brain called the basal ganglia in the T2 setting. MRI may also demonstrate the characteristic "face of the giant panda" pattern.There is no totally reliable test for Wilsons disease, but levels of ceruloplasmin and copper in the blood, as well of the amount of copper excreted in urine during a 24-hour period, are together used to form an impression of the amount of copper in the body. The gold standard—or most ideal test—is a liver biopsy.
Ceruloplasmin
Levels of ceruloplasmin are abnormally low (<0.2 g/L) in 80–95% of cases. It can, however, be present at normal levels in people with ongoing inflammation as it is an acute phase protein. Low ceruloplasmin is also found in Menkes disease and aceruloplasminemia, which are related to, but much rarer than Wilsons disease.The combination of neurological symptoms, Kayser–Fleischer rings and a low ceruloplasmin level is considered sufficient for the diagnosis of Wilsons disease. In many cases, however, further tests are needed.
Serum and urine copper
Serum copper is low, which may seem paradoxical given that Wilsons disease is a disease of copper excess. However, 95% of plasma copper is carried by ceruloplasmin which is often low in Wilsons disease. Urine copper is elevated in Wilsons disease and is collected for 24 hours in a bottle with a copper-free liner. Levels above 100 μg/24h (1.6 μmol/24h) confirm Wilsons disease, and levels above 40 μg/24h (0.6 μmol/24h) are strongly indicative. High urine copper levels are not unique to Wilsons disease; they are sometimes observed in autoimmune hepatitis and in cholestasis (any disease obstructing the flow of bile from the liver to the small bowel).In children, the penicillamine test may be used. A 500 mg oral dose of penicillamine is administered, and urine collected for 24 hours. If this contains more than 1600 μg (25 μmol), it is a reliable indicator of Wilsons disease. This test has not been validated in adults.
Liver biopsy
Once other investigations have indicated Wilsons disease, the ideal test is the removal of a small amount of liver tissue through a liver biopsy. This is assessed microscopically for the degree of steatosis and cirrhosis, and histochemistry and quantification of copper are used to measure the severity of the copper accumulation. A level of 250 μg of copper per gram of dried liver tissue confirms Wilsons disease. Occasionally, lower levels of copper are found; in that case, the combination of the biopsy findings with all other tests could still lead to a formal diagnosis of Wilsons.In the earlier stages of the disease, the biopsy typically shows steatosis (deposition of fatty material), increased glycogen in the nucleus, and areas of necrosis (cell death). In more advanced disease, the changes observed are quite similar to those seen in autoimmune hepatitis, such as infiltration by inflammatory cells, piecemeal necrosis and fibrosis (scar tissue). In advanced disease, finally, cirrhosis is the main finding. In acute liver failure, degeneration of the liver cells and collapse of the liver tissue architecture is seen, typically on a background of cirrhotic changes. Histochemical methods for detecting copper are inconsistent and unreliable, and taken alone are regarded as insufficient to establish a diagnosis.
Genetic testing
Mutation analysis of the ATP7B gene, as well as other genes linked to copper accumulation in the liver, may be performed. Once a mutation is confirmed, it is possible to screen family members for the disease as part of clinical genetics family counseling. Regional distributions of genes associated with Wilsons disease are important to follow, as this can help clinicians design appropriate screening strategies. Since mutations of the WD gene vary between populations, research and genetic testing done in countries like the USA or United Kingdom can pose problems as they tend to have more mixed populations.
Treatment
Diet
In general, a diet low in copper-containing foods is recommended with the avoidance of mushrooms, nuts, chocolate, dried fruit, liver, sesame seeds and sesame oil, and shellfish.
Medication
Medical treatments are available for Wilsons disease. Some increase the removal of copper from the body, while others prevent the absorption of copper from the diet.
Generally, penicillamine is the first treatment used. This binds copper (chelation) and leads to excretion of copper in the urine. Hence, monitoring of the amount of copper in the urine can be done to ensure a sufficiently high dose is taken. Penicillamine is not without problems: about 20% experience a side effect or complication of penicillamine treatment, such as drug-induced lupus (causing joint pains and a skin rash) or myasthenia (a nerve condition leading to muscle weakness). In those who presented with neurological symptoms, almost half experience a paradoxical worsening in their symptoms. While this phenomenon is observed in other treatments for Wilsons, it is usually taken as an indication for discontinuing penicillamine and commencing second-line treatment. Those intolerant to penicillamine may instead be commenced on trientine hydrochloride, which also has chelating properties. Some recommend trientine as first-line treatment, but experience with penicillamine is more extensive. A further agent, under clinical investigation by Wilson Therapeutics, with known activity in Wilsons disease is tetrathiomolybdate. This is regarded as experimental, though some studies have shown a beneficial effect.Once all results have returned to normal, zinc (usually in the form of a zinc acetate prescription called Galzin) may be used instead of chelators to maintain stable copper levels in the body. Zinc stimulates metallothionein, a protein in gut cells that binds copper and prevents their absorption and transport to the liver. Zinc therapy is continued unless symptoms recur or if the urinary excretion of copper increases.In rare cases where none of the oral treatments are effective, especially in severe neurological disease, dimercaprol (British anti-Lewisite) is occasionally necessary. This treatment is injected intramuscularly (into a muscle) every few weeks and has unpleasant side effects such as pain.People who are asymptomatic (for instance, those diagnosed through family screening or only as a result of abnormal test results) are generally treated, as the copper accumulation may cause long-term damage in the future. It is unclear whether these people are best treated with penicillamine or zinc acetate.
Physical and occupational therapies
Physiotherapy and occupational therapy are beneficial for patients with the neurologic form of the disease. The copper chelating treatment may take up to six months to start working, and these therapies can assist in coping with ataxia, dystonia, and tremors, as well as preventing the development of contractures that can result from dystonia.
Transplantation
Liver transplantation is an effective cure for Wilsons disease but is used only in particular scenarios because of the risks and complications associated with the procedure. It is used mainly in people with fulminant liver failure who fail to respond to medical treatment or in those with advanced chronic liver disease. Liver transplantation is avoided in severe neuropsychiatric illness, in which its benefit has not been demonstrated.
Prognosis
Left untreated, Wilsons disease tends to become progressively worse and is eventually fatal. With early detection and treatment, most of those affected can live relatively normal lives. Liver and neurologic damage that occurs prior to treatment may improve, but it is often permanent.
History
The disease bears the name of the British physician Samuel Alexander Kinnier Wilson (1878–1937), a neurologist who described the condition, including the pathological changes in the brain and liver, in 1912. Wilsons work had been predated by, and drew on, reports from German neurologist Carl Westphal (in 1883), who termed it "pseudosclerosis"; by the British neurologist William Gowers (in 1888); by the Finnish neuropathologist Ernst Alexander Homén (in 1889–1892), who noted the hereditary nature of the disease; and by Adolph Strümpell (in 1898), who noted hepatic cirrhosis. Neuropathologist John Nathaniel Cumings made the link with copper accumulation in both the liver and the brain in 1948. The occurrence of hemolysis was noted in 1967.In 1951, Cumings, and New Zealand neurologist Derek Denny-Brown, working in the United States, simultaneously reported the first effective treatment, using metal chelator British anti-Lewisite . This treatment had to be injected but was one of the first therapies available in the field of neurology, a field that classically was able to observe and diagnose but had few treatments to offer. The first effective oral chelation agent, penicillamine, was discovered in 1956 by British neurologist John Walshe. In 1982, Walshe also introduced trientine, and was the first to develop tetrathiomolybdate for clinical use. Zinc acetate therapy initially made its appearance in the Netherlands, where physicians Schouwink and Hoogenraad used it in 1961 and in the 1970s, respectively, but it was further developed later by Brewer and colleagues at the University of Michigan.The genetic basis of Wilsons disease, and its link to ATP7B mutations, was elucidated by several research groups in the 1980s and 1990s.
In other animals
Hereditary copper accumulation has been described in Bedlington Terriers, where it generally only affects the liver. It is due to mutations in the COMMD1 (or MURR1) gene. Despite this findings, COMMD1 mutations could not be detected in humans with non-Wilsonian copper accumulation states (such as Indian childhood cirrhosis) to explain their genetic origin.
See also
Copper in health
Menkes syndrome
References
External links
Wilsons disease at Curlie
Wilson disease at NLM Genetics Home Reference |
Cavernous sinus thrombosis | Cavernous sinus thrombosis (CST) is the formation of a blood clot within the cavernous sinus, a cavity at the base of the brain which drains deoxygenated blood from the brain back to the heart. This is a rare disorder and can be of two types–septic cavernous thrombosis and aseptic cavernous thrombosis. The most common form is septic cavernous sinus thrombosis. The cause is usually from a spreading infection in the nose, sinuses, ears, or teeth. Staphylococcus aureus and Streptococcus are often the associated bacteria.Cavernous sinus thrombosis symptoms include: decrease or loss of vision, chemosis, exophthalmos (bulging eyes), headaches, and paralysis of the cranial nerves which course through the cavernous sinus. This infection is life-threatening and requires immediate treatment, which usually includes antibiotics and sometimes surgical drainage. Aseptic cavernous sinus thrombosis is usually associated with trauma, dehydration, anemia, and other disorders.
Signs and symptoms
The clinical presentation of CST can be varied. Both acute, fulminant disease, and indolent, subacute presentations have been reported in the literature.
The most common signs of CST are related to anatomical structures affected within the cavernous sinus, notably cranial nerves III-VI, as well as symptoms resulting from impaired venous drainage from the orbit and eye.
Classic presentations are abrupt onset of unilateral periorbital edema, headache, photophobia, and bulging of the eye (exophthalmos).Other common signs and symptoms include:
Ptosis, chemosis, cranial nerve palsies (III, IV, V, VI). Sixth nerve palsy is the most common. Sensory deficits of the ophthalmic and maxillary branch of the fifth nerve are common. Periorbital sensory loss and impaired corneal reflex may be noted. Papilledema, retinal hemorrhages, and decreased visual acuity and blindness may occur from venous congestion within the retina. Fever, tachycardia and sepsis may be present. Headache with nuchal rigidity (neck stiffness) may occur. One or both pupils may be dilated and sluggishly reactive. Infection can spread to contralateral cavernous sinus within 24–48 hours of initial presentation.
Cause
Septic CST most commonly results from contiguous spread of infection from a nasal furuncle (50%), sphenoidal or ethmoidal sinuses (30%) and dental infections (10%). Less common primary sites of infection include tonsils, soft palate, middle ear, or orbit (orbital cellulitis). The highly anastomotic venous system of the paranasal sinuses allows retrograde spread of infection to the cavernous sinus via the superior and inferior ophthalmic veins. It was previously thought that veins in the area were valveless and that this was the major cause of the retrograde spread, but studies have since shown that the ophthalmic and facial veins are not valveless.Staphylococcus aureus is the most common infectious microbe, found in 70% of the cases. Streptococcus is the second leading cause. Gram-negative rods and anaerobes may also lead to cavernous sinus thrombosis. Rarely, Aspergillus fumigatus and mucormycosis cause CST.Aseptic cavernous sinus thrombosis is much less common and is usually associated with other disorders including trauma, circulatory problems, nasopharynx cancers and other tumors of the skull base, dehydration, and anemia.
Diagnosis
The diagnosis of cavernous sinus thrombosis is made clinically, with imaging studies to confirm the clinical impression. Proptosis, ptosis, chemosis, and cranial nerve palsy beginning in one eye and progressing to the other eye establish the diagnosis. Cavernous sinus thrombosis is a clinical diagnosis with laboratory tests and imaging studies confirming the clinical impression.
Laboratory tests
CBC, ESR, blood cultures and sinus cultures help establish and identify an infectious primary source. Lumbar puncture is necessary to rule out meningitis.
Imaging studies
Sinus films are helpful in the diagnosis of sphenoid sinusitis. Opacification, sclerosis, and air-fluid levels are typical findings. Contrast-enhanced CT scan may reveal underlying sinusitis, thickening of the superior ophthalmic vein, and irregular filling defects within the cavernous sinus; however, findings may be normal early in the disease course. An MRI using flow parameters and an MR venogram are more sensitive than a CT scan and are the imaging studies of choice to diagnose cavernous sinus thrombosis. Findings may include deformity of the internal carotid artery within the cavernous sinus, and an obvious signal hyperintensity within thrombosed vascular sinuses on all pulse sequences. Cerebral angiography can be performed, but it is invasive and not very sensitive. Orbital venography is difficult to perform, but it is excellent in diagnosing occlusion of the cavernous sinus.
Differential diagnosis
Orbital cellulitis
Internal carotid artery aneurysm
Stroke
Migraine headache
Allergic blepharitis
Thyroid exophthalmos
Brain tumor
Meningitis
Mucormycosis
Trauma
Treatment
Recognizing the primary source of infection (i.e., facial cellulitis, middle ear, and sinus infections) and treating the primary source expeditiously is the best way to prevent cavernous sinus thrombosis.
Antibiotics
Broad-spectrum intravenous antibiotics are used until a definite pathogen is found.
Nafcillin 1.5 g IV q4h
Cefotaxime 1.5 to 2 g IV q4h
Metronidazole 15 mg/kg load followed by 7.5 mg/kg IV q6hVancomycin may be substituted for nafcillin if significant concern exists for infection by methicillin-resistant Staphylococcus aureus or resistant Streptococcus pneumoniae. Appropriate therapy should take into account the primary source of infection as well as possible associated complications such as brain abscess, meningitis, or subdural empyema.
People with CST are usually treated with prolonged courses (3–4 weeks) of IV antibiotics. If there is evidence of complications such as intracranial suppuration, 6–8 weeks of total therapy may be warranted.All patients should be monitored for signs of complicated infection, continued sepsis, or septic emboli while antibiotic therapy is being administered.
Heparin
Anticoagulation with heparin is controversial. Retrospective studies show conflicting data. This decision should be made with subspecialty consultation. One systematic review concluded that anticoagulation treatment appeared safe and was associated with a potentially important reduction in the risk of death or dependency.
Steroids
Steroid therapy is also controversial in many cases of CST. However, corticosteroids are absolutely indicated in cases of pituitary insufficiency. Corticosteroid use may have a critical role in patients with Addisonian crisis secondary to ischemia or necrosis of the pituitary that complicates CST.
Surgery
Surgical drainage with sphenoidotomy is indicated if the primary site of infection is thought to be the sphenoidal sinuses.
Prognosis
Cavernous sinus thrombosis has a mortality rate of less than 20% in areas with access to antibiotics. Before antibiotics were available, the mortality was 80–100%. Morbidity rates also dropped from 70% to 22% due to earlier diagnosis and treatment.
References
Further reading
== External links == |
Meniscus tear | A tear of a meniscus is a rupturing of one or more of the fibrocartilage strips in the knee called menisci. When doctors and patients refer to "torn cartilage" in the knee, they actually may be referring to an injury to a meniscus at the top of one of the tibiae. Menisci can be torn during innocuous activities such as walking or squatting. They can also be torn by traumatic force encountered in sports or other forms of physical exertion. The traumatic action is most often a twisting movement at the knee while the leg is bent. In older adults, the meniscus can be damaged following prolonged wear and tear. Especially acute injuries (typically in younger, more active patients) can lead to displaced tears which can cause mechanical symptoms such as clicking, catching, or locking during motion of the joint. The joint will be in pain when in use, but when there is no load, the pain goes away.
A tear of the medial meniscus can occur as part of the unhappy triad, together with a tear of the anterior cruciate ligament and medial collateral ligament.
Signs and symptoms
The common signs and symptoms of a torn meniscus are knee pain, particularly along the joint line, and swelling. These are worse when the knee bears more weight (for example, when running). Another typical complaint is joint locking, when the affected person is unable to straighten the leg fully. This can be accompanied by a clicking feeling. Sometimes, a meniscal tear also causes a sensation that the knee gives way.A person with a torn meniscus can sometimes remember a specific activity during which the injury was sustained. A tear of the meniscus commonly follows a trauma that involves rotation of the knee while it was slightly bent. These maneuvers also exacerbate the pain after the injury; for example, getting out of a car is often reported as painful.
Causes
There are two menisci in the knee. They sit between the thigh bone and the shin bone. While the ends of the thigh bone and the shin bone have a thin covering of soft hyaline cartilage, the menisci are made of tough fibrocartilage and conform to the surfaces of the bones they rest on. One meniscus rests on the medial tibial plateau; this is the medial meniscus. The other meniscus rests on the lateral tibial plateau; this is the lateral meniscus.These menisci act to distribute body weight across the knee joint. Without the menisci, the weight of the body would be unevenly applied to the bones in the legs (the femur and tibia). This uneven weight distribution would cause the development of abnormal excessive forces leading to early damage of the knee joint. The menisci also contribute to the stability of the joint.The menisci are nourished by small blood vessels but have a large area in the center with no direct blood supply (avascular). This presents a problem when there is an injury to the meniscus, as the avascular areas tend not to heal. Without the essential nutrients supplied by blood vessels, healing cannot take place.The two most common causes of a meniscal tear are traumatic injury (often seen in athletes) and degenerative processes, which are the most common tear seen in all ages of patients. Meniscal tears can occur in all age groups. Traumatic tears are most common in active people aged 10–45. Traumatic tears are usually radial or vertical in the meniscus and more likely to produce a moveable fragment that can catch in the knee and therefore require surgical treatment.A meniscus can tear due to an internally or externally rotated knee in a flexed position, with the foot in a flexed position. It is not uncommon for a meniscal tear to occur along with injuries to the anterior cruciate ligament ACL and the medial collateral ligament MCL — these three problems occurring together are known as the "unhappy triad," which is seen in sports such as football when the player is hit on the outside of the knee. Individuals who experience a meniscal tear usually experience pain and swelling as their primary symptoms. Another common complaint is joint locking, or the inability to completely straighten the joint. This is due to a piece of the torn cartilage preventing the normal functioning of the knee joint.Degenerative tears are most common in people from age 40 upward but can be found at any age, especially with obesity. Degenerative meniscal tears are thought to occur as part of the aging process when the collagen fibers within the meniscus start to break down and lend less support to the structure of the meniscus. Degenerative tears are usually horizontal, producing both an upper and a lower segment of the meniscus. These segments do not usually move out of place and are therefore less likely to produce mechanical symptoms of catching or locking.
Risk factors
The meniscus is made of cartilage, a viscoelastic material, which makes it more susceptible to rate of loading injuries. Repetitive loading can also lead to injury. Recent studies have shown people who experience rapid rate of loading and/or repetitive loading to be the most susceptible to meniscus tears. People over the age of 60 who have working conditions in which squatting and kneeling are common are more susceptible to degenerative meniscal tears. Athletes who constantly experience a high rate of loading (e.g. soccer, rugby) are also susceptible to meniscus tears. Studies have also shown with increasing time between ACL injury and ACL reconstruction, there is an increasing chance of meniscus tears. This study showed meniscus tears occurring at a rate of 50–70% depending on how long after the ACL injury the surgery occurred. Meniscal ramp lesions (tears of the medial meniscus posterior horn at the menisco-capsular junction) occur in approximately 25% of ACL-injured knees. Lateral meniscal root tears occur in approximately 7% of ACL injured knees
Pathophysiology
The force distribution is across the knee joint, increasing force concentration on the cartilage and other joint structures.Damage to the meniscus due to rotational forces directed to a flexed knee (as may occur with twisting sports) is the usual underlying mechanism of injury. A valgus force applied to a flexed knee with the foot planted and the femur rotated externally can result in a lateral meniscus tear. A varus force applied to the flexed knee when the foot is planted and the femur rotated internally result in a tear of the medial meniscus.Tears produce rough surfaces inside the knee, which cause catching, locking, buckling, pain, or a combination of these symptoms. Abnormal loading patterns and rough surfaces inside the knee, especially when coupled with return to sports, significantly increase the risk of developing arthritis if not already present.
Anatomy
The menisci are C-shaped wedges of fibrocartilage located between the tibial plateau and femoral condyles. The menisci contain 70% type I collagen. The larger semilunar medial meniscus is attached more firmly than the loosely fixed, more circular lateral meniscus. The anterior and posterior horns of both menisci are secured to the tibial plateaus. Anteriorly, the transverse ligament connects the 2 menisci; posteriorly, the meniscofemoral ligament helps stabilize the posterior horn of the lateral meniscus to the femoral condyle. The coronary ligaments connect the peripheral meniscal rim loosely to the tibia. Although the lateral collateral ligament (LCL) passes in close proximity, the lateral meniscus has no attachment to this structure.The joint capsule attaches to the entire periphery of each meniscus but adheres more firmly to the medial meniscus. An interruption in the attachment of the joint capsule to the lateral meniscus, forming the popliteal hiatus, allows the popliteus tendon to pass through to its femoral attachment site. Contraction by the popliteus during knee flexion pulls the lateral meniscus posteriorly, avoiding entrapment within the joint space. The medial meniscus does not have a direct muscular connection. The medial meniscus may shift a few millimeters, while the less stable lateral meniscus may move at least 1 cm.In 1978, Shrive et al. reported that the collagen fibers of the menisci are oriented in a circumferential pattern. When a compressive force is applied in the knee joint, a tensile force is transmitted to the menisci. The femur attempts to spread the menisci anteroposteriorly in extension and mediolaterally in flexion. Shrive et al. further studied the effects of a radial cut in the peripheral rim of the menisci during loading. In joints with intact menisci, the force was applied through the menisci and articular cartilage; however, a lesion in the peripheral rim disrupted the normal mechanics of the menisci and allowed it to spread when a load was applied. The load now was distributed directly to the articular cartilage. In light of these findings, it is essential to preserve the peripheral rim during partial meniscectomy to avoid irreversible disruption of the structures hoop tension capability.
Diagnosis
Physical examination
After noting symptoms, a physician can perform clinical tests to determine if the pain is caused by compression and impingement of a torn meniscus. The knee is examined for swelling. In meniscal tears, pressing on the joint line on the affected side typically produces tenderness. The McMurray test involves pressing on the joint line while stressing the meniscus (using flexion–extension movements and varus or valgus stress). Similar tests are the Steinmann test (with the patient sitting) and the Apley grind test (a grinding maneuver while the person lies prone and the knee is bent 90°) and the Thessaly test (flexing the affected knee to 20 degrees, pivoting on the knee to see if the pain is reproduced). Bending the knee (into hyperflexion if tolerable), and especially squatting, is typically a painful maneuver if the meniscus is torn. The range of motion of the joint is often restricted.
Coopers sign is present in over 92% of tears. It is a subjective symptom of pain in the affected knee when turning over in bed at night. Osteoarthritic pain is present with weightbearing, but the meniscal tear causes pain with a twisting motion of the knee as the meniscal fragment gets pinched, and the capsular attachment gets stretched causing the complaint of pain.
Radiology
X-ray images (normally during weightbearing) can be obtained to rule out other conditions or to see if the patient also has osteoarthritis. The menisci themselves cannot be visualised with plain radiographs. If the diagnosis is not clear from the history and examination, the menisci can be imaged with magnetic resonance imaging (an MRI scan). This technique has replaced previous arthrography, which involved injecting contrast medium into the joint space. In straightforward cases, knee arthroscopy allows quick diagnosis and simultaneous treatment. Recent clinical data shows that MRI and clinical testing are comparable in sensitivity and specificity when looking for a meniscal tear.
Classification
A meniscal tear can be classified in various ways, such as by anatomic location or by proximity to blood supply. Various tear patterns and configurations have been described. These include:
Radial tears
Flap or parrot-beak tears
Peripheral, longitudinal tears
Bucket-handle tears
Horizontal cleavage tears
Complex, degenerative tearsThese tears can then be further classified by their proximity to the meniscus blood supply, namely whether they are located in the “red-red,” “red-white,” or “white-white” zones.
The functional importance of these classifications, however, is to ultimately determine whether a meniscus is repairable. The repairability of a meniscus depends on a number of factors. These include:
Age/strength
Activity level
Tear pattern
Chronicity of the tear
Associated injuries (anterior cruciate ligament injury)
Healing potential
Prevention
Tear of a meniscus is a common injury in many sports. The menisci hold 30–50% of the body load in standing position. Some sports where a meniscus tear is common are American football, association football, ice hockey and tennis. Regardless of what the activity is, it is important to take the correct precautions to prevent a meniscus tear from happening.
Footwear
There are three major ways of preventing a meniscus tear. The first of these is wearing the correct footwear for the sport and surface that the activity is taking place on. This means that if the sport being played is association football, cleats are an important item in reducing the risk of a meniscus tear. The proper footwear is imperative when engaging in physical activity because one off-balanced step could mean a meniscus tear.
It is highly advised that cleats contain a sole that molds around the foot, no fewer than fourteen cleats per shoe, no lower than a half inch diameter of the cleat tip, and at most, a three-eighths inch of cleat length.
Stretches
The second way to prevent a meniscus tear is to strengthen and stretch the major leg muscles. Those muscles include the hamstrings, quadriceps, and calf muscles. One popular exercise used to strengthen the hamstrings is the leg curl. It is also important to properly stretch the hamstrings; doing standing toe touches can do this. Seated leg extensions strengthen the quadriceps and doing the quadriceps stretch will help loosen the muscles. Toe raises are used to strengthen and stretch the calves.
Adequate muscle mass and strength may also aid in maintaining healthy knees. The use of the parallel squat increases much needed stability in the knee if executed properly. Execution of the parallel squat will develop the lower body muscles that will strengthen the hips, knees, and ankles.
Technique
The last major way to prevent a tear in the meniscus is learning proper technique for the movement that is taking place. For the sports involving quick powerful movements it is important to learn how to cut, turn, land from a jump, and stop correctly. It is important to take the time out to perfect these techniques when used. These three major techniques will significantly prevent and reduce the risk of a meniscus tear.
Treatment
Presently, treatments make it possible for quicker recovery. If the tear is not serious, physical therapy, compression, elevation and icing the knee can heal the meniscus. Meniscus tears are more likely to heal on their own if they are in what physicians call the "red zone," or the outer edge of the meniscus where blood supply is present. More serious tears may require surgical procedures. Surgery, however, does not appear to be better than non-surgical care. In the long term, degenerative meniscal tears are often associated with osteoarthritis. This leads to poor outcomes regardless of treatment type. In the short term, studies have shown arthroscopic partial meniscectomy (APM) is a more effective treatment with regards to function and pain management.
Conservative treatments
Initial treatment may include physical therapy, bracing, anti-inflammatory drugs, or corticosteroid injections to increase flexibility, endurance, and strength.Common anti-inflammatory drugs and painkillers prescribed for meniscus tears include acetaminophen, non-steroidal inflammatory drugs, and corticosteroids.Exercises can strengthen the muscles around the knee, especially the quadriceps. Stronger and bigger muscles will protect the meniscus cartilage by absorbing a part of the weight. The patient may be given paracetamol or anti-inflammatory medications.
For patients selecting non-surgical treatment, physical therapy may reduce symptoms of pain and swelling. This type of rehabilitation focuses on maintenance of full range of motion and functional progression without aggravating symptoms. Physical therapists can employ electric stimulation, cold therapy, and ultrasonography.
Accelerated rehabilitation programs can be as successful as the conservative program. The program reduces the time the patient spends using crutches and allows weight bearing activities. The less conservative approach allows the patient to apply a small amount of stress while protecting range of motion. It is likely that a patient with a peripheral tear can pursue the accelerated program, while a patient with a larger tear adopts the conservative program.
The use of platelet rich plasma (PRP) to aid in the healing process has become widely accepted among US athletes. Although the procedure has grown in popularity, studies assessing the efficacy of PRP treatment have yielded contradictory results.
Surgery
Arthroscopy is a surgical technique in which a joint is operated on using an endoscopic camera as opposed to open surgery on the joint. The meniscus can either be repaired or completely removed. Surgery is not appropriate for a degenerative meniscus tear, absent locking or catching of the knee, recurrent effusion or persistent pain. Evidence suggests that it is no better than conservative management in those with and without osteoarthritis. Surgery appears to offer no benefit to adults who have mild arthritis.An independent international guideline panel recommended against arthroscopy for degenerative meniscus tears; this conclusion derived from evidence of no lasting benefit and that less than 15% of patients experience even a short-term benefit. Disadvantages include a two to six week recovery time and rare but serious adverse effects that can occur, including blood clots in the legs, surgical site infections, and nerve damage. The BMJ Rapid Recommendation includes infographics and shared decision-making tools to facilitate a conversation between doctors and patients about the risks and benefits of arthroscopic surgery.If the injury is isolated, then the knee would be relatively stable. However, if an injury such as an anterior cruciate ligament injury (torn ACL) is coupled with a torn meniscus, then an arthroscopy is recommended. A meniscal repair has a higher success rate given an adequate blood supply to the peripheral rim. The interior of the meniscus is avascular, but the blood supply can penetrate up to about 6 millimetres (0.24 in). Therefore, meniscus tears that occur near the peripheral rim are able to heal after a meniscal repair. One study found that repair is better than removal (meniscectomy). The amount of rehabilitation time required for a repair is longer, but removing the meniscus can induce osteoarthritis. Meniscectomy rehab requires four to six weeks. Repair requires four to six months. If conservative treatment is ineffective, surgical intervention may be required. Younger patients are typically more resilient and respond well to this treatment, while older, more sedentary patients do not have a favorable outcome after a repair.
Transplants
Meniscus transplants are regularly successful, although the procedure is not common and many questions surrounding its use remain. Side effects of meniscectomy include:
The knee loses its ability to transmit and distribute load and absorb mechanical shock.
Persistent and significant swelling and stiffness in the knee.
The knee may be not be fully mobile; there may be the sensation of knee locking or buckling in the knee.
The full knee may be in full motion after tear of meniscus.
Increases progression of arthritis and time to knee replacement.
Implants
Another treatment approach in development is a meniscus implant or "artificial meniscus." While many artificial joints and bionic body parts are available, including arms, legs, joints and other body parts, a prosthetic meniscus replacement.The first to be implanted in humans is called the NUsurface Meniscus Implant. The implant is made from medical grade plastic and is designed not to require fixation to bone or soft tissue. The implant could be a good option for younger, active patients who are considered too young for knee replacement because that surgery lasts only about 10 years. The implant has been used in clinical trials in Europe since 2008. The first surgery as part of US clinical trials took place in January 2015 at Ohio State Universitys Wexner Medical Center. Two FDA-approved clinical trials evaluating the implant completed enrollment in June 2018. In September 2019, the manufacturer received breakthrough designation from the U.S. Food and Drug Administration, and the company expected to file for regulatory approval within the following year. In November 2019, the implant became commercially available in Israel.Other implants include TRAMMPOLIN and Orthonika.Scientists are working to grow an artificial meniscus in the lab. Scientists from Cornell and Columbia universities grew a meniscus inside the knee joint of a sheep using a 3-D printer and the sheeps stem cells. Similarly, researchers at Scripps Research Shiley Center for Orthopaedic Research and Education reported growing a meniscus.
Post-surgical rehabilitation
After a successful surgery for treating the destroyed part of the meniscus, patients must follow a rehabilitation program to have the best result. The rehabilitation following a meniscus surgery depends on whether the entire meniscus was removed or repaired.
If the destroyed part of the meniscus was removed, patients can usually start walking using a crutch a day or two after surgery. Although each case is different, patients return to their normal activities on average after a few weeks (2 or 3). Still, a completely normal walk will resume gradually, and its not unusual to take 2–3 months for the recovery to reach a level where a patient will walk totally smoothly. Many meniscectomy patients dont ever feel a 100% functional recovery, but even years after the procedure they sometimes feel tugging or tension in a part of their knee. There is little medical follow-up after meniscectomy and official medical documentation tends to ignore the imperfections and side-effects of this procedure.
If the meniscus was repaired, the rehabilitation program that follows is a lot more intensive. After the surgery, a hinged knee brace is sometimes placed on the patient. This brace allows controlled movement of the knee. The patient is encouraged to walk using crutches from the first day, and most of the times can put partial weight on the knee.
Improving symptoms, restoring function, and preventing further injuries are the main goals when rehabilitating. By the end of rehabilitation, normal range of motion, function of muscles and coordination of the body are restored. Personalized rehabilitation programs are designed considering the patients surgery type, location repaired (medial or lateral), simultaneous knee injuries, type of meniscal tear, age of patient, condition of the knee, loss of strength and ROM, and the expectations and motivations of the patient.
Phase I
There are three phases that follow meniscal surgery. Each phase consists of rehabilitation goals, exercises, and criteria to move on to the next phase. Phase I starts immediately following surgery to 4–6 weeks or until the patient is able meet progression criteria. The goals are to restore normal knee extension, reduce and eliminate swelling, regain leg control, and protect the knee (Fowler, PJ and D. Pompan, 1993). During the first 5 days following the surgery, a passive continuous motion machine is used to prevent a prolonged period of immobilization which leads to muscular atrophy and delays functional recovery. During the 4–6 weeks post-surgical, active and passive non-weight bearing motions which flex the knee up to 90° are recommended. For patients with meniscal transplantation, further knee flexion can damage the allograft because of the increased shear forces and stresses. If any weight-bearing exercises are applied, a controlled brace should be worn on the knee to keep the knee at near (<10°) or full extension.
The suggested exercises target increasing the patients ROM, muscular and neuromuscular strength, and cardiovascular endurance. Aquatic therapy, or swimming, can be used to rehab patients because it encompasses ROM, strength, and cardiovascular exercises while relieving stress on the body. It has also been shown to significantly improve dependent edema and pain symptoms. No pain gait without crutches, swelling and 4–6 weeks after surgery are the criteria to begin the next phase (Ulrich G.S., and S Aroncyzk, 1993).
Phase II
This phase of the rehabilitation program is 6 to 14 weeks after the surgery. The goals for Phase II include being able to restore full ROM, normalized gait, and performing functional movements with control and no pain (Fowler, PJ and D. Pompan, 1993). Also, muscular strengthening and neuromuscular training are emphasized using progressive weight bearing and balance exercises. Exercises in this phase can increase knee flexion for more than 90°. Advised exercises include stationary bicycle, standing on foam surface with two and one leg, abdominal and back strengthening, and quadriceps strengthening. The proposed criteria include normal gait on all surfaces and single leg balance longer than 15 seconds (Ulrich G.S., and S Aroncyzk, 1993).
Phase III
Patients begin exercises in phase III 14 to 22 weeks after surgery. Phase IIIs goal and final criterion is to perform sport/work specific movements with no pain or swelling (Fowler, PJ and D. Pompan, 1993). Drills for maximal muscle control, strength, flexibility, movements specific to patients work/sport, low to high rate exercises, and abdominal and back strengthening exercises are all recommended exercises (Ulrich G.S., and S Aroncyzk, 1993). Exercises to increase cardiovascular fitness are also applied to fully prepare the patients to return to their desired activities.
If the progression criteria are met, the patient can gradually return to "high-impact" activities (like running). However, "heavier activities", like running, skiing, basketball etc., generally any activities where knees bear sudden changes of the direction of movement can lead to repeated injuries. When planning sport activities it makes sense to consult a physical therapist and check how much impact the sport will have on the knee.
Epidemiology
The meniscal tear is the most common knee injury. It tends to be more frequent in sports that have rough contact or pivoting sports such as soccer. It is more common in males than females, with a ratio of about two and a half males to one female. Males between the ages of 31 and 40 tend to tear their meniscus more frequently than younger men. Females seem to be more likely to tear their meniscus between the ages of 11 and 20.
People who work in physically demanding jobs such as construction or professional sports are more at risk of a meniscal tear because of the different stresses to which their knees are subjected.
According to the United States National Library of Medicine, the isolated medial meniscal tear occurs more frequently than any other tear associated with the meniscus. The prevalence of meniscus tears is the same for both knees. In a few studies the having a higher BMI puts more weight on the joints, which can cause the knee to be non-aligned, resulting in an easier tear.In 2008 the U.S Department of Health and Human Services reported a combined total of 2,295 discharges for the principal diagnosis of tear of lateral cartilage/meniscus (836.0), tear of medial cartilage/meniscus (836.1), and tear of cartilage/meniscus (836.2). Females had a total of 53.49% discharges, while males had 45.72%. Individuals between the ages of 45 and 68 had an average of 31.73% discharges followed by age group 65–84, with 28.82%. The average length of stay for a patient diagnosed with torn menisci was 2.7 days for males and 3.7 days for females. There was a report of 6,941 hospital discharges for knee repair. Individuals between age 18 and 44 were among the highest with 37.37% total of discharges, followed by the age group 45–64, with a percentage of 36.34%. Males had a slightly higher number of discharges (50.78%) than females (48.66%). The average length of stay for both male and female patients in a hospital setting was 3.1.
References
== External links == |
Amphetamine dependence | Amphetamine dependence refers to a state of psychological dependence on a drug in the amphetamine class. Stimulants such as amphetamines and cocaine do not cause physical dependence.Signs of amphetamine intoxication manifest themselves in euphoria, hypersexuality, tachycardia, diaphoresis, and intensifications of the train of thought, speech, and movement. Over time, neurodegenerative changes become apparent in the form of altered behavior, reduced cognitive functions, and signs of neurological damage, such as a decrease in the levels of dopamine transporters (DAT) and serotonin transporters (SERT) in the brain. Amphetamine use within teenagers can have lasting effects on their brain, in particular the prefrontal cortex. Amphetamine use is rising among students due to the ability to easily access prescribed stimulants like Adderall. Also, in case of chronic use, vegetative disorders soon occur such as bouts of sweating, trouble sleeping, tremor, ataxia and diarrhea; the degradation of the personality takes place relatively slowly. Tolerance is expected to develop with regular substituted amphetamine use. When substituted amphetamines are used, drug tolerance develops rapidly. Amphetamine dependence has shown to have the highest remission rate compared to cannabis, cocaine, and opioids. Severe withdrawal associated with dependence from recreational substituted amphetamine use can be difficult for a user to cope with. Long-term use of certain substituted amphetamines, particularly methamphetamine, can reduce dopamine activity in the brain.
For amphetamine dependent individuals, psychotherapy is currently the best treatment option as no pharmacological treatment has been approved. Another treatment option for amphetamine dependence is aversion therapy based on classical conditioning module; this will combine the amphetamine with a negative thing or opposite stimulus. Treatment for amphetamines is growing at extremely high rates around the world. Psychostimulants that increase dopamine and mimic the effects of substituted amphetamines, but with lower abuse liability, could theoretically be used as replacement therapy in amphetamine dependence. However, the few studies that used amphetamine, bupropion, methylphenidate, and modafinil as a replacement therapy did not result in less methamphetamine use or craving.
References
External links
+ Media related to Amphetamine dependence at Wikimedia Commons |
Laryngeal cancer | Laryngeal cancers are mostly squamous-cell carcinomas, reflecting their origin from the epithelium of the larynx.
Cancer can develop in any part of the larynx. The prognosis is affected by the location of the tumour. For the purposes of staging, the larynx is divided into three anatomical regions: the glottis (true vocal cords, anterior and posterior commissures); the supraglottis (epiglottis, arytenoids and aryepiglottic folds, and false cords); and the subglottis.
Most laryngeal cancers originate in the glottis, with supraglottic and subglottic tumours being less frequent.
Laryngeal cancer may spread by: direct extension to adjacent structures, metastasis to regional cervical lymph nodes, or via the blood stream. The most common site of distant metastases is the lung. Laryngeal cancer occurred in 177,000 people in 2018, and resulted in 94,800 deaths (an increase from 76,000 deaths in 1990). Five-year survival rates in the United States are 60.3%.
Signs and symptoms
The symptoms of laryngeal cancer depend on the size and location of the tumour. Symptoms may include the following:
Hoarseness or other voice changes
A lump in the neck
A sore throat or feeling that something is stuck in the throat
Persistent cough
Stridor - a high-pitched wheezing sound indicative of a narrowed or obstructed airway
Bad breath
Earache (due to referred pain)
Difficulty swallowingAdverse effects of treatment can include changes in appearance, difficulty eating, dry mouth, or loss of voice that may require learning alternate methods of speaking.
Risk factors
The most important risk factor for laryngeal cancer is tobacco smoking. Death from laryngeal cancer is 20 times more likely for the heaviest smokers than for their non-smoking peers. Heavy chronic consumption of alcohol, particularly alcoholic spirits, is also a significant risk factor. When present in combination, the usages of alcohol and tobacco appear to have a synergistic effect. Other reported risk factors include being of low socioeconomic status, male sex, or age greater than 55 years.Occupational exposure to environmental factors such as wood dust, paint fumes, and certain chemicals used in the metalworking, petroleum, plastics, and textile industries is also believed to be a risk factor for laryngeal cancers. Infections by some strains of Papillomaviridae carry some risk of laryngeal carcinoma.People with a history of head and neck cancer are known to be at higher risk (about 25%) of developing a second, separate cancer of the head, neck, or lung. This is likely due to chronic exposure to the carcinogenic effects of alcohol and tobacco. In this situation, a field change effect may occur, where the epithelial tissues start to become diffusely dysplastic with a reduced threshold for malignant change. This risk may be reduced by quitting alcohol and tobacco.
Diagnosis
Diagnosis is made by the doctor on the basis of a medical history, physical examination, and special investigations which may include a chest x-ray, CT or MRI scans, and tissue biopsy. The examination of the larynx requires some expertise, which may require specialist referral.The physical exam includes a systematic examination of the whole patient to assess general health and to look for signs of associated conditions and metastatic disease. The neck and supraclavicular fossa are palpated to feel for cervical adenopathy, other masses, and laryngeal crepitus. The oral cavity and oropharynx are examined under direct vision. The larynx may be examined by indirect laryngoscopy using a small angled mirror with a long handle (akin to a dentists mirror) and a strong light. Indirect laryngoscopy can be highly effective, but requires skill and practice for consistent results. For this reason, many specialist clinics now use fibre-optic nasal endoscopy where a thin and flexible endoscope, inserted through the nostril, is used to clearly visualise the entire pharynx and larynx. Nasal endoscopy is a quick and easy procedure performed in clinic. Local anaesthetic spray may be used.If there is a suspicion of cancer, biopsy is performed, usually under general anaesthetic. This provides histological proof of cancer type and grade. If the lesion appears to be small and well localised, the surgeon may undertake excision biopsy, where an attempt is made to completely remove the tumour at the time of first biopsy. In this situation, the pathologist will not only be able to confirm the diagnosis, but can also comment on the completeness of excision, i.e., whether the tumour has been completely removed. A full endoscopic examination of the larynx, trachea, and esophagus is often performed at the time of biopsy.For small glottic tumours further imaging may be unnecessary. In most cases, tumour staging is completed by scanning the head and neck region to assess the local extent of the tumour and any pathologically enlarged cervical lymph nodes.
The final management plan will depend on the site, stage (tumour size, nodal spread, distant metastasis), and histological type. The overall health and wishes of the patient must also be taken into account. A prognostic multigene classifier has been shown to be potentially useful for the distinction of laryngeal cancer of low or high risk of recurrence and might influence the treatment choice in future.
Staging
Laryngeal tumours are classified according to the guidelines set by academic organisations such as the National Comprehensive Cancer Network (NCCN) . Overall classification, also known as "staging", can help predict treatment options for patients. Staging consists of three separate evaluations. The first is of the tumour/cancer itself ("T"). The second is the extent to which adjacent lymph nodes are involved in the tumour/cancers spread ("N"). The third is the presence or absence of any distant metastases ("M). The specific “staging” criteria for laryngeal cancer, as utilised in the NCCN’s 2019 Guidelines for Head and Neck Cancers, are:
T
TX: Unable to assess
Tis: Carcinoma in situ
Supraglottis
T1: Tumour present in only one subsite of the supraglottis. Vocal cords have normal mobility.
T2: Tumour invades mucosa. There is no fixation of the larynx.
T3: Tumour causes fixation of the vocal cords, with or without invasion of neighbouring areas.
T4:
T4A – Tumour invades at least one of the following: the outer cortex of the thyroid cartilage, extra-laryngeal tissue
T4B – Tumour invades at least one of the following: the pre-vertebral space, any structures of the mediastinum, the carotid sheath, or the structures within the carotid sheath.
Glottis
T1: Tumour only involves the vocal cords. Vocal cords have normal mobility.
T1A – One vocal cord
T1B – Both vocal cordsT2: Tumour meets at least one of the following criteria:
extends to supra- or sub-glottis
impairs vocal cord mobilityT3: Tumour meets at least one of the following criteria:
causes fixation of the vocal cords
invades the paraglottic space
involves the thyroid cartilage’s inner cortexT4: Same as “Supraglottis”
Subglottis
T1: Tumour is only in the subglottis
T2: Tumour involves both subglottis and vocal cords (regardless of cord mobility)
T3: Same as “Glottis”
T4: Same as “Supraglottis”
N
If Using Clinical (Non-Pathological) Diagnosis
NX: Unable to assess
N0: No involvement of neighbouring lymph nodes
N1: Tumour meets ALL of the following criteria:
involves single lymph node
involved lymph node on the same side of the body as tumour
involved lymph node less than 3 cm in “greatest dimension”
lacks extension beyond the lymph nodeN2: Tumour meets ANY of the following criteria
N2A – Same as N1, except size can be between 3–6 cm
N2B – Same as N2A, except lymph nodes can be multiple, and there is no minimum size
N2C – Same as N2B, except lymph nodes can be on any side of the bodyN3: Tumour meets ANY of the following criteria:
N3A – Same as N1, except size is greater than 6 cm
N3B – Tumour obviously extends beyond the lymph node border (regardless of number, size, or location of lymph nodes)If Using Pathological Diagnosis
NX: Same as “Clinical Diagnosis – NX”
N0: Same as “Clinical Diagnosis – N0”
N1: Same as “Clinical Diagnosis – N1”
N2: Tumour meets ANY of the following criteria
N2A – Same as “Clinical Diagnosis – N2A”, except tumour can extend beyond the involved lymph node
N2B – Same as “Clinical Diagnosis – N2B”
N2C – Same as “Clinical Diagnosis – N2C”N3: Tumour meets ANY of the following criteria:
N3A – Same as “Clinical Diagnosis – N3A”
N3B – Any provable presence of tumour extension beyond the lymph node
M
M0: No evidence of distant metastasis
M1: Evidence of distant metastasis
Treatment
Specific treatment depends on the location, type, and stage of the tumour. Treatment may involve surgery, radiotherapy, or chemotherapy, alone or in combination.Surgical Treatment
Surgical treatment may involve partial or full removal of the tumour. Neighbouring tissues and structures may or may not be removed, depending on their involvement in the tumour’s structure and spread. Full removal of the larynx may be necessary in some cases.
Adjunct Treatment
Adjunct treatment, most commonly the administration of chemotherapy or radiotherapy, may be necessary. Chemotherapy or radiotherapy may be necessary singly, in combination with each other, or in combination with surgery. Adjunct treatment may be necessary prior to surgical treatment, alongside surgical treatment, or after surgical treatment. Clinical decision-making can be difficult in circumstances where the patient is unable to access necessary adjunct treatment.
Multi-Disciplinary Treatment
Often, successful treatment of and recovery from laryngeal cancer will involve expertise outside of the realms of surgery or oncology. Physical therapists, occupational therapists, speech therapists, psychiatrists, psychologists, oral/maxillofacial surgeons, dentists, neurologists, neurosurgeons, and endocrinologists may all become involved in the care of patients with laryngeal cancer.
Epidemiology
Incidence is five in 100,000 (12,500 new cases per year) in the US. The American Cancer Society estimated that 9,510 men and women (7,700 men and 1,810 women) would be diagnosed with and 3,740 men and women would die of laryngeal cancer in 2006.According to the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, there were 177,422 new cases of laryngeal cancer worldwide in 2018 (1.0% of the global total.) Among worldwide cancer deaths, 94,771 (1.0%) were due to laryngeal cancer.
In 2019, it is estimated that there will be 12,410 new laryngeal cancer cases in the United States, (3.0 per 100,000). The number of new cases decreases every year at a rate of 2.4%, and this is believed to be related to decreased cigarette smoking in the general population.Laryngeal cancer is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH). This means that laryngeal cancer affects fewer than 200,000 people in the US.
See also
Voice prosthesis
References
External links
Staging cancer of the larynx
Cancer Management Handbook: Head and Neck Cancers
Clinically reviewed laryngeal cancer information for patients, from Cancer Research UK
UK laryngeal cancer statistics from Cancer Research UK |
Ductal carcinoma in situ | Ductal carcinoma in situ (DCIS), also known as intraductal carcinoma, is a pre-cancerous or non-invasive cancerous lesion of the breast. DCIS is classified as Stage 0. It rarely produces symptoms or a breast lump one can feel, typically being detected through screening mammography. It has been diagnosed in a significant percentage of men (see male breast cancer).In DCIS, abnormal cells are found in the lining of one or more milk ducts in the breast. In situ means "in place" and refers to the fact that the abnormal cells have not moved out of the mammary duct and into any of the surrounding tissues in the breast ("pre-cancerous" refers to the fact that it has not yet become an invasive cancer). In some cases, DCIS may become invasive and spread to other tissues, but there is no way of determining which lesions will remain stable without treatment, and which will go on to become invasive. DCIS encompasses a wide spectrum of diseases ranging from low-grade lesions that are not life-threatening to high-grade (i.e. potentially highly aggressive) lesions.
DCIS has been classified according to the architectural pattern of the cells (solid, cribriform, papillary, and micropapillary), tumor grade (high, intermediate, and low grade), the presence or absence of comedo histology, or the cell type forming the lesion in the case of the apocrine cell-based in situ carcinoma, apocrine ductal carcinoma in situ. DCIS can be detected on mammograms by examining tiny specks of calcium known as microcalcifications. Since suspicious groups of microcalcifications can appear even in the absence of DCIS, a biopsy may be necessary for diagnosis.
About 20–30% of those who do not receive treatment develop breast cancer. It is the most common type of pre-cancer in women. There is some disagreement on its status as a cancer; some bodies include DCIS when calculating breast cancer statistics, while others do not.
Terminology
Ductal carcinoma in situ (DCIS) literally means groups of "cancerous" epithelial cells which remained in their normal location (in situ) within the ducts and lobules of the mammary gland. Clinically, it is considered a premalignant (i.e. potentially malignant) condition, because the biologically abnormal cells have not yet crossed the basement membrane to invade the surrounding tissue. When multiple lesions (known as "foci" of DCIS) are present in different quadrants of the breast, this is referred to as "multicentric" disease.For statistical purposes, some count DCIS as a "cancer", whereas others do not. When classified as a cancer, it is referred to as a non-invasive or pre-invasive form. The National Cancer Institute describes it as a "noninvasive condition".
Signs and symptoms
Most of the women who develop DCIS do not experience any symptoms. The majority of cases (80-85%) are detected through screening mammography. The first signs and symptoms may appear if the cancer advances. Because of the lack of early symptoms, DCIS is most often detected at screening mammography.
In a few cases, DCIS may cause:
A lump or thickening in or near the breast or under the arm
A change in the size or shape of the breast
Nipple discharge or nipple tenderness; the nipple may also be inverted, or pulled back into the breast
Ridges or pitting of the breast; the skin may look like the skin of an orange
A change in the way the skin of the breast, areola, or nipple looks or feels such as warmth, swelling, redness or scaliness.
Causes
The specific causes of DCIS are still unknown. The risk factors for developing this condition are similar to those for invasive breast cancer.Some women are however more prone than others to developing DCIS. Women considered at higher risks are those who have a family history of breast cancer, those who have had their periods at an early age or who have had a late menopause. Also, women who have never had children or had them late in life are also more likely to get this condition.
Long-term use of estrogen-progestin hormone replacement therapy (HRT) for more than five years after menopause, genetic mutations (BRCA1 or BRCA2 genes), atypical hyperplasia, as well as radiation exposure or exposure to certain chemicals may also contribute in the development of the condition. Nonetheless, the risk of developing noninvasive cancer increases with age and it is higher in women older than 45 years.
Diagnosis
80% of cases in the United States are detected by mammography screening. More definitive diagnosis is made by breast biopsy for histopathology.
Treatment
There are different opinions on the best treatment of DCIS. Surgical removal, with or without additional radiation therapy or tamoxifen, is the recommended treatment for DCIS by the National Cancer Institute. Surgery may be either a breast-conserving lumpectomy or a mastectomy (complete or partial removal of the affected breast). If a lumpectomy is used it is often combined with radiation therapy. Tamoxifen may be used as hormonal therapy if the cells show estrogen receptor positivity. Research shows that survival is the same with lumpectomy as it is with mastectomy, whether or not a woman has radiation after lumpectomy. Chemotherapy is not needed for DCIS since the disease is noninvasive.While surgery reduces the risk of subsequent cancer, many people never develop cancer even without treatment and the associated side effects. There is no evidence comparing surgery with watchful waiting and some feel watchful waiting may be a reasonable option in certain cases.
Radiation therapy
Use of radiation therapy after lumpectomy provides equivalent survival rates to mastectomy, although there is a slightly higher risk of recurrent disease in the same breast in the form of further DCIS or invasive breast cancer. Systematic reviews (including a Cochrane review) indicate that the addition of radiation therapy to lumpectomy reduces recurrence of DCIS or later onset of invasive breast cancer in comparison with breast-conserving surgery alone, without affecting mortality. The Cochrane review did not find any evidence that the radiation therapy had any long-term toxic effects. While the authors caution that longer follow-up will be required before a definitive conclusion can be reached regarding long-term toxicity, they point out that ongoing technical improvements should further restrict radiation exposure in healthy tissues. They do recommend that comprehensive information on potential side effects is given to women who receive this treatment. The addition of radiation therapy to lumpectomy appears to reduce the risk of local recurrence to approximately 12%, of which approximately half will be DCIS and half will be invasive breast cancer; the risk of recurrence is 1% for women undergoing mastectomy.
Mastectomy
There is no evidence that mastectomy decreases the risk of death over a lumpectomy. Mastectomy; however, may decrease the rate of the DCIS or invasive cancer occurring in the same location.Mastectomies remain a common recommendation in those with persistent microscopic involvement of margins after local excision or with a diagnosis of DCIS and evidence of suspicious, diffuse microcalcifications.
Sentinel node biopsy
Some institutions that have encountered high rates of recurrent invasive cancers after mastectomy for DCIS have endorsed routine sentinel node biopsy (SNB). However, research indicates that sentinel node biopsy has risks that outweigh the benefits for most women with DCIS. SNB should be considered with tissue diagnosis of high risk DCIS (grade III with palpable mass or larger size on imaging) as well as in people undergoing mastectomy after a core or excisional biopsy diagnosis of DCIS.
Prognosis
With treatment, the prognosis is excellent, with greater than 97% long-term survival. If untreated, DCIS progresses to invasive cancer in roughly one-third of cases, usually in the same breast and quadrant as the earlier DCIS. About 2% of women who are diagnosed with this condition and treated died within 10 years. Biomarkers can identify which women who were initially diagnosed with DCIS are at high or low risk of subsequent invasive cancer.
Epidemiology
DCIS is often detected with mammographies but can rarely be felt. With the increasing use of screening mammography, noninvasive cancers are more frequently diagnosed and now constitute 15% to 20% of all breast cancers.Cases of DCIS have increased 5 fold between 1983 and 2003 in the United States due to the introduction of screening mammography. In 2009 about 62,000 cases were diagnosed.
References
== External links == |
Vestibular schwannoma | A vestibular schwannoma (VS), also called acoustic neuroma, is a benign tumor that develops on the vestibulocochlear nerve that passes from the inner ear to the brain. The tumor originates when Schwann cells that form the insulating myelin sheath on the nerve malfunction. Normally, Schwann cells function beneficially to protect the nerves which transmit balance and sound information to the brain. However, sometimes a mutation in the tumor suppressor gene, NF2, located on chromosome 22, results in abnormal production of the cell protein named Merlin, and Schwann cells multiply to form a tumor. The tumor originates mostly on the vestibular division of the nerve rather than the cochlear division, but hearing as well as balance will be affected as the tumor enlarges.
The great majority of these VSs (95%) are unilateral, in one ear only. They are called "sporadic" (i.e., by-chance, non-hereditary). Although non-cancerous, they can do harm or even become life-threatening if they grow to press on other cranial nerves and vital structures such as the brainstem. Variations in the mutation determine the nature of the tumors development. The only environmental exposure that has been definitely associated with the growth of a VS is therapeutic radiation exposure to the head.
Symptoms of Sporadic VS
Sporadic VSs originate within the confining bony walls of the small (ca. 2 cm long) internal auditory canal. The most common early symptoms of these intracanalicular (IAC) VSs are gradual hearing loss and a feeling of fullness in the affected ear, some imbalance or dizziness, and tinnitus (ringing or other noise in the ear). Gradual single-sided hearing loss in the high frequencies is the first most obvious symptom for the great majority of patients. Headache as a presenting symptom of VS specifically is rare; facial symptoms (facial numbness, weakness) usually occur only as the tumor grows out of the canal and/or after therapeutic treatment. Delayed diagnosis and misdiagnosis are not unusual. Initial hearing loss is usually subtle and may be attributed mistakenly to aging, earwax buildup, or perhaps exposure to some loud environmental noise. A sudden hearing loss, which is uncommon, might be misdiagnosed as Ménières disease, an abnormality of the inner ear that also has tinnitus as a symptom. The brains vestibular system usually compensates for early balance problems.
There have been cases of tumors that were actually asymptomatic until very large and at a critical stage. Tumor growth rates are highly variable: some small VSs (perhaps 50%) do not grow at all; some few grow for a time and then shrink; some appear dormant but suddenly grow rapidly. In general, although studies differ, VSs that grow are slow-growing at an average rate of 1.2 to 1.9 mm per year. IAC tumors that grow beyond 1.5 cm in diameter expand into the relatively empty space of the cerebellopontine angle, taking on the characteristic ice-cream-cone appearance seen on MRIs. As space-occupying-lesions, the tumors can reach 3 to 4 cm or more in size and infringe on the facial nerve (facial expression) and trigeminal nerve (facial sensation). Advanced hearing loss and spells of true vertigo may occur. Very large tumors are life-threatening when they press on the cerebellum or cause brainstem compression. Late symptoms of very large VS include headache, nausea, vomiting, sleepiness, mental confusion and eventually coma.
Neurofibromatosis Type 2 (NF2)
For the most part, unilateral sporadic vestibular schwannomas are readily treated successfully by modern medical techniques. Having bilateral VSs is a more troublesome condition. Bilateralism is considered to be the hallmark and main diagnostic criterion of Neurofibromatosis Type II (NF2), a genetic disorder that is heritable, progressive, difficult to manage, and has a 1 in 2 chance of being passed on to each offspring. NF2 patients tend to have a more severe mutation, although there are mild mosaic cases in which only some cells carry the mutation. Genetic testing confirming mutation of the NF2 gene is recommended. About 50% of people with NF2 have a de novo mutation, and about 50% of these new mutations will be mild mosaic cases which are less likely to be passed on. NF2 patients may develop other cranial and spine tumors. NF2 develops during the teens or early adulthood, whereas sporadic VSs are diagnosed mostly in patients between the ages of 40–60 years. Both varieties of VS (sporadic and NF2) are very rare, accounting for only about 8% of all primary brain tumors. The incidence of NF2 is approximately 1 per 60,000 people.
Tumor sizes
Patient surveys in the U.S. by the national Acoustic Neuroma Association (1998, 2007–08, 2012, 2014) showed that the percentage of diagnosed tumors 1.5 cm or less increased significantly from 23% to 47%. Researchers in Denmark reported (2004): "The size of diagnosed tumors has decreased from a median of 35 mm in 1979 to 10 mm in 2001." In general, tumor size (diameter) is described as small (less than 1.5 cm), medium (1.5 to 2.5 cm), large (2.5 to 4.0 cm) and giant (more than 4.0 cm). (Note: 1 inch = 2.54 cm) Radiologists reporting on MRI scans use the Koos Grading Scale which relates tumor size to its proximity to the brainstem and nearby cranial nerves. Thus Koos grade 1 is a purely intrameatal (IAC) tumor, 1–10 mm in size; Koos grade 2, 10–20 mm, has extended into the cerebellopontine angle (CPA), but with no brainstem contact; Koos grade 3, 20–30 mm, fills the CPA space and touches on the brainstem, but without compression; and Koos grade 4, more than 30 mm in size, compresses the brainstem and nearby nerves, and displaces critical arteries.
Diagnosis
Preliminary diagnostic procedures include ear examination, hearing and vestibular testing. The auditory brainstem response test (ABR) is a cost-effective test to see if a VS has perhaps compromised the cochlear nerve.Computed tomography (CT scan) of the head will detect moderate to large sized VS but can miss small sized VS. VS appears as isodense to surrounding brain parenchyma on CT. VS does not have calcifications in it. Large VS will expand the size of internal acoustic meatus (IAC), thus associated with poor hearing function because the nerves within the IAC are compressed, particularly the cochlear nerve. However, facial nerve is less commonly affected. The main advantage of CT scan is to assess the extent of bony involvement by VS. VS enhances when iodinated contrast is given. Contrasted CT scan of temporal bone can done if the subject is unsuitable to undergo MRI scan.MRI scan is the imaging of choice because it can more accurately differentiate the mass from other tumours such as meningioma, facial nerve schwannoma, epidermoid cyst, arachnoid cyst, aneurysm, and brain metastasis. MRI scan also helps in surgical planning and follow-up of the tumour after surgery. VC is usually isointense on T1 weighted images, hyperintense on T2 weighted images, and enhances after given gadolinium contrast.
Management
Microsurgery for Sporadic VS
The Guidelines on the Treatment of Adults with Vestibular Schwannoma issued in 2018 by the Congress of Neurological Surgeons in the U.S. looked at the long-term evolution of treatments for VS. The Introduction to the Guidelines stated: "The evolution in treatment over the last century has ultimately led to an environment where functional outcome has taken precedence over disease eradication. With multiple noninvasive management options available, the tolerance of cranial neuropathy in patients with small and medium-sized tumors is low. Today, hearing preservation, facial nerve function, and tumor control remain the primary benchmarks used to evaluate treatment effectiveness and compare outcomes." In other words, tumor management was able to give greater attention to preserving quality of life.
The three main surgical approaches to the tumor were the translabyrinthine (incision behind the ear to reach the bony labyrinth), the retrosigmoid (incision behind the ear to reach cerebellopontine angle) and the middle cranial fossa (incision in front of the ear to access the IAC from above). Tumor size was a major factor in determining approach selection. Adjunctive use of the endoscope for enhanced visualization during surgery for IAC tumors gained attention as an emerging technique with advancing technology. For large tumors, a facial nerve sparing surgery evolved offering partial removals, to be followed (as needed) by stereotactic radiosurgery or radiotherapy for residuals. The rate of tumor control appeared to be similar to that for gross total removal surgeries. For small to medium size tumors, the appropriateness of so-called hearing preservation surgery via either the Middle Fossa or Retrosigmoid approach remained controversial. Data from Denmark indicated that primary observation offered the best chance to preserve good hearing the longest. But preserving good hearing in the affected ear remained an elusive goal. Even during observation, although tumors showed no significant growth, hearing deterioration occurred. Stangerup et al. reported (2010) that most patients with 100% speech discrimination at diagnosis had the best chance of maintaining good hearing after ten years of observation.
Structured surgical training of neurosurgeons and official accreditation replaced the ages-old informal apprenticeship model. Advances in microsurgical instrumentation, the refinement of operative techniques including the introduction of intraoperative facial and cochlear nerve monitoring, and the development of multidisciplinary team-based patient care reduced the incidence of complications related to treatment. There was a trend toward the emergence of high-patient-volume centers for VS surgery where good outcomes and routine patient discharges could become commonplace. The mortality rate for VS surgery fell to less than 1%. In 1991 the NIH Consensus Statement for Acoustic Neuroma observed: "The best published surgical outcomes in the treatment of vestibular schwannoma are from medical centers that have highly organized and dedicated teams with a specific interest in these tumors and sufficient continuing experience to develop, refine and maintain proficiency."ref>Sweeney A, Breen JT, Vrabec JT (2019). "Chapter 29: Training in Vestibular Schwannoma Surgery". In Carlson ML, Link MJ, Driscoll CL, et al. (eds.). Comprehensive Management of Vestibular Schwannoma. New York. ISBN 978-1-62623-332-4.</ref>
Radiosurgery and radiotherapy
The 1991 NIH Consensus Statement recognized radiation therapy as "a treatment option limited in current practice primarily to patients unable or unwilling to undergo otherwise indicated surgery." The beneficiaries of radiation therapy soon greatly exceeded this limited clientele. The Patient Survey in the U.S. in 2014 by the national Acoustic Neuroma Association showed that 29% of VS patients reported radiosurgery (17%) or radiotherapy (12%) as their treatment of choice. Radiosurgery is the delivery to the VS of a concentrated high radiation dose in a one-day session, whereas radiotherapy involves multiple treatment sessions where the total radiation dose is spread out in fractions over a few days or 3–4 weeks. The main objective in either case is tumor control by damaging tumor cell DNA and stopping blood vessel proliferation (angiogenesis) needed for tumor growth.
Tumors may swell following radiation, but this increase in size is transient and does not signal a failed procedure. A failed radiosurgery is uncommon. Radiation doses are calculated in terms of Gray/Gy—the measure of energy deposited by ionizing radiation per kilogram of matter -- "named after the British physicist Louis Harold Gray (1905–1965), a pioneer in the measurement of X-ray and radium radiation and their effects on living tissue." Since VSs are noninvasive and well-demarcated from surrounding tissues, as is apparent on MRI scans, radiosurgeons are able to target the tumor volume closely and minimize normal tissue damage. Multisession radiotherapy recommends the advantage of giving time between sessions for biological repair of any damage to normal tissues that may occur, and allows for radiation of the tumor at different times in the cell growth cycle.
The CyberKnife radiation system introduced in 1994 recommends a protocol of three sessions known as hypofractionation. Radiation dosages overall were reduced over the years as experience showed that excellent tumor control rates could be maintained even as dosages were lowered to benefit hearing preservation and facial nerve function. Generally, single-session Gamma Knife radiosurgery is limited in use to VSs less than 3 cm in diameter to avoid possible complications with facial nerves, brainstem and the cochlea apparatus. The risk of radiation-induced secondary tumors is very small, in the range of 0.01-0.02%. The risk for NF2 patients appears to be slightly higher.
Medical and gene therapies
The 1991 NIH Consensus Statement recommended attention to "the development of pharmaceutical and other alternative medical treatments, such as tumor suppressing agents." Ideally, a drug could be found to permanently shrink or eradicate VSs, with minimal side effects. A key step forward in 1993 was the identification of the NF2 gene and its protein product Merlin, which modulates the complex molecular signaling pathways that control cell proliferation. These pathways that drive VS formation (tumorigenesis) and growth are currently under investigation.
A second important field of study in molecular biology investigates ways to stop the formation (angiogenesis) of the new blood vessels that are needed to support tumor growth by supplying nutrients and oxygen. In 1998, the glycoprotein named VEGF (vascular endothelial growth factor) that initiates proliferation was discovered. An anti-VEGF drug named bevacizumab (Avastin) was developed and showed promise in stopping this vascular proliferation. Unfortunately, when tested for NF2 tumors, the therapy required prolonged treatment resulting in hypertension and impaired wound healing. Clinical trials are in progress for other drugs such as everolimus, lapatinib and mifepristone. Common aspirin has been studied as a low-risk therapeutic option.
To date, there is no fully efficacious medical therapy for VS. The complexity of the molecular biology research involved is truly challenging. The development of a new generation of drugs may become a secondary therapy in view of advances in genome editing during the 1990s that led to the invention of CRISPR in 2009. CRISPR has become the preferred genome editing tool whereby diseases may be treated by correcting causative mutations directly in a patients genome.
Observation of Small VS
The 1991 NIH Consensus Statement observed: "There is evidence that some patients with unilateral vestibular schwannoma and a subgroup of patients with NF2 may have tumors that fail to progress rapidly, resulting in stable neurologic function for a long time. The use of MRI with contrast enhancement has resulted in the identification of patients with very small, relatively asymptomatic vestibular schwannomas for whom the natural history is unknown. Conservative management may be appropriate for these patients." At the time, conservative management (i.e., observation, wait-and-watch/wait-and-scan) was reserved mainly for elderly or infirm patients.
Data on tumor sizes at diagnosis and tumor growth behavior was sparse or contradictory and mainly short-term. The Central Brain Tumor Registry of the U.S., established in 1992, only began to keep records for benign tumors like VS in 2004. In 2006, a landmark study from Denmark, entitled "The Natural History of Vestibular Schwannoma," initiated a significant trend toward observation for managing small VS. Researchers in Copenhagen had the advantage that data for all Danish patients diagnosed with VS since 1976 was entered into a national database. The 2006 study by Stangerup et al. looked at the data for 1,818 patients (1976–2004) comparing intrameatal VS (in the auditory canal) and extrameatal VS (into the cerebellopontine angle). Remarkably, for the 729 patients having observation management via interval MRI scans, tumor growth was observed in only 17% of intrameatal tumors and 29% of extrameatal tumors. The mean observation time was 3.6 years (range 1–15 years). The researchers concluded: "VS growth occurs within the first 5 years after diagnosis in a limited number of tumors, primarily in tumors with an extrameatal extension. These findings justify primary observation of small tumors." The medical community and VS patients responded positively to these findings.
Patient Surveys in the U.S. by the national Acoustic Neuroma Association showed an increase in "Wait-and-Watch" from 4% of respondents in 1998 to 20% in 2012. An important study in 2015 entitled "The Changing Landscape of Vestibular Schwannoma Management in the United States – A Shift Toward Conservatism," predicted that half of all cases of VS would be managed initially with observation by 2026. Stangerup et al. have urged caution (2019): "Most studies show that if tumor growth occurs, it is usually detected within the first few years of diagnosis. However, long-term observational studies are desperately needed to guide the development of evidence-based surveillance algorithms designed to detect late tumor progression." Also (see Medical and Gene Therapies, above): "Basic science and identification of genes, molecular pathways, and networks related to tumor growth are likely to change our approach to treatment including conservative management."
Incidence of Sporadic VS
The U.S. National Institutes of Health (NIH) consensus statement for Acoustic Neuroma in 1991 estimated that 2–3,000 cases of VS were diagnosed in the U.S. annually—an incidence rate of about 10 per million of population per year. In 2015, researchers at the Cleveland Clinic in Ohio used population-based data of the Central Brain Tumor Registry of the U.S. to calculate an incidence of 10.9 per million of population, or about 3,300 cases of VS per year. A higher incidence up to 29.3 per million of population was found for the 65-74 year-old age group. There was no significant difference in incidence by gender. Incidence was higher in Asian Pacific Islanders, and lower in African Americans and Hispanics. The annual number of diagnosed VS increased significantly worldwide by the early 1990s with the introduction of magnetic resonance imaging (MRI). Notably, epidemiologists in Denmark (population of 5.7 million in 2015) reported 193 cases of VS for 2015—an incidence of 34 per million of population per year. The first MRI scanner in Denmark was functional in 1989, and by 2015 the number increased to approximately 100.
History
Early descriptions
In 1777, Eduard Sandifort of Leiden, the Netherlands, wrote a postmortem first description of a vestibular schwannoma. He observed "a certain hard body adherent to the auditory nerve," and concluded this cause of deafness was beyond the reach of medication or surgery and was therefore incurable. The Schwann cells that multiply to form a VS on the vestibulocochlear nerve were identified 60 years later in 1838 by the German physiologist Theodor Schwann, the co-founder with the botanist Matthias Schleiden of the critically important cell theory that all living things are composed of cells. In 1895, Thomas Annandale, a general surgeon at the Royal Infirmary in Edinburgh, Scotland, was the first to successfully localize and surgically remove a VS. His achievement was exceptional. Finger dissection of VS to shell out the tumor was typical. The main goal when dealing with large tumors was preservation of life.
Early surgeries
In the early 1900s the mortality rate for VS surgery was in the range of 75 to 85%. Surgeons typically delayed invasive intervention as long as possible as a last resort. Harvey Cushing (1869–1939) is known as the father of neurosurgery for VS. His basic study published in 1917 was entitled Tumors of the Nervus Acusticus and the Syndrome of the Cerebellopontine Angle. Cushing perfected the retrosigmoid surgical approach, and by doing suboccipital craniotomy and subtotal removals he was able to reduce mortality to 4% by 1931. Cushing worked at Brigham Hospital in Boston. An equally famous specialist for VS at Johns Hopkins in Baltimore was Walter E. Dandy (1886–1946), a former pupil of Cushing who advocated total tumor removals. In 1931, he reported a complete removal with preservation of the facial nerve.
Imaging
A major problem for the pioneers in VS neurosurgery was the lack of adequate imaging for spotting small tumors. Treating tumors that grew overly large in the cerebellopontine angle resulted in poor outcomes for the goals of facial nerve and hearing preservation. For imaging, conventional X-rays began to be used in the 1920s and CT scanners were introduced in the 1960s, but all were superseded by gold standard MRIs in the 1980s. Facial nerve monitoring was added in 1979. William F. House (1923–2012) pioneered the use of the operating microscope, and (with William Hitselberger) popularized the translabyrinthine and middle fossa surgery approaches for VS. The operating microscope would be used in virtually all operations by 1998. Houses son, John W. House, proposed (1983) and, with Derald E. Brackmann, developed the House-Brackmann grading system for reporting facial nerve outcomes following VS surgery.
Treatment
Surgical treatment
In 1986, at a meeting for neurosurgeons in San Francisco, the House group endorsed a guideline for the surgical treatment of VS: "The best opportunity for successful removal of an acoustic neuroma is when it is small: when first diagnosed." At the time of the NIH Consensus Development Conference for Acoustic Neuroma in 1991, microsurgery was definitely the predominant management strategy for VS. The consensus conferences panel of experts reported: "Currently, the ideal treatment for symptomatic patients with vestibular schwannoma is the total excision of the tumor in a single stage with minimal morbidity and mortality and with preservation of neurological function." Total surgical removal was not, however, the only treatment indicated at the time. Partial removals were in use to debulk very large VSs threatening to compress vital structures. And long-term observation management was deemed appropriate as MRI scans began to reveal more and more small tumors with stable neurological symptoms.
Radiosurgery
By the 1980s, radiation therapy was also becoming an attractive option for VS patients. At the Karolinska Institute in Stockholm, Sweden, Lars Leksell (1907–1986) pioneered Gamma Knife radiosurgery. In 1951, he published his landmark scientific paper, "The Stereotaxic Method and Radiosurgery of the Brain," defining radiosurgery as "the destruction of intracranial targets without opening the skull using very high doses of ionizing radiation in stereotactically directed beams." The first Gamma Knife machine was operable in Sweden in 1969, and the first Gamma Knife in the U.S. was installed in 1987 at the Presbyterian University Hospital in Pittsburgh, PA. Departments of radiation oncology at major medical centers began to modify X-ray linear accelerators (linacs) to do single-session radiosurgery and multiple-session radiotherapy. In 1991, the U.S. National Institutes of Health convened a Consensus Development Conference (December 11–13, 1991) for Acoustic Neuroma (Vestibular Schwannoma) to evaluate management of the disorder and recommend areas for future activity and research."
Notable people
American actor, director, humanitarian, social activist and film producer Mark Ruffalo was diagnosed with vestibular schwannoma in 2001 which resulted in a period of partial facial paralysis. He recovered from the paralysis; however, he became deaf in his left ear as a result of the tumor.Guitarist/composer/producer David Torn was diagnosed with an acoustic neuroma in 1992. It required intricate surgery that left him deaf in the right ear and burdened by many other health obstacles.American actress and designer Tara Subkoff was diagnosed with schwannoma in 2009. She successfully underwent surgery, but was left with permanent nerve damage and deafness in her right ear.Tionne Watkins, better known by her stage name T-Boz, R&B singer from the R&B/hip-hop group TLC, was diagnosed with a strawberry-sized acoustic neuroma on her vestibular nerve in 2006. Many physicians refused to remove the tumor due to her sickle-cell-related complications, leaving her alternatives grim. Ultimately, she underwent surgery at Cedars-Sinai Hospital in Los Angeles.
See also
Cerebellopontine angle syndrome
References
Further reading
External links
Vestibular schwannoma at Curlie |
Charcot–Marie–Tooth disease | Charcot–Marie–Tooth disease (CMT) is a hereditary motor and sensory neuropathy of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts of the body. This disease is the most commonly inherited neurological disorder, affecting about one in 2,500 people. It is named after those who classically described it: the Frenchman Jean-Martin Charcot (1825–1893), his pupil Pierre Marie (1853–1940), and the Briton Howard Henry Tooth (1856–1925).There is no known cure. Care focuses on maintaining function. CMT was previously classified as a subtype of muscular dystrophy.
Signs and symptoms
Symptoms of CMT usually begin in early childhood or early adulthood but can begin later. Some people do not experience symptoms until their early 30s or 40s. Usually, the initial symptom is foot drop early in the course of the disease. This can also cause hammertoe, where the toes are always curled. Wasting of muscle tissue of the lower parts of the legs may give rise to a "stork leg" or "inverted champagne bottle" appearance. Weakness in the hands and forearms occurs in many people as the disease progresses.Loss of touch sensation in the feet, ankles, and legs as well as in the hands, wrists, and arms occurs with various types of the disease. Early- and late-onset forms occur with on and off painful spasmodic muscular contractions that can be disabling when the disease activates. High-arched feet (pes cavus) or flat-arched feet (pes planus) are classically associated with the disorder. Sensory and proprioceptive nerves in the hands and feet are often damaged, while unmyelinated pain nerves are left intact. Overuse of an affected hand or limb can activate symptoms including numbness, spasm, and painful cramping.Symptoms and progression of the disease can vary. Involuntary grinding of teeth and squinting are prevalent and often go unnoticed by the person affected. Breathing can be affected in some, as can hearing, vision, and neck and shoulder muscles. Scoliosis is common, causing hunching and loss of height. Hip sockets can be malformed. Gastrointestinal problems can be part of CMT, as can difficulty chewing, swallowing, and speaking (due to atrophy of vocal cords). A tremor can develop as muscles waste. Pregnancy has been known to exacerbate CMT, as well as severe emotional stress. Patients with CMT must avoid periods of prolonged immobility such as when recovering from a secondary injury, as prolonged periods of limited mobility can drastically accelerate symptoms of CMT.Pain due to postural changes, skeletal deformations, muscle fatigue, and cramping is fairly common in people with CMT. It can be mitigated or treated by physical therapies, surgeries, and corrective or assistive devices. Analgesic medications may also be needed if other therapies do not provide relief from pain. Neuropathic pain is often a symptom of CMT, though, like other symptoms of CMT, its presence and severity vary from case to case. For some people, pain can be significant to severe and interfere with daily life activities. However, pain is not experienced by all people with CMT. When neuropathic pain is present as a symptom of CMT, it is comparable to that seen in other peripheral neuropathies, as well as postherpetic neuralgia and complex regional pain syndrome, among other diseases.
Causes
Charcot–Marie–Tooth disease is caused by genetic mutations that cause defects in neuronal proteins. Nerve signals are conducted by an axon with a myelin sheath wrapped around it. Most mutations in CMT affect the myelin sheath, but some affect the axon.
Classification
CMT is a heterogeneous disease and the mutations linked to it may occur in a number of different genes. Based on the affected gene, CMT is categorized into several types and subtypes.
Chromosome 17
The most common cause of CMT (70–80% of the cases) is the duplication of a large region on the short arm of chromosome 17 that includes the gene PMP22.Some mutations affect the gene MFN2, on chromosome 1, which codes for a mitochondrial protein. Mutated MFN2 causes the mitochondria to form large clusters, or clots, which are unable to travel down the axon towards the synapses. This prevents the synapses from functioning.
X-linked CMT and Schwann cells
CMT can also be produced by X-linked mutations and is named X-linked CMT (CMTX). In CMTX, mutated connexons create nonfunctional gap junctions that interrupt molecular exchange and signal transport.The mutation can appear in GJB1 coding for connexin 32, a gap junction protein expressed in Schwann cells. Because this protein is also present in oligodendrocytes, demyelination can appear in the CNS.Schwann cells create the myelin sheath, by wrapping its plasma membrane around the axon.Neurons, Schwann cells, and fibroblasts work together to create a functional nerve. Schwann cells and neurons exchange molecular signals by gap junctions that regulate survival and differentiation.Demyelinating Schwann cells causes abnormal axon structure and function. They may cause axon degeneration, or they may simply cause axons to malfunction.The myelin sheath allows nerve cells to conduct signals faster. When the myelin sheath is damaged, nerve signals are slower, and this can be measured by a common neurological test, electromyography. When the axon is damaged, though, this results in a reduced compound muscle action potential.GARS1-Related Axonal Neuropathy
CMT2 types are typically referred to as axonal neuropathies due to the axonal degeneration observed. CMT2 types are a result of damage to the nerve axons rather than damage to the myelin sheath (as is the case with CMT1). Damaged axons cause slowed transmission of signals to the muscles and brain, causing symptoms including muscle atrophy, weakness, decreased sensitivity, and foot deformity. Symptoms of CMT2 types typically appear between the ages of 5 and 25. CMT2D is one of 31 Charcot-Marie-Tooth type 2 forms 1 and is only diagnosed if sensory deficits (such as loss of sensation due to the degradation of sensory axons) are observed along with motor deficits; otherwise, distal hereditary motor neuropathy type V is diagnosed. It is unknown why sensory involvement is so varied between GARS1 neuropathy patients. Symptoms of CMT2D include foot deformity, muscle weakness and cramping, compromised reflexes, loss of sensation, and muscle atrophy and are similar to the symptoms of other both CMT1 and CMT2 types. Symptoms and severity vary from patient to patient.Mice are often used to model CMT2D and typically demonstrate aberrant neuromuscular function at the neuromuscular junction (NMJ). The neuromuscular junction is abnormal in CMT2D mice, with subjects showing neuromuscular junction degeneration in hind muscles. The dorsal root ganglia (DRG) is also affected via aberrant sensory neuron fate, meaning that sensory neuron cell fates are abnormally determined. CMT2D mice have fewer proprioceptive and mechanosensitive neurons, but have more nociceptive neurons, possibly due to mutant GlyRS aberrantly interacting with the extracellular region of tropomyosin receptor kinase, or Trk, receptors. Trk receptors are crucial to the survival and development of sensory neurons; when disrupted, nerve development and survival is disrupted as well, possibly leading to the abnormal sensory neuron counts observed in CMT2D mice.CMT2D is a result of autosomal dominant mutations in the human GARS1 gene located at 7p14.3 and is thought to be caused by aberrant gain-of-function missense mutations. The GARS1 gene is a protein-coding gene responsible for the encoding of glycyl-tRNA synthetase (GlyRS). Glycyl-tRNA synthetase is a class II aminoacyl-tRNA synthetase and acts as the catalyst for the synthesis of glycyl-tRNA by covalently bonding amino acids with their corresponding cognate tRNAs for protein translation. Glycyl-tRNA is integral to protein translation and attaches glycine to its cognate RNA.Many different mutations have been found in CMT2D patients and it remains unclear how mutations in GARS1 cause CMT2D. However, it is thought that mutant glycyl-tRNA synthetase (GlyRS) interferes with transmembrane receptors, causing motor disease and that mutations in the gene could disrupt the ability of GlyRS to interact with its cognate RNA, disrupting protein production. The GARS1 mutations present in CMT2D cause a deficient amount of glycyl-tRNA in cells, preventing the elongation phase of protein synthesis. Because elongation is a key step in protein production, ribosomes are unable to continue protein synthesis at glycine sites. GARS1 mutations also stall initiation of translation. Glycine addition failure causes a stress response that further stalls protein production, preventing initiation of translation. By stalling elongation and initiation of translation, CMT2D mutations in the GARS1 gene cause translational repression, meaning that overall translation is inhibited.GARS1-associated axonal neuropathy is progressive, meaning that it worsens over time. Unknown mechanisms are thought to cause the chronic neurodegeneration resulting from the aberrant GlyRS; however, one theory for disease is VEGF-deficiency. Mutant GlysRS interferes with neuronal transmembrane receptors, including neuropilin 1 (Nrp1) and vascular endothelial growth factor (VEGF), causing neuropathy. GARS-CMT2D mutations alter GlyRS and allow it to bind to the Nrp1 receptor, interfering with the normal binding of Nrp1 to VEGF. While enhanced expression of VEGF improves motor function, reduced expression of Nrp1 worsens CMT2D; because Nrp1 binds to mutant GlyRS in mutant GARS1-CMT2D individuals, Nrp1 expression is reduced, in turn worsening motor function. Mice with deficient VEGF demonstrate motor-neuron disease over time. Thus, the VEGF/Nrp1 pathway is considered to be targetable for CMT2D treatment.
Diagnosis
CMT can be diagnosed through three different forms of tests: measurement of the speed of nerve impulses (nerve conduction studies), a biopsy of the nerve, and DNA testing. DNA testing can give a definitive diagnosis, but not all the genetic markers for CMT are known. CMT is first most noticed when someone develops lower leg weakness, such as foot drop, or foot deformities, including hammertoes and high arches, but signs alone do not lead to diagnosis. Patients must be referred to a physician specialising in neurology or rehabilitation medicine. To see signs of muscle weakness, the neurologist may ask patients to walk on their heels or to move part of their leg against an opposing force. To identify sensory loss, the neurologist tests for deep-tendon reflexes, such as the knee jerk, which are reduced or absent in CMT. The doctor may also ask the patients family history since CMT is hereditary. The lack of family history does not rule out CMT, but is helpful to rule out other causes of neuropathy, such as diabetes or exposure to certain chemicals or drugs.In 2010, CMT was one of the first diseases where the genetic cause of a particular patients disease was precisely determined by sequencing the whole genome of an affected individual. This was done by the scientists employed by the Charcot Marie Tooth Association (CMTA). Two mutations were identified in a gene, SH3TC2, known to cause CMT. Researchers then compared the affected patients genome to the genomes of the patients mother, father, and seven siblings with and without the disease. The mother and father each had one normal and one mutant copy of this gene, and had mild or no symptoms. The offspring who inherited two mutant genes presented fully with the disease.
Histology
The constant cycle of demyelination and remyelination, which occurs in CMT, can lead to the formation of layers of myelin around some nerves, termed an "onion bulb". These are also seen in chronic inflammatory demyelinating polyneuropathy. Muscles show fiber type grouping, a similarly nonspecific finding that indicates a cycle of denervation/reinnervation. Normally, type I and type II muscle fibers show a checkerboard-like random distribution. However, when reinnervation occurs, the group of fibers associated with one nerve are of the same type. The standard for indicating fiber type is histoenzymatic adenosine triphosphatase (ATPase at pH 9.4).
Management
Often, the most important goal for patients with CMT is to maintain movement, muscle strength, and flexibility. Therefore, an interprofessional team approach with occupational therapy (OT), physical therapy (PT), orthotist, podiatrist, and or orthopedic surgeon is recommended. PT typically focuses on muscle-strength training, muscle stretching, and aerobic exercise, while OT can provide education on energy conservation strategies and activities of daily living. Physical therapy should be involved in designing an exercise program that fits a persons personal strengths and flexibility. Bracing can also be used to correct problems caused by CMT. An orthotist may address gait abnormalities by prescribing the use of orthotics.Appropriate footwear is also very important for people with CMT, but they often have difficulty finding well-fitting shoes because of their high arched feet and hammertoes. Due to the lack of good sensory reception in the feet, CMT patients may also need to see a podiatrist for assistance in trimming nails or removing calluses that develop on the pads of the feet. Lastly, patients can also decide to have surgery performed by a podiatrist or an orthopedic surgeon. Surgery may help to stabilize the patients feet or correct progressive problems. These procedures include straightening and pinning the toes, lowering the arch, and sometimes, fusing the ankle joint to provide stability. CMT patients must take extra care to avoid falling as fractures take longer to heal in someone with an underlying disease process. Additionally, the resulting inactivity may cause the CMT to worsen. The Charcot–Marie–Tooth Association classifies the chemotherapy drug vincristine as a "definite high risk" and states, "vincristine has been proven hazardous and should be avoided by all CMT patients, including those with no symptoms." Several corrective surgical procedures can be done to improve the physical condition of the affected individuals.
Orthotics
If the muscles of the lower extremities are weak, it makes sense to prescribe custom-fabricated orthotics. Depending on which muscle groups are affected, the correct orthoses with appropriate functional elements should be prescribed. A weakness of the Musculus tibialis anterior, which lifts the feet, is usually accompanied by an atrophy of the Musculus gastrocnemius which, together with the Musculus soleus, forms the Musculus triceps surae (distal calf muscles), occurs causing the known "stork leg deformity". In most cases, ankle-foot orthoses that have functional elements for the foot lifting and adjustable control of the lowering of the forefoot make sense. Weak calf muscles lead to insufficient activation of the forefoot lever. This leads to an additional increasing uncertainty when standing and walking. If the calf muscles are weak, an orthosis should therefore be equipped with functional elements to activate the forefoot lever. An orthotic joint with an adjustable dynamic dorsiflexion stop with strong spring in combination with a lower leg shell in front of the shin is recommended for this. Such orthoses help to control foot drop, instability of the foot and ankle and offer the patient a better sense of balance when standing and walking without restricting mobility and the dynamics of the ankle joint. Studies confirm the positive effect of orthoses with adjustable functional elements in patients with paralysis of these muscle groups. It is of great advantage if the resistances of the two functional elements can be set separately from one another in the two directions of movement, dorsiflexion and plantar flexion.
Prognosis
The severity of symptoms varies widely even for the same type of CMT. Cases of monozygotic twins with varying levels of disease severity have been reported, showing that identical genotypes are associated with different levels of severity (see penetrance). Some patients are able to live a normal life and are almost or entirely asymptomatic. A 2007 review stated that, "life expectancy is not known to be altered in the majority of cases."
History
The disease is named after those who classically described it: the Frenchman Jean-Martin Charcot (1825–1893), his pupil Pierre Marie (1853–1940), and the Briton Howard Henry Tooth (1856–1925).
See also
Charcot–Marie–Tooth disease classifications
Palmoplantar keratoderma and spastic paraplegia
Hereditary motor and sensory neuropathies
Hereditary motor neuropathies
Low copy repeats
Christinas World
References
External links
Media related to Charcot-Marie-Tooth disease at Wikimedia Commons
Charcot–Marie–Tooth disease at Curlie |
Bad breath | Bad breath, also known as halitosis, is a symptom in which a noticeably unpleasant breath odour is present. It can result in anxiety among those affected. It is also associated with depression and symptoms of obsessive compulsive disorder.The concerns of bad breath may be divided into genuine and non-genuine cases. Of those who have genuine bad breath, about 85% of cases come from inside the mouth. The remaining cases are believed to be due to disorders in the nose, sinuses, throat, lungs, esophagus, or stomach. Rarely, bad breath can be due to an underlying medical condition such as liver failure or ketoacidosis. Non-genuine cases occur when someone complains of having bad breath but other people cannot detect it. This is estimated to make up between 5% and 72% of cases.The treatment depends on the underlying cause. Initial efforts may include tongue cleaning, mouthwash, and flossing. Tentative evidence supports the use of mouthwash containing chlorhexidine or cetylpyridinium chloride. While there is tentative evidence of benefit from the use of a tongue cleaner it is insufficient to draw clear conclusions. Treating underlying disease such as gum disease, tooth decay, tonsil stones, or gastroesophageal reflux disease may help. Counselling may be useful in those who falsely believe that they have bad breath.Estimated rates of bad breath vary from 6% to 50% of the population. Concern about bad breath is the third most common reason people seek dental care, after tooth decay and gum disease. It is believed to become more common as people age. Bad breath is viewed as a social taboo and those affected may be stigmatized. People in the United States spend more than $1 billion per year on mouthwash to treat it.
Signs and symptoms
Bad breath is when a noticeably unpleasant odour is believed to be present on the breath. It can result in anxiety among those affected. It is also associated with depression and symptoms of obsessive compulsive disorder.
Causes
Mouth
In about 90% of genuine halitosis cases, the origin of the odour is in the mouth itself. This is known as intra-oral halitosis, oral malodour or oral halitosis.
The most common causes are odour producing biofilm on the back of the tongue or other areas of the mouth due to poor oral hygiene. This biofilm results in the production of high levels of foul odours. The odours are produced mainly due to the breakdown of proteins into individual amino acids, followed by the further breakdown of certain amino acids to produce detectable foul gases. Volatile sulfur compounds are associated with oral malodour levels, and usually decrease following successful treatment. Other parts of the mouth may also contribute to the overall odour, but are not as common as the back of the tongue. These locations are, in order of descending prevalence, inter-dental and sub-gingival niches, faulty dental work, food-impaction areas in between the teeth, abscesses, and unclean dentures. Oral based lesions caused by viral infections like herpes simplex and HPV may also contribute to bad breath.
The intensity of bad breath may differ during the day, due to eating certain foods (such as garlic, onions, meat, fish, and cheese), smoking, and alcohol consumption. Since the mouth is exposed to less oxygen and is inactive during the night, the odour is usually worse upon awakening ("morning breath"). Bad breath may be transient, often disappearing following eating, drinking, tooth brushing, flossing, or rinsing with specialized mouthwash. Bad breath may also be persistent (chronic bad breath), which affects some 25% of the population in varying degrees.
Tongue
The most common location for mouth-related halitosis is the tongue. Tongue bacteria produce malodourous compounds and fatty acids, and account for 80 to 90% of all cases of mouth-related bad breath. Large quantities of naturally occurring bacteria are often found on the posterior dorsum of the tongue, where they are relatively undisturbed by normal activity. This part of the tongue is relatively dry and poorly cleansed, and the convoluted microbial structure of the tongue dorsum provides an ideal habitat for anaerobic bacteria, which flourish under a continually-forming tongue coating of food debris, dead epithelial cells, postnasal drip and overlying bacteria, living and dead. When left on the tongue, the anaerobic respiration of such bacteria can yield either the putrescent smell of indole, skatole, polyamines, or the "rotten egg" smell of volatile sulfur compounds (VSCs) such as hydrogen sulfide, methyl mercaptan, allyl methyl sulfide, and dimethyl sulfide. The presence of halitosis-producing bacteria on the back of the tongue is not to be confused with tongue coating. Bacteria are invisible to the naked eye, and degrees of white tongue coating are present in most people with and without halitosis. A visible white tongue coating does not always equal the back of the tongue as an origin of halitosis, however a "white tongue" is thought to be a sign of halitosis. In oral medicine generally, a white tongue is considered a sign of several medical conditions. Patients with periodontal disease were shown to have sixfold prevalence of tongue coating compared with normal subjects. Halitosis patients were also shown to have significantly higher bacterial loads in this region compared to individuals without halitosis.
Gums
Gingival crevices are the small grooves between teeth and gums, and they are present in health, although they may become inflamed when gingivitis is present. The difference between a gingival crevice and periodontal pocket is that former is <3mm in depth and the latter is >3mm. Periodontal pockets usually accompany periodontal disease (gum disease). There is some controversy over the role of periodontal diseases in causing bad breath. However, advanced periodontal disease is a common cause of severe halitosis. People with uncontrolled diabetes are more prone to have multiple gingival and periodontal abscess. Their gums are evident with large pockets, where pus accumulation occurs. This nidus of infection can be a potential source for bad breath. Removal of the subgingival calculus (i.e. tartar or hard plaque) and friable tissue has been shown to improve mouth odour considerably. This is accomplished by subgingival scaling and root planing and irrigation with an antibiotic mouth rinse. The bacteria that cause gingivitis and periodontal disease (periodontopathogens) are invariably gram negative and capable of producing VSC. Methyl mercaptan is known to be the greatest contributing VSC in halitosis that is caused by periodontal disease and gingivitis. The level of VSC on breath has been shown to positively correlate with the depth of periodontal pocketing, the number of pockets, and whether the pockets bleed when examined with a dental probe. Indeed, VSC may themselves have been shown to contribute to the inflammation and tissue damage that is characteristic of periodontal disease. However, not all patients with periodontal disease have halitosis, and not all patients with halitosis have periodontal disease. Although patients with periodontal disease are more likely to develop halitosis than the general population, the halitosis symptom was shown to be more strongly associated with degree of tongue coating than with the severity of periodontal disease. Another possible symptom of periodontal disease is a bad taste, which does not necessarily accompany a malodour that is detectable by others.
Other causes
Other less common reported causes from within the mouth include:
Deep carious lesions (dental decay) – which cause localized food impaction and stagnation
Recent dental extraction sockets – fill with blood clot, and provide an ideal habitat for bacterial proliferation
Interdental food packing – (food getting pushed down between teeth) - this can be caused by missing teeth, tilted, spaced or crowded teeth, or poorly contoured approximal dental fillings. Food debris becomes trapped, undergoes slow bacterial putrefaction and release of malodourous volatiles. Food packing can also cause a localized periodontal reaction, characterized by dental pain that is relieved by cleaning the area of food packing with interdental brush or floss.
Acrylic dentures (plastic false teeth) – inadequate denture hygiene practises such as failing to clean and remove the prosthesis each night, may cause a malodour from the plastic itself or from the mouth as microbiota responds to the altered environment. The plastic is actually porous, and the fitting surface is usually irregular, sculpted to fit the edentulous oral anatomy. These factors predispose to bacterial and yeast retention, which is accompanied by a typical smell.
Oral infections
Oral ulceration
Fasting
Stress/anxiety
Menstrual cycle – at mid cycle and during menstruation, increased breath VSC were reported in women.
Smoking – Smoking is linked with periodontal disease, which is the second most common cause of oral maloduor. Smoking also has many other negative effects on the mouth, from increased rates of dental decay to premalignant lesions and even oral cancer.
Alcohol
Volatile foods – e.g. onion, garlic, durian, cabbage, cauliflower and radish. Volatile foodstuffs may leave malodourous residues in the mouth, which are the subject to bacterial putrefaction and VSC release. However, volatile foodstuffs may also cause halitoisis via the blood borne halitosis mechanism.
Medication – often medications can cause xerostomia (dry mouth) which results in increased microbial growth in the mouth.
Nose and sinuses
In this occurrence, the air exiting the nostrils has a pungent odour that differs from the oral odour. Nasal odour may be due to sinus infections or foreign bodies.Halitosis is often stated to be a symptom of chronic rhinosinusitis, however gold standard breath analysis techniques have not been applied. Theoretically, there are several possible mechanisms of both objective and subjective halitosis that may be involved.
Tonsils
There is disagreement as to the proportion of halitosis cases which are caused by conditions of the tonsils. Some claim that the tonsils are the most significant cause of halitosis after the mouth. According to one report, approximately 3% of halitosis cases were related to the tonsils. Conditions of the tonsils which may be associated with halitosis include chronic caseous tonsillitis (cheese-like material can be exuded from the tonsillar crypt orifi), tonsillolithiasis (tonsil stones), and less commonly peritonsillar abscess, actinomycosis, fungating malignancies, chondroid choristoma and inflammatory myofibroblastic tumor.
Esophagus
The lower esophageal sphincter, which is the valve between the stomach and the esophagus, may not close properly due to a hiatal hernia or GERD, allowing acid to enter the esophagus and gases to escape to the mouth. A Zenkers diverticulum may also result in halitosis due to aging food retained in the esophagus.
Stomach
The stomach is considered by most researchers as a very uncommon source of bad breath. The esophagus is a closed and collapsed tube, and continuous flow of gas or putrid substances from the stomach indicates a health problem—such as reflux serious enough to be bringing up stomach contents or a fistula between the stomach and the esophagus—which will demonstrate more serious manifestations than just foul odour.In the case of allyl methyl sulfide (the byproduct of garlics digestion), odour does not come from the stomach, since it does not get metabolized there.
Systemic diseases
There are a few systemic (non-oral) medical conditions that may cause foul breath odour, but these are infrequent in the general population. Such conditions are:
Fetor hepaticus: an example of a rare type of bad breath caused by chronic liver failure.
Lower respiratory tract infections (bronchial and lung infections).
Kidney infections and kidney failure.
Carcinoma.
Trimethylaminuria ("fish odour syndrome").
Diabetes mellitus.
Metabolic conditions, e.g. resulting in elevated blood dimethyl sulfide.Individuals affected by the above conditions often show additional, more diagnostically conclusive symptoms than bad breath alone.
Delusional halitosis
One quarter of the people seeking professional advice on bad breath have an exaggerated concern of having bad breath, known as halitophobia, delusional halitosis, or as a manifestation of olfactory reference syndrome. They are sure that they have bad breath, although many have not asked anyone for an objective opinion. Bad breath may severely affect the lives of some 0.5–1.0% of the adult population.
Diagnosis
Self diagnosis
Scientists have long thought that smelling ones own breath odour is often difficult due to acclimatization, although many people with bad breath are able to detect it in others. Research has suggested that self-evaluation of halitosis is not easy because of preconceived notions of how bad we think it should be. Some people assume that they have bad breath because of bad taste (metallic, sour, fecal, etc.), however bad taste is considered a poor indicator.
Patients often self-diagnose by asking a close friend.One popular home method to determine the presence of bad breath is to lick the back of the wrist, let the saliva dry for a minute or two, and smell the result. This test results in overestimation, as concluded from research, and should be avoided. A better way would be to lightly scrape the posterior back of the tongue with a plastic disposable spoon and to smell the drying residue. Home tests that use a chemical reaction to test for the presence of polyamines and sulfur compounds on tongue swabs are now available, but there are few studies showing how well they actually detect the odour. Furthermore, since breath odour changes in intensity throughout the day depending on many factors, multiple testing sessions may be necessary.
Testing
If bad breath is persistent, and all other medical and dental factors have been ruled out, specialized testing and treatment is required. Hundreds of dental offices and commercial breath clinics now claim to diagnose and treat bad breath. They often use some of several laboratory methods for diagnosis of bad breath:
Halimeter: a portable sulfide monitor used to test for levels of sulfur emissions (to be specific, hydrogen sulfide) in the mouth air. When used properly, this device can be very effective at determining levels of certain VSC-producing bacteria. However, it has drawbacks in clinical applications. For example, other common sulfides (such as mercaptan) are not recorded as easily and can be misrepresented in test results. Certain foods such as garlic and onions produce sulfur in the breath for as long as 48 hours and can result in false readings. The Halimeter is also very sensitive to alcohol, so one should avoid drinking alcohol or using alcohol-containing mouthwashes for at least 12 hours prior to being tested. This analog machine loses sensitivity over time and requires periodic recalibration to remain accurate.
Gas chromatography: portable machines are being studied. This technology is designed to digitally measure molecular levels of major VSCs in a sample of mouth air (such as hydrogen sulfide, methyl mercaptan, and dimethyl sulfide). It is accurate in measuring the sulfur components of the breath and produces visual results in graph form via computer interface.
BANA test: this test is directed to find the salivary levels of an enzyme indicating the presence of certain halitosis-related bacteria.
β-galactosidase test: salivary levels of this enzyme were found to be correlated with oral malodour.Although such instrumentation and examinations are widely used in breath clinics, the most important measurement of bad breath (the gold standard) is the actual sniffing and scoring of the level and type of the odour carried out by trained experts ("organoleptic measurements"). The level of odour is usually assessed on a six-point intensity scale.
Classification
Two main classification schemes exist for bad breath, although neither are universally accepted.The Miyazaki et al. classification was originally described in 1999 in a Japanese scientific publication, and has since been adapted to reflect North American society, especially with regards halitophobia. The classification assumes three primary divisions of the halitosis symptom, namely genuine halitosis, pseudohalitosis and halitophobia. This classification has been suggested to be most widely used, but it has been criticized because it is overly simplistic and is largely of use only to dentists rather than other specialties.
Genuine halitosis
A. Physiologic halitosis
B. Pathologic halitosis
(i) Oral
(ii) Extra-oral
Pseudohalitosis
HalitophobiaThe Tangerman and Winkel classification was suggested in Europe in 2002. This classification focuses only on those cases where there is genuine halitosis, and has therefore been criticized for being less clinically useful for dentistry when compared to the Miyazaki et al. classification.
Intra-oral halitosis
Extra-oral halitosis
A. Blood borne halitosis
(i) Systemic diseases
(ii) Metabolic diseases
(iii) Food
(iv) Medication
B. Non-blood borne halitosis
(i) Upper respiratory tract
(ii) Lower respiratory tractThe same authors also suggested that halitosis can be divided according to the character of the odour into 3 groups:
"Sulfurous or fecal" caused by volatile sulfur compounds (VSC), most notably methyl mercaptan, hydrogen sulfide and dimethyl sulfide.
"Fruity" caused by acetone, present in diabetes.
"Urine-like or ammoniacal" caused by ammonia, dimethyl amine and trimethylamine (TMA), present in trimethylaminuria and uremia.Based on the strengths and weaknesses of previous attempts at classification, a cause based classification has been proposed:
Type 0 (physiologic)
Type 1 (oral)
Type 2 (airway)
Type 3 (gastroesophageal)
Type 4 (blood-borne)
Type 5 (subjective)Any halitosis symptom is potentially the sum of these types in any combination, superimposed on the physiologic odour present in all healthy individuals.
Management
Approaches to improve bad breath may include physical or chemical means to decrease bacteria in the mouth, products to mask the smell, or chemicals to alter the odour creating molecules. Many different interventions have been suggested and trialed such as toothpastes, mouthwashes, lasers, tongue scraping, and mouth rinses. There is no strong evidence to indicate which interventions work and which are more effective. It is recommended that in those who use tobacco products stop. Evidence does not support the benefit of dietary changes or chewing gum.
Mechanical measures
Brushing the teeth may help. While there is evidence of tentative benefit from tongue cleaning it is insufficient to draw clear conclusions. A 2006 Cochrane review found tentative evidence that it might decrease levels of odour molecules. Flossing may be useful.
Mouthwashes
A 2008 systematic review found that antibacterial mouthrinses may help. Mouthwashes often contain antibacterial agents including cetylpyridinium chloride, chlorhexidine, zinc gluconate, zinc chloride, zinc lactate, hydrogen peroxide, chlorine dioxide, amine fluorides, stannous fluoride, hinokitiol, and essential oils. Listerine is one of the well-known mouthwash products composed of different essential oils. Other formulations containing herbal products and probiotics have also been proposed. Cetylpyridinium chloride and chlorhexidine can temporarily stain teeth.
Underlying disease
If gum disease and cavities are present, it is recommended that these be treated.If diseases outside of the mouth are believed to be contributing to the problem, treatment may result in improvements.Counselling may be useful in those who falsely believe that they have bad breath.
Epidemiology
It is difficult for researchers to make estimates of the prevalence of halitosis in the general population for several reasons. Firstly, halitosis is subject to societal taboo and stigma, which may impact individuals willingness to take part in such studies or to report accurately their experience of the condition. Secondly, there is no universal agreement about what diagnostic criteria and what detection methods should be used to define which individuals have halitosis and which do not. Some studies rely on self reported estimation of halitosis, and there is contention as to whether this is a reliable predictor of actual halitosis or not. In reflection of these problems, reported epidemiological data are widely variable.
History, society and culture
The earliest known mention of bad breath occurs in ancient Egypt, where detailed recipes for toothpaste are made before the Pyramids are built. The 1550 BC Ebers Papyrus describes tablets to cure bad breath based on incense, cinnamon, myrrh and honey. Hippocratic medicine advocated a mouthwash of red wine and spices to cure bad breath. Alcohol-containing mouthwashes are now thought to exacerbate bad breath as they dry the mouth, leading to increased microbial growth. The Hippocratic Corpus also describes a recipe based on marble powder for females with bad breath. The Ancient Roman physician Pliny wrote about methods to sweeten the breath.Ancient Chinese emperors required visitors to chew clove before an audience. The Talmud describes bad breath as a disability, which could be grounds for legal breaking of a marriage license. Early Islamic theology stressed that the teeth and tongue should be cleaned with a siwak, a stick from the plant Salvadora persica tree. This traditional chewing stick is also called a Miswak, especially used in Saudi Arabia, an essentially is like a natural toothbrush made from twigs. During the Renaissance era, Laurent Joubert, doctor to King Henry III of France states bad breath is "caused by dangerous miasma that falls into the lungs and through the heart, causing severe damages".In B. G. Jefferis and J. L. Nichols "Searchlights on Health" (1919), the following recipe is offered: "[One] teaspoonful of the following mixture after each meal: One ounce chloride of soda, one ounce liquor of potassa, one and one-half ounces phosphate of soda, and three ounces of water."
In the present day, bad breath is one of the biggest social taboos. The general population places great importance on the avoidance of bad breath, illustrated by the annual $1 billion that consumers in the United States spend on deodorant-type mouth (oral) rinses, mints, and related over-the-counter products. Many of these practices are merely short term attempts at masking the odour. Some authors have suggested that there is an evolutionary basis to concern over bad breath. An instinctive aversion to unpleasant odours may function to detect spoiled food sources and other potentially invective or harmful substances. Body odours in general are thought to play an important role in mate selection in humans, and unpleasant odour may signal disease, and hence a potentially unwise choice of mate. Although reports of bad breath are found in the earliest medical writings known, the social stigma has likely changed over time, possibly partly due to sociocultural factors involving advertising pressures. As a result, the negative psychosocial aspects of halitosis may have worsened, and psychiatric conditions such as halitophobia are probably more common than historically. There have been rare reports of people committing suicide because of halitosis, whether there is genuine halitosis or not.
Etymology
The word halitosis is derived from the Latin word halitus, meaning breath, and the Greek suffix -osis meaning diseased or a condition of. With modern consumerism, there has been a complex interplay of advertising pressures and the existing evolutionary aversion to malodour. Contrary to the popular belief that Listerine coined the term halitosis, its origins date to before the products existence, being coined by physician Joseph William Howe in his 1874 book The Breath, and the Diseases Which Give It a Fetid Odor, although it only became commonly used in the 1920s when a marketing campaign promoted Listerine as a solution for "chronic halitosis". The company was the first to manufacture mouth washes in the United States. According to Freakonomics: Listerine "...was invented in the nineteenth century as powerful surgical antiseptic. It was later sold, in distilled form, as both a floor cleaner and a cure for gonorrhea. But it wasnt a runaway success until the 1920s, when it was pitched as a solution for "chronic halitosis"— a then obscure medical term for bad breath. Listerines new ads featured forlorn young women and men, eager for marriage but turned off by their mates rotten breath. "Can I be happy with him in spite of that?" one maiden asked herself. Until that time, bad breath was not conventionally considered such a catastrophe, but Listerine changed that. As the advertising scholar James B. Twitchell writes, "Listerine did not make mouthwash as much as it made halitosis." In just seven years, the companys revenues rose from $115,000 to more than $8 million."
Alternative medicine
According to traditional Ayurvedic medicine, chewing areca nut and betel leaf is a remedy for bad breath. In South Asia, it was a custom to chew areca or betel nut and betel leaf among lovers because of the breath-freshening and stimulant drug properties of the mixture. Both the nut and the leaf are mild stimulants and can be addictive with repeated use. The betel nut will also cause dental decay and red or black staining of teeth when chewed. Both areca nut and betel leaf chewing, however, can cause premalignant lesions such as leukoplakia and submucous fibrosis, and are recognized risk factors for oral and oropharyngeal squamous cell carcinoma (oral cancer).Practitioners and purveyors of alternative medicine sell a vast range of products that claim to be beneficial in treating halitosis, including dietary supplements, vitamins, and oral probiotics. Halitosis is often claimed to be a symptom of "candida hypersensitivity syndrome" or related diseases, and is claimed to be treatable with antifungal medications or alternative medications to treat fungal infections.
Research
In 1996, the International Society for Breath Odor Research (ISBOR) was formed to promote multidisciplinary research on all aspects of breath odours.
References
== External links == |
Child abuse | Child abuse or child maltreatment is physical, sexual, and/or psychological maltreatment or neglect of a child or children, especially by a parent or a caregiver. Child abuse may include any act or failure to act by a parent or a caregiver that results in actual or potential harm to a child and can occur in a childs home, or in the organizations, schools, or communities the child interacts with.
The terms child abuse and child maltreatment are often used interchangeably, although some researchers make a distinction between them, treating child maltreatment as an umbrella term to cover neglect, exploitation, and trafficking.
Different jurisdictions have different requirements for mandatory reporting and have developed different definitions of what constitutes child abuse, and therefore have different criteria to remove children from their families or to prosecute a criminal charge.
History
As late as the 19th century, cruelty to children, perpetrated by employers and teachers, was commonplace and widespread, and corporal punishment was customary in many countries. But, in the first half of the 19th century, pathologists studying filicide (the parental killing of children) reported cases of death from paternal rage, recurrent physical maltreatment, starvation, and sexual abuse. In an 1860 paper, the great French forensic medical expert Auguste Ambroise Tardieu gathered together a series of 32 such cases, of which 18 were fatal, the children dying from starvation and/or recurrent physical abuse; it included the case of Adeline Defert, who was returned by her grandparents at the age of 8, and for 9 years tortured by her parents – whipped every day, hung up by her thumbs and beaten with a nailed plank, burnt with hot coals and her wounds bathed in nitric acid, and deflorated with a baton. Tardieu made home visits and observed the effect on the children; he noticed that the sadness and fear on their faces disappeared when they were placed under protection. He commented, "When we consider the tender age of these poor defenceless beings, subjected daily and almost hourly to savage atrocities, unimaginable tortures and harsh privation, their lives one long martyrdom – and when we face the fact that their tormentors are the very mothers who gave them life, we are confronted with one of the most appalling problems that can disturb the soul of a moralist, or the conscience of justice". His observations were echoed by Boileau de Castélnau (who introduced the term misopédie – hatred of children), and confirmed by Aubry and several theses.These early French observations failed to cross the language barrier, and other nations remained ignorant of the cause of many traumatic lesions in infants and toddlers; almost one hundred years would pass before humankind began to systematically confront Tardieus "appalling problem". In the 20th century, evidence began to accumulate from pathology and paediatric radiology, particularly in relation to chronic subdural haematoma and limb fractures: subdural haematoma had a curious bimodal distribution, idiopathic in infants and traumatic in adults, while unexplained ossifying periostitis of the long bones was similar to that occurring after breech extractions. In 1946, John Caffey, the American founder of paediatric radiology, drew attention to the association of long bone fractures and chronic subdural haematoma, and, in 1955, it was noticed that infants removed from the care of aggressive, immature and emotionally ill parents developed no new lesions.As a result, professional inquiry into the topic began again in the 1960s. The July 1962 publication of the paper "The Battered Child-Syndrome" authored principally by a pediatric psychiatrist C. Henry Kempe and published in The Journal of the American Medical Association represents the moment that child maltreatment entered mainstream awareness. Before the articles publication, injuries to children—even repeated bone fractures—were not commonly recognized as the results of intentional trauma. Instead, physicians often looked for undiagnosed bone diseases or accepted parents accounts of accidental mishaps such as falls or assaults by neighborhood bullies.: 100–103 The study of child abuse emerged as an academic discipline in the early 1970s in the United States. Elisabeth Young-Bruehl maintained that despite the growing numbers of child advocates and interest in protecting children which took place, the grouping of children into "the abused" and the "non-abused" created an artificial distinction that narrowed the concept of childrens rights to simply protection from maltreatment, and blocked investigation of how children are discriminated against in society generally. Another effect of the way child abuse and neglect have been studied, according to Young-Bruehl, was to close off consideration of how children themselves perceive maltreatment and the importance they place on adults attitudes toward them. Young-Bruehl wrote that when the belief in childrens inherent inferiority to adults is present in society, all children suffer whether or not their treatment is labeled as "abuse".: 15–16
Definitions
Definitions of what constitutes child abuse vary among professionals, between social and cultural groups, and across time. The terms abuse and maltreatment are often used interchangeably in the literature.: 11 Child maltreatment can also be an umbrella term covering all forms of child abuse and child neglect. Defining child maltreatment depends on prevailing cultural values as they relate to children, child development, and parenting. Definitions of child maltreatment can vary across the sectors of society which deal with the issue, such as child protection agencies, legal and medical communities, public health officials, researchers, practitioners, and child advocates. Since members of these various fields tend to use their own definitions, communication across disciplines can be limited, hampering efforts to identify, assess, track, treat, and prevent child maltreatment.: 3 In general, abuse refers to (usually deliberate) acts of commission while neglect refers to acts of omission. Child maltreatment includes both acts of commission and acts of omission on the part of parents or caregivers that cause actual or threatened harm to a child. Some health professionals and authors consider neglect as part of the definition of abuse, while others do not; this is because the harm may have been unintentional, or because the caregivers did not understand the severity of the problem, which may have been the result of cultural beliefs about how to raise a child. Delayed effects of child abuse and neglect, especially emotional neglect, and the diversity of acts that qualify as child abuse, are also factors.The World Health Organization (WHO) defines child abuse and child maltreatment as "all forms of physical and/or emotional ill-treatment, sexual abuse, neglect or negligent treatment or commercial or other exploitation, resulting in actual or potential harm to the childs health, survival, development or dignity in the context of a relationship of responsibility, trust or power." The WHO also says, "Violence against children includes all forms of violence against people under 18 years old, whether perpetrated by parents or other caregivers, peers, romantic partners, or strangers." In the United States, the Centers for Disease Control and Prevention (CDC) uses the term child maltreatment to refer to both acts of commission (abuse), which include "words or overt actions that cause harm, potential harm, or threat of harm to a child", and acts of omission (neglect), meaning "the failure to provide for a childs basic physical, emotional, or educational needs or to protect a child from harm or potential harm".: 11 The United States federal Child Abuse Prevention and Treatment Act defines child abuse and neglect as, at minimum, "any recent act or failure to act on the part of a parent or caretaker which results in death, serious physical or emotional harm, sexual abuse or exploitation" or "an act or failure to act which presents an imminent risk of serious harm".
Forms of abuse
As of 2006, the World Health Organization distinguishes four types of child maltreatment: physical abuse; sexual abuse; emotional (or psychological) abuse; and neglect.
Physical abuse
Among professionals and the general public, there is disagreement as to what behaviors constitute physical abuse of a child. Physical abuse often does not occur in isolation but as part of a constellation of behaviors including authoritarian control, anxiety-provoking behavior, and a lack of parental warmth. The WHO defines physical abuse as:
Intentional use of physical force against the child that results in – or has a high likelihood of resulting in – harm for the childs health, survival, development, or dignity. This includes hitting, beating, kicking, shaking, biting, strangling, scalding, burning, poisoning, and suffocating. Much physical violence against children in the home is inflicted with the object of punishing.
Overlapping definitions of physical abuse and physical punishment of children highlight a subtle or non-existent distinction between abuse and punishment, but most physical abuse is physical punishment "in intent, form, and effect". As of 2006, for instance, Paulo Sergio Pinheiro wrote in the UN Secretary-Generals Study on Violence Against Children:
Corporal punishment involves hitting (smacking, slapping, spanking) children, with the hand or with an implement – whip, stick, belt, shoe, wooden spoon, etc. But it can also involve, for example, kicking, shaking or throwing children, scratching, pinching, biting, pulling hair or boxing ears, forcing children to stay in uncomfortable positions, burning, scalding, or forced ingestion (for example, washing childrens mouths out with soap or forcing them to swallow hot spices).
Most nations with child abuse laws deem the deliberate infliction of serious injuries, or actions that place the child at obvious risk of serious injury or death, to be illegal. Bruises, scratches, burns, broken bones, lacerations — as well as repeated "mishaps," and rough treatment that could cause physical injuries — can be physical abuse. Multiple injuries or fractures at different stages of healing can raise suspicion of abuse.
The psychologist Alice Miller, noted for her books on child abuse, took the view that humiliations, spankings, and beatings, slaps in the face, etc. are all forms of abuse, because they injure the integrity and dignity of a child, even if their consequences are not visible right away.Physical abuse as a child can lead to physical and mental difficulties in the future, including re-victimization, personality disorders, post-traumatic stress disorder (PTSD), dissociative disorders, depression, anxiety, suicidal ideation, eating disorders, substance use disorders, and aggression. Physical abuse in childhood has also been linked to homelessness in adulthood.
Sexual abuse
Child sexual abuse (CSA) is a form of child abuse in which an adult or older adolescent abuses a child for sexual stimulation. Sexual abuse refers to the participation of a child in a sexual act aimed toward the physical gratification or the financial profit of the person committing the act. Forms of CSA include asking or pressuring a child to engage in sexual activities (regardless of the outcome), indecent exposure of the genitals to a child, displaying pornography to a child, actual sexual contact with a child, physical contact with the childs genitals, viewing of the childs genitalia without physical contact, or using a child to produce child pornography. Selling the sexual services of children may be viewed and treated as child abuse rather than simple incarceration.Effects of child sexual abuse on the victim(s) include guilt and self-blame, flashbacks, nightmares, insomnia, fear of things associated with the abuse (including objects, smells, places, doctors visits, etc.), self-esteem difficulties, sexual dysfunction, chronic pain, addiction, self-injury, suicidal ideation, somatic complaints, depression, PTSD, anxiety, other mental illnesses including borderline personality disorder and dissociative identity disorder, propensity to re-victimization in adulthood, bulimia nervosa, and physical injury to the child, among other problems. Children who are the victims are also at an increased risk of sexually transmitted infections due to their immature immune systems and a high potential for mucosal tears during forced sexual contact. Sexual victimization at a young age has been correlated with several risk factors for contracting HIV including decreased knowledge of sexual topics, increased prevalence of HIV, engagement in risky sexual practices, condom avoidance, lower knowledge of safe sex practices, frequent changing of sexual partners, and more years of sexual activity.As of 2016, in the United States, about 15% to 25% of women and 5% to 15% of men were sexually abused when they were children. Most sexual abuse offenders are acquainted with their victims; approximately 30% are relatives of the child, most often brothers, sisters, fathers, mothers, uncles or cousins; around 60% are other acquaintances such as friends of the family, babysitters, or neighbours; strangers are the offenders in approximately 10% of child sexual abuse cases. In over one-third of cases, the perpetrator is also a minor.In 1999 the BBC reported on the RAHI Foundations survey of sexual abuse in India, in which 76% of respondents said they had been abused as children, 40% of those stating the perpetrator was a family member.United States federal prosecutors registered multiple charges against a South Korean man for reportedly running the worlds "largest dark web child porn marketplace." Reportedly, the English translated website "Welcome to Video", which has now been taken consisted of more than 200,000 videos or 8TB of data showing sexual acts involving infants, children and toddlers and processed about 7,300 Bitcoin, i.e. $730,000 worth of transactions.
Psychological abuse
There are multiple definitions of child psychological abuse:
In 2013, the American Psychiatric Association (APA) added Child Psychological Abuse to the DSM-5, describing it as "nonaccidental verbal or symbolic acts by a childs parent or caregiver that result, or have reasonable potential to result, in significant psychological harm to the child."
In 1995, APSAC defined it as: spurning, terrorizing, isolating, exploiting, corrupting, denying emotional responsiveness, or neglect" or "A repeated pattern of caregiver behavior or extreme incident(s) that convey to children that they are worthless, flawed, unloved, unwanted, endangered, or only of value in meeting anothers needs"
In the United States, states laws vary, but most have laws against "mental injury"
Some have defined it as the production of psychological and social defects in the growth of a child as a result of behavior such as loud yelling, coarse and rude attitude, inattention, harsh criticism, and denigration of the childs personality. Other examples include name-calling, ridicule, degradation, destruction of personal belongings, torture or killing of a pet, excessive criticism, inappropriate or excessive demands, withholding communication, and routine labeling or humiliation.In 2014, the APA found that child psychological abuse is the most prevalent form of childhood abuse in the United States, affecting nearly 3 million children annually. Research has suggested that the consequences of child psychological abuse may be equally as harmful as those of sexual or physical abuse.Victims of emotional abuse may react by distancing themselves from the abuser, internalizing the abusive words, or fighting back by insulting the abuser. Emotional abuse can result in abnormal or disrupted attachment development, a tendency for victims to blame themselves (self-blame) for the abuse, learned helplessness, and overly passive behavior.
Neglect
Child neglect is the failure of a parent or other person with responsibility for the child, to provide needed food, clothing, shelter, medical care, or supervision to the degree that the childs health, safety or well-being may be threatened with harm. Neglect is also a lack of attention from the people surrounding a child, and the non-provision of the relevant and adequate necessities for the childs survival, which would be a lack of attention, love, and nurturing.Some observable signs of child neglect include: the child is frequently absent from school, begs or steals food or money, lacks needed medical and dental care, is consistently dirty, or lacks appropriate clothing for the weather. The 2010 Child Maltreatment Report (NCANDS), a yearly United States federal government report based on data supplied by state Child Protective Services (CPS) Agencies in the U.S., found that neglect/neglectful behavior was the "most common form of child maltreatment ".Neglectful acts can be divided into six sub-categories:
Supervisory neglect: characterized by the absence of a parent or guardian which can lead to physical harm, sexual abuse, or criminal behavior;
Physical neglect: characterized by the failure to provide the basic physical necessities, such as a safe and clean home;
Medical neglect: characterized by the lack of providing medical care;
Emotional neglect: characterized by a lack of nurturance, encouragement, and support;
Educational neglect: characterized by the caregivers lack to provide an education and additional resources to actively participate in the school system; and
Abandonment: when the parent or guardian leaves a child alone for a long period of time without a babysitter or caretaker.Neglected children may experience delays in physical and psychosocial development, possibly resulting in psychopathology and impaired neuropsychological functions including executive function, attention, processing speed, language, memory and social skills. Researchers investigating maltreated children have repeatedly found that neglected children in the foster and adoptive populations manifest different emotional and behavioral reactions to regain lost or secure relationships and are frequently reported to have disorganized attachments and a need to control their environment. Such children are not likely to view caregivers as being a source of safety, and instead typically show an increase in aggressive and hyperactive behaviors which may disrupt healthy or secure attachment with their adopted parents. These children seem to have learned to adapt to an abusive and inconsistent caregiver by becoming cautiously self-reliant, and are often described as glib, manipulative and disingenuous in their interactions with others as they move through childhood. Children who are victims of neglect can have a more difficult time forming and maintaining relationships, such as romantic or friendship, later in life due to the lack of attachment they had in their earlier stages of life.
Effects
Child abuse can result in immediate adverse physical effects but it is also strongly associated with developmental problems and with many chronic physical and psychological effects, including subsequent ill-health, including higher rates of chronic conditions, high-risk health behaviors and shortened lifespan. Child abuse has also been linked to suicide, according to a May 2019 study, published in the Cambridge University Press.Maltreated children may be at risk to become maltreating adults. A 1991 source reported that studies indicate that 90 percent of maltreating adults were maltreated as children.
Emotional
Physical and emotional abuse have comparable effects on a childs emotional state and have been linked to childhood depression, low self-compassion, and negative automatic thoughts. Some research suggests that high stress levels from child abuse may cause structural and functional changes within the brain, and therefore cause emotional and social disruptions. Abused children can grow up experiencing insecurities, low self-esteem, and lack of development. Many abused children experience ongoing difficulties with trust, social withdrawal, trouble in school, and forming relationships.Babies and other young children can be affected differently by abuse than their older counterparts. Babies and pre-school children who are being emotionally abused or neglected may be overly affectionate towards strangers or people they have not known for very long. They can lack confidence or become anxious, appear to not have a close relationship with their parent, exhibit aggressive behavior or act nasty towards other children and animals. Older children may use foul language or act in a markedly different way to other children at the same age, struggle to control strong emotions, seem isolated from their parents, lack social skills or have few, if any, friends.Children can also experience reactive attachment disorder (RAD). RAD is defined as markedly disturbed and developmentally inappropriate social relatedness, that usually begins before the age of 5 years. RAD can present as a persistent failure to start or respond in a developmentally appropriate fashion to most social situations. The long-term impact of emotional abuse has not been studied widely, but recent studies have begun to document its long-term consequences. Emotional abuse has been linked to increased depression, anxiety, and difficulties in interpersonal relationships (Spertus, Wong, Halligan, & Seremetis, 2003). Victims of child abuse and neglect are more likely to commit crimes as juveniles and adults.Domestic violence also takes its toll on children; although the child is not the one being abused, the child witnessing the domestic violence is greatly influential as well. Research studies conducted such as the "Longitudinal Study on the Effects of Child Abuse and Childrens Exposure to Domestic Violence", show that 36.8% of children engage in felony assault compared to the 47.5% of abused/assaulted children. Research has shown that children exposed to domestic violence increases the chances of experienced behavioral and emotional problems (depression, irritability, anxiety, academic problems, and problems in language development).Overall, emotional effects caused by child abuse and even witnessing abuse can result in long-term and short-term effects that ultimately affect a childs upbringing and development.
Physical
The immediate physical effects of abuse or neglect can be relatively minor (bruises or cuts) or severe (broken bones, hemorrhage, death). Certain injuries, such as rib fractures or femoral fractures in infants that are not yet walking, may increase suspicion of child physical abuse, although such injuries are only seen in a fraction of children suffering physical abuse. Cigarette burns or scald injuries may also prompt evaluation for child physical abuse.The long-term impact of child abuse and neglect on physical health and development can be:
Shaken baby syndrome. Shaking a baby is a common form of child abuse that often results in permanent neurological damage (80% of cases) or death (30% of cases). Damage results from intracranial hypertension (increased pressure in the skull) after bleeding in the brain, damage to the spinal cord and neck, and rib or bone fractures.
Impaired brain development. Child abuse and neglect have been shown, in some cases, to cause important regions of the brain to fail to form or grow properly, resulting in impaired development. Structural brain changes as a result of child abuse or neglect include overall smaller brain volume, hippocampal atrophy, prefrontal cortex dysfunction, decreased corpus callosum density, and delays in the myelination of synapses. These alterations in brain maturation have long-term consequences for cognitive, language, and academic abilities. In addition, these neurological changes impact the amygdala and hypothalamic-pituitary-adrenal (HPA) axis which are involved in stress response and may cause PTSD symptoms.
Poor physical health. In addition to possible immediate adverse physical effects, household dysfunction and childhood maltreatment are strongly associated with many chronic physical and psychological effects, including subsequent ill-health in childhood, adolescence and adulthood, with higher rates of chronic conditions, high-risk health behaviors and shortened lifespan. Adults who experienced abuse or neglect during childhood are more likely to have physical ailments such as allergies, arthritis, asthma, bronchitis, high blood pressure, and ulcers. There may be a higher risk of developing cancer later in life, as well as possible immune dysfunction.
Exposure to violence during childhood is associated with shortened telomeres and with reduced telomerase activity. The increased rate of telomere length reduction correlates to a reduction in lifespan of 7 to 15 years.
Data from a recent study supports previous findings that specific neurobiochemical changes are linked to exposure to violence and abuse, several biological pathways can possibly lead to the development of illness, and certain physiological mechanisms can moderate how severe illnesses become in patients with past experience with violence or abuse.
Recent studies give evidence of a link between stress occurring early in life and epigenetic modifications that last into adulthood.
Adverse Childhood Experiences Study
The Adverse Childhood Experiences Study is a long-running investigation into the relationship between childhood adversity, including various forms of abuse and neglect, and health problems in later life. The initial phase of the study was conducted in San Diego, California from 1995 to 1997. The World Health Organization summarizes the study as: "childhood maltreatment and household dysfunction contribute to the development – decades later – of the chronic diseases that are the most common causes of death and disability in the United States... A strong relationship was seen between the number of adverse experiences (including physical and sexual abuse in childhood) and self-reports of cigarette smoking, obesity, physical inactivity, alcoholism, drug abuse, depression, attempted suicide, sexual promiscuity and sexually transmitted diseases in later life."A long-term study of adults retrospectively reporting adverse childhood experiences including verbal, physical and sexual abuse, as well as other forms of childhood trauma found 25.9% of adults reported verbal abuse as children, 14.8% reported physical abuse, and 12.2% reported sexual abuse. Data from the Centers for Disease Control and Prevention (CDC) and Behavioral Risk Factor Surveillance System corroborate these high rates. There is a high correlation between the number of different adverse childhood experiences (A.C.E.s) and risk for poor health outcomes in adults including cancer, heart attack, mental illness, reduced longevity, and drug and alcohol abuse. An anonymous self-reporting survey of Washington State students finds 6–7% of 8th, 10th and 12th grade students actually attempt suicide. Rates of depression are twice as high. Other risk behaviors are even higher. There is a relationship between child physical and sexual abuse and suicide. For legal and cultural reasons as well as fears by children of being taken away from their parents most childhood abuse goes unreported and unsubstantiated.
It has been discovered that childhood abuse can lead to the addiction of drugs and alcohol in adolescence and adult life. Studies show that any type of abuse experienced in childhood can cause neurological changes making an individual more prone to addictive tendencies. A significant study examined 900 court cases of children who had experienced sexual and physical abuse along with neglect. The study found that a large sum of the children who were abused are now currently addicted to alcohol. This case study outlines how addiction is a significant effect of childhood abuse.
Psychological
Children who have a history of neglect or physical abuse are at risk of developing psychiatric problems, or a disorganized attachment style. In addition, children who experience child abuse or neglect are 59% more likely to be arrested as juveniles, 28% more likely to be arrested as adults, and 30% more likely to commit violent crime. Disorganized attachment is associated with a number of developmental problems, including dissociative symptoms, as well as anxiety, depressive, and acting out symptoms. A study by Dante Cicchetti found that 80% of abused and maltreated infants exhibited symptoms of disorganized attachment. When some of these children become parents, especially if they have PTSD, dissociative symptoms, and other sequelae of child abuse, they may encounter difficulty when faced with their infant and young childrens needs and normative distress, which may in turn lead to adverse consequences for their childs social-emotional development. Additionally, children may find it difficult to feel empathy towards themselves or others, which may cause them to feel alone and unable to make friends. Despite these potential difficulties, psychosocial intervention can be effective, at least in some cases, in changing the ways maltreated parents think about their young children.Victims of childhood abuse also have different types of physical health problems later in life. Some reportedly have some type of chronic head, abdominal, pelvic, or muscular pain with no identifiable reason. Even though the majority of childhood abuse victims know or believe that their abuse is, or can be, the cause of different health problems in their adult life, for the great majority their abuse was not directly associated with those problems, indicating that they were most likely diagnosed with other possible causes for their health problems, instead of their childhood abuse. One long-term study found that up to 80% of abused people had at least one psychiatric disorder at age 21, with problems including depression, anxiety, eating disorders, and suicide attempts. One Canadian hospital found that between 36% and 76% of women mental health outpatients had been sexually abused, as had 58% of women and 23% of men schizophrenic inpatients. A recent study has discovered that a crucial structure in the brains reward circuits is compromised by childhood abuse and neglect, and predicts Depressive Symptoms later in life.In the case of 23 of the 27 illnesses listed in the questionnaire of a French INSEE survey, some statistically significant correlations were found between repeated illness and family traumas encountered by the child before the age of 18 years. According to Georges Menahem, the French sociologist who found out these correlations by studying health inequalities, these relationships show that inequalities in illness and suffering are not only social. Health inequality also has its origins in the family, where it is associated with the degrees of lasting affective problems (lack of affection, parental discord, the prolonged absence of a parent, or a serious illness affecting either the mother or father) that individuals report having experienced in childhood.Many children who have been abused in any form develop some sort of psychological disorder. These disorders may include: anxiety, depression, eating disorders, OCD, co-dependency, |
Child abuse | or even a lack of human connections. There is also a slight tendency for children who have been abused to become child abusers themselves. In the U.S. in 2013, of the 294,000 reported child abuse cases only 81,124 received any sort of counseling or therapy. Treatment is greatly important for abused children.On the other hand, there are some children who are raised in child abuse, but who manage to do unexpectedly well later in life regarding the preconditions. Such children have been termed dandelion children, as inspired from the way that dandelions seem to prosper irrespective of soil, sun, drought, or rain. Such children (or currently grown-ups) are of high interest in finding factors that mitigate the effects of child abuse.
Causes
Child abuse is a complex phenomenon with multiple causes. No single factor can be identified as to why some adults behave abusively or neglectfully toward children. The World Health Organization (WHO) and the International Society for Prevention of Child Abuse and Neglect (ISPCAN) identify multiple factors at the level of the individual, their relationships, their local community, and their society at large, that combine to influence the occurrence of child maltreatment. At the individual level, studies have shown that age, mental health, and substance use, and a personal history of abuse may serve as risk factors of child abuse. At the level of society, factors contributing to child maltreatment include cultural norms that encourage harsh physical punishment of children, economic inequality, and the lack of social safety nets. WHO and ISPCAN state that understanding the complex interplay of various risk factors is vital for dealing with the problem of child maltreatment.Factors related to relationships include marital strife and tension. Parents who physically abuse their spouses are more likely than others to physically abuse their children. However, it is impossible to know whether marital strife is a cause of child abuse, or if both the marital strife and the abuse are caused by tendencies in the abuser. Parents may also set expectations for their child that are clearly beyond the childs capability (e.g., preschool children who are expected to be totally responsible for self-care or provision of nurturance to parents), and the resulting frustration caused by the childs non-compliance may function as a contributory factor of the occurrence of child abuse.
Most acts of physical violence against children are undertaken with the intent to punish. In the United States, interviews with parents reveal that as many as two thirds of documented instances of physical abuse begin as acts of corporal punishment meant to correct a childs behavior, while a large-scale Canadian study found that three quarters of substantiated cases of physical abuse of children have occurred within the context of physical punishment. Other studies have shown that children and infants who are spanked by parents are several times more likely to be severely assaulted by their parents or suffer an injury requiring medical attention. Studies indicate that such abusive treatment often involves parents attributing conflict to their childs willfulness or rejection, as well as "coercive family dynamics and conditioned emotional responses". Factors involved in the escalation of ordinary physical punishment by parents into confirmed child abuse may be the punishing parents inability to control their anger or judge their own strength, and the parent being unaware of the childs physical vulnerabilities.Children resulting from unintended pregnancies are more likely to be abused or neglected. In addition, unintended pregnancies are more likely than intended pregnancies to be associated with abusive relationships, and there is an increased risk of physical violence during pregnancy. They also result in poorer maternal mental health, and lower mother-child relationship quality.There is some limited evidence that children with moderate or severe disabilities are more likely to be victims of abuse than non-disabled children. A study on child abuse sought to determine: the forms of child abuse perpetrated on children with disabilities; the extent of child abuse; and the causes of child abuse of children with disabilities. A questionnaire on child abuse was adapted and used to collect data in this study. Participants comprised a sample of 31 pupils with disabilities (15 children with vision impairment and 16 children with hearing impairment) selected from special schools in Botswana. The study found that the majority of participants were involved in doing domestic chores. They were also sexually, physically and emotionally abused by their teachers. This study showed that children with disabilities were vulnerable to child abuse in their schools.Substance use disorder can be a major contributing factor to child abuse. One U.S. study found that parents with documented substance use, most commonly alcohol, cocaine, and heroin, were much more likely to mistreat their children, and were also much more likely to reject court-ordered services and treatments. Another study found that over two-thirds of cases of child maltreatment involved parents with substance use disorders. This study specifically found relationships between alcohol and physical abuse, and between cocaine and sexual abuse. Also, parental stress caused by substance increases the likelihood of the minor exhibiting internalizing and externalizing behaviors. Although the abuse victim does not always realize the abuse is wrong, the internal confusion can lead to chaos. Inner anger turns to outer frustration. Once aged 17/18, drink and drugs are used to numb the hurt feelings, nightmares, and daytime flashbacks. Acquisitive crimes to pay for the chemicals are inevitable if the victim is unable to find employment.Unemployment and financial difficulties are associated with increased rates of child abuse. In 2009 CBS News reported that child abuse in the United States had increased during the economic recession. It gave the example of a father who had never been the primary care-taker of the children. Now that the father was in that role, the children began to come in with injuries. Parental mental health has also been seen as a factor towards child maltreatment. According to a recent Childrens HealthWatch study, mothers with positive symptoms of depression display a greater rate of food insecurity, poor health care for their children, and greater number of hospitalizations.The American psychoanalyst Elisabeth Young-Bruehl maintains that harm to children is justified and made acceptable by widely held beliefs in childrens inherent subservience to adults, resulting in a largely unacknowledged prejudice against children she terms childism. She contends that such prejudice, while not the immediate cause of child maltreatment, must be investigated in order to understand the motivations behind a given act of abuse, as well as to shed light on societal failures to support childrens needs and development in general.: 4–6 Founding editor of the International Journal of Childrens Rights, Michael Freeman, also argues that the ultimate causes of child abuse lie in prejudice against children, especially the view that human rights do not apply equally to adults and children. He writes, "the roots of child abuse lie not in parental psycho-pathology or in socio-environmental stress (though their influences cannot be discounted) but in a sick culture which denigrates and depersonalizes, which reduces children to property, to sexual objects so that they become the legitimate victims of both adult violence and lust".
Worldwide
Child abuse is an international public health crisis. Poverty and substance use disorders are common social problems worldwide, and no matter the location, show a similar trend in the correlation to child abuse. Differences in cultural perspectives play a significant role in how children are treated. Laws reflect the populations views on what is acceptable - for example whether child corporal punishment is legal or not.A study conducted by members from several Baltic and Eastern European countries, together with specialists from the United States, examined the causes of child abuse in the countries of Latvia, Lithuania, Macedonia and Moldova. In these countries, respectively, 33%, 42%, 18% and 43% of children reported at least one type of child abuse. According to their findings, there was a series of correlations between the potential risk factors of parental employment status, alcohol abuse, and family size within the abuse ratings. In three of the four countries, parental substance use was considerably correlated with the presence of child abuse, and although it was a lower percentage, still showed a relationship in the fourth country (Moldova). Each country also showed a connection between the father not working outside of the home and either emotional or physical child abuse. After the fall of the communism regime, some positive changes have followed with regard to tackling child abuse. While there is a new openness and acceptance regarding parenting styles and close relationships with children, child abuse has certainly not ceased to exist. While controlling parenting may be less of a concern, financial difficulty, unemployment, and substance use remain dominating factors in child abuse throughout Eastern Europe.There is some evidence that countries in conflict or transitioning out of conflict have increased rates of child abuse. This increasing prevalence may be secondary to displacement and family disruption, as well as trauma.Asian parenting perspectives hold different ideals from American culture. Many have described their traditions as including physical and emotional closeness that ensures a lifelong bond between parent and child, as well as establishing parental authority and child obedience through harsh discipline. Balancing disciplinary responsibilities within parenting is common in many Asian cultures, including China, Japan, Singapore, Vietnam and Korea. To some cultures, forceful parenting may be seen as abuse, but in other societies such as these, the use of force is looked at as a reflection of parental devotion.These cultural differences can be studied from many perspectives. Most importantly, overall parental behavior is genuinely different in various countries. Each culture has their own "range of acceptability," and what one may view as offensive, others may seem as tolerable. Behaviors that are normal to some may be viewed as abusive to others, all depending on the societal norms of that particular country. The differences in these cultural beliefs demonstrate the importance of examining all cross-cultural perspectives when studying the concept of child abuse. Some professionals argue that cultural norms that sanction physical punishment are one of the causes of child abuse, and have undertaken campaigns to redefine such norms.As of 2006, between 25,000 and 50,000 children in Kinshasa, Democratic Republic of the Congo, had been accused of witchcraft and abandoned. In Malawi it is common practice to accuse children of witchcraft and many children have been abandoned, abused and even killed as a result. In the Nigerian, Akwa Ibom State and Cross River State about 15,000 children were branded as witches.In April 2015, public broadcasting reported that the rate of child abuse in South Korea had increased to 13% compared with the previous year, and 75% of attackers were the childrens own parents.
Possible link to animal abuse
There are studies providing evidence of a link between child abuse and cruelty to animals. A large national survey by the Norwegian Centre for Violence and Traumatic Stress Studies found a "substantial overlap between companion animal abuse and child abuse" and that cruelty to animals "most frequently co-occurred with psychological abuse and less severe forms of physical child abuse," which "resonates with conceptualizations of domestic abuse as an ongoing pattern of psychological abuse and coercive control."
Disclosure and assessment
Suspicion for physical abuse is recommended when injuries occur in a child who is not yet able to walk independently. Additionally, having multiple injuries that are in different stages of healing and having injuries in unusual location, such as the torso, ears, face, or neck, may prompt evaluation for child abuse. Medical professionals may also become suspicious of child abuse when a caregiver is not able to provide an explanation for an injury that is consistent with the type or severity of the injury.In many jurisdictions, suspected abuse, even if not necessarily proven, requires reporting to child protection agencies, such as the Child Protection Services in the United States. Recommendations for healthcare workers, such as primary care providers and nurses, who are often suited to encounter suspected abuse are advised to firstly determine the childs immediate need for safety. A private environment away from suspected abusers is desired for interviewing and examining. Leading statements that can distort the story are avoided. As disclosing abuse can be distressing and sometimes even shameful, reassuring the child that he or she has done the right thing by telling and that they are not bad or that the abuse was not their fault helps in disclosing more information. Dolls are sometimes used to help explain what happened. In Mexico, psychologists trial using cartoons to speak to children who may be more likely to disclose information than to an adult stranger. For the suspected abusers, it is also recommended to use a nonjudgmental, nonthreatening attitude towards them and to withhold expressing shock, in order to help disclose information.A key part of child abuse work is assessment. A few methods of assessment include projective tests, clinical interviews, and behavioral observations.
Projective tests allow for the child to express themselves through drawings, stories, or even descriptions in order to get help establish an initial understanding of the abuse that took place
Clinical interviews are comprehensive interviews performed by professionals to analyze the mental state of the one being interviewed
Behavioral observation gives an insight into things that trigger a childs memory of the abuse through observation of the childs behavior when interacting with other adults or childrenA particular challenge arises where child protection professionals are assessing families where neglect is occurring. Neglect is a complex phenomenon without a universally-accepted definition and professionals cite difficulty in knowing which questions to ask to identify neglect. Younger children, children living in poverty, and children with more siblings are at increased risk of neglect.
Prevention
A support-group structure is needed to reinforce parenting skills and closely monitor the childs well-being. Visiting home nurse or social-worker visits are also required to observe and evaluate the progress of the child and the caretaking situation. The support-group structure and visiting home nurse or social-worker visits are not mutually exclusive. Many studies have demonstrated that the two measures must be coupled together for the best possible outcome.
Studies show that if health and medical care personnel in a structured way ask parents about important psychosocial risk factors in connection with visiting pediatric primary care and, if necessary, offering the parent help may help prevent child maltreatment.Childrens school programs regarding "good touch … bad touch" can provide children with a forum in which to role-play and learn to avoid potentially harmful scenarios. Pediatricians can help identify children at risk of maltreatment and intervene with the aid of a social worker or provide access to treatment that addresses potential risk factors such as maternal depression. Videoconferencing has also been used to diagnose child abuse in remote emergency departments and clinics. Unintended conception increases the risk of subsequent child abuse, and large family size increases the risk of child neglect. Thus, a comprehensive study for the National Academy of Sciences concluded that affordable contraceptive services should form the basis for child abuse prevention. "The starting point for effective child abuse programming is pregnancy planning," according to an analysis for US Surgeon General C. Everett Koop.Findings from research published in 2016 support the importance of family relationships in the trajectory of a childs life: family-targeted interventions are important for improving long-term health, particularly in communities that are socioeconomically disadvantaged.Resources for child-protection services are sometimes limited. According to Hosin (2007), "a considerable number of traumatized abused children do not gain access to protective child-protection strategies." Briere (1992) argues that only when "lower-level violence" of children ceases to be culturally tolerated will there be changes in the victimization and police protection of children.
United States
Child sexual abuse prevention programs were developed in the United States of America during the 1970s and originally delivered to children. Programmes delivered to parents were developed in the 1980s and took the form of one-off meetings, two to three hours long. In the last 15 years, web-based programmes have been developed.
Since 1983, April has been designated Child Abuse Prevention Month in the United States. U.S. President Barack Obama continued that tradition by declaring April 2009 Child Abuse Prevention Month. One way the Federal government of the United States provides funding for child-abuse prevention is through Community-Based Grants for the Prevention of Child Abuse and Neglect (CBCAP).An investigation by The Boston Globe and ProPublica published in 2019 found that the 50 states, the District of Columbia, and Puerto Rico were all out of compliance with the requirements of the Child Abuse Prevention and Treatment Act, and that underfunding of child welfare agencies and substandard procedures in some states caused failures to prevent avoidable child injuries and deaths.
A number of policies and programs have been put in place in the U.S. to try to better understand and to prevent child abuse fatalities, including: safe-haven laws, child fatality review teams, training for investigators, shaken baby syndrome prevention programs, and child abuse death laws which mandate harsher sentencing for taking the life of a child.
Treatments
A number of treatments are available to victims of child abuse. However, children who experience childhood trauma do not heal from abuse easily. Trauma-focused cognitive behavioral therapy, first developed to treat sexually abused children, is now used for victims of any kind of trauma. It targets trauma-related symptoms in children including PTSD, clinical depression and anxiety. It also includes a component for non-offending parents. Several studies have found that sexually abused children undergoing TF-CBT improved more than children undergoing certain other therapies. Data on the effects of TF-CBT for children who experienced non-sexual abuse was not available as of 2006. The purpose of dealing with the thoughts and feelings associated with the trauma is to deal with nightmares, flashbacks and other intrusive experiences that might be spontaneously brought on by any number of discriminative stimuli in the environment or in the individuals brain. This would aid the individual in becoming less fearful of specific stimuli that would arouse debilitating fear, anger, sadness or other negative emotion. In other words, the individual would have some control or mastery over those emotions.Rational Cognitive Emotive Behavior Therapy is another available treatment and is intended to provide abused children and their adoptive parents with positive behavior change, corrective interpersonal skills, and greater control over themselves and their relationships.Parent–child interaction therapy was designed to improve the child-parent relationship following the experience of domestic violence. It targets trauma-related symptoms in infants, toddlers, and preschoolers, including PTSD, aggression, defiance, and anxiety. It is supported by two studies of one sample.School-based programs have also been developed to treat children who are survivors of abuse. This approach teaches children, parents, teachers, and other school staff how to identify the signs of child maltreatment as well as skills that can be helpful in preventing child maltreatment.Other forms of treatment include group therapy, play therapy, and art therapy. Each of these types of treatment can be used to better assist the client, depending on the form of abuse they have experienced. Play therapy and art therapy are ways to get children more comfortable with therapy by working on something that they enjoy (coloring, drawing, painting, etc.). The design of a childs artwork can be a symbolic representation of what they are feeling, relationships with friends or family, and more. Being able to discuss and analyze a childs artwork can allow a professional to get a better insight of the child.Interventions targeting the offending parents are rare. Parenting training can prevent child abuse in the short term, and help children with a range of emotional, conduct and behavioral challenges, but there is insufficient evidence about whether it has impact on parents who already abuse their children. Abuse-focused cognitive behavioral therapy may target offending parents, but most interventions exclusively target victims and non-offending parents.
Prevalence
Child abuse is complex and difficult to study. According to the World Health Organization (WHO), estimates of the rates of child maltreatment vary widely by country, depending on how child maltreatment is defined, the type of maltreatment studied, the scope and quality of data gathered, and the scope and quality of surveys that ask for self-reports from victims, parents, and caregivers. Despite these limitations, international studies show that a quarter of all adults report experiencing physical abuse as children, and that 1 in 5 women and 1 in 13 men report experiencing childhood sexual abuse. Emotional abuse and neglect are also common childhood experiences.As of 2014, an estimated 41,000 children under 15 are victims of homicide each year. The WHO states that this number underestimates the true extent of child homicide; a significant proportion of child deaths caused by maltreatment are incorrectly attributed to unrelated factors such as falls, burns, and drowning. Also, girls are particularly vulnerable to sexual violence, exploitation and abuse in situations of armed conflict and refugee settings, whether by combatants, security forces, community members, aid workers, or others.
United States
The National Research Council wrote in 1993 that "...the available evidence suggests that child abuse and neglect is an important, prevalent problem in the United States [...] Child abuse and neglect are particularly important compared with other critical childhood problems because they are often directly associated with adverse physical and mental health consequences in children and families".: 6 In 2012, Child Protective Services (CPS) agencies estimated that about 9 out of 1000 children in the United States were victims of child maltreatment. Most (78%) were victims of neglect. Physical abuse, sexual abuse, and other types of maltreatment, were less common, making up 18%, 9%, and 11% of cases, respectively ("other types" included emotional abuse, parental substance use, and inadequate supervision). According to data reported by the Childrens Bureau of the US Department of Health and Human Services, more than 3.5 million allegations of child abuse were looked into by child protective services who in turn confirmed 674,000 of those cases in 2017. However, CPS reports may underestimate the true scope of child maltreatment. A non-CPS study estimated that one in four children experience some form of maltreatment in their lifetimes, according to the Centers for Disease Control and Prevention (CDC).In February 2017, the American Public Health Association published a Washington University study estimating 37% of American children experienced a child protective services investigation by age 18 (or 53% if African American).According to David Finkelhor who tracked Child Maltreatment Report (NCANDS) data from 1990 to 2010, sexual abuse had declined 62% from 1992 to 2009 and the long-term trend for physical abuse was also down by 56% since 1992. He stated: "It is unfortunate that information about the trends in child maltreatment are not better publicized and more widely known. The long-term decline in sexual and physical abuse may have important implications for public policy."In 1998, Douglas Besharov, the first Director of the U.S. Center on Child Abuse and Neglect, stated "the existing laws are often vague and overly broad" and there was a "lack of consensus among professionals and Child Protective Services (CPS), personnel about what the terms abuse and neglect mean".A child abuse fatality occurs when a childs death is the result of abuse or neglect, or when abuse or neglect are contributing factors to a childs death. In the United States, 1,730 children died in 2008 due to factors related to abuse; this is a rate of 2 per 100,000 U.S. children. Family situations which place children at risk include moving, unemployment, and having non-family members living in the household. A number of policies and programs have been put in place in the U.S. to try to better understand and to prevent child abuse fatalities, including: safe-haven laws, child fatality review teams, training for investigators, shaken baby syndrome prevention programs, and child abuse death laws which mandate harsher sentencing for taking the life of a child.In 1995, a one-off judicial decision found that parents failing to sufficiently speak the national standard language at home to their children was a form of child abuse by a judge in a child custody matter.
Examples
Child labor
Child trafficking is the recruitment, transportation, transfer, harbouring or receipt of children for the purpose of exploitation. Children are trafficked for purposes such as of commercial sexual exploitation, bonded labour, camel jockeying, child domestic labour, drug couriering, child soldiering, illegal adoptions, and begging. It is difficult to obtain reliable estimates concerning the number of children trafficked each year, primarily due to the covert and criminal nature of the practice. The International Labour Organization estimates that 1.2 million children are trafficked each year.Child labor refers to the employment of children in any work that deprives children of their childhood, interferes with their ability to attend regular school, or is mentally, physically, socially or morally dangerous and harmful. The International Labour Organization considers such labor to be a form of exploitation and abuse of children. Child labor refers to those occupations which infringe the development of children (due to the nature of the job or lack of appropriate regulation) and does not include age appropriate and properly supervised jobs in which minors may participate. According to ILO, globally, around 215 million children work, many full-time. Many of these children do not go to school, do not receive proper nutrition or care, and have little or no time to play. More than half of them are exposed to the worst forms of child labor, such as child prostitution, drug trafficking, armed conflicts and other hazardous environments. There exist several international instruments protecting children from child labor, including the Minimum Age Convention, 1973 and the Worst Forms of Child Labour Convention.
More girls under 16 work as domestic workers than any other category of child labor, often sent to cities by parents living in rural poverty such as in restaveks in Haiti.
Forced adoption
Removing children of ethnic minorities from their families to be adopted by those of the dominant ethnic group has been used as a method of forced assimilation. The Stolen Generations in Australia involved Australian Aboriginal and Torres Strait Islander children. In Canada, the Canadian Indian residential school system involved First Nations, Métis and Inuit children, who often suffering severe abuse. As part of the Uyghur genocide, in 2017 alone at least half a million children were also forcefully separated from their families, and placed in pre-school camps with prison-style surveillance systems and 10,000 volt electric fences.In Switzerland, between the 1850s and the mid-20th century, hundreds of thousands of children mostly from poor or single parents were forcefully removed from their parents by the authorities, and sent to work on farms, living with new families. They were known as contract children or Verdingkinder.Most of the children living in institutions around the world have a surviving parent or close relative, and they most commonly entered orphanages because of poverty. It is speculated that, flush with money, for profit orphanages are increasing and push for children to join even though demographic data show that even the poorest extended families usually take in children whose parents have died and it would be cheaper to aid close relatives who want to take in the orphans. Experts and child advocates maintain that separating children from their families often harm childrens development. During the One Child Policy in China, women were only allowed to have one child. Local governments would allow the woman to give birth and then they would take the baby away stating the mother violated the one child policy. Child traffickers, often paid by the government, would sell the children to orphanages that would arrange international adoptions worth tens of thousands of dollars, turning a profit for the government.
Targeted violence against girls
Infanticide
Under natural conditions, mortality rates for girls under five are slightly lower than boys for biological reasons. However, after birth, neglect and diverting resources to male children can lead to some countries having a skewed ratio with more boys than girls, with such practices killing an approximate 230,000 girls under five in India each year. While sex-selective abortion is more common among the higher income population, who can access medical technology, abuse after birth, such as infanticide and abandonment, is more common among the lower income population. Female infanticide in Pakistan was a common practice.
Methods proposed to deal with the issue are baby hatches to drop off unwanted babies and safe-haven laws, which decriminalize abandoning babies unharmed.
Female genital mutilation
Female genital mutilation (FGM) is defined by the World Health Organization (WHO) as "all procedures that involve partial or total removal of the external female genitalia, or other injury to the female genital organs for non-medical reasons." It is practiced mainly in 28 countries in Africa, and in parts of Asia and the Middle East. FGM is mostly found in a geographical area ranging across Africa, from east to west – from Somalia to Senegal, and from north to south – from Egypt to Tanzania. FGM is most often carried out on young girls aged between infancy and 15 years. FGM is classified into four types, of which type 3 – infibulation – is the most extreme form. The consequences of FGM include physical, emotional and sexual problems, and include serious risks during childbirth. In Western countries this practice is illegal and considered a form of child abuse. The countries which choose to ratify the Istanbul Convention, the first legally binding instrument in Europe in the field of violence against women and domestic violence, are bound by its provisions to ensure that FGM is criminalized. In Australia, all states and territories have outlawed FGM. In the United States, performing FGM on anyone under the age of 18 became illegal in |
Child abuse | 1996 with the Federal Prohibition of Female Genital Mutilation Act.
Sexual initiation of virgins
A tradition often performed in some regions in Africa involves a man initiating a girl into womanhood by having sex with her, usually after her first period, in a practice known as "sexual cleansing". The rite can last for three days and there is an increased risk of contracting sexually transmitted infections as the ritual requires condoms not be worn.
Breast ironing
The practice of using hot stones or other implements to flatten the breast tissue of pubescent girls is widespread in Cameroon and exists elsewhere in West Africa as well. It is believed to have come with that diaspora to Britain, where the government declared it a form of child abuse and said that it could be prosecuted under existing assault laws.
Violence against girl students
In some parts of the world, girls are strongly discouraged from attending school, which some argue is because men favored with elevated and patriarchal status fear losing power to women. They are sometimes attacked by members of the community if they do so. In parts of South Asia, girls schools are set on fire by vigilante groups. Such attacks are common in Afghanistan and Pakistan. Notable examples include the kidnapping of hundreds of female students in Chibok in 2014 and Dapchi in 2018.
Child marriage
A child marriage is a marriage in which one or both participants are minors, often before the age of puberty. Child marriages are common in many parts of the world, especially in parts of Asia and Africa. The United Nations considers those below the age of 18 years to be incapable of giving valid consent to marriage and therefore regards such marriages as a form of forced marriage; and that marriages under the age of majority have significant potential to constitute a form of child abuse. In many countries, such practices are lawful or — even where laws prohibit child marriage — often unenforced. India has more child brides than any other nation, with 40% of the world total. The countries with the highest rates of child marriage are: Niger (75%), Central African Republic and Chad (68%), and Bangladesh (66%).
Bride kidnapping, also known as marriage by abduction or marriage by capture, has been practiced around the world and throughout history, and sometimes involves minors. It is still practiced in parts of Central Asia, the Caucasus region, and some African countries. In Ethiopia, marriage by abduction is widespread, and many young girls are kidnapped this way. In most countries, bride kidnapping is considered a criminal offense rather than a valid form of marriage. In many cases, the groom also rapes his kidnapped bride, in order to prevent her from returning to her family due to shame.Money marriage refers to a marriage where a girl, usually, is married off to a man to settle debts owed by her parents. The female is referred to as a "money wife"Sacred prostitution often involves girls being pledged to priests or those of higher castes, such as fetish slaves in West Africa.
Violence against children with superstitious accusations
Customary beliefs in witchcraft are common in many parts of the world, even among the educated. Anthropologists have argued that those with disabilities are often viewed as bad omens as raising a child with a disability in such communities are an insurmountable hurdle. A 2010 UNICEF report notes that accusations against children are a recent phenomenon with women and the elderly usually being accused 10–20 years ago. Greater urbanization and the growing economic burden of raising children is attributed as a factor. This practice is found in Africa and in communities in the Amazon. Children who are specifically at risk include orphans, street-children, albinos, disabled children, children who are unusually gifted, children who were born prematurely or in unusual positions, twins, children of single mothers and children who express gender identity issues and can involve children as young as eight. Consequently, those accused of being a witch are ostracized and subjected to punishment, torture and even murdered, often by being buried alive or left to starve. For example, in southern Ethiopia, children with physical abnormalities are considered to be ritually impure or mingi, the latter are believed to exert an evil influence upon others, so disabled infants have traditionally been disposed of without a proper burial. Reports by UNICEF, UNHCR, Save The Children and Human Rights Watch have highlighted the violence and abuse towards children accused of witchcraft in Africa.
Ethics
One of the most challenging ethical dilemmas arising from child abuse relates to the parental rights of abusive parents or caretakers with regard to their children, particularly in medical settings. In the United States, the 2008 New Hampshire case of Andrew Bedner drew attention to this legal and moral conundrum. Bedner, accused of severely injuring his infant daughter, sued for the right to determine whether or not she remain on life support; keeping her alive, which would have prevented a murder charge, created a motive for Bedner to act that conflicted with the apparent interests of his child. Bioethicists Jacob M. Appel and Thaddeus Mason Pope recently argued, in separate articles, that such cases justify the replacement of the accused parent with an alternative decision-maker.Child abuse also poses ethical concerns related to confidentiality, as victims may be physically or psychologically unable to report abuse to authorities. Accordingly, many jurisdictions and professional bodies have made exceptions to standard requirements for confidentiality and legal privileges in instances of child abuse. Medical professionals, including doctors, therapists, and other mental health workers typically owe a duty of confidentiality to their patients and clients, either by law or the standards of professional ethics, and cannot disclose personal information without the consent of the individual concerned. This duty conflicts with an ethical obligation to protect children from preventable harm. Accordingly, confidentiality is often waived when these professionals have a good faith suspicion that child abuse or neglect has occurred or is likely to occur and make a report to local child protection authorities. This exception allows professionals to breach confidentiality and make a report even when children or their parents or guardians have specifically instructed to the contrary. Child abuse is also a common exception to physician–patient privilege: a medical professional may be called upon to testify in court as to otherwise privileged evidence about suspected child abuse despite the wishes of children or their families. Some child abuse policies in Western countries have been criticized both by some conservatives, who claim such policies unduly interfere in the privacy of the family, and by some feminists of the left wing, who claim such policies disproportionally target and punish disadvantaged women who are often themselves in vulnerable positions. There has also been concern that ethnic minority families are disproportionally targeted.
Legislation
Canada
Laws and legislation against child abuse are enacted on the provincial and Federal Territories level. Investigations into child abuse are handled by Provincial and Territorial Authorities through government social service departments and enforcement is through local police and courts.
Germany
In Germany, the abuse of vulnerable persons (including children) is punishable according to the German Criminal code § 225 with a from 6 months to 10 years, in aggravated cases at least 1 year (to 15 years pursuant to § 38). If the case is only attempt, the penalty can be lower (§ 23). However, crimes against children must be prosecuted within 10 years (in aggravated cases 20 years) of the victims reaching 30 years of age (§ 78b and § 78).As of 2020, Germany and the Netherlands are 2 out of all 27 EU countries that do not have any reporting obligations for civilians or professionals. There is no mandatory reporting law, which would grant reporters of child abuse anonymity and immunity.
United States
In the 1960s, mandatory reporting in the United States was introduced and had been adopted in some form by all 50 states by 1970.: 3
In 1974, the Child Abuse Prevention and Treatment Act (CAPTA) was introduced and began an upswing in reported child sexual abuse cases which lasted until the 1990s. The Child Abuse Victims Rights Act of 1986 gave victims of child abuse the ability to file lawsuits against abuse perpetrators and their employers after the statue of limitations had expired. The Victims of Child Abuse Act of 1990 further gave victims of abuse capacity to press charges by permitting the court to assign lawyers to advise, act in the best interest of, and elevate the voices of child victims of abuse. The Adoption and Safe Families Act (1997) followed, shifting emphasis away from court-sanctioned reunification of families to giving parents or guardians time-bound opportunities for rehabilitation prior to making long term plans for children. Child Abuse Reform and Enforcement Act was enacted in 2000 to further reduce the incidence of child abuse and neglect.
Shifting legislative focus more heavily towards sexual abuse and exploitation of children, Adam Walsh Child Protection and Safety Act was passed in 2006 to increase penalties and registration for child sexual abuse, exploitation, and transportation crimes. top Exploitation Through Trafficking Act passed in 2013 aimed at preventing the prosecution of sexually exploited youth being sex trafficked, redirecting abused and exploited youth from the criminal justice system to the child welfare system. This and other laws redirecting victims of child sex trafficking to the child welfare system are known as "Safe Harbor" laws.As of April 2019, 18 states had legislation requiring that mandated reporters report based on suspicion of child abuse of neglect.
Advocacy organizations
United States
There are organizations at national, state, and county levels in the United States that provide community leadership in preventing child abuse and neglect.
Mary Ellen Wilson, also called Mary Ellen McCormack, was an American whose case of child abuse, the first documented case of child abuse in the United States, led to the creation of the New York Society for the Prevention of Cruelty to Children, which was incorporated in 1875. It was the worlds first child protective agency.Prevent Child Abuse America, founded in 1976, operates in 46 states to provide child abuse and neglect protection.Founded in 1985, the National Childrens Advocacy Center, along with National Childrens Alliance, coordinates efforts and sets standards and policy for child advocacy centers across the US and abroad.
The Childrens Trust Fund Alliance, established in 1989, provides funding support to state level child abuse organisations.
Many investigations into child abuse in the US are handled on the local level by 924 child advocacy centers, some of which are distributed among 34 other countries.
Other organizations focus on specific prevention strategies. The National Center on Shaken Baby Syndrome focuses its efforts on the specific issue of preventing child abuse that is manifested as shaken baby syndrome.NICHD, also known as the National Institute of Child Health & Human Development is an organization that helps victims of child abuse through one of its branches. Through the Child Development and Behavior (CDB) Branch, NICHD raises awareness efforts by supporting research projects to better understand the short- and long-term impacts of child abuse and neglect. They provide programs and observe National Child Abuse Prevention Month every April since 1984. The United States Childrens Bureau, a federal agency tasked to improve child abuse protection leads activities for the Month, including the release of updated statistics about child abuse and neglect, candlelight vigils, and fundraisers to support prevention activities and treatment for victims. The Bureau also sponsors a "Blue Ribbon Campaign," in which people wear blue ribbons in memory of children who have died from abuse, or in honor of individuals and organizations that have taken important steps to prevent child abuse and neglect.
Canada
Charitable organizations exist in each province to assist children and families with abuse. Organizations such as the Canadian Red Cross, Kids Help Phone, and Guardians of the Children Canada, are able to direct people to locally available resources.
See also
References
Further reading
Crosson-Tower, C. (2008). Understanding Child Abuse and Neglect. Boston, MA: Pearson Education. ISBN 978-0-205-50326-1. OCLC 150902303.
Finkelhor, D. (19 February 2008). Childhood Victimization: Violence, Crime, and Abuse in the Lives of Young People. Oxford; New York: Oxford University Press. p. 244. ISBN 978-0-19-534285-7. OCLC 162501989.
Hoyano, L.; Keenan C. (2007). Child Abuse: Law and Policy Across Boundaries. Oxford; New York: Oxford University Press. ISBN 978-0-19-829946-2. OCLC 79004390.
Korbin, Jill E. (1983). Child abuse and neglect: cross-cultural perspectives. Berkeley, CA: University of California Press. ISBN 978-0-520-05070-9. OCLC 144570871.
Miller, Alice (1990). "Thou Shalt Not Be Aware": Societys Betrayal of the Child, in series, Meridian Book[s]. Trans. by Heildegarde and Hunter Hannum. New York: Penguin. x, 329 p. Trans. from the German, titled Du sollst nicht merken. ISBN 0-452-00929-4 pbk
Turton, Jackie (2008). Child Abuse, Gender, and Society. New York: Routledge. p. 161. ISBN 978-0-415-36505-5. OCLC 144570871.
Young, Leontine (1964). Wednesdays children: A study of child neglect and abuse. New York: McGraw-Hill. OCLC 192177.
External links
Child abuse at Curlie
Child maltreatment, World Health Organization
World Report on Violence Against Children, Secretary-General of the United Nations
Prevent Child Abuse America
Pete (award-winning 2004 short film)
"Cold-nosed Comfort" (using a service dog to aid child abuse victims), Maryland Lawyer
nspcc.org.uk |
Tricuspid regurgitation | Tricuspid regurgitation (TR), also called tricuspid insufficiency, is a type of valvular heart disease in which the tricuspid valve of the heart, located between the right atrium and right ventricle, does not close completely when the right ventricle contracts (systole). TR allows the blood to flow backwards from the right ventricle to the right atrium, which increases the volume and pressure of the blood both in the right atrium and the right ventricle, which may increase central venous volume and pressure if the backward flow is sufficiently severe.
The causes of TR are divided into hereditary and acquired; and also primary and secondary. Primary TR refers to a defect solely in the tricuspid valve, such as infective endocarditis; secondary TR refers to a defect in the valve as a consequence of some other pathology, such as left ventricular failure or pulmonary hypertension.The mechanism of TR is either a dilatation of the base (annulus) of the valve due to right ventricular dilatation, which results in the three leaflets being too far apart to reach one another; or an abnormality of one or more of the three leaflets.
Signs and symptoms
The symptoms of TR depend on its severity. Severe TR causes right-sided heart failure, with the development of ascites and peripheral edema.A pansystolic heart murmur may be heard on auscultation of the chest. The murmur is usually of low frequency and best heard on the lower left sternal border. It increases with inspiration, and decreases with expiration: this is known as Carvallos sign. However, the murmur may be inaudible due to the relatively low pressures in the right side of the heart. A third heart sound may also be present, also heard at the lower sternal border, and increasing in intensity with inspiration.On examination of the neck, there may be giant C-V waves in the jugular pulse. With severe TR, there may be an enlarged liver detected on palpation of the right upper quadrant of the abdomen; the liver may be pulsatile on palpation and even on inspection.
Causes
The causes of TR may be classified as congenital or acquired; another classification divides the causes into primary or secondary. Congenital abnormalities are much less common than acquired. The most common acquired TR is due to right ventricular dilatation. Such dilatation is most often due left heart failure or pulmonary hypertension. Other causes of right ventricular dilatation include right ventricular infarction, inferior myocardial infarction, and cor pulmonale.In regards to primary and secondary causes they are:
Mechanism
In terms of the mechanism of tricuspid insufficiency, it involves the expansion of the tricuspid annulus (fibrous rings of heart). Tricuspid insufficiency is linked to geometric changes of the tricuspid annulus (decreased tricuspid annular release). The leaflets shape are normal but prevented from normal working mechanism due to a distortion of spatial relationships of leaflets and chords. It is also contemplated that the process via which tricuspid regurgitation emerges, is a decrease of contraction of the myocardium around the annulus.
Diagnosis
The diagnosis of TR may be suspected if the typical murmur of TR is heard. Severe TR may be suspected if right ventricular enlargement is seen on chest x-ray, and other causes of this enlargement are ruled out.Definitive diagnosis is made by echocardiogram, which is capable of measuring both the presence and the severity of the TR, as well as right ventricular dimensions and systolic pressures.
Management
Medical
Medical therapy of Tricuspid regurgitation consists of diuretics, but as the disease progresses, they become inefficient.
Surgical
Indications for surgical fixation of tricuspidal issues include organic lesion(s) in the valve or severe functional regurgitation. During open heart surgery for another issue (e.g. mitral valve), fixing the tricuspid valve may be considered, but medical consensus is unclear. Some argue that even mild to moderate tricuspid regurgitation should be addressed, while others take a more conservative approach. Infective endocarditis or traumatic lesions are other indications.Surgical options include annuloplasty or replacement of the valve. Adding a rigid prosthetic ring aims to decrease the diameter of the valve and stabilize it. Another annuloplasty modality is the "De Vega technique", in which the valve diameter is decreased by two sutures placed around the periphery of the valve. In cases of severe organic lesions of the valve, such as endocarditis, the valve may be excised. Tricuspid valve replacement with either a mechanical valve or a bioprosthesis may be indicated depending on the patient. Mechanical prostheses can cause thromboembolic phenomena, while bioprostheses may degenerate with use. Some evidence suggests that there is no significant difference between the survival rates of recipients of mechanical versus biological tricuspid valves.When controlled for severity of TR, tricuspid valve surgery performed on TR patients as considered appropriate is associated with improved outcomes (HR = .74).
Prognosis
The prognosis of TR is less favorable for males than females. Survival rates are proportional to TR severity; but even mild TR reduces survival compared to those with no TR. If the TR is due to left heart failure or pulmonary hypertension, prognosis is usually dictated by these conditions, not the TR.
Epidemiology
Tricuspid regurgitation is common and is estimated to occur in 65–85% of the population. In The Framingham Heart Study presence of any severity of tricuspid regurgitation, ranging from trace to above moderate was in 82% of men and in 85.7% of women. Mild tricuspid regurgitation tend to be common and benign and in structurally normal tricuspid valve apparatus can be considered a normal variant. Moderate or severe tricuspid regurgitation is usually associated with tricuspid valve leaflet abnormalities and/or possibly annular dilation and is usually pathologic which can lead to irreversible damage of cardiac muscle and worse outcomes due to chronic prolonged right ventricular volume overload.In a study of 595 male elite football players aged 18–38, and 47 sedentary non-athletes, it was found that 58% of the athletes had tricuspid regurgitation vs. 36% in non-athletes. Football players with tricuspid regurgitation had larger tricuspid annulus diameter, compared to athletes without tricuspid regurgitation. Athletes with tricuspid regurgitation also had enlarged right atrium diameter when compared to control group.
See also
Heart valves
References
Sources
Mestres, Carlos A.; Bernal, Jose M.; Pomar, Jose L. (2016). "Surgical Treatment of Tricuspid Valve Diseases". In Frank Sellke; Pedro J. del Nido (eds.). Sabiston and Spencer Surgery of the Chest. ISBN 978-0-323-24126-7.
Further reading
Haddad, F; Doyle, R; Murphy, D. J; Hunt, S. A (2008). "Right Ventricular Function in Cardiovascular Disease, Part II: Pathophysiology, Clinical Importance, and Management of Right Ventricular Failure". Circulation. 117 (13): 1717–1731. doi:10.1161/CIRCULATIONAHA.107.653584. PMID 18378625.
Desai, Ravi R; Vargas Abello, Lina Maria; Klein, Allan L; Marwick, Thomas H; Krasuski, Richard A; Ye, Ying; Nowicki, Edward R; Rajeswaran, Jeevanantham; Blackstone, Eugene H; Pettersson, Gösta B (2013). "Tricuspid regurgitation and right ventricular function after mitral valve surgery with or without concomitant tricuspid valve procedure". The Journal of Thoracic and Cardiovascular Surgery. 146 (5): 1126–1132.e10. doi:10.1016/j.jtcvs.2012.08.061. PMC 4215162. PMID 23010580.
Badano, Luigi P; Muraru, Denisa; Enriquez-Sarano, Maurice (2013). "Assessment of functional tricuspid regurgitation". European Heart Journal. 34 (25): 1875–1885. doi:10.1093/eurheartj/ehs474. PMID 23303656.
al.], Hugh D. Allen ... [et; Shaddy, Robert E.; Feltes, Timothy F. (2013). Moss and Adams heart disease in infants, children, and adolescents : including the fetus and young adult (8th ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 9781451118933.
== External links == |
Varicose veins | Varicose veins, also known as varicoses, are a medical condition in which superficial veins become enlarged and twisted. These veins typically develop in the legs, just under the skin. Varicose veins usually cause few symptoms. However, some individuals may experience fatigue or pain in the area. Complications can include bleeding or superficial thrombophlebitis. Varices in the scrotum are known as a varicocele, while those around the anus are known as hemorrhoids. Due to the various physical, social, and psychological effects of varicose veins, they can negatively affect ones quality of life.Varicose veins have no specific cause. Risk factors include obesity, lack of exercise, leg trauma, and family history of the condition. They also develop more commonly during pregnancy. Occasionally they result from chronic venous insufficiency. Underlying causes include weak or damaged valves in the veins. They are typically diagnosed by examination, including observation by ultrasound.By contrast, spider veins affect the capillaries and are smaller.Treatment may involve lifestyle changes or medical procedures with the goal of improving symptoms and appearance. Lifestyle changes may include wearing compression stockings, exercising, elevating the legs, and weight loss. Possible medical procedures include sclerotherapy, laser surgery, and vein stripping. Reoccurrence is common following treatment.Varicose veins are very common, affecting about 30% of people at some time in their lives. They become more common with age. Women develop varicose veins about twice as often as men. Varicose veins have been described throughout history and have been treated with surgery since at least A.D. 400.
Signs and symptoms
Aching, heavy legs
Appearance of spider veins (telangiectasia) in the affected leg
Ankle swelling
A brownish-yellow shiny skin discoloration near the affected veins
Redness, dryness, and itchiness of areas of skin, termed stasis dermatitis or venous eczema
Muscle cramps when making sudden movements, such as standing
Abnormal bleeding or healing time for injuries in the affected area
Lipodermatosclerosis or shrinking skin near the ankles
Restless legs syndrome appears to be a common overlapping clinical syndrome in people with varicose veins and other chronic venous insufficiency
Atrophie blanche, or white, scar-like formations
Burning or throbbing sensation in the legsPeople with varicose veins might have a positive D-dimer blood test result due to chronic low-level thrombosis within dilated veins (varices).
Complications
Most varicose veins are reasonably benign, but severe varicosities can lead to major complications, due to the poor circulation through the affected limb.
Pain, tenderness, heaviness, inability to walk or stand for long hours
Skin conditions / dermatitis which could predispose skin loss
Skin ulcers especially near the ankle, usually referred to as venous ulcers
Development of carcinoma or sarcoma in longstanding venous ulcers. Over 100 reported cases of malignant transformation have been reported at a rate reported as 0.4% to 1%
Severe bleeding from minor trauma, of particular concern in the elderly
Blood clotting within affected veins, termed superficial thrombophlebitis. These are frequently isolated to the superficial veins, but can extend into deep veins, becoming a more serious problem.
Acute fat necrosis can occur, especially at the ankle of overweight people with varicose veins. Females have a higher tendency of being affected than males
Causes
Varicose veins are more common in women than in men and are linked with heredity. Other related factors are pregnancy, obesity, menopause, aging, prolonged standing, leg injury and abdominal straining. Varicose veins are unlikely to be caused by crossing the legs or ankles. Less commonly, but not exceptionally, varicose veins can be due to other causes, such as post-phlebitic obstruction or incontinence, venous and arteriovenous malformations.Venous reflux is a significant cause. Research has also shown the importance of pelvic vein reflux (PVR) in the development of varicose veins. Varicose veins in the legs could be due to ovarian vein reflux. Both ovarian and internal iliac vein reflux causes leg varicose veins. This condition affects 14% of women with varicose veins or 20% of women who have had vaginal delivery and have leg varicose veins. In addition, evidence suggests that failing to look for and treat pelvic vein reflux can be a cause of recurrent varicose veins.There is increasing evidence for the role of incompetent perforator veins (or "perforators") in the formation of varicose veins. and recurrent varicose veins.Varicose veins could also be caused by hyperhomocysteinemia in the body, which can degrade and inhibit the formation of the three main structural components of the artery: collagen, elastin and the proteoglycans. Homocysteine permanently degrades cysteine disulfide bridges and lysine amino acid residues in proteins, gradually affecting function and structure. Simply put, homocysteine is a corrosive of long-living proteins, i.e. collagen or elastin, or lifelong proteins, i.e. fibrillin. These long-term effects are difficult to establish in clinical trials focusing on groups with existing artery decline. Klippel–Trenaunay syndrome and Parkes Weber syndrome are relevant for differential diagnosis.Another cause is chronic alcohol consumption due to the vasodilatation side effect in relation to gravity and blood viscosity.
Diagnosis
Clinical test
Clinical tests that may be used include:
Trendelenburg test–to determine the site of venous reflux and the nature of the saphenofemoral junction
Investigations
Traditionally, varicose veins were investigated using imaging techniques only if there was a suspicion of deep venous insufficiency, if they were recurrent, or if they involved the saphenopopliteal junction. This practice is now less widely accepted. People with varicose veins should now be investigated using lower limbs venous ultrasonography. The results from a randomised controlled trial on patients with and without routine ultrasound have shown a significant difference in recurrence rate and reoperation rate at 2 and 7 years of follow-up.
Stages
The CEAP (Clinical, Etiological, Anatomical, and Pathophysiological) Classification, developed in 1994 by an international ad hoc committee of the American Venous Forum, outlines these stages
C0 – no visible or palpable signs of venous disease
C1 – telangectasia or reticular veins
C2 – varicose veins
C2r - recurrent varicose veins
C3 – edema
C4- changes in skin and subcutaneous tissue due to Chronic Venous Disease
C4a – pigmentation or eczema
C4b – lipodermatosclerosis or atrophie blanche
C4c- Corona phlebectatica
C5 – healed venous ulcer
C6 – active venous ulcer
C6r- recurrent active ulcerEach clinical class is further characterized by a subscript depending upon whether the patient is symptomatic (S) or asymptomatic (A), e.g. C2S.
Treatment
Treatment can be either active or conservative.
Active
Treatment options include surgery, laser and radiofrequency ablation, and ultrasound-guided foam sclerotherapy. Newer treatments include cyanoacrylate glue, mechanochemical ablation, and endovenous steam ablation. No real difference could be found between the treatments, except that radiofrequency ablation could have a better long-term benefit.
Conservative
The National Institute for Health and Clinical Excellence (NICE) produced clinical guidelines in July 2013 recommending that all people with symptomatic varicose veins (C2S) and worse should be referred to a vascular service for treatment. Conservative treatments such as support stockings should not be used unless treatment was not possible.
The symptoms of varicose veins can be controlled to an extent with the following:
Elevating the legs often provides temporary symptomatic relief.
Advice about regular exercise sounds sensible but is not supported by any evidence.
The wearing of graduated compression stockings with variable pressure gradients (Class II or III) has been shown to correct the swelling, nutritional exchange, and improve the microcirculation in legs affected by varicose veins. They also often provide relief from the discomfort associated with this disease. Caution should be exercised in their use in patients with concurrent peripheral arterial disease.
The wearing of intermittent pneumatic compression devices have been shown to reduce swelling and pain.
Diosmin/hesperidin and other flavonoids.
Anti-inflammatory medication such as ibuprofen or aspirin can be used as part of treatment for superficial thrombophlebitis along with graduated compression hosiery – but there is a risk of intestinal bleeding. In extensive superficial thrombophlebitis, consideration should be given to anti-coagulation, thrombectomy, or sclerotherapy of the involved vein.
Topical gel application helps in managing symptoms related to varicose veins such as inflammation, pain, swelling, itching, and dryness.
Procedures
Stripping
Stripping consists of removal of all or part the saphenous vein (great/long or lesser/short) main trunk. The complications include deep vein thrombosis (5.3%), pulmonary embolism (0.06%), and wound complications including infection (2.2%). There is evidence for the great saphenous vein regrowing after stripping. For traditional surgery, reported recurrence rates, which have been tracked for 10 years, range from 5% to 60%. In addition, since stripping removes the saphenous main trunks, they are no longer available for use as venous bypass grafts in the future (coronary or leg artery vital disease).
Other
Other surgical treatments are:
CHIVA method (ambulatory conservative haemodynamic correction of venous insufficiency) is a relatively low-invasive surgical technique that incorporates venous hemodynamics and preserves the superficial venous system. The overall effectiveness compared to stripping, radiofrequency ablation treatment, or endovenous laser therapy is not clear and there is no strong evidence to suggest that CHIVA is superior to stripping, radiofrequency ablation, or endovenous laser therapy for recurrence of varicose veins. There is some low-certainty evidence that CHIVA may result in more bruising compared to radiofrequency ablation treatment.
Ambulatory phlebectomy.
Vein ligation is done at the saphenofemoral junction after ligating the tributaries at the sephanofemoral junction without stripping the long saphenous vein provided the perforator veins are competent and absent DVT in the deep veins. With this method, the long saphenous vein is preserved.
Cryosurgery- A cryoprobe is passed down the long saphenous vein following saphenofemoral ligation. Then the probe is cooled with NO2 or CO2 to −85o F. The vein freezes to the probe and can be retrogradely stripped after 5 seconds of freezing. It is a variant of Stripping. The only point of this technique is to avoid a distal incision to remove the stripper.
Sclerotherapy
A commonly performed non-surgical treatment for varicose and "spider leg veins" is sclerotherapy, in which medicine called a sclerosant is injected into the veins to make them shrink. The medicines that are commonly used as sclerosants are polidocanol (POL branded Asclera in the United States, Aethoxysklerol in Australia), sodium tetradecyl sulphate (STS), Sclerodex (Canada), Hypertonic Saline, Glycerin and Chromated Glycerin. STS (branded Fibrovein in Australia) liquids can be mixed at varying concentrations of sclerosant and varying sclerosant/gas proportions, with air or CO2 or O2 to create foams. Foams may allow more veins to be treated per session with comparable efficacy. Their use in contrast to liquid sclerosant is still somewhat controversial and there is no clear evidence that foam are superior. Sclerotherapy has been used in the treatment of varicose veins for over 150 years. Sclerotherapy is often used for telangiectasias (spider veins) and varicose veins that persist or recur after vein stripping. Sclerotherapy can also be performed using foamed sclerosants under ultrasound guidance to treat larger varicose veins, including the great saphenous and small saphenous veins.There is some evidence that sclerotherapy is a safe and may be an effective treatment option for improving the cosmetic appearance, reducing residual varicose veins, improving the quality of life, and reducing symptoms that may be present due to the varicose veins. There is also weak evidence that this treatment option may have a slightly higher risk of deep vein thrombosis. It is not known if sclerotherapy decreases the change that varicose veins return (recurrent varicose veins). It is also not known if the type of liquid, substance, or foam used for the sclerotherapy procedure is the most effective and comes with the lowest risk of complications.Complications of sclerotherapy are rare but can include blood clots and ulceration. Anaphylactic reactions are "extraordinarily rare but can be life-threatening," and doctors should have resuscitation equipment ready. There has been one reported case of stroke after ultrasound-guided sclerotherapy when an unusually large dose of sclerosant foam was injected.
Endovenous thermal ablation
There are three kinds of endovenous thermal ablation treatment possible: laser, radiofrequency, and steam.The Australian Medical Services Advisory Committee (MSAC) in 2008 determined that endovenous laser treatment/ablation (ELA) for varicose veins "appears to be more effective in the short term, and at least as effective overall, as the comparative procedure of junction ligation and vein stripping for the treatment of varicose veins." It also found in its assessment of available literature, that "occurrence rates of more severe complications such as DVT, nerve injury, and paraesthesia, post-operative infections, and haematomas, appears to be greater after ligation and stripping than after EVLT". Complications for ELA include minor skin burns (0.4%) and temporary paresthesia (2.1%). The longest study of endovenous laser ablation is 39 months.Two prospective randomized trials found speedier recovery and fewer complications after radiofrequency ablation (ERA) compared to open surgery. Myers wrote that open surgery for small saphenous vein reflux is obsolete. Myers said these veins should be treated with endovenous techniques, citing high recurrence rates after surgical management, and risk of nerve damage up to 15%. By comparison ERA has been shown to control 80% of cases of small saphenous vein reflux at 4 years, said Myers. Complications for ERA include burns, paraesthesia, clinical phlebitis and slightly higher rates of deep vein thrombosis (0.57%) and pulmonary embolism (0.17%). One 3-year study compared ERA, with a recurrence rate of 33%, to open surgery, which had a recurrence rate of 23%.Steam treatment consists in injection of pulses of steam into the sick vein. This treatment which works with a natural agent (water) has similar results than laser or radiofrequency. The steam presents a lot of post-operative advantages for the patient (good aesthetic results, less pain, etc.)ELA and ERA require specialized training for doctors and special equipment. ELA is performed as an outpatient procedure and does not require an operating theatre, nor does the patient need a general anaesthetic. Doctors use high-frequency ultrasound during the procedure to visualize the anatomical relationships between the saphenous structures.Some practitioners also perform phlebectomy or ultrasound-guided sclerotherapy at the time of endovenous treatment. Follow-up treatment to smaller branch varicose veins is often needed in the weeks or months after the initial procedure. Steam is a very promising treatment for both doctors (easy introduction of catheters, efficient on recurrences, ambulatory procedure, easy and economic procedure) and patients (less post-operative pain, a natural agent, fast recovery to daily activities).
Medical Adhesive
Also called medical super glue, medical adhesive is an advanced non-surgical treatment for varicose veins during which a solution is injected into the diseased vein through a small catheter and under the assistance of ultrasound-guided imagery. The "super glue" solution is made of cyanoacrylate, aiming at sealing the vein and rerouting the blood flow to other healthy veins.Post-treatment, the body will naturally absorb the treated vein which will disappear. Involving only a small incision and no hospital stay, medical super glue has generated great interest within the last years, with a success rate of about 96.8%.A follow-up consultation is required after this treatment, just like any other one, in order to re-assess the diseased vein and further treat it if needed.
Epidemiology
Varicose veins are most common after age 50. It is more prevalent in females. There is a hereditary role. It has been seen in smokers, those who have chronic constipation, and in people with occupations which necessitate long periods of standing such as lecturers, nurses, conductors (musical and bus), stage actors, umpires (cricket, javelin, etc.), the Kings guards, lectern orators, security guards, traffic police officers, vendors, surgeons, etc.
References
External links
Media related to Varicose veins at Wikimedia Commons |
Squamous cell skin cancer | Squamous-cell skin cancer, also known as cutaneous squamous-cell carcinoma (cSCC), is one of the main types of skin cancer along with basal cell cancer and melanoma. It usually presents as a hard lump with a scaly top but can also form an ulcer. Onset is often over months. Squamous-cell skin cancer is more likely to spread to distant areas than basal cell cancer. When confined to the outermost layer of the skin, a precancerous or in situ form of cSCC is known as Bowens disease.The greatest risk factor is high total exposure to ultraviolet radiation from the sun. Other risks include prior scars, chronic wounds, actinic keratosis, lighter skin, Bowens disease, arsenic exposure, radiation therapy, tobacco smoking, poor immune system function, previous basal cell carcinoma, and HPV infection. Risk from UV radiation is related to total exposure, rather than early exposure. Tanning beds are becoming another common source of ultraviolet radiation. Risk is also elevated in certain genetic skin disorders, such as xeroderma pigmentosum and certain forms of epidermolysis bullosa. It begins from squamous cells found within the skin. Diagnosis is often based on skin examination and confirmed by tissue biopsy.New in vivo and in vitro studies have proven that the upregulation of FGFR2, a subset of the fibroblast growth factor receptor (FGFR) immunoglobin family, has a critical role to play in the progression of cSCC cells. Mutation in the TPL2 gene causes overexpression of FGFR2, which activates mTORC1 and AKT pathways in both primary and metastatic cSCC cell lines. Only by using FGFR pan-inhibitor, AZD4547, could cell migration and cell proliferation on cSCC be attenuated Additionally, research has identified common driver mutations in cSCC, with alterations in the NOTCH and p53 pathways occurring at high frequency and mutations in the Hippo and Ras/MAPK/PI3K occurring at lower frequency Decreasing exposure to ultraviolet radiation and the use of sunscreen appear to be effective methods of preventing squamous-cell skin cancer. Treatment is typically by surgical removal. This can be by simple excision if the cancer is small otherwise Mohs surgery is generally recommended. Other options may include application of cold and radiation therapy. In the cases in which distant spread has occurred chemotherapy or biologic therapy may be used.As of 2015, about 2.2 million people have cSCC at any given time. It makes up about 20% of all skin cancer cases. About 12% of males and 7% of females in the United States developed cSCC at some point in time. While prognosis is usually good, if distant spread occurs five-year survival is ~34%. In 2015 it resulted in about 51,900 deaths globally. The usual age at diagnosis is around 66. Following the successful treatment of one case of cSCC people are at high risk of developing further cases.
Signs and symptoms
SCC of the skin begins as a small nodule and as it enlarges the center becomes necrotic and sloughs and the nodule turns into an ulcer, and generally are developed from an actinic keratosis. Once keratinocytes begin to grow uncontrollably, they have the potential to become cancerous and produce squamous cell carcinoma.
The lesion caused by SCC is often asymptomatic
Ulcer or reddish skin plaque that is slow growing
Intermittent bleeding from the tumor, especially on the lip
The clinical appearance is highly variable
Usually the tumor presents as an ulcerated lesion with hard, raised edges
The tumor may be in the form of a hard plaque or a papule, often with an opalescent quality, with tiny blood vessels
The tumor can lie below the level of the surrounding skin, and eventually ulcerates and invades the underlying tissue
The tumor commonly presents on sun-exposed areas (e.g. back of the hand, scalp, lip, and superior surface of pinna)
On the lip, the tumor forms a small ulcer, which fails to heal and bleeds intermittently
Evidence of chronic skin photodamage, as in multiple actinic keratoses (solar keratoses)
The tumor grows relatively slowly
Spread
Unlike basal-cell carcinoma (BCC), squamous cell carcinoma (SCC) has a higher risk of metastasis.
Risk of metastasis is higher clinically in SCC arising in scars, on the lower lips or mucosa, and occurring in immunosuppressed and solid organ transplant patients. Risk of metastasis is also higher in SCC that are >2 cm in diameter, growth into the fat layer and along nerves, thickness >6mm.
Causes
Squamous cell carcinoma is the second-most common cancer of the skin (after basal-cell carcinoma but more common than melanoma). It usually occurs in areas exposed to the sun. Sunlight exposure and immunosuppression are risk factors for SCC of the skin, with chronic sun exposure being the strongest environmental risk factor. There is a risk of metastasis starting more than 10 years after diagnosable appearance of squamous cell carcinoma, but the risk is low, though much higher than with basal-cell carcinoma. Squamous cell cancers of the lip and ears have high rates of local recurrence and distant metastasis. In a recent study, it has also been shown that the deletion or severe down-regulation of a gene titled Tpl2 (tumor progression locus 2) may be involved in the progression of normal keratinocytes into becoming squamous cell carcinoma.SCCs represent about 20% of the non-melanoma skin cancers, but 80-90% of those with metastatic potential are located on the head and neck.Tobacco smoking also increases the risk for cutaneous squamous cell carcinoma.The vast majority of SCCs are those of the skin, and are often the result of ultraviolet exposure. SCCs usually occur on portions of the body commonly exposed to the Sun; the face, ears, neck, hands, or arm. The main symptom is a growing bump that may have a rough, scaly surface and flat reddish patches.
Unlike basal-cell carcinomas, SCCs carry a higher risk of metastasis, and may spread to the regional lymph nodes,Erythroplasia of Queyrat (SCC in situ of the glans or prepuce in males, M: 733 : 656 or the vulvae in females.) may be induced by human papilloma virus. It is reported to occur in the corneoscleral limbus. Erythroplasia of Queyrat may also occur on the anal mucosa or the oral mucosa. Some sources state that this condition is synonymous with Bowens disease, however generally speaking Bowens disease refers to carcinoma in situ of any location on the skin such as the lower leg.
Genetically, SCC tumors harbor high frequencies of NOTCH and p53 mutations as well as less frequent alterations in histone acetyltransferase EP300, subunit of the SWI/SNF chromatin remodeling complex PBRM1, DNA-repair deubiquitinase USP28, and NF-κB signaling regulator CHUK.
Immunosuppression
People who have received solid organ transplants are at a significantly increased risk of developing squamous cell carcinoma due to the use of chronic immunosuppressive medication. While the risk of developing all skin cancers increases with these medications, this effect is particularly severe for SCC, with hazard ratios as high as 250 being reported, versus 40 for basal cell carcinoma. The incidence of SCC development increases with time posttransplant. Heart and lung transplant recipients are at the highest risk of developing SCC due to more intensive immunosuppressive medications used.Squamous cell cancers of the skin in individuals on immunotherapy or who have lymphoproliferative disorders (e.g. leukemia) tend to be much more aggressive, regardless of their location. The risk of SCC, and non-melanoma skin cancers generally, varies with the immunosuppressive drug regimen chosen. The risk is greatest with calcineurin inhibitors like cyclosporine and tacrolimus, and least with mTOR inhibitors, such as sirolimus and everolimus. The antimetabolites azathioprine and mycophenolic acid have an intermediate risk profile.
Diagnosis
Diagnosis is confirmed via biopsy of the tissue or tissues suspected to be affected by SCC. For the skin, look under skin biopsy.
The pathological appearance of a squamous cell cancer varies with the depth of the biopsy. For that reason, a biopsy including the subcutaneous tissue and basilar epithelium, to the surface is necessary for correct diagnosis. The performance of a shave biopsy (see skin biopsy) might not acquire enough information for a diagnosis. An inadequate biopsy might be read as actinic keratosis with follicular involvement. A deeper biopsy down to the dermis or subcutaneous tissue might reveal the true cancer. An excision biopsy is ideal, but not practical in most cases. An incisional or punch biopsy is preferred. A shave biopsy is least ideal, especially if only the superficial portion is acquired.
Characteristics
Histopathologically, the epidermis in SCC in situ (Bowens disease) will show hyperkeratosis and parakeratosis. There will also be marked acanthosis with elongation and thickening of the rete ridges. These changes will overly keratinocytic cells which are often highly atypical and may in fact have a more unusual appearance than invasive SCC. The atypia spans the full thickness of the epidermis, with the keratinocytes demonstrating intense mitotic activity, pleomorphism, and greatly enlarged nuclei. They will also show a loss of maturity and polarity, giving the epidermis a disordered or "windblown" appearance.Two types of multinucleated cells may be seen: the first will present as a multinucleated giant cell, and the second will appear as a dyskeratotic cell engulfed in the cytoplasm of a keratinocyte. Occasionally, cells of the upper epidermis will undergo vacuolization, demonstrating an abundant and strongly eosinophilic cytoplasm. There may be a mild to moderate lymphohistiocytic infiltrate detected in the upper dermis.
In situ disease
Bowens disease is essentially equivalent to and used interchangeably with SCC in situ, when not having invaded through the basement membrane. Depending on source, it is classified as precancerous or SCC in situ (technically cancerous but non-invasive). In SCC in situ (Bowens disease), atypical squamous cells proliferate through the whole thickness of the epidermis. The entire tumor is confined to the epidermis and does not invade into the dermis. The cells are often highly atypical under the microscope, and may in fact look more unusual than the cells of some invasive squamous cell carcinomas.
Erythroplasia of Queyrat is a particular type of Bowens disease that can arise on the glans or prepuce in males,: 733 : 656 and the vulvae in females. It mainly occurs in uncircumcised males, over the age of 40. It is named for French dermatologist Louis Queyrat (1856–1933), who was head of the dermatology service of lHôpital Ricord, a venereal hospital in Paris, now Hôpital Cochin.
Invasive disease
In invasive SCC, tumor cells infiltrate through the basement membrane. The infiltrate can be somewhat difficult to detect in the early stages of invasion: however, additional indicators such as full thickness epidermal atypia and the involvement of hair follicles can be used to facilitate the diagnosis. Later stages of invasion are characterized by the formation of nests of atypical tumor cells in the dermis, often with a corresponding inflammatory infiltrate.
Degree of differentiation
Prevention
Appropriate sun-protective clothing, use of broad-spectrum (UVA/UVB) sunscreen with at least SPF 50, and avoidance of intense sun exposure may prevent skin cancer. A 2016 review of sunscreen for preventing squamous cell skin cancer found insufficient evidence to demonstrate whether it was effective.
Management
Most squamous cell carcinomas are removed with surgery. A few selected cases are treated with topical medication. Surgical excision with a free margin of healthy tissue is a frequent treatment modality. Radiotherapy, given as external beam radiotherapy or as brachytherapy (internal radiotherapy), can also be used to treat squamous cell carcinomas. There is little evidence comparing the effectiveness of different treatments for non-metastatic SCC of the skin.Mohs surgery is frequently utilized; considered the treatment of choice for squamous cell carcinoma of the skin, physicians have also utilized the method for the treatment of squamous cell carcinoma of the mouth, throat, and neck. An equivalent method of the CCPDMA standards can be utilized by a pathologist in the absence of a Mohs-trained physician. Radiation therapy is often used afterward in high risk cancer or patient types. Radiation or radiotherapy can also be a standalone option in treating SCCs. As a non invasive option brachytherapy serves a painless possibility to treat in particular but not only difficult to operate areas like the earlobes or genitals. An example of this kind of therapy is the High dose brachytherapy Rhenium-SCT which makes use of the beta rays emitting property of Rhenium-188. The radiation source is enclosed in a compound which is applied to a thin protection foile directly over the lesion. This way the radiation source can be applied to complex locations and minimize radiation to healthy tissue.After removal of the cancer, closure of the skin for patients with a decreased amount of skin laxity involves a split-thickness skin graft. A donor site is chosen and enough skin is removed so that the donor site can heal on its own. Only the epidermis and a partial amount of dermis is taken from the donor site which allows the donor site to heal. Skin can be harvested using either a mechanical dermatome or Humby knife.Electrodessication and curettage (EDC) can be done on selected squamous cell carcinoma of the skin. In areas where SCCs are known to be non-aggressive, and where the patient is not immunosuppressed, EDC can be performed with good to adequate cure rate.Treatment options for SCC in situ (Bowens disease) include photodynamic therapy with 5-aminolevulinic acid, cryotherapy, topical 5-fluorouracil or imiquimod, and excision. A meta-analysis showed evidence that PDT is more effective than cryotherapy and has better cosmetic outcomes. There is generally a lack of evidence comparing the effectiveness of all treatment options.High-risk squamous cell carcinoma, as defined by those occurring around the eye, ear, or nose, is of large size, is poorly differentiated, and grows rapidly, requires more aggressive, multidisciplinary management.
Nodal spread:
Surgical block dissection if palpable nodes or in cases of Marjolins ulcers but the benefit of prophylactic block lymph node dissection with Marjolins ulcers is not proven.
Radiotherapy
Adjuvant therapy may be considered in those with high-risk SCC even in the absence of evidence for local metastasis. Imiquimod (Aldara) has been used with success for squamous cell carcinoma in situ of the skin and the penis, but the morbidity and discomfort of the treatment is severe. An advantage is the cosmetic result: after treatment, the skin resembles normal skin without the usual scarring and morbidity associated with standard excision. Imiquimod is not FDA-approved for any squamous cell carcinoma.In general, squamous cell carcinomas have a high risk of local recurrence, and up to 50% do recur. Frequent skin exams with a dermatologist is recommended after treatment.
Prognosis
The long-term outcome of squamous cell carcinomas is dependent upon several factors: the sub-type of the carcinoma, available treatments, location and severity, and various patient health-related variables (accompanying diseases, age, etc.). Generally, the long-term outcome is positive, as less than 4% of Squamous cell carcinoma cases are at risk of metastasis. When it does metastasize, the most common involved organs are the lungs, brain, bone and other skin locations.One study found squamous cell carcinoma of the penis had a much greater rate of mortality than some other forms of squamous cell carcinoma, that is, about 23%, although this relatively high mortality rate may be associated with possibly latent diagnosis of the disease due to patients avoiding genital exams until the symptoms are debilitating, or refusal to submit to a possibly scarring operation upon the genitalia. Squamous cell carcinoma occurring in the organ transplant population is also associated with a higher risk of mortality.
Epidemiology
The incidence of squamous cell carcinoma continues to rise around the world. A recent study estimated that there are between 180,000 and 400,000 cases of SCC in the United States in 2013. Risk factors for squamous cell carcinoma varies with age, gender, race, geography, and genetics. The incidence of SCC increases with age and the peak incidence is usually around 60 years old. Males are affected with SCC at a ratio of 2:1 in comparison to females. Caucasians are more likely to be affected, especially those with fair skin or those chronically exposed to UV radiation.Squamous cell carcinoma of the skin can be found on all areas of the body but is most common on frequently sun-exposed areas, such as the face, legs and arms. Solid organ transplant recipients (heart, lung, liver, pancreas, among others) are also at a heightened risk of developing aggressive, high-risk SCC. There are also a few rare congenital diseases predisposed to cutaneous malignancy. In certain geographic locations, exposure to arsenic in well water or from industrial sources may significantly increase the risk of SCC.
Additional images
See also
List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer
References
External links
DermNet NZ: Squamous cell carcinoma |
Brief psychotic disorder | Brief psychotic disorder — according to the classifications of mental disorders DSM-IV-TR and DSM-5 — is a psychotic condition involving the sudden onset of at least one psychotic symptom (such as disorganized thought/speech, delusions, hallucinations, or grossly disorganized or catatonic behavior) lasting 1 day to 1 month, often accompanied by emotional turmoil. Remission of all symptoms is complete with patients returning to the previous level of functioning. It may follow a period of extreme stress including the loss of a loved one. Most patients with this condition under DSM-5 would be classified as having acute and transient psychotic disorders under ICD-10. Prior to DSM-IV, this condition was called "brief reactive psychosis." This condition may or may not be recurrent, and it should not be caused by another condition.
The term bouffée délirante describes an acute non-affective and non-schizophrenic psychotic disorder, which is largely similar to DSM-III-R and DSM-IV brief psychotic and schizophreniform disorders.
Presentation
BPD is characterized by a sudden onset of psychotic symptoms, which may include delusions, hallucinations, disorganized speech or behavior, or catatonic behavior.Symptoms generally last at least a day, but not more than a month, and there is an eventual return to full baseline functioning. BPD may occur in response to a significant stressor in ones life, or in other situations where a stressor is not apparent, including in the weeks following birth.In diagnosis, a careful distinction is considered for culturally appropriate behaviors, such as religious beliefs and activities. It is believed to be connected to or synonymous with a variety of culture-specific phenomena such as latah, koro, and amok.
Classification
There are three forms of brief psychotic disorder:
BPD with a marked stressor (a.k.a. brief reactive psychosis): if BPD symptoms occur in following personal events (single or multiple) that would be expected to cause significant stress to an average individual.
BPD without a marked stressor: if BPD symptoms do not occur in following personal events (single or multiple) that would be expected to cause significant stress to an average individual.
BPD with postpartum onset: if onset of BPD symptoms is during pregnancy or within 4 weeks after birth.
BPD with a marked stressor (brief reactive psychosis)
Brief reactive psychosis (designated since the DSM IV-TR as "brief psychotic disorder with marked stressor(s), BRP"), is the psychiatric term for psychosis which can be triggered by an extremely stressful event in the life of an individual and eventually yielding to a return to normal functioning.Brief reactive psychosis generally follows a recognisably traumatic life event like divorce or homelessness, but may be triggered by any subjective experience which appears catastrophic to the person affected. Among such stressors are the death of a loved one, professional loss such as unexpectedly losing ones job or otherwise becoming unemployed, or serious adverse changes in the patients personal life, such as the breakdown of their family through divorce, etc. It must be emphasised that this is by no means an exhaustive list of stressful life events, because the events which trigger brief reactive psychosis tend, due to the individualistic nature of human psychology, to be extremely personalized. BRP may be the first breakdown for someone with a chronic psychiatric disorder but only time will tell whether the disorder will be brief or lifelong, whether BRP or a chronic condition that is controlled well enough by medication that symptoms do not return.The condition usually resolves spontaneously within a time span of weeks to months, with the severity of the symptoms reducing continuously over the period in question. A primary goal of treatment is to prevent patients who are either suicidal or homicidal from harming themselves or others during the episode.
Cause/pathophysiology
The exact cause of brief psychotic disorder is not known. One theory suggests a genetic link, because the disorder is more common in people who have family members with mood disorders, such as depression or bipolar disorder. Another theory suggests that the disorder is caused by poor coping skills, as a defense against or escape from a particularly frightening or stressful situation. These factors may create a vulnerability to develop brief psychotic disorder. In most cases, the disorder is triggered by a major stress or traumatic event.
In females, a low estrogen state (which may occur premenstrual, postpartum, or perimenopausal) can trigger sudden, short-lived psychosis. The psychosis is often linked to an underlying bipolar or schizophrenic condition. Such psychosis (when diagnosed as such), is often considered "premenstrual exacerbation" or "menstrual psychosis", or postpartum psychosis. Childbirth may trigger the disorder in some women. Approximately 1 in 10,000 women experience brief psychotic disorder shortly after childbirth.
Diagnosis
The symptoms must not be caused by schizophrenia, schizoaffective disorder, delusional disorder, or mania in bipolar disorder. They must also not be caused by a drug (such as amphetamines) or medical condition (such as a brain tumor).
Differential diagnosis
There are general medical causes of brief psychosis that should be considered during evaluation, including postnatal depression, HIV and AIDS, malaria, syphilis, Alzheimers disease, Parkinsons disease, hypoglycaemia (an abnormally low level of glucose in the blood), lupus, multiple sclerosis, brain tumor, SARS-CoV-2 (COVID-19) infection and pediatric autoimmune neuropsychiatric disorders (PANS).
Epidemiology
The exact incidence and prevalence of brief psychotic disorder is not known, but it is generally considered uncommon. Internationally, it occurs twice as often in women than men, and even more often in women in the United States. It typically occurs in the late 30s and early 40s. Approximately 1 in 10,000 women experience brief psychotic disorder shortly after childbirth.
History
Otto Fenichel noted how such short psychotic breaks were more common in World War II than in World War I, in the wake of traumatic shocks: he considered in such cases that "enough preconscious attention remains to re-establish the contact with reality as soon as it becomes bearable again".
BPD in Film/TV/Media
BPD and its symptoms were featured in the Kevin Spacey and Daniel Wu-starring film Inseparable. Daniel Wus character developed BPD after a series of tragedies.
See also
Bouffée délirante
Menstrual psychosis
Mental breakdown
Schizophreniform disorder
References
Further reading
External links
Causes of Psychosis |
Subsets and Splits