page_title
stringlengths 1
91
| page_text
stringlengths 0
34.2k
|
|---|---|
Williams syndrome | Williams syndrome (WS) is a genetic disorder that affects many parts of the body. Facial features frequently include a broad forehead, underdeveloped chin, short nose, and full cheeks. Mild to moderate intellectual disability is observed in people with WS, with particular challenges with visual spatial tasks such as drawing. Verbal skills are relatively unaffected. Many people with WS have an outgoing personality, an openness to engaging with other people, and a happy disposition. Medical issues with teeth, heart problems (especially supravalvular aortic stenosis), and periods of high blood calcium are common.Williams syndrome is caused by a genetic abnormality, specifically a deletion of about 27 genes from the long arm of one of the two chromosome 7s. Typically, this occurs as a random event during the formation of the egg or sperm from which a person develops. In a small number of cases, it is inherited from an affected parent in an autosomal dominant manner. The different characteristic features have been linked to the loss of specific genes. The diagnosis is typically suspected based on symptoms and confirmed by genetic testing.Treatment of WS includes special education programs and various types of therapy. Surgery may be done to correct heart problems. Dietary changes or medications may be required for high blood calcium. The syndrome was first described in 1961 by New Zealander John C. P. Williams. Williams syndrome affects between one in 20,000 and one in 7,500 people at birth. Life expectancy is less than that of the general population, mostly due to the increased rates of heart disease.
Signs and symptoms
The most common symptoms of Williams syndrome are heart defects and unusual facial features. Other symptoms include failure to gain weight appropriately in infancy (failure to thrive) and low muscle tone. People with WS tend to have widely spaced teeth, a long philtrum, and a flattened nasal bridge.Most people with WS are highly verbal relative to their intelligence, and are often very sociable, having what has been described as a "cocktail party"-type personality. People with Williams syndrome hyperfocus on the eyes of others in social engagements.
Physical
People with WS experience many cardiac problems, commonly heart murmurs and the narrowing of major blood vessels, as well as supravalvular aortic stenosis. Other symptoms may include gastrointestinal problems, such as severe or prolonged colic, abdominal pain and diverticulitis, nocturnal enuresis (bed wetting) and urinary difficulties, dental irregularities and defective tooth enamel, and hormone problems, the most common being hypercalcemia. Hypothyroidism has been reported to occur in children, although no proof has been found of it occurring in adults; adults with WS have a higher risk of developing type-2 diabetes, with some cases apparent as young as 21 years old.People with WS often have hyperacusia and phonophobia, which resembles noise-induced hearing loss, but this may be due to a malfunctioning auditory nerve. People with WS can also tend to demonstrate a love of music, and they appear significantly more likely to possess absolute pitch. Also, higher prevalences of left-handedness and left-eye dominance seem to occur.Ophthalmologic issues are common in WS. Up to 75% of subjects in some studies have strabismus (ocular misalignment), particularly esotropia, due to inherent subnormal binocular visual function
and cognitive deficits in visuospatial construction. People with WS have problems with visual processing, but this is related to difficulty in dealing with complex spatial relationships rather than depth perception per se.
Nervous system
Because of missing multiple genes, many effects on the brain are seen, including abnormalities in the cerebellum, right parietal lobe, and left frontal cortical regions. This pattern is consistent with the visual-spatial disabilities and problems with behavioral timing often seen in WS.Frontal-cerebellar pathways, involved in behavioral timing, are often abnormally developed in people with WS, which may be related to their deficits in coordination and execution of fine motor tasks such as drawing and writing. In addition, people with WS often exhibit gross motor difficulties, including trouble walking downstairs, overactive motor reflexes (hyperreflexia), and hyperactive, involuntary movement of the eyes (nystagmus).Williams syndrome is also noteworthy for exhibiting abnormalities in the parietal-dorsal areas of the neocortex, but not the ventral areas. The parietal-dorsal area handles visual processing that supports visual-spatial analysis of the environment, while the ventral is related to semantic recognition of visual stimuli, and the recognition of faces. Thus, people with WS are often able to visually identify and recognize whole objects, and refer to them by name, but struggle with visuospatial construction (seeing an object as being composed of many smaller parts, and recreating it) and orienting themselves in space.People with WS are often affable and hyperverbal, demonstrating the decreased inhibition ability that stems from dorsal-frontal deficits. Some studies suggest that the amygdala of a person with Williams syndrome has greater volume than the average persons (though it is smaller than average in childhood).
In general, neuroimaging studies demonstrate that people with WS have diminished amygdala reactivity in response to socially frightening stimuli (such as disapproving faces), but demonstrate hyperreactivity in the amygdala when presented with nonsocial fear stimuli (such as frightening animals). This may partially account for the apparent absence of social inhibition observed in people with the syndrome, as well as the prevalence of anxious symptoms (but see fear for details on the relationship between the amygdala and fear response). Also, some evidence indicates that people with WS exhibit amygdalal hyperactivity when viewing happy facial expressions. They are talkative and eager to please, indicating a cocktail party personality.Increased volume and activation of the left auditory cortex has been observed in people with WS, which has been interpreted as a neural correlation of patients rhythm propensity and fondness of music. Similar sizes of the auditory cortex have been previously reported only in professional musicians.
Development
The earliest observable symptoms of WS include low birth weight, failure to thrive, trouble breastfeeding, nocturnal irritability, and gastroesophageal reflux. Facial dysmorphies thought to be characteristic of the syndrome are also present early in development, as are heart murmurs. Research on the development of the syndrome suggests that congenital heart disease is typically present at an early age, often at the infants first pediatric appointment. Heart problems in infancy often lead to the initial diagnosis of WS.Developmental delays are present in most cases of WS, and include delay of language abilities and delayed motor-skill development. People with WS develop language abilities quite late relative to other children, with the childs first word often occurring as late as 3 years of age. Language abilities are often observed to be deficient until adolescence, in terms of semantics, morphology, and phonology, though not in vocabulary.Williams syndrome is also marked by a delay in the development of motor skills. Infants with WS develop the ability to lift their heads and sit without support months later than typically developing children. These delays continue into childhood, where patients with WS are delayed in learning to walk. In young children, the observed motor delay is around 5–6 months, though some research suggests that children with WS have a delay in development that becomes more extreme with age. Children with motor delays as a result of WS are particularly behind in the development of coordination, fine motor skills such as writing and drawing, response time, and strength and dexterity of the arms. Impaired motor ability persists (and possibly worsens) as children with WS reach adolescence.Adults and adolescents with Williams syndrome typically achieve a below-average height and weight, compared with unaffected populations. As people with WS age, they frequently develop joint limitations and hypertonia, or abnormally increased muscle tone. Hypertension, gastrointestinal problems, and genitourinary symptoms often persist into adulthood, as well as cardiovascular problems. Adults are typically limited in their ability to live independently or work in competitive employment settings, but this developmental impairment is attributed more to psychological symptoms than physiological problems.
Social and psychological
People with Williams syndrome report higher anxiety levels as well as phobia development, which may be associated with hyperacusis (high sensitivity to certain frequencies of sound). Compared with other children with delays, those with Williams syndrome display a significantly greater number of fears. 35% of these children met the DSM definition of having a phobia as compared with 1–4.3% for those with other types of developmental delays. Williams syndrome is also strongly associated with attention deficit hyperactivity disorder and related psychological symptoms such as poor concentration, hyperactivity, and social disinhibition.Furthermore, cognitive abilities (IQs) of people with WMS typically range from mild to moderate levels of intellectual disability. One study of 306 children with Williams syndrome found IQ scores ranging from 40 to 112 with a mean of 69.32 (the mean IQ score of the general population is 100). IQ scores above this range have been reported in people with smaller genetic deletions. In particular, people with Williams syndrome experience challenges in visual-motor skills and visuospatial construction. Most affected people are unable to spatially orient themselves and many experience difficulty when given a task that requires even the most basic visual problem-solving. Many adults with Williams syndrome cannot complete a simple six-piece puzzle designed for young children, for example. These visuospatial deficits may be related to damage to the dorsal cortical pathway for visual processing.Despite their physical and cognitive deficits, people with Williams syndrome exhibit impressive social and verbal abilities. Williams patients can be highly verbal relative to their IQ. When children with Williams syndrome are asked to name an array of animals, they may well list a wild assortment of creatures such as a koala, saber-toothed cat, vulture, unicorn, sea lion, yak, ibex and Brontosaurus, a far greater verbal array than would be expected of children with IQs in the 60s. Some other strengths that have been associated with Williams syndrome are auditory short-term memory and facial recognition skills. The language used by people with Williams syndrome differs notably from unaffected populations, including people matched for IQ. People with Williams syndrome tend to use speech that is rich in emotional descriptors, high in prosody (exaggerated rhythm and emotional intensity), and features unusual terms and strange idioms.Among the hallmark traits of people with Williams syndrome is an apparent lack of social inhibition. Dykens and Rosner (1999) found that 100% of those with Williams syndrome were kind-spirited, 90% sought the company of others, 87% empathize with others pain, 84% are caring, 83% are unselfish/forgiving, 75% never go unnoticed in a group, and 75% are happy when others do well. Infants with Williams syndrome make normal and frequent eye contact, and young children with Williams will often approach and hug strangers. People affected by Williams syndrome typically have high empathy, showing relative strength in reading peoples eyes to gauge intentions, emotions, and mental states. The level of friendliness observed in people with Williams is often inappropriate for the social setting, however, and teens and adults with Williams syndrome often experience social isolation, frustration, and loneliness despite their clear desire to connect to other people.While these children often came off as happy due to their sociable nature, often there are internal drawbacks to the way they act. 76–86% of these children were reported as believing that they either had few friends or problems with their friends. This is possibly due to the fact that although they are very friendly to strangers and love meeting new people, they may have trouble interacting on a deeper level. 73–93% were reported as unreserved with strangers, 67% highly sensitive to rejection, 65% susceptible to teasing, and the statistic for exploitation and abuse was unavailable. There are external problems as well. 91–96% demonstrate inattention, 75% impulsivity, 59–71% hyperactivity 46–74% tantrums, 32–60% disobedience, and 25–37% fighting and aggressive behavior.In one experiment, a group of children with Williams syndrome showed no signs of racial bias, unlike children without the syndrome. They did show gender bias, however, to a similar degree to children without the syndrome, suggesting separate mechanisms for these biases.
Cause
Williams syndrome is a microdeletion syndrome caused by the spontaneous deletion of genetic material from the chromosomal region 7q11.23. This is a hemizygous deletion, which results in haploinsufficient expression of the 25–27 genes in this region. CLIP2, ELN, GTF2I, GTF2IRD1, and LIMK1 are among the genes typically deleted. Hemizygosity for the ELN gene, which codes for the extracellular matrix protein elastin, is associated with connective-tissue abnormalities and cardiovascular disease (specifically supravalvular aortic stenosis and supravalvular pulmonary stenosis). Elastin insufficiency may also contribute to distinct faces, harsh or hoarse voice, hernias, and bladder diverticula often found in those with Williams syndrome. Hemizygosity in LIMK1, GTF2I, GTF2IRD1, and perhaps other genes may help explain the characteristic difficulties with visual–spatial tasks. Additionally, some evidence shows that the hemizygosity in several of these genes, including CLIP2, may contribute to the unique behavioral characteristics, learning disabilities, and other cognitive difficulties seen in WS.
Diagnosis
According to the Williams Syndrome Association, its diagnosis begins with the recognition of physical symptoms and markers, which is followed by a confirmatory genetic test. The physical signs that often indicate a suspected case of WS include puffiness around the eyes, a long philtrum, and a stellate pattern in the iris. Physiological symptoms that often contribute to a WS diagnosis are cardiovascular problems, particularly aortic or pulmonary stenosis, and feeding disturbance in infants. Developmental delays are often taken as an initial sign of the syndrome, as well.If a physician suspects a case of WS, the diagnosis is confirmed using one of two possible genetic tests: Micro-array analysis or the fluorescent in situ hybridization test, which examines chromosome 7 and probes for the existence of two copies of the elastin gene. Since 98-99% of individuals with WS lack half of the 7q11.23 region of chromosome 7, where the elastin gene is located, the presence of only one copy of the gene is a strong sign of WS. This confirmatory genetic test has been validated in epidemiological studies and has been demonstrated to be a more effective method of identifying WS than previous methods, which often relied on the presence of cardiovascular problems and facial features (which, while common, are not always present).Reliance on facial features to identify WS may cause a misdiagnosis of the condition. Among the more reliable features suggestive of WS are congenital heart disease, periorbital fullness ("puffy" eyes), and the presence of a long, smooth philtrum. Less reliable signs of the syndrome include anteverted nostrils, a wide mouth, and an elongated neck. Even with significant clinical experience, reliably identifying Williams syndrome based on facial features alone is difficult.This is particularly the case in individuals of non-white backgrounds, where typical WS facial features (such as full lips) are more prevalent.
Treatment
No cure for Williams syndrome has been found. Suggested treatments include avoidance of extra calcium and vitamin D, and treating high levels of blood calcium. Blood-vessel narrowing can be a significant health problem and is treated on an individual basis.
Physical therapy is helpful to patients with joint stiffness and low muscle tone. Developmental and speech therapy can also help children and increase the success of their social interactions. Other treatments are based on a patients particular symptoms.The American Academy of Pediatrics recommends annual cardiology evaluations for individuals with WS. Other recommended assessments include ophthalmologic evaluations, an examination for inguinal hernia, objective hearing assessment, blood-pressure measurement, developmental and growth evaluation, orthopedic assessments on joints and muscle tone, and ongoing feeding and dietary assessments to manage constipation and urinary problems.Behavioral treatments have been shown to be effective. In regards to social skills, it may be effective to channel their nature by teaching basic skills. Some of these are the appropriate way to approach someone, how and when to socialize in settings such as school or the workplace, and warning of the signs and dangers of exploitation. For the fear that they demonstrate cognitive-behavioral approaches, such as therapy, they are the recommended treatments. One of the things to be careful of with this approach is to make sure that the patients charming nature does not mask any underlying feelings.Perhaps the most effective treatment for those with WS is music. Those affected have shown relative strength in regards to music, albeit only in pitch and rhythm tasks. Not only do they show strength in the field, but also a particular fondness for it. Music may help with the internal and external anxiety with which these people are more likely to be afflicted. Notably, the typical person processes music in the superior temporal and middle temporal gyri. Those with WS have reduced activation in these areas, but an increase in the right amygdala and cerebellum.People affected by WS are supported by multiple organizations, including the Canadian Association for Williams Syndrome and the Williams Syndrome Registry.
Epidemiology
Williams syndrome has historically been estimated to occur in roughly one in every 20,000 live births, but more recent epidemiological studies have placed the occurrence rate at closer to one in every 7,500 live births, a significantly larger prevalence. As increasing evidence suggests WS is more common than originally noted (about 6% of all genetic cases of developmental disability), researchers have begun to theorize past underdiagnosis of the syndrome. One theorized reason for the increase in epidemiological estimates is that a substantial minority of individuals with the genetic markers of WS syndrome lack the characteristic facial features or the diminished intelligence considered to be diagnostic of the syndrome, and often are not immediately recognized as having the syndrome.
History
Williams syndrome was first described by J. C. P. Williams and his colleagues, who wrote in 1961 of four patients with supravalvular aortic stenosis, mental disability, and facial features including a broad forehead, large chin, low-set, "drooping" cheeks, widely spaced eyes, and wide-set mouth. A year after this report, German physician A. J. Beuren described three new patients with the same presentation. This led to the syndromes full original name, Williams-Beuren syndrome, which is still used in some medical publications. From 1964 to 1975, small research reports broadened medical knowledge of this syndromes cardiovascular problems. Then in 1975, K. Jones and D. Smith conducted a large-scale report on numerous patients with WS, ranging in age from infancy to adulthood, and described the behavioral and observable physical symptoms in greater detail than previously recorded.
Society and culture
The adjective "elfin" may have originated to describe the facial features of people with WS; before its scientific cause was understood, people believed that individuals with the syndrome, who have exceptionally charming and kind personalities, had extraordinary, even magical, powers. This has been proposed to be the origin of the folklore of elves, fairies, and other forms of the good people or wee folk present in English folklore.In a review of the symptoms and features of the syndrome, Laskari, Smith, and Graham emphasized that many family members of individuals with WS reject use of terminology such as "elfin", as well as descriptions of social symptoms as "cocktail party syndrome". Physicians, family members of individuals with WS syndrome, and WS associations alike have called for the curtailment of such terms.One notable person with the syndrome is Gabrielle Marion-Rivard, a Canadian actress and singer who won the Canadian Screen Award for Best Actress in 2014 for her performance in the film Gabrielle. Another is Jeremy Vest, member of the Hows Your News? team, featured in the TV series and film of the same name.
Further reading
Articles
Fung, Lawrence K.; Quintin, Eve-Marie; Haas, Brian W.; Reiss, Allan L. (2012). "Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome". Current Opinion in Neurology (Review). 25 (2): 112–24. doi:10.1097/WCO.0b013e328351823c. PMC 3680360. PMID 22395002.
Karmiloff-Smith, A.; dSouza, D.; Dekker, T. M.; Van Herwegen, J.; Xu, F.; Rodic, M.; Ansari, D. (2012). "Genetic and environmental vulnerabilities in children with neurodevelopmental disorders". Proceedings of the National Academy of Sciences (Review). 109: 17261–5. Bibcode:2012PNAS..109S7261K. doi:10.1073/pnas.1121087109. JSTOR 41763522. PMC 3477396. PMID 23045661.
Kitagawa, Hirochika; Fujiki, Ryoji; Yoshimura, Kimihiro; Oya, Hiroyuki; Kato, Shigeaki (2011). "Williams syndrome is an epigenome-regulator disease". Endocrine Journal (Review). 58 (2): 77–85. doi:10.1507/endocrj.k10e-393. PMID 21242649.
Musolino, Julien; Landau, Barbara (2012). "Genes, language, and the nature of scientific explanations: The case of Williams syndrome". Cognitive Neuropsychology (Review). 29 (1–2): 123–48. doi:10.1080/02643294.2012.702103. PMC 3478137. PMID 23017087.
Books
Latson, Jennifer (2017). The Boy Who Loved Too Much: A True Story of Pathological Friendliness. Simon & Schuster. ISBN 978-1476774046.
Films
THE MAYOR: A Chronicle of Williams Syndrome, with Josh Duffy
External links
GeneReview entry on Williams syndrome
== References == |
Generalized pustular psoriasis | Generalized pustular psoriasis (GPP) is an extremely rare type of psoriasis that can present in a variety of forms. Unlike the most general and common forms of psoriasis, GPP usually covers the entire body and with pus-filled blisters rather than plaques. GPP can present at any age, but is rarer in young children. It can appear with or without previous psoriasis conditions or history, and can reoccur in periodic episodes.
Signs and symptoms
GPP presents as pustules and plaques over a wide area of the body. It differs from the localized form of pustular psoriasis in that patients are often febrile and systemically ill.However, the most prominent symptom, as described in the Archives of Dermatology, is "sheeted, pinhead-sized, sterile, sub-corneal pustules". The IPC roundtable adds that these pustules often occur either at the edges "of expanding, intensely inflammatory plaques" or "within erythrodermic skin".
Causes
Most cases of generalized pustular psoriasis present in patients with existing or prior psoriasis conditions. However, there are many cases of GPP that arise without a history of psoriasis.The Department of Dermatology of the University of São Paulo proposed a classification for these two conditions. Pso+ represents patients with a personal history of psoriasis and pso- represents patients with no history of psoriasis. They also identified a common factor among patients in each group: In the pso+ group, the most common precipitating factor is corticosteroid withdrawal. In the pso- group, the most common precipitating factor is infection.In a large portion of cases, the disease is brought on by some triggering factor. Through research and observation, many of these factors have been identified. The following table, from an article in Cutis, lists a few factors that have been observed as influential in the onset of GPP.
Source: "Table II", "Pustular Psoriasis" Farber and Nall, 1993
Genetic factors
Although there are likely to be multiple genetic factors and environmental triggers, mutations causing defects in the IL-36RN, CARD14 and AP1S3 genes have been shown to cause GPP.
Diagnosis
Classification
It is important to note that while there are different forms of GPP, they are not exclusive of each other. One can morph into another, or multiple forms can occur simultaneously.
von Zumbusch acute generalized pustular psoriasis
Von Zumbusch psoriasis is named after the German dermatologist Leo Ritter von Zumbusch (1874–1940), son of Kaspar von Zumbusch, who described the first documented case of generalized pustular psoriasis in the early 1900s. See Case Report #1.
Sometimes all or any of GPP is referred to as von Zumbusch psoriasis, but in the literature it is often distinguished as one specific form of GPP.Eugene M. Farber, MD and colleagues provide a description of von Zumbusch psoriasis in "Pustular Psoriasis", published in Cutis. They describe the pattern as having "waves of widespread or universally fiery redness". The affected areas are "painful and tender". Small sub-corneal pustules form, with sizes originally between 1 and 10 mm in diameter. These pustules may merge to form "yellow-green lakes of pus". The pustules dry out, and "Waves of scarlatiniform [resembling scarlet fever] peeling follow, removing the desiccating pustules". In regards to the onset, the von Zumbusch form may "supervene on any previous pattern of psoriasis". It also may or may not recur periodically.
Generalized pustular psoriasis of pregnancy (Impetigo herpetiformis)
This form of GPP tends to have symmetrical and grouped features. It usually onsets early in the third trimester of pregnancy, and generally persists until the child is born, but occasionally long after.
In 2009, Dr. Debeeka Hazarika, president of the North East States branch of the Indian Association of Dermatologists, Venereologists and Leprologists (IADVL), published an article titled "Generalized pustular psoriasis of pregnancy successfully treated with cyclosporine" in Indian J Dermatol Venereol Leprol. As reported by Hazarika, there have been up to nine instances where the disease was recurrent in subsequent pregnancies.
See Case Report 2
In 1979, Frank R. Murphy, MD and Lewis P. Stolman, MD reported on the case of a woman who developed generalized pustular psoriasis in response to doses of progestins, suggesting a link between progestogens and GPP. Most cases of GPP in pregnancy occur late in the third trimester, generally when production of progesterone increases.
Infantile and juvenile
GPP is a rare disease in general, but even more so in children. In 2010, an article was published in Pediatric Dermatology by the Department of Dermatology, University of São Paulo. The report acknowledged that psoriasis is a relatively common skin condition in children, but "the pustular variant is rare." Out of 1,262 cases of psoriasis in children, a "0.6% rate of pustular variants" was found. When GPP does occur in children, it usually appears during the first year of life.Khan et al. reported that in GPP patients ten or younger, less than 12% of cases are preceded by ordinary psoriasis. This differs greatly from GPP cases in adults, where 85% of GPP is preceded by typical psoriatic lesions.According to the article by the University of São Paulo, mentioned above, "The onset of childhood GPP is generally abrupt and accompanied by toxic features." The original acute episode usually lasts a few days, but "repeated waves of inflammation and pustulation may follow." It is important that the disease is managed immediately in order to prevent life-threatening complications, such as infection or [sepsis]. Other complications include "metabolical, hemo-dynamic, and thermoregulatory disturbances" which occur as a result of "alterations of the epidermal barrier."See Case Report 3
Circinate and annular
This type of psoriasis appears as round lesions. It begins as discrete areas that become raised and swollen. Pustules appear at the edges of the round lesions, creating rings. The pustules then dry out and leave a trail of scale as the lesion grows.See Case Report 4
Treatments
Treatments vary widely, and many different drugs have been documented as being successful. Some medications are successful in some patients, while unsuccessful in others. Below is a list of some medications used to treat GPP:
Etanercept
PUVA
Hydroxyurea
Dapsone
Systemic corticosteroids
Cyclosporin A
Adalimumab
Etretinate
Isotretinoin
Acitretin
Prognosis
GPP is a rare and severe type of psoriasis. It in rare cases it is said to be fatal and in some cases has driven patients to intensive burn units. An article published in Pediatric Dermatology said, "The GPP pattern is as an acute, episodic, and potentially life-threatening form of psoriasis." There is no cure-all treatment for GPP, and as such, the mortality rate is high. Ryan and Baker observed 155 patients with GPP, 106 of which were followed up with. 26 of those 106 died as a result of the psoriasis or the treatment. Their data gives a 25% mortality rate.
Case reports
Case report 1
Von Zumbusch observed a male patient, who had had classic psoriasis for several years, and who then went through recurrent episodes of bright [erythema] and [edema], which became studded with multiple pustules. Von Zumbusch observed this patient through nine hospital admissions over 10 years.
Case report 2
Hazarika gave a report of a 29-year-old woman with no family history of psoriasis, having had a normal first pregnancy, who presented with GPP in the twenty-eighth week of her second pregnancy. Steroid therapy caused a worsening of the symptoms. With cyclosporine the lesions cleared in 10–14 days, but new lesions appeared. The patient gave birth to a healthy baby in the thirty-eighth week of pregnancy. A month and a half after delivery, the woman presented with a psoriatic plaque on her leg.
Case report 3
An eleven-year-old boy had an eight-year history of recurrent GPP. He suffered from "fever, malaise and pain". He was treated with acitretin, and improvement was seen in five weeks.
Case report 4
In 1991, a case was reported of a man having plaque psoriasis and treating it with UV radiation at a tanning salon. After receiving a partial thickness burn from overexposure, he presented with annular pustular psoriasis, which cleared after 21 days, only to reoccur every 3 to 6 weeks for a year.
Case report 5
A case report published in the Journal of Dermatological Treatment documents the successful use of adalimumab to control symptoms and induce relapse for 72 weeks. "Adalimumab is ... approved for the treatment of moderate to severe rheumatoid arthritis ... and more recently for the treatment of psoriatic arthritis".
See also
List of cutaneous conditions
Psoriasis
References
== External links == |
Plasma cell leukemia | Plasma cell leukemia (PCL) is a plasma cell dyscrasia, i.e. a disease involving the malignant degeneration of a subtype of white blood cells called plasma cells. It is the terminal stage and most aggressive form of these dyscrasias, constituting 2% to 4% of all cases of plasma cell malignancies. PCL may present as primary plasma cell leukemia, i.e. in patients without prior history of a plasma cell dyscrasia or as secondary plasma cell dyscrasia, i.e. in patients previously diagnosed with a history of its predecessor dyscrasia, multiple myeloma. The two forms of PCL appear to be at least partially distinct from each other. In all cases, however, PCL is an extremely serious, life-threatening, and therapeutically challenging disease.
Signs and symptoms
Primary PCL
The clinical presentation of primary PCL (pPCL) indicates a far more aggressive disease than that of a typical multiple myeloma case with its clinical features being a combination of those found in multiple myeloma and acute leukemia. Like multiple myeloma patients, pPCL patients exhibit pathologically high levels of monoclonal plasma cells in their bone marrow plus a malignant plasma cell-secreted circulating monoclonal myeloma protein, either IgG, IgA, a light chain, or none in 28-56%, 4-7%, 23-44%, or 0-12% of cases, respectively. Similar to B cell leukemias, but unlike multiple myeloma, pPCL patients exhibit relative high frequencies of splenomegaly, lymphadenopathy, hepatomegaly, kidney failure, bone marrow failure (i.e. thrombocytopenia, anemia, and/or, rarely, leukopenia), central nervous system defects, and peripheral neuropathies due to the invasion of these tissues by plasma cells and/or the deposition of their circulating monoclonal immunoglobulin in them. Compared to multiple myeloma patients, pPCL patients also: exhibit 1) high rates of developing a hypercalcemic crisis, i.e. a potentially life-threatening episode of high ionic calcium (Ca2+) levels in the blood due to excess bone re-absorption and/or renal failure; b) higher levels of serum lactate dehydrogenase and Beta-2 microglobulin; and c) lower rates of bone but higher rates of soft tissue plasma cell tumors termed plasmacytomas.
Secondary PCL
Secondary PCL (sPCL) is diagnosed in 1-4% of patients known to have had multiple myeloma for a median time of ~21 months. It is the terminal phase of these patients myeloma disease. sPCL patients typically are highly symptomatic due to extensive disease with malignant plasma cell infiltrations in, and failures of, not only the bone marrow but also other organs. They have failed or broken through one or more treatment regimens and therefore may also show some of the toxic effects of these treatments.
Cause
PCL is caused by the development of an excessively high number of genetic abnormalities in plasma cells or, more particularly, their precursor B cells and plasmablasts (see plasma cells). This genetic instability is due to a myriad of acquired abnormalities including gene mutations; single nucleotide polymorphisms; depletions and duplications of parts of a gene, larger portion of a chromosome, or even an entire arm of a chromosome; translocations, deletions, and duplications of entire chromosomes; and increases and decreases in the expression of intact genes due to, e.g. the methylation of gene promotors and various less direct effects. These genetic abnormalities effect the Wnt signaling pathway, regulation of the cell cycle, RNA metabolism, protein folding, and cadherin-related cell adherence to extracellular matrix. These effects in turn control plasma cell proliferation, survival, apoptosis, adhesion to bone marrow, genome stability, and secretion of monoclonal immunoglobulins.Secondary plasma cell leukemia (sPCL) results from the comparatively slow development of plasma cell/plasma cell precursor genetic abnormalities which initially create a clone of cells that cause the premalignant condition of monoclonal gammopathy of undetermined significance. In a very small percentage of these cases, the progressive development of further genetic abnormalities serially create a clone(s) of plasma cells that cause the more serious but still premalignant disorder of smoldering multiple myeloma, overt myeloma cancer, and ultimately sPCL. In contrast to sPCL, pPCL presents de novo with a broad range of genetic abnormalities. For example, advanced methods for examining the genome viz., whole-exome sequencing and gene expression profiling, have identified 166 non-silent gene variants per pPCL patient sample at the time of diagnosis. These abnormalities are similar but not identical to those detected in sPCL while the abnormalities detected in sPCL more closely resemble those detected in multiple myeloma than do those of pPCL: the genetic data support the clinical data in suggesting that sPCL and pPCL are distinct diseases with sPCL among the two PCLs being more closely related to multiple myeloma. Examination of plasma cell immunophenotype by measuring certain of their cell surface antigens, particularly Cluster of differentiation. CD markers on plasma cells from patients with pPCL differ from those taken form multiple myeloma or sPCL patients. For example: pPCL plasma cells more often express CD20 antigen, which is considered important in anchoring plasma cells to the bone marrow stroma, than do those on plasma cells taken from myeloma patients (50% vs. 17%); pPCL plasma cells often lack CD56 antigen which is present on the majority of plasma cells taken form multiple myeloma patients; and pPCL plasma cells more frequently express CD28 than do sPCL plasma cells. Thus, immunophenotyping supports that notion that multiple myeloma, sPCL, and pPCL show critically important fundamental differences that may explain their different clinical presentations, courses, responses to therapy, and prognoses.
Diagnosis
The International Myeloma Working Group has defined the diagnostic criteria for plasma cell leukemia as the presence in blood of >2x109 plasma cells per liter or, alternatively, >20% of nucleated blood cells being plasma cells. More recently, the Group has suggested that values of 0.5x109 or 5%, respectively, may be more appropriate from a therapeutic viewpoint and therefore should be studied as a definitive criterion for the disease. A recent study supported this suggestion in finding that multiple myeloma patients with >5% circulating plasma cells had a prognosis much worse than that for multiple myeloma and similar to that for plasma cell leukemia. Flow cytometry immunophenotyping of blood cells to detect clonal phenotypes of plasma cells seen in multiple myeloma (e.g. the CD138+, CD38+, CD19−, CD45+/- phenotype) may be a more sensitive method to enumerate circulating clonal plasma cells and diagnose plasma cell leukemia.
Treatments
Prior to the use of newly developed drugs and treatment regimens, median survival rates from the time of diagnosis for pPCL and sPCL were 8–11 months and 2–8 months, respectively, even when treated very aggressively with the VAD regimen of vincristine, doxorubicin, and dexamethasone or the VCMP regimen of vincristine, carmustine, melphalan, and prednisone alternating with vincristine, carmustine, doxorubicin, and prednisone. The treatment of PCL patients, particularly pPCL patients, with newer methods appears to have made modest improvements in survival rates. However, the rarity of these two leukemias has limited individual studies to case reports on a small number of patients or retrospective analyses of patient records. Randomized controlled trials on these patients have not been reported. One flaw of these methods is patient selection bias, i.e. patients selected for treatment with a new regimen may be less ill than average patients with the disease and therefore have an intrinsically less aggressive (i.e. longer overall survival time) disease.
Primary plasma cell leukemia
Recent case report studies suggest that treatment regimens which include a proteasome inhibitor drug, particularly bortezomib, and/or autologous stem-cell transplantation have improved pPCL survival. For example, 28 patients treated with a bortezomib-based induction regimen followed by autologous stem-cell transplantation and then a maintenance regimen of lenaldomide (an immunosuppressant related to thalidomide), bortezomib, and dexamethasone (a corticosteroid) has a progression free survival rate of 66% at 3 years and an overall survival rate of 73% at 4 years. In one study, patients receiving intensive chemotherapy plus autologous stem-cell transplantation had a median survival of 34 months while those receiving chemotherapy alone had a median survival of 11 months. Two other studies that included bortezomib in their chemotherapy regimens likewise found that the addition of autologous stem-cell transplantation improved results. Current recommendations for treating pPCL often include induction with a three drug regimen such as borezomib-lenalidomide-dexamethasone followed by autologous stem-cell transplantion and consolidation/maintenance with of combination of immunomodulator agents (e.g. thalidomide, lenalidomide, or pomalidomide) plus a proteasome inhibitor (bortezomib, ixazomib, or carfilzomib.
Secondary plasma cell leukemia
As the end stage of multiple myeloma that has failed or broken through one or more therapeutic regimens, sPCL continues to be highly refractory to various treatment regimens (<50%), very short response times of these regiments, and poor overall survival rates (median survival of 2–8 to months). Patients with sPCL may have short-lived responses to treatment regimens (as communicated in case reports) that include bortezomid but there are no established therapeutic regimens that have clearly been shown to improve their overall or median survival.
See also
Plasma cell dyscrasia
Multiple myeloma
References
BibliographyGreer JP, Foerster J, and Lukens JN, "Wintrobes Clinical Hematology", Lippincott Williams & Wilkins 11th ed., 2003.
Hoffman R, Benz E, Shattil S, Furie B, Cohen H, "Hematology: Basic Principles and Practice", Churchill Livingstone, 4th ed, 2004.
Hoffbrand AV, Catovsky D, and Tuddenham E, "Postgraduate Haematology", Blackwell, 5th ed., 2005.
Hoffbrand AV, Moss PAH, and Pettit JE, "Essential Haematology", Blackwell, 5th ed., 2006.
== External links == |
Vernal keratoconjunctivitis | Vernal keratoconjunctivitis (VKC) is a recurrent, bilateral, and self-limiting inflammation of conjunctiva, having a periodic seasonal incidence.
Vernal keratopathy
Corneal involvement in VKC may be primary or secondary due to extension of limbal lesions. Vernal keratopathy includes 5 types of lesions.
Punctuate epithelial keratitis.
Ulcerative vernal keratitis (shield ulceration).
Vernal corneal plaques.
Subepithelial scarring.
Pseudogerontoxon.
Sign and symptoms
Symptoms- VKC is characterised by marked burning and itchy sensations which may be intolerable and accentuates when patient comes in a warm humid atmosphere. Associated symptoms include mild photophobia in case of corneal involvement, lacrimation, stringy discharge and heaviness of eyelids.
Signs of VKC can be described in three clinical forms (Cameron Classification):Palpebral form- Usually upper tarsal conjunctiva of both the eyes is involved. Typical lesion is characterized by the presence of hard, flat-topped papillae arranged in cobblestone or pavement stone fashion. In severe cases papillae undergo hypertrophy to produce cauliflower-like excrescences of giant papillae.
Bulbar form- It is characterised by dusky red triangular congestion of bulbar conjunctiva in palpebral area, gelatinous thickened accumulation of tissue around limbus and presence of discrete whitish raised dots along the limbus (Trantas spots).
Mixed form- Shows the features of both palpebral and bulbar types.
Cause
VKC is thought to be an allergic disorder in which IgE mediated mechanism play a role. Such patients often give family history of other atopic diseases such as hay fever, asthma or eczema, and their peripheral blood shows eosinophilia and increased serum IgE levels.
Risk factors
Age and sex – 4–20 years; more common in boys than girls.
Season – More common in summer. Hence, the name Spring catarrh is a misnomer. Recently it is being labelled as Warm weather conjunctivitis.
Climate – More prevalent in the tropics. VKC cases are mostly seen in hot months of summer, therefore, more suitable term for this condition is "summer catarrh" Ref.
Pathology
Conjunctival epithelium undergoes hyperplasia and sends downward projection into sub-epithelial tissue.
Adenoid layer shows marked cellular infiltration by eosinophils, lymphocytes, plasma cells and histiocytes.
Fibrous layer show proliferation which later undergoes hyaline changes.
Conjunctival vessels also show proliferation, increased permeability and vasodilation.
Diagnosis
Classification
Based on severity, authors have classified VKC into clinical grades:Grade 0 - Absence of symptoms
Grade 1 MILD - Symptoms but no corneal involvement
Grade 2 MODERATE - Symptoms with photophobia but no corneal involvement
Grade 3 SEVERE - Symptoms, photophobia, mild to moderate SPKs OR with Diffuse SPK or corneal ulcer
Treatment
Local therapy- Topical steroids are effective. Commonly used solutions are of fluorometholone, medrysone, betamethasone or dexamethasone. Mast cell stabilizers such as sodium cromoglycate (2%) drops 4–5 times a day are quite effective in controlling VKC, especially atopic ones. Azelastine eyedrops are also effective. Topical antihistamines can be used. Acetyl cysteine (0.5%) used topically has mucolytic properties and is useful in the treatment of early plaque formation. Topical Cyclosporine is reserved for unresponsive cases.
Systemic therapy- Oral antihistamines and oral steroids for severe cases.
Treatment of large papillae- Cryo application, surgical excision or supratarsal application of long-acting steroids.
General measures include use of dark goggles to prevent photophobia, cold compresses and ice pack for soothing effects, change of place from hot to cold areas.
Desensitization has also been tried without much rewarding results.
Treatment of vernal keratopathy- Punctuate epithelial keratitis require no extra treatment except that instillation of steroids should be increased. Large vernal plaque requires surgical excision. Ulcerative vernal keratitis require surgical treatment in the form of debridement, superficial keratectomy, excimer laser therapeutic keratectomy, as well as amniotic membrane transplantation to enhance re-epithelialisation.
Recently treatment with tacrolimus ointment (0.1%) used topically twice daily is showing encouraging results.
See also
Conjunctivitis
Allergic conjunctivitis
References
Further reading
Khurana, A. K. (2014). Comprehensive ophthalmology. Anshan. ISBN 978-1-84829-072-3.
== External links == |
Synchysis scintillans | Synchysis scintillans is a degenerative condition of the eye resulting in liquefied vitreous humor and the accumulation of cholesterol crystals within the vitreous. It is also known as cholesterolosis bulbi. The vitreous liquifies in a process known as syneresis. Synchysis scintillans appears as small white floaters that freely move in the posterior part of the eye, giving a snow globe effect. It is most commonly seen in eyes that have suffered from a degenerative disease and are end-stage.The condition is seen rarely. Associated with the advanced stages of diabetic retinopathy, but the exact pathogenesis is unknown.
The condition is symptomless and untreatable. In ophthalmoscopic examination it appears as small, flat, yellow, highly refractive crystals of cholesterol floating freely in the vitreous. These will settle, due to gravity, if the eye is immobilized.
== References == |
Sickle cell retinopathy | Sickle cell retinopathy can be defined as retinal changes due to blood vessel damage in the eye of a person with a background of sickle cell disease. It can likely progress to loss of vision in late stages due to vitreous hemorrhage or retinal detachment. Sickle cell disease is a structural red blood cell disorder leading to consequences in multiple systems. It is characterized by chronic red blood cell destruction, vascular injury, and tissue ischemia causing damage to the brain, eyes, heart, lungs, kidneys, spleen, and musculoskeletal system.People affected by sickle cell disease are commonly of African or Asian descent. Emigration patterns towards the Western Hemisphere have led to increased numbers of persons affected by sickle cell disease in regions where it was previously uncommon. Knowledge and understanding of sickle cell disease and its management are now increasingly relevant in areas such as the European Union. At a young age, a great proportion of people living with sickle cell disease can develop retinal changes. Sickle cell disease consists of several subtypes; however, the Haemoglobin type C (HbSC) subtype carries the gravest prognosis for sickle cell retinopathy and vision changes.Regular retinal examinations can aid in early detection and treatment, thus reducing the impact of the condition and the risk of vision loss. Development and progression of sickle cell retinopathy can be favorably modified through management of the underling sickle cell disease. Treatment of the general disease can ameliorate its systemic effects.
Classification
Sickle cell retinopathy can be classified based on retinal changes into non-proliferative and proliferative subtypes.
Non-proliferative sickle cell retinopathy (NPSCR)
Non-proliferative sickle cell retinopathy (NPSCR) can feature the following retinal manifestations:
Venous tortuousity is commonly observed in patients with homozygous HbSS sickle cell disease. Numerous diseases that feature blood hyperviscosity similar to sickle cell disease can manifest as retinal venous tortuousity. Tortuosity is caused by arteriovenous shunting from the retinal periphery.
It can feature small bleeds of the retina known as intra-retinal hemorrhages, due to blockage of blood vessels by the sickled blood cells, thus triggering vessel wall necrosis. The resulting hemorrhages are initially bright red and oval shaped. As the hemorrhage ages over a period of days to weeks, the color then changes to a salmon hue known as a salmon patch. They are usually seen adjacent to the retinal arteriole.
Bleeding in the deeper layers of the retina leads to the appearance of dark lesions known as black sunburst spots. These oval or round shaped pigmented spots are formed due to RPE proliferation.
As the haemoglobin within the hemorrhage breaks down over time, yellow spots known as iridescent bodies are formed within the layers of the sensory retina.
Maculopathy occurs in a significant portion of patients affected by sickle cell retinopathy. It is more prevalent in homozygous HbSS type sickle cell disease. The fovea can be found within the macula and is known as the center of the visual field. Maculopathy in sickle cell retinopathy is due to long term changes of capillaries that interact at the fovea. Although ischemic changes may be apparent on the retina, maculopathy may be asymptomatic at first leaving visual acuity unchanged.
Central retinal artery occlusion is a known feature of non-proliferative sickle cell retinopathy that has a low incidence in patients with non proliferative sickle cell retinopathy.
Optic nerve sign is represented by dilated capillaries that can be visualized in the nerve using fluorescein angiography. Visual acuity often remains unchanged with this finding.
Angioid streaks: Angioid streaks may be seen in up to 6% of cases.
Proliferative sickle cell retinopathy (PSCR)
Proliferative sickle retinopathy is the most severe ocular complication of sickle cell disease. Even though PSCR begins in the first decade of life, the condition remains asymptomatic and unnoticed until visual symptoms occur due to vitreous hemorrhage or retinal detachment.
Goldberg classification
Goldberg classified PSR into following 5 different self-explanatory stages:
Stage of peripheral arterial occlusion and ischemia: It is the earliest abnormality that can be visualized by fundus examination. The occluded arterioles can be seen as dark red lines. They eventually turn into white silver-wire vessels.
Stage of peripheral arteriolar-venular anastomoses: Arteriolar-venular anastomoses develop as blood is diverted from blocked arteries to nearby venules.
Stage of neovascularization and fibrous proliferation: Neovascularization starts from the arteriolar-venular anastomoses, and grow into the ischemic retina. Characteristic fan-shaped appearance due to neovasularization is known as sea fan neovascularization.
Stage of vitreous hemorrhage. Peripheral neovascular tufts bleed and cause vitreous hemorrhage.
Stage of vitreoretinal traction bands and tractional retinal detachment: Traction on the sea fan and adjacent retina causes traction retinal detachment.
Signs and Symptoms
Comma sign: Comma shaped vessels in the bulbar conjunctiva is due to vascular occlusion of conjunctival vessels.
Vitreoretinal traction or retinal detachment cause flashes, floaters or dark shadows.
Sudden loss of vision may occur due to retinal artery occlusion, vitreous hemorrhage or retinal detachment.
Intravascular occlusions may be seen in optic disc vessels.
Cause
Normal adult hemoglobin A molecule comprises two α and two β globin chains associated with a heme ring. Mutation at the 6th position of the beta chain is the cause of sickle cell disease. Due to sickle cell disease, vascular occlusion may occur in the conjunctiva, iris, retina, or choroid. Retinal changes occur due to blockage of retinal blood vessels by abnormal RBCs.
Diagnosis
Diagnostic Techniques
Diagnosis is conducted in a multidisciplinary manner. The diagnosis of sickle cell disease can be confirmed by cation high performance liquid chromatography, haemoglobin electrophoresis in adolescents and adults and molecular genetic diagnosis in prenatal and neonatal populations. Anterior segment signs including the conjunctival sign and iris atrophy are ocular manifestations that are strongly indicative of sickle cell disease. Early stages of sickle cell retinopathy are asymptomatic. However, retinal changes that are diagnostic of sickle cell retinopathy can be visualized using fundoscopic examinations, retinography, fluorescein angiography and coherence tomography. Ultra Widefield Fluorescein Angiography is the gold standard for diagnosis of proliferative sickle cell retinopathy. It is an invasive method that assesses both anterior and posterior segment structures. Spectral Domain Optical Coherence Tomography and Coherence Tomography Angiography are non invasive methods of diagnosing proliferative retinopathy. Visual acuity and intraocular pressure assessments can also yield results that are diagnostic of sickle cell retinopathy.
Differential diagnosis
Sickle cell retinopathy should be differentiated from other retinal conditions that arise due to similar pathologies. The following differentials are classified by those pathologies.
Additional causes of macular ischemiaDiabetic retinopathy
Retinal embolization (talc retinopathy, internal carotid artery embolism)
Retinal vascular occlusion
Infectious retinopathyInflammatory diseases leading to ischemiaSarcoidosis
Retinal vasculitis
Intermediate uveitis
Acute retinal necrosisAlternative causes of ischemic vascular diseaseProliferative diabetic retinopathy
Central retinal vein occlusion
Branch retinal vein occlusion
Ocular ischemic syndromE
Radiation retinopathy
Retinopathy of prematurityUnclassified causesIncontinentia pigmenti
Autosomal dominant vitreoretinochoroidopathy
Chronic rhegmatogenous retinal detachment
Scleral buckle
Retinitis pigmentosa
Prevention
Screening
Screening is an important pillar of prevention of sickle cell retinopathy as it provides the benefit of early detection and treatment thus reducing complications. Screening also provides an opportunity for education of families predisposed to retinopathy as a result of a family history of sickle cell disease. Screening can take the form of DNA screening at birth and Ophthalmology-related examinations later in life.
DNA screening in newborns at risk of having sickle cell disease allows the early diagnosis of the disease. Families can then be educated on the possible effects of sickle cell disease at each stage of life.
Ophthalmology-related examinations - dilated fundoscopic examination is recommended from the age of 10 and biannually thereafter in patients with no abnormal retinal findings. Fluorescein angiography and angioscopy is recommended for patients with abnormal findings that may be indicative of proliferative sickle cell retinopathy. The frequency of follow up appointments is determined by the ophthalmologist based on the severity of the findings.
Care of systemic disease
Sickle cell disease is a systemic disease that affects several organs in the body. Management of the underlying disease can therefore prevent the development of retinopathy and slow its progression.
Fetal haemoglobin transfusion - Fetal haemoglobin (HbF) is a form of haemoglobin that is found in children up to 6 months after birth. This type of haemoglobin is beneficial in sickle cell patients as it resists modification to the sickled shape. As a result, transfusion of HbF in younger populations can prevent and slow the progression of sickle cell retinopathy.
Hydroxyurea administration - Hydroxyurea is a drug that can be used as an alternative method of increasing fetal haemoglobin levels in the blood of a patient with sickle cell disease. Hydroxyurea also provides the benefit of reducing inflammation.
Haematopoetic stem cell transplantation - This process is more commonly known as a bone marrow transplant. It is useful in the management of sickle cell disease. However, access to this method is limited due to cost and the need for a donor that is biologically compatible with the person requiring the transplant.
Anti-inflammatory and anti-adhesive drugs reduce the likelihood of occlusions in the small blood vessels of the retina therefore preventing the development of sickle cell retinopathy. There drugs include anti adhesive antibodies, anti-integrin antibodies, anti-Willebrand factor, sulfasalazine and statins.
Gene therapy has also been proven beneficial in the prevention of sickle cell retinopathy.
Treatment
Medical
Vascular endothelial growth factor (VEGF) is known to be associated with sea fan lesions which are types of neovascularization. Bevacizumab is an anti-VEGF drug used in intravitreal injection that is known to cause reversal of sea fan lesions and reduce the duration of vitreous hemorrhage. Intravitreal injection of anti-VEGF drugs can also be used prior to surgery to aid separation of tissues involved in the sea fan lesion and to reduce intraoperative and postoperative hemorrhage. It is useful in combination with photocoagulation.
Laser
Indications for laser photocoagulation include
Peripheral neovascularization of upwards of 60° circumference
Sickle cell retinopathy affecting both eyes
Large elevated sea fans
Rapid progression of neovascularizationThere are two methods of photocoagulation mainly used; feeder vessel coagulation and scatter laser coagulation. The first method closes the vessels that supply the neovascularized areas using laser burns. Both the xenon arc and argon laser can be used however, the argon laser carries a reduced risk of complications. In comparison, scatter laser coagulation has an indirect effect. Ischemic retina produces vascular endothelial growth factor (VEGF) which promotes neovascularization. Scatter laser coagulation destroys this ischemic retina using laser burns thus preventing vitreous hemorrhage, retinal detachment and vision loss.
Surgery
Surgical intervention is indicated for severely advanced disease that poses a threat to visual acuity. Indications include longstanding vitreous haemorrhage, vitreous haemorrhage in both eyes, vitreous haemorrhage in patients with only one eye, epiretinal membranes, macular holes and the various forms of retinal detachment. Scleral buckle was a previously popular surgical intervention however, its complications include anterior segment ischemia as a result of vascular occlusion. The vascular occlusion can in turn lead to phthisis bulbi. Pars plans vitrectomy is useful for the management of vitreous haemorrhage. Its complications include cataracts, hyphema, glaucoma and unresolved vitreous haemorrhage.
== References == |
Hemifacial microsomia | Hemifacial microsomia (HFM) is a congenital disorder that affects the development of the lower half of the face, most commonly the ears, the mouth and the mandible. It usually occurs on one side of the face, but both sides are sometimes affected. If severe, it may result in difficulties in breathing due to obstruction of the trachea—sometimes even requiring a tracheotomy. With an incidence in the range of 1:3500 to 1:4500, it is the second most common birth defect of the face, after cleft lip and cleft palate.[1] HFM shares many similarities with Treacher Collins syndrome.
Presentation
The clinical presentation of HFM is quite variable. The severity may depend on the extent of the area with an insufficient blood supply in utero, and the gestational age of the fetus at which this occurs. In some people, the only physical manifestation may be a small and underdeveloped external ear. In more severe cases, multiple parts of the face may be affected. Some people with HFM may have sensorineural hearing loss and decreased visual acuity or even blindness.It can be thought of as a particularly severe form of HFM, in which extracranial anomalies are present to some extent. Some of the internal organs (especially the heart, kidneys, and lungs) may be underdeveloped, or in some cases even absent altogether. The affected organs are typically on the same side as the affected facial features, but bilateral involvement occurs in approximately 10% of cases. Deformities of the vertebral column such as scoliosis may also be observed.While there is no universally accepted grading scale, the OMENS scale (standing for Orbital, Mandible, Ear, Nerves and Soft tissue) was developed to help describe the heterogeneous phenotype that makes up this sequence or syndrome.Intellectual disability is not typically seen in people with HFM. Hemifacial microsomia sometimes results in temporomandibular joint disorders.
Cause
The condition develops in the fetus at approximately 4 weeks gestational age, when some form of vascular problem such as blood clotting leads to insufficient blood supply to the face. This can be caused by physical trauma, though there is some evidence of it being hereditary [2]. This restricts the developmental ability of that area of the face. Currently there are no definitive reasons for the development of the condition.
Diagnosis
Classification
Figueroa and Pruzanksky classified HFM patients into three different types:
Type I : Mild hypoplasia of the ramus, and the body of the mandible is slightly affected.
Type II : The condyle and ramus are small, the head of the condyle is flattened, the glenoid fossa is absent, the condyle is hinged on a flat, often convex, infratemporal surface, the coronoid may be absent.
Type III: The ramus is reduced to a thin lamina of bone or is completely absent. There is no evidence of a TMJ.
Treatment
Depending upon the treatment required, it is sometimes most appropriate to wait until later in life for a surgical remedy – the childhood growth of the face may highlight or increase the symptoms. When surgery is required, particularly when there is a severe disfiguration of the jaw, it is common to use a rib graft to help correct the shape.According to literature, HFM patients can be treated with various treatment options such as functional therapy with an appliance, distraction osteogenesis, or costochondral graft. The treatment is based on the type of severity for these patients. According to Pruzankskys classification, if the patient has moderate to severe symptoms, then surgery is preferred. If patient has mild symptoms, then a functional appliance is generally used.According to Dr. Harry Pepe, a pediatrician from Hollywood, Fl, the goal of treatment in hemifacial microsomia is to elongate the deficient jaw bone to restore facial symmetry and correct the slanting bite (occlusion).Patients can also benefit from a Bone Anchored Hearing Aid (BAHA).
Terminology
The condition is also known by various other names:
Lateral facial dysplasia
First and second branchial arch syndrome
Oral-mandibular-auricular syndrome
Otomandibular dysostosis
Craniofacial microsomia
See also
Condylar hypoplasia
Goldenhar syndrome
Parry–Romberg syndrome
References
^ "Hemifacial Microsomia" at the Tennessee Craniofacial Center. Accessed 20 January 2008.
^ "Hemifacial Microsomia" at the Childrens Hospital and Health System of Wisconsin. Accessed 20 January 2008.
External links
GeneReviews/NCBI/NIH/UW entry on Craniofacial Microsomia Overview |
Gradenigos syndrome | Gradenigos syndrome, also called Gradenigo-Lannois syndrome, is a complication of otitis media and mastoiditis involving the apex of the petrous temporal bone. It was first described by Giuseppe Gradenigo in 1904.
Symptoms
Components of the syndrome include:
retroorbital pain due to pain in the area supplied by the ophthalmic branch of the trigeminal nerve (fifth cranial nerve),
abducens nerve palsy (sixth cranial nerve)
otitis mediaOther symptoms can include photophobia, excessive lacrimation, fever, and reduced corneal sensitivity. The syndrome is classically caused by the spread of an infection into the petrous apex of the temporal bone.
Diagnosis
The constellation of symptoms was first described as a consequence of severe, advanced ear infection which has spread to a central portion of the temporal bone of the skull. This type of presentation was common prior to development of antibiotic treatments, and is now a rare complication.In persons with longstanding ear infection and typical symptoms, medical imaging such as CT or MRI of the head may show changes that confirm disease involvement of the petrous apex of temporal bone.
Treatment
The medical treatment is done with antibiotics: ceftriaxone plus metronidazole (which covers anaerobic bacteria). Depending on the duration of the infection, the severity, and which complications have arisen, it may also be necessary to perform surgery. Due to critical structures that block surgical access, it is not possible to completely remove the petrous apex. The focus is therefore on providing adequate drainage of the affected air cells.
Eponym
It is named after Count Giuseppe Gradenigo, an Italian Otolaryngologist, and Maurice Lannois.
References
== External links == |
Photic retinopathy | Photic retinopathy is damage to the eyes retina, particularly the macula, from prolonged exposure to solar radiation or other bright light, e.g., lasers or arc welders. The term includes solar, laser, and welders retinopathy and is synonymous with retinal phototoxicity. It usually occurs due to staring at the Sun, watching a solar eclipse, or viewing an ultraviolet, Illuminant D65, or other bright light.[1]
Signs and symptoms
Long-term reduced eyesight
Central or paracentral scotomaVision loss due to solar retinopathy is typically reversible, lasting for as short as one month to over one year. The fundus changes are variable and usually bilateral, mild cases often show no alteration and moderate to severe cases show a foveal yellow spot on the first days after exposure. After a few days it is replaced by a reddish dot often surrounded by pigment.
Permanent holes and lesions are possible; prognosis worsens with dilated pupils or prolonged exposure.
Pathophysiology
Although it is frequently claimed that the retina is burned by looking at the Sun, retinal damage appears to occur primarily due to photochemical injury rather than thermal injury. The temperature rise from looking at the Sun with a 3-mm pupil only causes a 4 °C increase in temperature, insufficient to photocoagulate. The energy is still phototoxic: since light promotes oxidation, chemical reactions occur in the exposed tissues with unbonded oxygen molecules. It also appears that central serous retinopathy can be a result of a depression in a treated solar damaged eye.The duration of exposure necessary to cause injury varies with the intensity of light, and also affects the possibility and length of recovery.
Diagnosis
A person with photic retinopathy may notice an impairment in their vision, for example a spot that does not go away after a reasonable recovery time, or blurring. They may also have eye pain or headaches. Vision impairment is usually in both eyes, but can be in just one. Impairment of a person with 20/20 vision usually ends up being about 20/40 or 20/60, but can be better or far worse.A doctor examining an eye with retinopathy may be able to see no signs at all, or a slight macular edema, which is a sort of blister on or under the macula, an oval colored spot normally visible to an eye doctor on each persons retina.
But while even that edema goes away, within a few days the patient will generally develop a discoloration of the retina at the injured point, often yellow or white, turning red over the next few weeks.
Treatment
Photic retinopathy generally goes away on its own over time, but there is no specific treatment known to be reliable for speeding recovery. One path sometimes attempted, which has unclear results, is to treat the initial macular edema with corticosteroids.
Prognosis
Generally speaking, people diagnosed with photic retinopathy recover visual acuity completely within two months, though more severe cases may take longer, or not see complete recovery at all.
See also
Retinopathy
References
7. ^ Stokkermans TJ, Dunbar MT. "Solar retinopathy in a hospital-based primary care clinic." J Am Optom Assoc. 1998 Oct;69(10):625-36. PMID 9805443 |
Alopecia totalis | Alopecia totalis is the loss of all hair on the head and face. Its causes are unclear, but believed to be autoimmune. Research suggests there may be a genetic component linked to developing alopecia totalis; the presence of DRB1*0401 and DQB1*0301, both of which are Human Leukocyte Antigens (HLA), were found to be associated with long-standing alopecia totalis.
Treatment
Methotrexate and corticosteroids are proposed treatments.Scalp cooling has specifically been used to prevent alopecia in docetaxel chemotherapy, although it has been found prophylactic in other regimens as well. Treatment effects may take time to resolve, with one study showing breast cancer survivors wearing wigs up to 2 years after chemotherapy.
See also
Alopecia areata
Alopecia universalis
References
== External links == |
Lupus vulgaris | Lupus vulgaris (also known as tuberculosis luposa) are painful cutaneous tuberculosis skin lesions with nodular appearance, most often on the face around the nose, eyelids, lips, cheeks, ears and neck. It is the most common Mycobacterium tuberculosis skin infection. The lesions may ultimately develop into disfiguring skin ulcers if left untreated.
Signs and symptoms
It begins as painless reddish-brown nodules which slowly enlarge to form irregularly shaped red plaque.
Cause
Lupus vulgaris often develops due to inadequately treated pre-existing tuberculosis. It may also develop at site of BCG vaccination. Rarely, it has been shown to be associated with tattoo marks.
Histopathology
Histologically, it shows presence of epithelioid cell granulomas with Langhans giant cells with or without central caseation necrosis in the dermis.
Diagnosis
On diascopy, it shows characteristic "apple-jelly" color. Biopsy will reveal tuberculoid granuloma with few bacilli. Mantoux test is positive.
Differential diagnosis
The condition should be distinguished from:
Basal cell carcinoma
Sarcoidosis
Discoid lupus erythomatosus
Leprosy
Deep fungal infection
Management
A dermatologist or general physician usually administers combination therapy of drugs used for tuberculosis, such as Rifampicin, Isoniazid and Pyrazinamide (possibly with either streptomycin or ethambutol).
Prognosis
In longstanding scarred lesions, squamous cell carcinoma can develop.
History
In the 19th century, the chronic and progressive nature of this disease was particularly marked: it remained active for ten years, twenty years, or even longer and, proved resistant to all treatment until the breakthrough by Niels Ryberg Finsen using a form of "concentrated light radiation" now known as Photobiomodulation which won him a Nobel Prize.
Queen Alexandra of Great Britain, (1844–1925), consort to Edward the VII, as the inscription on the bronze statue of her at the London Hospital, notes, "Introduced to England the Finsen light cure for Lupus, and presented the first lamp to this hospital".
Etymology
The term "lupus" (meaning "wolf" in Latin) to describe an ulcerative skin disease dates to the late thirteenth century, though it was not until the mid-nineteenth that two specific skin diseases were classified as lupus erythematosus and lupus vulgaris. The term may derive from the rapacity and virulence of the disease; a 1590 work described it as "a malignant ulcer quickly consuming the neather parts; ... very hungry like unto a woolfe".
See also
Miliary tuberculosis
Metastatic tuberculous abscess or ulceration
List of cutaneous conditions
References
External links
Image at University of Iowa (graphic)
Image of lupus vulgaris, 1914 from Our Friend, the Sun: Images of Light Therapeutics from the Osler Library Collection, c. 1901-1944. Digital exhibition by the Osler Library of the History of Medicine, McGill University. |
Meconium peritonitis | Meconium peritonitis refers to rupture of the bowel prior to birth, resulting in fetal stool (meconium) escaping into the surrounding space (peritoneum) leading to inflammation (peritonitis). Despite the bowel rupture, many infants born after meconium peritonitis in utero have normal bowels and have no further issues.
Infants with cystic fibrosis are at increased risk for meconium peritonitis.
Signs and symptoms
Diagnosis
Twenty percent of infants born with meconium peritonitis will have vomiting and dilated bowels on x-rays which necessitates surgery.
Meconium peritonitis is sometimes diagnosed on prenatal ultrasound where it appears as calcifications within the peritoneum.
Treatment
Adhesiolysis
partial resection of pseudocyst
covering enterostomy.
History
Meconium peritonitis was first described in 1838 by Carl von Rokitansky.
References
== External links == |
Occult macular dystrophy | Occult macular dystrophy (OMD) is a rare inherited degradation of the retina, characterized by progressive loss of function in the most sensitive part of the central retina (macula), the location of the highest concentration of light-sensitive cells (photoreceptors) but presenting no visible abnormality. "Occult" refers to the degradation in the fundus being difficult to discern. The disorder is called "dystrophy" instead of "degradation" to distinguish its genetic origin from other causes, such as age. OMD was first reported by Y. Miyake et al. in 1989.
Symptoms
Symptoms entail a loss of visual acuity in both eyes, including darkened vision, ring scotoma (ring of blindness close to the center of vision), color blindness, and difficulty with bright lights. The scotoma may cause text slightly away from the center of vision to disappear; the appearance would not be black (in early stages) but of the same color as the nearby background. Many lines of an Amsler grid would be faded or invisible to the patient. The area of invisibility on the Amsler grid spreads with time. Symptoms do not include headaches or eye pain. The loss of acuity tends to be symmetric between the eyes.
Etiology
OMD that is caused by mutations of the retinitis pigmentosa 1-like 1 (RP1L1) gene (OMIM 608581) is called Miyakes disease. While the mutation is dominant, OMD may manifest more strongly and earlier in children than in the parent (anticipation). However, cases have presented with no mutation to RP1L1. One study suggests that OMD arises because of two mutations arising simultaneously, one in RP1L1 and another in ABCA4.OMD is generally believed to be autosomal dominant, meaning that if you get the abnormal gene from only one parent, you can get the disease. However, this does not always seem to be the case.OMD differentiates from Stargardt macular dystrophy in which gene is mutated (RP1L1 instead of ABCA4), the process of OMD isnt a buildup of toxic lipofuscin, and Stargardt is regressive.
Physiology
The connection between these mutations and OMD is unclear, but cone density is significantly lower in patients with OMD compared to the general population. Use of adaptive optics to obtain high-resolution retinal images reveal abnormal changes in patients with OMD, including thinning of the foveal thickness and the outer nuclear layer and disruption of the IS/OS line and COST line.
Diagnosis
OMD returns negative results for a funduscopic inspection, fluorescein angiogram, and full-field electroretinogram (ERG), for both rod and cone components. The key to diagnosing this disorder is the multifocal ERG (mfERG), providing a single procedure for diagnosis. Onset is known to range from age 6 to 81, with about half of onsets occurring after age 65.
Differential diagnosis
A visual field test can differentiate between whether the reduced visual acuity is centered on the optic nerve or the fundus.
Once a neurological problem has, therefore, been ruled out, the disorders reduced visual acuity without visible fundus abnormalities may be misdiagnosed as optic neuritis, dominant optic atrophy, amblyopia, or nonorganic visual disorder.The combination of weak amplitudes in the mfERG with no visible fundus abnormalities then rules out other explanations. For example, OMD presents negative for a full-field ERG while retinitis pigmentosa presents abnormal.
Prognosis
Since the abnormality is not in the eye lens, the disease is not correctable with eyeglasses. Vision becomes dimmer over the course of years as the macula loses function. Eventually the patient may become legally blind. The peripheral vision field is preserved. In other words, OMD does not cause total blindness, due to the concentration of the degradation at the cone-rich (color-sensitive) region of the retina. No treatment is known to slow the progression. The speed of progression varies by case — even between donor and recipient of the mutation — and can last for 10 to 30 years.
Future research
Because of the rarity of OMD, no clinical trials are in the pipeline as of January 2019. However, mutations in RP1L1 might play a role in retinitis pigmentosa (RP), raising hope for a spillover effect for OMD patients should an RP1L1-related treatment be developed for RP. Given the possible relation between ABCA4 and OMD, progress with Stargardt disease via gene therapy might have a spillover effect for OMD patients as well.
Adeno-associated viral (AAV) vectors have been particularly successful in gene therapy of eyes and muscles. Unfortunately, their size is limited--too limited to hold the RP1L1 gene. Therefore, a non-viral approach would need to be developed for gene therapy to treat OMD. Since RP1 has the same size problem, a gene therapy for RP could have a spillover effect for OMD.
A stem-cell approach might entail taking stem cells from the patient, editing the mutation with CRISR, and inserting the stem cells in the eye. However, as of 2014, researchers did not yet know if retinal stem cell surgery would work.
Prevalence
Prevalence is unknown, but seems to be elevated in Asian populations, given that most OMD studies are of Japanese and Korean subjects. Given that Stargardts, the most common macular dystrophy, has a prevalence of 1 in 10,000 in the US, the prevalence of OMD is likely well below 1 in 100,000.
== References == |
Cold injury | A cold injury is defined as one in which cold temperature is the agent that causes tissue damage. Types of cold injury include chilblains, trenchfoot, frostbite, and immersion foot.
Notes
References
Whayne, Tom French; DeBakey, Michael E. (1984). Cold Injury, Ground Type (PDF). Medical Department, United States Army, in World War II. Washington, D.C.: U.S. Army Center of Military History. OCLC 19967629. Retrieved 25 June 2021. |
Chilblains | Chilblains, also known as pernio, is a medical condition in which damage occurs to capillary beds in the skin, most often in the hands or feet, when blood perfuses into the nearby tissue resulting in redness, itching, inflammation, and possibly blisters. It occurs most frequently when predisposed individuals, predominantly women, are exposed to cold and humidity. Ulcerated chilblains are referred to as kibes. Temperature-related chilblains can be prevented by keeping the feet and hands warm in cold weather and avoiding exposing these areas to extreme temperature changes. Once the diagnosis of chilblains is made, first-line treatment includes avoiding cold, damp environments and wearing gloves and warm socks.Chilblains can be idiopathic (spontaneous and unrelated to another disease), but similar symptoms may also be a manifestation of another serious medical condition that must be investigated. Related medical conditions include Raynaud syndrome, erythromelalgia, frostbite, and trench foot, as well as connective tissue diseases such as lupus or vasculitis. In infants affected by Aicardi–Goutières syndrome (a rare inherited condition which affects the nervous system) chilblain-like symptoms occur together with severe neurologic disturbances and unexplained fevers.
Signs and symptoms
The areas most affected are the toes, fingers, earlobes, nose.
Blistering of affected area
Burning and itching sensation in extremities
Dermatitis in extremities
Ulceration (severe cases only)
Erythema (blanchable redness of the skin)
Pain in affected area
Skin discoloration, red to dark blueChilblains caused by exposure to low temperatures usually heal within 7–14 days.
Prevention
Exposure
Keep affected area warm, and avoid any extreme temperature changes (including very hot water).
Keep affected area dry.
Wear warm shoes, socks and gloves.
Wear a hat and a scarf to protect the ears and the nose.
Avoid tight fitting socks/shoes.
Other
Exercise at least four times a week to improve circulation.
Quit smoking, as it damages circulation.
Treatment
Nifedipine and amlodipine, which are vasodilators in the class of drugs known as calcium channel blockers, may help in some cases. Vasodilation may reduce pain, facilitate healing, and prevent recurrences. It is typically available in an oral pill but can be compounded into a topical formula.
Diltiazem, a vasodilator, may help.
Apply a mixture of friars balsam and a weak iodine solution.
History
The medieval Balds Leechbook recommended treating chilblains with a mixture of eggs, wine, and fennel root. A modern-day home remedy is to put garlic on the chilblains. Neither of these remedies has been supported by scientific research.
COVID-19
Chilblain-like symptoms have also been linked to COVID-19. COVID toes, as they are commonly known, have mostly been reported in older children and adolescents, who often have not had other symptoms of COVID-19. The symptoms are usually mild and disappear without treatment. Their cause is debated: it is uncertain whether COVID toes are a delayed consequence of the viral infection itself or are, at least partially, connected to environmental factors during the COVID-19 pandemic. They may share some of the microscopic features of chilblains caused by lupus. It has been suggested that in the absence of exposure to cold and damp, COVID-19 should be considered as a possible cause of chilblains.In a study at the dermatology department of Saint-Louis Hospital in Paris, researchers found that most of their study participants carried high levels of autoantibodies, proteins generated by the immune system that inadvertently attack the bodys own tissues. Compared with healthy individuals, the participants showed high activity of proteins called type 1 interferons, which switch on pathogen-fighting genes in immune cells.
See also
Equestrian perniosis
Erythrocyanosis crurum
Raynauds disease
References
External links
DermAtlas 1683395337
Cold stress, National Institute for Occupational Safety and Health |
Savant syndrome | Savant syndrome () is a rare condition in which someone with significant mental disabilities demonstrates certain abilities far in excess of average. The skills that savants excel at are generally related to memory. This may include rapid calculation, artistic ability, map making, or musical ability. Usually, only one exceptional skill is present.Those with the condition generally have a neurodevelopmental disorder such as autism spectrum disorder or have a brain injury. About half of cases are associated with autism, and these individuals may be known as "autistic savants". While the condition usually becomes apparent in childhood, some cases develop later in life. It is not recognized as a mental disorder within the DSM-5.Savant syndrome is estimated to affect around one in a million people. The condition affects more males than females, at a ratio of 6:1. The first medical account of the condition was in 1783. Among those with autism, 1 in 10 to 1 in 200 have savant syndrome to some degree. It is estimated that there are fewer than a hundred prodigious savants, with skills so extraordinary that they would be considered spectacular even for a non-impaired person, currently living.
Signs and symptoms
Savant skills are usually found in one or more of five major areas: art, memory, arithmetic, musical abilities, and spatial skills. The most common kinds of savants are calendrical savants, "human calendars" who can calculate the day of the week for any given date with speed and accuracy, or recall personal memories from any given date. Advanced memory is the key "superpower" in savant abilities.Approximately half of savants are autistic; the other half often have some form of central nervous system injury or disease. It is estimated that up to 10% of those with autism have some form of savant abilities.
Calendrical savants
A calendrical savant (or calendar savant) is someone who – despite having an intellectual disability – can name the day of the week of a date, or vice versa, on a limited range of decades or certain millennia. The rarity of human calendar calculators is possibly due to the lack of motivation to develop such skills among the general population, although mathematicians have developed formulas that allow them to obtain similar skills. Calendrical savants, on the other hand, may not be prone to invest in socially engaging skills.
Mechanism
Psychological
No widely accepted cognitive theory explains savants combination of talent and deficit. It has been suggested that individuals with autism are biased towards detail-focused processing and that this cognitive style predisposes individuals either with or without autism to savant talents. Another hypothesis is that savants hyper-systemize, thereby giving an impression of talent. Hyper-systemizing is an extreme state in the empathizing–systemizing theory that classifies people based on their skills in empathizing with others versus systemizing facts about the external world. Also, the attention to detail of savants is a consequence of enhanced perception or sensory hypersensitivity in these unique individuals. It has also been hypothesized that some savants operate by directly accessing deep, unfiltered information that exists in all human brains that is not normally available to conscious awareness.
Neurological
In some cases, savant syndrome can be induced following severe head trauma to the left anterior temporal lobe. Savant syndrome has been artificially replicated using low-frequency transcranial magnetic stimulation to temporarily disable this area of the brain.
Epidemiology
There are no objectively definitive statistics about how many people have savant skills. The estimates range from "exceedingly rare" to one in ten people with autism having savant skills in varying degrees. A 2009 British study of 137 parents of autistic children found that 28% believe their children met the criteria for a savant skill, defined as a skill or power "at a level that would be unusual even for normal people". As many as 50 cases of sudden or acquired savant syndrome have been reported.Males with savant syndrome outnumber females by roughly 6:1 (in Finland), slightly higher than the sex ratio disparity for autism spectrum disorders of 4.3:1.
History
The term idiot savant (French for "learned idiot") was first used to describe the condition in 1887 by John Langdon Down, who is known for his description of Down syndrome. The term idiot savant was later described as a misnomer because not all reported cases fit the definition of idiot, originally used for a person with a very severe intellectual disability. The term autistic savant was also used as a description of the disorder. Like idiot savant, the term came to be considered a misnomer because only half of those who were diagnosed with savant syndrome were autistic. Upon realization of the need for accuracy of diagnosis and dignity towards the individual, the term savant syndrome became widely accepted terminology.
Society and culture
Notable cases
Aleksander Vinter, known as "Savant", musician and producer
Daniel Tammet, British author and polyglot
Derek Paravicini, British blind musical prodigy and pianist
Henriett Seth F., Hungarian autistic writer and artist
Kim Peek, American "megasavant"
Leslie Lemke, American musician
Rex Lewis-Clack, American pianist and musical savant
Matt Savage, American musician
Stephen Wiltshire, British architectural artist
Temple Grandin, American professor of animal science
David M. Nisson, American scientist
Tom Wiggins, American blind pianist and composer
Tommy McHugh, British artist and poet
Kodi Lee, 2019 Americas Got Talent winner (musician)
Acquired cases
Alonzo Clemons, American acquired savant sculptor
Anthony Cicoria, American acquired savant pianist and medical doctor
Derek Amato, American composer and pianist, he has developed savant syndrome and synesthesia
Patrick Fagerberg, American acquired savant artist, inventor and former lawyer.
Orlando Serrell, American acquired savant
Jason Padgett, American mathematician, acquired after being hit in the back of the head while at a bar
Fictional cases
Raymond Babbitt, autistic savant in the 1988 film Rain Man (inspired by Kim Peek)
Park Shi-on, autistic savant in the 2013 South Korean medical drama Good Doctor
Shaun Murphy, autistic savant in the 2017 U.S. medical drama The Good Doctor
Kazan, autistic savant in the 1997 film Cube
Kazuo Kiriyama, main antagonist in the Japan 1999 novel Battle Royale
Jeong Jae-hee, autistic savant in the 2021 South Korean psychological drama Mouse
Patrick Obyedkov, autistic savant in a 2007 episode of the U.S. medical drama House.
Woo Young-woo, autistic savant in the 2022 South Korean legal drama Extraordinary Attorney Woo.
See also
Autistic art
Child prodigy
Creativity and mental illness
Idiot
Mental calculator
Hyperthymesia
Ideasthesia
Twice exceptional
== References == |
Pott disease | Pott disease is tuberculosis of the spine, usually due to haematogenous spread from other sites, often the lungs. The lower thoracic and upper lumbar vertebrae areas of the spine are most often affected.
It causes a kind of tuberculous arthritis of the intervertebral joints. The infection can spread from two adjacent vertebrae into the adjoining intervertebral disc space. If only one vertebra is affected, the disc is normal, but if two are involved, the disc, which is avascular, cannot receive nutrients, and collapses. In a process called caseous necrosis, the disc tissue dies, leading to vertebral narrowing and eventually to vertebral collapse and spinal damage. A dry soft-tissue mass often forms and superinfection is rare.
Spread of infection from the lumbar vertebrae to the psoas muscle, causing abscesses, is not uncommon.The disease is named after Percivall Pott, the British surgeon who first described it in the late 18th century.
Diagnosis
Blood tests– Complete blood count: leukocytosis
– Elevated erythrocyte sedimentation rate: >100 mm/hTuberculin skin test– Tuberculin skin test (purified protein derivative [PPD]) results are positive in 84–95% of patients with Pott disease who are not infected with HIV.
Radiographs of the spine– Radiographic changes associated with Pott disease present relatively late. These radiographic changes are characteristic of spinal tuberculosis on plain radiography:
Lytic destruction of anterior portion of vertebral body
Increased anterior wedging
Collapse of vertebral body
Reactive sclerosis on a progressive lytic process
Enlarged psoas shadow with or without calcification
– Additional radiographic findings may include:
Vertebral end plates are osteoporotic.
Intervertebral disks may be shrunken or destroyed.
Vertebral bodies show variable degrees of destruction.
Fusiform paravertebral shadows suggest abscess formation.
Bone lesions may occur at more than one level.Bone scan
Computed tomography of the spine
Bone biopsy
MRI
Prevention
Controlling the spread of tuberculosis infection can prevent tuberculous spondylitis and arthritis. Patients who have a positive PPD test (but not active tuberculosis) may decrease their risk by properly taking medicines to prevent tuberculosis. To effectively treat tuberculosis, patients must take their medications exactly as prescribed.
Management
Nonoperative – antituberculous drugs
Analgesics
Immobilization of the spine region using different types of braces and collars
Surgery may be necessary, especially to drain spinal abscesses or debride bony lesions fully or to stabilize the spine. A 2007 review found just two randomized clinical trials with at least one-year follow-up that compared chemotherapy plus surgery with chemotherapy alone for treating people diagnosed with active tuberculosis of the spine. As such, no high-quality evidence exists, but the results of this study indicates that surgery should not be recommended routinely and clinicians have to selectively judge and decide on which patients to operate.
Thoracic spinal fusion with or without instrumentation as a last resort.
Physical therapy for pain-relieving modalities, postural education, and teaching a home-exercise program for strength and flexibility
Prognosis
Vertebral collapse resulting in kyphosis
Spinal cord compression
Sinus formation
Paraplegia (so-called Potts paraplegia)
History
Saint Gemma of Lucca had tuberculosis of the spine.
English poets Alexander Pope and William Ernest Henley both had Pott disease.
Anna Roosevelt Cowles, sister of President Theodore Roosevelt, had Pott disease.
Søren Kierkegaard may have died from Pott disease, according to professor Kaare Weismann and literature scientist Jens Staubrand
Chick Webb, a swing-era drummer and band leader, was affected by tuberculosis of the spine as a child, which left him hunchbacked, and eventually caused his death.
The Sicilian mafia boss Luciano Leggio had the disease and wore a brace.
Italian writer, poet, and philosopher Giacomo Leopardi had the disease.
It features prominently in the book This Is a Soul, which chronicles the work of American physician Rick Hodes in Ethiopia.
Jane Addams, social activist and Nobel Peace Prize winner, had Pott disease.
Willem Ten Boom, brother of Corrie Ten Boom, died of tuberculosis of the spine in December 1946
Writer Max Blecher had Pott disease. His story is portrayed in the 2016 film Scarred Hearts.
Marxist thinker and Communist leader Antonio Gramsci had Pott disease, probably due to the bad conditions of his incarceration in fascist Italy during the 1930s.
Gavrilo Princip, who assassinated Archduke Franz Ferdinand of Austria, leading to World War I, died in prison of bone tuberculosis.
English writer Denton Welch (1915–1948) died of spinal tuberculosis after being involved in a motor accident (1935) that irreparably damaged his spine.
Louis Joseph, Dauphin of France, son of King Louis XVI and Marie Antoinette
In works of fiction
In Ernest Pooles Pulitzer Prize-winning novel, His Family, young Johnny Geer has a terminal case of Pott disease.
The fictional Hunchback of Notre Dame has a gibbus deformity similar to the type caused by tuberculosis.
In Henrik Ibsens play A Dolls House, Dr. Rank has "consumption of the spine".
Jocelin, the dean who wanted a spire on his cathedral in William Goldings The Spire, probably died as a result of the disease.
Morton, the railroad magnate in the film Once Upon a Time in the West, has the disease and needs crutches to walk.
Imogen, in the novella "The Princess with the Golden Hair", part of Memoirs of Hecate County by Edmund Wilson (1946), has Pott disease.
In the story Two Gentlemen of Verona, written by A. J. Cronin, Lucia had tuberculosis of spine.
References
External links
Pott Disease — Tuberculous Spondylitis (medical article with MRI picture), eMedicine, 2018-08-30.
"Tuberculous arthritis", MedlinePlus, USA: NIH. Public domain.
Potts Disease of the Thoracic Spine |
Drug-induced lupus erythematosus | Drug-induced lupus erythematosus is an autoimmune disorder caused by chronic use of certain drugs. These drugs cause an autoimmune response (the body attacks its own cells) producing symptoms similar to those of systemic lupus erythematosus (SLE). There are 38 known medications to cause DIL but there are three that report the highest number of cases: hydralazine, procainamide, and quinidine. While the criteria for diagnosing DIL has not been thoroughly established, symptoms of DIL typically present as muscle pain and joint pain. Generally, the symptoms recede after discontinuing use of the drugs.
Signs and symptoms
Signs and symptoms of drug-induced lupus erythematosus include the following:
Joint pain (arthralgia) and muscle pain (myalgia)
Fatigue
Serositis—inflammation of the tissues lining the heart and lungs.
Anti-histone antibodies in 95% of cases among those taking procainamide, hydralazine, chlorpromazine, and quinidine; however, these antibodies have been found in a smaller proportion of patients associated with other medications, including minocycline, propylthiouracil, and statins.These signs and symptoms are not side effects of the drugs taken which occur during short term use. DIL occurs over long-term and chronic use of the medications listed below. While these symptoms are similar to those of systemic lupus erythematosus, they are generally not as severe unless they are ignored which leads to more harsh symptoms, and in some reported cases, death.
Causes
The processes that lead to drug-induced lupus erythematosus are not entirely understood. The exact processes that occur are not known even after 50 years since its discovery, but many studies present theories on the mechanisms of DIL.A predisposing factor to developing DIL is N-acetylation speed, or the rate at which the body can metabolize the drug. This is greatly decreased in patients with a genetic deficiency of the enzyme N-acetyltransferase. A study showed that 29 of 30 patients with DIL were slow acetylators. In addition, these patients had more hydralazine metabolites in their urine than fast acetylators. These metabolites (byproducts of the interactions between the drug and constituents in the body) of hydralazine are said to have been created when white blood cells have been activated, meaning they are stimulated to produce a respiratory burst. Respiratory burst in white blood cells induces an increased production of free radicals and oxidants such as hydrogen peroxide. These oxidants have been found to react with hydralazine to produce a reactive species that is able to bond to protein. Monocytes, one type of white blood cell, detect the antigen and relay the recognition to T helper cells, creating antinuclear antibodies leading to an immune response. Further studies on the interactions between oxidants and hydralazine are necessary to understand the processes involved in DIL.Of the drugs that cause DIL, hydralazine has been found to cause a higher incidence. Hydralazine is a medication used to treat high blood pressure. Approximately 5% of the patients who have taken hydralazine over long periods of time and in high doses have shown DIL-like symptoms. Many of the other drugs have a low to very low risk to develop DIL. The following table shows the risk of development of DIL of some of these drugs on a high to very low scale.
High risk:
Procainamide (antiarrhythmic)
Hydralazine (antihypertensive)
Moderate risk:
Quinidine (antiarrhythmic)
Low to Very Low Risk:
Infliximab anti (TNF-α)
Etanercept anti (TNF-α)
Isoniazid (antibiotic)
Minocycline (antibiotic)
Pyrazinamide (antibiotic)
D-Penicillamine (anti-inflammatory)
Carbamazepine (anticonvulsant)
Oxcarbazepine (anticonvulsant)
Phenytoin (anticonvulsant)
Propafenone (antiarrhythmic)
Chlorpromazine (antipsychotic)
Minoxidil (antihypertensive vasodilator)
Diagnosis
Antinuclear antibodies are usually positive in drug-induced Lupus. Anti-Neutrophil Cytoplasmic antibodies (ANCA) can also be positive in association with certain drugs. Furthermore, anti-histone antibodies can also be positive in drug-induced lupus.Anti-Histone antibodies are positive in up to 95% of patients with drug induced lupus. The most common medications associated with drug induced lupus are hydralazine, procainamide, isoniazid, methyldopa, chlorpromazine, quinidine, and minocycline.
Treatment
It is important to recognize early that these drugs are causing DIL like symptoms and discontinue use of the drug. Symptoms of drug-induced lupus erythematosus generally disappear days to weeks after medication use is discontinued. Non-steroidal anti-inflammatory drugs (NSAIDs) will quicken the healing process. Corticosteroids may be used if more severe symptoms of DIL are present.
See also
Anti-histone antibody
Lupus erythematosus
Hydralazine
Discoid lupus erythematosus
List of cutaneous conditions
References
External links
eMedicine |
Anisomelia | Anisomelia is a genus of moths in the family Geometridae described by Warren in 1895.
== References == |
Spigelian hernia | A Spigelian is the type of ventral hernia where aponeurotic fascia pushes through a hole in the junction of the linea semilunaris and the arcuate line creating a bulge. It appears in the abdomen lower quadrant between an area of dense fibrous tissue and abdominal wall muscles causing a (Spigelian aponeurosis).It is the protuberance, of omentum, adipose tissue, or bowel in that weak space between the abdominal wall muscles, that ultimately pushes the intestines or superficial fatty tissue through a hole causing a defect. As a result, it creates the movement of an organ or a loop of intestine in the weakened body space that it is not supposed to be in. It is at this separation (aponeurosis) in the ventral abdominal region, that herniation most commonly occurs.
Spigelian hernias are rare compared to other types of hernias because they do not develop under abdominal layers of fat but between fascia tissue that connects to muscle. The Spigelian hernia is generally smaller in diameter, typically measuring 1–2 cm., and the risk of tissue becoming strangulated is high.
Signs and symptoms
Individuals typically present with either intermittent pain (coming and going), a lump, or mass all which are classic signs of a bowel obstruction. The patient may have a protuberance when standing in an upright position although discomfort can sometimes be confused by its anatomical region for a peptic ulceration. The bulge may be painful when the patient stretches but then goes away when they are lying down in a resting position. However, a number of patients present with no obvious symptoms but vague tenderness along the area in which the Spigelian fascia is located.
Diagnosis
Ultrasound Imaging or a CT Scan will provide better imaging for the detection of a hernia than an xray. The ultrasound probe should move from lateral to medially, a hypoechoic mass should appear anteriorly and medially to the inferior epigastric artery during Valsalva maneuver. The diagnosis of a Spigelian hernia is traditionally difficult if only given a history and physical examination. People who are good candidates for elective Spigelian hernia surgery, not only but also, after receiving an initial diagnostic consultation by a licensed medical professional, will be advised to see a physician to schedule surgery.
Treatment
The Spigelian hernia can be repaired by either an open procedure or laproscopic surgery because of the high risk of strangulation; surgery is straightforward, with only larger defects requiring a mesh prosthesis. In contrast to the laparoscopic intraperitoneal onlay mesh plan of action there is a significant higher risk associated with complications and recurrence rates during the period following a surgical operation. A Spigelian hernia becomes immediately operative once the risk of incarceration is confirmed. Today, a Spigelian hernia can be repaired by doing robotic laparoscopy and most patients can go home the same day. This novel uncomplicated approach to small Spigelian hernias combines the benefits of laparoscopic localization, reduction, and closure without the morbidity and cost associated with foreign material. Mesh-free laparoscopic suture repair is an uncomplicated approach to small Spigelian hernias combined with the benefits of a closure without the anguish and cost associated with foreign material.
Eponym
Adriaan van den Spiegel, born in Brussels, was an anatomist at the University of Padua during the 17th century. In 1619 he became a professor of surgery. Spiegel was the first to described this rare hernia in 1627. The history of the Spigelian hernia became acknowledged in 1645, twenty years after Spiegels death. In 1764, almost a century later, the Flemish anatomist, Josef Klinkosch was acknowledged for recognizing and describing a hernia located in the Spigelian fascia, and coined the term Spigelian hernia.
Raveenthiran syndrome
Raveenthiran described a new syndrome in which Spigelian hernia and cryptorchidism (undescended testis) occur together. Some common complications of this distinct syndrome cryptorchidism are testicular torsion, and its link to testicular cancer.
References
External links
Adriaan van den Spiegel at Who Named It?
Laparoscopic Repair of Spigelian Hernia Medtube |
Brachydactyly | Brachydactyly (Greek βραχύς = "short" plus δάκτυλος = "finger"), is a medical term which literally means "short finger". The shortness is relative to the length of other long bones and other parts of the body. Brachydactyly is an inherited, usually dominant trait. It most often occurs as an isolated dysmelia, but can also occur with other anomalies as part of many congenital syndromes. Brachydactyly can also be a signal that one will be at risk for heart problems as they age.Nomograms for normal values of finger length as a ratio to other body measurements have been published. In clinical genetics, the most commonly used index of digit length is the dimensionless ratio of the length of the third (middle) finger to the hand length. Both are expressed in the same units (centimeters, for example) and are measured in an open hand from the fingertip to the principal creases where the finger joins the palm and where the palm joins the wrist.
Types
There are several types of Brachydactyly:
Other syndromes
In the above brachydactyly syndromes, short digits are the most prominent of the anomalies, but in many other syndromes (Down syndrome, Rubinstein–Taybi syndrome, etc.), brachydactyly is a minor feature compared to the other anomalies or problems comprising the syndrome.
See also
Hypertension and brachydactyly syndrome
Thumb stiffness-brachydactyly-intellectual disability syndrome
Clubbed thumb
Syndactyly
References
External links
Type A2
Brachydactyly type A1 at NIHs Office of Rare Diseases
Brachydactyly type A2 at NIHs Office of Rare Diseases
Brachydactyly type A3 at NIHs Office of Rare Diseases
Brachydactyly type A6 at NIHs Office of Rare Diseases
Brachydactyly type A7 at NIHs Office of Rare Diseases
Brachydactyly type B at NIHs Office of Rare Diseases
Brachydactyly type C at NIHs Office of Rare Diseases
Brachydactyly type E at NIHs Office of Rare Diseases
Brachydactyly types B and E combined at NIHs Office of Rare Diseases |
Aquagenic urticaria | Aquagenic urticaria, also known as water allergy and water urticaria, is a rare form of physical urticaria in which hives develop on the skin after contact with water, regardless of its temperature. The condition typically results from contact with water of any type, temperature or additive.
Signs and symptoms
The main symptom of aquagenic urticaria is the development of physical hives, which may or may not itch. Itching after contact with water, without the development of physical hives, is known as aquagenic pruritus. Aquadynia is a condition in which pain occurs after contact with water.In severe cases, drinking water can result in swelling of the oral cavity , swelling of the throat and in extreme cases, anaphylaxis. The hives associated with aquagenic urticaria are typically small (approximately 1–3 mm), red- or skin-colored welts (called wheals) with clearly defined edges. It most commonly develops on the neck, upper trunk and arms, although it can occur anywhere on the body. Once the water source is removed, the rash generally fades within 30 to 60 minutes.Water in all forms, such as tap or sea water, swimming pool water, sweat, tears, and saliva can induce the lesions.
Cause
The cause of aquagenic urticaria is not fully understood; however, several mechanisms have been proposed. Interaction between water and a component in or on the skin or sebum has been suggested. This theory suggests that a substance is formed by this interaction, the absorption of which causes perifollicular mast cell degranulation with release of histamine. Another proposed theory is of a water-soluble allergen in the epithelial tissues. Water dissolves the allergen, causing it to diffuse into the tissues, causing histamine release from sensitized mast cells.
Diagnosis
Diagnosis of aquagenic urticaria begins with a clinical history and water challenge test. The water challenge test consists of application of a 35°C water compress to the upper body for 30 minutes. Water of any temperature can provoke aquagenic urticaria; however, keeping the compress at a similar temperature to that of the human body (37 °C) avoids confusion with cold urticaria or cholinergic urticaria. In addition, a forearm or hand can be immersed in water of varying temperatures to determine whether temperature is a factor in the patients condition. Aquagenic urticaria differs from aquagenic pruritus, in which contact with water evokes intense itching without visible hives or rash.Once known as a separate, rare disease, aquagenic urticaria is now considered a subtype of general urticaria. The first case was reported by Walter B Shelley et al. in 1964. The condition is more common in women than men, and typically presents for the first time during puberty. Genetics may play a part, and the condition may be related to other sensitivities such as lactose intolerance.
Prevention
Desensitization does not seem to work for aquagenic urticaria; a patient will continue to react to water no matter how gradually or frequently it is introduced. Topical application of antihistamines like 1% diphenhydramine before water exposure is reported to reduce the hives. Oil in water emulsion creams, or petrolatum, applied as barrier agents prior to a shower or bath may control symptoms. Therapeutic effectiveness of various classes of drugs differs from case to case.
Treatment
There is currently no treatment that will permanently cure the condition. Avoidance of water is recommended as a first line of defense, and most treatments are palliative in nature rather than curative
Oral or topical antihistamine
Topical corticosteroids: specifically stanozolol.
Phototherapy
Barrier cream
See also
Aquagenic pruritus
Aquadynia
Cholinergic urticaria
Solar urticaria
List of cutaneous conditions
== References == |
Acute uric acid nephropathy | Acute uric acid nephropathy (AUAN, also acute urate nephropathy) is a rapidly worsening (decreasing) kidney function (acute kidney injury) that is caused by high levels of uric acid in the urine (hyperuricosuria).
Causes
Acute uric acid nephropathy is usually seen as part of the acute tumour lysis syndrome in patients undergoing chemotherapy or radiation therapy for the treatment of malignancies with rapid cell turnover, such as leukemia and lymphoma. It may also occur in these patients before treatment is begun, due to spontaneous tumor cell lysis (high incidence in Burkitts lymphoma).
Acute uric acid nephropathy can also be caused by an acute attack of gout.
Pathophysiology
Acute uric acid nephropathy is caused by deposition of uric acid crystals within the kidney interstitium and tubules, leading to partial or complete obstruction of collecting ducts, renal pelvis, or ureter. This obstruction is usually bilateral, and patients follow the clinical course of acute kidney failure.
Diagnosis
The picture of acute kidney failure is observed: decreased urine production and rapidly rising serum creatinine levels. Acute uric acid nephropathy is differentiated from other forms of acute kidney failure by the finding of a urine uric acid/creatinine ratio > 1 in a random urine sample.
Prevention
Patients at risk for acute uric acid nephropathy can be given allopurinol or rasburicase (a recombinant urate oxidase) prior to treatment with cytotoxic drugs.
Treatment
Treatment is focused on preventing deposition of uric acid within the urinary system by increasing urine volume with potent diuretics such as furosemide. Raising the urinary pH to a level higher than 7 (alkalinization) is often difficult to attain, although sodium bicarbonate and/or acetazolamide are sometimes used in an attempt to increase uric acid solubility.
Dialysis (preferably hemodialysis) is started if the above measures fail.
References
Conger JD (1990). "Acute uric acid nephropathy". Med Clin North Am. 74 (4): 859–71. PMID 2195258.
Robinson RR, Yarger WE (1977). "Acute uric acid nephropathy". Arch Intern Med. 137 (7): 839–40. doi:10.1001/archinte.137.7.839. PMID 879920.
Yu AS, Brenner BM (2005). "Chapter 266: Tubulointerstitial diseases of the kidney". In Kasper DL, Braunwald E, Fauci A, Hauser S, Longo D, Jameson JL (eds.). Harrisons Principles of Internal Medicine (16th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-140235-4 |
Median nail dystrophy | Median nail dystrophy (also known as "Dystrophia unguis mediana canaliformis," "Median canaliform dystrophy of Heller,": 657 and "Solenonychia") consists of longitudinal splitting or canal formation in the midline of the nail, a split which often resembles a fir tree, occurring at the cuticle and proceeding outward as the nail grows.: 788 Thumbs, which are the most commonly involved, usually show an enlarged lunula resulting probably from repeated pressure applied on the base of the nail.: 657
See also
Nail (anatomy)
Habit-tic deformity
== References == |
Cyclothymia | Cyclothymia ( siy-kluh-THIY-mee-uh), also known as cyclothymic disorder, psychothemia/psychothymia, bipolar III, affective personality disorder and cyclothymic personality disorder, is a mental and behavioural disorder that involves numerous periods of symptoms of depression and periods of symptoms of elevated mood. These symptoms, however, are not sufficient to indicate a major depressive episode or a manic episode. Symptoms must last for more than one year in children and two years in adults.The cause of cyclothymia is unknown. Risk factors include a family history of bipolar disorder. Cyclothymia differs from bipolar in that major depression and mania are not found.Treatment is generally achieved with counseling and mood stabilizers such as lithium. It is estimated that 0.4-1% of people have cyclothymia at some point in their life. The disorders onset typically occurs in late childhood to early adulthood. Males and females are affected equally often.
Symptoms
People with cyclothymia experience both depressive phases and hypomanic phases (which are less severe than full manic episodes). The depressive and hypomanic symptoms in cyclothymia last for variable amounts of time due to the unstable and reactive nature of the disorder. The depressive phases are similar to major depressive disorder and are characterized by dulled thoughts and sensations and the lack of motivation for intellectual or social activities. Most people with cyclothymia are generally fatigued and tend to sleep frequently and for long periods of time. However, other people experience insomnia.Other symptoms of cyclothymic depression include indifference toward people or activities that used to be extremely important. Cyclothymic depression also leads to difficulty making decisions. In addition, people with this condition tend to be critical and complain easily. Suicidal thoughts are common, even in mild forms of cyclothymia. In the depressive state, people with cyclothymia also experience physical complaints including frequent headaches, tightness in the head and chest, an empty sensation in the head, weakness, weight loss, and hair loss.The distinguishing factor between typical depression and cyclothymic depression is that in cyclothymic depression, there are instances of hypomania. People with cyclothymia can switch from the depressive state to the hypomanic state without warning to them or others. The duration and frequency of phases is unpredictable.In the hypomanic state, peoples thoughts become faster and they become more sociable and talkative. They may engage in spending sprees, spontaneous actions, have heightened self-esteem, and greater vanity. In contrast to a regular manic state that would be associated with bipolar I, symptoms in the hypomanic phase generally occur in a less severe form.Cyclothymia commonly occurs in conjunction with other disorders. Between 20 and 50 percent of people with depression, anxiety, and related disorders also have cyclothymia. When people with cyclothymia seek mental health resources it tends to be for symptoms of their comorbid condition rather than for their symptoms of cyclothymia. In children and adolescents, the most common comorbidities with cyclothymia are anxiety disorders, impulse control issues, eating disorders, and ADHD. In adults, cyclothymia also tends to be comorbid with impulse control issues. Sensation-seeking behaviors occur in hypomanic states. These often include gambling and compulsive sexuality in men, or compulsive buying and binge eating in women.In addition to sensation-related disorders, cyclothymia has also been associated with atypical depression. In one study, a connection was found between interpersonal sensitivity, mood reactivity (i.e., responding to actual or potential positive events with brighter mood), and cyclothymic mood swings, all of which are symptoms of atypical depression. Cyclothymia also tends to occur in conjunction with separation anxiety, where a person has anxiety as a result of separation from a caregiver, friend, or loved one. Other issues that tend to co-occur with cyclothymia include social anxiety, fear of rejection and a tendency toward hostility to those connected with past pain and rejection. People with cyclothymia tend to seek intense interpersonal relationships when in a hypomanic state and isolation when in a depressed state. This generally leads to short, tumultuous relationships.
Causes
The cause is unknown. Risk factors include a family history of bipolar disorder.First-degree relatives of people with cyclothymia have major depressive disorder, bipolar I disorder, and bipolar II disorder more often than the general population. Substance-related disorders also may be at a higher risk within the family. First-degree relatives of a bipolar I individuals may have a higher risk of cyclothymic disorder than the general population.
Diagnosis
Cyclothymia is classified in DSM-5 as a subtype of bipolar disorder. The criteria are:
Periods of elevated mood and depressive symptoms for at least half the time during the last two years for adults and one year for children and teenagers.
Periods of stable moods last only two months at most.
Symptoms create significant problems in one or more areas of life.
Symptoms do not meet the criteria for bipolar disorder, major depression, or another mental disorder.
Symptoms are not caused by substance use or a medical condition.The DSM-5 criteria for cyclothymia are restrictive according to some researchers. This affects the diagnosis of cyclothymia because fewer people get diagnosed than potentially could. This means that a person who has some symptoms of the disorder might not be able to get treatment because they do not meet all of the necessary criteria described in DSM-5. Furthermore, it also leads to more attention being placed on depression and other bipolar-spectrum disorders because if a person does not meet all the criteria for cyclothymia they are often given a depression or bipolar spectrum diagnosis. Improper diagnosis may lead some people with cyclothymia to be treated for a comorbid disorder rather than having their cyclothymic tendencies addressed.Cyclothymia is often not recognized by the affected individual or medical professionals due to its ostensibly mild symptoms. In addition, it is difficult to identify and classify. Due to disagreement and misconceptions among health and mental health professionals, cyclothymia is often diagnosed as "bipolar not otherwise specified". Cyclothymia is also often confused with borderline personality disorder due to their similar symptoms, especially in older adolescents and young adults.Most people with the disorder present in a depressive state, not realizing that their hypomanic states are abnormal. Mild manic episodes tend to be interpreted as part of the persons personality or simply a heightened mood. In addition, the disorder often manifests during childhood or adolescence, making it even more difficult for the person to distinguish between symptoms of the disorder and their personality. For example, people may think that they just have mood swings and not realize that these are a result of a psychiatric condition.
Management
Cognitive behavioral therapy (CBT) is considered potentially effective for people diagnosed with cyclothymia.Medication can be used in addition to behavioral approaches. However, mood stabilizers should be used before antidepressants, and if antidepressants are used they should be used with caution. Antidepressants are a concern due to the possibility of inducing hypomanic switches or rapid cycling.
History
In 1883, Karl Ludwig Kahlbaum identified a disorder characterized by recurring mood cycles. The disorder contained both melancholic and manic episodes that occurred in a milder form than in bipolar disorder. This condition was coined "cyclothymia" by Kahlbaum and his student Ewald Hecker. Kahlbaum developed his theory of cyclothymia through his work with people presenting with these symptoms at the Kahlbaum Sanitarium in Goerlitz, Silesia (Germany). He was recognized as a leading hypnotherapist and psychotherapist of his day. He was a progressive in the field of mental health, believing that mental illness should not carry a stigma and that people dealing with mental health issues should be treated humanely. Kalhbaum was the first to recognize that people with cyclothymia often do not seek help for the disorder due to its milder symptoms.Cyclothymia has been conceptualized in a variety of ways, including as a subtype of bipolar disorder, a temperament, a personality trait, and a personality disorder. There is also an argument that cyclothymia should be considered a neurodevelopmental disorder. The two defining features of the disorder, according to DSM-5, are the presence of depressive and hypomanic symptoms, not meeting the threshold for a depressive or hypomanic episode. Cyclothymia is also classified as a subtype of bipolar disorder in DSM-5, but some researchers disagree with this classification and argue that it should be primarily defined as an exaggeration of mood and emotional instability. In the past, cyclothymia has been conceptualized to include other characteristics in addition to the flux between depression and hypomania, such as mood reactivity, impulsivity, and anxiety.
Epidemiology
Cyclothymia, known today as Cyclothymic Disorder, tends to be underdiagnosed due to its low intensity. The exact rates for Cyclothymia have not been widely studied. Some studies estimate that between 5 and 8% are affected at some point in their life whereas other studies suggest a rate ranging from 0.4 to 2.5%.Males appear to be affected equally often, though women are more likely to receive treatment. Cyclothymia is diagnosed in around fifty percent of people with depression who are evaluated in psychiatric outpatient settings.
Etymology
Cyclothymia is derived from the Greek word κυκλοθυμία (from κῦκλος, kyklos, "circle" and θυμός, thymos, "mood, emotion"). Therefore, it means "to cycle or circle between moods or emotions".
Research
Whether subtypes of bipolar disorder, such as cyclothymia, truly represent separate disorders or are part of a unique bipolar spectrum is debated in research. Cyclothymia is typically not described in research studies or diagnosed in clinical settings, making it less recognizable and less understood by professionals. This absence of cyclothymia in research and clinical settings suggests that cyclothymia is either being diagnosed as another mood disorder or as a non-affective psychiatric disorder or not coming to scientific or clinical attention due to a lack of diagnostic clarity or because the nature of cyclothymia is still highly contested. Additionally, the current diagnostic criterion for cyclothymia emphasizes that symptoms are persistent, which suggests that they are enduring traits rather than a psychological state, thus, it has been argued that it should be diagnosed as a personality disorder. Since the symptoms tend to overlap with personality disorders, the validity and distinction between these two diagnostic categories has been debated.Lastly, the tendency of cyclothymia to be comorbid with other mental disorders makes diagnosis difficult. These issues prevent consensus on the definition of cyclothymia and its relationship with other mental disorders among researchers and clinicians. This lack of consensus on an operational definition and symptom presentation is especially pronounced with children and adolescents because the diagnostic criteria have not been adequately adapted to take into account their developmental level.
Society and culture
Actor Stephen Fry has spoken about his experience with cyclothymia, which was depicted in the documentary Stephen Fry: The Secret Life of the Manic Depressive.Singer Charlene Soraia has cyclothymia and wrote a song about her experiences with the disorder.
See also
References
Cited sources
Sadock, Benjamin; Sadock, Virginia; Ruiz, Pedro, eds. (2017). "13. Mood Disorders". Kaplan and Sadocks Comprehensive Textbook of Psychiatry (10th ed.). New York: Wolters Kluwer.
== External links == |
Hydrothorax | Hydrothorax is a type of pleural effusion in which transudate accumulates in the pleural cavity. This condition is most likely to develop secondary to congestive heart failure, following an increase in hydrostatic pressure within the lungs. More rarely, hydrothorax can develop in 10% of patients with ascites which is called hepatic hydrothorax. It is often difficult to manage in end-stage liver failure and often fails to respond to therapy.
Pleural effusions may also develop following the accumulation of other fluids within the pleural cavity; if the fluid is blood it is known as hemothorax (as in major chest injuries), if the fluid is pus it is known as pyothorax (resulting from chest infections), and if the fluid is lymph it is known as chylothorax (resulting from rupture of the thoracic duct).
Treatment
Treatment of hydrothorax is difficult for several reasons. The underlying condition needs to be corrected; however, often the source of the hydrothorax is end stage liver disease and correctable only by transplant. Chest tube placement should not occur. Other measures such as a TIPS procedure are more effective as they treat the cause of the hydrothorax, but have complications such as worsened hepatic encephalopathy.
See also
Pleural effusion
Pneumothorax
References
https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/hydrothorax
Garbuzenko D.V., Arefyev N.O. Hepatic hydrothorax: An update and review of the literature. World J. Hepatol. 2017; 9 (31): 1197-1204
== External links == |
Pseudostrabismus | Pseudostrabismus is the false appearance of crossed eyes. When the eyes are actually crossed or not completely aligned with one another, it is called strabismus. Pseudostrabismus is more likely to be observed in East Asian or Native American infants, due to the presence of epicanthic folds obscuring the medial aspect of each eye.
Pseudostrabismus generally occurs in infants and toddlers, whose facial features are not fully developed. The bridge of their nose is wide and flat, creating telecanthus (increased distance between medial canthus of both eyes). With age, the bridge will narrow, and the epicanthic folds in the corner of the eyes will go away. This will cause the eyes to appear wider and thus not have the appearance of strabismus.
To detect the difference between strabismus and pseudostrabismus, clinicians use a flashlight to shine into the childs eyes. When the child is looking at the light, a reflection can be seen on the front surface of the pupil. If the eyes are aligned with one another, the reflection from the light will be in the same spot of each eye. If strabismus is present, the reflection from the light will not be in the same spot of each eye.
Rakels Textbook of Family Medicine states, "A common misconception is that children with crossed eyes outgrow the condition, but this is generally not the case. This belief stems from the confusion between true strabismus and pseudostrabismus. When a childs eyes are truly crossed, it is always a serious condition and requires the care of an ophthalmologist."
References
American Academy of Ophthalmology |
Tooth decay | Tooth decay, also known as cavities or caries, is the breakdown of teeth due to acids produced by bacteria. The cavities may be a number of different colors from yellow to black. Symptoms may include pain and difficulty with eating. Complications may include inflammation of the tissue around the tooth, tooth loss and infection or abscess formation.The cause of cavities is acid from bacteria dissolving the hard tissues of the teeth (enamel, dentin and cementum). The acid is produced by the bacteria when they break down food debris or sugar on the tooth surface. Simple sugars in food are these bacterias primary energy source and thus a diet high in simple sugar is a risk factor. If mineral breakdown is greater than build up from sources such as saliva, caries results. Risk factors include conditions that result in less saliva such as: diabetes mellitus, Sjögren syndrome and some medications. Medications that decrease saliva production include antihistamines and antidepressants. Dental caries are also associated with poverty, poor cleaning of the mouth, and receding gums resulting in exposure of the roots of the teeth.Prevention of dental caries includes regular cleaning of the teeth, a diet low in sugar, and small amounts of fluoride. Brushing ones teeth twice per day and flossing between the teeth once a day is recommended. Fluoride may be acquired from water, salt or toothpaste among other sources. Treating a mothers dental caries may decrease the risk in her children by decreasing the number of certain bacteria she may spread to them. Screening can result in earlier detection. Depending on the extent of destruction, various treatments can be used to restore the tooth to proper function or the tooth may be removed. There is no known method to grow back large amounts of tooth. The availability of treatment is often poor in the developing world. Paracetamol (acetaminophen) or ibuprofen may be taken for pain.Worldwide, approximately 3.6 billion people (48% of the population) have dental caries in their permanent teeth as of 2016. The World Health Organization estimates that nearly all adults have dental caries at some point in time. In baby teeth it affects about 620 million people or 9% of the population. They have become more common in both children and adults in recent years. The disease is most common in the developed world due to greater simple sugar consumption and less common in the developing world. Caries is Latin for "rottenness".
Signs and symptoms
A person experiencing caries may not be aware of the disease. The earliest sign of a new carious lesion is the appearance of a chalky white spot on the surface of the tooth, indicating an area of demineralization of enamel. This is referred to as a white spot lesion, an incipient carious lesion or a "micro-cavity". As the lesion continues to demineralize, it can turn brown but will eventually turn into a cavitation ("cavity"). Before the cavity forms, the process is reversible, but once a cavity forms, the lost tooth structure cannot be regenerated.
A lesion that appears dark brown and shiny suggests dental caries were once present but the demineralization process has stopped, leaving a stain. Active decay is lighter in color and dull in appearance.As the enamel and dentin are destroyed, the cavity becomes more noticeable. The affected areas of the tooth change color and become soft to the touch. Once the decay passes through the enamel, the dentinal tubules, which have passages to the nerve of the tooth, become exposed, resulting in pain that can be transient, temporarily worsening with exposure to heat, cold, or sweet foods and drinks. A tooth weakened by extensive internal decay can sometimes suddenly fracture under normal chewing forces. When the decay has progressed enough to allow the bacteria to overwhelm the pulp tissue in the center of the tooth, a toothache can result and the pain will become more constant. Death of the pulp tissue and infection are common consequences. The tooth will no longer be sensitive to hot or cold but can be very tender to pressure.
Dental caries can also cause bad breath and foul tastes. In highly progressed cases, an infection can spread from the tooth to the surrounding soft tissues. Complications such as cavernous sinus thrombosis and Ludwig angina can be life-threatening.
Cause
Four things are required for caries to form: a tooth surface (enamel or dentin), caries-causing bacteria, fermentable carbohydrates (such as sucrose), and time. This involves adherence of food to the teeth and acid creation by the bacteria that makes up the dental plaque. However, these four criteria are not always enough to cause the disease and a sheltered environment promoting development of a cariogenic biofilm is required. The caries disease process does not have an inevitable outcome, and different individuals will be susceptible to different degrees depending on the shape of their teeth, oral hygiene habits, and the buffering capacity of their saliva. Dental caries can occur on any surface of a tooth that is exposed to the oral cavity, but not the structures that are retained within the bone.Tooth decay is caused by biofilm (dental plaque) lying on the teeth and maturing to become cariogenic (causing decay). Certain bacteria in the biofilm produce acid in the presence of fermentable carbohydrates such as sucrose, fructose, and glucose.Caries occur more often in people from the lower end of the socio-economic scale than people from the upper end of the socio-economic scale, due to lack of education about dental care, and lack of access to professional dental care which may be expensive.
Bacteria
The most common bacteria associated with dental cavities are the mutans streptococci, most prominently Streptococcus mutans and Streptococcus sobrinus, and lactobacilli. However, cariogenic bacteria (the ones that can cause the disease) are present in dental plaque, but they are usually in too low concentrations to cause problems unless there is a shift in the balance. This is driven by local environmental change, such as frequent sugar intake or inadequate biofilm removal (toothbrushing). If left untreated, the disease can lead to pain, tooth loss and infection.The mouth contains a wide variety of oral bacteria, but only a few specific species of bacteria are believed to cause dental caries: Streptococcus mutans and Lactobacillus species among them. Streptococcus mutans are gram-positive bacteria which constitute biofilms on the surface of teeth. These organisms can produce high levels of lactic acid following fermentation of dietary sugars and are resistant to the adverse effects of low pH, properties essential for cariogenic bacteria. As the cementum of root surfaces is more easily demineralized than enamel surfaces, a wider variety of bacteria can cause root caries, including Lactobacillus acidophilus, Actinomyces spp., Nocardia spp., and Streptococcus mutans. Bacteria collect around the teeth and gums in a sticky, creamy-coloured mass called plaque, which serves as a biofilm. Some sites collect plaque more commonly than others, for example, sites with a low rate of salivary flow (molar fissures). Grooves on the occlusal surfaces of molar and premolar teeth provide microscopic retention sites for plaque bacteria, as do the interproximal sites. Plaque may also collect above or below the gingiva, where it is referred to as supra- or sub-gingival plaque, respectively.
These bacterial strains, most notably S. mutans, can be inherited by a child from a caretakers kiss or through feeding pre-masticated food.
Dietary sugars
Bacteria in a persons mouth convert glucose, fructose, and most commonly sucrose (table sugar) into acids such as lactic acid through a glycolytic process called fermentation. If left in contact with the tooth, these acids may cause demineralization, which is the dissolution of its mineral content. The process is dynamic, however, as remineralization can also occur if the acid is neutralized by saliva or mouthwash. Fluoride toothpaste or dental varnish may aid remineralization. If demineralization continues over time, enough mineral content may be lost so that the soft organic material left behind disintegrates, forming a cavity or hole. The impact such sugars have on the progress of dental caries is called cariogenicity. Sucrose, although a bound glucose and fructose unit, is in fact more cariogenic than a mixture of equal parts of glucose and fructose. This is due to the bacteria utilising the energy in the saccharide bond between the glucose and fructose subunits. S.mutans adheres to the biofilm on the tooth by converting sucrose into an extremely adhesive substance called dextran polysaccharide by the enzyme dextran sucranase.
Exposure
The frequency with which teeth are exposed to cariogenic (acidic) environments affects the likelihood of caries development. After meals or snacks, the bacteria in the mouth metabolize sugar, resulting in an acidic by-product that decreases pH. As time progresses, the pH returns to normal due to the buffering capacity of saliva and the dissolved mineral content of tooth surfaces. During every exposure to the acidic environment, portions of the inorganic mineral content at the surface of teeth dissolve and can remain dissolved for two hours. Since teeth are vulnerable during these acidic periods, the development of dental caries relies heavily on the frequency of acid exposure.
The carious process can begin within days of a tooths erupting into the mouth if the diet is sufficiently rich in suitable carbohydrates. Evidence suggests that the introduction of fluoride treatments has slowed the process. Proximal caries take an average of four years to pass through enamel in permanent teeth. Because the cementum enveloping the root surface is not nearly as durable as the enamel encasing the crown, root caries tend to progress much more rapidly than decay on other surfaces. The progression and loss of mineralization on the root surface is 2.5 times faster than caries in enamel. In very severe cases where oral hygiene is very poor and where the diet is very rich in fermentable carbohydrates, caries may cause cavities within months of tooth eruption. This can occur, for example, when children continuously drink sugary drinks from baby bottles (see later discussion).
Teeth
There are certain diseases and disorders affecting teeth that may leave an individual at a greater risk for cavities.
Molar incisor hypo-mineralization, which seems to be increasingly common. While the cause is unknown it is thought to be a combination of genetic and environmental factors. Possible contributing factors that have been investigated include systemic factors such as high levels of dioxins or polychlorinated biphenyl (PCB) in the mothers milk, premature birth and oxygen deprivation at birth, and certain disorders during the childs first 3 years such as mumps, diphtheria, scarlet fever, measles, hypoparathyroidism, malnutrition, malabsorption, hypo-vitaminosis D, chronic respiratory diseases, or undiagnosed and untreated coeliac disease, which usually presents with mild or absent gastrointestinal symptoms.Amelogenesis imperfecta, which occurs in between 1 in 718 and 1 in 14,000 individuals, is a disease in which the enamel does not fully form or forms in insufficient amounts and can fall off a tooth. In both cases, teeth may be left more vulnerable to decay because the enamel is not able to protect the tooth.In most people, disorders or diseases affecting teeth are not the primary cause of dental caries. Approximately 96% of tooth enamel is composed of minerals. These minerals, especially hydroxyapatite, will become soluble when exposed to acidic environments. Enamel begins to demineralize at a pH of 5.5. Dentin and cementum are more susceptible to caries than enamel because they have lower mineral content. Thus, when root surfaces of teeth are exposed from gingival recession or periodontal disease, caries can develop more readily. Even in a healthy oral environment, however, the tooth is susceptible to dental caries.
The evidence for linking malocclusion and/or crowding to dental caries is weak; however, the anatomy of teeth may affect the likelihood of caries formation. Where the deep developmental grooves of teeth are more numerous and exaggerated, pit and fissure caries is more likely to develop (see next section). Also, caries is more likely to develop when food is trapped between teeth.
Other factors
Reduced salivary flow rate is associated with increased caries since the buffering capability of saliva is not present to counterbalance the acidic environment created by certain foods. As a result, medical conditions that reduce the amount of saliva produced by salivary glands, in particular the submandibular gland and parotid gland, are likely to lead to dry mouth and thus to widespread tooth decay. Examples include Sjögren syndrome, diabetes mellitus, diabetes insipidus, and sarcoidosis. Medications, such as antihistamines and antidepressants, can also impair salivary flow. Stimulants, most notoriously methylamphetamine, also occlude the flow of saliva to an extreme degree. This is known as meth mouth. Tetrahydrocannabinol (THC), the active chemical substance in cannabis, also causes a nearly complete occlusion of salivation, known in colloquial terms as "cotton mouth". Moreover, 63% of the most commonly prescribed medications in the United States list dry mouth as a known side-effect. Radiation therapy of the head and neck may also damage the cells in salivary glands, somewhat increasing the likelihood of caries formation.Susceptibility to caries can be related to altered metabolism in the tooth, in particular to fluid flow in the dentin. Experiments on rats have shown that a high-sucrose, cariogenic diet "significantly suppresses the rate of fluid motion" in dentin.The use of tobacco may also increase the risk for caries formation. Some brands of smokeless tobacco contain high sugar content, increasing susceptibility to caries. Tobacco use is a significant risk factor for periodontal disease, which can cause the gingiva to recede. As the gingiva loses attachment to the teeth due to gingival recession, the root surface becomes more visible in the mouth. If this occurs, root caries is a concern since the cementum covering the roots of teeth is more easily demineralized by acids than enamel. Currently, there is not enough evidence to support a causal relationship between smoking and coronal caries, but evidence does suggest a relationship between smoking and root-surface caries.
Exposure of children to secondhand tobacco smoke is associated with tooth decay.Intrauterine and neonatal lead exposure promote tooth decay. Besides lead, all atoms with electrical charge and ionic radius similar to bivalent calcium,
such as cadmium, mimic the calcium ion and therefore exposure to them may promote tooth decay.Poverty is also a significant social determinant for oral health. Dental caries have been linked with lower socio-economic status and can be considered a disease of poverty.Forms are available for risk assessment for caries when treating dental cases; this system using the evidence-based Caries Management by Risk Assessment (CAMBRA). It is still unknown if the identification of high-risk individuals can lead to more effective long-term patient management that prevents caries initiation and arrests or reverses the progression of lesions.Saliva also contains iodine and EGF. EGF results effective in cellular proliferation, differentiation and survival. Salivary EGF, which seems also regulated by dietary inorganic iodine, plays an important physiological role in the maintenance of oral (and gastro-oesophageal) tissue integrity, and, on the other hand, iodine is effective in prevention of dental caries and oral health.
Pathophysiology
Teeth are bathed in saliva and have a coating of bacteria on them (biofilm) that continually forms. The development of biofilm begins with pellicle formation. Pellicle is an acellular proteinaceous film which covers the teeth. Bacteria colonize on the teeth by adhering to the pellicle-coated surface. Over time, a mature biofilm is formed and this create a cariogenic environment on the tooth surface. The minerals in the hard tissues of the teeth (enamel, dentin and cementum) are constantly undergoing processes of demineralization and remineralization. Dental caries results when the demineralization rate is faster than the remineralization and there is net mineral loss. This happens when there is an ecologic shift within the dental biofilm, from a balanced population of micro-organisms to a population that produce acids and can survive in an acid environment.
Enamel
Tooth enamel is a highly mineralized acellular tissue, and caries act upon it through a chemical process brought on by the acidic environment produced by bacteria. As the bacteria consume the sugar and use it for their own energy, they produce lactic acid. The effects of this process include the demineralization of crystals in the enamel, caused by acids, over time until the bacteria physically penetrate the dentin. Enamel rods, which are the basic unit of the enamel structure, run perpendicularly from the surface of the tooth to the dentin. Since demineralization of enamel by caries, in general, follows the direction of the enamel rods, the different triangular patterns between pit and fissure and smooth-surface caries develop in the enamel because the orientation of enamel rods are different in the two areas of the tooth.As the enamel loses minerals, and dental caries progresses, the enamel develops several distinct zones, visible under a light microscope. From the deepest layer of the enamel to the enamel surface, the identified areas are the: translucent zone, dark zones, body of the lesion, and surface zone. The translucent zone is the first visible sign of caries and coincides with a one to two percent loss of minerals. A slight remineralization of enamel occurs in the dark zone, which serves as an example of how the development of dental caries is an active process with alternating changes. The area of greatest demineralization and destruction is in the body of the lesion itself. The surface zone remains relatively mineralized and is present until the loss of tooth structure results in a cavitation.
Dentin
Unlike enamel, the dentin reacts to the progression of dental caries. After tooth formation, the ameloblasts, which produce enamel, are destroyed once enamel formation is complete and thus cannot later regenerate enamel after its destruction. On the other hand, dentin is produced continuously throughout life by odontoblasts, which reside at the border between the pulp and dentin. Since odontoblasts are present, a stimulus, such as caries, can trigger a biologic response. These defense mechanisms include the formation of sclerotic and tertiary dentin.In dentin from the deepest layer to the enamel, the distinct areas affected by caries are the advancing front, the zone of bacterial penetration, and the zone of destruction. The advancing front represents a zone of demineralized dentin due to acid and has no bacteria present. The zones of bacterial penetration and destruction are the locations of invading bacteria and ultimately the decomposition of dentin. The zone of destruction has a more mixed bacterial population where proteolytic enzymes have destroyed the organic matrix. The innermost dentin caries has been reversibly attacked because the collagen matrix is not severely damaged, giving it potential for repair.
Sclerotic dentin
The structure of dentin is an arrangement of microscopic channels, called dentinal tubules, which radiate outward from the pulp chamber to the exterior cementum or enamel border. The diameter of the dentinal tubules is largest near the pulp (about 2.5 μm) and smallest (about 900 nm) at the junction of dentin and enamel. The carious process continues through the dentinal tubules, which are responsible for the triangular patterns resulting from the progression of caries deep into the tooth. The tubules also allow caries to progress faster.
In response, the fluid inside the tubules brings immunoglobulins from the immune system to fight the bacterial infection. At the same time, there is an increase of mineralization of the surrounding tubules. This results in a constriction of the tubules, which is an attempt to slow the bacterial progression. In addition, as the acid from the bacteria demineralizes the hydroxyapatite crystals, calcium and phosphorus are released, allowing for the precipitation of more crystals which fall deeper into the dentinal tubule. These crystals form a barrier and slow the advancement of caries. After these protective responses, the dentin is considered sclerotic.
According to hydrodynamic theory, fluids within dentinal tubules are believed to be the mechanism by which pain receptors are triggered within the pulp of the tooth. Since sclerotic dentin prevents the passage of such fluids, pain that would otherwise serve as a warning of the invading bacteria may not develop at first.
Tertiary dentin
In response to dental caries, there may be production of more dentin toward the direction of the pulp. This new dentin is referred to as tertiary dentin. Tertiary dentin is produced to protect the pulp for as long as possible from the advancing bacteria. As more tertiary dentin is produced, the size of the pulp decreases. This type of dentin has been subdivided according to the presence or absence of the original odontoblasts. If the odontoblasts survive long enough to react to the dental caries, then the dentin produced is called "reactionary" dentin. If the odontoblasts are killed, the dentin produced is called "reparative" dentin.
In the case of reparative dentin, other cells are needed to assume the role of the destroyed odontoblasts. Growth factors, especially TGF-β, are thought to initiate the production of reparative dentin by fibroblasts and mesenchymal cells of the pulp. Reparative dentin is produced at an average of 1.5 μm/day, but can be increased to 3.5 μm/day. The resulting dentin contains irregularly shaped dentinal tubules that may not line up with existing dentinal tubules. This diminishes the ability for dental caries to progress within the dentinal tubules.
Cementum
The incidence of cemental caries increases in older adults as gingival recession occurs from either trauma or periodontal disease. It is a chronic condition that forms a large, shallow lesion and slowly invades first the roots cementum and then dentin to cause a chronic infection of the pulp (see further discussion under classification by affected hard tissue). Because dental pain is a late finding, many lesions are not detected early, resulting in restorative challenges and increased tooth loss.
Diagnosis
The presentation of caries is highly variable. However, the risk factors and stages of development are similar. Initially, it may appear as a small chalky area (smooth surface caries), which may eventually develop into a large cavitation. Sometimes caries may be directly visible. However other methods of detection such as X-rays are used for less visible areas of teeth and to judge the extent of destruction. Lasers for detecting caries allow detection without ionizing radiation and are now used for detection of interproximal decay (between the teeth).
Primary diagnosis involves inspection of all visible tooth surfaces using a good light source, dental mirror and explorer. Dental radiographs (X-rays) may show dental caries before it is otherwise visible, in particular caries between the teeth. Large areas of dental caries are often apparent to the naked eye, but smaller lesions can be difficult to identify. Visual and tactile inspection along with radiographs are employed frequently among dentists, in particular to diagnose pit and fissure caries. Early, uncavitated caries is often diagnosed by blowing air across the suspect surface, which removes moisture and changes the optical properties of the unmineralized enamel.
Some dental researchers have cautioned against the use of dental explorers to find caries, in particular sharp ended explorers. In cases where a small area of tooth has begun demineralizing but has not yet cavitated, the pressure from the dental explorer could cause a cavity. Since the carious process is reversible before a cavity is present, it may be possible to arrest caries with fluoride and remineralize the tooth surface. When a cavity is present, a restoration will be needed to replace the lost tooth structure.
At times, pit and fissure caries may be difficult to detect. Bacteria can penetrate the enamel to reach dentin, but then the outer surface may remineralize, especially if fluoride is present. These caries, sometimes referred to as "hidden caries", will still be visible on X-ray radiographs, but visual examination of the tooth would show the enamel intact or minimally perforated.
The differential diagnosis for dental caries includes dental fluorosis and developmental defects of the tooth including hypomineralization of the tooth and hypoplasia of the tooth.The early carious lesion is characterized by demineralization of the tooth surface, altering the tooths optical properties. Technology utilizing laser speckle image (LSI) techniques may provide a diagnostic aid to detect early carious lesions.
Classification
Caries can be classified by location, etiology, rate of progression, and affected hard tissues. These forms of classification can be used to characterize a particular case of tooth decay in order to more accurately represent the condition to others and also indicate the severity of tooth destruction. In some instances, caries is described in other ways that might indicate the cause. The G. V. Black classification is as follows:
Class I – occlusal surfaces of posterior teeth, buccal or lingual pits on molars, lingual pit near cingulum of maxillary incisors
Class II – proximal surfaces of posterior teeth
Class III – interproximal surfaces of anterior teeth without incisal edge involvement
Class IV – interproximal surfaces of anterior teeth with incisal edge involvement
Class V – cervical third of facial or lingual surface of tooth
Class VI – incisal or occlusal edge is worn away due to attrition
Early childhood caries
Early childhood caries (ECC), also known as "baby bottle caries," "baby bottle tooth decay" or "bottle rot," is a pattern of decay found in young children with their deciduous (baby) teeth. This must include the presence of at least one carious lesion on a primary tooth in a child under the age of 6 years. The teeth most likely affected are the maxillary anterior teeth, but all teeth can be affected. The name for this type of caries comes from the fact that the decay usually is a result of allowing children to fall asleep with sweetened liquids in their bottles or feeding children sweetened liquids multiple times during the day.Another pattern of decay is "rampant caries", which signifies advanced or severe decay on multiple surfaces of many teeth. Rampant caries may be seen in individuals with xerostomia, poor oral hygiene, stimulant use (due to drug-induced dry mouth), and/or large sugar intake. If rampant caries is a result of previous radiation to the head and neck, it may be described as radiation-induced caries. Problems can also be caused by the self-destruction of roots and whole tooth resorption when new teeth erupt or later from unknown causes.
Children at 6–12 months are at increased risk of developing dental caries. For other children aged 12–18 months, dental caries develop on primary teeth and approximately twice yearly for permanent teeth.A range of studies have reported that there is a correlation between caries in primary teeth and caries in permanent teeth.
Rate of progression
Temporal descriptions can be applied to caries to indicate the progression rate and previous history. "Acute" signifies a quickly developing condition, whereas "chronic" describes a condition that has taken an extended time to develop, in which thousands of meals and snacks, many causing some acid demineralization that is not remineralized, eventually result in cavities.
Recurrent caries, also described as secondary, are caries that appear at a location with a previous history of caries. This is frequently found on the margins of fillings and other dental restorations. On the other hand, incipient caries describes decay at a location that has not experienced previous decay. Arrested caries describes a lesion on a tooth that was previously demineralized but was remineralized before causing a cavitation. Fluoride treatment can help recalcification of |
Tooth decay | tooth enamel as well as the use of amorphous calcium phosphate.
Micro-invasive interventions (such as dental sealant or resin infiltration) have been shown to slow down the progression of proximal decay.
Affected hard tissue
Depending on which hard tissues are affected, it is possible to describe caries as involving enamel, dentin, or cementum. Early in its development, caries may affect only enamel. Once the extent of decay reaches the deeper layer of dentin, the term "dentinal caries" is used. Since cementum is the hard tissue that covers the roots of teeth, it is not often affected by decay unless the roots of teeth are exposed to the mouth. Although the term "cementum caries" may be used to describe the decay on roots of teeth, very rarely does caries affect the cementum alone.
Prevention
Oral hygiene
The primary approach to dental hygiene care consists of tooth-brushing and flossing. The purpose of oral hygiene is to remove and prevent the formation of plaque or dental biofilm, although studies have shown this effect on caries is limited. While there is no evidence that flossing prevents tooth decay, the practice is still generally recommended.A toothbrush can be used to remove plaque on accessible surfaces, but not between teeth or inside pits and fissures on chewing surfaces. When used correctly, dental floss removes plaque from areas that could otherwise develop proximal caries but only if the depth of sulcus has not been compromised. Additional aids include interdental brushes, water picks, and mouthwashes. The use of rotational electric toothbrushes might reduce the risk of plaque and gingivitis, though it is unclear whether they are of clinical importance.However, oral hygiene is effective at preventing gum disease (gingivitis / periodontal disease). Food is forced inside pits and fissures under chewing pressure, leading to carbohydrate-fuelled acid demineralisation where the brush, fluoride toothpaste, and saliva have no access to remove trapped food, neutralise acid, or remineralise tooth enamel. (Occlusal caries accounts for between 80 and 90% of caries in children (Weintraub, 2001).) Unlike brushing, fluoride leads to proven reduction in caries incidence by approximately 25%; higher concentrations of fluoride (>1,000 ppm) in toothpaste also helps prevents tooth decay, with the effect increasing with concentration up to a plateau. A randomized clinical trial demonstrated that toothpastes that contain arginine have greater protection against tooth cavitation than the regular fluoride toothpastes containing 1450 ppm alone. A Cochrane review has confirmed that the use of fluoride gels, normally applied by a dental professional from once to several times a year, assists in the prevention of tooth decay in children and adolescents, reiterating the importance of fluoride as the principal means of caries prevention. Another review concluded that the supervised regular use of a fluoride mouthwash greatly reduced the onset of decay in the permanent teeth of children.Professional hygiene care consists of regular dental examinations and professional prophylaxis (cleaning). Sometimes, complete plaque removal is difficult, and a dentist or dental hygienist may be needed. Along with oral hygiene, radiographs may be taken at dental visits to detect possible dental caries development in high-risk areas of the mouth (e.g. "bitewing" X-rays which visualize the crowns of the back teeth).
Alternative methods of oral hygiene also exist around the world, such as the use of teeth cleaning twigs such as miswaks in some Middle Eastern and African cultures. There is some limited evidence demonstrating the efficacy of these alternative methods of oral hygiene.
Dietary modification
People who eat more free sugars get more cavities, with cavities increasing exponentially with increasing sugar intake. Populations with less sugar intake have fewer cavities. In one population, in Nigeria, where sugar consumption was about 2g/day, only two percent of the population, of any age, had had a cavity.Chewy and sticky foods (such as candy, cookies, potato chips, and crackers) tend to adhere to teeth longer. However, dried fruits such as raisins and fresh fruit such as apples and bananas disappear from the mouth quickly, and do not appear to be a risk factor. Consumers are not good at guessing which foods stick around in the mouth.For children, the American Dental Association and the European Academy of Paediatric Dentistry recommend limiting the frequency of consumption of drinks with sugar, and not giving baby bottles to infants during sleep (see earlier discussion). Parents are also recommended to avoid sharing utensils and cups with their infants to prevent transferring bacteria from the parents mouth.Xylitol is a naturally occurring sugar alcohol that is used in different products as an alternative to sucrose (table sugar). As of 2015 the evidence concerning the use of xylitol in chewing gum was insufficient to determine if it is effective at preventing caries.
Other measures
The use of dental sealants is a means of prevention. A sealant is a thin plastic-like coating applied to the chewing surfaces of the molars to prevent food from being trapped inside pits and fissures. This deprives resident plaque bacteria of carbohydrate, preventing the formation of pit and fissure caries. Sealants are usually applied on the teeth of children, as soon as the teeth erupt but adults are receiving them if not previously performed. Sealants can wear out and fail to prevent access of food and plaque bacteria inside pits and fissures and need to be replaced so they must be checked regularly by dental professionals. Dental sealants have been shown to be more effective at preventing occlusal decay when compared to fluoride varnish applications.Calcium, as found in food such as milk and green vegetables, is often recommended to protect against dental caries. Fluoride helps prevent decay of a tooth by binding to the hydroxyapatite crystals in enamel. Streptococcus mutans is the leading cause of tooth decay. Low concentration fluoride ions act as bacteriostatic therapeutic agent and high concentration fluoride ions are bactericidal. The incorporated fluorine makes enamel more resistant to demineralization and, thus, resistant to decay. Fluoride can be found in either topical or systemic form. Topical fluoride is more highly recommended than systemic intake to protect the surface of the teeth. Topical fluoride is used in toothpaste, mouthwash and fluoride varnish. Standard fluoride toothpaste (1,000–1,500 ppm) is more effective than low fluoride toothpaste (< 600ppm) to prevent dental caries. It is recommended that all adult patients to use fluoridated toothpaste with at least 1350ppm fluoride content, brushing at least 2 times per day and brush right before bed. For children and young adults, use fluoridated toothpaste with 1350ppm to 1500ppm fluoride content, brushing 2 times per day and also brush right before bed. American Dental Association Council suggest that for children <3 years old, caregivers should begin brushing their teeth by using fluoridated toothpaste with an amount no more than a smear. Supervised toothbrushing must also be done to children below 8 years of age to prevent swallowing of toothpaste. After brushing with fluoride toothpaste, rinsing should be avoided and the excess spat out. Many dental professionals include application of topical fluoride solutions as part of routine visits and recommend the use of xylitol and amorphous calcium phosphate products. Silver diamine fluoride may work better than fluoride varnish to prevent cavities. Systemic fluoride is found as lozenges, tablets, drops and water fluoridation. These are ingested orally to provide fluoride systemically. Water fluoridation has been shown to be beneficial to prevent tooth decay, especially in low social economical areas, where other forms of fluoride is not available. However, a Cochrane systematic review found no evidence to suggest that taking fluoride systemically daily in pregnant women was effective in preventing dental decay in their offspring. While some products containing chlorhexidine have been shown to limit the progression of existing tooth decay; there is currently no evidence suggesting that chlorhexidine gels and varnishes can prevent dental caries or reduce the population of Streptococcus mutans in the mouth.An oral health assessment carried out before a child reaches the age of one may help with management of caries. The oral health assessment should include checking the childs history, a clinical examination, checking the risk of caries in the child including the state of their occlusion and assessing how well equipped the childs parent or carer is to help the child prevent caries. In order to further increase a childs cooperation in caries management, good communication by the dentist and the rest of the staff of a dental practice should be used. This communication can be improved by calling the child by their name, using eye contact and including them in any conversation about their treatment.Vaccines are also under development.
Treatment
Most importantly, whether the carious lesion is cavitated or non-cavitated dictates the management. Clinical assessment of whether the lesion is active or arrested is also important. Noncavitated lesions can be arrested and remineralization can occur under the right conditions. However, this may require extensive changes to the diet (reduction in frequency of refined sugars), improved oral hygiene (toothbrushing twice per day with fluoride toothpaste and daily flossing), and regular application of topical fluoride. More recently, Immunoglobulin Y specific to Streptococcus mutans has been used to suppress growth of S mutans. Such management of a carious lesion is termed "non-operative" since no drilling is carried out on the tooth. Non-operative treatment requires excellent understanding and motivation from the individual, otherwise the decay will continue.
Once a lesion has cavitated, especially if dentin is involved, remineralization is much more difficult and a dental restoration is usually indicated ("operative treatment"). Before a restoration can be placed, all of the decay must be removed otherwise it will continue to progress underneath the filling. Sometimes a small amount of decay can be left if it is entombed and there is a seal which isolates the bacteria from their substrate. This can be likened to placing a glass container over a candle, which burns itself out once the oxygen is used up. Techniques such as stepwise caries removal are designed to avoid exposure of the dental pulp and overall reduction of the amount of tooth substance which requires removal before the final filling is placed. Often enamel which overlies decayed dentin must also be removed as it is unsupported and susceptible to fracture. The modern decision-making process with regards the activity of the lesion, and whether it is cavitated, is summarized in the table.Destroyed tooth structure does not fully regenerate, although remineralization of very small carious lesions may occur if dental hygiene is kept at optimal level. For the small lesions, topical fluoride is sometimes used to encourage remineralization. For larger lesions, the progression of dental caries can be stopped by treatment. The goal of treatment is to preserve tooth structures and prevent further destruction of the tooth. Aggressive treatment, by filling, of incipient carious lesions, places where there is superficial damage to the enamel, is controversial as they may heal themselves, while once a filling is performed it will eventually have to be redone and the site serves as a vulnerable site for further decay.In general, early treatment is quicker and less expensive than treatment of extensive decay. Local anesthetics, nitrous oxide ("laughing gas"), or other prescription medications may be required in some cases to relieve pain during or following treatment or to relieve anxiety during treatment. A dental handpiece ("drill") is used to remove large portions of decayed material from a tooth. A spoon, a dental instrument used to carefully remove decay, is sometimes employed when the decay in dentin reaches near the pulp. Some dentists remove dental caries using a laser rather than the traditional dental drill. A Cochrane review of this technique looked at Er:YAG (erbium-doped yttrium aluminium garnet), Er,Cr:YSGG (erbium, chromium: yttrium-scandium-gallium-garnet) and Nd:YAG (neodymium-doped yttrium aluminium garnet) lasers and found that although people treated with lasers (compared to a conventional dental "drill") experienced less pain and had a lesser need for dental anaesthesia, that overall there was little difference in caries removal. Another alternative to drilling or lasers for small caries is the use of air abrasion, in which small abrasive particles are blasted at decay using pressurized air (similar to sand blasting). Once the cary is removed, the missing tooth structure requires a dental restoration of some sort to return the tooth to function and aesthetic condition.
Restorative materials include dental amalgam, composite resin, glass ionomer cement, porcelain, and gold. Composite resin and porcelain can be made to match the color of a patients natural teeth and are thus used more frequently when aesthetics are a concern. Composite restorations are not as strong as dental amalgam and gold; some dentists consider the latter as the only advisable restoration for posterior areas where chewing forces are great. When the decay is too extensive, there may not be enough tooth structure remaining to allow a restorative material to be placed within the tooth. Thus, a crown may be needed. This restoration appears similar to a cap and is fitted over the remainder of the natural crown of the tooth. Crowns are often made of gold, porcelain, or porcelain fused to metal.
For children, preformed crowns are available to place over the tooth. These are usually made of metal (usually stainless steel but increasingly there are aesthetic materials). Traditionally teeth are shaved down to make room for the crown but, more recently, stainless steel crowns have been used to seal decay into the tooth and stop it progressing. This is known as the Hall Technique and works by depriving the bacteria in the decay of nutrients and making their environment less favorable for them. It is a minimally invasive method of managing decay in children and does not require local anesthetic injections in the mouth.
In certain cases, endodontic therapy may be necessary for the restoration of a tooth. Endodontic therapy, also known as a "root canal", is recommended if the pulp in a tooth dies from infection by decay-causing bacteria or from trauma. In root canal therapy, the pulp of the tooth, including the nerve and vascular tissues, is removed along with decayed portions of the tooth. The canals are instrumented with endodontic files to clean and shape them, and they are then usually filled with a rubber-like material called gutta percha. The tooth is filled and a crown can be placed. Upon completion of root canal therapy, the tooth is non-vital, as it is devoid of any living tissue.
An extraction can also serve as treatment for dental caries. The removal of the decayed tooth is performed if the tooth is too far destroyed from the decay process to effectively restore the tooth. Extractions are sometimes considered if the tooth lacks an opposing tooth or will probably cause further problems in the future, as may be the case for wisdom teeth. Extractions may also be preferred by people unable or unwilling to undergo the expense or difficulties in restoring the tooth.
Epidemiology
Worldwide, approximately 3.6 billion people have dental caries in their permanent teeth. In baby teeth it affects about 620 million people or 9% of the population. The disease is most common in Latin American countries, countries in the Middle East, and South Asia, and least prevalent in China. In the United States, dental caries is the most common chronic childhood disease, being at least five times more common than asthma. It is the primary pathological cause of tooth loss in children. Between 29% and 59% of adults over the age of 50 experience caries.Treating dental cavities costs 5–10% of health-care budgets in industrialized countries, and can easily exceed budgets in lower-income countries.The number of cases has decreased in some developed countries, and this decline is usually attributed to increasingly better oral hygiene practices and preventive measures such as fluoride treatment. Nonetheless, countries that have experienced an overall decrease in cases of tooth decay continue to have a disparity in the distribution of the disease. Among children in the United States and Europe, twenty percent of the population endures sixty to eighty percent of cases of dental caries. A similarly skewed distribution of the disease is found throughout the world with some children having none or very few caries and others having a high number. Australia, Nepal, and Sweden (where children receive dental care paid for by the government) have a low incidence of cases of dental caries among children, whereas cases are more numerous in Costa Rica and Slovakia.The classic DMF (decay/missing/filled) index is one of the most common methods for assessing caries prevalence as well as dental treatment needs among populations. This index is based on in-field clinical examination of individuals by using a probe, mirror and cotton rolls. Because the DMF index is done without X-ray imaging, it underestimates real caries prevalence and treatment needs.Bacteria typically associated with dental caries have been isolated from vaginal samples from females who have bacterial vaginosis.
History
There is a long history of dental caries. Over a million years ago, hominins such as Paranthropus had cavities. The largest increases in the prevalence of caries have been associated with dietary changes.Archaeological evidence shows that tooth decay is an ancient disease dating far into prehistory. Skulls dating from a million years ago through the Neolithic period show signs of caries, including those from the Paleolithic and Mesolithic ages. The increase of caries during the neolithic period may be attributed to the increased consumption of plant foods containing carbohydrates. The beginning of rice cultivation in South Asia is also believed to have caused an increase in caries especially for women, although there is also some evidence from sites in Thailand, such as Khok Phanom Di, that shows a decrease in overall percentage of dental caries with the increase in dependence on rice agriculture.A Sumerian text from 5000 BC describes a "tooth worm" as the cause of caries. Evidence of this belief has also been found in India, Egypt, Japan, and China. Unearthed ancient skulls show evidence of primitive dental work. In Pakistan, teeth dating from around 5500 BC to 7000 BC show nearly perfect holes from primitive dental drills. The Ebers Papyrus, an Egyptian text from 1550 BC, mentions diseases of teeth. During the Sargonid dynasty of Assyria during 668 to 626 BC, writings from the kings physician specify the need to extract a tooth due to spreading inflammation. In the Roman Empire, wider consumption of cooked foods led to a small increase in caries prevalence. The Greco-Roman civilization, in addition to the Egyptian civilization, had treatments for pain resulting from caries.The rate of caries remained low through the Bronze Age and Iron Age, but sharply increased during the Middle Ages. Periodic increases in caries prevalence had been small in comparison to the 1000 AD increase, when sugar cane became more accessible to the Western world. Treatment consisted mainly of herbal remedies and charms, but sometimes also included bloodletting. The barber surgeons of the time provided services that included tooth extractions. Learning their training from apprenticeships, these health providers were quite successful in ending tooth pain and likely prevented systemic spread of infections in many cases. Among Roman Catholics, prayers to Saint Apollonia, the patroness of dentistry, were meant to heal pain derived from tooth infection.There is also evidence of caries increase when Indigenous people in North America changed from a strictly hunter-gatherer diet to a diet with maize. Rates also increased after contact with colonizing Europeans, implying an even greater dependence on maize.During the European Age of Enlightenment, the belief that a "tooth worm" caused caries was also no longer accepted in the European medical community. Pierre Fauchard, known as the father of modern dentistry, was one of the first to reject the idea that worms caused tooth decay and noted that sugar was detrimental to the teeth and gingiva. In 1850, another sharp increase in the prevalence of caries occurred and is believed to be a result of widespread diet changes. Prior to this time, cervical caries was the most frequent type of caries, but increased availability of sugar cane, refined flour, bread, and sweetened tea corresponded with a greater number of pit and fissure caries.
In the 1890s, W. D. Miller conducted a series of studies that led him to propose an explanation for dental caries that was influential for current theories. He found that bacteria inhabited the mouth and that they produced acids that dissolved tooth structures when in the presence of fermentable carbohydrates. This explanation is known as the chemoparasitic caries theory. Millers contribution, along with the research on plaque by G. V. Black and J. L. Williams, served as the foundation for the current explanation of the etiology of caries. Several of the specific strains of lactobacilli were identified in 1921 by Fernando E. Rodríguez Vargas.
In 1924 in London, Killian Clarke described a spherical bacterium in chains isolated from carious lesions which he called Streptococcus mutans. Although Clarke proposed that this organism was the cause of caries, the discovery was not followed up. Later, in 1954 in the US, Frank Orland working with hamsters showed that caries was transmissible and caused by acid-producing Streptococcus thus ending the debate whether dental caries were resultant from bacteria. It was not until the late 1960s that it became generally accepted that the Streptococcus isolated from hamster caries was the same as S. mutans.Tooth decay has been present throughout human history, from early hominids millions of years ago, to modern humans. The prevalence of caries increased dramatically in the 19th century, as the Industrial Revolution made certain items, such as refined sugar and flour, readily available. The diet of the "newly industrialized English working class" then became centered on bread, jam, and sweetened tea, greatly increasing both sugar consumption and caries.
Etymology and usage
Naturalized from Latin into English (a loanword), caries in its English form originated as a mass noun that means "rottenness", that is, "decay". The word is an uncountable noun.
Cariesology or cariology is the study of dental caries.
Society and culture
It is estimated that untreated dental caries results in worldwide productivity losses in the size of about US$27 billion yearly.
Other animals
Dental caries are uncommon among companion animals.
See also
Cariogram
References
Cited sources
Nanci, A. (2013). Ten Cates Oral Histology. Elsevier. ISBN 978-0323078467.
External links
Tooth decay at Curlie
Centers for Disease Control: Dental Caries |
Molar incisor hypomineralisation | Molar incisor hypomineralisation (MIH) is a type of enamel defect affecting, as the name suggests, the first molars and incisors in the permanent dentition. MIH is considered a worldwide problem and usually occurs in children under 10 years old. This developmental condition is caused by the lack of mineralisation of enamel during its maturation phase, due to interruption to the function of ameloblasts. Many factors have been suggested, such as genetics and medical problems during pregnancy, but only childhood illness, fever in particular, seems to be associated with MIH. However, further studies on the aetiology of MIH are required because it is believed to be multifactorial.MIH often presents as discolouration on one to four affected permanent molars and the associated incisors. The enamel of the affected teeth appears yellow, brown, cream or white and thus are sometimes referred to as ‘cheese molars’. These teeth are deemed less aesthetically pleasing, hence causing distress in children with MIH and their parents. It is important to note that although there is difference in enamel translucency in the affected teeth, there should not be any changes to the enamel thickness, unlike in enamel hypoplasia.As a consequence, children with MIH are more likely to experience tooth decay compared to those without the condition. Moreover, the development of tooth decay is very rapid due to the less mineralised enamel. MIH only becomes visible once the permanent molars start to erupt and that is when opacities on the tooth can be observed if it is affected. It will be useful for the children who are suspected to suffer from MIH to visit their dentist more frequently during the eruption of their first permanent molars to prevent any further complications affecting their oral health.
Signs and symptoms
The distribution of disease in those affected with MIH can vary greatly. It can be common for the enamel of one molar to be affected while the enamel of the contralateral molar is clinically unaffected, or with minor defects only.
Lesions
The lesions that appear in teeth affected with MIH can present as opacities that vary from white to yellow-brown. They are usually asymmetrical in appearance, with a sharp demarcation that distinguishes between normal and affected enamel. The lesions usually do not involve the cervical third of affected teeth.
Post-eruptive breakdown
Post-eruptive breakdown (PEB) is a clinical feature, often observed in the majority of severely affected cases. The rate of PEB may be increased by the loading of masticatory forces on enamel weakened by MIH. The lesions resulting from PEB are irregularly shaped, with rough margins from the shearing of the enamel. PEB is more likely to occur in MIH affected teeth with yellow or brown opacities rather than those with white opacities, as darker lesions reflect a greater deficit in mineral content.
Atypical caries
Teeth affected with MIH are at an increased risk of acquiring dental caries. This is because the properties of the enamel are altered by increased porosity and decreased hardness. Essentially, the balance between mineralisation and demineralisation shifts to favour demineralisation of enamel, giving the tooth less resilience in structure, thereby making it vulnerable to caries.The poor structural properties of the enamel in teeth with MIH also increase the likelihood of cavitation of any lesions, thereby causing the lesion to progress at a faster rate. Progression of the carious lesion is also more rapid in teeth with MIH as patients may experience tooth sensitivity while carrying out oral hygiene, causing them to avoid doing so and consequentially accelerating the decay.
Hypersensitivity
Teeth affected by MIH are often affected by hypersensitivity due to changes in temperature or toothbrushing. A study has suggested that a possible cause of hypersensitivity in MIH is the inflammatory reactions in the pulp due to oral bacteria penetrating through the hypomineralised enamel into the dentinal tubules.
Difficult to anaesthetise
It has been reported that MIH-affected teeth were more difficult to anaesthetise. Difficulty achieving anaesthesia in MIH-affected teeth may be caused by the chronic inflammation of the pulp due to the penetration of bacteria as the presence of inflammation can reduce the efficacy of local anaesthetics which may then result in more anaesthetic being given to achieve anaesthesia. Some dental treatment has been undertaken without local anaesthesia which could result in a child becoming more fearful and anxious when receiving dental treatment. This can be especially challenging in paediatric dentistry thus more specialised methods may be needed to increase the efficiency of anaesthetising teeth.Opacities due to MIH can be quite visible especially on anterior teeth which could present as a problem aesthetically. Patients frequently claim aesthetic discomfort when anterior teeth are involved. The discoloured appearance of the anterior teeth could also have negative effects on a child’s psychological development and self-esteem.
Tooth breakdown and restoration problems
MIH-affected teeth are more prone to breakdown as they are hypomineralised which weakens the enamel structure. Restorations placed on MIH-affected teeth were found to be more prone to failure due to both loss of tooth structure and material loss. The enamel can also fracture more easily due to chewing forces.
Causes
The exact cause of MIH is unknown but thought to be multifactorial.Pre-natally: risks, such as infection, maternal psychological stress and frequent exposure to ultrasonic scans were all correlated with increased risks of MIH.
During the perinatal stage, Pitiphat found that cesarean section and complications during vaginal delivery could contribute to an increased chance of MIH. Children born preterm and those with poor general health or systemic conditions in their first 3 years of development also run a higher risk of developing MIH. It has also been proposed that developmental dental defects were associated with long-term breastfeeding due to exposure to dioxin.
More recent evidence has suggested a relationship between respiratory diseases and oxygen shortage of the ameloblasts and MIH. Lastly oxygen shortage combined with low birth weight is suspected to be a contributing factor
Diagnosis
Differential diagnosis
It is essential to exclude other causes of enamel opacities, differentiating MIH from them, to ensure an appropriate treatment plan is made. These conditions include:
Dental caries, which is the most common cause of destruction of dental hard tissues. This is more unlikely in a patient with a previously intact primary dentition. White spot lesions are also uncommon on incisors, hence ruling out dental caries.
Fluorosis, which can result from an intake of a high fluoride concentration while the tooth is still undergoing mineralisation. Fluorosis presents as irregular, diffuse enamel opacities which affect more than 1 tooth, in contrast to the well-demarcated borders of hypomineralised enamel seen in MIH.
Amelogenesis imperfecta, a genetic condition, and thus there may be a history of similar defects in other family members. This condition affects both the primary and permanent dentition, and all surfaces tend to be equally affected, differentiating it from MIH.
Trauma to primary incisors resulting in discolouration of permanent incisors.
Administration of tetracycline during pregnancy and to children under 6 resulting in tooth staining (grey or yellow).
Enamel hypoplasia, caused by defective enamel matrix formation, is a quantitative defect which presents as a localised reduction in enamel thickness. This differs from hypomineralisation, which is a qualitative defect affecting the translucency of enamel.
Classification
MIH examination should be carried out on clean, wet teeth. The ideal age for examination is when the child is 8 years old - the age where all permanent first molars and most of the incisors are erupted. The permanent first molar will also still be in a comparatively sound condition without excessive post-eruption breakdown. Judgements of each individual teeth should be recorded, aiding the correct diagnosis of the condition.
There is currently a lack of standardisation in the scoring system and severity indices used to record the diagnosis of MIH. Various systems commonly employed in studies include:
Modified Defect of Dental Enamel (DDE) Index: This set of criteria allows for enamel defects to be detected, enabling a distinction between demarcated and diffused opacities.
European Academy of Paediatric Dentistry (EAPD) judgement criteria: This set of criteria was developed in 2003 to standardise classifications for use in epidemiological studies. However, while it allows the categorisation of the enamel condition, it does not address the severity of the enamel condition.
Molar Hypomineralisation Severity Index (MHSI): This set of criteria has been developed to address deficiencies in indices concerning the severity of hypomineralisation. It is based on both the clinical characteristics of hypomineralised defects and the EAPD judgement criteria. It was found to be effective in guiding the clinical management of children by predicting treatment undertaken for affected permanent first molars.
Ghanim et al index: The index combines principles of the EAPD judgement criteria and DDE index in order to grade the clinical status, amount of tooth surface area affected, and other enamel defects comparable to MIH. The index has been validated and a training manual was developed to assist researchers in implementing the index in a standardised manner.
Prevention
Prevention is of prior importance at an early developmental age as the defective tooth is more likely to have caries and post-eruptive breakdown due to its increased porosity. Appropriate dietary advice and toothpaste with a fluoride level of at least 1,000 ppm F should be recommended. For treating spontaneous hypersensitivity professional applications of fluoride varnish (e.g. Duraphat 22,600ppm F) or 0.4% stannous fluoride gel may be helpful.Casein Phosphopepetide-Amorphus Calcium Phosphate (CPP-ACP) provides a supersaturated environment of calcium and phosphate on the enamel surface to enhance remineralisation in the form of toothpaste or sugar free chewing gum. Its clinical effectiveness is still debatable but may benefit those patients who complain of mild pain to external stimuli.
Treatment
The frequency of first permanent molar treatment for children with MIH is nearly 10 times greater compared to children without MIH. The available treatment modalities for MIH is extensive but the decision on which treatment should be used is complex and multi-factorial. Factors may include: condition severity, the patient’s dental age, the child/parent’s social background and expectations. There are treatment modalities available to manage children affected by MIH; however, the evidence supporting these modalities are still weak.
Anterior teeth
Etch-bleach-seal technique
Involves repeated cycles of etching with 37% phosphoric acid followed by applying 5% sodium hypochlorite until improvement of discolouration is achieved. Clear resin composite or resin infiltrate can be used to seal the lesion after the technique.
Microabrasion
The aesthetics of a child’s anterior teeth is a concern for both children and their parents alike.
Yellow or brownish-yellow defects are of full thickness, and therefore may respond to bleaching with carbamide peroxide. However, careful consideration should be made of the risks including hypersensitivity, mucosal irritation and enamel surface alterations.Creamy-yellow or whitish-creamy defects are less porous and variable in depth, and may respond to microabrasion with 18% hydrochloric acid or 37.5% phosphoric acid and abrasive paste. Again, this should be undertaken cautiously as microabrasion may result in loss of enamel.
Veneers
Direct or indirect composite veneers can be effective in improving aesthetics with minimal tooth tissue removal. Ceramic veneers as a treatment option should be delayed due to the risks of resulting in a short clinical crown height, immature tooth pulp irritation and also the instability of the gingival margins during the eruption of teeth.
Posterior teeth
Fissure sealants
The placement of fissure sealants on permanent molars without post-eruptive breakdown should be undertaken. Use of a 5th generation bonding adhesive prior to fissure sealant application may improve retention rates of fissure sealants.For partially erupted molars with inadequate moisture control, glass ionomer cements (GIC) can be considered as an interim treatment option. As the retention rate of GIC is often poor, replacement with a resin-based fissure sealant is recommended following tooth eruption.Resin-based fissure sealants can be beneficial to patients affected with mild MIH where the first permanent molars have fully erupted, although the degree of hypomineralization affects the bond strength of said sealants. The bond strength of resin based fissure sealants to affected MIH can be enhanced by pre-treating with 5% sodium hypochlorite for one minute after etching, and applying a bonding agent. However, more evidence is needed from clinical based studies.
Direct restorations
Cavity design
There is still much debate of whether margin extension should include removal of all defective enamel or only the porous enamel. The former provides sound enamel for bonding but leads to excessive tooth tissue loss. The latter is less invasive, but the margins may have a high risk of breakdown due to defective bonding. Yet, it is agreed that adhesive restorations should be used as opposed to those reliant upon mechanical retention (such as amalgam).
Composite resin restorations
Composite resin material has been shown to have longer-term stability in MIH teeth, with a median survival rate of 5.2 years and a success rate of 74%-100% during a 4-year follow-up period. Self-etching adhesive was found to have better bond strength to enamel affected by MIH compared to total etch single-bottle adhesive. The use of composite should be considered both for permanent molars affected by MIH, as well as incisors. Furthermore, composite veneers may achieve a better aesthetic result where deep lesions are seen in incisors.
Glass ionomer cement (GIC) restorations
GIC materials have adhesive capabilities with both enamel and dentine, long-term fluoride release and hydrophilicity when there is inadequate moisture control intra-orally, during early post-eruptive stages. However, GIC’s poorer mechanical properties suggest avoidance in stress-bearing areas. In later post-eruptive stages GIC may be valuable as sub-layer beneath composite restorations.
Indirect restorations
Preformed metal crowns
Pre-formed metal crowns (PMC), also known as stainless steel crowns, can be used to reduce the risk of marginal breakdown, coronal leakage and has a good longevity. The use of preformed metal crowns on MIH-affected molars can prevent further tooth loss, control hypersensitivity and aim to establish correct interproximal and occlusal contact. They are relatively inexpensive and require little preparation.To prevent further tooth preparation and tissue loss, use of the Hall Technique should also be considered. There advantage is use during any stage of post-eruptive breakdown, but evidence of their efficacy is limited. Although the PMC has evidence to show that it is well accepted, a few of the children and their carers expressed their concerns about the metallic appearances of the restoration.
Cast restorations
Cast restorations may include full coverage crowns for MIH-affected permanent teeth. Generally cast restorations requiring tooth preparation are not recommended in young children due to large pulp size, short crown height and potential difficulties in obtaining a good impression for subgingival crown margins.
Extractions
A list of considerations can affect the final decision on whether extraction of the affected teeth should be carried out or should it be retained such as: severity of MIH; patient’s aesthetic expectations; whether the patient is suitable to undergo orthodontic treatment; orthodontic concerns (e.g. crowding, facial profile, missing or supernumerary teeth, presence of third molars).Timely extractions are often the preferred treatment plan for first permanent molars that are severely affected and symptomatic. The facilitation of eruption of the second permanent molars to the space of the first permanent molar removes the burden of continuous restorative treatment.A favourable occlusion may be acquired following a well-planned treatment and this eliminates the need for fixed orthodontic appliances therapy. However, a comprehensive discussion of the possible need of orthodontic sequelae and treatment is important.Favorable eruption position of the second permanent molar may result if the first permanent molar is extracted when the child is at the age of between 8–10 years old. This is when the crown formation of the second permanent molar is complete and the mineralization of the bifurcation is commenced.Extraction of first permanent molars before 8 years old increases the chances of the unerupted second permanent premolar drifting distally. Extraction after the age of 10 years reduces the likelihood of the mesial movement of the second permanent molar in to the first permanent molar space and may result in tilting of the second permanent molar.
Epidemiology
Since first recognised in the late 1970s, the condition has puzzled many people. It is thought to be a unique defect unlike other enamel disturbances e.g. fluorosis or amelogenesis imperfecta.Many prevalence studies have now been published from findings across the globe. However, there is a large amount of variation across the results of these studies. It is reported that the prevalence of MIH ranges from 3.6% to 40.2% with an estimate of 14.2% of the global population suffering. Worldwide there is much variation between continents with South America having the highest prevalence (18%), closely followed by Oceania (16.3%). The continent found to have least sufferers was Africa (10.9%).Multiple studies have provided evidence that there is no gender difference. However, a study by Kathmandu University reports that post eruptive breakdown occurs more frequently in boys than it does in girls. A different study found that children under the age of 10 are more highly affected by the disease (15.1%) compared to older children (12.1%).
== References == |
Heavy chain disease | Heavy chain disease is a form of paraproteinemia and plasma cell dyscrasia that involves the proliferation of cells producing immunoglobulin heavy chains.This disease is characterized by an excessive production of heavy chains that are short and truncated. These heavy chain disease proteins have various deletions, mainly in their amino-terminal part, which causes the heavy chains to lose the ability to form disulfide bonds with the light chains. The defect in the immunoglobulins presumably arises during somatic hypermutation. Deletion of the N-terminal part of the heavy chain disease protein leads to aggregation and signaling of the B cell receptor, presumably due to the loss of the anti-aggregating properties of the light chain.
Classification
There are four forms:
alpha chain disease (Seligmanns disease)
gamma chain disease (Franklins disease)
mu chain disease
delta chain disease
IgA/αHCD
The most common type of heavy chain disease is the IgA type, known as αHCD. The most common type of αHCD is the gastrointestinal form (known as immunoproliferative small intestine disease or IPSID), but it has also been reported in the respiratory tract, and other areas of the body.
IgG/γHCD
Franklins disease (gamma heavy chain disease)
It is a very rare B-cell lymphoplasma cell proliferative disorder which may be associated with autoimmune diseases and infection is a common characteristic of the disease. It is characterized by lymphadenopathy, fever, anemia, malaise, hepatosplenomegaly, and weakness. The most distinctive symptom is palatal edema, caused by nodal involvement of Waldeyers ring.
Diagnosis is made by the demonstration of an anomalous serum M component that reacts with anti-IgG but not anti-light chain reagents. Bone marrow examination is usually nondiagnostic.
Patients usually have a rapid downhill course and die of infection if left untreated or misdiagnosed.
Patients with Franklin disease usually have a history of progressive weakness, fatigue, intermittent fever, night sweats and weight loss and may present with lymphadenopathy (62%), splenomegaly (52%) or hepatomegaly (37%). The fever is considered secondary to impaired cellular and humoral immunity, and thus recurrent infections are the common clinical presentation in Franklin disease. Weng et al. described the first case of Penicillium sp. infection in a patient with Franklin disease and emphasized the importance of proper preparation for biopsy, complete hematologic investigation, culture preparation and early antifungal coverage to improve the outcome.The γHCD can be divided into three categories based on the various clinical and pathological features. These categories are disseminated lymphoproliferative disease, localized proliferative disease and no apparent proliferative disease.
Disseminated lymphoproliferative disease is found in 57-66% of patients diagnosed with γHCD. Lymphadenopathy and constitutional symptoms are the usual features.
Localized proliferative disease is found in approximately 25% of γHCD patients. This is characterized by a localization of the mutated heavy chains in extramedullary tissue, or solely in the bone marrow.
No apparent proliferative disease is seen in 9-17% of patients with γHCD, and there is almost always an underlying autoimmune disorder.
IgM/μHCD
The IgM type of heavy chain disease, μHCD, is often misdiagnosed as chronic lymphoid leukemia (CLL) because the two diseases are often associated with each other and show similar symptoms.
References
== External links == |
Focal facial dermal dysplasia | Focal facial dermal dysplasia is a rare genetically heterogeneous group of disorders that are characterized by congenital bilateral scar like facial lesions, with or without associated facial anomalies. It is characterized by hairless lesions with fingerprint like puckering of the skin, especially at the temples, due to alternating bands of dermal and epidermal atrophy.
This condition is also known as Brauer syndrome (hereditary symmetrical aplastic nevi of temples, bitemporal aplasia cutis congenita, bitemporal aplasia cutis congenita: OMIM 136500) and Setleis syndrome (facial ectodermal dysplasia: OMIM 227260).
Presentation
This condition is characterised by symmetrical lesions on the temples resembling forceps marks. It is characterized a puckered skin due to a virtual absence of subcutaneous fat. It is apparent at birth. Other lesions that may be present include puffy, wrinkled skin around the eyes and/or abnormalities of the eyelashes, eyebrows, and eyelids. The eyebrows may be up slanting or outward slanting. Occasionally the bridge of the nose may appear flat, while the tip may appear unusually rounded. The chin may be furrowed. The upper lip may be prominent with a down turned mouth. Other features that have been reported include dysplastic and low set ears, linear radiatory impressions on the forehead and congenital horizontal nystagmus.
Those with the Setleis syndrome may be missing eyelashes on both the upper and lower lids or may have multiple rows of lashes on the upper lids but none on the lower lids.A possible association with intra abdominal cancer has been reported but to date this has not been confirmed in other studies.
Genetics
Type II appears to be due to mutations in the transcription factor TWIST2 on chromosome 2.Type IV is due to mutations in the Cyp26c1 gene.
Pathology
Under the temporal lesions the skeletal muscle is almost in direct continuity with the epidermis.
Diagnosis
Classification
There are at least four types of FFDD:
Type I: autosomal dominant FFDD
Type II: autosomal recessive FFDD
Type III: FFDD with other facial features : Setleis syndrome
Type IV: facial lesions resembling aplasia cutis in a preauricular distribution along the line of fusion of the maxillary and mandibular prominences. Autosomal recessive.
Treatment
History
The syndrome was first described by Brauer in 1929 in a large five generation family (38 members). The affected progenitor (Johann Jokeb Van Bargen) was a man who had migrated to Germany from Holland in the 16th century. As many as 155 family members were thought to have been affected.
References
== External links == |
Ventricular outflow tract obstruction | A ventricular outflow tract obstruction is one type of congenital heart defect in which either the right or left ventricular outflow tract is blocked or obstructed. These obstructions represent a spectrum of disorders.
Right side
A right ventricular outflow tract obstruction (RVOTO) may be due to a defect in the pulmonic valve, the supravalvar region, the infundibulum, or the pulmonary artery.
Pulmonary atresia
Pulmonary valve stenosis
Hypoplastic right heart syndrome
Tetralogy of Fallot
Left side
A left ventricular outflow tract obstruction (LVOTO) may be due to a defect in the aortic valve, or a defect located at the subvalvar or supravalvar level.
Aortic valve stenosis
Supravalvar aortic stenosis
Coarctation of the aorta
Hypoplastic left heart syndrome
== References == |
Bunion | A bunion, also known as hallux valgus, is a deformity of the joint connecting the big toe to the foot. The big toe often bends towards the other toes and the joint becomes red and painful. The onset of bunions is typically gradual. Complications may include bursitis or arthritis.The exact cause is unclear. Proposed factors include wearing overly tight shoes, high-heeled shoes, family history, and rheumatoid arthritis. Diagnosis is generally based on symptoms and supported by X-rays. A similar condition of the little toe is referred to as a bunionette.Treatment may include proper shoes, orthotics, or NSAIDs. If this is not effective for improving symptoms, surgery may be performed. It affects about 23% of adults. Females are affected more often than males. Usual age of onset is between 20 and 50 years old. The condition also becomes more common with age. It was first clearly described in 1870. Archaeologists have found a high incidence of bunions in skeletons from 14th- and 15th-century England, coinciding with a fashion for pointy shoes.
Signs and symptoms
Symptoms may include irritation of the skin around the bunion, and blisters may form more easily at the site. Pain may be worse when walking.
Bunions can lead to difficulties finding properly fitting footwear and may force a person to buy a larger size shoe to accommodate the width of the bunion. If the bunion deformity becomes severe enough, the foot can hurt in different places even without the constriction of shoes. It is then considered as being a mechanical function problem of the forefoot.
Cause
The exact cause is unclear. It may be due to a combination of internal and external causes. Proposed factors include wearing overly tight shoes, high-heeled shoes, family history and rheumatoid arthritis. The American College of Foot and Ankle Surgeons states that footwear only worsens a problem caused by genetics.Excessive pronation of the foot causes increased pressure on the inside of the big toe that can result in a deformation of the medial capsular structures of the joint, subsequently increasing the risk of developing bunions.
Pathophysiology
The bump itself is partly due to the swollen bursal sac or an osseous (bony) anomaly on the metatarsophalangeal joint. The larger part of the bump is a normal part of the head of the first metatarsal bone that has tilted sideways to stick out at its distal (far) end (metatarsus primus varus).
Bunions are commonly associated with a deviated position of the big toe toward the second toe, and the deviation in the angle between the first and second metatarsal bones of the foot. The small sesamoid bones found beneath the first metatarsal (which help the flexor tendon bend the big toe downwards) may also become deviated over time as the first metatarsal bone drifts away from its normal position. Osteoarthritis of the first metatarsophalangeal joint, diminished and/or altered range of motion, and discomfort with pressure applied to the bump or with motion of the joint, may all accompany bunion development. Atop of the first metatarsal head either medially or dorso-medially, there can also arise a bursa that when inflamed (bursitis), can be the most painful aspect of the process.
Diagnosis
Bunion can be diagnosed and analyzed with a simple x-ray, which should be taken with the weight on the foot. The hallux valgus angle (HVA) is the angle between the long axes of the proximal phalanx and the first metatarsal bone of the big toe. It is considered abnormal if greater than 15–18°. The following HV angles can also be used to grade the severity of hallux valgus:
Mild: 15–20°
Moderate: 21–39°
Severe: ≥ 40°The intermetatarsal angle (IMA) is the angle between the longitudinal axes of the first and second metatarsal bones, and is normally less than 9°. The IM angle can also grade the severity of hallux valgus as:
Mild: 9–11°
Moderate: 12–17°
Severe: ≥ 18°
Treatment
Conservative treatment for bunions include changes in footwear, the use of orthotics (accommodative padding and shielding), rest, ice, and pain medications such as acetaminophen or nonsteroidal anti-inflammatory drugs. These treatments address symptoms but do not correct the actual deformity. If the discomfort persists and is severe or when aesthetic correction of the deformity is desired, surgical correction by an orthopedic surgeon or a podiatric surgeon may be necessary.
Orthotics
Orthotics are splints or regulators while conservative measures include various footwear like toe spacers, valgus splints, and bunion shields. Toe spacers seem to be effective in reducing pain, but there is not evidence that any of these techniques reduces the physical deformity. There are a variety of available orthotics including off-the-shelf commercial products and custom-molded orthotics, which may be prescribed medical devices.
Surgery
Procedures are designed and chosen to correct a variety of pathologies that may be associated with the bunion. For instance, procedures may address some combination of:
removing the abnormal bony enlargement of the first metatarsal,
realigning the first metatarsal bone relative to the adjacent metatarsal bone,
straightening the great toe relative to the first metatarsal and adjacent toes,
realigning the cartilaginous surfaces of the great toe joint,
addressing arthritic changes associated with the great toe joint,
repositioning the sesamoid bones beneath the first metatarsal bone,
shortening, lengthening, raising, or lowering the first metatarsal bone,
correcting any abnormal bowing or misalignment within the great toe,
connecting two parallel long bones side by side by syndesmosis procedureAt present there are many different bunion surgeries for different effects. The age, health, lifestyle and activity level of the patient may also play a role in the choice of procedure.
Traditional bunion surgery can be performed under local, spinal or general anesthetic. A person who has undergone bunion surgery can expect a 6- to 8-week recovery period during which crutches are usually required to aid mobility. An orthopedic cast is much less common today as newer, more stable procedures and better forms of fixation (stabilizing the bone with screws and other hardware) are used. Hardware may even include absorbable pins that perform their function and are then broken down by the body over the course of months. After recovery long term stiffness or limited range of motion may occur in some patients. Visible or limited scarring may also occur for patients.
References
External links
Textbook of Hallux Valgus and Forefoot Surgery, links to complete text in PDF files |
Acral fibrokeratoma | Acral fibrokeratoma (also known as an "Acquired digital fibrokeratoma," and "Acquired periungual fibrokeratoma": 668 ) is a skin lesion characterized by a pinkish, hyperkeratotic, hornlike projection occurring on a finger, toe, or palm.: 609 : 1817
See also
Skin lesion
List of cutaneous conditions
== References == |
Schwannoma | A schwannoma (or neurilemmoma) is a usually benign nerve sheath tumor composed of Schwann cells, which normally produce the insulating myelin sheath covering peripheral nerves.
Schwannomas are homogeneous tumors, consisting only of Schwann cells. The tumor cells always stay on the outside of the nerve, but the tumor itself may either push the nerve aside and/or up against a bony structure (thereby possibly causing damage). Schwannomas are relatively slow-growing. For reasons not yet understood, schwannomas are mostly benign and less than 1% become malignant, degenerating into a form of cancer known as neurofibrosarcoma. These masses are generally contained within a capsule, so surgical removal is often successful.Schwannomas can be associated with neurofibromatosis type II, which may be due to a loss-of-function mutation in the protein merlin. They are universally S-100 positive, which is a marker for cells of neural crest cell origin.
Schwannomas of the head and neck are a fairly common occurrence and can be found incidentally in 3–4% of patients at autopsy. Most common of these is a vestibular schwannoma, a tumor of the vestibulocochlear nerve that may lead to tinnitus and hearing loss on the affected side. Outside the cranial nerves, schwannomas may present on the flexor surfaces of the limbs. Rare occurrences of these tumors in the penis have been documented in the literature.Verocay bodies are seen histologically in schwannomas.
Variants
Pleural schwannoma is extremely rare. A unique subtype of schwannoma that typically develops in superficial (cutaneous or subcutaneous) sites and may be identified by its development pattern, which is plexiform (intraneuralnodular).The correlation with schwannoma predisposition disorders like NF2 and schwannomatosis, however, is minimal (approximately 5 percent of cases).These tumors might lack a capsule or be less encapsulated than a typical schwannoma.More challenging to identify from MPNST are the infrequent plexiform schwannomas that develop in deep anatomical sites, such as soft tissue or major peripheral nerves. These tumors may exhibit enhanced cellularity and mitotic activity. Although the likelihood of these tumors developing into cancer is extremely low, local recurrence is possible in around half of cases. On MRI, it usually shows hyper or iso-intensity on T1-weighted images and heterogenous hyperintensities on T2 weighted images. Pleural schwannoma typically shows fatty degeneration, hemorrhage, perivascular hyalinization, and cystic formation thus giving heterogenous hyperintensities on T2 weighted images. Complete surgical removal of pleural schwannoma is the usual treatment.
Cellular schwannoma is a relatively rare variation. Cellular schwannoma is nearly exclusively made up of a fascicular proliferation of well-differentiated Schwann cells that are cytologically bland, missing Verocay bodies, and just slightly exhibiting Antoni B pattern growth (10% of the tumor area). Local recurrence is Variable (5-40%) and perhaps greater than in normal schwannomas.
Melanotic schwannoma is an uncommon, unique, and possibly cancerous neoplasm defined by epithelioid cells with variable-sized nuclei, substantial melanin deposition in neoplastic cells, and associated melanophages.
Gallery
See also
Intranodal palisaded myofibroblastoma
List of inclusion bodies that aid in diagnosis of cutaneous conditions
Neurofibroma
Palisaded encapsulated neuroma
References
== External links == |
Subacute lymphocytic thyroiditis | Subacute lymphocytic thyroiditis is a form of thyroiditis. Subacute lymphocytic thyroiditis may occur at any age and is more common in females. A variant of subacute lymphocytic thyroiditis occurs postpartum: postpartum thyroiditis. Both of these entities can be considered subtypes of Hashimotos thyroiditis and have an autoimmune basis. Anti-thyroid antibodies are common in all three and the underlying histology is similar. This disorder should not be confused with de Quervains thyroiditis which is another form of subacute thyroiditis.
Symptoms and signs
Subacute lymphocytic thyroiditis features a small goiter without tenderness. This condition tends to have a phase of hyperthyroidism followed by a return to a euthyroid state, and then a phase of hypothyroidism, followed again by a return to the euthyroid state. The time span of each phase can vary; however, each phase usually lasts 2–3 months.
Diagnosis
Subacute lymphocytic thyroiditis can only be diagnosed correctly by taking a radioactive iodine uptake test (RAIU) test. During both the hyperthyroid and hypothyroid phases, radioiodine uptake is decreased. This situation contrasts greatly with the elevated iodine uptake found in patients with Graves disease.
Treatment
Treatment is based on symptoms. Beta-blockers relieve rapid heart rate and excessive sweating during the hyperthyroid phase.
== References == |
Hyperacusis | Hyperacusis is the increased sensitivity to sound and a low tolerance for environmental noise. Definitions of hyperacusis can vary significantly; it can refer to normal noises being perceived as: loud, annoying, painful, fear-inducing, or a combination of those, and is often categorized into four subtypes: loudness, pain, annoyance, and fear.It can be a highly debilitating hearing disorder. Hyperacusis is often coincident with tinnitus. The latter is more common and there are important differences between their involved mechanisms.Little is known about the prevalence of hyperacusis, in part due to the degree of variation in the terms definition. Reported prevalence in children and adolescents ranges from 3% to 17%.
Signs and symptoms
In hyperacusis, the symptoms are ear pain, annoyance, distortions, and general intolerance to many sounds that most people are unaffected by. Crying spells or panic attacks may result from the experience of hyperacusis. It may affect only one or both ears. Hyperacusis can also be accompanied by tinnitus. Hyperacusis can result in anxiety, stress and phonophobia. Avoidant behavior is often a response to prevent the effects of hyperacusis and this can include avoiding social situations.
Loudness Hyperacusis
Hyperacusis is most often characterized by a sensitivity to sound, where the perception of loudness is much greater than for a typical person; it is often associated with certain volumes and/or frequencies. Hyperacusis can occur in children and adults, and can be either "short-term" in a duration of weeks to less than a year before recovery, or, less-commonly, "long-term", spanning years and in some cases becoming permanent. Sensitivity is often different between ears.
Noxacusis (Pain Hyperacusis)
In some instances, hyperacusis is accompanied by pain, which is known as noxacusis. Noxacusis is characterized by pain resulting from sounds, often initiated at certain volumes or frequencies; pain can be immediate or delayed, and sometimes persists for an extended period of time following exposure. Pain can be acute or chronic, and is often described as stabbing, burning, acid, or nerve pain, and is sometimes equated with the pain of a root canal or a broken tooth.
Loudness Discomfort Level (LDL)
The threshold of sound at which discomfort is initially experienced; measured in decibels (dB).
Setback
After a period of some relief from symptoms, discomfort resumes; often resulting from exposure to sound, or, in some cases, ototoxic medications or injuries. Setback prevention is an important focus among those affected.
Associated conditions
Some conditions that are associated with hyperacusis include:
Causes
The most common cause of hyperacusis is overexposure to excessively high decibel (sound pressure) levels.Some affected people acquire hyperacusis suddenly as a result of taking ear sensitizing drugs, Lyme disease, Ménières disease, head injury, or surgery. Others are born with sound sensitivity, develop superior canal dehiscence syndrome, have had a history of ear infections, or come from a family that has had hearing problems. Bells palsy can trigger hyperacusis if the associated flaccid paralysis affects the tensor tympani, and stapedius, two small muscles of the middle ear. Paralysis of the stapedius muscle prevents its function in dampening the oscillations of the ossicles, causing sound to be abnormally loud on the affected side. Age may also be a significant factor.
Some psychoactive drugs such as LSD, methaqualone, or phencyclidine can cause hyperacusis. An antibiotic, ciprofloxacin, has also been seen to be a cause, known as ciprofloxacin-related hyperacusis. Benzodiazepine withdrawal syndrome is also a possible cause.
Neurophysiological mechanisms
As one important mechanism, adaptation processes in the auditory brain that influence the dynamic range of neural responses, are assumed to be distorted by irregular input from the inner ear. This is mainly caused by hearing loss related damage in the inner ear. The mechanism behind hyperacusis is not currently known, but it is suspected to be caused by damage to the inner ear and cochlea. It is theorized that type II afferent fibers become excited after damage to hair cells and synapses, triggering a release of ATP in response. This release of ATP results in pain, sound sensitivity, and cochlear inflammation.
Diagnosis
The basic diagnostic test is similar to a normal audiogram. The difference is that additionally to the hearing threshold at each test frequency also the lowest uncomfortable sound level is measured. This level is called loudness discomfort level (LDL), uncomfortable listening level (UCL), or uncomfortable loudness level (ULL). In patients with hyperacusis this level is considerably lower than in normal subjects, and usually across most parts of the auditory spectrum.
Treatment
Avoidance and Hearing Protection
Setback prevention and reduction of pain symptoms are high priorities among those with hyperacusis and noxacusis, which is often managed through a combination of controlling the environment so as to avoid loud sounds, soundproofing, and wearing hearing protection, such as earplugs and/or safety earmuffs, such as the type used at firing ranges or industrial applications
Diet
Diet may play a role in symptom management in some cases of hyperacusis, with response to a migraine diet, low-histamine diet, or low sodium diet.
Sound Therapy
Sound therapy is sometimes recommended for those with hyperacusis, though its application among those with pain (noxacusis) should be used with caution. Tinnitus retraining therapy, a treatment originally used to treat tinnitus, uses broadband noise to treat hyperacusis. Pink noise can also be used to treat hyperacusis. By listening to broadband noise at soft levels for a disciplined period of time each day, some patients can rebuild (i.e., re-establish) their tolerances to sound. More research is needed on the efficacy of sound therapy techniques when hyperacusis is the primary complaint, rather than a secondary symptom, indicating that "no strong conclusions can be made" about its efficacy at this time.
Cognitive Behavioral Therapy
Another possible treatment is cognitive behavioral therapy (CBT), which may also be combined with sound therapy. However, randomized controlled trials with active control groups are still needed to establish the effectiveness of CBT for hyperacusis and the usefulness of CBT for noxacusis (pain hyperacusis) is not yet demonstrated in the scientific literature.
Society and culture
Notable cases
Musician Jason DiEmilio, who recorded under the name Azusa Plane, had hyperacusis and ultimately went on to commit suicide due in part to his sensitivity to noise.
Musician Stephin Merritt has monaural hyperacusis in his left ear, which influences the instrumentation of his band, The Magnetic Fields, leads him to wear earplugs during performances and to cover his affected ear during audience applause.
Musician Laura Ballance of Superchunk has hyperacusis and no longer tours with the band.
American politician, activist, and film producer Michael Huffington has mild hyperacusis and underwent sound therapy after finding that running tap water caused ear pain.
Vladimir Lenin, the Russian communist revolutionary, politician, and political theorist, was reported seriously ill by the latter half of 1921, having hyperacusis and symptoms such as regular headache and insomnia.
Musician Chris Singleton had hyperacusis, but made a full recovery.
Musician Peter Silberman of The Antlers had hyperacusis and tinnitus which put his musical career on hold, until the conditions reduced down to a "manageable level". He has now resumed his musical career.
Voice actor Liam OBrien has hyperacusis, and was insomniac as a consequence.
In April 2021, Internet personality, singer-songwriter and voice actor Tay Zonday stated that he has "debilitating autistic hyperacusis".
See also
Misophonia
Otoacoustic emission
Sensory processing sensitivity
Recruitment (medicine)
References
== Further reading == |
Lassa fever | Lassa fever, also known as Lassa hemorrhagic fever (LHF), is a type of viral hemorrhagic fever caused by the Lassa virus. Many of those infected by the virus do not develop symptoms. When symptoms occur they typically include fever, weakness, headaches, vomiting, and muscle pains. Less commonly there may be bleeding from the mouth or gastrointestinal tract. The risk of death once infected is about one percent and frequently occurs within two weeks of the onset of symptoms. Of those who survive, about a quarter have hearing loss, which improves within three months in about half of these cases.The disease is usually initially spread to people via contact with the urine or feces of an infected multimammate mouse. Spread can then occur via direct contact between people. Diagnosis based on symptoms is difficult. Confirmation is by laboratory testing to detect the viruss RNA, antibodies for the virus, or the virus itself in cell culture. Other conditions that may present similarly include Ebola, malaria, typhoid fever, and yellow fever. The Lassa virus is a member of the Arenaviridae family of viruses.There is no vaccine. Prevention requires isolating those who are infected and decreasing contact with the mice. Other efforts to control the spread of disease include having a cat to hunt vermin, and storing food in sealed containers. Treatment is directed at addressing dehydration and improving symptoms. The antiviral medication ribavirin has been recommended, but evidence to support its use is weak.Descriptions of the disease date from the 1950s. The virus was first described in 1969 from a case in the town of Lassa, in Borno State, Nigeria. Lassa fever is relatively common in West Africa including the countries of Nigeria, Liberia, Sierra Leone, Guinea, and Ghana. There are about 300,000 to 500,000 cases which result in 5,000 deaths a year.
Signs and symptoms
Onset of symptoms is typically 7 to 21 days after exposure. In 80% of those who are infected few or no symptoms occur. These mild symptoms may include fever, tiredness, weakness, and headache. In 20% of people more severe symptoms such as bleeding gums, breathing problems, vomiting, chest pain, or dangerously low blood pressure may occur. Long term complications may include hearing loss. In those who are pregnant, miscarriage may occur in 95% of child-bearing women. Lassa fever can be difficult to distinguish clinically from other viral hemorrhagic fevers, such as Ebola virus disease. A combination of pharyngitis, pain behind the sternum, presence of excess protein in the urine and fever can indicate Lassa fever with higher specificity.In cases in which death occurs, this typically occurs within 14 days of onset. About 1% of all Lassa virus infections result in death. Approximately 15%-20% of those who have required hospitalization for Lassa fever die. The risk of death is greater in those who are pregnant. A "Swollen baby syndrome" may occur in newborns, infants and toddlers with pitting edema, abdominal distension and bleeding.
Cause
Virology
Lassa virus is a member of the Arenaviridae, a family of negative-sense, single-stranded RNA viruses. Specifically it is an old world arenavirus, which is enveloped, single-stranded, and bi-segmented RNA. This virus has both a large and a small genome section, with four lineages identified to date: Josiah (Sierra Leone), GA391 (Nigeria), LP (Nigeria) and strain AV.
Spread
Lassa virus commonly spreads to humans from other animals, specifically the Natal multimammate mouse or African rat, also called the Natal multimammate rat (Mastomys natalensis). This is probably the most common mouse in equatorial Africa, common in human households and eaten as a delicacy in some areas.The multimammate mouse can quickly produce a large number of offspring, tends to colonize human settlements, increasing the risk of rodent-human contact, and is found throughout the west, central and eastern parts of the African continent.Once the mouse has become a carrier, it will excrete the virus throughout the rest of its lifetime through feces and urine creating ample opportunity for exposure. The virus is probably transmitted by contact with the feces or urine of animals accessing grain stores in residences. No study has proven presence in breast milk, but the high level of viremia suggests it may be possible.Individuals who are at a higher risk of contracting the infection are those who live in rural areas where Mastomys are discovered, and where sanitation is not prevalent. Infection typically occurs by direct or indirect exposure to animal excrement through the respiratory or gastrointestinal tracts. Inhalation of tiny particles of infectious material (aerosol) is believed to be the most significant means of exposure. It is possible to acquire the infection through broken skin or mucous membranes that are directly exposed to infectious material. Transmission from person to person has been established, presenting a disease risk for healthcare workers. The virus is present in urine for between three and nine weeks after infection, and it can be transmitted in semen for up to three months after becoming infected.
Diagnosis
A range of laboratory investigations are performed, where possible, to diagnose the disease and assess its course and complications. The confidence of a diagnosis can be compromised if laboratory tests are not available. One comprising factor is the number of febrile illnesses present in Africa, such as malaria or typhoid fever that could potentially exhibit similar symptoms, particularly for non-specific manifestations of Lassa fever. In cases with abdominal pain, in countries where Lassa is common, Lassa fever is often misdiagnosed as appendicitis and intussusception which delays treatment with the antiviral ribavirin. In West Africa, where Lassa is most common, it is difficult to diagnose due to the absence of proper equipment to perform testing.The FDA has yet to approve a widely validated laboratory test for Lassa, but there are tests that have been able to provide definitive proof of the presence of the LASV virus. These tests include cell cultures, PCR, ELISA antigen assays, plaque neutralization assays, and immunofluorescence essays. However, immunofluorescence essays provide less definitive proof of Lassa infection. An ELISA test for antigen and Immunoglobulin M antibodies give 88% sensitivity and 90% specificity for the presence of the infection. Other laboratory findings in Lassa fever include lymphocytopenia (low white blood cell count), thrombocytopenia (low platelets), and elevated aspartate transaminase levels in the blood. Lassa fever virus can also be found in cerebrospinal fluid.
Prevention
Control of the Mastomys rodent population is impractical, so measures focus on keeping rodents out of homes and food supplies, encouraging effective personal hygiene, storing grain and other foodstuffs in rodent-proof containers, and disposing of garbage far from the home to help sustain clean households. Gloves, masks, laboratory coats, and goggles are advised while in contact with an infected person, to avoid contact with blood and body fluids. These issues in many countries are monitored by a department of public health. In less developed countries, these types of organizations may not have the necessary means to effectively control outbreaks.
Vaccine
There is no vaccine for humans as of 2019. Researchers at the United States Army Medical Research Institute of Infectious Diseases facility had a promising vaccine candidate in 2002. They have developed a replication-competent vaccine against Lassa virus based on recombinant vesicular stomatitis virus vectors expressing the Lassa virus glycoprotein. After a single intramuscular injection, test primates have survived lethal challenge, while showing no clinical symptoms.
Treatment
Treatment is directed at addressing dehydration and improving symptoms. All persons suspected of Lassa fever infection should be admitted to isolation facilities and their body fluids and excreta properly disposed of.
Medications
The antiviral medication ribavirin has been recommended, but evidence to support its use is weak. Some evidence has found that it may worsen outcomes in certain cases. Fluid replacement, blood transfusions, and medication for low blood pressure may be required. Intravenous interferon therapy has also been used.
Pregnancy
When Lassa fever infects pregnant women late in their third trimester, inducing delivery is necessary for the mother to have a good chance of survival. This is because the virus has an affinity for the placenta and other highly vascular tissues. The fetus has only a one in ten chance of survival no matter what course of action is taken; hence, the focus is always on saving the life of the mother. Following delivery, women should receive the same treatment as other people with Lassa fever.
Prognosis
About 15–20% of hospitalized people with Lassa fever will die from the illness. The overall case fatality rate is estimated to be 1%, but during epidemics, mortality can climb as high as 50%. The mortality rate is greater than 80% when it occurs in pregnant women during their third trimester; fetal death also occurs in nearly all those cases. Abortion decreases the risk of death to the mother. Some survivors experience lasting effects of the disease, and can include partial or complete deafness.Because of treatment with ribavirin, fatality rates have declined.
Epidemiology
There are about 300,000 to 500,000 cases which result in 5,000 deaths a year. One estimate places the number as high as 3 million cases per year.Estimates of Lassa fever are complicated by the lack of easy-available diagnosis, limited public health surveillance infrastructure, and high clustering of incidence near high intensity sampling.The infection affects females 1.2 times more than males. The age group predominantly infected is 21–30 years.
Geography
Lassa high risk areas are near the western and eastern extremes of West Africa. As of 2018, the Lassa belt includes Guinea, Nigeria, Sierra Leone and Liberia. As of 2003, 10-16% of people in Sierra Leone and Liberia admitted to hospital had the virus. The case fatality rate for those who are hospitalized for the disease is about 15-20%. Research showed a twofold increase risk of infection for those living in close proximity to someone with infection symptoms within the last year.
The high risk areas cannot be well defined by any known biogeographical or environmental breaks except for the multimammate rat, particularly Guinea (Kindia, Faranah and Nzérékoré regions), Liberia (mostly in Lofa, Bong, and Nimba counties), Nigeria (in about 10 of 36 states) and Sierra Leone (typically from Kenema and Kailahun districts). It is less common in the Central African Republic, Mali, Senegal and other nearby countries, and less common yet in Ghana and the Democratic Republic of the Congo. Benin had its first confirmed cases in 2014, and Togo had its first confirmed cases in 2016.As of 2013, the spread of Lassa outside of West Africa had been very limited. Twenty to thirty cases had been described in Europe, as being caused by importation through infected individuals. These cases found outside of West Africa were found to have a high fatality risk because of the delay of diagnosis and treatment due to being unaware of the risk associated with the symptoms. Imported cases have not manifested in larger epidemics outside of Africa due to a lack of human to human transmission in hospital settings. An exception had occurred in 2003 when a healthcare worker became infected before the person showed clear symptoms.
Nigeria
2018 outbreak
An outbreak of Lassa fever occurred in Nigeria during 2018 and spread to 18 of the countrys states; it was the largest outbreak of Lassa recorded. On 25 February 2018, there were 1081 suspected cases and 90 reported deaths; 317 of the cases and 72 deaths were confirmed as Lassa which increased to a total of 431 reported cases in 2018.
2019 outbreak
The total cases in Nigeria in 2019 was 810 with 167 deaths, the largest case fatality rate(23.3%) until then.
2020 outbreak
The epidemic started from the second week of the January. By the tenth week the total number of cases has risen to 855 and deaths to 144, the case fatality rate of 16.8%.2021 Outbreak
On the 8th of December 2021, the Nigeria Centre for Disease Control (NCDC) was notified of the death of two persons from Lassa fever.2022 Outbreak
The epidemic took a new form, from 3 to 30 January 2022, 211 laboratory confirmed Lassa fever cases including 40 deaths (case fatality ratio: 19%) have been cumulatively reported in 14 of the 36 Nigerian states and the Federal Capital Territory across the country. In total from January until March, 132 deaths have been reported with a case fatality rate (CFR) of 19.1% which is lower than the CFR for the same period in 2021 (21.0%).
Liberia
Lassa fever is endemic in Liberia. From 1 January 2017 through 23 January 2018, 91 suspected cases were reported from six counties: Bong, Grand Bassa, Grand Kru, Lofa, Margibi, and Nimba. Thirty-three of these cases were laboratory confirmed, including 15 deaths (case fatality rate for confirmed cases = 45.4%).In February 2020, a total of 24 confirmed cases with nine associated deaths has been reported from nine health districts in six counties. Grand Bossa and Bong counties account for 20 of the confirmed cases.
History
The disease was identified in Nigeria in 1969. It is named after the town of Lassa, where it was discovered.A prominent expert in the disease, Aniru Conteh, died from the disease.
Research
The Lassa virus is one of several viruses identified by WHO as a likely cause of a future epidemic. They therefore list it for urgent research and development to develop new diagnostic tests, vaccines, and medicines.In 2007, SIGA Technologies, studied a medication in guinea pig with Lassa fever. Work on a vaccine is continuing, with multiple approaches showing positive results in animal trials.
References
Further reading
Echioya, Deborah U.; Hass, Meike; Olshlager, Stephan; Becker-Ziaja, Beate; Chukwu, Christian O. Onyebuchi; Coker, Jide; Nasidi, Abdulsalam; Ogugua, Osi-Ogdu; Gunther, Stephan; Omilabu, Sunday A. (2010). "Lassa Fever, Nigeria, 2005-2008". Emerging Infectious Diseases. 6. 16 (6): 1040–41. doi:10.3201/eid1606.100080. PMC 3086228. PMID 20507773.
Branco, Luis M.; Grove, Jessica N.; Boisen, Matt L.; Shaffer, Jeffrey G.; Goba, Augustine; Fullah, Mohammed; Momoh, Mambu; Grant, Donald S.; Garry, Robert F. (4 October 2011). "Emerging Trends in Lassa Fever: Redefining the Role of Immunoglobulin M and Inflammation in Diagnosing Acute Infection". Virology Journal. 8: 478. doi:10.1186/1743-422x-8-478. PMC 3223505. PMID 22023795. |
Hereditary spastic paraplegia | Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder. The disease presents with progressive stiffness (spasticity) and contraction in the lower limbs. HSP is also known as hereditary spastic paraparesis, familial spastic paraplegia, French settlement disease, Strumpell disease, or Strumpell-Lorrain disease. The symptoms are a result of dysfunction of long axons in the spinal cord. The affected cells are the primary motor neurons; therefore, the disease is an upper motor neuron disease. HSP is not a form of cerebral palsy even though it physically may appear and behave much the same as spastic diplegia. The origin of HSP is different from cerebral palsy. Despite this, some of the same anti-spasticity medications used in spastic cerebral palsy are sometimes used to treat HSP symptoms.
HSP is caused by defects in transport of proteins, structural proteins, cell-maintaining proteins, lipids, and other substances through the cell. Long nerve fibers (axons) are affected because long distances make nerve cells particularly sensitive to defects in these mentioned mechanisms.The disease was first described in 1880 by the German neurologist Adolph Strümpell. It was described more extensively in 1888 by Maurice Lorrain, a French physician. Due to their contribution in describing the disease, it is still called Strümpell-Lorrain disease in French-speaking countries. The term hereditary spastic paraplegia was coined by Anita Harding in 1983.
Signs and symptoms
Symptoms depend on the type of HSP inherited. The main feature of the disease is progressive spasticity in the lower limbs due to pyramidal tract dysfunction. This also results in brisk reflexes, extensor plantar reflexes, muscle weakness, and variable bladder disturbances. Furthermore, among the core symptoms of HSP are also included abnormal gait and difficulty in walking, decreased vibratory sense at the ankles, and paresthesia.
Individuals with HSP can experience extreme fatigue associated with central nervous system and neuromuscular disorders, which can be disabling. Initial symptoms are typically difficulty with balance, stubbing the toe or stumbling. Symptoms of HSP may begin at any age, from infancy to older than 60 years. If symptoms begin during the teenage years or later, then spastic gait disturbance usually progresses over many years. Canes, walkers, and wheelchairs may eventually be required, although some people never require assistance devices. Disability has been described as progressing more rapidly in adult onset forms.More specifically, patients with the autosomal dominant pure form of HSP reveal normal facial and extraocular movement. Although jaw jerk may be brisk in older subjects, there is no speech disturbance or difficulty of swallowing. Upper extremity muscle tone and strength are normal. In the lower extremities, muscle tone is increased at the hamstrings, quadriceps and ankles. Weakness is most notable at the iliopsoas, tibialis anterior, and to a lesser extent, hamstring muscles.
In the complex form of the disorder, additional symptoms are present. These include: peripheral neuropathy, amyotrophy, ataxia, intellectual disability, ichthyosis, epilepsy, optic neuropathy, dementia, deafness, or problems with speech, swallowing or breathing.Anita Harding classified the HSP in a pure and complicated form. Pure HSP presents with spasticity in the lower limbs, associated with neurogenic bladder disturbance as well as lack of vibration sensitivity (pallhypesthesia). On the other hand, HSP is classified as complex when lower limb spasticity is combined with any additional neurological symptom.This classification is subjective and patients with complex HSPs are sometimes diagnosed as having cerebellar ataxia with spasticity, intellectual disability (with spasticity), or leukodystrophy. Some of the genes listed below have been described in other diseases than HSP before. Therefore, some key genes overlap with other disease groups.
Age of onset
In the past, HSP has been classified as early onset beginning in early childhood or later onset in adulthood. The age of onsets has two points of maximum at age 2 and around age 40. New findings propose that an earlier onset leads to a longer disease duration without loss of ambulation or the need for the use of a wheelchair. This was also described earlier, that later onset forms evolve more rapidly.
Cause
HSP is a group of genetic disorders. It follows general inheritance rules and can be inherited in an autosomal dominant, autosomal recessive or X-linked recessive manner. The mode of inheritance involved has a direct impact on the chances of inheriting the disorder. Over 70 genotypes had been described, and over 50 genetic loci have been linked to this condition. Ten genes have been identified with autosomal dominant inheritance. One of these, SPG4, accounts for ~50% of all genetically solved cases, or approximately 25% of all HSP cases. Twelve genes are known to be inherited in an autosomal recessive fashion. Collectively this latter group account for ~1/3 cases.Most altered genes have known function, but for some the function havent been identified yet. All of them are listed in the gene list below, including their mode of inheritance. Some examples are spastin (SPG4) and paraplegin (SPG7) are both AAA ATPases.
Genotypes
The genes are designated SPG (Spastic gait gene). The gene locations are in the format: chromosome - arm (short or p: long or q) - band number. These designations are for the human genes only. The locations may (and probably will) vary in other organisms.
Despite the number of genes known to be involved in this condition ~40% of cases have yet to have their cause identified. In the table below SPG? is used to indicate a gene that has been associated with HSP but has not yet received an official HSP gene designation.
Pathophysiology
The major feature of HSP is a length-dependent axonal degeneration. These include the crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis. The spinocerebellar tract is involved to a lesser extent. Neuronal cell bodies of degenerating axons are preserved and there is no evidence of primary demyelination. Loss of anterior horn cells of the spinal cord are observed in some cases. Dorsal root ganglia, posterior roots and peripheral nerves are not directly affected.HSP affects several pathways in motor neurons. Many genes were identified and linked to HSP. It remains a challenge to accurately define the key players in each of the affected pathways, mainly because many genes have multiple functions and are involved in more than one pathway.
Axon pathfinding
Pathfinding is important for axon growth to the right destination (e.g. another nerve cell or a muscle). Significant for this mechanism is the L1CAM gene, a cell surface glycoprotein of the immunoglobulin superfamily. Mutations leading to a loss-of-function in L1CAM are also found in other X-linked syndromes. All of these disorders display corticospinal tract impairment (a hallmark feature of HSP). L1CAM participates in a set of interactions, binding other L1CAM molecules as well as extracellular cell adhesion molecules, integrins, and proteoglycans or intracellular proteins like ankyrins.The pathfinding defect occurs via the association of L1CAM with neuropilin-1. Neuropilin-1 interacts with Plexin-A proteins to form the Semaphorin-3A receptor complex. Semaphorin-a3A is then released in the ventral spinal cord to steer corticospinal neurons away from the midline spinal cord / medullary junction. If L1CAM does not work correctly due to a mutation, the cortiocospinal neurons are not directed to the correct position and the impairment occurs.
Lipid metabolism
Axons in the central and peripheral nervous system are coated with an insulation, the myelin layer, to increase the speed of action potential propagation. Abnormal myelination in the CNS is detected in some forms of hsp HSP. Several genes were linked to myelin malformation, namely PLP1, GFC2 and FA2H. The mutations alter myelin composition, thickness and integrity.Endoplasmic reticulum (ER) is the main organelle for lipid synthesis. Mutations in genes encoding proteins that have a role in shaping ER morphology and lipid metabolism were linked to HSP. Mutations in ATL1, BSCL2 and ERLIN2 alter ER structure, specifically the tubular network and the formation of three-way junctions in ER tubules. Many mutated genes are linked to abnormal lipid metabolism. The most prevalent effect is on arachidonic acid (CYP2U1) and cholesterol (CYP7B1) metabolism, phospholipase activity (DDHD1 and DDHD2), ganglioside formation (B4GALNT-1) and the balance between carbohydrate and fat metabolism (SLV33A1).
Endosomal trafficking
Neurons take in substances from their surrounding by endocytosis. Endocytic vesicles fuse to endosomes in order to release their content. There are three main compartments that have endosome trafficking: Golgi to/from endosomes; plasma membrane to/from early endosomes (via recycling endosomes) and late endosomes to lysosomes. Dysfunction of endosomal trafficking can have severe consequences in motor neurons with long axons, as reported in HSP. Mutations in AP4B1 and KIAA0415 are linked to disturbance in vesicle formation and membrane trafficking including selective uptake of proteins into vesicles. Both genes encode proteins that interact with several other proteins and disrupt the secretory and endocytic pathways.
Mitochondrial function
Mitochondrial dysfunctions have been connected with developmental and degenerative neurological disorders. Only a few HSP genes encode mitochondrial proteins. Two mitochondrial resident proteins are mutated in HSP: paraplegin and chaperonin 60. Paraplegin is a m-AAA metalloprotease of the inner mitochondrial membrane. It functions in ribosomal assembly and protein quality control. The impaired chaperonin 60 activity leads to impaired mitochondrial quality control. Two genes DDHD1 and CYP2U1 have shown alteration of mitochondrial architecture in patient fibroblasts. These genes encode enzymes involved in fatty-acid metabolism.
Diagnosis
Initial diagnosis of HSPs relies upon family history, the presence or absence of additional signs and the exclusion of other nongenetic causes of spasticity, the latter being particular important in sporadic cases.Cerebral and spinal MRI is an important procedure performed in order to rule out other frequent neurological conditions, such as multiple sclerosis, but also to detect associated abnormalities such as cerebellar or corpus callosum atrophy as well as white matter abnormalities. Differential diagnosis of HSP should also exclude spastic diplegia which presents with nearly identical day-to-day effects and even is treatable with similar medicines such as baclofen and orthopedic surgery; at times, these two conditions may look and feel so similar that the only perceived difference may be HSPs hereditary nature versus the explicitly non-hereditary nature of spastic diplegia (however, unlike spastic diplegia and other forms of spastic cerebral palsy, HSP cannot be reliably treated with selective dorsal rhizotomy).Ultimate confirmation of HSP diagnosis can only be provided by carrying out genetic tests targeted towards known genetic mutations.
Classification
Hereditary spastic paraplegias can be classified based on the symptoms; mode of inheritance; the patients age at onset; the affected genes; and biochemical pathways involved.
Treatment
No specific treatment is known that would prevent, slow, or reverse HSP. Available therapies mainly consist of symptomatic medical management and promoting physical and emotional well-being. Therapeutics offered to HSP patients include:
Baclofen – a voluntary muscle relaxant to relax muscles and reduce tone. This can be administered orally or intrathecally. (Studies in HSP )
Tizanidine – to treat nocturnal or intermittent spasms (studies available )
Diazepam and clonazepam – to decrease intensity of spasms
Oxybutynin chloride – an involuntary muscle relaxant and spasmolytic agent, used to reduce spasticity of the bladder in patients with bladder control problems
Tolterodine tartrate – an involuntary muscle relaxant and spasmolytic agent, used to reduce spasticity of the bladder in patients with bladder control problems
Cro System – to reduce muscle overactivity (existing studies for spasticity )
Botulinum toxin – to reduce muscle overactivity (existing studies for HSP patients)
Antidepressants (such as selective serotonin re-uptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors) – for patients experiencing clinical depression
Physical therapy – to restore and maintain the ability to move; to reduce muscle tone; to maintain or improve range of motion and mobility; to increase strength and coordination; to prevent complications, such as frozen joints, contractures, or bedsores.
Prognosis
Although HSP is a progressive condition, the prognosis for individuals with HSP varies greatly. It primarily affects the legs although there can be some upperbody involvement in some individuals. Some cases are seriously disabling while others are less disabling and are compatible with a productive and full life. The majority of individuals with HSP have a normal life expectancy.
Epidemiology
Worldwide, the prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people. A Norwegian study of more than 2.5 million people published in March 2009 has found an HSP prevalence rate of 7.4/100,000 of population – a higher rate, but in the same range as previous studies. No differences in rate relating to gender were found, and average age at onset was 24 years. In the United States, Hereditary Spastic Paraplegia is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health which means that the disorder affects less than 200,000 people in the US population.
References
Further reading
GeneReviews/NCBI/NIH/UW entry on Spastic Paraplegia 3A
GeneReviews/NCBI/NIH/UW entry on Hereditary Spastic Paraplegia Overview
Warner, Tom (January–February 2007). "Hereditary Spastic Paraplegia" (PDF). Advances in Clinical Neuroscience and Rehabilitation. 6 (6): 16–17.
External links
Spastic Paraplegia Foundation |
Barbiturate overdose | Barbiturate overdose is poisoning due to excessive doses of barbiturates. Symptoms typically include difficulty thinking, poor coordination, decreased level of consciousness, and a decreased effort to breathe (respiratory depression). Complications of overdose can include noncardiogenic pulmonary edema. If death occurs this is typically due to a lack of breathing.Barbiturate overdose may occur by accident or purposefully in an attempt to cause death. The toxic effects are additive to those of alcohol and benzodiazepines. The lethal dose varies with a persons tolerance and how the drug is taken. The effects of barbiturates occur via the GABA neurotransmitter. Exposure may be verified by testing the urine or blood.Treatment involves supporting a persons breathing and blood pressure. While there is no antidote, activated charcoal may be useful. Multiple doses of charcoal may be required. Hemodialysis may occasionally be considered. Urine alkalinisation has not been found to be useful. While once a common cause of overdose, barbiturates are now a rare cause.
Mechanism
Barbiturates increase the time that the chloride pore of the GABAA receptor is opened, thereby increasing the efficacy of GABA. In contrast, benzodiazepines increase the frequency with which the chloride pore is opened, thereby increasing GABAs potency.
Treatment
Treatment involves supporting a persons breathing and blood pressure. While there is no antidote, activated charcoal may be useful. Multiple doses of charcoal may be required. Hemodialysis may occasionally be considered. Urine alkalinisation has not been found to be useful.If a person is drowsy but awake and can swallow and breathe without difficulty, the treatment can be as simple as monitoring the person closely. If the person is not breathing, it may involve mechanical ventilation until the drug has worn off. Psychiatric consult is generally recommended.
Notable cases
People who are known to have died by suicide from barbiturate overdose include, Gillian Bennett, Charles Boyer, Ruan Lingyu, Victor Folke Nelson, Dalida, Jeannine "The Singing Nun" Deckers, Felix Hausdorff, Abbie Hoffman, Phyllis Hyman, Marilyn Monroe, C. P. Ramanujam, George Sanders, Jean Seberg, Lupe Vélez and the members of Heavens Gate cult. Others who have died as a result of barbiturate overdose include Pier Angeli, Brian Epstein, Judy Garland, Jimi Hendrix, Inger Stevens, Dinah Washington, Ellen Wilkinson, and Alan Wilson; in some cases these have been speculated to be suicides as well. Those who died of a combination of barbiturates and other drugs include Rainer Werner Fassbinder, Dorothy Kilgallen, Malcolm Lowry, Edie Sedgwick and Kenneth Williams. Dorothy Dandridge died of either an overdose or an unrelated embolism. Ingeborg Bachmann may have died of the consequences of barbiturate withdrawal (she was hospitalized with burns, the doctors treating her not being aware of her barbiturate addiction). Maurice Chevalier attempted suicide in March 1971 by swallowing a large amount of barbiturates and slitting his wrists. While he lived, he suffered severe organ damage as a result and died from multiple organ failure nine months later.
Differential diagnosis
The differential diagnosis should include intoxication by other substances with sedative effects, such as benzodiazepines, anticonvulsants (carbamazepine), alcohols (ethanol, ethylene glycol, methanol), opioids, carbon monoxide, sleep aids, and gamma-Hydroxybutyric acid (GHB – a known date rape drug). Natural disease that can result in disorientation may be in the differential, including hypoglycemia and myxedema coma. In the right setting, hypothermia should be ruled out.
References
== External links == |
Conversion disorder | Conversion disorder (CD), or functional neurologic symptom disorder, is a diagnostic category used in some psychiatric classification systems. It is sometimes applied to patients who present with neurological symptoms, such as numbness, blindness, paralysis, or fits, which are not consistent with a well-established organic cause, which cause significant distress, and can be traced back to a psychological trigger. It is thought that these symptoms arise in response to stressful situations affecting a patients mental health or an ongoing mental health condition such as depression. Conversion disorder was retained in DSM-5, but given the subtitle functional neurological symptom disorder. The new criteria cover the same range of symptoms, but remove the requirements for a psychological stressor to be present and for feigning to be disproved. ICD-10 classifies conversion disorder as a dissociative disorder while DSM-IV classifies it as a somatoform disorder.
Signs and symptoms
Conversion disorder begins with some stressor, trauma, or psychological distress. Usually the physical symptoms of the syndrome affect the senses or movement. Common symptoms include blindness, partial or total paralysis, inability to speak, deafness, numbness, difficulty swallowing, incontinence, balance problems, seizures, tremors, and difficulty walking. The symptom of feeling unable to breathe, but where the lips are not turning blue, can indicate conversion disorder or sleep paralysis. Sleep paralysis and narcolepsy can be ruled out with sleep tests. These symptoms are attributed to conversion disorder when a medical explanation for the conditions cannot be found. Symptoms of conversion disorder usually occur suddenly. Conversion disorder is typically seen in people aged 10 to 35, and affects between 0.011% and 0.5% of the general population.Conversion disorder can present with motor or sensory symptoms including any of the following:
Motor symptoms or deficits:
Impaired coordination or balance
Weakness/paralysis of a limb or the entire body (hysterical paralysis or motor conversion disorders)
Impairment or loss of speech (hysterical aphonia)
Difficulty swallowing (dysphagia) or a sensation of a lump in the throat
Urinary retention
Psychogenic non-epileptic seizures or convulsions
Persistent dystonia
Tremor, myoclonus or other movement disorders
Gait problems (astasia-abasia)
Loss of consciousness (fainting)Sensory symptoms or deficits:
Impaired vision (hysterical blindness), double vision
Impaired hearing (deafness)
Loss or disturbance of touch or pain sensationConversion symptoms typically do not conform to known anatomical pathways and physiological mechanisms. It has sometimes been stated that the presenting symptoms tend to reflect the patients own understanding of anatomy and that the less medical knowledge a person has, the more implausible are the presenting symptoms. However, no systematic studies have yet been performed to substantiate this statement.
Diagnosis
Definition
Conversion disorder is now contained under the umbrella term functional neurological symptom disorder. In cases of conversion disorder, there is a psychological stressor.
The diagnostic criteria for functional neurological symptom disorder, as set out in DSM-5, are:
Specify type of symptom or deficit as:
With weakness or paralysis
With abnormal movement (e.g. tremor, dystonic movement, myoclonus, gait disorder)
With swallowing symptoms
With speech symptoms (e.g. dysphonia, slurred speech)
With attacks or seizures
With amnesia or memory loss
With special sensory loss symptoms (e.g. visual blindness, olfactory loss, or hearing disturbance)
With mixed symptoms.Specify if:
Acute episode: symptoms present for less than six months
Persistent: symptoms present for six months or more.Specify if:
Psychological stressor (conversion disorder)
No psychological stressor (functional neurological symptom disorder)
Exclusion of neurological disease
Conversion disorder presents with symptoms that typically resemble a neurological disorder such as stroke, multiple sclerosis, epilepsy, hypokalemic periodic paralysis or narcolepsy. The neurologist must carefully exclude neurological disease, through examination and appropriate investigations. However, it is not uncommon for patients with neurological disease to also have conversion disorder.In excluding neurological disease, the neurologist has traditionally relied partly on the presence of positive signs of conversion disorder, i.e. certain aspects of the presentation that were thought to be rare in neurological disease but common in conversion. The validity of many of these signs has been questioned, however, by a study showing they also occur in neurological disease. One such symptom, for example, is la belle indifférence, described in DSM-IV as "a relative lack of concern about the nature or implications of the symptoms". In a later study, no evidence was found that patients with functional symptoms are any more likely to exhibit this than patients with a confirmed organic disease. In DSM-V, la belle indifférence was removed as a diagnostic criterion.
Another feature thought to be important was that symptoms tended to be more severe on the non-dominant (usually left) side of the body. There have been a number of theories about this, such as the relative involvement of cerebral hemispheres in emotional processing, or more simply, that it was "easier" to live with a functional deficit on the non-dominant side. However, a literature review of 121 studies established that this was not true, with publication bias the most likely explanation for this commonly held view. Although agitation is often assumed to be a positive sign of conversion disorder, release of epinephrine is a well-demonstrated cause of paralysis from hypokalemic periodic paralysis.Misdiagnosis does sometimes occur. In a highly influential study from the 1960s, Eliot Slater demonstrated that misdiagnoses had occurred in one third of his 112 patients with conversion disorder. Later authors have argued that the paper was flawed, however, and a meta-analysis has shown that misdiagnosis rates since that paper was published are around four percent, the same as for other neurological diseases.
Deliberate feigning
Conversion disorder, by its nature, is more prone to deliberate feigning. One neuroimaging study suggested that feigning may be distinguished from conversion by the pattern of frontal lobe activation.
Psychological mechanism
The psychological mechanism of conversion can be the most difficult aspect of a conversion diagnosis. Even if there is a clear antecedent trauma or other possible psychological trigger, it is still not clear exactly how this gives rise to the symptoms observed. Patients with medically unexplained neurological symptoms may not have any psychological stressor, hence the use of the term "functional neurological symptom disorder" in DSM-5 as opposed to "conversion disorder", and DSM-5s removal of the need for a psychological trigger.
Treatment
There are a number of different treatments available to treat and manage conversion syndrome. Treatments for conversion syndrome include hypnosis, psychotherapy, physical therapy, stress management, and transcranial magnetic stimulation. Treatment plans will consider duration and presentation of symptoms and may include one or multiple of the above treatments. This may include the following:
Occupational therapy to maintain autonomy in activities of daily living;
Physiotherapy where appropriate.
Treatment of comorbid depression or anxiety if present.
Educating patients on the causes of their symptoms might help them learn to manage both the psychiatric and physical aspects of their condition. Psychological counseling is often warranted given the known relationship between conversion disorder and emotional trauma. This approach ideally takes place alongside other types of treatment.There is little evidence-based treatment of conversion disorder. Other treatments such as cognitive behavioral therapy, hypnosis, EMDR, and psychodynamic psychotherapy, EEG brain biofeedback need further trials. Psychoanalytic treatment may possibly be helpful. However, most studies assessing the efficacy of these treatments are of poor quality and larger, better controlled studies are urgently needed. Cognitive Behavioural Therapy is the most common treatment, however boasts a mere 13% improvement rate.
Prognosis
Empirical studies have found that the prognosis for conversion disorder varies widely, with some cases resolving in weeks, and others enduring for years or decades. There is also evidence that there is no cure for conversion disorder, and that although patients may go into remission they can relapse at any point. Furthermore, many patients can get rid of their symptoms with time, treatments and reassurance.
Epidemiology
Frequency
Information on the frequency of conversion disorder in the West is limited, in part due to the complexities of the diagnostic process. In neurology clinics, the reported prevalence of unexplained symptoms among new patients is very high (between 30 and 60%). However, diagnosis of conversion typically requires an additional psychiatric evaluation, and since few patients will see a psychiatrist it is unclear what proportion of the unexplained symptoms are actually due to conversion. Large scale psychiatric registers in the US and Iceland found incidence rates of 22 and 11 newly diagnosed cases per 100,000 person-years, respectively. Some estimates claim that in the general population, between 0.011% and 0.5% of the population have conversion disorder.
Culture
Although it is often thought that the frequency of conversion may be higher outside of the West, perhaps in relation to cultural and medical attitudes, evidence of this is limited. A community survey of urban Turkey found a prevalence of 5.6%. Many authors have found occurrence of conversion to be more frequent in rural, lower socio-economic groups, where technological investigation of patients is limited and people may know less about medical and psychological concepts.
Gender
Historically, the concept of hysteria was originally understood to be a condition exclusively affecting women, though the concept was eventually extended to men. In recent surveys of conversion disorder (formerly classified as "hysterical neurosis, conversion type"), females predominate, with between two and six female patients for every male but some research suggests this gender disparity may be confounded by higher rates of violence against women.
Age
Conversion disorder may present at any age but is rare in children younger than ten or in the elderly. Studies suggest a peak onset in the mid-to-late 30s.
History
The first evidence of functional neurological symptom disorder dates back to 1900 BC, when the symptoms were blamed on the uterus moving within the female body. The treatment varied "depending on the position of the uterus, which must be forced to return to its natural position. If the uterus had moved upwards, this could be done by placing malodorous and acrid substances near the womans mouth and nostrils, while scented ones were placed near her vagina; on the contrary, if the uterus had lowered, the document recommends placing the acrid substances near her vagina and the perfumed ones near her mouth and nostrils."In Greek mythology, hysteria, the original name for functional neurological symptom disorder, was thought to be caused by a lack of orgasms, uterine melancholy and not procreating. Plato, Aristotle and Hippocrates believed a lack of sex upsets the uterus. The Greeks believed it could be prevented and cured with wine and orgies. Hippocrates argued that a lack of regular sexual intercourse led to the uterus producing toxic fumes and caused it to move in the body, and that this meant all women should be married and enjoy a satisfactory sexual life.From the 13th century, women with hysteria were exorcised, as it was believed that they were possessed by the devil. It was believed that if doctors could not find the cause of a disease or illness, it must be caused by the devil.At the beginning of the 16th century, women were sexually stimulated by midwives in order to relieve their symptoms. Gerolamo Cardano and Giambattista della Porta believed polluted water and fumes caused the symptoms of hysteria. Towards the end of the century, however, the role of the uterus was no longer thought central to the disorder, with Thomas Willis discovering that the brain and central nervous system were the cause of the symptoms. Thomas Sydenham argued that the symptoms of hysteria may have an organic cause. He also proved the uterus is not the cause of symptom.In 1692, in the US town of Salem, Massachusetts, there was an outbreak of hysteria. This led to the Salem witch trials, where the women accused of being witches had symptoms such as sudden movements, staring eyes and uncontrollable jumping.During the 18th century, there was a move from the idea of hysteria being caused by the uterus to it being caused by the brain. This led to an understanding that it could affect both sexes. Jean-Martin Charcot argued that hysteria was caused by "a hereditary degeneration of the nervous system, namely a neurological disorder".In the 19th century, hysteria moved from being considered a neurological disorder to being considered a psychological disorder, when Pierre Janet argued that "dissociation appears autonomously for neurotic reasons, and in such a way as to adversely disturb the individuals everyday life". However, as early as 1874, doctors including W. B. Carpenter and J. A. Omerod began to speak out against the hysteria phenomenon as there was no evidence to prove its existence.Sigmund Freud referred to the condition as both hysteria and conversion disorder throughout his career. He believed those with the condition could not live in a mature relationship, and that those with the condition were unwell in order to achieve a "secondary gain", in that they are able to manipulate their situation to fit their needs or desires. He also found that both men and women could have the disorder.Freuds model suggested the emotional charge deriving from painful experiences would be consciously repressed as a way of managing the pain, but that the emotional charge would be somehow "converted" into neurological symptoms. Freud later argued that the repressed experiences were of a sexual nature. As Peter Halligan comments, conversion has "the doubtful distinction among psychiatric diagnoses of still invoking Freudian mechanisms".Pierre Janet, the other great theoretician of hysteria, argued that symptoms arose through the power of suggestion, acting on a personality vulnerable to dissociation. In this hypothetical process, the subjects experience of their leg, for example, is split off from the rest of their consciousness, resulting in paralysis or numbness in that leg.
Later authors have attempted to combine elements of these various models, but none of them has a firm empirical basis. In 1908, Steyerthal predicted that: "Within a few years the concept of hysteria will belong to history ... there is no such disease and there never has been. What Charcot called hysteria is a tissue woven of a thousand threads, a cohort of the most varied diseases, with nothing in common but the so-called stigmata, which in fact may accompany any disease." However, the term "hysteria" was still being used well into the 20th century.
Some support for the Freudian model comes from findings of high rates of childhood sexual abuse in conversion patients. Support for the dissociation model comes from studies showing heightened suggestibility in conversion patients. However, critics argue that it can be challenging to find organic pathologies for all symptoms, and so the practice of diagnosing patients with such symptoms as having hysteria led to the disorder being meaningless, vague and a sham diagnosis, as it does not refer to any definable disease. Furthermore, throughout its history, many patients have been misdiagnosed with hysteria or conversion disorder when they had organic disorders such as tumours or epilepsy or vascular diseases. This has led to patient deaths, a lack of appropriate care and suffering for the patients. Eliot Slater, after studying the condition in the 1950s, stated: "The diagnosis of hysteria is all too often a way of avoiding a confrontation with our own ignorance. This is especially dangerous when there is an underlying organic pathology, not yet recognised. In this penumbra we find patients who know themselves to be ill but, coming up against the blank faces of doctors who refuse to believe in the reality of their illness, proceed by way of emotional lability, overstatement and demands for attention ... Here is an area where catastrophic errors can be made. In fact it is often possible to recognise the presence though not the nature of the unrecognisable, to know that a man must be ill or in pain when all the tests are negative. But it is only possible to those who come to their task in a spirit of humility. In the main the diagnosis of hysteria applies to a disorder of the doctor–patient relationship. It is evidence of non-communication, of a mutual misunderstanding ... We are, often, unwilling to tell the full truth or to admit to ignorance ... Evasions, even untruths, on the doctors side are among the most powerful and frequently used methods he has for bringing about an efflorescence of hysteria".Much recent work has been done to identify the underlying causes of conversion and related disorders and to better understand why conversion disorder and hysteria appear more commonly in women. Current theoreticians tend to believe there is no single cause for these disorders. Instead, the emphasis tends to be on the patients understanding and a variety of psychotherapeutic techniques. In some cases, the onset of conversion disorder correlates to a traumatic or stressful event. There are also certain populations that are considered at risk for conversion disorder, including people with a medical illness or condition, people with personality disorders or dissociative identity disorder. However, no biomarkers have yet been found to support the idea that conversion disorder is caused by a psychiatric condition.
There has been much recent interest in using functional neuroimaging to study conversion. As researchers identify the mechanisms which underlie conversion symptoms, it is hoped they will enable the development of a neuropsychological model. A number of such studies have been performed, including some which suggest the blood-flow in patients brains may be abnormal while they are unwell. However, the studies have all been too small to be confident of the generalisability of their findings, so no neuropsychological model has been clearly established.
An evolutionary psychology explanation for conversion disorder is that the symptoms may have been evolutionarily advantageous during warfare. A non-combatant with these symptoms signals non-verbally, possibly to someone speaking a different language, that she or he is not dangerous as a combatant and also may be carrying some form of dangerous infectious disease. This can explain that conversion disorder may develop following a threatening situation, that there may be a group effect with many people simultaneously developing similar symptoms (as in mass psychogenic illness), and the gender difference in prevalence.The Lacanian model accepts conversion disorder as a common phenomenon inherent in specific psychical structures. The higher prevalence of it among women is based on somewhat different intrapsychic relations to the body from those of typical males, which allows the formation of conversion symptoms.
See also
Body-centred countertransference
Hysterical contagion
Mass hysteria
Posttraumatic stress disorder (PTSD) and Complex posttraumatic stress disorder (C-PTSD)
Somatization disorder
Functional neurological symptom disorder
References
== External links == |
Kabuki syndrome | Kabuki syndrome (also previously known as Kabuki-makeup syndrome (KMS) or Niikawa–Kuroki syndrome) is a congenital disorder of genetic origin. It affects multiple parts of the body, with varying symptoms and severity, although the most common is the characteristic facial appearance.It is quite rare, affecting roughly one in 32,000 births. It was first identified and described in 1981 by two Japanese groups, led by scientists Norio Niikawa and Yoshikazu Kuroki. It is named Kabuki syndrome because of the facial resemblance of affected individuals to stage makeup used in kabuki, a Japanese traditional theatrical form.
Signs and symptoms
Specific symptoms for Kabuki syndrome vary, with large differences between affected individuals. Most people with Kabuki syndrome have distinctive facial features that include arched eyebrows, long eyelashes, elongated eyelids with lower lids that turn out, prominent ears, a flat tip of the nose and a downward slant to the mouth.Overlapping phenotypic features for patients between KDM6A and KDM6B variations include prominent ears, abnormal dentition, congenital heart disease, feeding difficulties, cryptorchidism, joint hypermobility, developmental delay, hypotonia, and behavioral difficulties.
Other common symptoms are skeletal abnormalities, short stature, heart defects, feeding difficulties and a failure to thrive, vision and hearing difficulties, weak muscle tone (hypotonia), small head size (microcephaly), and frequent infections.Mild to moderate intellectual disability and mild to severe developmental delay are often associated with Kabuki syndrome. Infants and young children often experience difficulties relating to hypotonia, feeding issues/failure to thrive, infections, surgical repair of heart and palate defects and developmental delays.Young children with Kabuki syndrome benefit from early intervention services. School age children tend to have fewer medical issues requiring hospitalization, though frequent infections, hearing loss and feeding issues occur. In addition, intellectual impairment, difficulty with visuospatial tasks and maintaining attention usually require an IEP (individualized education plan) if the child attends public school. Older children and adults report difficulties with anxiety. Endocrine abnormalities and immune system abnormalities such as ITP (idiopathic thrombocytopenia) and CVID (common variable immune deficiency) are medical issues that tend to present in older children, adolescents and adults.
Causes
Type 1 Kabuki syndrome is caused by germline heterozygous loss of function variants in KMT2D (formerly known as the MLL2), located on human chromosome 12. It is estimated that between 55 and 80% of cases of Kabuki syndrome are of Type 1. Type 1 Kabuki syndrome demonstrates an autosomal dominant pattern of inheritance.
Type 2 Kabuki syndrome is caused by germline hemizygous (in males) or heterozygous (in females) chromosome deletions or loss of function point variants involving KDM6A, located on the X chromosome. Approximately 5% of cases of Kabuki syndrome are of Type 2. Type 2 Kabuki syndrome demonstrates an X-linked dominant pattern of inheritance.Most cases of Kabuki syndrome occur de novo, that is, the parents are unaffected and the gene was mutated early in embryological development. However, several cases of inherited mutations causing Type 1 or Type 2 Kabuki syndrome are now known.About 30% of cases have no identifiable causative mutation. These may represent individuals with types of mutations that are challenging to detect via current routine investigations or patients who have disorders that share some features with Kabuki syndrome.
Pathophysiology
The KMT2D and KDM6A genes belong to a family of genes called chromatin-modifying enzymes. Specifically, these genes code for a histone methyltransferase (KMT2D) and a histone demethylase (KDM6A), and play a part in the regulation of gene expression. Under normal circumstances, these enzymes transfer methyl groups on and off histones to regulate genes via epigenetic pathways. When the genes that encode these enzymes are mutated, epigenetic activation of certain developmental genes is impaired and developmental abnormalities occur, leading to the characteristics of Kabuki syndrome patients. The specific developmental genes that are affected by the impaired epigenetic mechanisms in Kabuki syndrome are not yet fully known.There are hundreds of different mutations that have been identified in Kabuki syndrome patients. Most of these mutations are in the KMT2D gene and involve a change in amino acid sequence that creates a shortened and nonfunctional chromatin-modifying enzyme.
Diagnosis
A consensus on clinical diagnostic criteria for Kabuki syndrome (KS) was defined in December 2018 by an international group of experts. The authors propose that a definitive diagnosis can be made in an individual of any age with a history of infantile hypotonia, developmental delay and/or intellectual disability, and one or both of the following major criteria: (1) a pathogenic or likely pathogenic variant in KMT2D or KDM6A; and (2) typical dysmorphic features (defined below) at some point of life. Typical dysmorphic features include long palpebral fissures with eversion of the lateral third of the lower eyelid and two or more of the following: (1) arched and broad eyebrows with the lateral third displaying notching or sparseness; (2) short columella with depressed nasal tip; (3) large, prominent or cupped ears; and (4) persistent fingertip pads. Further criteria for a probable and possible diagnosis, including a table of suggestive clinical features, were included in the publication.The original description of Kabuki syndrome by Niikawa et al. defined five cardinal manifestations, although some of these “cardinal manifestations” may or may not be present in a patient with Kabuki syndrome.
Typical facial features: Elongated palpebral fissures with eversion of the lateral third of the lower eyelid; arched and broad eyebrows with the lateral third displaying sparseness or notching; short columella with depressed nasal tip; large, prominent, or cupped ears
Skeletal anomalies: Spinal column abnormalities, including sagittal cleft vertebrae, butterfly vertebrae, narrow intervertebral disc space, and/or scoliosis, Brachydactyly V Brachymesophalangy Clinodactyly of fifth digits
Dermatoglyphic abnormalities: persistence of fetal fingertip pads
Mild to moderate intellectual disability
Postnatal growth deficiencyKabuki syndrome is diagnosed clinically (through identifying symptoms, physical exams, and lab results), most commonly by a geneticist. Alternatively, it may be discovered using genetic testing (whole exome or whole genome sequencing).Diagnosis can be difficult given the large spectrum of disease. The fact that some patients do not carry one of the two known mutations or can carry multiple mutations complicates the diagnosis further.
Screening
Due to its rarity, Kabuki syndrome is not screened for in routine prenatal testing including blood tests, chorionic villus sampling (CVS), or amniocentesis. Although not routine for the general population, if Kabuki syndrome is a specific concern (i.e. expectant mother who has been diagnosed with Kabuki syndrome or sibling with KS), it is possible to test for one of the specific mutations. This prenatal testing does require a CVS or amniocentesis. However Kabuki syndrome is usually not inherited and therefore most cases do not have a positive family history. Kabuki syndrome can have positive screening tests, such as cystic hygroma seen on nuchal translucency ultrasound screening, although these findings are non-specific and have a wide differential diagnosis.
Management
Newly diagnosed patients with Kabuki syndrome will often undergo tests that are aimed at detecting common abnormalities associated with the syndrome. They include an echocardiogram (ultrasound of the heart) for detection of structural heart defects, kidney ultrasound for detection of structural renal abnormalities, immunoglobulin levels, pneumococcal titers and a hearing screening test. Further evaluation and testing by specialists may be indicated in addition to cardiology, nephrology, allergy/immunology, audiology-mentioned above. This may include orthopedics (such as hip dysplasia), pulmonary (sleep study to rule out obstructive sleep apnea due to hypotonia), ophthalmology evaluation (vision screen), ENT evaluation (hearing evaluation), Neurology evaluation (i.e. if seizures present), Hematology evaluation (if bleeding disorder), GI evaluation (if gi abnormalities), or others as needed.
There is no specific treatment for Kabuki syndrome. Treatment plans are customized to address the symptoms the individual is experiencing. For example, someone experiencing seizures will be treated with the standard anti-epilepsy therapies. Additionally, patients with Kabuki syndrome are routinely evaluated and monitored to address problems that may develop, such as vision or hearing problems, or cognitive difficulties. If congenital heart disease is present, prophylactic antibiotics may be recommended before any procedures such as dental work that might cause infection.
Prognosis
Life expectancy is not shortened in most cases of Kabuki syndrome. Some patients have coexisting conditions which may shorten life expectancy, such as hypoplastic left heart syndrome or kidney dysfunction. It is important that patients with cardiac, renal, or immunologic issues are identified and well-managed.
Epidemiology
Kabuki syndrome occurs about once in every 32,000 births. The disease appears to affect all population groups equally, with no differences based on sex, race, or environment.
Research
Research on Kabuki syndrome is extremely limited due to its low incidence. Despite this, several groups around the world are studying Kabuki syndrome. In the United States, these include the Epigenetics and Chromatin Clinic at Johns Hopkins University (led by Dr. Hans Bjornsson), The Roya Kabuki Program at Boston Childrens Hospital, Dr. Mark Hannibal at the University of Michigan, groups at University of Colorado, University of Utah, University of South Florida and others. In the UK, Prof Siddharth Bankas group at the University of Manchester and Manchester University Hospitals has a research program for Kabuki syndrome. Several European groups based in Italy, France, Germany and the Netherlands are also actively working on improving understanding of the condition and to identifying potential treatments.
History
In 1969, Norio Niikawa MD, a geneticist in Japan was treating a child patient presenting with unique facial characteristics and various health problems. Never having seen this constellation of symptoms before, Dr Niikawa wondered if he was faced with an undiagnosed condition, a disorder with a genetic basis. Over the next several years, this physician treated several other patients with the same symptoms in his outpatient genetics clinic, furthering support for a disorder never before diagnosed.In 1979, Dr Niikawa presented his findings and hypothesis at the first Japan Dysmorphology Conference. A fellow physician at this conference, Yoshikazu Kuroki, recognised the symptoms, and realised that he had also seen several paediatric patients with this presentation; he presented two of his own cases at the second annual conference the following year. In 1981, the two doctors separately submitted articles on this new diagnosis to the Journal of Pediatrics.Dr Niikawa coined the term ‘Kabuki syndrome’ (also known as Kabuki make-up syndrome or Niikawa–Kuroki syndrome) as a reference to traditional Japanese theatre which he respected greatly. Many of the children presenting with this diagnosis had unusual, elongated lower eyelids, and this feature was reminiscent of the theatrical make-up worn by actors in Kabuki theatre.As reported by Dr. Niikawa "The name, “Kabuki make-up”, of the syndrome was given by myself, because the facial appearance of patients, especially eversion of their lower eyelids, is reminiscent of the makeup of actors in Kabuki, the traditional form of Japanese theater. Kabuki was founded early in the 17th century in Japan and over the next 300 years developed into a sophisticated form of theater. Kabuki actors usually apply traditional makeup to strengthen their eyes, especially in a hero play, and they are very proud of their performing art."The individual kanji, from left to right, mean sing (歌), dance (舞), and skill (伎). Kabuki is therefore sometimes translated as "the art of singing and dancing".
References
== External links == |
Bethlem myopathy | Bethlem myopathy is an autosomal dominant myopathy, classified as a congenital form of muscular dystrophy, that is caused by a mutation in one of the three genes coding for type VI collagen. These include COL6A1, COL6A2, and COL6A3. Gowers sign, tiptoe-walking and contractures of the joints (especially the fingers) are typical signs and symptoms of the disease. Bethlem myopathy could be diagnosed based on clinical examinations and laboratory tests may be recommended. Currently there is no cure for the disease and symptomatic treatment is used to relieve symptoms and improve quality of life. Bethlem myopathy affects about 1 in 200,000 people.
Signs and symptoms
The onset of this disease can begin even before birth but is more commonly in childhood or later into adult life. The progression is slow, with symptoms of weakness and walking difficulties sometimes not presenting until middle age. Early symptoms include Gowers sign ("climbing" up the thighs with the hands when rising from the floor) and tiptoe-walking caused by the beginning of contractures.Contractures of the fingers are a typical symptom of Bethlem myopathy but not of the related Ullrichs myopathy (which does include contractures of arms and legs, as does Bethlem myopathy). Serum creatine kinase is elevated in Bethlem myopathy, as there is ongoing muscle cell death. Patients with Bethlem myopathy may expect a normal life span and continued mobility into adulthood.
Diagnosis
The disease could be diagnosed based on a clinical examination, which identifies signs and symptoms generally associated with the people who have the condition. Additional laboratory tests may be recommended. Creatine kinase (CK) blood test results will generally be normal or only slightly elevated. Skin biopsy, MRI of the muscles, electromyography (EMG) are the main testing methods of the disease. The diagnosis can be confirmed with genetic testing of the COL6A1, COL6A2, and COL6A3 genes.Phenotypes of overlap between Ullrich congenital muscular dystrophy (UCMD) and Bethlem can be assumed. In the differential diagnosis of UCDM, even in patients without finger contractures, Bethlem myopathy could be considered.
Treatment
Currently there is no cure for the disease. Symptomatic treatment, which aims to relieve symptoms and improve quality of life is the main treatment method of Bethlem myopathy. It is believed that physical therapy, stretching exercises, orthoses such as braces and splints, and mobility aids like a walker or wheelchair are beneficial to patients condition.Surgical options could be considered in rare instances, in order to help with joint contractures or scoliosis. Contractures of the legs can be alleviated with heel-cord surgery followed by bracing and regular physical therapy. Repeated surgeries to lengthen the heel cords may be needed as the child grows to adulthood.
Epidemiology
According to a Japanese study from 2007 Bethlem myopathy affects about 1 in 200,000 people. A 2009 study concerning the prevalence of genetic muscle disease in Northern England estimated the prevalence of Bethlem myopathy to be at 0.77:100,000. Together with the UCMD it is believed to be underdiagnosed. Both conditions have been described in individuals from a variety of ethnic backgrounds.
References
== External links == |
Minimally conscious state | A minimally conscious state (MCS) is a disorder of consciousness distinct from persistent vegetative state and locked-in syndrome. Unlike persistent vegetative state, patients with MCS have partial preservation of conscious awareness. MCS is a relatively new category of disorders of consciousness. The natural history and longer term outcome of MCS have not yet been thoroughly studied. The prevalence of MCS was estimated to be 112,000 to 280,000 adult and pediatric cases.
Pathophysiology
Neuroimaging
Because minimally conscious state is a relatively new criterion for diagnosis, there are very few functional imaging studies of patients with this condition. Preliminary data has shown that overall cerebral metabolism is less than in those with conscious awareness (20–40% of normal) and is slightly higher but comparable to those in vegetative states. Activation in the medial parietal cortex and adjacent posterior cingulate cortex are brain regions that seem to differ between patients in MCS and those from vegetative states. These areas are most active during periods of conscious waking and are least active when in altered states of consciousness, such as general anesthesia, propofol, hypnotic state, dementia, and Wernicke–Korsakoff syndrome. Auditory stimulation induced more widespread activation in the primary and pre-frontal associative areas of MCS patients than vegetative state patients. There were also more cortiocortical functional connectivity between the auditory cortex and a large network of temporal and prefrontal cortices in MCS than vegetative states. These findings encourage treatments based on neuromodulatory and cognitive revalidation therapeutic strategies for patients with MCS.
One study used diffusion tensor imaging (DTI) in two case studies. They found that there were widespread cerebral atrophy in both patients. The lateral ventricles were increased in size, and the corpus callosum and the periventricular white matter were diminished. The DTI maps showed that there was significant reduction of volume in the medial corpus callosum and other parts of the brain compared to normal subjects. They also found markedly lower diffusion values in white matter and increased cerebral spinal fluid compartments. Cortical injuries at this level provides a particular favorable environment for sprouting of new axons to occur in the intact areas of the cortex, which may explain some of the greater recovery rates in minimally conscious state patients. The axonal regrowth has been correlated with functional motor recovery. The regrowth and rerouting of the axons may explain some of the changes to brain structure. These findings support the efforts to prospectively and longitudinally characterize neuroplasticity in both brain structure and function following severe injuries. Utilizing DTI and other neuroimaging techniques may further shed light on the debates on long-distance cortical rewiring and may lead to better rehabilitation strategies.Some areas of the brain that are correlated with the subjective experience of pain were activated in MCS patients when noxious stimulation was present. Positron emission tomography (PET) scans found increased blood flow to the secondary sensory cortex, posterior parietal cortex, premotor cortex, and the superior temporal cortex. The pattern of activation, however, was with less spatial extent. Some parts of the brain were less activated than normal patients during noxious stimulus processing. These were the posterior cingulate, medial prefrontal cortex, and the occipital cortex. Even though functional brain imaging can objectively measure changes in brain function during noxious stimulation, the role of different areas of the brain in pain processing is only partially understood. Furthermore, there is still the problem of the subjective experience. MCS patients by definition cannot consistently and reliably communicate their experiences. Even if they were able to answer the question "are you in pain?", there would not be a reliable response. Further clinical trials are needed to access the appropriateness of the use of analgesia in patients with MCS.
Residual language function
A functional magnetic resonance imaging (fMRI) study found that minimally conscious state patients showed activation in auditory networks when they heard narratives that had personally meaningful content that were read forwards by a familiar voice. These activations were not seen when the narratives were read backwards.Another study compared patients in vegetative state and minimally conscious state in their ability to recognize language. They found that some patients in minimally conscious state demonstrated some evidence of preserved speech processing. There was more activation in response to sentences compared to white noise.
Diagnostic
Medical definition
Minimally conscious state (MCS) is defined as a condition of severely altered consciousness in which minimal but definite behavioral evidence of self or environmental awareness is demonstrated.
Diagnosis
Although MCS patients are able to demonstrate cognitively mediated behaviors, they occur inconsistently. They are, however, reproducible or can be sustained long enough to be differentiated from reflexive behavior. Because of this inconsistency, extended assessment may be required to determine if a simple response (e.g. a finger movement or a blink) occurred because of a specific environmental event (e.g. a command to move the finger or to blink) or was merely a coincidental behavior. Distinguishing between VS and MCS is often difficult because the diagnosis is dependent on observation of behavior that show self or environmental awareness and because those behavioral responses are markedly reduced. One of the more common diagnostic errors involving disorders of consciousness is mistaking MCS for VS which may lead to serious repercussions related to clinical management.Giacino et al. have suggested demonstration of the following behaviors in order to make the diagnosis of MCS.
Following simple commands.
Gestural or verbal yes/no responses (regardless of accuracy).
Intelligible verbalization.
Purposeful behavior such as those that are contingent due to appropriate environmental stimuli and are not reflexive. Some examples of purposeful behavior include:
appropriate smiling or crying in response to the linguistic or visual content of emotional but not to neutral topics or stimuli.
vocalizations or gestures that occur in direct response to the linguistic content of questions.
reaching for objects that demonstrates a clear relationship between object location and direction of reach.
touching or holding objects in a manner that accommodates the size and shape of the object.
pursuit eye movement or sustained fixation that occurs in direct response to moving or salient stimuli.
Treatment
There is currently no definitive evidence that support altering the course of the recovery of minimally conscious state. There are currently multiple clinical trials underway investigating potential treatments.
In one case study, stimulation of thalamus using deep brain stimulation (DBS) led to some behavioral improvements. The patient was a 38-year-old male who had remained in minimally conscious state following a severe traumatic brain injury. He had been unresponsive to consistent command following or communication ability and had remained non-verbal over two years in inpatient rehabilitation. fMRI scans showed preservation of a large-scale, bi-hemispheric cerebral language network, which indicates that possibility for further recovery may exist. Positron emission tomography showed that the patients global cerebral metabolism levels were markedly reduced. He had DBS electrodes implanted bilaterally within his central thalamus. More specifically, the DBS electrodes targeted the anterior intralaminar nuclei of thalamus and adjacent paralaminar regions of thalamic association nuclei. Both electrodes were positioned within the central lateral nucleus, the paralaminar regions of the median dorsalis, and the posterior-medial aspect of the centromedian/parafasicularis nucleus complex. This allowed maximum coverage of the thalamic bodies. A DBS stimulation was conducted such that the patient was exposed to various patterns of stimulation to help identify optimal behavioral responses. Approximately 140 days after the stimulation began, qualitative changes in behavior emerged. There were longer periods of eye opening and increased responses to command stimuli as well as higher scores on the JFK coma recovery scale (CRS). Functional object use and intelligible verbalization was also observed. The observed improvements in arousal level, motor control, and consistency of behavior could be a result of direct activation of frontal cortical and basal ganglia systems that were innervated by neurons within the thalamic association nuclei. These neurons act as a key communication relay and form a pathway between the brainstem arousal systems and frontal lobe regions. This pathway is crucial for many executive functions such as working memory, effort regulation, selective attention, and focus.In another case study of a 50-year-old woman who had symptoms consistent with MCS, administration of zolpidem, a sedative hypnotic drug improved the patients condition significantly. Without treatment, the patient showed signs of mutism, athetoid movements of the extremities, and complete dependence for all personal care. 45 minutes after 5 to 10 mg of zolpidem was administered, the patient ceased the athetoid movements, regained speaking ability, and was able to self-feed. The effect lasted 3–4 hours from which she returned to the former state. The effects were repeated on a daily basis. PET scans showed that after zolpidem was administered, there was a marked increase in blood flow to areas of the brain adjacent to or distant from damaged tissues. In this case, these areas were the ipsilateral cerebral hemispheres and the cerebellum. These areas are thought to have been inhibited by the site of injury through a GABA-mediated mechanism and the inhibition was modified by zolpidem which is a GABA agonist. The fact that zolpidem is a sedative drug that induces sleep in normal people but causes arousal in a MCS patient is paradoxical. The mechanisms to why this effect occurs is not entirely clear.There is recent evidence that transcranial direct current stimulation (tDCS), a technique that supplies a small electric current in the brain with non-invasive electrodes, may improve the clinical state of patients with MCS. In one study with 10 patients with disorders of consciousness (7 in VS, 3 in MCS), tDCS was applied for 20 minutes every day for 10 days, and showed clinical improvement in all 3 patients who were in MCS, but not in those with VS. These results remained at 12-month follow-up. Two of the patients in MCS that had their brain insult less that 12 months recovered consciousness in the following months. One of these patients received a second round of tDCS treatment 4 months after his initial treatment, and showed further recovery and emerged into consciousness, with no change of clinical status between the two treatments.
Prognosis
One of the defining characteristics of minimally conscious state is the more continuous improvement and significantly more favorable outcomes post injury when compared with vegetative state. One study looked at 100 patients with severe brain injury. At the beginning of the study, all the patients were unable to follow commands consistently or communicate reliably. These patients were diagnosed with either MCS or vegetative state based on performance on the JFK Coma Recovery Scale and the diagnostic criteria for MCS as recommended by the Aspen Consensus Conference Work-group. Both patient groups were further separated into those that had traumatic brain injury and those that had non-traumatic brain injures (anoxia, tumor, hydrocephalus, infection). The patients were assessed multiple times over a period of 12 months post injury using the Disability Rating Scale (DRS) which ranges from a score of 30=dead to 0=no disabilities. The results show that the DRS scores for the MCS subgroups showed the most improvement and predicted the most favorable outcomes 12 months post injury. Amongst those diagnosed with MCS, DRS scores were significantly lower for those with non-traumatic brain injuries in comparison to the vegetative state patients with traumatic brain injury. DRS scores were also significantly lower for the MCS non-traumatic brain injury group compared to the MCS traumatic brain injury group. Pairwise comparisons showed that DRS scores were significantly higher for those that suffered from non-traumatic brain injuries than those with traumatic brain injuries. For the patients in vegetative states there were no significant differences between patients with non-traumatic brain injury and those with traumatic brain injuries. Out of the 100 patients studied, 3 patients fully recovered (had a DRS score of 0). These 3 patients were diagnosed with MCS and had suffered from traumatic brain injuries.In summary, those with minimally conscious state and non-traumatic brain injuries will not progress as well as those with traumatic brain injuries while those in vegetative states have an all around lower to minimal chance of recovery.
Because of the major differences in prognosis described in this study, this makes it crucial that MCS be diagnosed correctly. Incorrectly diagnosing MCS as vegetative state may lead to serious repercussions related to clinical management.
History
Prior to the mid-1990s, there was a lack of operational definitions available to clinicians and researchers to guide the differential diagnosis among disorders of consciousness. As a result, patients were lumped together into broad categories often based on the severity of the disability (e.g. moderate, severe, extremely severe). These diagnoses were performed without regard to salient differences in behavioral and pathological characteristics. In a three-year period spanning from 1994 to 1996, three position statements regarding the diagnostic criteria of disorder of consciousness were published. The "Medical Aspects of the Persistent Vegetative State" was published by
the American Academy of Neurology (AAN) in 1994. In 1995, "Recommendations for Use of Uniform Nomenclature Pertinent to Patients With Severe Alterations in Consciousness" was published by the American Congress of Rehabilitation Medicine (ACRM). In 1996 the "International Working Party on the Management of the Vegetative State: Summary Report" was published by a group of international delegates from neurology, rehabilitation, neurosurgery, and neuropsychology. However, because the diagnostic criteria were published independently from one another, the final recommendations differed greatly from one another. The Aspen Neurobehavioral Work-group was convened to explore the underlying causes of these disparities. In the end, the Aspen Work-group provided a consensus statement regarding definitions and diagnostic criteria disorder of consciousness which include the vegetative state (VS) and the minimally conscious state (MCS).
Ethical issues
One of the major ethical concerns involving patients with severe brain damage is their inability to communicate. By definition, patients who are unconscious or are minimally conscious are incapable of giving informed consent which is required for participation in clinical research. Typically, written approval is obtained from family members or legal representatives. The inability to receive informed consent has led to much research being refused grants, ethics committee approval, or research publication. This puts patients in these conditions at risk of being denied therapy that may be life-saving.
The right to die
The right to die in patients with severe cognitive impairment has developed over time because of their grave neurological state and the perceived futility of continued treatment. Such cases have been debated vigorously in the past, as in the case with Terri Schiavo who was diagnosed with persistent vegetative state. In the case of minimally conscious state patients, they are neither permanently unconscious nor are they necessarily hopelessly damaged. Thus, these patients warrant additional evaluation. On one hand, some argue that entertaining the possibility of intervention in some patients may erode the "right to die" moral obligation. Conversely, there is also fear that people may associate attitudes with higher-functioning people in minimally conscious state with people in persistent vegetative state, thus minimizing the value of their lives.
Regulating therapeutic nihilism
Currently, risk aversion dominates the ethical landscape when research involves those with impaired decision-making abilities. Fears of therapeutic adventurism has led to a disproportionate view about the under-appreciation of potential benefits and an overstatement of risks. Thus, recognizing this distortion is important in order to calculate the right balance between protecting vulnerable populations that cannot provide autonomous consent and potentially restorative clinical trials.
Notable examples
Jackie Wilson (June 9, 1934 – January 21, 1984) American soul and rock and roll singer who fell into a coma after collapsing on stage, woke up but quickly fell back into a coma for the rest of his life.
Jan Grzebski (1942–2008), a Polish railroad worker who fell into a minimally conscious state in 1988 and woke up in 2007.
Terry Wallis (1964-2022). This American man was in a coma for nearly a year after a truck accident, then a minimally conscious state for 19 years.
Martin Pistorius (born 1975). Because of a mystery illness, the South African spent three years in a vegetative state, four years in a minimally conscious state, and five years unable to move anything other than his eyes (locked-in syndrome). In 1999, he fully awakened, and has since recovered to the point that he was able to become a web designer, developer, and author. In 2011, he wrote a book called Ghost Boy, in which he describes his many years of being comatose.
References
== External links == |
Retiform parapsoriasis | Retiform parapsoriasis is a cutaneous condition, considered to be a type of large-plaque parapsoriasis. It is characterized by widespread, ill-defined plaques on the skin, that have a net-like or zebra-striped pattern. Skin atrophy, a wasting away of the cutaneous tissue, usually occurs within the area of these plaques.
See also
Parapsoriasis
Poikiloderma vasculare atrophicans
List of cutaneous conditions
References
== External links == |
Perforating granuloma annulare | Perforating granuloma annulare is a skin condition of unknown cause, usually appearing on the dorsal hands, presenting as papules with a central keratotic core.: 704 These lesions are often seen on the hands, arms, and ankles. Granuloma Annulare is characterized by rings of closely set, small, smooth, firm papules, usually skin colored, but they also may be slightly erythematous or have a purplish hue. Lesions vary in size from 1cm to 5cm. They are generally asymptomatic and nonpruritic (Fairlie, 2004).
Reports of associations between Granuloma Annulare and diabetes mellitus, thyroid disease, malignancies, drug allergies, hypertension, arthritis, AIDS, and other conditions are being evaluated, but to date, no consistent association has been found (Rigopoulos et al., 2005).
See also
Granuloma annulare
Skin lesion
References
== External links == |
Erdheim–Chester disease | Erdheim–Chester disease (ECD) is an extremely rare disease characterized by the abnormal multiplication of a specific type of white blood cells called histiocytes, or tissue macrophages (technically, this disease is termed a non-Langerhans-cell histiocytosis). It was declared a histiocytic neoplasm by the World Health Organization in 2016. Onset typically is in middle age. The disease involves an infiltration of lipid-laden macrophages, multinucleated giant cells, an inflammatory infiltrate of lymphocytes and histiocytes in the bone marrow, and a generalized sclerosis of the long bones.
Signs and symptoms
Long bone involvement is almost universal in ECD patients and is bilateral and symmetrical in nature. More than 50% of cases have some sort of extraskeletal involvement. This can include kidney, skin, brain and lung involvement, and less frequently retroorbital tissue, pituitary gland and heart involvement is observed.Bone pain is the most frequent of all symptoms associated with ECD and mainly affects the lower limbs, knees and ankles. The pain is often described as mild but permanent, and juxtaarticular in nature. Exophthalmos occurs in some patients and is usually bilateral, symmetric and painless, and in most cases it occurs several years before the final diagnosis. Recurrent pericardial effusion can be a manifestation, as can morphological changes in adrenal size and infiltration.A review of 59 case studies by Veyssier-Belot et al. in 1996 reported the following symptoms in order of frequency of occurrence:
Bone pain
Retroperitoneal fibrosis
Diabetes insipidus
Exophthalmos
Xanthomas
Neurological signs (including ataxia)
Dyspnea caused by interlobular septal and pleural thickening.
Kidney failure
Hypopituitarism
Liver failure
Diagnosis
Radiologic osteosclerosis and histology are the main diagnostic features. Diagnosis can often be difficult because of the rareness of ECD as well as the need to differentiate it from LCH. A diagnosis from neurological imaging may not be definitive. The presence of symmetrical cerebellar and pontine signal changes on T2-weighted images seem to be typical of ECD, however, multiple sclerosis and metabolic diseases must also be considered in the differential diagnosis. ECD is not a common cause of exophthalmos but can be diagnosed by biopsy. However, like all biopsies, this may be inconclusive. Video-assisted thoracoscopic surgery may be used for diagnostic confirmation and also for therapeutic relief of recurrent pericardial fluid drainage.
Histology
Histologically, ECD differs from Langerhans cell histiocytosis (LCH) in a number of ways. Unlike LCH, ECD does not stain positive for S-100 proteins or Group 1 CD1a glycoproteins, and electron microscopy of cell cytoplasm does not disclose Birbeck granules. Tissue samples show xanthomatous or xanthogranulomatous infiltration by lipid-laden or foamy histiocytes, and are usually surrounded by fibrosis. Bone biopsy is said to offer the greatest likelihood of reaching a diagnosis. In some, there is histiocyte proliferation, and on staining, the section is CD68+ and CD1a-.
Treatment
Current treatment options include:
Surgical debulking
High-dose corticosteroid therapy
Ciclosporin
Interferon-α
Chemotherapy
Vemurafenib. It would appear that approximately half these patients harbor point mutations of the BRAF gene at codon 600 substituting the amino acid glutamine for valine. Vemurafenib, an oral FDA approved targeted agent to the BRAF protein for melanoma, shows dramatic activity in patients Erdheim–Chester disease whose tumor contains the same mutation. In 2017 the US FDA approved vemurafenib for this indication.
Radiation therapyAll current treatments have had varying degrees of success.
The vinca alkaloids and anthracyclines have been used most commonly in ECD treatment.
Prognosis
Erdheim–Chester disease was previously associated with high mortality rates. In 2005, the survival rate was below 50% at three years from diagnosis. More recent reports of patients treated with Interferon therapy describe an overall 5-year survival of 68%. Long-term survival is currently even more promising, although this impression is not reflected in the recent literature.
More recent studies have reported that patients receiving targeted therapies showed no disease progression. It was concluded that targeted therapies (BRAF and/or MEK inhibitors) were dramatically efficacious.
Epidemiology
Approximately 500 cases have been reported in the literature to date. ECD affects predominantly adults, with a mean age of 53 years.
History
The first case of ECD was reported by the American pathologist William Chester in 1930, during his visit to the Austrian pathologist Jakob Erdheim in Vienna.
Society and culture
The Erdheim–Chester Disease Global Alliance is a support and advocacy group with the goal of raising awareness of and promoting research into ECD. ECD families and patients are also supported by the Histiocytosis Association, Inc.
Media
In the TV show House, season 2 episode 17, "All In", the final diagnosis of a 6-year-old boy who presents with bloody diarrhea and ataxia is Erdheim–Chester disease.
References
Further reading
External links
01067 at CHORUS |
Dentigerous cyst | Dentigerous cyst, also known as follicular cyst is an epithelial-lined developmental cyst formed by accumulation of fluid between the reduced enamel epithelium and crown of an unerupted tooth. It is formed when there is an alteration in the reduced enamel epithelium and encloses the crown of an unerupted tooth at the cemento-enamel junction. Fluid is accumulated between reduced enamel epithelium and the crown of an unerupted tooth. Dentigerous cyst is the second most common form of benign developmental odontogenic cysts.
Dentigerous cyst is the second most prevalent type of odontogenic cysts after radicular cyst. 70 percent of the cases occurs in the mandible. Dentigerous cyst is usually painless. Patient usually comes with a concern of delayed tooth eruption or facial swelling. Dentigerous cyst can go unnoticed and may be discovered coincidentally on a regular radiographic examination.
Pathogenesis
Odontogenesis happens by means of a complex interaction between oral epithelium and surrounding mesenchymal tissue. Abnormal tissue interaction during this process can result in ectopic tooth development. Ectopic tooth eruption may result due to pathological process, such as a tumor or cyst or developmental disturbance. The pathogenesis of dentigerous cyst is still controversial.
The accumulation of fluid either between the reduced enamel epithelium and enamel or in between the layers of enamel organ seems to be the key to the formation of dentigerous cysts.
A potentially erupting tooth on an impacted follicle can obstruct the venous outflow, inducing rapid transudation of serum across the capillary walls.
Main suggested that this may exert pressure, causing the accumulation of fluid. On the contrary, Toiler suggested that the breakdown of proliferating cells of the follicle after impeded eruption is likely to be the origin of the dentigerous cyst. The breakdown products may result in increased osmotic tension, resulting in cyst formation.
The exact histogenesis of dentigerous cysts remains unknown, but most authors favor a developmental origin from the tooth follicle. In 1928, Bloch-Jorgensen suggested that the overlying necrotic deciduous tooth is the origin of all dentigerous cysts. The resultant periapical inflammation might spread to involve the follicle of the unerupted permanent successor, an inflammatory exudate ensued with resultant dentigerous cyst formation. He reported 22 cases of follicular cysts and stated that in each case a deciduous tooth or the remnants thereof was found in direct contact with the cyst cavity and that the related deciduous tooth always was diseased.
Azaz and Shteyer similarly suggested that the persistent and prolonged periapical inflammation caused chronic irritation to the follicle of the successors. This may trigger and hasten the formation of a dentigerous cyst developing around the permanent teeth. They reported five cases of dentigerous cysts which involved the second mandibular premolar in four children aged 8 to 11 years old. These children were referred for extraction of carious, nonvital primary molars with swelling of the surrounding soft tissue. Occlusal radiographs showed buccal expansion of bone at the affected site. The primary teeth were not in direct contact with the underlying dentigerous cyst.
It has been suggested that dentigerous cysts may be either extrafollicular or intrafollicular in origin. There were three possible mechanisms exist. Firstly, surrounding the crowns of affected teeth, the intrafollicular developmental dentigerous cysts may be formed. These cysts may be secondarily inflamed and infected as a result of periapical inflammation spreading from non vital deciduous predecessors. Benn and Altini (1996) claimed that this possibility was unlikely as all the cases reported were not associated with tooth impaction.
Secondly, radicular cysts developed at the apices of non vital primary teeth. These radicular cysts may fuse with the follicles of the unerupted successors, causing the eruption of the successors into the cyst cavity. This may result in the formation of extrafollicular dentigerous cyst. Shear regarded this to be exceptionally rare because radicular cyst is uncommon in the primary dentition.
The third possibility is that periapical inflammation could be of any source but usually from a non vital deciduous tooth spreading to involve the follicles of unerupted permanent successors. The inflammatory exudate causes separation of reduced enamel epithelium from the enamel with resultant cyst formation.
Clinical Features
The dentigerous cyst commonly involves a single tooth and rarely affects multiple teeth. The most frequently involved tooth is the mandibular third molar followed by the maxillary canine, but they may be associated with supernumerary or ectopic tooth. Any permanent tooth can be involved. Regezi and Sciubba stated that the impacted teeth were most commonly seen in the third molar and maxillary canine teeth, and hence dentigerous cysts occur most frequently in these teeth. The involved teeth may be displaced into ectopic positions. In the maxilla, these teeth are often displaced into the maxillary sinus. Classic symptoms of sinus disease such as headache, facial pain, purulent nasal discharge or nasolacrimal obstruction may occur when maxillary sinus is involved.
According to a study, 45.7 percent of dentigerous cysts involved mandibular third molar. On the other hand, only 2.7 percent of dentigerous cysts involved the maxillary premolar. Mourshed stated that the incidence of dentigerous cyst has been reported as 1.44 in every 100 unerupted teeth, so dentigerous cysts involving the premolars are rare.
Dentigerous cysts most commonly occur in the 2nd and 3rd decades of life. Males have been reported to be more prevalent than females with a ratio of 1.8:1. These cysts can also be found in young children and adolescents. The age of presentation of these cysts range from 3 years to 57 years with a mean of 22.5 years.
These cysts are commonly single lesions. Bilateral and multiple dentigerous cysts are very rare although they have been reported. Bilateral or multiple dentigerous cysts have been reported in Maroteaux-Lamy syndrome, cleidocranial dysplasia and Gardners syndrome In the absence of these syndromes, the occurrence of multiple dentigerous cysts is rare. Sometimes multiple dentigerous cysts are suggested to be induced by prescribed drugs. The combined effect of cyclosporine and a calcium channel blocker is reported to cause bilateral dentigerous cyst
Dentigerous cyst is potentially capable of becoming an aggressive lesion. The possible sequelae of continuous enlargement of dentigerous cyst are expansion of the alveolar bone, displacement of teeth, severe root resorption of teeth, expansion of buccal and lingual cortex and pain.
Potential complications are development of cellulitis, deep neck infection, ameloblastoma, epidermoid carcinoma or mucoepidermoid carcinoma.
Investigations
Early detection and removal of the cysts is essential to reduce morbidity since dentigerous cyst can attain considerable size without any symptoms. Patient who presents with unerupted teeth should be thoroughly examined with radiographic examinations to check our for dentigerous cysts. Panoramic radiographs may be indicated for this purpose. CT imaging becomes necessary for extensive lesion.
Pathologic analysis of the lesion is important for the definitive diagnosis even though radiographs provide valuable information.
Histopathologic Features
The histopathologic features of dentigerous cyst are dependent on the nature of the cyst, whether it is inflamed or not inflamed.
Non-inflamed dentigerous cystThe specimen will present with loosely arranged fibrous connective tissue wall that contains considerable glycosaminoglycan ground substance. Small islands or cords of inactive-appearing odontogenic epithelial rests are usually scattered within the connective tissue and most commonly located near the epithelial lining. These rests may appear numerous in the fibrous connective tissue wall occasionally, which may be misinterpreted as ameloblastoma by some pathologists who are unfamiliar with oral lesions. The epithelial lining is composed of two to four layers of flattened non-keratinizing cells, with a flat epithelium and connective tissue interface.
Inflamed dentigerous cystOccurrence of inflamed dentigerous cyst is fairly common. Histologic examination reveals a more collagenized fibrous connective tissue wall, with a variable infiltration of chronic inflammatory cells. Cholesterol slits and their associated multinucleated giant cells may be present and are generally associated with the connective tissue wall. The cyst is lined mostly or entirely by non-keratinizing squamous epithelium which display varying amounts of hyperplasia with the development of anastomosing rete ridges and more definite squamous features. Dentigerous cysts presenting with these features may histologically be indistinguishable from radicular cysts. A keratinized surface is occasionally present, which must be differentiated from those observed in the odontogenic keratocyst(OKC). Focal areas of mucus cells or rarely, ciliated columnar cells may be found in the epithelial lining of dentigerous cysts. In addition, small nests of sebaceous cells infrequently may be present within the fibrous connective tissue wall. These mucous, ciliated and sebaceous elements are postulated to represent the multipotentiality of the odontogenic epithelial lining in a dentigerous cyst.
One or several areas of nodular thickening may be seen on the luminal surface in the gross examination of the fibrous wall of a dentigerous cyst. Careful examination of these areas microscopically is mandatory to rule out the presence of early neoplastic change.
As the dental follicle surrounding the crown of an unerupted tooth usually is lined by a thin layer of reduced enamel epithelium, this may render it difficult to distinguish a small dentigerous cyst from a normal or enlarged dental follicle based on microscopic features alone.
Imaging Features
As the epithelial lining is derived from the reduced enamel epithelium, on radiographic examination, a dentigerous cyst appears as a unilocular radiolucent area that is associated with just the crown of an unerupted tooth and is attached to the tooth at the cementoenamel junction. Dentigerous cysts may also involve odontomas, which by their nature also have “tooth crowns”. The radiolucency is generally well-defined and well-corticated. The radiolucency often have a sclerotic border indicating bony reaction, but a secondarily infected cyst may display ill-defined borders. However, a large dentigerous cyst may give the impression of a multilocular process due to the persistence of bone trabeculae within the radiolucency.
The cyst-to-crown relationship presents several radiographic variations which are explained as follows:
Central variantThis is the most common variant which the cyst surrounds the crown of the tooth and the crown projects into the cyst.
Lateral variantThis variant is usually associated with a mesioangular impacted mandibular third molar that is partially erupted. The cyst develops laterally along the root surface and partially surrounds the crown.
Circumferential variantThe cyst surrounds the crown and extends for some distance along the root surface so that a significant portion of the root appears to lie within the cyst, as if the tooth was erupting through the centre of the cyst.
The radiographic distinction between an enlarged dental follicle and a small dentigerous cyst can be difficult and fairly arbitrary. Generally, any pericoronal radiolucency that is greater than 3 to 4mm in diameter is considered suggestive of cyst formation.
Some dentigerous cysts may result in considerable displacement of the involved tooth. Infrequently, a third molar may be displaced to the lower border of the mandible or into the ascending ramus. On the other hand, maxillary anterior teeth may be displaced into the floor of the nasal cavity, while other maxillary teeth may be displaced through the maxillary sinus to the floor of the orbit. Furthermore, larger cysts can lead to resorption of adjacent unerupted teeth. Some dentigerous cysts may also grow to considerable size and produce bony expansion that is usually painless, unless secondarily infected. However, any particularly large dentigerous radiolucency should clinically be suspected of a more aggressive odontogenic lesion such as an odontogenic keratocyst or ameloblastoma. For this reason, biopsy is mandated for all significant pericoronal radiolucencies to confirm the diagnosis.
The role of CT (computerized tomography) imaging in the evaluation of cystic lesions has been well-documented. CT imaging aids to rule out solid and fibro-osseous lesions, displays bony detail, and provides precise information about the size, origin, content, and relationships of the lesions.On CT imaging, a mandibular dentigerous cyst appears as a well-circumscribed unilocular area of osteolysis that incorporates the crown of a tooth. Displacement of adjacent teeth may be seen and they may be partly eroded. Dentigerous cysts in the maxilla often extend into the antrum, displacing and remodeling the bony sinus wall. Large cysts which may project into the nasal cavity or infratemporal fossa and may elevate the floor of the orbit can be noted on CT imaging. In the mandible, buccal or lingual cortical expansion and thinning are noted.On MR imaging, the contents of the cyst display low to intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. The tooth itself is a zone of signal void. The lining of the cyst is thin with regular thickness and may show slight enhancement after contrast injection.
Treatment and Prognosis
The treatment of choice for dentigerous cyst is enucleation along with extraction of the impacted teeth. If eruption of the unerupted tooth is considered feasible, the tooth may be left in place after partial removal of the cyst wall. Orthodontic treatment may subsequently be required to assist eruption. Similarly, if displacement of the associated tooth by the cyst has occurred and extraction may prove to be difficult, orthodontic movement of the tooth to a more advantageous location for extraction may be accomplished. Marsupialization may also be used to treat large dentigerous cysts. This permits the decompression of the cyst, with a resulting decrease in the size of the bone defect. The cyst can then be excised at a later date, with a less extensive surgical procedure.
The prognosis for the dentigerous cyst is excellent, and recurrence is rare. This is related to the exhausted nature of the reduced enamel epithelium, which has differentiated and formed tooth crown enamel before developing into a cyst. Nevertheless, several potential complications must be considered. The possibility that the lining of a dentigerous cyst might undergo neoplastic transformation to an ameloblastoma has been well-documented. Mourshed showed that 33% of ameloblastomas arose from the epithelial lining of a dentigerous cyst. Although undeniably this can occur, the frequency of such neoplastic transformation is low. In addition, a squamous cell carcinoma may rarely arise in the lining of a dentigerous cyst. Transformation from normal epithelial cyst lining to SCC is due to chronic inflammation. It is likely that some intraosseous mucoepidermoid carcinomas develop from mucous cells in the lining of a dentigerous cyst. Malignancy in the cyst wall is usually unexpected at the time of presentation and the diagnosis is usually made following enucleation. Jagged or irregular margins with indentations and indistinct borders are considered to be suggestive of possible malignant change. Due to the potential for occurrence of an odontogenic keratocyst or the development of an ameloblastoma or, more rarely, mucoepidermoid carcinoma, all such lesions, when excised, should be submitted for histopathologic evaluation.
Differential Diagnosis
The differential diagnoses of dentigerous cysts are as follows:
Radicular cystIt is an odontogenic cyst that is a sequela of periapical granuloma in a carious tooth.
Odontogenic keratocyst(OKC)It is often multilocular and most commonly located in the body or the ramus of the mandible.Histologically, the epithelium is uniform in nature, usually four to eight cells in thickness. The basilar layer consists of a palisaded row of cuboidal to columnar cells that may demonstrate hyperchromatism. Characteristically, a corrugated or wavy layer of parakeratin is produced on the epithelial surface and desquamated keratin may be present in the cyst lumen.
Odontogenic keratocysts do not result in the same degree of bony expansion as dentigerous cysts and teeth resorption are less likely to be seen in association with odontogenic keratocysts. In addition, dentigerous cysts are more likely to have smooth periphery and odontogenic keratocysts are more likely to display a scalloped periphery.
Unicystic ameloblastomaIt is the most common radiolucent, benign odontogenic tumor that may be unilocular or multilocular. It may result in expansion and destruction of the maxilla and mandible. It is not possible to differentiate unicystic ameloblastomas from dentigerous cysts with clinical and radiographic examinations.
Histopathologic examination revealed that the basilar cells in unicystic ameloblastoma become columnar and demonstrate prominent nuclear hyperchromatism. The polarization of nuclei may be away from the basement membrane (reverse polarization). Besides, the superficial epithelial layers may become loosely arranged and resemble the stellate reticulum of the enamel organ.
Pindborg tumorIt is a rare odontogenic tumor that is radiolucent with well-defined border and associated calcified radiopaque foci.
Adenomatoid odontogenic tumorAdenomatoid odontogenic tumor also shows similar features as dentigerous cyst; however, the differentiation is by the presence of intra-cystic radio-opaque structures. In younger patients, the periapical radiolucencies associated with deciduous teeth may mimic pericoronal radiolucencies of succedaneous permanent teeth and may result in a false impression of dentigerous cyst. A definitive diagnosis will not be made based on radiographs alone. The diagnosis can only be confirmed by histopathological examination.
OdontomaIt is a lytic lesion that is frequently accompanied by amorphous calcification.
Odontogenic fibromyxomaIt usually has multiple radiolucent areas of varying size and bony septations, but unilocular lesions have also been described.
CementomaIt is a lytic lesion that is most often seen with amorphous calcification.
See also
Teratoma, a type of tumor in which tooth tissue occasionally grows in ectopic places
References
== External links == |
Granular cell tumor | Granular cell tumor is a tumor that can develop on any skin or mucosal surface, but occurs on the tongue 40% of the time.
It is also known as Abrikossoffs tumor, Granular cell myoblastoma, Granular cell nerve sheath tumor, and Granular cell schwannoma.)Granular cell tumors (GCTs) affect females more often than males.
Pathology
Granular cell tumors are derived from neural tissue, as can be demonstrated by immunohistochemistry and ultrastructural evidence using electron microscopy. These lesions characteristically consist of polygonal cells with bland nuclei, abundant cytoplasm and fine eosinophilic cytoplasmic granules. The tumor cells stain positively for S-100 as they are of Schwann cell origin. Both malignant and benign versions of the tumor exist, where malignant tumors are characterized histologically by features such as spindling, high nuclear to cytoplasmic ratios, pleomorphism, and necrosis. Multiple granular cell tumors may seen in the context of LEOPARD syndrome, due to a mutation in the PTPN11 gene.These tumors, on occasion, may appear similar to neoplasms of renal (relating to the kidneys) origin or other soft tissue neoplasms.
Treatment
The primary method for treatment is surgical, not medical. Radiation and chemotherapy are not needed for benign lesions and are not effective for malignant lesions.
Benign granular cell tumors have a recurrence rate of 2% to 8% when resection margins are deemed clear of tumor infiltration. When the resection margins of a benign granular cell tumor are positive for tumor infiltration the recurrence rate is increased to 20%. Malignant lesions are aggressive and difficult to eradicate with surgery and have a recurrence rate of 32%.
Epidemiology
Granular cell tumors can affect all parts of the body; however, the head and neck areas are affected 45% to 65% of the time. Of the head and neck cases 70% of lesions are located intraorally (tongue, oral mucosa, hard palate). The next most common location that lesions are found in the head and neck area is the larynx (10%). Granular cell tumors are also found in the internal organs, particularly in the upper aerodigestive tract. Vaginal granular cell tumors are generally rare.Breast granular cell tumors arise from intralobular breast stroma and occurs within the distribution of the cutaneous branches of the supraclavicular nerve. As they do follow the innervation of the skin, they may demonstrate skin changes like contraction or shrinkage. Unlike traditional breast cancers, glandular cell tumors are mostly found in the upper inner quadrant of the breast. They can erroneously diagnosed as an invasive ductal carcinoma via ultrasound and mammography, therefore, it is necessary to consider a diagnosis of invasive ductal carcinoma.
The usual presentation is of a slow growing behavior, forming a polygonal accumulation of secondary lysosomes in the cytoplasm. Granular cell tumors are typically solitary and rarely larger than three centimeters. However, proliferative growth and development of an ulcer indicates likely malignancy as this type of tumor can be either benign or malignant. Malignancy is rare and constitutes only 2% of all granular cell tumors.
See also
List of cutaneous conditions
Glassy cell carcinoma
References
== External links == |
Butchers wart | Butchers wart is a cutaneous (skin) condition with a prevalence of 8.5% to 23.8% among butchers and other meat-handling professions caused by a small group of viruses that infect the skin.An association with Human Papillomavirus 7 has been suggested.
See also
List of cutaneous conditions
== References == |
Human penis size | Human penises vary in size on a number of measures, including length and circumference when flaccid and erect. Besides the natural variability of human penises in general, there are factors that lead to minor variations in a particular male, such as the level of arousal, time of day, room temperature, anxiety level, sport activity and frequency of sexual activity. Compared to other primates, including large examples such as the gorilla, the human penis is thickest, both in absolute terms and relative to the rest of the body.
Measurements vary, with studies that rely on self-measurement reporting a significantly higher average than those with a health professional measuring. As of 2015, a systematic review of 15,521 men, who were measured by health professionals rather than themselves, concluded that the average length of an erect human penis is 13.12 cm (5.17 inches) long, while the average circumference of an erect human penis is 11.66 cm (4.59 inches). Flaccid penis length can sometimes be a poor predictor of erect length.
Most human penis growth occurs between infancy and the age of five, and between about one year after the onset of puberty and, at latest, approximately 17 years of age.Limited to no statistically significant correlation between penis size and the size of other body parts has been found in research. Some environmental factors in addition to genetics, such as the presence of endocrine disruptors, can affect penis growth. An adult penis with an erect length of less than 7 cm (2.8 in), but otherwise formed normally, is referred to in medicine as a micropenis.
Studies
While results vary slightly across reputable studies, the consensus is that the mean human penis, when erect, is in the range 12.9–15 cm (5.1–5.9 in) in length.
A 2015 systematic review published by Veale et al. of medical research on the topic over the previous 30 years published in BJU International showed similar results, giving mean flaccid, stretched non-erect, and erect lengths of 9.16 cm, 13.24 cm, and 13.12 cm respectively, and mean flaccid and erect circumferences of 9.31 cm and 11.66 cm respectively. Erect lengths in the included studies were measured by pushing the pre-pubic fat pad to the bone, and flaccid or erect girth (circumference) was measured at the base or mid-shaft of the penis.
Length
Flaccid
One study (published in 1996) found the mean flaccid penis length to be 3.5 inches (8.9 cm) (measured by staff). A review of several studies found average flaccid length to be 9–10 cm (3.5–3.9 in). Length of the flaccid penis does not necessarily correspond to length of the erect penis; some smaller flaccid penises grow much longer, while some larger flaccid penises grow comparatively less.The penis and scrotum can contract involuntarily in reaction to cold temperatures, anxious or nervous level and participation in sports. This decrease of flaccid penis size is referred to by the slang term "shrinkage", due to action by the cremaster muscle. The same phenomenon affects cyclists and exercise bike users, with prolonged pressure on the perineum from the bicycle saddle and the straining of the exercise causing the penis and scrotum to contract involuntarily. An incorrect saddle may ultimately cause erectile dysfunction (see crotch pressure for more information). Individuals with hard flaccid syndrome or other pelvic floor disorders may temporarily have an abnormally small penis.
Stretched
Neither age nor size of the flaccid penis accurately predicted erectile length. Stretched length has correlated with erect length in some cases. However, studies have also shown drastic differences between stretched and erect length. One study found that a minimal tension force of approximately 450 g during stretching of the penis was required to reach a full potential erection length. this study also found that tension forces exerted in this study by the urologist were shown to be significantly (P<0.01) lower than 450g. This may account for differences between stretched and erect length.
The 2015 study of 15,521 men found that the average length of a stretched flaccid penis was 13.24 cm (5.21 inches) long, which is near identical to the average length of an erect human penis which is 13.12 cm (5.17 inches) long.
An 2001 study of about 3,300 men published in European Urology concluded that flaccid stretched length was measured on average to about 12.5 cm (4.9 in). In addition, they checked for correlations in a random subset of the sample consisting of 325 men. They found a few statistically significant Spearmans correlations: between flaccid length and height of 0.208, −0.140 with weight, and −0.238 with BMI, flaccid circumference and height 0.156, stretched length and height 0.221, weight −0.136, BMI −0.169. They also reported a few non-significant correlations.
Erect
Scientific studies have been performed on the erect length of the adult penis. Studies that have relied on self-measurement, including those from Internet surveys, consistently reported a higher average length than those that used medical or scientific methods to obtain measurements.The following staff-measured studies are composed of different subgroups of the human population (in other words, specific age range or race; selection of those with sexual medical concerns or self-selection) that could cause a sample bias.
In a study of 80 healthy males published in the September 1996 Journal of Urology an average erect penis length of 12.9 cm (5.1 in) was measured. The purpose of the study was to "provide guidelines of penile length and circumference to assist in counseling patients considering penile augmentation." Erection was pharmacologically induced in 80 physically normal American men (varying ethnicity, average age 54). It was concluded: "Neither patient age nor size of the flaccid penis accurately predicted erectile length."
A study published in the December 2000 International Journal of Impotence Research found that average erect penis length in 50 Jewish Caucasian males was 13.6 cm (5.4 in) (measured by staff). The study intended "to identify clinical and engineering parameters of the flaccid penis for prediction of penile size during erection." Erection was pharmacologically induced in 50 Jewish Caucasian patients who had been evaluated for erectile dysfunction (ED) (average age 47±14y). Patients with penis abnormalities or whose ED could be attributed to more than one psychological origin were omitted from the study.
A review published in the 2007 issue of BJU International showed the average erect penis length to be 14–16 cm (5.5–6.3 in) and girth to be 12–13 cm (4.7–5.1 in). The paper compared results of twelve studies conducted on different populations in several countries. Various methods of measurements were included in the review.
A 2015 study by BJU International concluded the average erect penis length to be 13.12 cm (5.16 inches).
A 2013 study of 253 men from Tanzania found that the average erect penis length of Tanzanian males was 13.12 cm (5.17 inches)
An Indian study (published in 2007) of 301 men ages 18 to 60 published in the International Journal of Impotence Research found flaccid, stretched and erect length to be 8.21 cm (3.23 in), 10.88 cm (4.28 in) and 13.01 cm (5.12 in), respectively.
A Korean study (published in 1971) of 702 men ages 21 to 31 identified the average erect penis length to be 12.70 cm (5.00 in). Another study (from 1998) of 150 Koreans found the average erect penis length to be 13.42 cm (5.28 in). The most recent study (published in 2016) of 248 Korean men identified the average erect penis length to be 13.53 cm (5.33 in).
A 2020 review in the Journal of Sex & Marital Therapy found that the majority of men believed that the average erect penis length is more than 15.24 cm (6 inches). This inaccurate belief has likely been fed by inaccurate and exaggerated data presented in studies where the size of the participants erect penis is self-reported. Participants may report overestimates of the size of their penis in the belief that a larger penis is more socially desirable. The same review analyzed the results from ten prior studies where measurements of erect penis size were made by researchers. They reported an erect penis to be between 12.95 and 13.92 cm (5.1 and 5.5 inches, respectively) in length, a result significantly below the average obtained in self-reported studies. The authors commented that results of such measurement studies may still be inflated due to volunteer bias – the possibility that men with larger penises may be more likely to choose to participate in such studies.
Erect circumference
Similar results exist regarding studies of the circumference of the adult fully erect penis, with the measurement usually taken mid-shaft. As with length, studies that relied on self-measurement consistently reported a significantly higher average than those with staff measuring. In a study of penis size where measurements were taken in a laboratory setting, the average penis circumference when erect was 11.66 cm (4.59 inches).
Size at birth
The average stretched penile length at birth is about 4 cm (1.6 in), and 90% of newborn boys will be between 2.4 and 5.5 cm (0.94 and 2.17 in). Limited growth of the penis occurs between birth and 5 years of age, but very little occurs between 5 years and the onset of puberty. The average size at the beginning of puberty is 6 cm (2.4 in) with adult size reached about 5 years later. W.A. Schonfeld published a penis growth curve in 1943.
Size with ageing
Authors of a paper reviewing research on area of penis sizes conclude that "flaccid penile length is just under 4 cm (1.6 in) at birth and changes very little until puberty, when there is marked growth."Age is not believed to negatively correlate with penis size. "Individual research studies have... suggested that penis size is smaller in studies focusing on older men, but Wylie and Eardley found no overall differences when they collated the results of various studies [over a 60 year period]."
Size and height
A 2015 review of the literature found two studies finding height and stretched or flaccid length to be moderately correlated, seven studies finding weak correlation for flaccid, stretched, or erect length, and two studies that found no correlation between flaccid length and height.
Size and hands
One study investigated the relationship with digit ratio and found that men with longer ring fingers than index fingers had slightly longer penises. However, the common misconception that hand size predicts penis size has been widely discredited.
Size and other body parts
One study, Siminoski and Bain (1988), found a weak correlation between the size of the stretched penis and foot size and height; however, it was too weak to be used as a practical estimator. Another investigation, Shah and Christopher (2002), which cited Siminoski and Bain (1988), failed to find any evidence for a link between shoe size and stretched penis size, stating "the supposed association of penile length and shoe size has no scientific basis".A study by Ikegaya et al. (2021) concluded that nose size was highly related to stretched penile length in Japanese male cadavers.There may be a link between the malformation of the genitalia and the human limbs. The development of the penis in an embryo is controlled by some of the same Hox genes (in particular HOXA13 and HOXD13) as those that control the development of the limbs. Mutations of some Hox genes that control the growth of limbs cause malformed genitalia (hand-foot-genital syndrome).
Size and race
Alleged differences in races have led to the creation of sexual myths.
A 2005 study reported that "there is no scientific background to support the alleged oversized penis in black people".A study of 253 men from Tanzania found that the average stretched flaccid penis length of Tanzanian males is 11.5 cm (4.53 inches) long, smaller than the worldwide average, stretched flaccid penis length of 13.24 cm (5.21 inches), and average erect penis length of 13.12 cm (5.17 inches).A 2016 study of 248 Korean men identified the average erect penis length to be 13.53 cm (5.33 in). A study of 115 men from Nigeria found that the average flaccid stretched penis length of Nigerian males is 13.37 cm (5.26 inches) long, which is near identical to the worldwide average, stretched flaccid penis length of 13.24 cm (5.21 inches) and average erect penis length of 13.12 cm (5.17 inches).
A 2014 American study by Herbenick et al. of 1,661 sexually active men involving Asian American, Black American, White American, Pacific Islander/Hawaiian, and Native American men, found average
racial differences in erect penile length and circumference to be generally less than one centimeter, with averages in length being: 14.14 cm (5.56 inches) for Asian Americans, 14.66 cm (5.77 inches) for Black Americans, 14.88 cm (5.85 inches) for Pacific Islanders/Hawaiians, 12.86 cm for Native Americans (5.06 inches), and 14.18 cm (5.58 inches) for White Americans (And in circumference: Asians 12.10 cm, Blacks 12.29 cm, Pacific Islanders 11.88 cm, Native Americans 11.36 cm, and Whites 12.25 cm).
A 2015 systematic review of 15,521 men found "no indications of differences in racial variability", and stated that it was not possible to draw any conclusions about size and race from the available literature and that further research needed to be conducted.According to Aaron Spitz, a urologist, many websites and studies promoting variation of penis size between races use unscientific methods of collecting information and often ignore contradictory evidence. He concludes that "when you really take a good look at the naked data, there’s not a whole lot there [showing racial variation in penis size]."
Size preferences among sexual partners
In a 1994 cover story by Psychology Today, 1,500 readers (about two-thirds women) were surveyed about male body image. Many of the women were not particularly concerned with penis size, and over 71% thought men overemphasized the importance of penis size and shape. Generally, the women polled cared more about width than men thought, and less about length than men thought, although the strength of caring for either among women showed a similar pattern.
In a small study conducted by University of Texas–Pan American and published in 2001 in BMC Womens Health, 50 undergraduate women were surveyed by two popular male athletes on campus about their perceptions of sexual satisfaction and it was concluded that the width of a penis feels better than the length of a penis, when subjects are asked to choose between the two (size was left unspecified). It was also concluded that this may show that penis size overall affects sexual satisfaction since women chose between the two options they were given.A study published in 2002, conducted at Groningen University Hospital, asked 375 sexually active women (who had recently given birth) the importance of penis size. The results showed that 21% of women felt length was important and 32% felt that girth was important.A study conducted at the Australian National University, published in early 2013, showed that penis size influences a mans sex appeal, and the taller the man, the bigger the effect. The study showed 3D computer generated images at life-size, altering the height and other physical attributes, with women typically registering preferences in under 3 seconds. A preference for taller mens larger penis size was indicated.
A US study published in 2015 of the stated preferences of a panel of 75 women using 3D-printed models as scale references showed a preferred penis length of 16 cm (6.3 inches) and a preferred circumference of 12.2 cm for long-term sexual partners, with slightly larger preferred sizes of a length of 16.3 cm (6.4 inches) and circumference of 12.7 cm for one-time sexual encounters.
According to the study, however, when asked to estimate the length of their partnerss penis, most women would say a size significantly smaller than what their partner was recorded to be. This suggests that perception of size is not entirely accurate. The visual impression of the size is not necessarily in correlation with the feeling in the vulva and vagina. A very long penis can cause dispareunia, if the man doesnt understand how to use it carefully.
Condom use
One Australian study of 184 men looked at penis length and circumference in relationship to condom breakage or slippage. 3,658 condoms were used. The study found that when used correctly, condoms had a breakage rate of 1.34% and a slippage rate of 2.05%, for a total failure rate of 3.39%. Penile dimensions did not influence slippage, although penis circumference and broken condoms were strongly correlated, with larger sizes increasing the rate of breakage.
Biochemistry
Androgens like testosterone are responsible for penis enlargement and elongation during puberty. Penis size is positively correlated with increasing testosterone levels during puberty. But after puberty, administration of testosterone does not affect penis size, and androgen deficiency in adult men only results in a small decrease in size. Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are also involved in penis size, with deficiency (such as that observed in growth hormone deficiency or Laron syndrome) at critical developmental stages having the potential to result in micropenis.
Variance
Grower vs shower
A 2018 study differentiates two types of penises based on the change they experience from flaccid to erect. It distinguishes between growers and showers. Growers or penises of blood grow more than 4 cm with respect to their flaccid state, and showers or penises of meat grow less of 4 cm.
Genetics
There are certain genes, like homeobox (Hox a and d) genes, which may have a role in regulating penis size. In humans, the AR gene, located on the X chromosome at Xq11-12, may affect penis size. The SRY gene located on the Y chromosome may have a role to play. Variance in size can often be attributed to de novo mutations. Deficiency of pituitary growth hormone or gonadotropins or mild degrees of androgen insensitivity can cause small penis size in males and can be addressed with growth hormone or testosterone treatment in early childhood.
Conditions
An adult penis with an erect length of less than 7 cm or 2.76 inches but otherwise formed normally is referred to in a medical context as having the micropenis condition. The condition affects 0.6% of men. Some of the identifiable causes are deficiency of pituitary growth hormone or gonadotropins, mild degrees of androgen insensitivity, a variety of genetic syndromes and variations in certain homeobox genes. Some types of micropenis can be addressed with growth hormone or testosterone treatment in early childhood. Operations are also available to increase penis size in cases of micropenis in adults.
Environmental influence
It has been suggested that differences in penis size between individuals are caused not only by genetics, but also by environmental factors such as culture, diet and chemical or pollution exposure. Endocrine disruption resulting from chemical exposure has been linked to genital deformation in both sexes (among many other problems). Chemicals from both synthetic (e.g., pesticides, anti-bacterial triclosan, plasticizers for plastics) and natural (e.g., chemicals found in tea tree oil and lavender oil) sources have been linked to various degrees of endocrine disruption.
Both PCBs and the plasticizer DEHP have been associated with smaller penis size. DEHP metabolites measured from the urine of pregnant women have been significantly associated with the decreased penis width, shorter anogenital distance and the incomplete descent of testicles of their newborn sons, replicating effects identified in animals. According to a 2008 study published by the US National Library of Medicine, approximately 25% of US women have phthalate levels similar to those observed in animals.A 2007 study by the University of Ankara, Faculty of Medicine found that penile size may decrease as a result of some hormonal therapy combined with external beam radiation therapy. In addition, some estrogen-based fertility drugs like diethylstilbestrol (DES) have been linked to genital abnormalities or a smaller than normal penis (microphallus).A 2016 Korean study found that newborn male circumcision is associated with shorter penile length.
Historical perceptions
Prehistory
Perceptions of penis size are culture-specific. Some prehistoric sculptures and petroglyphs depict male figures with exaggerated erect penises. Ancient Egyptian cultural and artistic conventions generally prevented large penises from being shown in art, as they were considered obscene, but the scruffy, balding male figures in the Turin Erotic Papyrus are shown with exaggeratedly large genitals. The Egyptian god Geb is sometimes shown with a massive erect penis and the god Min is almost always shown with an erection.
Ancient
The ancient Greeks believed that small penises were ideal. Scholars believe that most ancient Greeks probably had roughly the same size penises as most other Europeans, but Greek artistic portrayals of handsome youths show them with inordinately small, uncircumcised penises with disproportionately large foreskins, indicating that these were seen as ideal. Large penises in Greek art are reserved exclusively for comically grotesque figures, such as satyrs, a class of hideous, horse-like woodland spirits, who are shown in Greek art with absurdly massive penises. Actors portraying male characters in ancient Greek comedy wore enormous, fake, red penises, which dangled underneath their costumes; these were intended as ridiculous and were meant to be laughed at.In Aristophaness comedy The Clouds, "Mr. Good Reason" gives the character Pheidippides a description of the ideal youth: "A glistening chest and glowing skin / Broad shoulders, a small tongue /A mighty bottom and a tiny prong." In Greek mythology, Priapus, the god of fertility, had an impossibly large penis that was always permanently erect. Priapus was widely seen as hideous and unattractive. A scholion on Apollonius of Rhodess Argonautica states that, when Priapuss mother Aphrodite, the goddess of love and beauty, gave birth to him, she was so horrified by the size of his penis, his massive potbelly, and his huge tongue that she abandoned him to die in the wilderness. A herdsman found him and raised him as his son, later discovering that Priapus could use his massive penis to aid in the growth of plants.Nonetheless, there are indications that the Greeks had an open mind about large penises. A statue of the god Hermes with an exaggerated penis stood outside the main gate of Athens and in Alexandria in 275 BC, a procession in honor of Dionysus hauled a 180-foot phallus through the city and people venerated it by singing hymns and reciting poems. The Romans, in contrast to the Greeks, seem to have admired large penises and large numbers of large phalli have been recovered from the ruins of Pompeii. Depictions of Priapus were very popular in Roman erotic art and literature. Over eighty obscene poems dedicated to him have survived.Penis size is alluded to in the Bible:
18 And she revealed her whorings, and she revealed her nakedness, and so I turned from her just as I turned from her sister. 19 Yet she increased her whorings, recalling the days of her childhood when she was prostituted in the land of Egypt. 20 And she lusted after her male lovers whose genitalia were the genitalia of male donkeys and their seminal emission was the seminal emission of horses. Ezekiel 23:18-20 Lexham English Bible
Ancient Chinese legend holds that a man named Lao Ai had the largest penis in history and that he had an affair with Queen Dowager Zhao (c. 280–228 BC), the mother of Qin Shi Huang, by pretending to be a eunuch. Ancient Koreans admired large penises and King Jijeung (437–514 AD) of the Silla Dynasty is said to have had a forty-five-centimeter penis that was so large his subordinates had to search for a woman that fit him. Traditional Japanese erotic paintings usually show genitals as exaggeratedly large. The oldest known painting of this type, found in the Hōryū-ji Temple in Ikaruga, dates to the eighth century AD and depicts a fairly large penis.The ancient Indian sexual treatise Kama Sutra, originally written in Sanskrit, probably between the second and fourth centuries AD, divides men into three classes based on penis size: "hare" size (about 5–7 cm, or 2–3 inches, when erect), "bull" size (10–15 cm, or 4–6 inches), and "horse" size (18–20 cm, or 7–8 inches). The treatise also divides womens vaginas into three sizes ("deer", "mare", and "elephant") and advises that a man match the size of the vagina of the woman he is having sex with to the size of his own penis. It also gives medically dubious advice on how to enlarge ones penis using wasp stings.
Postclassical
In medieval Arabic literature, a longer penis was preferred, as described in an Arabian Nights tale called "Ali with the Large Member". As a witty satire of this fantasy, the 9th-century Afro-Arab author Al-Jahiz wrote: "If the length of the penis were a sign of honor, then the mule would belong to the Quraysh" (the tribe to which Muhammad belonged and from which he descended).The medieval Norsemen considered the size of a mans penis as the measure of his manliness, and a thirteenth-century Norse magic talisman from Bergen, a wooden stave inscribed with writing in runic script, promises its wearer: "You will fuck Rannveig the Red. It will be bigger than a mans prick and smaller than a horses prick." A late fourteenth century account of the life of Saint Óláfr from the Flateyjarbók describes a pagan ritual which centered around a preserved horses penis used as a cult artifact which members of the cult would pass around in a circle, making up verses in praise of it, encouraging it and the other members of the group to behave in sexually suggestive ways.During the Renaissance, some men in Europe began to wear codpieces, which accentuated their genitals. There is no direct evidence that it was necessarily worn to enhance the apparent size of the wearers penis, but larger codpieces were seen as more fashionable.
Contemporary perceptions
Male self-perception
Males may quite easily underestimate the size of their own penis relative to those of others. A survey by sexologists showed that many men who believed that their penis was of inadequate size had average-sized penises. Another study found sex education of standard penile measurements to be helpful and relieving for patients concerned about small penis size, most of whom had incorrect beliefs of what is considered medically normal. The study found that almost all of their patients that were concerned about their penis size overestimated the average penis size. The perception of having a large penis is often linked to higher self-esteem. Fears of shrinking of the penis in folklore have led to a type of mass hysteria called penis panic, though the penis legitimately can shrink in size due to scar tissue formation in the penis from a medical condition called Peyronies disease. Marketers of penis enlargement products exploit fears of inadequacy, but there is no consensus in the scientific community of any non-surgical technique that |
Human penis size | permanently increases either the thickness or length of the erect penis that already falls into the normal range.
Shrinking and enlarging
Widespread private concerns related to penis size have led to a number of folklore sayings and popular culture reflections related to penis size. Penis panic is a form of mass hysteria involving the believed removal or shrinking of the penis, known as genital retraction syndrome. The penis can significantly shrink due to scar tissue formation from a condition called Peyronies disease which affects up to 10% of men. Products such as penis pumps, pills, and other dubious means of penis enlargement are some of the most marketed products in email spam. At present there is no consensus in the scientific community of any non-surgical technique that permanently increases either the thickness or length of the erect penis that already falls into the normal range (4.5" to 7").
Among male homosexuals
A study undertaken at Utrecht University found that the majority of gay men in the study regarded a large penis as ideal, and having one was linked to self-esteem. One study analysing the self-reported Kinsey data set found that the average penis of a homosexual man was larger than the average penis of their heterosexual counterparts (6.32 inches [16.05 cm] in length amongst gay men versus 5.99 in [15.21 cm] in heterosexuals, and 4.95 inches [12.57 cm] circumference amongst gay men versus 4.80 in [12.19 cm] in heterosexual men).
Evolution
The human penis is thicker than that of any other primate, both in absolute terms and relative to the rest of the body. Early research, based on inaccurate measurements, concluded that the human penis was also longer. In fact, the penis of the common chimpanzee is no shorter than in humans, averaging 14.4 cm (5.7 inches), and some other primates have comparable penis sizes relative to their body weight.The evolutionary reasons for the increased thickness have not been established. One explanation is that thicker penises are an adaptation to a corresponding increase in vaginal size. The vaginal canal is believed to have expanded in humans to accommodate the larger size of a newborns skull. Women may then have sexually selected men with penises large enough to fit their vagina, to provide sexual stimulation and ensure ejaculation.Other evolutionary hypotheses to explain humans relatively large penis length and girth include a sperm competition hypothesis and a mate competition hypothesis. The sperm competition hypothesis does not have much support as in other mammals where sperm competition is present, larger testes evolve, not larger penises. The mate competition hypothesis involves the prediction that a human with a larger penis would be able to displace the sperm of another. Studies have found that larger penises do not displace other sperm more effectively than smaller penises, but rather longer penises may ejaculate sperm inside the vagina in places that would be harder for a following penis to displace. The depth of pelvic thrusting was correlated to the displacement of competing sperm.
See also
Digit ratio
Human vaginal size
Jonah Falcon
Penis enlargement
Penis envy
Phalloplasty
Sexual selection in humans
The Third Chimpanzee
Why Is Sex Fun?
References
Citations
General and cited sources
"Men worry more about penile size than women, says 60-year-old research review" (Press release). Blackwell. 31 May 2007. Retrieved 11 August 2018.
Lee, P. A; Mazur, T; Danish, R; Amrhein, J; Blizzard, R. M; Money, J; Migeon, C. J (1980). "Micropenis. I. Criteria, etiologies and classification". The Johns Hopkins Medical Journal. 146 (4): 156–63. PMID 7366061. NAID 10010056499.
Lauersen, Niels; Whitney, Steven (1983). Its Your Body: A Womans Guide to Gynecology (3rd ed.). New York: Berkley Publishing. p. 480. ISBN 978-0-425-09917-9.
Rushton, J.Philippe; Bogaert, Anthony F (1987). "Race differences in sexual behavior: Testing an evolutionary hypothesis". Journal of Research in Personality. 21 (4): 529–51. doi:10.1016/0092-6566(87)90038-9.
Sutherland, Ronald S; Kogan, Barry A; Baskin, Laurence S; Mevorach, Robert A; Conte, Felix; Kaplan, Selna L; Grumbach, Melvin M (1996). "The Effect of Prepubertal Androgen Exposure on Adult Penile Length". The Journal of Urology. 156 (2): 783–7, discussion 787. doi:10.1016/S0022-5347(01)65814-2. PMID 8683783.
== External links == |
Occlusal trauma | Occlusal trauma is the damage to teeth when an excessive force is acted upon them and they do not align properly.When the jaws close, for instance during chewing or at rest, the relationship between the opposing teeth is referred to as occlusion. When trauma, disease or dental treatment alters occlusion by changing the biting surface of any of the teeth, the teeth will come together differently, and their occlusion will change. When that change has a negative effect on how the teeth occlude, this may cause tenderness, pain, and damage to or movement of the teeth. This is called traumatic occlusion.Traumatic occlusion may cause a thickening of the cervical margin of the alveolar bone and widening of the periodontal ligament, although the latter can also be caused by other processes.
Signs and symptoms
Clinically, there is a number of physiological results that serve as evidence of occlusal trauma:,
Progressive Tooth mobility
Fremitus
Tooth migration
Pain
Thermal sensitivity
Pain on chewing or percussion
Wear facets
Diagnosis
Microscopically, there will be a number of features that accompany occlusal trauma:
Hemorrhage
Necrosis
Widening of the periodontal ligament, or PDL (also serves as a very common radiographic feature)
Bone resorption
Cementum loss and tearsIt was concluded that widening of the periodontal ligament was a "functional adaptation to changes in functional requirements".
Primary vs. secondary
There are two types of occlusal trauma, primary and secondary.
Primary
Primary occlusal trauma occurs when greater than normal occlusal forces are placed on teeth, as in the case of parafunctional habits, such as bruxism or various chewing or biting habits, including but not limited to those involving fingernails and pencils or pens.
The associated excessive forces can be grouped into three categories. Excesses of:
Duration
Frequency and
MagnitudePrimary occlusal trauma will occur when there is a normal periodontal attachment apparatus and, thus, no periodontal disease.
Secondary
Secondary occlusal trauma occurs when normal or excessive occlusal forces are placed on teeth with compromised periodontal attachment, thus contributing harm to an already damaged system. As stated, secondary occlusal trauma occurs when there is a compromised periodontal attachment and, thus, a pre-existing periodontal condition.
Cause and treatment
Teeth are constantly subject to both horizontal and vertical occlusal forces. With the center of rotation of the tooth acting as a fulcrum, the surface of bone adjacent to the pressured side of the tooth will undergo resorption and disappear, while the surface of bone adjacent to the tensioned side of the tooth will undergo apposition and increase in volume.In both primary and secondary occlusal trauma, tooth mobility might develop over time, with it occurring earlier and being more prevalent in secondary occlusal trauma. To treat mobility due to primary occlusal trauma, the cause of the trauma must be eliminated. Likewise for teeth subject to secondary occlusal trauma, though these teeth may also require splinting together to the adjacent teeth so as to eliminate their mobility.
In primary occlusal trauma, the cause of the mobility was the excessive force being applied to a tooth with a normal attachment apparatus, otherwise known as a periodontally-uninvolved tooth. The approach should be to eliminate the cause of the pain and mobility by determining the causes and removing them; the mobile tooth or teeth will soon cease exhibiting mobility. This could involve removing a high spot on a recently restored tooth, or even a high spot on a non-recently restored tooth that perhaps moved into hyperocclusion. It could also involve altering ones parafunctional habits, such as refraining from chewing on pens or biting ones fingernails. For a bruxer, treatment of the patients primary occlusal trauma could involve selective grinding of certain interarch tooth contacts or perhaps employing a nightguard to protect the teeth from the greater than normal occlusal forces of the patients parafunctional habit. For someone who is missing enough teeth in non-strategic positions so that the remaining teeth are forced to endure a greater per square inch occlusal force, treatment might include restoration with either a removable prosthesis or implant-supported crown or bridge.
In secondary occlusal trauma, simply removing the "high spots" or selective grinding of the teeth will not eliminate the problem, because the teeth are already periodontally involved. After splinting the teeth to eliminate the mobility, the cause of the mobility (in other words, the loss of clinical attachment and bone) must be managed; this is achieved through surgical periodontal procedures such as soft tissue and bone grafts, as well as restoration of edentulous areas. As with primary occlusal trauma, treatment may include either a removable prosthesis or implant-supported crown or bridge.
References
== External links == |
Linear verrucous epidermal nevus | Linear verrucous epidermal nevus is a skin lesion characterized by a verrucous skin-colored, dirty-gray or brown papule.: 771 : 633 Generally, multiple papules present simultaneously, and coalesce to form a serpiginous plaque.: 633 When this nevus covers a diffuse or extensive portion of the bodys surface area, it may be referred to as a systematized epidermal nevus, when it involved only one-half of the body it is called a nevus unius lateris.: 771
See also
Inflammatory linear verrucous epidermal nevus
Epidermis
Skin lesion
List of cutaneous conditions
References
== External links == |
Bálints syndrome | Bálints syndrome is an uncommon and incompletely understood triad of severe neuropsychological impairments: inability to perceive the visual field as a whole (simultanagnosia), difficulty in fixating the eyes (oculomotor apraxia), and inability to move the hand to a specific object by using vision (optic ataxia). It was named in 1909 for the Austro-Hungarian neurologist and psychiatrist Rezső Bálint who first identified it.Bálints syndrome occurs most often with an acute onset as a consequence of two or more strokes at more or less the same place in each hemisphere. Therefore, it occurs rarely. The most frequent cause of complete Bálints syndrome is said by some to be sudden and severe hypotension, resulting in bilateral borderzone infarction in the occipito-parietal region. More rarely, cases of progressive Bálints syndrome have been found in degenerative disorders such as Alzheimers disease or certain other traumatic brain injuries at the border of the parietal and the occipital lobes of the brain.
Lack of awareness of this syndrome may lead to a misdiagnosis and resulting inappropriate or inadequate treatment. Therefore, clinicians should be familiar with Bálints syndrome and its various etiologies.
Presentation
Bálints syndrome symptoms can be quite debilitating since they impact visuospatial skills, visual scanning and attentional mechanisms. Since it represents impairment of both visual and language functions, it is a significant disability that can affect the patients safety—even in ones own home environment, and can render the person incapable of maintaining employment. In many cases the complete trio of symptoms—inability to perceive the visual field as a whole (simultanagnosia), difficulty in fixating the eyes (oculomotor apraxia), and inability to move the hand to a specific object by using vision (optic ataxia)—may not be noticed until the patient is in rehabilitation. Therapists unfamiliar with Bálints syndrome may misdiagnose a patients inability to meet progress expectations in any of these symptom areas as simply indicating incapability of benefiting from further traditional therapy. The very nature of each Bálint symptom frustrates rehabilitation progress in each of the other symptoms. Much more research is needed to develop therapeutic protocols that address Bálint symptoms as a group since the disabilities are so intertwined.
Simultanagnosia
Simultanagnosia is the inability to perceive simultaneous events or objects in ones visual field. People with Bálints syndrome perceive the world erratically, as a series of single objects rather than seeing the wholeness of a scene.This spatial disorder of visual attention—the ability to identify local elements of a scene, but not the global whole—has been referred to as a constriction of the individuals global gestalt window—their visual "window" of attention. People fixate their eyes to specific images in social scenes because they are informative to the meaning of the scene. Any forthcoming recovery in simultanagnosia may be related to somehow expanding the restricted attentional window that characterizes this disorder.Simultanagnosia is a profound visual deficit. It impairs the ability to perceive multiple items in a visual display, while preserving the ability to recognize single objects. One study suggests that simultanagnosia may result from an extreme form of competition between objects which makes it difficult for attention to be disengaged from an object once it has been selected. Patients with simultanagnosia have a restricted spatial window of visual attention and cannot see more than one object at a time. They see their world in a patchy, spotty manner. Therefore, they pick out a single object, or even components of an individual object, without being able to see the global "big picture."A study which directly tested the relationship between the restriction of the attentional window in simultanagnosia compared with the vision of healthy participants with normal limits of visual processing confirmed the limitations of difficulties of patients with simultanagnosia.There is considerable evidence that a persons cortex is essentially divided into two functional streams: an occipital-parietal-frontal pathway that processes "where" information and an occipital-temporal-frontal pathway that provides "what" information to the individual.
Oculomotor apraxia
Bálint referred to this as "psychic paralysis of gaze"—the inability to voluntarily guide eye movements, changing to a new location of visual fixation. A major symptom of Oculomotor apraxia is that a person has no control over their eye movements, however, vertical eye movements are typically unaffected. For example, they often have difficulty moving their eyes in the desired direction. In other words, the saccades (rapid eye movements) are abnormal. Because of this, most patients with Oculomotor apraxia have to turn their heads in order to follow objects coming from their peripherals.
Optic ataxia
Optic ataxia is the inability to guide the hand toward an object using visual information where the inability cannot be explained by motor, somatosensory, visual field deficits or acuity deficits. Optic ataxia is seen in Bálints syndrome where it is characterized by an impaired visual control of the direction of arm-reaching to a visual target, accompanied by defective hand orientation and grip formation. It is considered a specific visuomotor disorder, independent of visual space misperception.Optic ataxia is also known as misreaching or dysmetria (English: difficult to measure), secondary to visual perceptual deficits. A patient with Bálints syndrome likely has defective hand movements under visual guidance, despite normal limb strength. The patient is unable to grab an object while looking at the object, due to a discoordination of eye and hand movement. It is especially true with their contralesional hand.Dysmetria refers to a lack of coordination of movement, typified by the undershoot or overshoot of intended position with the hand, arm, leg, or eye. It is sometimes described as an inability to judge distance or scale.
As Bálint states, optic ataxia impaired his patients daily activities, since, while cutting a slice of meat...which he held with a fork in his left hand, ...would search for it outside the plate with the knife in his right hand, or ...while lighting a cigarette he often lit the middle and not the end. Bálint pointed out the systematic nature of this disorder, which was evident in the patients behaviour when searching in space. Thus, when asked to grasp a presented object with his right hand, he would miss it regularly, and would find it only when his hand knocked against it.
The reaching ability of the patient is also altered. It takes them longer to reach toward an object. Their ability to grasp an object is also impaired. The patients performance is even more severely deteriorated when vision of either the hand or the target is prevented.
Cause
The visual difficulties in Bálints syndrome are usually due to damage to the parieto-occipital lobes on both sides of the brain. The parietal lobe is the middle area of the top part of the brain and the occipital lobe is the back part of the brain. (It usually does not affect the temporal lobes)
Diagnosis
Lack of awareness of the syndrome may lead to misdiagnosis such as blindness, psychosis, or dementia. Symptoms of Bálints syndrome are most likely to be noticed first by optometrtists or ophthalmologists during an eye check up, or therapists providing rehabilitation following brain lesions. However, due to the scarcity among practitioners of familiarity with the syndrome, the symptoms are often explained away incorrectly without being considered as a possibility and followed by medical confirmation of clinical and neuroradiological findings. Any severe disturbance of space representation, spontaneously appearing following bilateral parietal damage, strongly suggests the presence of Bálints syndrome and should be investigated as such. One study reports that damage to the bilateral dorsal occipitoparietal regions appeared to be involved in Bálints syndrome.
Neuroanatomical evidence
Bálints syndrome has been found in patients with bilateral damage to the posterior parietal cortex. The primary cause of the damage and the syndrome can originate from multiple strokes, Alzheimers disease, intracranial tumors, or brain injury. Progressive multifocal leukoencephalopathy and Creutzfeldt–Jakob disease have also been found to cause this kind of damage. This syndrome is caused by damage to the posterior superior watershed areas, also known as the parietal-occipital vascular border zone (Brodmanns areas 19 and 7).
Manifestations
Some telltale signs suggesting Bálints syndrome following bilateral brain insults may include:
limitation to perceive only stimuli that is presented at 35 to 40 degrees to the right. They are able to move their eyes but cannot fixate on specific visual stimuli (optic apraxia).
patients field of attention is limited to one object at a time. making activities like reading difficult because each letter is perceived separately (simultanagnosia).
figure/ground defects in which a patient can see either the background but not the object residing somewhere in the whole scene, or conversely can see the object but sees no background around it (simultanagnosia)
a patient, while attempting to put one foot into a slipper by trying to insert the foot into a nonexistent slipper several inches from the real slipper, even as the patient focuses on the actual slipper (optic ataxia)
a patient raising a fork or spoon containing food to a point on the patients face above or below the mouth, and possibly finding the mouth by trial and error by manually moving the utensil on the face (optic ataxia)
Treatment
In terms of the specific rehabilitation of visuoperceptual disorders such as Bálints syndrome, the literature is extremely sparse. According to one study, rehabilitation training should focus on the improvement of visual scanning, the development of visually guided manual movements, and the improvement of the integration of visual elements. Very few treatment strategies have been proposed, and some of those have been criticized as being poorly developed and evaluated.Three approaches to rehabilitation of perceptual deficits, such as those seen in Bálints syndrome, have been identified:
The adaptive (functional) approach, which involves functional tasks utilising the persons strengths and abilities, helping them to compensate for problems or altering the environment to lessen their disabilities. This is the most popular approach.
The remedial approach, which involves restoration of the damaged CNS by training in the perceptual skills, which may be generalised across all activities of daily living. This could be achieved by tabletop activities or sensorimotor exercises.
The multicontext approach, which is based on the fact that learning is not automatically transferred from one situation to another. This involves practicing of a targeted strategy in a multiple environment with varied tasks and movement demands, and it incorporates self-awareness tasks.
Case studies
Symptoms of Bálints syndrome were found in the case of a 29-year-old with migraines. In the aura before the migraine headache, she experienced an inability to see all of the objects in the visual field simultaneously; an inability to coordinate hand and eye movements; and an inability to look at an object on command. Symptoms were not present before the onset of the migraine or after it passed.A study of a patient with Corticobasal Ganglionic Degeneration (CGBD) also showed a development of Bálints syndrome. As a result of CGBD, the patient developed an inability to move his eyes to specific visual objects in his peripheral fields. He also was unable to reach out and touch objects in his peripheral fields. An inability to recognize more than one item at a time was also experienced when presented with the Cookie Theft Picture from the Boston Diagnostic Aphasia Examination.A 58-year-old male presented with Bálints syndrome secondary to severe traumatic brain injury 4-months post-injury onset. He had completed a comprehensive post-acute brain injury rehabilitation program. He received 6 months of rehabilitation services as an inpatient. A three-pronged approach included the implementation of (a) compensatory strategies, (b) remediation exercises and (c) transfer of learned skills in multiple environments and situations. Comprehensive neuropsychological and occupational therapy evaluations were performed at admission and at discharge. Neuropsychological test improvements were noted on tasks that assess visuospatial functioning, although most gains were noted for functional and physical abilities.A patient with congenital deafness exhibited partial Bálints syndrome symptoms. This patient experienced an inability to perceive simultaneous events in her visual field. She was also unable to fixate and follow an object with her eyes. In addition, her ability to point at targets under visual guidance was impaired.Bálints syndrome is rarely reported in children, but some recent studies provide evidence that cases do exist in children. A case involving a 10-year-old male child with Bálints syndrome has been reported Similar results were seen in a 7-year-old boy. In children this syndrome results in a variety of occupational difficulties, but most notably difficulties in schoolwork, especially reading. The investigators encourage more careful recognition of the syndrome to allow adequate rehabilitation and environmental adaptation.
Criticism
The validity of Bálints syndrome has been questioned by some. The components in the syndromes triad of defects (simultanagnosia, oculomotor apraxia, optic ataxia) each may represent a variety of combined defects.
Because Bálints syndrome is not common and is difficult to assess with standard clinical tools, the literature is dominated by case reports and confounded by case selection bias, non-uniform application of operational definitions, inadequate study of basic vision, poor lesion localisation, and failure to distinguish between deficits in the acute and chronic phases of recovery.
References
External links
National Institute on Deafness and Other Communication Disorders - Apraxia of speech |
Hemiballismus | Hemiballismus or hemiballism is a basal ganglia syndrome resulting from damage to the subthalamic nucleus in the basal ganglia. Hemiballismus is a rare hyperkinetic movement disorder, that is characterized by violent involuntary limb movements, on one side of the body, and can cause significant disability. Ballismus affects both sides of the body and is much rarer. Symptoms can decrease during sleep.Hemiballismus differs from chorea in that the movements occur in the proximal limbs whereas in chorea the limb movements are in the distal limbs. Also in chorea the movements are more dance-like, flowing from one region to another.
Presentation
Ballism was defined by Meyers in 1968 as "Repetitive, but constantly varying, large amplitude involuntary movements of the proximal parts of the limbs. This activity is almost ceaseless and movements are often complex and combined". Hemiballismus is usually characterized by involuntary flinging motions of the extremities. The movements are often violent and have wide amplitudes of motion. They are continuous and random and can involve proximal or distal muscles on one side of the body. Some cases even include the facial muscles. It is common for arms and legs to move together. The more a patient is active, the more the movements increase. With relaxation comes a decrease in movements. Physicians can measure the severity of the disorder by having the patient perform a series of basic, predetermined tasks and counting the hemiballistic movements during a set time session. The physicians then rate the patient on a severity scale. This scale gives scientists and clinicians a way to compare patients and determine the range of the disorder.The name hemiballismus literally means "half ballistic", referring to the violent, flailing movements observed on one side of the body.
Causes
In examining the causes of hemiballismus, it is important to remember that this disorder is extremely rare. While hemiballismus can result from the following list, just because a patient has one of these disorders does not mean they will also experience hemiballismus.
Stroke
Hemisballismus as a result of stroke occurs in only about 0.45 cases per hundred thousand stroke patients. Even at such a small rate, stroke is by far the most common cause of hemiballismus. A stroke causes tissue to die due to a lack of oxygen resulting from an impaired blood supply. In the basal ganglia, this can result in the death of tissue that helps to control movement. As a result, the brain is left with damaged tissue that sends damaged signals to the skeletal muscles in the body. The result is occasionally a patient with hemiballismus.
Traumatic brain injury
Hemiballismus can also occur as a result of a traumatic brain injury. There are cases in which survivors of assault or other forms of violence have developed hemiballismus. Through these acts of violence, the survivors brain has been damaged and the hemiballistic movements have developed.
Amyotrophic lateral sclerosis
This disease causes neuronal loss and gliosis, which can include the subthalamic nucleus and other areas of the brain. Essentially any disorder that causes some form of neuronal loss or gliosis in the basal ganglia has the potential to cause hemiballismus.
Nonketotic hyperglycemia
Patients with nonketotic hyperglycemia can develop hemiballismus as a complication to the disease through the development of a subthalamic nucleus lesion. This is the second most common reported cause of hemiballismus. It can be found primarily in the elderly and many of the reported cases have come from East Asian origin, which suggests that there may be some genetic disposition to development of hemiballismus as a result of hyperglycemia. Hemiballistic movements appear when blood glucose levels get too high and then subside once glucose levels return to normal. This time scale for this is usually several hours. In patients with this type of hemiballismus, imaging reveals abnormalities in the putamen contralateral to the movements as well as the globus pallidus and caudate nucleus. While the hyperglycemia itself is not the cause of the hemiballistic movements, it has been suggested that petechial hemorrhage or a decreased production of GABA and acetylcholine could result secondary to the hyperglycemia. One of these issues could be responsible for the hemiballistic movements.
Neoplasms
A neoplasm is an abnormal growth of cells. Cases have shown that if this occurs somewhere in the basal ganglia, hemiballismus can result.
Vascular malformations
Vascular malformations can cause abnormal blood flow to areas of the brain. If too little blood is delivered to the basal ganglia, a stroke can occur.
Tuberculomas
This is another form of tumor that can result in the brain as a result of a tuberculous meningitis infection. This type of tumor can also damage parts of the basal ganglia, sometimes resulting in hemiballismus.
Demyelinating plaques
Demyelinating plaques attack the myelin sheaths on neurons. This decreases the conduction velocity of the neurons, making the signals received by the basal ganglia garbled and incomplete. This disorganized signal can also cause the chaotic movements characterized by hemiballismus.
Complications from HIV infection
Patients with HIV often have complications that arise along with AIDS. Hypoglycemia due to pentamidine use in patients with AIDS has been known to cause hemiballismus. In some patients, hemiballismus has been the only visible symptom to alert the physician that the patients may have AIDS. It is typically a result of a secondary infection that occurs due to the compromised immune system and the most common infection causing hemiballismus is cerebral toxoplasmosis. Most of the lesions that result from this infection are found in the basal ganglia. As long as the diagnosis is not missed, this type of hemiballismus can be treated just as well as in patients without HIV.
Anatomy
Basal ganglia
The basal ganglia are a collection of nuclei that connects to several other areas of the brain. Due to the diverse nuclei that they contain, the basal ganglia are involved in numerous functions, including motor control. It is within this structure that hemiballismus primarily occurs in the brain.
Subthalamic nucleus
This structure within the basal ganglia innervates other structures, including a very important connection to the internal globus pallidus. The subthalamic nucleus essentially provides the excitement needed to drive the globus pallidus. Injury to this area or its efferent or afferent connections can induce this disorder contralateral to the side of the lesion. The structure itself is a regulator of motor function and is also involved in associative and limbic functions. It was traditionally thought that the disorder was only caused by injury to the subthalamic nucleus, but later studies have shown that damage to other basal ganglia regions can also be responsible for causing this disorder. Hemiballismus caused by lesions in the subthalamic nucleus is more severe than other forms of the disorder.
Globus pallidus
From recent studies, it is now thought that hemiballismus can be associated with a decreased output of the globus pallidus. This is because studies have shown that firing rates decrease from 70/s to 40/s. In addition to a decreased firing rate, degenerative neurological disorders that cause patients to exhibit hemiballistic movements show a marked decrease in the globus pallidus mass as well. Increases in activity in this area causes there to be an inhibition of the motor thalamus. This causes cortical activation and thus a movement inhibition. In the case of hemiballismus, the opposite occurs, leading to the characteristic large, irregular movements.
Putamen
The putamen is also part of the basal ganglia and can be involved in hemiballismus due to the fact that it projects to the premotor cortex through the globus pallidus. As a result, damage to this area can also cause hemiballistic movements to be seen as it is also part of the chain in movement.
Caudate nucleus
The caudate nucleus is the portion of the basal ganglia that helps control voluntary movement. Damage to this area can also result in hemiballismus as it is directly related to voluntary movement.
Cortical structures
While the majority of damage that causes hemiballismus occurs within the basal ganglia, there are still cases that have been documented on which damage to cortical structures has caused hemiballistic movements.
Diagnosis
Diagnosis of hemiballismus is a clinical one, made with observation during clinical examination. Hemiballismus is a clinical sign with a number of different causes. Therefore, a diagnosis underlying this clinical sign should be sought. The observer should note sudden, flinging movements of a limb(s) and occasionally the face. This is commonly unilateral ("Hemiballismus"). The movements must be distinguished from other hyperkinetic movement disorders such as tremor (generally more rhythmic, and smaller amplitude) and chorea, akathisia and athetosis (all are often of lower amplitude and less violent).
Treatments
When treating hemiballismus, it is first important to treat whatever may be causing the manifestation of this disorder. This could be hyperglycemia, infections, or neoplastic lesions. Some patients may not even need treatment because the disorder is not severe and can be self-limited.
Dopamine blockers
When pharmacological treatment is necessary, the most standard type of drug to use is an antidopaminergic drug. Blocking dopamine is effective in about ninety percent of patients. Perphenazine, pimozide, haloperidol, and chlorpromazine are standard choices for treatment. Scientists are still unsure as to why this form of treatment works, as dopamine has not been directly linked to hemiballismus.
Anticonvulsants
An anticonvulsant called topiramate has helped patients in three cases and may be a viable treatment for the future.
ITB therapy
Intrathecal baclofen (ITB) therapy is used to treat a variety of movement disorders such as cerebral palsy and multiple sclerosis. It can also be a possibility to help treat hemiballismus. In one case, before ITB the patient had an average of 10–12 ballism episodes of the right lower limb per hour. During episodes, the right hip would flex up to about 90 degrees, with a fully extended knee. After an ITB pump was implanted and the correct dosage was found, the frequency of ballistic right leg movements decreased to about three per day, and the right hip flexed to only 30 degrees. The patient was also able to better isolate individual distal joint movements in the right lower limb. The patient currently receives 202.4 microg/day of ITB and continues to benefit almost 6 years after the ITB pump was implanted.
Botulinum injections
New uses for botulinum toxin have included treatment of hemiballismus. However, this is still in the early stages of testing. This treatment deals with the muscular manifestations of hemiballismus as opposed to the neurological causes.
Tetrabenazine
Tetrabenazine has been used to treat other movement disorders, but is now being used to treat hemiballismus. Patients using this medication have had a dramatic response. However, lowering the dosage leads to a return of symptoms. This drug works by depleting dopamine.
Antipsychotics
In one case, a patient had not been responding to haloperidol, thus the physician tried olanzapine. The patient made a significant recovery. More research is being performed on the use of these types of drugs in treating hemiballismus.
Functional neurosurgery
Surgery as a treatment should only be used on patients with severe hemiballismus that has not responded to treatment. Lesioning of the globus pallidus or deep brain stimulation of the globus pallidus are procedures that can be used on humans. Usually, lesioning is favored over deep brain stimulation because of the maintenance required to continue stimulating the brain correctly and effectively.
Prognosis
In the past, the prognosis for patients with this disease had been very poor; with many patients experiencing severe disability or death. Now, patients are responding remarkably well to current treatments and the majority of patients go into spontaneous remission. For those that do not go into remission, the symptoms of hemiballismus can generally be very well controlled with medication.
Due to the rarity of this disorder, scientists know very little about the details of hemiballismus.
There appears to be a discrepancy between this disorder in humans and animals that has yet to be explained.
Hemiballismus can also be induced by damage to other areas of the basal ganglia besides the subthalamic nucleus. Research is being done in these areas in order to give scientists and clinicians a better model for this disease that will ultimately lead to better diagnosis and treatment of this disorder.
Research is also being done on why certain treatments seem to help hemiballistic patients when they should seemingly do more harm. An example of this is why lesioning the globus pallidus seems to reduce hemiballistic movements.
The mechanism behind the effect of dopamine on patients symptoms remains unknown.
History
The work of J.R. Whittier, F.A. Mettler, and M.B. Carpenter in the mid-1900s helped scientists and clinicians form a more complete picture of hemiballismus. In their experiments, several lesions were made in the basal ganglia structures in monkeys and then they monitored the results. They noticed that the majority of the time, the monkeys did not have any unusual movements. However, when at least twenty percent of the subthalamic nucleus was damaged, abnormal movements were seen in the limbs opposite to the side of the brain that was damaged. This observation caused scientists to believe that hemiballismus outside the subthalamic nucleus did not occur. It was not until much later that this classical model began to expand to include other areas of the basal ganglia and even some cortical structures. They also noticed that unlike human patients, the unusual movements in the monkeys were mainly in the lower extremities. In about half of the monkeys, the hemiballismus continued until the monkey died.Other scientists have also worked on this perplexing disorder and have found that the symptoms can be induced by injecting kainic acid or ibotenic acid into the subthalamic nucleus. I. Hamada and M.R. DeLong found that by using these chemicals, they could destroy only four percent of the subthalamic nucleus and still see hemiballistic movements. However, the abnormal movements would usually disappear within four to five hours even though it did not appear as though the damaged tissue had healed. This suggests that the subthalamic nucleus is plastic enough to adapt to small amounts of damage in order to resume normal function.
See also
Movement disorders
References
== External links == |
Sensorineural hearing loss | Sensorineural hearing loss (SNHL) is a type of hearing loss in which the root cause lies in the inner ear or sensory organ (cochlea and associated structures) or the vestibulocochlear nerve (cranial nerve VIII). SNHL accounts for about 90% of reported hearing loss. SNHL is usually permanent and can be mild, moderate, severe, profound, or total. Various other descriptors can be used depending on the shape of the audiogram, such as high frequency, low frequency, U-shaped, notched, peaked, or flat.
Sensory hearing loss often occurs as a consequence of damaged or deficient cochlear hair cells. Hair cells may be abnormal at birth or damaged during the lifetime of an individual. There are both external causes of damage, including infection, and ototoxic drugs, as well as intrinsic causes, including genetic mutations. A common cause or exacerbating factor in SNHL is prolonged exposure to environmental noise, or noise-induced hearing loss. Exposure to a single very loud noise such as a gun shot or bomb blast can cause noise-induced hearing loss. Using headphones at high volume over time, or being in loud environments regularly, such as a loud workplace, sporting events, concerts, and using noisy machines can also be a risk for noise-induced hearing loss.
Neural, or "retrocochlear", hearing loss occurs because of damage to the cochlear nerve (CVIII). This damage may affect the initiation of the nerve impulse in the cochlear nerve or the transmission of the nerve impulse along the nerve into the brainstem.
Most cases of SNHL present with a gradual deterioration of hearing thresholds occurring over years to decades. In some, the loss may eventually affect large portions of the frequency range. It may be accompanied by other symptoms such as ringing in the ears (tinnitus) and dizziness or lightheadedness (vertigo). The most common kind of sensorineural hearing loss is age-related (presbycusis), followed by noise-induced hearing loss (NIHL).
Frequent symptoms of SNHL are loss of acuity in distinguishing foreground voices against noisy backgrounds, difficulty understanding on the telephone, some kinds of sounds seeming excessively loud or shrill, difficulty understanding some parts of speech (fricatives and sibilants), loss of directionality of sound (especially with high frequency sounds), perception that people mumble when speaking, and difficulty understanding speech. Similar symptoms are also associated with other kinds of hearing loss; audiometry or other diagnostic tests are necessary to distinguish sensorineural hearing loss.
Identification of sensorineural hearing loss is usually made by performing a pure tone audiometry (an audiogram) in which bone conduction thresholds are measured. Tympanometry and speech audiometry may be helpful. Testing is performed by an audiologist.
There is no proven or recommended treatment or cure for SNHL; management of hearing loss is usually by hearing strategies and hearing aids. In cases of profound or total deafness, a cochlear implant is a specialised hearing aid that may restore a functional level of hearing. SNHL is at least partially preventable by avoiding environmental noise, ototoxic chemicals and drugs, and head trauma, and treating or inoculating against certain triggering diseases and conditions like meningitis.
Signs and symptoms
Since the inner ear is not directly accessible to instruments, identification is by patient report of the symptoms and audiometric testing. Of those who present to their doctor with sensorineural hearing loss, 90% report having diminished hearing, 57% report having a plugged feeling in ear, and 49% report having ringing in ear (tinnitus). About half report vestibular (vertigo) problems.
For a detailed exposition of symptoms useful for screening, a self-assessment questionnaire was developed by the American Academy of Otolaryngology, called the Hearing Handicap Inventory for Adults (HHIA). It is a 25-question survey of subjective symptoms.
Causes
Sensorineural hearing loss may be genetic or acquired (i.e. as a consequence of disease, noise, trauma, etc.). People may have a hearing loss from birth (congenital) or the hearing loss may come on later. Many cases are related to old age (age-related).
Genetic
Hearing loss can be inherited. More than 40 genes have been implicated in the cause of deafness. There are 300 syndromes with related hearing loss, and each syndrome may have causative genes.
Recessive, dominant, X-linked, or mitochondrial genetic mutations can affect the structure or metabolism of the inner ear. Some may be single point mutations, whereas others are due to chromosomal abnormalities. Some genetic causes give rise to a late onset hearing loss. Mitochondrial mutations can cause SNHL i.e. m.1555A>G, which makes the individual sensitive to the ototoxic effects of aminoglycoside antibiotics.
The most common cause of recessive genetic congenital hearing impairment in developed countries is DFNB1, also known as Connexin 26 deafness or GJB2-related deafness.
The most common syndromic forms of hearing impairment include (dominant) Stickler syndrome and Waardenburg syndrome, and (recessive) Pendred syndrome and Usher syndrome.
Mitochondrial mutations causing deafness are rare: MT-TL1 mutations cause MIDD (Maternally inherited deafness and diabetes) and other conditions which may include deafness as part of the picture.
TMPRSS3 gene was identified by its association with both congenital and childhood onset autosomal recessive deafness. This gene is expressed in fetal cochleae and many other tissues, and is thought to be involved in the development and maintenance of the inner ear or the contents of the perilymph and endolymph. It was also identified as a tumor associated gene that is overexpressed in ovarian tumors.
Charcot–Marie–Tooth disease an inherited neurological disorder with delayed onset that can affect the ears as well as other organs. The hearing loss in this condition is often ANSD (auditory neuropathy spectrum disorder) a neural cause of hearing loss.
Muckle–Wells syndrome, a rare inherited autoinflammatory disorder, can lead to hearing loss.
Autoimmune disease: although probably rare, it is possible for autoimmune processes to target the cochlea specifically, without symptoms affecting other organs. Granulomatosis with polyangiitis, an autoimmune condition, may precipitate hearing loss.
Congenital
Infections:
Congenital rubella syndrome, CRS, results from transplacental transmission of the rubella virus during pregnancy. CRS has been controlled by universal vaccination (MMR or MMRV vaccine).
Cytomegalovirus (CMV) infection is the most common cause of progressive sensorineural hearing loss in children. It is a common viral infection contracted by contact with infected bodily fluids such as saliva or urine and easily transmitted in nurseries and thus from toddlers to expectant mothers. CMV infection during pregnancy can affect the developing foetus and lead to learning difficulties as well as hearing loss.
Toxoplasmosis, a parasitic disease affecting 23% of the population in the U.S., can cause sensorineural deafness to the fetus in utero.
Hypoplastic auditory nerves or abnormalities of the cochlea. Abnormal development of the inner ear can occur in some genetic syndromes such as LAMM syndrome (labyrinthine aplasia, microtia and microdontia), Pendred syndrome, branchio-oto-renal syndrome, CHARGE syndrome
GATA2 deficiency, a grouping of several disorders caused by common defect, viz., familial or sporadic inactivating mutations in one of the two parental GATA2 genes. These autosomal dominant mutations cause a reduction, i.e. a haploinsufficiency, in the cellular levels of the genes product, GATA2. The GATA2 protein is a transcription factor critical for the embryonic development, maintenance, and functionality of blood-forming, lympathic-forming, and other tissue-forming stem cells. In consequence of these mutations, cellular levels of GATA2 are deficient and individuals develop over time hematological, immunological, lymphatic, and/or other disorders. GATA2 deficiency-induced abnormalities in the lymphatic system are proposed to be responsible for a failure in generating the perilymphatic space around the inner ears semicircular canals, which in turn underlies the development of sensorineural hearing loss.
Presbycusis
Progressive age-related loss of hearing acuity or sensitivity can start as early as age 18, primarily affecting the high frequencies, and men more than women. Such losses may not become apparent until much later in life. Presbycusis is by far the dominant cause of sensorineural hearing loss in industrialized societies. A study conducted in Sudan, with a population free from loud noise exposures, found significantly less cases of hearing loss when compared with age-matched cases from an industrialized country. Similar findings were reported by a study conducted of a population from Easter island, which reported worse hearing among those that spent time in industrialized countries when compared with those that never left the island. Researchers have argued that factors other than differences in noise exposure, such as genetic make up, might also have contributed to the findings. Hearing loss that worsens with age but is caused by factors other than normal aging, such as noise-induced hearing loss, is not presbycusis, although differentiating the individual effects of multiple causes of hearing loss can be difficult. One in three persons have significant hearing loss by age 65; by age 75, one in two. Age-related hearing loss is neither preventable nor reversible.
Noise
Most people living in modern society have some degree of progressive sensorineural (i.e. permanent) noise-induced hearing loss (NIHL) resulting from overloading and damaging the sensory or neural apparatus of hearing in the inner ear. NIHL is typically a drop-out or notch centered at 4000 Hz. Both intensity (SPL) and duration of exposure, and repetitive exposure to unsafe levels of noise contribute to cochlear damage that results in hearing loss. The louder the noise is, the shorter the safe amount of exposure is. NIHL can be either permanent or temporary, called a threshold shift. Unsafe levels of noise can be as little as 70 dB (about twice as loud as normal conversation) if there is prolonged (24-hour) or continuous exposure. 125 dB (a loud rock concert is ~120 dB) is the pain level; sounds above this level cause instant and permanent ear damage.
Noise and ageing are the primary causes of presbycusis, or age-related hearing loss, the most common kind of hearing loss in industrial society. The dangers of environmental and occupational noise exposure are widely recognized. Numerous national and international organizations have established standards for safe levels of exposure to noise in industry, the environment, military, transportation, agriculture, mining and other areas. Sound intensity or sound pressure level (SPL) is measured in decibels (dB). For reference:
An increase of 6 dB represents a doubling of the SPL, or energy of the sound wave, and therefore its propensity to cause ear damage. Because human ears hear logarithmically, not linearly, it takes an increase of 10 dB to produce a sound that is perceived to be twice as loud. Ear damage due to noise is proportional to sound intensity, not perceived loudness, so its misleading to rely on subjective perception of loudness as an indication of the risk to hearing, i.e. it can significantly underestimate the danger.
While the standards differ moderately in levels of intensity and duration of exposure considered safe, some guidelines can be derived.The safe amount of exposure is reduced by a factor of 2 for every exchange rate (3 dB for NIOSH standard or 5 dB for OSHA standard) increase in SPL. For example, the safe daily exposure amount at 85 dB (90 dB for OSHA) is 8 hours, while the safe exposure at 94 dB(A) (nightclub level) is only 1 hour. Noise trauma can also cause a reversible hearing loss, called a temporary threshold shift. This typically occurs in individuals who are exposed to gunfire or firecrackers, and hear ringing in their ears after the event (tinnitus).
Ambient environmental noise: Populations living near airports, railyards and train stations, freeways and industrial areas are exposed to levels of noise typically in the 65 to 75 dBA range. If lifestyles include significant outdoor or open window conditions, these exposures over time can degrade hearing. U.S. Dept. of Housing and Urban Development sets standards for noise impact in residential and commercial construction zones. HUDs noise standards may be found in 24 CFR Part 51, Subpart B. Environmental noise above 65 dB defines a noise-impacted area.
Personal audio electronics: Personal audio equipment such as iPods (iPods often reach 115 decibels or higher), can produce powerful enough sound to cause significant NIHL.
Acoustic trauma: Exposure to a single event of extremely loud noise (such as explosions) can also cause temporary or permanent hearing loss. A typical source of acoustic trauma is a too-loud music concert.
Workplace noise: The OSHA standards 1910.95 General Industry Occupational Noise Exposure and 1926.52 Construction Industry Occupational Noise Exposure identify the level of 90 dB(A) for 8 hour exposure as the level necessary to protect workers from hearing loss.
Disease or disorder
Inflammatory
Suppurative labyrinthitis or otitis interna (inflammation of the inner ear)
Diabetes mellitus A recent study found that hearing loss is twice as common in people with diabetes as it is in those who dont have the disease. Also, of the 86 million adults in the U.S. who have prediabetes, the rate of hearing loss is 30 percent higher than in those with normal blood glucose. It has not been established how diabetes is related to hearing loss. It is possible that the high blood glucose levels associated with diabetes cause damage to the small blood vessels in the inner ear, similar to the way in which diabetes can damage the eyes and the kidneys. Similar studies have shown a possible link between that hearing loss and neuropathy (nerve damage).
Tumor
Cerebellopontine angle tumour (junction of the pons and cerebellum) – The cerebellopontine angle is the exit site of both the facial nerve(CN7) and the vestibulocochlear nerve(CN8). Patients with these tumors often have signs and symptoms corresponding to compression of both nerves.
Acoustic neuroma (vestibular schwannoma) – benign neoplasm of Schwann cells affecting the vestibulocochlear nerve
Meningioma – benign tumour of the pia and arachnoid mater
Ménières disease – causes sensorineural hearing loss in the low frequency range (125 Hz to 1000 Hz). Ménières disease is characterized by sudden attacks of vertigo, lasting minutes to hours preceded by tinnitus, aural fullness, and fluctuating hearing loss. It is relatively rare and commonly over diagnosed.
Bacterial meningitis e.g. pneumococcal, meningococcal, haemophilus influenzae may damage the cochlea – Hearing loss is one of the most common after-effects of bacterial meningitis. It has been estimated that 30% of bacterial meningitis cases result in mild to profound hearing loss. Children are most at risk: seventy percent of all bacterial meningitis occurs in young children under the age of five.
Viral
AIDS and ARC patients frequently experience auditory system anomalies.
Mumps(epidemic parotitis) may result in profound sensorineural hearing loss (90 dB or more), unilaterally (one ear) or bilaterally (both ears).
Measles may result in auditory nerve damage but more commonly gives a mixed (sensorineural plus conductive) hearing loss, and can be bilaterally.
Ramsay Hunt syndrome type II (herpes zoster oticus)
Bacterial
Syphilis is commonly transmitted from pregnant women to their fetuses, and about a third of the infected children will eventually become deaf.
Ototoxic and neurotoxic drugs and chemicals
Some over-the-counter as well as prescription drugs and certain industrial chemicals are ototoxic. Exposure to these can result in temporary or permanent hearing loss.
Some medications cause irreversible damage to the ear, and are limited in their use for this reason. The most important group is the aminoglycosides (main member gentamicin). A rare mitochondrial mutation, m.1555A>G, can increase an individuals susceptibility to the ototoxic effect of aminoglycosides. Long term hydrocodone (Vicodin) abuse is known to cause rapidly progressing sensorineural hearing loss, usually without vestibular symptoms. Methotrexate, a chemotherapy agent, is also known to cause hearing loss. In most cases hearing loss does not recover when the drug is stopped. Paradoxically, methotrexate is also used in the treatment of autoimmune-induced inflammatory hearing loss.
Various other medications may reversibly degrade hearing. This includes loop diuretics, sildenafil (Viagra), high or sustained dosing of NSAIDs (aspirin, ibuprofen, naproxen, and various prescription drugs: celecoxib, etc.), quinine, and macrolide antibiotics (erythromycin, etc.). Cytotoxic agents such as carboplatinum, used to treat malignancies can give rise to a dose dependent SNHL, as can drugs such as desferrioxamine, used for haematological disorders such as thalassaemia; patients prescribed these drugs need to have hearing monitored.
Prolonged or repeated environmental or work-related exposure to ototoxic chemicals can also result in sensorineural hearing loss. Some of these chemicals are:
butyl nitrite – chemical used recreationally known as poppers
carbon disulfide – a solvent used as a building block in many organic reactions
styrene, an industrial chemical precursor of polystyrene, a plastic
carbon monoxide, a poisonous gas resulting from incomplete combustion
heavy metals: tin, lead, manganese, mercury
hexane, an industrial solvent and one of the significant constituents of gasoline
ethylbenzene, an industrial solvent used in the production of styrene
toluene and xylene, highly poisonous petrochemical solvents. Toluene is a component of high-octane gasoline; xylene is used in the production of polyester fibers and resins.
trichloroethylene, an industrial degreasing solvent
Organophosphate pesticides
Head trauma
There can be damage either to the ear itself or to the central auditory pathways that process the information conveyed by the ears. People who sustain head injury are susceptible to hearing loss or tinnitus, either temporary or permanent. Contact sports like football (U.S. NFL), hockey and cricket have a notable incidence of head injuries (concussions). In one survey of retired NFL players, all of whom reported one or more concussions during their playing careers, 25% had hearing loss and 50% had tinnitus.
Perinatal conditions
These are much more common in premature babies, particularly those under 1500 g at birth. Premature birth can be associated with problems that result in sensorineural hearing loss such as anoxia or hypoxia (poor oxygen levels), jaundice, intracranial haemorrhages, meningitis. Fetal alcohol syndrome is reported to cause hearing loss in up to 64% of infants born to alcoholic mothers, from the ototoxic effect on the developing fetus, plus malnutrition during pregnancy from the excess alcohol intake.
Iodine deficiency / Hypothyroidism
Iodine deficiency and endemic hypothyroidism are associated with hearing loss. If a pregnant mother has insufficient iodine intake during pregnancy it affects the development of the inner ear in the foetus leading to sensorineural deafness. This occurs in certain areas of the world, such as the Himalayas, where iodine is deficient in the soil and thus the diet. In these areas there is a high incidence of endemic goitre. This cause of deafness is prevented by adding iodine to salt.
Brain stroke
Brain stroke in a region affecting auditory function such as a posterior circulation infarct has been associated with deafness.
Pathophysiology
Sensory hearing loss is caused by abnormal structure or function of the hair cells of the organ of Corti in the cochlea. Neural hearing impairments are consequent upon damage to the eighth cranial nerve (the vestibulocochlear nerve) or the auditory tracts of the brainstem. If higher levels of the auditory tract are affected this is known as central deafness. Central deafness may present as sensorineural deafness but should be distinguishable from the history and audiological testing.
Cochlear dead regions in sensory hearing loss
Hearing impairment may be associated with damage to the hair cells in the cochlea. Sometimes there may be complete loss of function of inner hair cells (IHCs) over a certain region of the cochlea; this is called a "dead region". The region can be defined in terms of the range of characteristic frequencies (CFs) of the IHCs and/or neurons immediately adjacent to the dead region.
Cochlear hair cells
Outer hair cells (OHCs) contribute to the structure of the Organ of Corti, which is situated between the basilar membrane and the tectorial membrane within the cochlea (See Figure 3). The tunnel of corti, which runs through the Organ of Corti, divides the OHCs and the inner hair cells (IHCs). OHCs are connected to the reticular laminar and the Deiters’ cells. There are roughly twelve thousand OHCs in each human ear, and these are arranged in up to five rows. Each OHC has small tufts of hairs, or cilia, on their upper surface known as stereocilia, and these are also arranged into rows which are graded in height. There are approximately 140 stereocilia on each OHC.The fundamental role of the OHCs and the IHCs is to function as sensory receptors. The main function of the IHCs is to transmit sound information via afferent neurons. They do this by transducing mechanical movements or signals into neural activity. When stimulated, the stereocilia on the IHCs move, causing a flow of electric current to pass through the hair cells. This electric current creates action potentials within the connected afferent neurons.
OHCs are different in that they actually contribute to the active mechanism of the cochlea. They do this by receiving mechanical signals or vibrations along the basilar membrane, and transducing them into electrochemical signals. The stereocilia found on OHCs are in contact with the tectorial membrane. Therefore, when the basilar membrane moves due to vibrations, the stereocilia bend. The direction in which they bend, dictates the firing rate of the auditory neurons connected to the OHCs.The bending of the stereocilia towards the basal body of the OHC causes excitation of the hair cell. Thus, an increase in firing rate of the auditory neurons connected to the hair cell occurs. On the other hand, the bending of the stereocilia away from the basal body of the OHC causes inhibition of the hair cell. Thus, a decrease in firing rate of the auditory neurons connected to the hair cell occurs. OHCs are unique in that they are able to contract and expand (electromotility). Therefore, in response to the electrical stimulations provided by the efferent nerve supply, they can alter in length, shape and stiffness. These changes influence the response of the basilar membrane to sound. It is therefore clear that the OHCs play a major role in the active processes of the cochlea. The main function of the active mechanism is to finely tune the basilar membrane, and provide it with a high sensitivity to quiet sounds. The active mechanism is dependent on the cochlea being in good physiological condition. However, the cochlea is very susceptible to damage.
Hair cell damage
SNHL is most commonly caused by damage to the OHCs and the IHCs. There are two methods by which they might become damaged. Firstly, the entire hair cell might die. Secondly, the stereocilia might become distorted or destroyed. Damage to the cochlea can occur in several ways, for example by viral infection, exposure to ototoxic chemicals, and intense noise exposure. Damage to the OHCs results in either a less effective active mechanism, or it may not function at all. OHCs contribute to providing a high sensitivity to quiet sounds at a specific range of frequencies (approximately 2–4 kHz). Thus, damage to the OHCs results in the reduction of sensitivity of the basilar membrane to weak sounds. Amplification to these sounds is therefore required, in order for the basilar membrane to respond efficiently. IHCs are less susceptible to damage in comparison to the OHCs. However, if they become damaged, this will result in an overall loss of sensitivity.
Neural tuning curves
Frequency selectivity
The traveling wave along the basilar membrane peaks at different places along it, depending on whether the sound is low or high frequency. Due to the mass and stiffness of the basilar membrane, low frequency waves peak in the apex, while high frequency sounds peak in the basal end of the cochlea. Therefore, each position along the basilar membrane is finely tuned to a particular frequency. These specifically tuned frequencies are referred to as characteristic frequencies (CF).If a sound entering the ear is displaced from the characteristic frequency, then the strength of response from the basilar membrane will progressively lessen. The fine tuning of the basilar membrane is created by the input of two separate mechanisms. The first mechanism being a linear passive mechanism, which is dependent on the mechanical structure of the basilar membrane and its surrounding structures. The second mechanism is a non-linear active mechanism, which is primarily dependent on the functioning of the OHCs, and also the general physiological condition of the cochlea itself. The base and apex of the basilar membrane differ in stiffness and width, which cause the basilar membrane to respond to varying frequencies differently along its length. The base of the basilar membrane is narrow and stiff, resulting in it responding best to high frequency sounds. The apex of the basilar membrane is wider and much less stiff in comparison to the base, causing it to respond best to low frequencies.This selectivity to certain frequencies can be illustrated by neural tuning curves. These demonstrate the frequencies a fiber responds to, by showing threshold levels (dB SPL) of auditory nerve fibers as a function of different frequencies. This demonstrates that auditory nerve fibers respond best, and hence have better thresholds at the fibers characteristic frequency and frequencies immediately surrounding it. The basilar membrane is said to be ‘sharply tuned’ due to the sharp ‘V’ shaped curve, with its ‘tip’ centered at the auditory fibers characteristic frequency. This shape shows how few frequencies a fiber responds to. If it were a broader ‘V’ shape, it would be responding to more frequencies (See Figure 4).
IHC vs OHC hearing loss
A normal neural tuning curve is characterised by a broadly tuned low frequency ‘tail’, with a finely tuned middle frequency ‘tip’. However, where there is partial or complete damage to the OHCs, but with unharmed IHCs, the resulting tuning curve would show the elimination of sensitivity at the quiet sounds. I.e. where the neural tuning curve would normally be most sensitive (at the ‘tip’) (See Figure 5).Where both the OHCs and the IHCs are damaged, the resulting neural tuning curve would show the elimination of sensitivity at the ‘tip. However, due to IHC damage, the whole tuning curve becomes raised, giving a loss of sensitivity across all frequencies (See Figure 6). It is only necessary for the first row of OHCs to be damaged for the elimination of the finely tuned ‘tip’ to occur. This supports the idea that the incidence of OHC damage and thus a loss of sensitivity to quiet sounds, occurs more than IHC loss.When the IHCs or part of the basilar membrane are damaged or destroyed, so that they no longer function as transducers, the result is a ‘dead region’. Dead regions can be defined in terms of the characteristic frequencies of the IHC, related to the specific place along the basilar membrane where the dead region occurs. Assuming that there has been no shift in the characteristic frequencies relating to certain regions of the basilar membrane, due to the damage of OHCs. This often occurs with IHC damage. Dead regions can also be defined by the anatomical place of the non-functioning IHC (such as an “apical dead region”), or by the characteristic frequencies of the IHC adjacent to the dead region.
Dead region audi |
Sensorineural hearing loss | ometry
Pure tone audiometry (PTA)
Dead regions affect audiometric results, but perhaps not in the way expected. For example, it may be expected that thresholds would not be obtained at the frequencies within the dead region, but would be obtained at frequencies adjacent to the dead region. Therefore, assuming normal hearing exists around the dead region, it would produce an audiogram that has a dramatically steep slope between the frequency where a threshold is obtained, and the frequency where a threshold cannot be obtained due to the dead region.
However, it appears that this is not the case. Dead regions cannot be clearly found via PTA audiograms. This may be because although the neurons innervating the dead region, cannot react to vibration at their characteristic frequency. If the basilar membrane vibration is large enough, neurons tuned to different characteristic frequencies such as those adjacent to the dead region, will be stimulated due to the spread of excitation. Therefore, a response from the patient at the test frequency will be obtained. This is referred to as “off-place listening”, and is also known as ‘off-frequency listening’. This will lead to a false threshold being found. Thus, it appears a person has better hearing than they actually do, resulting in a dead region being missed. Therefore, using PTA alone, it is impossible to identify the extent of a dead region (See Figure 7 and 8).Consequently, how much is an audiometric threshold affected by a tone with its frequency within a dead region? This depends on the location of the dead region. Thresholds at low frequency dead regions, are more inaccurate than those at higher frequency dead regions. This has been attributed to the fact that excitation due to vibration of the basilar membrane spreads upwards from the apical regions of the basilar membrane, more than excitation spreads downwards from higher frequency basal regions of the cochlea. This pattern of the spread of excitation is similar to the ‘upward spread of masking’ phenomenon. If the tone is sufficiently loud to produce enough excitation at the normally functioning area of the cochlea, so that it is above that areas threshold. The tone will be detected, due to off-frequency listening which results in a misleading threshold.To help to overcome the issue of PTA producing inaccurate thresholds within dead regions, masking of the area beyond the dead region that is being stimulated can be used. This means that the threshold of the responding area is sufficiently raised, so that it cannot detect the spread of excitation from the tone. This technique has led to the suggestion that a low frequency dead region may be related to a loss of 40-50 dB. However, as one of the aims of PTA is to determine whether or not there is a dead region, it may be difficult to assess which frequencies to mask without the use of other tests.Based on research it has been suggested that a low frequency dead region may produce a relatively flat loss, or a very gradually sloping loss towards the higher frequencies. As the dead region will be less detectable due to the upward spread of excitation. Whereas, there may be a more obvious steeply sloping loss at high frequencies for a high frequency dead region. Although it is likely that the slope represents the less pronounced downward spread of excitation, rather than accurate thresholds for those frequencies with non-functioning hair cells. Mid-frequency dead regions, with a small range, appear to have less effect on the patients ability to hear in everyday life, and may produce a notch in the PTA thresholds. Although it is clear that PTA is not the best test to identify a dead region.
Psychoacoustic tuning curves (PTC) and threshold equalizing noise (TEN) tests
Although some debate continues regarding the reliability of such tests, it has been suggestedthat psychoacoustic tuning curves (PTCs) and threshold-equalising noise (TEN) results may be useful in detecting dead regions, rather than PTA. PTCs are similar to neural tuning curves. They illustrate the level of a masker (dB SPL) tone at threshold, as a function of deviation from center frequency (Hz). They are measured by presenting a fixed low intensity pure tone while also presenting a narrow-band masker, with a varying center frequency. The masker level is varied, so that the level of masker needed to just mask the test signal is found for the masker at each center frequency. The tip of the PTC is where the masker level needed to just mask the test signal is the lowest. For normal hearing people this is when the masker center frequency is closest to the frequency of the test signal (See Figure 9).In the case of dead regions, when the test signal lies within the boundaries of a dead region, the tip of the PTC will be shifted to the edge of the dead region, to the area that is still functioning and detecting the spread of excitation from the signal. In the case of a low frequency dead region, the tip is shifted upwards indicating a low frequency dead region starting at the tip of the curve. For a high frequency dead region, the tip is shifted downwards from the signal frequency to the functioning area below the dead region. However, the traditional method of obtaining PTCs is not practical for clinical use, and it has been argued that TENs are not accurate enough. A fast method for finding PTCs has been developed and it may provide the solution. However, more research to validate this method is required, before it can be accepted clinically.
Perceptual consequences of a dead region
Audiogram configurations are not good indicators of how a dead region will affect a person functionally, mainly due to individual differences. For example, a sloping audiogram is often present with a dead region, due to the spread of excitation. However, the individual may well be affected differently from someone with a corresponding sloped audiogram caused by partial damage to hair cells rather than a dead region. They will perceive sounds differently, yet the audiogram suggests that they have the same degree of loss. Huss and Moore investigated how hearing impaired patients perceive pure tones, and found that they perceive tones as noisy and distorted, more (on average) than a person without a hearing impairment. However, they also found that the perception of tones as being like noise, was not directly related to frequencies within the dead regions, and was therefore not an indicator of a dead region. This therefore suggests that audiograms, and their poor representation of dead regions, are inaccurate predictors of a patients perception of pure tone quality.Research by Kluk and Moore has shown that dead regions may also affect the patients perception of frequencies beyond the dead regions. There is an enhancement in the ability to distinguish between tones that differ very slightly in frequency, in regions just beyond the dead regions compared to tones further away. An explanation for this may be that cortical re-mapping has occurred. Whereby, neurons which would normally be stimulated by the dead region, have been reassigned to respond to functioning areas near it. This leads to an over-representation of these areas, resulting in an increased perceptual sensitivity to small frequency differences in tones.
Vestibulocochlear nerve pathology
congenital deformity of the internal auditory canal,
neoplastic and pseudo-neoplastic lesions, with special detailed emphasis on schwannoma of the eighth cranial nerve (acoustic neuroma),
non-neoplastic Internal Auditory Canal/CerebelloPontine Angle pathology, including vascular loops,
Diagnosis
Case history
Before examination, a case history provides guidance about the context of the hearing loss.
major concern
pregnancy and childbirth information
medical history
development history
family history
Otoscopy
Direct examination of the external canal and tympanic membrane (ear drum) with an otoscope, a medical device inserted into the ear canal that uses light to examine the condition of the external ear and tympanic membrane, and
middle ear through the semi-translucent membrane.
Differential testing
Differential testing is most useful when there is unilateral hearing loss, and distinguishes conductive from sensorineural loss. These are conducted with a low frequency tuning fork, usually 512 Hz, and contrast measures of air and bone conducted sound transmission.
Weber test, in which a tuning fork is touched to the midline of the forehead, localizes to the normal ear in people with unilateral sensorineural hearing loss.
Rinne test, which tests air conduction vs. bone conduction is positive, because both bone and air conduction are reduced equally.
less common Bing and Schwabach variants of the Rinne test.
absolute bone conduction (ABC) test.Table 1. A table comparing sensorineural to conductive hearing loss
Other, more complex, tests of auditory function are required to distinguish the different types of hearing loss. Bone conduction thresholds can differentiate sensorineural hearing loss from conductive hearing loss. Other tests, such as oto-acoustic emissions, acoustic stapedial reflexes, speech audiometry and evoked response audiometry are needed to distinguish sensory, neural and auditory processing hearing impairments.
Tympanometry
A tympanogram is the result of a test with a tympanometer. It tests the function of the middle ear and mobility of the eardrum. It can help identify conductive hearing loss due to disease of the middle ear or eardrum from other kinds of hearing loss including SNHL.
Audiometry
An audiogram is the result of a hearing test. The most common type of hearing test is pure tone audiometry (PTA). It charts the thresholds of hearing sensitivity at a selection of standard frequencies between 250 and 8000 Hz. There is also high frequency pure tone audiometry which tests frequencies from 8000-20,000 Hz. PTA can be used to differentiate between conductive hearing loss, sensorineural hearing loss and mixed hearing loss. A hearing loss can be described by its degree i.e. mild, moderate, severe or profound, or by its shape i.e. high frequency or sloping, low frequency or rising, notched, U-shaped or cookie-bite, peaked or flat.
There are also other kinds of audiometry designed to test hearing acuity rather than sensitivity (speech audiometry), or to test
auditory neural pathway transmission (evoked response audiometry).
Magnetic resonance imaging
MRI scans can be used to identify gross structural causes of hearing loss. They are used for congenital hearing loss when changes to the shape of the inner ear or nerve of hearing may help diagnosis of the cause of the hearing loss. They are also useful in cases where a tumour is suspected or to determine the degree of damage in a hearing loss caused by bacterial infection or auto-immune disease. Scanning is of no value in age-related deafness.
Prevention
Presbycusis is the leading cause of SNHL and is progressive and nonpreventable, and at this time, we do not have either somatic or gene therapy to counter heredity-related SNHL. But other causes of acquired SNHL are largely preventable, especially nosocusis type causes. This would involve avoiding environmental noise, and traumatic noise such as rock concerts and nightclubs with loud music. Use of noise attenuation measures like ear plugs is an alternative, as well as learning about the noise levels one is exposed to. Currently, several accurate sound level measurement apps exist. Reducing exposure time can also help manage risk from loud exposures.
Treatment
Treatment modalities fall into three categories: pharmacological, surgical, and management. As SNHL is a physiologic degradation and considered permanent, there are as of this time, no approved or recommended treatments.
There have been significant advances in identification of human deafness genes and elucidation of their cellular mechanisms as well as their physiological function in mice. Nevertheless, pharmacological treatment options are very limited and clinically unproven. Such pharmaceutical treatments as are employed are palliative rather than curative, and addressed to the underlying cause if one can be identified, in order to avert progressive damage.
Profound or total hearing loss may be amenable to management by cochlear implants, which stimulate cochlear nerve endings directly. A cochlear implant is surgical implantation of a battery powered electronic medical device in the inner ear. Unlike hearing aids, which make sounds louder, cochlear implants do the work of damaged parts of the inner ear (cochlea) to provide sound signals to the brain. These consist of both internal implanted electrodes and magnets and external components. The quality of sound is different than natural hearing but may enable the recipient to better recognize speech and environmental sounds.
Because of risk and expense, such surgery is reserved for cases of severe and disabling hearing impairment
Management of sensorineural hearing loss involves employing strategies to support existing hearing such as lip-reading, enhanced communication etc. and amplification using hearing aids. Hearing aids are specifically tuned to the individual hearing loss to give maximum benefit.
Research
Pharmaceuticals
Antioxidant vitamins – Researchers at the University of Michigan report that a combination of high doses of vitamins A, C, and E, and Magnesium, taken one hour before noise exposure and continued as a once-daily treatment for five days, was very effective at preventing permanent noise-induced hearing loss in animals.
Tanakan – a brand name for an international prescription drug extract of Ginkgo biloba. It is classified as a vasodilator. Among its research uses is treatment of sensorineural deafness and tinnitus presumed to be of vascular origin.
Coenzyme Q10 – a substance similar to a vitamin, with antioxidant properties. It is made in the body, but levels fall with age.
Ebselen, a synthetic drug molecule that mimics glutathione peroxidase (GPx), a critical enzyme in the inner ear that protects it from damage caused by loud sounds or noise
Stem cell and gene therapy
Hair cell regeneration using stem cell and gene therapy is years or decades away from being clinically feasible. However, studies are currently underway on the subject, with the first FDA-approved trial beginning in February 2012.
Sudden sensorineural hearing loss
Sudden sensorineural hearing loss (SSHL or SSNHL), commonly known as sudden deafness, occurs as an unexplained, rapid loss of hearing—usually in one ear—either at once or over several days. Nine out of ten people with SSHL lose hearing in only one ear. It should be considered a medical emergency. Delaying diagnosis and treatment may render treatment less effective or ineffective.
Experts estimate that SSHL strikes one person per 100 every year, typically adults in their 40s and 50s. The actual number of new cases of SSHL each year could be much higher because the condition often goes undiagnosed.
Presentation
Many people notice that they have SSHL when they wake up in the morning. Others first notice it when they try to use the deafened ear, such as when they use a phone. Still others notice a loud, alarming "pop" just before their hearing disappears. People with sudden deafness often become dizzy, have ringing in their ears (tinnitus), or both.
Diagnosis
SSHL is diagnosed via pure tone audiometry. If the test shows a loss of at least 30 dB in three adjacent frequencies, the hearing loss is diagnosed as SSHL. For example, a hearing loss of 30 dB would make conversational speech sound more like a whisper.
Causes
Only 10 to 15 percent of the cases diagnosed as SSHL have an identifiable cause. Most cases are classified as idiopathic, also called sudden idiopathic hearing loss (SIHL) and idiopathic sudden sensorineural hearing loss (ISSHL or ISSNHL) The majority of evidence points to some type of inflammation in the inner ear as the most common cause of SSNHL.
Viral – The swelling may be due to a virus. A herpes type virus is believed to be the most common cause of sudden sensorineural hearing loss. The herpes virus lies dormant in our bodies and reactivates for an unknown reason.
Vascular ischemia of the inner ear or cranial nerve VIII (CN8)
Perilymph fistula, usually due to a rupture of the round or oval windows and the leakage of perilymph. The patient will usually also experience vertigo or imbalance. A history of trauma is usually present and changes to hearing or vertigo occur with alteration in intracranial pressure such as with straining; lifting, blowing etc.
Autoimmune – can be due to an autoimmune illness such as systemic lupus erythematosus, granulomatosis with polyangiitis
Treatment
Hearing loss completely recovers in around 35-39% of patients with SSNHL, usually within one to two weeks from onset. Eighty-five percent of those who receive treatment from an otolaryngologist (sometimes called an ENT surgeon) will recover some of their hearing.
vitamins and antioxidants
vasodilators
betahistine (Betaserc), an anti-vertigo drug
hyperbaric oxygen
rheologic agents that reduce blood viscosity (such as hydroxyethyl starch, dextran and pentoxifylline)
anti-inflammatory agents, primarily oral corticosteroids such as prednisone, methylprednisone
Intratympanic administration – Gel formulations are under investigation to provide more consistent drug delivery to the inner ear. Local drug delivery can be accomplished through intratympanic administration, a minimally invasive procedure where the ear drum is anesthetized and a drug is administered into the middle ear. From the middle ear, a drug can diffuse across the round window membrane into the inner ear. Intratympanic administration of steroids may be effective for sudden sensorineural hearing loss for some patients, but high quality clinical data has not been generated. Intratympanic administration of an anti-apoptotic peptide (JNK inhibitor) is currently being evaluated in late-stage clinical development.
Epidemiology
General hearing loss affects close to 10% of the global population. In the United States alone, it is expected that 13.5 million Americans have sensorineural hearing loss. Of those with sensorineural hearing loss, approximately 50% are congenitally related. The other 50% are due to maternal or fetal infections, post-natal infections, viral infections due to rubella or cytomegalovirus, ototoxic drugs, exposure to loud sounds, severe head trauma, and premature births Of the genetically related sensorineural hearing loss cases, 75% are autosomal recessive, 15-20% autosomal dominant, and 1-3% sex-linked. While the specific gene and protein is still unknown, mutations in the connexin 26 gene near the DFNB1 locus of chromosome 13 are thought to account for most of the autosomal recessive genetic-related sensorineural hearing loss At least 8.5 per 1000 children younger than age 18 have sensorineural hearing loss. General hearing loss is proportionally related to age. At least 314 per 1000 people older than age 65 have hearing loss. Several risk factors for sensorineural hearing loss have been studied over the past decade. Osteoporosis, stapedectomy surgery, pneumococcal vaccinations, mobile phone users, and hyperbilirubinemia at birth are among some of the known risk factors.
See also
Conductive hearing loss, hearing loss caused primarily by conditions in the middle ear
Cortical deafness, another kind of nerve deafness
Hearing loss
Inner ear, the innermost portion of the ear containing the sensorineural apparatus of hearing
Otosclerosis, a sometimes associated or predecessor conductive hearing loss condition of the middle ear
Tinnitus, ringing in the ears, a common accompaniment of SNHL
Notes
References
38.Ghazavi H,Kargoshaei A-A,Jamshidi-Koohsari M,"Investigation of vitamin D levels in patients with Sudden Sensory-Neural Hearing Loss and its effect on treatment",American journal of otolaryngology and head and neck medicine and suegery,November 2019
https://doi.org/10.1016/j.amjoto.2019.102327
External links
Hearing Loss Web |
Triphalangeal thumb | Triphalangeal thumb (TPT) is a congenital malformation where the thumb has three phalanges instead of two. The extra phalangeal bone can vary in size from that of a small pebble to a size comparable to the phalanges in non-thumb digits. The true incidence of the condition is unknown, but is estimated at 1:25,000 live births. In about two-thirds of the patients with triphalangeal thumbs, there is a hereditary component. Besides the three phalanges, there can also be other malformations. It was first described by Columbi in 1559.
Signs and symptoms
The triphalangeal thumb has a different appearance than normal thumbs. The appearance can differ widely; the thumb can be a longer thumb, it can be deviated in the radio-ulnar plane (clinodactyly), or thumb strength can be diminished. In the case of a five fingered-hand it has a finger-like appearance, with the position in the plane of the four fingers, thenar muscle deficiency, and additional length. There is often a combination with radial polydactyly.
Complications
Generally, triphalangeal thumbs are non-opposable. In contrast to most people with opposable thumbs, a person suffering from TPT cannot easily place his or her thumb opposite the other four digits of the same hand. The opposable thumbs ability to effortlessly utilize fingers in a "pinch" formation is critical in precision gripping. For the thumb to adequately grip, certain thumb criteria must be met (e.g. suitable position and length, stable joints and good thenar muscle strength). Because triphalangeal thumbs cannot easily oppose and do not possess many of the optimal qualities found in most opposable thumbs, they tend to cause the hand to be less effective in use and, therefore, prove to be more problematic in daily life.
Cause
Malformations of the upper extremities can occur in the third to seventh embryonic week. In some cases the TPT is hereditary. In these cases, there is a mutation on chromosome 7q36. If the TPT is hereditary, it is mostly inherited as an autosomal dominant trait, non-opposable and bilateral. The sporadic cases are mostly opposable and unilateral.
Syndromes
Triphalangeal thumb can occur in syndromes but it can also be isolated. The triphalangeal thumb can appear in combination with other malformations or syndromes.Syndromes include:
Holt-Oram syndrome
Aase syndrome
Diamond-Blackfan anemia
Townes-Brocks syndromeMalformations include:
Radial polydactyly
Syndactyly
Claw-like hand or foot
Diagnosis
Classifications
There are multiple classifications for the triphalangeal thumb. The reason for these different classifications is the heterogeneity in appearance of the TPT.
The classification according to Wood describes the shape of the extra phalanx: delta (Fig. 4), rectangular or full phalanx (Table 1). With the classification made by Buck-Gramcko a surgical treatment can be chosen (Table 1). Buck-Gramcko differentiates between six different shapes of the extra phalanx and associated malformations.Table 1: Classifications of Wood and Buck-Gramcko
Treatment
The goals of surgical treatment are: reducing length of the thumb, creating a good functioning, a stable and non-deviated joint and improving the position of the thumb if necessary. Hereby improving function of the hand and thumb.
In general the surgical treatment is done for improvement of the thumb function. However, an extra advantage of the surgery is the improvement in appearance of the thumb. In the past, surgical treatment of the triphalangeal thumb was not indicated, but now it is generally agreed that operative treatment improves function and appearance. Because an operation was not indicated in the past, there’s still a population with an untreated triphalangeal thumb. The majority of this population doesn’t want surgery, because the daily functioning of the hand is good. The main obstacle for the untreated patients might not be the diminished function, but the appearance of the triphalangeal thumb.
The timing of surgery differs between Wood and Buck-Gramcko. Wood advises operation between the age of six months and two years, while Buck-Gramcko advises to operate for all indications before the age of six years.
For TPT types I and II of the Buck-Gramcko classification, the surgical treatment typically consists of removing the extra phalanx and reconstructing the ulnar collateral ligament and the radial collateral ligament if necessary.
For type III of Buck-Gramcko classification proposable surgical treatments:- smaller trapezoidal phalanx and under six years: removal of the extra phalanx and reconstruction of the ulnar collateral ligament. Lengthening of the radial collateral ligament is only indicated when the clinodactyly is still present after reconstruction of the ulnar collateral ligament.
- trapezoidal phalanx and older than six years: partial removal of the extra phalanx with correction of the angle. Arthrodesis of the distal interphalangeal joint (DIP).For type IV of Buck-Gramcko classification the surgical treatment typically consists of an osteotomy which reduces the middle phalanx and arthrodesis of the DIP. This gives a shortening of 1 to 1.5 cm. In most cases, this technique is combined with a shortening, rotation and palmar abduction osteotomy at metacarpal level to correct for position and length of the thumb. The extensor tendons and the intrinsic muscles are shortened as well.
For type V of the Buck-Gramcko classification the surgical treatment proposably consists of a "pollicization". With a pollicization the malpositioned thumb is repositioned, rotated and shortened, the above-described rotation reduction osteotomy of the first metacarpal can be performed as well.
For type VI of the Buck-Gramcko classification, the surgical treatment typically consists of removing the additional mostly hypoplastic thumb(s). Further procedures of reconstruction of the triphalangeal thumb are performed according to the shape of the extra phalanx as described above.
References
== External links == |
Vitiligo | Vitiligo is a disorder that causes the skin to lose its color. Specific causes are unknown but studies suggest a link to immune system changes.
Signs and symptoms
The only sign of vitiligo is the presence of pale patchy areas of depigmented skin which tend to occur on the extremities. Some people may experience itching before a new patch occurs. The patches are initially small, but often grow and change shape. When skin lesions occur, they are most prominent on the face, hands and wrists. The loss of skin pigmentation is particularly noticeable around body orifices, such as the mouth, eyes, nostrils, genitalia and umbilicus. Some lesions have increased skin pigment around the edges. Those affected by vitiligo who are stigmatized for their condition may experience depression and similar mood disorders.
Causes
Although multiple hypotheses have been suggested as potential triggers that cause vitiligo, studies strongly imply that changes in the immune system are responsible for the condition. Vitiligo has been proposed to be a multifactorial disease with genetic susceptibility and environmental factors both thought to play a role.The TYR gene encodes the protein tyrosinase, which is not a component of the immune system, but is an enzyme of the melanocyte that catalyzes melanin biosynthesis, and a major autoantigen in generalized vitiligo. The National Institutes of Health states that some believe that sunburns can cause or exacerbate the condition, but that this idea is not well-supported by good evidence.
Immune
Variations in genes that are part of the immune system or part of melanocytes have both been associated with vitiligo. It is also thought to be caused by the immune system attacking and destroying the melanocytes of the skin. A genome wide association study found approximately 36 independent susceptibility loci for generalized vitiligo.
Autoimmune associations
Vitiligo is sometimes associated with autoimmune and inflammatory diseases such as Hashimotos thyroiditis, scleroderma, rheumatoid arthritis, type 1 diabetes mellitus, psoriasis, Addisons disease, pernicious anemia, alopecia areata, systemic lupus erythematosus, and celiac disease.Among the inflammatory products of NALP1 are caspase 1 and caspase 7, which activate the inflammatory cytokine interleukin-1β. Interleukin-1β and interleukin-18 are expressed at high levels in people with vitiligo. In one of the mutations, the amino acid leucine in the NALP1 protein was replaced by histidine (Leu155 → His). The original protein and sequence is highly conserved in evolution, and is found in humans, chimpanzee, rhesus monkey, and the bush baby. Addisons disease (typically an autoimmune destruction of the adrenal glands) may also be seen in individuals with vitiligo.
Diagnosis
An ultraviolet light can be used in the early phase of this disease for identification and to determine the effectiveness of treatment. Using a Woods light, skin will change colour (fluoresce) when it is affected by certain bacteria, fungi, and changes to pigmentation of the skin.
Classification
Classification attempts to quantify vitiligo have been analyzed as being somewhat inconsistent, while recent consensus have agreed to a system of segmental vitiligo (SV) and non-segmental vitiligo (NSV). NSV is the most common type of vitiligo.
Non-segmental
In non-segmental vitiligo (NSV), there is usually some form of symmetry in the location of the patches of depigmentation. New patches also appear over time and can be generalized over large portions of the body or localized to a particular area. Extreme cases of vitiligo, to the extent that little pigmented skin remains, are referred to as vitiligo universalis. NSV can come about at any age (unlike segmental vitiligo, which is far more prevalent in teenage years).Classes of non-segmental vitiligo include the following:
Generalized vitiligo: the most common pattern, wide and randomly distributed areas of depigmentation
Universal vitiligo: depigmentation encompasses most of the body
Focal vitiligo: one or a few scattered macules in one area, most common in children
Acrofacial vitiligo: fingers and periorificial areas
Mucosal vitiligo: depigmentation of only the mucous membranes
Segmental
Segmental vitiligo (SV) differs in appearance, cause, and frequency of associated illnesses. Its treatment is different from that of NSV. It tends to affect areas of skin that are associated with dorsal roots from the spinal cord and is most often unilateral. It is much more stable/static in course and its association with autoimmune diseases appears to be weaker than that of generalized vitiligo. SV does not improve with topical therapies or UV light, however surgical treatments such as cellular grafting can be effective.
Differential diagnosis
Chemical leukoderma is a similar condition due to multiple exposures to chemicals. Vitiligo however is a risk factor. Triggers may include inflammatory skin conditions, burns, intralesional steroid injections and abrasions.Other conditions with similar symptoms include the following:
Albinism
Halo nevus
Idiopathic guttate hypomelanosis (white sunspots)
Piebaldism
Pityriasis alba
Postinflammatory hypopigmentation
Primary adrenal insufficiency
Progressive macular hypomelanosis
Tinea versicolor
Tuberculoid leprosy
Treatment
There is no cure for vitiligo but several treatment options are available. The best evidence is for applied steroids and the combination of ultraviolet light in combination with creams. Due to the higher risks of skin cancer, the United Kingdoms National Health Service suggests phototherapy be used only if primary treatments are ineffective. Lesions located on the hands, feet, and joints are the most difficult to repigment; those on the face are easiest to return to the natural skin color as the skin is thinner in nature.
Immune mediators
Topical preparations of immune suppressing medications including glucocorticoids (such as 0.05% clobetasol or 0.10% betamethasone) and calcineurin inhibitors (such as tacrolimus or pimecrolimus) are considered to be first-line vitiligo treatments.In July 2022, ruxolitinib cream (sold under the brand name Opzelura) was approved for medical use in the United States for the treatment of vitiligo.
Phototherapy
Phototherapy is considered a second-line treatment for vitiligo. Exposing the skin to light from UVB lamps is the most common treatment for vitiligo. The treatments can be done at home with an UVB lamp or in a clinic. The exposure time is managed so that the skin does not suffer overexposure. Treatment can take a few weeks if the spots are on the neck and face and if they existed not more than 3 years. If the spots are on the hands and legs and have been there for more than 3 years, it can take a few months. Phototherapy sessions are done 2–3 times a week. Spots on a large area of the body may require full body treatment in a clinic or hospital. UVB broadband and narrowband lamps can be used, but narrowband ultraviolet peaked around 311 nm is the choice. It has been constitutively reported that a combination of UVB phototherapy with other topical treatments improves re-pigmentation. However, some people with vitiligo may not see any changes to skin or re-pigmentation occurring. A serious potential side effect involves the risk of developing skin cancer, the same risk as an overexposure to natural sunlight.Ultraviolet light (UVA) treatments are normally carried out in a hospital clinic. Psoralen and ultraviolet A light (PUVA) treatment involves taking a drug that increases the skins sensitivity to ultraviolet light, then exposing the skin to high doses of UVA light. Treatment is required twice a week for 6–12 months or longer. Because of the high doses of UVA and psoralen, PUVA may cause side effects such as sunburn-type reactions or skin freckling.Narrowband ultraviolet B (NBUVB) phototherapy lacks the side-effects caused by psoralens and is as effective as PUVA. As with PUVA, treatment is carried out twice weekly in a clinic or every day at home, and there is no need to use psoralen. Longer treatment is often recommended, and at least 6 months may be required for effects to phototherapy. NBUVB phototherapy appears better than PUVA therapy with the most effective response on the face and neck.With respect to improved repigmentation: topical calcineurin inhibitors plus phototherapy are better than phototherapy alone, hydrocortisone plus laser light is better than laser light alone, gingko biloba is better than placebo, and oral mini-pulse of prednisolone (OMP) plus NB-UVB is better than OMP alone.
Skin camouflage
In mild cases, vitiligo patches can be hidden with makeup or other cosmetic camouflage solutions. If the affected person is pale-skinned, the patches can be made less visible by avoiding tanning of unaffected skin.
De-pigmenting
In cases of extensive vitiligo the option to de-pigment the unaffected skin with topical drugs like monobenzone, mequinol, or hydroquinone may be considered to render the skin an even color. The removal of all the skin pigment with monobenzone is permanent and vigorous. Sun-safety must be adhered to for life to avoid severe sunburn and melanomas. Depigmentation takes about a year to complete.
History
Descriptions of a disease believed to be vitiligo date back to a passage in the medical text Ebers Papyrus c. 1500 BCE in ancient Egypt. Mentions of whitening of the skin were also present c. 1400 BCE in sacred Indian texts such as Atharvaveda. The Hebrew word "Tzaraath" from the Old Testament book of Leviticus dating to 1280 BCE (or 1312 BCE) described a group of skin diseases associated with white spots, and a subsequent translation to Greek led to continued conflation of those with vitiligo with leprosy and spiritual uncleanliness.Medical sources in the ancient world such as Hippocrates often did not differentiate between vitiligo and leprosy, often grouping these diseases together. The name "vitiligo" was first used by the Roman physician Aulus Cornelius Celsus in his classic medical text De Medicina.The etymology of the term "vitiligo" is believed to be derived from "vitium", meaning "defect" or "blemish".
Society and culture
The change in appearance caused by vitiligo can affect a persons emotional and psychological well-being and may create difficulty in becoming or remaining employed, particularly if vitiligo develops on visible areas of the body, such as the face, hands or arms. Participating in a vitiligo support group may improve social coping skills and emotional resilience. Notable cases include US pop singer Michael Jackson, Canadian fashion model Winnie Harlow, US actor David Dastmalchian and Argentine musician Charly García. French actor Michaël Youn is also affected, as is former French Prime Minister Edouard Philippe.
Research
As of July 2013, afamelanotide is in phase II and III clinical trials for vitiligo and other skin diseases.A medication for rheumatoid arthritis, tofacitinib, has been tested for the treatment of vitiligo.In October 1992, a scientific report was published of successfully transplanting melanocytes to vitiligo-affected areas, effectively re-pigmenting the region. The procedure involved taking a thin layer of pigmented skin from the persons gluteal region. Melanocytes were then separated out to a cellular suspension that was expanded in culture. The area to be treated was then denuded with a dermabrader and the melanocytes graft applied. Between 70 and 85 percent of people with vitiligo experienced nearly complete repigmentation of their skin. The longevity of the repigmentation differed from person to person.
References
External links
Vitiligo at Curlie
Questions and Answers about Vitiligo – US National Institute of Arthritis and Musculoskeletal and Skin Diseases |
Thin basement membrane disease | Thin basement membrane disease is, along with IgA nephropathy, the most common cause of hematuria without other symptoms. The only abnormal finding in this disease is a thinning of the basement membrane of the glomeruli in the kidneys. Its importance lies in the fact that it has a benign prognosis, with patients maintaining a normal kidney function throughout their lives.
Signs and symptoms
Most patients with thin basement membrane disease are incidentally discovered to have microscopic hematuria on urinalysis. The blood pressure, kidney function, and the urinary protein excretion are usually normal. Mild proteinuria (less than 1.5 g/day) and hypertension are seen in a small minority of patients. Frank hematuria and loin pain should prompt a search for another cause, such as kidney stones or loin pain-hematuria syndrome. Also, there are no systemic manifestations, so presence of hearing impairment or visual impairment should prompt a search for hereditary nephritis such as Alport syndrome.
Genetics
The molecular basis for thin basement membrane disease has yet to be elucidated fully; however, defects in type IV collagen have been reported in some families.Some individuals with TBMD are thought to be carriers for genes that cause Alport syndrome.
Diagnosis
Thin basement membrane disease must be differentiated from the other two common causes of glomerular hematuria, IgA nephropathy and Alport syndrome. The history and presentation are helpful in this regard:
In Alport syndrome, there is often a family history of kidney failure, which may be associated with hearing impairment. Also, males tend to be more affected as Alport syndrome is X-linked in most cases.
In IgA nephropathy, episodes of frank hematuria are more common, and a family history is less common.A kidney biopsy is the only way to diagnose thin basement membrane disease. It reveals thinning of the glomerular basement membrane from the normal 300 to 400 nanometers (nm) to 150 to 250 nm. However, a biopsy is rarely done in cases where the patient has isolated microscopic hematuria, normal kidney function, and no proteinuria. The prognosis is excellent in this setting unless the clinical manifestations progress, as occurs in most males and some females with Alport syndrome and many patients with IgA nephropathy.
Treatment
Most patients with thin basement membrane disease need only reassurance. Indeed, this disease was previously referred to as "benign familial hematuria" because of its usually benign course. Angiotensin converting enzyme inhibitors have been suggested to reduce the episodes of hematuria, though controlled studies are lacking. Treating co-existing hypercalciuria and hyperuricosuria will also be helpful in reducing hematuria.The molecular basis for thin basement membrane disease has yet to be elucidated fully; however, defects in the gene encoding the a4 chain of type IV collagen have been reported in some families.
Prognosis
Overall, most people with thin basement membrane disease have an excellent prognosis. Some reports, however, suggest that a minority might develop hypertension.Thin basement membrane disease may co-exist with other kidney diseases, which may in part be explained by the high prevalence of thin basement membrane disease.
References
Further reading
GeneReviews/NCBI/NIH/UW entry on Collagen IV-Related Nephropathies (Alport Syndrome and Thin Basement Membrane Nephropathy)
== External links == |
Dislocated shoulder | A dislocated shoulder is a condition in which the head of the humerus is detached from the shoulder joint. Symptoms include shoulder pain and instability. Complications may include a Bankart lesion, Hill-Sachs lesion, rotator cuff tear, or injury to the axillary nerve.A shoulder dislocation often occurs as a result of a fall onto an outstretched arm or onto the shoulder. Diagnosis is typically based on symptoms and confirmed by X-rays. They are classified as anterior, posterior, inferior, and superior with most being anterior.Treatment is by shoulder reduction which may be accomplished by a number of techniques. These include traction-countertraction, external rotation, scapular manipulation, and the Stimson technique. After reduction X-rays are recommended for verification. The arm may then be placed in a sling for a few weeks. Surgery may be recommended in those with recurrent dislocations.Not all patients require surgery following a shoulder dislocation. There is moderate quality evidence that patients who receive physical therapy after an acute shoulder dislocation will not experience recurrent dislocations. It has been shown that patients who do not receive surgery after a shoulder dislocation do not experience recurrent dislocations within two years of the initial injury.About 1.7% of people have a shoulder dislocation within their lifetime. In the United States this is about 24 per 100,000 people per year. They make up about half of major joint dislocations seen in emergency departments. Males are affected more often than females. Most shoulder dislocations occur as a result of sports injuries.
Signs and symptoms
Significant pain, sometimes felt along the arm past the shoulder.
Sensation that the shoulder is slipping out of the joint during abduction and external rotation.
Shoulder and arm held in external rotation (anterior dislocation), or adduction and internal rotation (posterior dislocation). Resistance of all movement.
Numbness of the arm.
Visibly displaced shoulder. Some dislocations result in the shoulder appearing unusually square.
No palpable bone on the side of the shoulder.
Diagnosis
A diagnosis of shoulder dislocation is often suspected based on the persons history and physical examination. Radiographs are made to confirm the diagnosis. Most dislocations are apparent on radiographs showing incongruence of the glenohumeral joint. Posterior dislocations may be hard to detect on standard AP radiographs, but are more readily detected on other views. After reduction, radiographs are usually repeated to confirm successful reduction and to detect bone damage. After repeated shoulder dislocations, an MRI scan may be used to assess soft tissue damage. In regards to recurrent dislocations, the apprehension test (anterior instability) and sulcus sign (inferior instability) are useful methods for determining predisposition to future dislocation.There are three main types of dislocations: anterior, posterior, and inferior.
Anterior (forward)
In over 95% of shoulder dislocations, the humerus is displaced anteriorly. In most of those, the head of the humerus comes to rest under the coracoid process, referred to as sub-coracoid dislocation. Sub-glenoid, subclavicular, and, very rarely, intrathoracic or retroperitoneal dislocations may also occur.Anterior dislocations are usually caused by a direct blow to, or fall on, an outstretched arm. The person typically holds his/her arm externally rotated and slightly abducted.A Hill–Sachs lesion is an impaction of the head of the humerus left by the glenoid rim during dislocation. Hill-Sachs deformities occur in 35–40% of anterior dislocations. They can be seen on a front-facing X-ray when the arm is in internal rotation. Bankart lesions are disruptions of the glenoid labrum with or without an avulsion of bone fragment.Damage to the axillary artery and axillary nerve (C5, C6) may result. The axillary nerve is injured in 37% making it the most commonly injured structure with this type of injury. Other common, associated, nerve injuries include injury to the suprascapular nerve (29%) and the radial nerve (22%). Axillary nerve damage results in a weakened or paralyzed deltoid muscle and as the deltoid atrophies unilaterally, the normal rounded contour of the shoulder is lost. A person with injury to the axillary nerve will have difficulty in abducting the arm from approximately 15° away from the body. The supraspinatus muscle initiates abduction from a fully adducted position.
Posterior (backward)
Posterior dislocations are uncommon, and are typically due to the muscle contraction from electric shock or seizure. They may be caused by strength imbalance of the rotator cuff muscles. People with dislocated shoulders typically present holding their arm internally rotated and adducted, and exhibiting flattening of the anterior shoulder with a prominent coracoid process.Posterior dislocations may go unrecognized, especially in an elderly person and in people who are in the state of unconscious trauma. An average interval of 1 year was noted between injury and diagnosis in a series of 40 people.
Inferior (downward)
Inferior dislocation is the least likely, occurring in less than 1%. This condition is also called luxatio erecta because the arm appears to be permanently held upward or behind the head. It is caused by a hyper abduction of the arm that forces the humeral head against the acromion. Such injuries have a high complication rate as many vascular, neurological, tendon, and ligament injuries are likely to occur from this mechanism of injury.
Treatment
Prompt medical treatment should be sought for suspected dislocation.
Usually, the shoulder is kept in its current position by use of a splint or sling. A pillow between the arm and torso may provide support and increase comfort. Strong analgesics are needed to allay the pain of a dislocation and the distress associated with it.
Reduction
Shoulder reduction may be accomplished with a number of techniques including traction-countertraction, external rotation, scapular manipulation, Stimson technique, Cunningham technique, or Milch technique. Pain can be managed during the procedures either by procedural sedation and analgesia or injected lidocaine into the shoulder joint. Injecting lidocaine into the joint may be less expensive and faster. If a shoulder cannot be relocated in the emergency room, relocation in the operating room may be required. This situation occurs in about 7% of cases. Stimson procedure is the least painful, widely used shoulder reduction technique. In this procedure a weight is attached to the wrist while the injured arm is hanging off an examination table for between 20 and 30 minutes. The arm is then slowly rotated until the shoulder is relocated. Sedatives are used in Stimson procedure and first time Stimson reduction for acute shoulder dislocation requires wearing arm slings for between 2 and 4 weeks.
Post-reduction
There is no strong evidence of a difference in outcomes when the arm is immobilized in internal versus external rotation following an anterior shoulder dislocation. A 2008 study of 300 people for almost six years found that conventional shoulder immobilisation in a sling offered no benefit.
Surgery
In young adults engaged in highly demanding activities shoulder surgery may be considered. Arthroscopic surgery techniques may be used to repair the glenoidal labrum, capsular ligaments, biceps long head anchor or SLAP lesion or to tighten the shoulder capsule.Arthroscopic stabilization surgery has evolved from the Bankart repair, a time-honored surgical treatment for recurrent anterior instability of the shoulder. However, the failure rate following Bankart repair has been shown to increase markedly in people with significant bone loss from the glenoid (socket). In such cases, improved results have been reported with some form of bone augmentation of the glenoid such as the Latarjet operation.Although posterior dislocation is much less common, instability following it is no less challenging and, again, some form of bone augmentation may be required to control instability. Damaged ligaments, including labral tears, occurring as a result of posterior dislocations may be treated arthroscopically.There remains those situations characterized by multidirectional instability, which have failed to respond satisfactorily to rehabilitation, falling under the AMBRI classification previously noted. This is usually due to an overstretched and redundant capsule which no longer offers stability or support. Traditionally, this has responded well to a reefing procedure known as an open inferior capsular shift. More recently, the procedure has been carried out as an arthroscopic procedure, rather than open surgery, again with comparable results. Most recently, the procedure has been carried out using radio frequency technology to shrink the redundant shoulder capsule (thermal capsular shrinkage); while long-term results of this development are currently unproven, recent studies show thermal capsular shrinkage have higher failure rates with the highest number of cases of instability recurrence and re-operation.
Prognosis
After an anterior shoulder dislocation, the risk of a future dislocation is about 20%. This risk is greater in males than females.
See also
Shoulder problems
References
== External links == |
Neonatal hepatitis | Neonatal hepatitis refers to many forms of liver dysfunction that affects fetuses and neonates. It is most often caused by viruses or metabolic diseases, and many cases are of an unknown cause.
Signs and symptoms
The infant with neonatal hepatitis usually has jaundice that appears at one to two months of age, is not gaining weight and growing normally, and has an enlarged liver and spleen. Infants with this condition are usually jaundiced. Jaundice that is caused by neonatal hepatitis is not the same as physiologic neonatal jaundice. In contrast with physiologic neonatal jaundice, infants with neonatal hepatitis present with dark urine. Infants may also present with delayed growth.
Causes
The causes of neonatal hepatitis are many. Viruses that have been identified include cytomegalovirus, rubella virus, hepatitis A and B viruses, herpes simplex viruses, coxsackievirus, echovirus, and paramyxovirus. Metabolic and immune disorders can also cause neonatal hepatitis. Giant cell transformation throughout the parenchyma is common.
Diagnosis
Differential diagnosis
Conditions that can present similarly include galactosaemia, hereditary fructose intolerance, cystic fibrosis, and biliary atresia.
See also
Neonatal jaundice
References
== External links == |
Amastia | Amastia refers to a rare clinical anomaly in which both internal breast tissue and the visible nipple are absent on one or both sides. It affects both men and women. Amastia can be either isolated (the only medical condition) or comorbid with other syndromes, such as ectodermal dysplasia, syndactaly (Polands syndrome) and lipoatrophic diabetes. This abnormality can be classified into various types, and each could result from different pathologies. Amastia differs from amazia and athelia. Amazia is the absence of one or both mammary glands but the nipples remain present, and athelia is the absence of one or both nipples, but the mammary gland remains.Amastia is presumably due to failure of embryologic (before birth) mammary ridge development or incomplete involution. People with amastia often suffer from ectodermal defects, which include various syndromes such as cleft palate, isolated pectoral muscle and abnormal formation of the arms.Treatment for female amastia particularly includes psychological guidance and breast reconstruction. Because there is no breast tissue, breastfeeding is not possible. If amastia only appears on one side, then it is possible to breastfeed on the other side. Often, people with amastia decide against treatment.
Classification
Amastia can be either iatrogenic or congenital. The congenital amastia are further divided into syndromic type and non-syndromic type respectively.
As the definition suggests, syndromic amastia is often associated with obvious symptoms. The common case is hypoplasia of ectodermal tissue, such as hair and skin defects.
On the other hand, non-syndromic amastia, shows no defects in body parts other than breast. This type of amastia can be further classified into unilateral and bilateral amastia. Unilateral amastia can be defined as amastia involving only one side of breast, while bilateral type refers to amastia on both sides of breast. Unilateral amastia is less common than bilateral amastia. Almost all the non-syndromic amastia patients are female.
Signs and symptoms
Typically, amastia patients have both their nipple and areola missing, and the nipple may be absent on one or both sides of the breasts. Abnormalities are not often associated with the breasts. However, symptoms such as hypertelorism, saddle nose, cleft palate, urologic disorders and dysfunction of muscle, upper and lower limb have been observed. Sometimes several members of a family can be diagnosed as amastia simultaneously, all of them are carriers of mutations in TBX3 gene. This mutation could cause various abnormalities, not only amastia, but also deformation of limb and teeth.Cases of unilateral amastia are uncommon, and they are often associated with hypoplasia of pectoral major muscle and/or the thorax. Bilateral amastia is more common because it is often associated with other different syndromes. Therefore, the symptoms of bilateral amastia are easier to be diagnosed. Various associated syndromes are listed below.
Associated syndromes
Amastia, particularly if it is bilateral, often related to various syndromes, including ectodermal dysplasia and Polands syndrome, which is characterised by anomalies of underlying mesoderm and abnormal pectoral muscle respectively. Other syndromes, such as FIG4 associated Yunis Varon syndrome (MIM 216340), acro-der-mato-ungual-lacrimal-tooth (ADULT) syndrome, TP63 associated limb mammary syndrome (MIM 603543), TBX3 associated ulnar syndrome (MIM 181450) and KCTD1 associated scalp-ear-nipple syndrome (MIM 181270) have also been clinically observed.
Ectodermal dysplasia
Ectodermal dysplasia is commonly associated with syndromic amastia. The symptoms of ectodermal dysplasia can be referred to abnormal development of several ectodermal-derived structure such as hair, teeth, nails and sweat glands. Other symptoms may include the inability to sweat, vision or hearing loss, missing or underdeveloped fingers or toes and maldevelopment of breast tissue. Genetic mutations may cause ectodermal dysplasia, and these genes can pass from parents to children. The most common case is the mutation of EDA1 gene which is in X chromosome, and this mutation results in X-linked form hypohidrotic ectodermal dysplasia (XLHED). There is strong association between amastia and XLHED. Over 30% male patients with XLHED have absent nipples. 79% female carriers decrease the ability of breastfeeding. This suggests people with amastia should have a comprehensive skin test to exclude this syndrome.
Polands syndrome
Polands syndrome is a genetic disorder associated with abnormal breast development. The prevalence rate of this syndrome is approximately 1 in 20000 to 30000. Both chest wall and upper limb lost normal function, and this syndrome usually occurs unilaterally. Mild and partial forms of Polands syndrome are common, which often been undiagnosed because the clinical feature is only breast asymmetry and a horizontal anterior axillary fold, without severe symptoms. Other abnormalities include deformation of ribs, absence of pectoralis muscle, hypoplasia or abnormalities of breast and subcutaneous tissue. Patients may also have webbed fingers on one hand, short bones in the forearm or sparse underarm hair.
Al Awadi/Raas-Rothschild syndrome
Al Awadi/Raas-Rothschild syndrome is a rare genetic disorder. Symptoms are often associated with absence or maldevelopment of skeletal part of limbs.
Scalp-ear-nipple syndrome
As the name suggests, Scalp-ear-nipple syndrome is characterized by congenital absence of skin, abnormalities of scalp, malformation of ear structures, and undeveloped nipples.
Mechanism
Mammary glands are arranged in breasts of the primates to produce milk for feeding offspring. They are enlarged and modified sweat glands. In the embryological development, mammary glands firstly appear after six weeks of pregnancy in the form of ectodermal ridges. The ectodermal ridge grows thicker and compresses to form mesoderm. As the proliferation persists, mesodermal layer continues to form clusters. The clusters grow and become lobules. At the same time, the clusters also form a pit, which protrudes to generate the nipples. Impairment in some of these processes may cause aplasia of the breast tissue, which may result in amastia.For example, in normal condition, mammary ridge (milk line) would extend from the bilateral axillary tail to the inguinal region. If this extension does not occur in normal way, the breast would not develop successfully.Amastia may also be caused by the inability of producing parathyroid hormone related protein. The absence of this protein will disrupt the normal development of mammary gland. Therefore, when amastia patients receive medical ultrasound examination, asymmetry or disproportioned mammary tissue may be found.
Causes
Unilateral amastia is usually caused by Polands syndrome, which is characterized by one side absence of breast. The absence or dysfunction of pectoralis muscle and ribs are common case. It can also be part of other syndromes as described in the previous contents.
Other causes may include intra-uterine exposure to teratogenic drugs such as dehydroipiandrosterone and methiamozole/carbimazole treatment during first trimester.For bilateral amastia, the cause has not been well understood so far. It may be related to gene mutation since often patients with bilateral amastia are diagnosed as autosomal dominant and recessive inheritance. Decreasing blood flow in the subclavian artery may also be a cause of amastia.Amastia can also be caused by injuries. These injuries may happen when patients receive surgery, such as thoracotomy, chest tube placement, or when they are treated by radiotherapy. Improper biopsy or severe burns of breast tissue may also result in amastia.
Genetics
Congenital amastia can be associated with both autosomal dominant and recessive inheritance. However, in clinical research, autosomal recessive heritage amastia is uncommon.Mutation of genes may disrupt the normal process and results in abnormity of breast. The protein tyrosine receptor type F gene (PTPRF) is particularly important in nipple-areola region development. PTPRF encodes protein phosphatase which can localize at adherent junction. This phosphatase may also regulate epithelial cell to enable cell- cell interaction. PTPRF is also responsible for growth factor signalling and Wnt pathway. Homozygous frameshift mutation in PTPRF may cause amastia, which suggests the causative relationship between PTPRF defect and syndromic amastia.
Management
Since bilateral and unilateral amastia may be attributed to different pathologies, appropriate managements should be adopted accordingly. Bilateral amastia can occur in isolation or associated with other disorders. This case is less understood and difficult to treat. On the other hand, Polands syndrome is the most common cause of unilateral amastia. Managements such as muscle/breast reconstruction and nipple areola relocation should be provided to these patients.
Breast reconstruction
Surgical treatment for breast defects such as mastectomy is also applicable to treat patients with amastia. Tissue expansion is the most common technique and can be done by using either autologous or prosthetic tissue. For autologous reconstruction, different tissues may be chosen according to patients’ physical condition or their preferences. Prosthetic reconstruction may follow the same principles. Flap reconstruction is another method to rebuild the breast surgically. There are various kinds of flaps to choose depending on different situation.
Nipple areola relocation
Amastia is often associated with Polands syndrome, which requires appropriate reconstructive procedure to stabilize chest wall, transfer dynamic muscle and reposition nipple areola region. The treatment of nipple areola relocation provides space for secondary breast enlargement. In this treatment, the tissue expander can be inserted either beforehand or delayed. It can be placed in different parts of body depending on how many overlying soft tissues the patient has. In order to guide the dissection and make sure the correct location of these tissues, marking of the inframammary crease is required before operation.
See also
Amazia
Athelia
Micromastia
References
== External links == |
Pseudoexfoliation syndrome | Pseudoexfoliation syndrome, often abbreviated as PEX and sometimes as PES or PXS, is an aging-related systemic disease manifesting itself primarily in the eyes which is characterized by the accumulation of microscopic granular amyloid-like protein fibers. Its cause is unknown, although there is speculation that there may be a genetic basis. It is more prevalent in women than men, and in persons past the age of seventy. Its prevalence in different human populations varies; for example, it is prevalent in Scandinavia. The buildup of protein clumps can block normal drainage of the eye fluid called the aqueous humor and can cause, in turn, a buildup of pressure leading to glaucoma and loss of vision (pseudoexfoliation glaucoma, exfoliation glaucoma). As worldwide populations become older because of shifts in demography, PEX may become a matter of greater concern.
Signs and symptoms
Patients may have no specific symptoms. In some cases, patients may complain of lessened visual acuity or changes in their perceived visual field, and such changes may be secondary to or different from symptoms normally associated with cataracts or glaucoma.PEX is characterized by tiny microscopic white or grey granular flakes which are clumps of proteins within the eye which look somewhat like dandruff when seen through a microscope and which are released by cells. The abnormal flakes, sometimes compared to amyloid-like material, are visible during an examination of the lens of an eye by an ophthalmologist or optometrist, which is the usual diagnosis. The white fluffy material is seen in many tissues both ocular and extraocular, such as in the anterior chamber structures, trabecular meshwork, central disc, zonular fibres, anterior hyaloid membrane, pupillary and anterior iris, trabecula, and occasionally the cornea. The flakes are widespread. One report suggested that the granular flakes were from abnormalities of the basement membrane in epithelial cells, and that they were distributed widely throughout the body and not just within structures of the eye. There is some research suggesting that the material may be produced in the iris pigment epithelium, ciliary epithelium, or the peripheral anterior lens epithelium. A similar report suggests that the proteins come from the lens, iris, and other parts of the eye. A report in 2010 found indications of an abnormal ocular surface in PEX patients, discovered by an eye staining method known as rose bengal.
PEX can become problematic when the flakes become enmeshed in a "spongy area" known as the trabecular meshwork and block its normal functioning, and may interact with degenerative changes in the Schlemms canal and the juxtacanalicular area. The blockage leads to greater-than-normal elevated intraocular pressure which, in turn, can damage the optic nerve. The eye produces a clear fluid called the aqueous humor which subsequently drains such that there is a constant level of safe pressure within the eye, but glaucoma can result if this normal outflow of fluid is blocked. Glaucoma is an umbrella term indicating ailments which damage the neural cable from the eye to the brain called the optic nerve, and which can lead to a loss of vision. In most cases of glaucoma, typically called primary open-angle glaucoma, the outflow does not happen normally but doctors can not see what is causing the blockage; with PEX, however, the flakes are believed to be a cause of the blockage. PEX flakes by themselves do not directly cause glaucoma, but can cause glaucoma indirectly by blocking the outflow of aqueous humor, which leads to higher intraocular pressure, and this can cause glaucoma. PEX has been known to cause a weakening of structures within the eye which help hold the eyes lens in place, called lens zonules.
Causes
The cause of pseudoexfoliation glaucoma is generally unknown.PEX is generally believed to be a systemic disorder, possibly of the basement membrane of the eye. Researchers have noticed deposits of PEX material in various parts of the body, including in the skin, heart, lungs, liver, kidneys, and elsewhere. Nevertheless, what is puzzling is that PEX tends to happen in only one eye first, which scientists call unilaterality, and in some cases, gradually affects the other eye, which is termed bilaterality. According to this reasoning, if PEX were a systemic disorder, then both eyes should be affected at the same time, but they are not. There are contrasting reports about the extent and speed with which PEX moves from one eye to both eyes. According to one report, PEX develops in the second eye in 40% of cases. A contrasting report was that PEX can be found in both eyes in almost all situations if an electron microscope is used to examine the second eye, or if a biopsy of the conjunctiva was done, but that the extent of PEX is the second eye was much less than the first one. A different report suggested that two thirds of PEX patients had flakes in only one eye. In one long-term study, patients with PEX in only one eye were studied, and it was found that over time, 13% progressed to having both eyes affected by PEX. Scientists believe that elevated levels of plasma homocysteine are a risk factor for cardiovascular disease, and two studies have found higher levels of plasma homocysteine in PEX patients, or elevated homocysteine concentrations in tear fluids produced by the eye.There is speculation that PEX may be caused by oxidative damage and the presence of free radicals, although the exact nature of how this might happen is still under study. Studies of PEX patients have found a decrease in the concentrations of ascorbic acid, increase in concentrations of malondialdehyde, and an increase in concentrations of 8-iso-prostaglandinF2a.There is speculation that genetics may play a role in PEX. A predisposition to develop PEX later in life may be an inherited characteristic, according to one account. One report suggested the genetic component was "strong". One study performed in Iceland and Sweden has associated PEX with polymorphisms in gene LOXL1. A report suggested that a specific gene named LOXL1 which was a member of the family of enzymes which play a role in the linking of collagen and elastin inside cells. LOXL1 was responsible for "all the heritability" of PEX, according to one source. Two distinct mutations in which a single nucleotide was changed, or called a single nucleotide polymorphism or SNP, was discovered in Scandinavian populations and confirmed in other populations, and may be involved with the onset of PEX.
The gene is called LOXL1 ... Because pseudoexfoliation syndrome is associated with abnormalities of the extracellular matrix and the basement membrane, this gene could reasonably play a role in the pathophysiology of the condition.
Researchers are investigating whether factors such as exposure to ultraviolet light, living in northern latitudes, or altitude influence the onset of PEX. One report suggested that climate was not a factor related to PEX. Another report suggested a possible link to sunlight as well as a possible autoimmune response, or possibly a virus.
Diagnosis
PEX is usually diagnosed by an eye doctor who examines the eye using a microscope. The method is termed slit lamp examination and it is done with an "85% sensitivity rate and a 100% specificity rate." Since the symptom of increased pressure within the eye is generally painless until the condition becomes rather advanced, it is possible for people affected by glaucoma to be in danger yet not be aware of it. As a result, it is recommended that persons have regular eye examinations to have their levels of intraocular pressure measured, so that treatments can be prescribed before there is any serious damage to the optic nerve and subsequent loss of vision.
Treatment
While PEX itself is untreatable as of 2011, it is possible for doctors to minimize the damage to vision and to the optic nerves by the same medical techniques used to prevent glaucoma.
Eyedrops. This is usually the first treatment method. Eyedrops can help reduce intraocular pressure within the eye. The medications within the eyedrops can include beta blockers (such as levobunolol or timolol) which slow the production of the aqueous humor. And other medications can increase its outflow, such as prostaglandin analogues (e.g. latanoprost). And these medicines can be used in various combinations. In most cases of glaucoma, eyedrops alone will suffice to solve the problem.
Laser surgery. A further treatment is a type of laser therapy known as trabeculoplasty in which a high-energy laser beam is pointed at the trabecular meshwork to cause it to "remodel and open" and improve the outflows of the aqueous humor. These can be done as an outpatient procedure and take less than twenty minutes. One report suggests this procedure is usually effective.
Eye surgery. Surgery is the treatment method of last resort if the other methods have not worked. It is usually effective at preventing glaucoma. Eye surgery on PEX patients can be subject to medical complications if the fibers which hold the lens have become weakened because of a buildup from the flakes; if the lens-holding fibers have weakened, then the lens may become loose, and complications from eye surgery may result. In such cases, it is recommended that surgeons act quickly to repair the phacodonesis before the lenses have dropped. A surgeon cuts an opening in the white portion of the eye known as the sclera, and removes a tiny area of the trabecular meshwork which enables the aqueous humor to discharge. This lowers the internal pressure within the eye and lessens the chance of future damage to the optic nerve. Cases with pseudophacodonesis and dislocated IOL have been increasing in number, according to one report. In cataract surgery, complications resulting from PEX include capsular rupture and vitreous loss.
Drug therapy. There are speculations that if genetics plays a role in PEX, and if the specific genes involved can be identified, that possibly drugs can be developed to counteract these mutations or their effects. But such drugs have not been developed as of 2011.Patients should continue to have regular eye examinations so that physicians can monitor pressure levels and check whether medicines are working.
Epidemiology
Scientists are studying different populations and relationships to try to learn more about the disease. They have found associations with different groups but it is not yet clear what the underlying factors are and how they affect different peoples around the world.
Glaucoma patients. While PEX and glaucoma are believed to be related, there are cases of persons with PEX without glaucoma, and persons with glaucoma without PEX. Generally, a person with PEX is considered as having a risk of developing glaucoma, and vice versa. One study suggested that the PEX was present in 12% of glaucoma patients. Another found that PEX was present in 6% of an "open-angle glaucoma" group. Pseudoexfoliation syndrome is considered to be the most common of identifiable causes of glaucoma. If PEX is diagnosed without glaucoma, there is a high risk of a patient subsequently developing glaucoma.
Country and region. Prevalence of PEX varies by geography. In Europe, differing levels of PEX were found; 5% in England, 6% in Norway, 4% in Germany, 1% in Greece, and 6% in France. One contrary report suggested that levels of PEX were higher among Greek people. One study of a county in Minnesota found that the prevalence of PEX was 25.9 cases per 100,000 people. It is reportedly high in northern European countries such as Norway, Sweden and Finland, as well as among the Sami people of northern Europe, and high among Arabic populations, but relatively rare among African Americans and Eskimos. In southern Africa, prevalence was found to be 19% of patients in a glaucoma clinic attending to persons of the Bantu tribes.
Race. It varies considerably according to race.
Gender. It affects women more than men. One report was that women were three times more likely than men to develop PEX.
Age. Older persons are more likely to develop PEX. And persons younger than 50 are highly unlikely to have PEX. A study in Norway found that the prevalence of PEX of persons aged 50–59 was 0.4% while it was 7.9% for persons aged 80–89 years. If a person is going to develop PEX, the average age in which this will happen is between 69 and 75 years, according to the Norwegian study. A second corroborating report suggested that it happens primarily to people 70 and older. While older people are more likely to develop PEX, it is not seen as a "normal" part of aging.
Other diseases. Sometimes PEX is associated with the development of medical problems other than merely glaucoma. There are conflicting reports about whether PEX is associated with problems of the heart or brain; one study suggested no correlations while other studies found statistical links with Alzheimers disease, senile dementia, cerebral atrophy, chronic cerebral ischemia, stroke, transient ischemic attacks, heart disease, and hearing loss.
History
Pseudoexfoliation syndrome (PEX) was first described by an ophthalmologist from Finland named John G. Lindberg in 1917. He built his own slit lamp to study the condition and reported "grey flakes on the lens capsule", as well as glaucoma in 50% of the eyes, and an "increasing prevalence of the condition with age." Several decades later, an ocular pathologist named Georgiana Dvorak-Theobald suggested the term pseudoexfoliation to distinguish it from a similar ailment which sometimes affected glassblowers called true exfoliation syndrome that was described by Anton Elschnig in 1922. The latter ailment is caused by heat or "infrared-related changes in the anterior lens capsule" and is characterized by "lamellar delamination of the lens capsule." Sometimes the two terms "pseudoexfoliation" and "true exfoliation" are used interchangeably but the more precise usage is to treat each case separately.
Research
Scientists and doctors are actively exploring how PEX happens, its causes, and how it might be prevented or mitigated. Research activity to explore what causes glaucoma has been characterized as "intense". There has been research into the genetic basis of PEX. One researcher speculated about a possible "two-hit hypothesis" in which a single mutation in the LOXL1 gene puts people at risk for PEX, but that a second still-to-be-found mutation has some effect on the proteins, possibly affecting bonds between chemicals, such that the proteins are more likely to clump together and disrupt the outflow of aqueous humor.
Alternative names
Exfoliation glaucoma; XFG
Pseudoexfoliation glaucoma
Pseudoexfoliation of the lens
Exfoliation syndrome; XFS
References
== External links == |
Complement deficiency | Complement deficiency is an immunodeficiency of absent or suboptimal functioning of one of the complement system proteins. Because of redundancies in the immune system, many complement disorders are never diagnosed. Some studies estimate that less than 10% are identified. Hypocomplementemia may be used more generally to refer to decreased complement levels, while secondary complement disorder means decreased complement levels that are not directly due to a genetic cause but secondary to another medical condition.
Signs and symptoms
The following symptoms (signs) are consistent with complement deficiency in general:
Complications
Vaccinations for encapsulated organisms (e.g., Neisseria meningitidis and Streptococcus pneumoniae) is crucial for preventing infections in complement deficiencies. Among the possible complications are the following:
Deficiencies of the terminal complement components increases susceptibility to infections by Neisseria.
Causes
The cause of complement deficiency is genetics (though cases of an acquired nature do exist post infection). The majority of complement deficiencies are inherited as autosomal recessive conditions, while properdin deficiency occurs through X-linked inheritance. MBL deficiency can be inherited by either manner.
Inherited
Properdin deficiency is an X-linked disorder that also causes susceptibility to Neisseria infections.
C1-inhibitor deficiency or hereditary angioedema will have low C4 with normal C1 levels.
Acquired
Acquired hypocomplementemia may occur in the setting of bone infections (osteomyelitis), infection of the lining of the heart (endocarditis), and cryoglobulinemia. Systemic lupus erythematosus is associated with low C3 and C4. Membranoproliferative glomerulonephritis usually has low C3.
Mechanism
The mechanism of complement deficiency consists of:
C2: In regard to C2 deficiency, about 5 different mutations in the C2 gene are responsible. In turn, immune function decreases and infection opportunities increase. One of the most common mutations deletes 28 DNA nucleotides from the C2 gene. Therefore, no C2 protein which can help make C3-convertase is produced. Ultimately, this delays/decreases immune response.
C3: In terms of deficiency of C3, it has been found that 17 mutations in the C3 gene cause problems with C3. This rare condition mutates or prevents C3 protein from forming, lowering the immune systems ability to protect.
C4: C4 deficiency is highly associated with systemic lupus erythematosus. Aβ42, a protein involved in Alzheimers disease, can cause activation of C4 (even in plasma deficient of C1q). At least one study indicates that the genetic variation of C4 plays a role in schizophrenia.
Diagnosis
The diagnostic tests used to diagnose a complement deficiency include:
CH50 measurement
Immunochemical methods/test
C3 deficiency screening
Mannose-binding lectin (lab study)
Plasma levels/regulatory proteins (lab study)
Types
Disorders of the proteins that act to inhibit the complement system (such as C1-inhibitor) can lead to an overactive response, causing conditions such as hereditary angioedema.
Disorders of the proteins that act to activate the complement system (such as C3) can lead to an underactive response, causing greater susceptibility to infections.
Treatment
In terms of management for complement deficiency, immunosuppressive therapy should be used depending on the disease presented. A C1-INH concentrate can be used for angio-oedema (C1-INH deficiency).Pneumococcus and Haemophilus infections can be prevented via immunization. Epsilon-aminocaproic acid could be used to treat hereditary C1-INH deficiency, though the possible side effect of intravascular thrombosis should be weighed.
Epidemiology
C2 deficiency has a prevalence of 1 in about 20,000 people in Western countries.
See also
Paroxysmal nocturnal hemoglobinuria
References
Further reading
Botto, Marina (1 January 2001). "Links between complement deficiency and apoptosis". Arthritis Research & Therapy. 3 (4): 207–210. doi:10.1186/ar301. ISSN 1478-6362. PMC 128896. PMID 11438036.
Aghamohammadi, Asghar; Rezaei, Nima (2012). Clinical cases in primary immunodeficiency diseases a problem-solving approach. Berlin: Springer. ISBN 9783642317859. Retrieved 21 September 2016.
== External links == |
Gustatory hyperhidrosis | Gustatory hyperhidrosis is excessive sweating classified under focal hyperhidrosis, that is, it is restricted to certain regions of the body. Affected people regularly experience this on the forehead (scalp), upper lip, perioral region, or sternum a few moments after eating spicy foods, tomato sauce, chocolate, coffee, tea, or hot soups.A common cause is trauma or damage to the nerve that passes through the parotid gland, which can be due to surgery of the parotid gland (parotidectomy). This type of sweating is known as Freys syndrome. Gustatory hyperhidrosis has been observed in diabetics with autonomic neuropathy, and a variant of this disorder has been reported following surgical sympathectomy.Around 10% of affected people require treatment. One of the more effective treatments is oral or topically applied glycopyrrolate.
== References == |
Vasodilatory shock | Vasodilatory shock, vasogenic shock, or vasoplegic shock is a medical emergency belonging to shock along with cardiogenic shock, septic shock, allergen-induced shock and hypovolemic shock. When the blood vessels suddenly relax, it results in vasodilation. In vasodilatory shock, the blood vessels are too relaxed leading to extreme vasodilation and blood pressure drops and blood flow becomes very low. Without enough blood pressure, blood and oxygen wont be pushed to reach the bodys organs. If vasodilatory shock lasts more than a few minutes, the lack of oxygen starts to damage the bodys organs. Vasodilatory shock like other types of shock should be treated quickly, otherwise it can cause permanent organ damage or death as a result of multiple organ dysfunction.Treatment typically involves uses of vasopressor, inotropes, fluid boluses, and introduction of resuscitation. In case vasodilatory shock fails to respond to high doses of vasopressors (defined as ≥ 0.5 mg/kg/min norepinephrine-equivalent dose), meaning its vasopressor-resistant and advances to being called refractory vasodilatory shock or simply refractory shock. Adjunctive therapies include angiotensin II, hydrocortisone, thiamine, catecholamines, ascorbic acid and combinations of thereof.
Signs and symptoms
Confusion or lack of alertness
Loss of consciousness
A sudden and ongoing rapid heartbeat
Sweating
Pale skin
A weak pulse
Rapid breathing
Decreased or no urine output
Cool hands and feet
Cause
A bacterial infection in the bloodstream, a severe allergic reaction (anaphylaxis), systemic inflammatory response syndrome, or damage to the nervous system (brain and nerves) may cause vasodilatory shock. Besides, nearly all kinds of distributive shock such as septic shock, neurogenic shock, anaphylactic shock, drug and toxin-induced shock, endocrine shock can turn out into refractory vasodilatory shock when the original shock becomes more severe.The most common cause of vasodilatory shock is sepsis. Except sepsis, other causes comprise severe acute pancreatitis, post cardiopulmonary bypass vasoplegia and other triggers for a systemic inflammatory response syndrome. Low serum calcium values might take a role in vasodilatory shock.
Pathophysiology
In the cases of cardiogenic shock resulting from heart failure or acute hemorrhagic shock caused by a large volume of blood loss, the body constricts peripheral vessels to reverse the low arterial pressure that causes inadequate tissue perfusion. With vasodilatory shock, it is difficult for the peripheral vascular smooth muscle to constrict. In refractory vasodilatory shock, peripheral vascular smooth muscle responds poorly to therapy with vasopressor drugs.Vasopressin deficiency may play an important role in vasodilatory shock. In refractory vasodilatory shock, the patient has both vasopressin secretion deficit and an advanced resistance to vasopressin-induced blood-pressure changes. Some have hypothesized that patients with vasopressin deficiency, including a decrease in baroreceptor stimulation, appear to have impaired autonomic reflexes. Tone may be inhibited by atrial stretch receptors and vasopressin release may be inhibited by nitric oxide or high circulating levels of norepinephrine.Vasodilatory shock is often involved with the dysfunction of physiologic compensatory mechanisms such as the sympathetic nervous system, vasopressin arginine system and renin-angiotensin aldosterone system.
Diagnosis
The definition of refractory shock or vasodilatory shock varies. In 2018, the American College of Chest Physician stated that it is presents if there is an inadequate response to high-dose vasopressor therapy defined as ≥ 0.5 mg/kg/min norepinephrine-equivalent dose.
Management
Reversing the underlying causes of vasodilatory shock, stabilizing hemodynamic, preventing renal, myocardial, and other organs from injuries due to hypoperfusion and hypoxia, and taking necessary measures to safeguard against complications including venous thromboembolism are served as the top priorities during the treatment.The initial treatment aiming at restoring effective blood pressure in patients that have refractory shock typically starts with introducing norepinephrine and dopamine. Vasopressin comes as the second-line agent.However, high-dose therapy is linked to excessive coronary, splanchnic vasoconstriction, and hypercoagulation. Excessive vasoconstriction can cause cardiac output reduction or even fatal heart complication particularly in those with weak myocardial function.In those whose vasodilatory shock is caused by hypocalcemic cardiomyopathy in the context of dilated cardiomyopathy with documented both reduced heart ejection fraction and contractile performance, the uses of calcium and active vitamin D or recombinant human parathyroid hormone treatment are viable since there were many successful cases reported while given the physiological role of calcium on muscle contraction.A successful treatment requires leveraging the respective unique contributions of a multi-disciplinary team not only critical care doctors and often, infectious disease specialists but also respiratory therapy, nursing, pharmacy and others in collaboration.
Epidemiology
Observational studies suggest that, about 6% to 7% of critically ill people may end up developing refractory shock.
Prognosis
Early recognition and rapid treatment initiation are crucial to saving life. If vasodilatory shock being left untreated, even brief hypotensive periods can result in myocardial and renal injury. It can also increased mortality in the critically ill. Refractory shock has an all-cause mortality rate greater than 50% within a month.
== References == |
Epithelioid hemangioendothelioma | Epithelioid hemangioendothelioma (eHAE) is a rare tumor, first characterized by Sharon Weiss and Franz Enzinger in 1982 that both clinically and histologically is intermediate between angiosarcoma and hemangioma. However, a distinct, disease-defining genetic alteration recently described for EHE indicates that it is an entirely separate entity from both angiosarcoma and hemangioma.
EHE is a soft tissue sarcoma and is generally considered a vascular cancer insofar as the ‘lesional’ cells have surface markers typical of endothelial cells (cells lining the interior of blood vessels). EHE was originally described as occurring most commonly in the veins of the extremities (arms and legs) and two organs, the liver and lungs. It has since been described in organs throughout the body. In addition to liver and lungs, bones and skin have been the most frequent organs.
Before the initial description of Weiss, the tumor had been reported under a variety of other names, including histiocytoid hemangioendothelioma, intravascular bronchoalveolar tumor (in the lung), and sclerosing cholangiocarcinoma. In the lung and liver, common sites of metastatic tumor, it was most likely to be confused with carcinoma a far more common type of tumor.
EHE typically occurs in the 20 – 40 age range although the overall age range involved is much broader and a modest predilection for females over males. It often has an indolent course, and many affected people have survived for decades with multi-organ disease.[1]:601 The extent and number of organs involved apparently has little effect on longevity.
Genetics
The cytogenetics of EHE gave some of the first clues of an underlying genetic alteration. A balanced, reciprocal translocation t(1;3)(p36.3;q25) in EHE tumor cells was first described by Mendlick et al. in 2001 (Mendlick MR, Nelson M, Pickering D, Johansson SL, Seemayer TA, Neff JR, Vergara G, Rosenthal H, Bridge JA (2001). "Translocation t(1;3)(p36.3;q25) is a nonrandom aberration in epithelioid hemangioendothelioma". Am. J. Surg. Pathol. 25 (5): 684–7. doi:10.1097/00000478-200105000-00019. PMID 11342784.{{cite journal}}: CS1 maint: multiple names: authors list (link)). This led to the landmark paper by Tanas et al. in 2011(Tanas MR, Sboner A, Oliveira AM, Erickson-Johnson MR, Hespelt J, Hanwright PJ, Flanagan J, Luo Y, Fenwick K, Natrajan R, Mitsopoulos C, Zvelebil M, Hoch BL, Weiss SW, Debiec-Rychter M, Sciot R, West RB, Lazar AJ, Ashworth A, Reis-Filho JS, Lord CJ, Gerstein MB, Rubin MA, Rubin BP (2011). "Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma". Sci Transl Med. 3 (98): 98ra82. doi:10.1126/scitranslmed.3002409. PMID 21885404.{{cite journal}}: CS1 maint: multiple names: authors list (link)) describing the specific genes involved in the translocation associated with the most common forms of EHE. This alteration results in the fusion of genes coding for two transcription co-activators (transcriptional regulators): TAZ (transcriptional co-activator with PDZ-binding motif) also known as WWTR1 (WW domain-containing transcription regulator protein 1) and CAMTA1 (calmodulin-binding transcription activator 1). The names in parenthesis are not relevant to casual (or even science) readers but are included to help distinguish them from other genes. For instance, another gene with an entirely different function, Tafazzin, is unrelated to EHE but confusingly, also referred to as TAZ. In any case, the EHE translocation results in an abnormal ‘fusion gene’ that expresses an abnormal mRNA resulting in synthesis of a fusion protein variant of TAZ that is always turned on. This form of TAZ always resides in the nucleus and therefore is constitutively active. It binds and turns on a very important member of the TEAD family of transcription factors and this causes cells to proliferate. It is this production of the TAZ-TEAD transcriptome that causes the affected endothelial cells to grow into tumors. In normal cells, TAZ is considered a major negative transducer of the Hippo pathway, a signaling system that regulates organ size by causing cells to stop growing when they touch each other (contact inhibition). Many upstream inputs regulate the Hippo signal which normally functions to turn off or de-activate TAZ by keeping it in the cytoplasm and out of the nucleus. In EHE cells, the abnormal fusion TAZ is ‘immune’ to this input and just stays in the nucleus, and continuing to stimulate cell growth.
Note that about 10% of EHE patients harbor a different translocation. This one similarly results in the constitutive activation of YAP, an orthologue of TAZ (i.e., a gene that has sequence and function that are very similar to TAZ). This also results in persistent, unregulated growth of the affected cells and therefore causes EHE-type tumors.
Treatment
•Sirolimus: Also known as rapamycin, this oral medication suppresses the immune system and slows the growth of abnormal lymphatic vessels that form the tumor. This can help shrink EHE tumors and improve symptoms, including pain
•Tyrosine kinase inhibitors: These drugs, designed as targeted therapies for cancers, have shown short-term success with EHE. Examples include sorafenib, sunitinib and pazopanib.
•Vincristine: This chemotherapy drug targets all dividing cells within the body and is therefore used to treat many cancers. It is also used for aggressive benign vascular tumors.
•Interferon: The body produces interferon to combat infections or control inflammation. It has been formulated into a medication that targets blood vessel growth.
•Multi-agent chemotherapy: EHE tumors that grow rapidly, spread to other tissues or do not respond to other medications may require more aggressive drug therapy. However, this combination of medications is rarely needed in children and young adults with EHE.
•Others like surgery can be done as treatment for the virus during its most severe.
Prognosis
Although Epithelioid Hemangioendothelioma typically presents as a low-grade tumor, occasionally, eHAE presents as high grade and more aggressive. eHAE presenting in the pleura, for example, is associated with a much more aggressive and hard to treat course. There is no standard chemotherapy treatment for eHAE at current but success with drugs such as Interferon, Paclitaxel, MAID combination chemotherapy, Thalidomide and Doxorubicin have been reported.
Epidemiology
It is so rare that only 0.01 percent of the cancer population has it and it affects about 1 person in every 1,000,000 worldwide. Around 20 cases are diagnosed in America every year – the cause is unknown. It is unresponsive to any known strain of chemotherapy, making treatment very difficult.
Society
There is a Facebook site set up for people with EHE.
There is also a Registry for patients to enter their medical history.
CRAVAT Center for Research and Analysis of VAscular Tumors is a website for the EHE community. The EHE Rare Cancer Foundation Australia was established in 2015 by Australians with Epithelioid Hemangioendothelioma (EHE). The core objective of the EHE Rare Cancer Foundation Australia is to proactively fundraise in order to support research into this rare cancer in the hope that a maintenance program or cure can be found.In 2003 photographer and actress Kris Carr was diagnosed with a stable and low grade version of eHAE. Carr has become a success as a Wellness Warrior advocating a vegan lifestyle as a way to avoid and stabilize disease.
See also
List of cutaneous conditions
Skin lesion
References
== External links == |
Acute proliferative glomerulonephritis | Acute proliferative glomerulonephritis is a disorder of the small blood vessels of the kidney. It is a common complication of bacterial infections, typically skin infection by Streptococcus bacteria types 12, 4 and 1 (impetigo) but also after streptococcal pharyngitis, for which it is also known as postinfectious glomerulonephritis (PIGN) or poststreptococcal glomerulonephritis (PSGN). It can be a risk factor for future albuminuria. In adults, the signs and symptoms of infection may still be present at the time when the kidney problems develop, and the terms infection-related glomerulonephritis or bacterial infection-related glomerulonephritis are also used. Acute glomerulonephritis resulted in 19,000 deaths in 2013, down from 24,000 deaths in 1990 worldwide.
Signs and symptoms
Among the signs and symptoms of acute proliferative glomerulonephritis are the following:
Hematuria
Oliguria
Edema
Hypertension
Fever (headache, malaise, anorexia, nausea.)
Causes
Acute proliferative glomerulonephritis (post-streptococcal glomerulonephritis) is caused by an infection with streptococcus bacteria, usually three weeks after infection, usually of the pharynx or the skin, given the time required to raise antibodies and complement proteins. The infection causes blood vessels in the kidneys to develop inflammation, this hampers the renal organs ability to filter urine. Acute proliferative glomerulonephritis most commonly occurs in children.
Pathophysiology
The pathophysiology of this disorder is consistent with an immune-complex-mediated mechanism, a type III hypersensitivity reaction. This disorder produces proteins that have different antigenic determinants, which in turn have an affinity for sites in the glomerulus. As soon as binding occurs to the glomerulus, via interaction with properdin, the complement is activated. Complement fixation causes the generation of additional inflammatory mediators.Complement activation is very important in acute proliferative glomerulonephritis. Apparently immunoglobulin (Ig)-binding proteins bind C4BP. Complement regulatory proteins (FH and FHL-1), may be removed by SpeB, and therefore restrain FH and FHL-1 recruitment in the process of infection.
Diagnosis
The following diagnostic methods can be used for acute proliferative glomerulonephritis:
Kidney biopsy
Complement profile
Imaging studies
Blood chemistry studiesClinically, acute proliferative glomerulonephritis is diagnosed following a differential diagnosis between (and, ultimately, diagnosis of) staphylococcal and streptococcal impetigo. Serologically, diagnostic markers can be tested; specifically, the streptozyme test is used and measures multiple streptococcal antibodies: antistreptolysin, antihyaluronidase, antistreptokinase, antinicotinamide-adenine dinucleotidase, and anti-DNAse B antibodies.
Differential diagnosis
The differential diagnosis of acute proliferative glomerulonephritisis is based on the following:
Prevention
It is unclear whether or not acute proliferative glomerulonephritis (i.e., poststreptococcal glomerulonephritis) can be prevented with early prophylactic antibiotic therapy, with some authorities arguing that antibiotics can prevent development of acute proliferative glomerulonephritis
Treatment
Acute management of acute proliferative glomerulonephritis mainly consists of blood pressure (BP) control. A low-sodium diet may be instituted when hypertension is present. In individuals with oliguric acute kidney injury, the potassium level should be controlled. Thiazide or loop diuretics can be used to simultaneously reduce edema and control hypertension; however electrolytes such as potassium must be monitored. Beta-blockers, calcium channel blockers, and/or ACE inhibitors may be added if blood pressure is not effectively controlled through diureses alone.
Epidemiology
Acute glomerulonephritis resulted in 19,000 deaths in 2013 down from 24,000 deaths in 1990.
References
Further reading
Group A Streptococcal Infections - National Institute of Allergy and Infectious Diseases
Wilkins, Lippincott Williams & (2004-01-01). Rapid Assessment: A Flowchart Guide to Evaluating Signs and Symptoms. Lippincott Williams & Wilkins. ISBN 9781582552729.
== External links == |
Focal dermal hypoplasia | Focal dermal hypoplasia is a form of ectodermal dysplasia. It is a multisystem disorder characterized primarily by skin manifestations to the atrophic and hypoplastic areas of skin which are present at birth. These defects manifest as yellow-pink bumps on the skin and pigmentation changes. The disorder is also associated with shortness of stature and some evidence suggests that it can cause epilepsy.
Genetics
Focal dermal hypoplasia has been associated with PORCN gene mutations on the X chromosome. 90% of the individuals who are affected with the syndrome are female: the commonly accepted, though unconfirmed, explanation for this is that the non-mosaic hemizygous males are not viable.The differential diagnosis of focal dermal hypoplasia (Goltz) syndrome includes autosomal recessive Setleis syndrome due to TWIST2 gene mutations. It associated with morning glory anomaly, polymicrogyria, incontinentia pigmenti, oculocerebrocutaneous syndrome, Rothmund-Thomson syndrome and microphthalmia with linear skin defects (also known as MLS) syndrome because they are all caused by deletions or point mutations in the HCCS gene.
Diagnosis
Goltz Syndrome is a very rare diagnosis. To date, there are under 25 cases of Goltz Syndrome in the United States.
Treatment
Management is targeted toward the various soft tissue and skeletal anomalies, with the goal of achieving optimal functional and cosmetic results.
Eponyms
Jessner-Cole syndrome
The disorder was first formally recognized by dermatologists, Max Jessner and Harold Newton Cole, in the early 20th century. Jessner and Coles papers were referenced more than any others in the first half of the 20th century.
Goltz-Gorlin
Besides its formal name, it is most commonly referred to as Goltz-Gorlin syndrome, after Robert Goltz and Robert Gorlin. Goltz and Gorlin worked together at the University of Minnesota and are credited for describing the symptoms of the disorder in more detail than ever before and tracking its genetic trends. The name became popular during the second half of the 20th century.
See also
List of cutaneous conditions
List of radiographic findings associated with cutaneous conditions
References
External links
http://www.orpha.net/consor/www/cgi-bin/OC_Exp.php?lng=EN&Expert=2092
GeneReview/NIH/UW entry on Focal dermal hypoplasia |
Rubeosis iridis | Rubeosis iridis is a medical condition of the iris of the eye in which new abnormal blood vessels (formed by neovascularization) are found on the surface of the iris.
Causes
This condition is often associated with diabetes in advanced proliferative diabetic retinopathy. Other conditions causing rubeosis iridis include central retinal vein occlusion, ocular ischemic syndrome, and chronic retinal detachment.
Pathophysiology
It is usually associated with disease processes in the retina, which involve the retina becoming starved of oxygen (ischaemic). The ischemic retina releases a variety of factors, the most important of which is vascular endothelial growth factor (VEGF). These factors stimulate the formation of new blood vessels (angiogenesis). These new vessels do not have the same characteristics as the blood vessels originally formed in the eye. In addition, new blood vessels can form in areas that do not have them. Specifically, new blood vessels can be observed on the iris. In addition to the blood vessels in the iris, they can grow into the angle of the eye. These blood vessels eventually go through a process called fibrosis which closes the normal physiologic anatomy of the angle. The closing of the angle prevents fluid from leaving the eye resulting in an increase in intraocular pressure. This is called neovascular glaucoma.
Treatment
If caught early, the neovascularization can be reversed with prompt panretinal photocoagulation (PRP), or injection of anti-VEGF medications with subsequent PRP. The injection blocks the direct effect of VEGF and acts more quickly but will wear off in about six weeks. PRP has a slower onset of action but can last permanently. Once the neovascularization has been longstanding, the new vessels recruit fibrous tissue, and as this forms and contracts, the angle can be permanently damaged, and will not respond to treatment. If this occurs, then surgical intervention is required to reduce the pressure (such as a glaucoma drainage implant)
See also
CNV (choroidal neovascularization)
CNV (corneal neovascularization)
NVD (neovascularization of the disc)
References
== External links == |
Wernicke–Korsakoff syndrome | Wernicke–Korsakoff syndrome (WKS) is the combined presence of Wernicke encephalopathy (WE) and Korsakoff syndrome. Due to the close relationship between these two disorders, people with either are usually diagnosed with WKS as a single syndrome. It mainly causes vision changes, ataxia and impaired memory.The cause of the disorder is thiamine (vitamin B1) deficiency. This can occur due to Wernicke encephalopathy, eating disorders, malnutrition, and alcohol abuse. These disorders may manifest together or separately. WKS is usually secondary to prolonged alcohol abuse.
Wernicke encephalopathy and WKS are most commonly seen in people with an alcohol use disorder. Failure in diagnosis of WE and thus treatment of the disease leads to death in approximately 20% of cases, while 75% are left with permanent brain damage associated with WKS. Of those affected, 25% require long-term institutionalization in order to receive effective care.
Signs and symptoms
The syndrome is a combined manifestation of two namesake disorders, Wernicke encephalopathy and alcoholic Korsakoff syndrome. It involves an acute Wernicke-encephalopathy phase, followed by the development of a Korsakoff syndrome phase.
Wernicke encephalopathy
WE is characterized by the presence of a triad of symptoms:
Ocular disturbances (ophthalmoplegia)
Changes in mental state (confusion)
Unsteady stance and gait (ataxia)This triad of symptoms results from a deficiency in vitamin B1 which is an essential coenzyme. The aforementioned changes in mental state occur in approximately 82% of patients symptoms of which range from confusion, apathy, inability to concentrate, and a decrease in awareness of the immediate situation they are in. If left untreated, WE can lead to coma or death. In about 29% of patients, ocular disturbances consist of nystagmus and paralysis of the lateral rectus muscles or other muscles in the eye. A smaller percentage of patients experience a decrease in reaction time of the pupils to light stimuli and swelling of the optic disc which may be accompanied by retinal hemorrhage. Finally, the symptoms involving stance and gait occur in about 23% of patients and result from dysfunction in the cerebellum and vestibular system. Other symptoms that have been present in cases of WE are stupor, low blood pressure (hypotension), elevated heart rate (tachycardia), as well as hypothermia, epileptic seizures and a progressive loss of hearing.About 19% of patients have none of the symptoms in the classic triad at first diagnosis of WE; however, usually one or more of the symptoms develops later as the disease progresses.
Korsakoff syndrome
The DSM-V classifies Korsakoff syndrome under Substance/Medication-Induced Major or Mild Neurocognitive Disorders, specifically alcohol-induced amnestic confabulatory. The diagnostic criteria defined as necessary for diagnosis includes prominent amnesia, forgetting quickly, and difficulty learning. Presence of thiamine deficient encephalopathy can occur in conjunction with these symptoms.Despite the assertion that alcoholic Korsakoff syndrome must be caused by the use of alcohol, there have been several cases where it has developed from other instances of thiamine deficiency resulting from gross malnutrition due to conditions such as stomach cancer, anorexia nervosa, and gastrectomy.
Cognitive effects
Several cases have been documented where Wernicke–Korsakoff syndrome has been seen on a large scale. In 1947, 52 cases of WKS were documented in a prisoner of war hospital in Singapore where the prisoners diets included less than 1 mg of thiamine per day. Such cases provide an opportunity to gain an understanding of what effects this syndrome has on cognition. In this particular case, cognitive symptoms included insomnia, anxiety, difficulties in concentration, loss of memory for the immediate past, and gradual degeneration of mental state; consisting of confusion, confabulation, and hallucinations. In other cases of WKS, cognitive effects such as severely disrupted speech, giddiness, and heavy-headedness have been documented. In addition to this, it has been noted that some patients displayed an inability to focus, and the inability of others to catch patients attention.In a study conducted in 2003 by Brand et al. on the cognitive effects of WKS, the researchers used a neuropsychological test battery which included tests of intelligence, speed of information processing, memory, executive function and cognitive estimation. They found that subjects with WKS showed impairments in all aspects of this test battery but most noticeably, on the cognitive estimation tasks. This task required subjects to estimate a physical quality such as size, weight, quantity or time (e.g. What is the average length of a shower?), of a particular item. Patients with WKS performed worse than normal control participants on all of the tasks in this category. The patients found estimations involving time to be the most difficult, whereas quantity was the easiest estimation to make. Additionally, the study included a category for classifying "bizarre" answers, which included any answer that was far outside of the normal range of expected responses. WKS patients did give answers that could fall into such a category and these included answers such as 15s or 1 hour for the estimated length of a shower, or 4 kg or 15 tonnes as the weight of a car.
Memory deficits
As mentioned previously, the amnesic symptoms of WKS include both retrograde and anterograde amnesia. The retrograde deficit has been demonstrated through an inability of WKS patients to recall or recognize information for recent public events. The anterograde memory loss is demonstrated through deficits in tasks that involve encoding and then recalling lists of words and faces, as well as semantic learning tasks. WKS patients have also demonstrated difficulties in perseveration as evidenced by a deficit in performance on the Wisconsin Card Sorting Test. The retrograde amnesia that accompanies WKS can extend as far back as twenty to thirty years, and there is generally a temporal gradient seen, where earlier memories are recalled better than more recent memories. It has been widely accepted that the critical structures that lead to the memory impairment in WKS are the mammillary bodies, and the thalamic regions. Despite the aforementioned memory deficits, non-declarative memory functions appear to be intact in WKS patients. This has been demonstrated through measures that assess perceptual priming.Other studies have shown deficits in recognition memory and stimulus-reward associative functions in patients with WKS. The deficit in stimulus-reward functions was demonstrated by Oscar-Berman and Pulaski who presented patients with reinforcements for certain stimuli but not others, and then required the patients to distinguish the rewarded stimuli from the non-rewarded stimuli. WKS patients displayed significant deficits in this task. The researchers were also successful in displaying a deficit in recognition memory by having patients make a yes/no decision as to whether a stimulus was familiar (previously seen) or novel (not previously seen). The patients in this study also showed a significant deficit in their ability to perform this task.
Confabulation
People with WKS often show confabulation, spontaneous confabulation being seen more frequently than provoked confabulation. Spontaneous confabulations refer to incorrect memories that the patient holds to be true, and may act on, arising spontaneously without any provocation. Provoked confabulations can occur when a patient is cued to give a response, this may occur in test settings. The spontaneous confabulations viewed in WKS are thought to be produced by an impairment in source memory, where they are unable to remember the spatial and contextual information for an event, and thus may use irrelevant or old memory traces to fill in for the information that they cannot access. It has also been suggested that this behaviour may be due to executive dysfunction where they are unable to inhibit incorrect memories or because they are unable to shift their attention away from an incorrect response.
Causes
WKS is usually found in people who have used alcohol chronically. Wernicke–Korsakoff syndrome results from thiamine deficiency. It is generally agreed that Wernicke encephalopathy results from severe acute deficiency of thiamine (vitamin B1), whilst Korsakoffs psychosis is a chronic neurologic sequela of Wernicke encephalopathy. The metabolically active form of thiamine is thiamine pyrophosphate, which plays a major role as a cofactor or coenzyme in glucose metabolism. The enzymes that are dependent on thiamine pyrophosphate are associated with the citric acid cycle (also known as the Krebs cycle), and catalyze the oxidation of pyruvate, α-ketoglutarate and branched chain amino acids. Thus, anything that encourages glucose metabolism will exacerbate an existing clinical or sub-clinical thiamine deficiency.As stated above, Wernicke–Korsakoff syndrome in the United States is usually found in malnourished chronic alcoholics, though it is also found in patients who undergo prolonged intravenous (IV) therapy without vitamin B1 supplementation, gastric stapling, intensive care unit (ICU) stays, hunger strikes, or people with eating disorders. In some regions, physicians have observed thiamine deficiency brought about by severe malnutrition, particularly in diets consisting mainly of polished rice, which is thiamine-deficient. The resulting nervous system ailment is called beriberi. In individuals with sub-clinical thiamine deficiency, a large dose of glucose (either as sweet food, etc. or glucose infusion) can precipitate the onset of overt encephalopathy.Wernicke–Korsakoff syndrome in people with chronic alcohol use particularly is associated with atrophy/infarction of specific regions of the brain, especially the mammillary bodies. Other regions include the anterior region of the thalamus (accounting for amnesic symptoms), the medial dorsal thalamus, the basal forebrain, the median and dorsal raphe nuclei, and the cerebellum.One as-yet-unreplicated study has associated susceptibility to this syndrome with a hereditary deficiency of transketolase, an enzyme that requires thiamine as a coenzyme.
Post-gastrectomy
The fact that gastrointestinal surgery can lead to the development of WKS was demonstrated in a study that was completed on three patients who recently undergone a gastrectomy. These patients had developed WKS but were not alcoholics and had never suffered from dietary deprivation. WKS developed between 2 and 20 years after the surgery. There were small dietary changes that contributed to the development of WKS but overall the lack of absorption of thiamine from the gastrointestinal tract was the cause. Therefore, it must be ensured that patients who have undergone gastrectomy have a proper education on dietary habits, and carefully monitor their thiamine intake. Additionally, an early diagnosis of WKS, should it develop, is very important.
Alcohol–thiamine interactions
Strong evidence suggests that ethanol interferes directly with thiamine uptake in the gastrointestinal tract. Ethanol also disrupts thiamine storage in the liver and the transformation of thiamine into its active form. The role of alcohol consumption in the development of WKS has been experimentally confirmed through studies in which rats were subjected to alcohol exposure and lower levels of thiamine through a low-thiamine diet. In particular, studies have demonstrated that clinical signs of the neurological problems that result from thiamine deficiency develop faster in rats that have received alcohol and were also deficient in thiamine than rats who did not receive alcohol. In another study, it was found that rats that were chronically fed alcohol had significantly lower liver thiamine stores than control rats. This provides an explanation for why alcoholics with liver cirrhosis have a higher incidence of both thiamine deficiency and WKS.
Pathophysiology
The vitamin thiamine also referred to as Vitamin B1, is required by three different enzymes to allow for conversion of ingested nutrients into energy. Thiamine can not be produced in the body and must be obtained through diet and supplementation. The duodenum is responsible for absorbing thiamine. The liver can store thiamine for 18 days. Prolonged and frequent consumption of alcohol causes a decreased ability to absorb thiamine in the duodenum. Thiamine deficiency is also related to malnutrition from poor diet, impaired use of thiamine by the cells and impaired storage in the liver. Without thiamine the Krebs Cycle enzymes pyruvate dehydrogenase complex (PDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH) are impaired. The impaired functioning of the Krebs Cycle results in inadequate production of adenosine triphosphate (ATP) or energy for the cells functioning. Energy is required by the brain for proper functioning and use of its neurotransmitters. Injury to the brain occurs when neurons that require high amounts of energy from thiamine dependent enzymes are not supplied with enough energy and die.Brain atrophy associated with WKS occurs in the following regions of the brain:
the mammillary bodies,
the thalamus,
the periaqueductal grey,
the walls of the 3rd ventricle,
the floor of the 4th ventricle,
the cerebellum, and
the frontal lobe.In addition to the damage seen in these areas there have been reports of damage to cortex, although it was noted that this may be due to the direct toxic effects of alcohol as opposed to thiamine deficiency that has been attributed as the underlying cause of Wernicke-Korsakoff Syndrome.The amnesia that is associated with this syndrome is a result of the atrophy in the structures of the diencephalon (the thalamus, hypothalamus and mammillary bodies), and is similar to amnesia that is presented as a result of other cases of damage to the medial temporal lobe. It has been argued that the memory impairments can occur as a result of damage along any part of the mammillo-thalamic tract, which explains how WKS can develop in patients with damage exclusively to either the thalamus or the mammillary bodies.
Diagnosis
Diagnosis of Wernicke–Korsakoff syndrome is by clinical impression and can sometimes be confirmed by a formal neuropsychological assessment. Wernicke encephalopathy typically presents with ataxia and nystagmus, and Korsakoffs psychosis with anterograde and retrograde amnesia and confabulation upon relevant lines of questioning.Frequently, secondary to thiamine deficiency and subsequent cytotoxic edema in Wernicke encephalopathy, patients will have marked degeneration of the mammillary bodies. Thiamine (vitamin B1) is an essential coenzyme in carbohydrate metabolism and is also a regulator of osmotic gradient. Its deficiency may cause swelling of the intracellular space and local disruption of the blood-brain barrier. Brain tissue is very sensitive to changes in electrolytes and pressure and edema can be cytotoxic. In Wernicke this occurs specifically in the mammillary bodies, medial thalami, tectal plate, and periaqueductal areas. People with the condition may also exhibit a dislike for sunlight and so may wish to stay indoors with the lights off. The mechanism of this degeneration is unknown, but it supports the current neurological theory that the mammillary bodies play a role in various "memory circuits" within the brain. An example of a memory circuit is the Papez circuit.
Prevention
As described, Korsakoff syndrome usually follows or accompanies Wernicke encephalopathy. If treated quickly, it may be possible to prevent the development of WKS with thiamine treatments. This treatment is not guaranteed to be effective and the thiamine needs to be administered adequately in both dose and duration. A study on Wernicke–Korsakoff syndrome showed that with consistent thiamine treatment there were noticeable improvements in mental status after only 2–3 weeks of therapy. Thus, there is hope that with treatment Wernicke encephalopathy will not necessarily progress to WKS.In order to reduce the risk of developing WKS it is important to limit the intake of alcohol in order to ensure that proper nutrition needs are met. A healthy diet is imperative for proper nutrition which, in combination with thiamine supplements, may reduce the chance of developing WKS. This prevention method may specifically help heavy drinkers who refuse to or are unable to quit.A number of proposals have been put forth to fortify alcoholic beverages with thiamine to reduce the incidence of WKS among those heavily abusing alcohol. To date, no such proposals have been enacted.Daily recommendations of thiamine requirements are 0.66 mg per 8,400 kilojoules (2,000 kilocalories) of food energy intake – approximately equivalent to 1.2 mg for men and 1.1 mg for women.
Treatment
The onset of Wernicke encephalopathy is considered a medical emergency, and thus thiamine administration should be initiated immediately when the disease is suspected. Prompt administration of thiamine to patients with Wernicke encephalopathy can prevent the disorder from developing into Wernicke–Korsakoff syndrome, or reduce its severity. Treatment can also reduce the progression of the deficits caused by WKS, but will not completely reverse existing deficits. WKS will continue to be present, at least partially, in 80% of patients. Patients with WE should be given a minimum dose of 500 mg of thiamine hydrochloride, delivered by infusion over a 30-minute period for two to three days. If no response is seen then treatment should be discontinued but for those patients that do respond, treatment should be continued with a 250 mg dose delivered intravenously or intramuscularly for three to five days unless the patient stops improving. Such prompt administration of thiamine may be a life-saving measure. Banana bags, a bag of intravenous fluids containing vitamins and minerals, is one means of treatment.
Epidemiology
WKS occurs more frequently in men than women and has the highest prevalence in the ages 55–65. Approximately 71% are unmarried.Internationally, the prevalence rates of WKS are relatively standard, being anywhere between zero and two percent. Despite this, specific sub-populations seem to have higher prevalence rates including people who are homeless, older individuals (especially those living alone or in isolation), and psychiatric inpatients. Additionally, studies show that prevalence is not connected to alcohol consumption per capita. For example, in France, a country that is well known for its consumption and production of wine, prevalence was only 0.4% in 1994, while Australia had a prevalence of 2.8%.
History
Wernicke encephalopathy
Carl Wernicke discovered Wernicke encephalopathy in 1881. His first diagnosis noted symptoms including paralyzed eye movements, ataxia, and mental confusion. Also noticed were hemorrhages in the gray matter around the third and fourth ventricles and the cerebral aqueduct. Brain atrophy was only found upon post-mortem autopsy. Wernicke believed these hemorrhages were due to inflammation and thus the disease was named polioencephalitis haemorrhagica superior. Later, it was found that Wernicke encephalopathy and alcoholic Korsakoff syndrome are products of the same cause.
Korsakoff syndrome
Sergei Korsakoff was a Russian physician after whom the disease "Korsakoffs syndrome" was named. In the late 1800s Korsakoff was studying long-term alcoholic patients and began to notice a decline in their memory function. At the 13th International Medical Congress in Moscow in 1897, Korsakoff presented a report called: "On a special form of mental illness combined with degenerative polyneuritis". After the presentation of this report the term "Korsakoffs syndrome" was coined.Although WE and AKS were discovered separately, these two syndromes are usually referred to under one name, Wernicke–Korsakoff syndrome, due to the fact that they are part of the same cause and because the onset of AKS usually follows WE if left untreated.
Society and culture
The British neurologist Oliver Sacks describes case histories of some of his patients with the syndrome in the book The Man Who Mistook His Wife for a Hat (1985).Frontman and lead vocalist of the hard rock band Breaking Benjamin, Benjamin Burnley, is well known to be living with Wernicke–Korsakoff syndrome due to his past alcoholism. He has written multiple songs about addiction and his experiences with alcohol, with many of such songs being found on the bands 2009 album Dear Agony as it was the first album Burnley had written and recorded completely sober.
See also
Alcoholic dementia
Dementia
Malabsorption
References
== External links == |
Pneumothorax | A pneumothorax is an abnormal collection of air in the pleural space between the lung and the chest wall. Symptoms typically include sudden onset of sharp, one-sided chest pain and shortness of breath. In a minority of cases, a one-way valve is formed by an area of damaged tissue, and the amount of air in the space between chest wall and lungs increases; this is called a tension pneumothorax. This can cause a steadily worsening oxygen shortage and low blood pressure. This leads to a type of shock called obstructive shock, which can be fatal unless reversed. Very rarely, both lungs may be affected by a pneumothorax. It is often called a "collapsed lung", although that term may also refer to atelectasis.A primary spontaneous pneumothorax is one that occurs without an apparent cause and in the absence of significant lung disease. A secondary spontaneous pneumothorax occurs in the presence of existing lung disease. Smoking increases the risk of primary spontaneous pneumothorax, while the main underlying causes for secondary pneumothorax are COPD, asthma, and tuberculosis. A traumatic pneumothorax can develop from physical trauma to the chest (including a blast injury) or from a complication of a healthcare intervention.Diagnosis of a pneumothorax by physical examination alone can be difficult (particularly in smaller pneumothoraces). A chest X-ray, computed tomography (CT) scan, or ultrasound is usually used to confirm its presence. Other conditions that can result in similar symptoms include a hemothorax (buildup of blood in the pleural space), pulmonary embolism, and heart attack. A large bulla may look similar on a chest X-ray.A small spontaneous pneumothorax will typically resolve without treatment and requires only monitoring. This approach may be most appropriate in people who have no underlying lung disease. In a larger pneumothorax, or if there is shortness of breath, the air may be removed with a syringe or a chest tube connected to a one-way valve system. Occasionally, surgery may be required if tube drainage is unsuccessful, or as a preventive measure, if there have been repeated episodes. The surgical treatments usually involve pleurodesis (in which the layers of pleura are induced to stick together) or pleurectomy (the surgical removal of pleural membranes). About 17–23 cases of pneumothorax occur per 100,000 people per year. They are more common in men than women.
Signs and symptoms
A primary spontaneous pneumothorax (PSP) tends to occur in a young adult without underlying lung problems, and usually causes limited symptoms. Chest pain and sometimes mild breathlessness are the usual predominant presenting features. People who are affected by a PSP are often unaware of the potential danger and may wait several days before seeking medical attention. PSPs more commonly occur during changes in atmospheric pressure, explaining to some extent why episodes of pneumothorax may happen in clusters. It is rare for a PSP to cause a tension pneumothorax.Secondary spontaneous pneumothoraces (SSPs), by definition, occur in individuals with significant underlying lung disease. Symptoms in SSPs tend to be more severe than in PSPs, as the unaffected lungs are generally unable to replace the loss of function in the affected lungs. Hypoxemia (decreased blood-oxygen levels) is usually present and may be observed as cyanosis (blue discoloration of the lips and skin). Hypercapnia (accumulation of carbon dioxide in the blood) is sometimes encountered; this may cause confusion and – if very severe – may result in comas. The sudden onset of breathlessness in someone with chronic obstructive pulmonary disease (COPD), cystic fibrosis, or other serious lung diseases should therefore prompt investigations to identify the possibility of a pneumothorax.Traumatic pneumothorax most commonly occurs when the chest wall is pierced, such as when a stab wound or gunshot wound allows air to enter the pleural space, or because some other mechanical injury to the lung compromises the integrity of the involved structures. Traumatic pneumothoraces have been found to occur in up to half of all cases of chest trauma, with only rib fractures being more common in this group. The pneumothorax can be occult (not readily apparent) in half of these cases, but may enlarge – particularly if mechanical ventilation is required. They are also encountered in people already receiving mechanical ventilation for some other reason.Upon physical examination, breath sounds (heard with a stethoscope) may be diminished on the affected side, partly because air in the pleural space dampens the transmission of sound. Measures of the conduction of vocal vibrations to the surface of the chest may be altered. Percussion of the chest may be perceived as hyperresonant (like a booming drum), and vocal resonance and tactile fremitus can both be noticeably decreased. Importantly, the volume of the pneumothorax may not be well correlated with the intensity of the symptoms experienced by the victim, and physical signs may not be apparent if the pneumothorax is relatively small.
Tension pneumothorax
Tension pneumothorax is generally considered to be present when a pneumothorax (primary spontaneous, secondary spontaneous, or traumatic) leads to significant impairment of respiration and/or blood circulation. This causes a type of circulatory shock, called obstructive shock. Tension pneumothorax tends to occur in clinical situations such as ventilation, resuscitation, trauma, or in people with lung disease. It is a medical emergency and may require immediate treatment without further investigations (see Treatment section).The most common findings in people with tension pneumothorax are chest pain and respiratory distress, often with an increased heart rate (tachycardia) and rapid breathing (tachypnea) in the initial stages. Other findings may include quieter breath sounds on one side of the chest, low oxygen levels and blood pressure, and displacement of the trachea away from the affected side. Rarely, there may be cyanosis (bluish discoloration of the skin due to low oxygen levels), altered level of consciousness, a hyperresonant percussion note on examination of the affected side with reduced expansion and decreased movement, pain in the epigastrium (upper abdomen), displacement of the apex beat (heart impulse), and resonant sound when tapping the sternum.Tension pneumothorax may also occur in someone who is receiving mechanical ventilation, in which case it may be difficult to spot as the person is typically receiving sedation; it is often noted because of a sudden deterioration in condition. Recent studies have shown that the development of tension features may not always be as rapid as previously thought. Deviation of the trachea to one side and the presence of raised jugular venous pressure (distended neck veins) are not reliable as clinical signs.
Cause
Primary spontaneous
Spontaneous pneumothoraces are divided into two types: primary, which occurs in the absence of known lung disease, and secondary, which occurs in someone with underlying lung disease. The cause of primary spontaneous pneumothorax is unknown, but established risk factors include being of the male sex, smoking, and a family history of pneumothorax. Smoking either cannabis or tobacco increases the risk. The various suspected underlying mechanisms are discussed below.
Secondary spontaneous
Secondary spontaneous pneumothorax occurs in the setting of a variety of lung diseases. The most common is chronic obstructive pulmonary disease (COPD), which accounts for approximately 70% of cases. Known lung diseases that may significantly increase the risk for pneumothorax are
In children, additional causes include measles, echinococcosis, inhalation of a foreign body, and certain congenital malformations (congenital pulmonary airway malformation and congenital lobar emphysema).11.5% of people with a spontaneous pneumothorax have a family member who has previously experienced a pneumothorax. The hereditary conditions – Marfan syndrome, homocystinuria, Ehlers–Danlos syndromes, alpha 1-antitrypsin deficiency (which leads to emphysema), and Birt–Hogg–Dubé syndrome – have all been linked to familial pneumothorax. Generally, these conditions cause other signs and symptoms as well, and pneumothorax is not usually the primary finding. Birt–Hogg–Dubé syndrome is caused by mutations in the FLCN gene (located at chromosome 17p11.2), which encodes a protein named folliculin. FLCN mutations and lung lesions have also been identified in familial cases of pneumothorax where other features of Birt–Hogg–Dubé syndrome are absent. In addition to the genetic associations, the HLA haplotype A2B40 is also a genetic predisposition to PSP.
Traumatic
A traumatic pneumothorax may result from either blunt trauma or penetrating injury to the chest wall. The most common mechanism is due to the penetration of sharp bony points at a new rib fracture, which damages lung tissue. Traumatic pneumothorax may also be observed in those exposed to blasts, even though there is no apparent injury to the chest.They may be classified as "open" or "closed". In an open pneumothorax, there is a passage from the external environment into the pleural space through the chest wall. When air is drawn into the pleural space through this passageway, it is known as a "sucking chest wound". A closed pneumothorax is when the chest wall remains intact.Medical procedures, such as the insertion of a central venous catheter into one of the chest veins or the taking of biopsy samples from lung tissue, may lead to pneumothorax. The administration of positive pressure ventilation, either mechanical ventilation or non-invasive ventilation, can result in barotrauma (pressure-related injury) leading to a pneumothorax.Divers who breathe from an underwater apparatus are supplied with breathing gas at ambient pressure, which results in their lungs containing gas at higher than atmospheric pressure. Divers breathing compressed air (such as when scuba diving) may develop a pneumothorax as a result of barotrauma from ascending just 1 metre (3 ft) while breath-holding with their lungs fully inflated. An additional problem in these cases is that those with other features of decompression sickness are typically treated in a diving chamber with hyperbaric therapy; this can lead to a small pneumothorax rapidly enlarging and causing features of tension.
Newborn infants
Newborn babies between 3–9 days of birth with low birth weight have a higher risk of pneumothorax.
Mechanism
The thoracic cavity is the space inside the chest that contains the lungs, heart, and numerous major blood vessels. On each side of the cavity, a pleural membrane covers the surface of lung (visceral pleura) and also lines the inside of the chest wall (parietal pleura). Normally, the two layers are separated by a small amount of lubricating serous fluid. The lungs are fully inflated within the cavity because the pressure inside the airways (intrapulmonary pressure) is higher than the pressure inside the pleural space (intrapleural pressure). Despite the low pressure in the pleural space, air does not enter it because there are no natural connections to an air-containing passage, and the pressure of gases in the bloodstream is too low for them to be forced into the pleural space. Therefore, a pneumothorax can only develop if air is allowed to enter, through damage to the chest wall or damage to the lung itself, or occasionally because microorganisms in the pleural space produce gas. Once air enters the pleural cavity, the intrapleural pressure increases resulting in the difference between the intrapulmonary pressure and the intrapleural pressure (defined as the transpulmonary pressure) to equal zero which cause the lungs to deflate in contrast to a normal transpulmonary pressure of ~4 mm Hg.Chest-wall defects are usually evident in cases of injury to the chest wall, such as stab or bullet wounds ("open pneumothorax"). In secondary spontaneous pneumothoraces, vulnerabilities in the lung tissue are caused by a variety of disease processes, particularly by rupturing of bullae (large air-containing lesions) in cases of severe emphysema. Areas of necrosis (tissue death) may precipitate episodes of pneumothorax, although the exact mechanism is unclear. Primary spontaneous pneumothorax (PSP) has for many years been thought to be caused by "blebs" (small air-filled lesions just under the pleural surface), which were presumed to be more common in those classically at risk of pneumothorax (tall males) due to mechanical factors. In PSP, blebs can be found in 77% of cases, compared to 6% in the general population without a history of PSP. As these healthy subjects do not all develop a pneumothorax later, the hypothesis may not be sufficient to explain all episodes; furthermore, pneumothorax may recur even after surgical treatment of blebs. It has therefore been suggested that PSP may also be caused by areas of disruption (porosity) in the pleural layer, which are prone to rupture. Smoking may additionally lead to inflammation and obstruction of small airways, which account for the markedly increased risk of PSPs in smokers. Once air has stopped entering the pleural cavity, it is gradually reabsorbed.Tension pneumothorax occurs when the opening that allows air to enter the pleural space functions as a one-way valve, allowing more air to enter with every breath but none to escape. The body compensates by increasing the respiratory rate and tidal volume (size of each breath), worsening the problem. Unless corrected, hypoxia (decreased oxygen levels) and respiratory arrest eventually follow.
Diagnosis
The symptoms of pneumothorax can be vague and inconclusive, especially in those with a small PSP; confirmation with medical imaging is usually required. In contrast, tension pneumothorax is a medical emergency and may be treated before imaging – especially if there is severe hypoxia, very low blood pressure, or an impaired level of consciousness. In tension pneumothorax, X-rays are sometimes required if there is doubt about the anatomical location of the pneumothorax.
Chest X-ray
A plain chest radiograph, ideally with the X-ray beams being projected from the back (posteroanterior, or "PA"), and during maximal inspiration (holding ones breath), is the most appropriate first investigation. It is not believed that routinely taking images during expiration would confer any benefit. Still, they may be useful in the detection of a pneumothorax when clinical suspicion is high but yet an inspiratory radiograph appears normal. Also, if the PA X-ray does not show a pneumothorax but there is a strong suspicion of one, lateral X-rays (with beams projecting from the side) may be performed, but this is not routine practice.
It is not unusual for the mediastinum (the structure between the lungs that contains the heart, great blood vessels, and large airways) to be shifted away from the affected lung due to the pressure differences. This is not equivalent to a tension pneumothorax, which is determined mainly by the constellation of symptoms, hypoxia, and shock.The size of the pneumothorax (i.e. the volume of air in the pleural space) can be determined with a reasonable degree of accuracy by measuring the distance between the chest wall and the lung. This is relevant to treatment, as smaller pneumothoraces may be managed differently. An air rim of 2 cm means that the pneumothorax occupies about 50% of the hemithorax. British professional guidelines have traditionally stated that the measurement should be performed at the level of the hilum (where blood vessels and airways enter the lung) with 2 cm as the cutoff, while American guidelines state that the measurement should be done at the apex (top) of the lung with 3 cm differentiating between a "small" and a "large" pneumothorax. The latter method may overestimate the size of a pneumothorax if it is located mainly at the apex, which is a common occurrence. The various methods correlate poorly but are the best easily available ways of estimating pneumothorax size. CT scanning (see below) can provide a more accurate determination of the size of the pneumothorax, but its routine use in this setting is not recommended.Not all pneumothoraces are uniform; some only form a pocket of air in a particular place in the chest. Small amounts of fluid may be noted on the chest X-ray (hydropneumothorax); this may be blood (hemopneumothorax). In some cases, the only significant abnormality may be the "deep sulcus sign", in which the normally small space between the chest wall and the diaphragm appears enlarged due to the abnormal presence of fluid.
Computed tomography
A CT scan is not necessary for the diagnosis of pneumothorax, but it can be useful in particular situations. In some lung diseases, especially emphysema, it is possible for abnormal lung areas such as bullae (large air-filled sacs) to have the same appearance as a pneumothorax on chest X-ray, and it may not be safe to apply any treatment before the distinction is made and before the exact location and size of the pneumothorax is determined. In trauma, where it may not be possible to perform an upright film, chest radiography may miss up to a third of pneumothoraces, while CT remains very sensitive.A further use of CT is in the identification of underlying lung lesions. In presumed primary pneumothorax, it may help to identify blebs or cystic lesions (in anticipation of treatment, see below), and in secondary pneumothorax, it can help to identify most of the causes listed above.
Ultrasound
Ultrasound is commonly used in the evaluation of people who have sustained physical trauma, for example with the FAST protocol. Ultrasound may be more sensitive than chest X-rays in the identification of pneumothorax after blunt trauma to the chest. Ultrasound may also provide a rapid diagnosis in other emergency situations, and allow the quantification of the size of the pneumothorax. Several particular features on ultrasonography of the chest can be used to confirm or exclude the diagnosis.
Treatment
The treatment of pneumothorax depends on a number of factors and may vary from discharge with early follow-up to immediate needle decompression or insertion of a chest tube. Treatment is determined by the severity of symptoms and indicators of acute illness, the presence of underlying lung disease, the estimated size of the pneumothorax on X-ray, and – in some instances – on the personal preference of the person involved.In traumatic pneumothorax, chest tubes are usually inserted. If mechanical ventilation is required, the risk of tension pneumothorax is greatly increased and the insertion of a chest tube is mandatory. Any open chest wound should be covered with an airtight seal, as it carries a high risk of leading to tension pneumothorax. Ideally, a dressing called the "Asherman seal" should be utilized, as it appears to be more effective than a standard "three-sided" dressing. The Asherman seal is a specially designed device that adheres to the chest wall and, through a valve-like mechanism, allows air to escape but not to enter the chest.Tension pneumothorax is usually treated with urgent needle decompression. This may be required before transport to the hospital, and can be performed by an emergency medical technician or other trained professional. The needle or cannula is left in place until a chest tube can be inserted. Critical care teams are able to incise the chest to create a larger conduit as performed when placing a chest drain, but without inserting the chest tube. This is called a simple thoracostomy. If tension pneumothorax leads to cardiac arrest, needle decompression or simple thoracostomy is performed as part of resuscitation as it may restore cardiac output.
Conservative
Small spontaneous pneumothoraces do not always require treatment, as they are unlikely to proceed to respiratory failure or tension pneumothorax, and generally resolve spontaneously. This approach is most appropriate if the estimated size of the pneumothorax is small (defined as <50% of the volume of the hemithorax), there is no breathlessness, and there is no underlying lung disease. It may be appropriate to treat a larger PSP conservatively if the symptoms are limited. Admission to hospital is often not required, as long as clear instructions are given to return to hospital if there are worsening symptoms. Further investigations may be performed as an outpatient, at which time X-rays are repeated to confirm improvement, and advice given with regard to preventing recurrence (see below). Estimated rates of resorption are between 1.25% and 2.2% the volume of the cavity per day. This would mean that even a complete pneumothorax would spontaneously resolve over a period of about 6 weeks. There is, however, no high quality evidence comparing conservative to non conservative management.Secondary pneumothoraces are only treated conservatively if the size is very small (1 cm or less air rim) and there are limited symptoms. Admission to the hospital is usually recommended. Oxygen given at a high flow rate may accelerate resorption as much as fourfold.
Aspiration
In a large PSP (>50%), or in a PSP associated with breathlessness, some guidelines recommend that reducing the size by aspiration is equally effective as the insertion of a chest tube. This involves the administration of local anesthetic and inserting a needle connected to a three-way tap; up to 2.5 liters of air (in adults) are removed. If there has been significant reduction in the size of the pneumothorax on subsequent X-ray, the remainder of the treatment can be conservative. This approach has been shown to be effective in over 50% of cases. Compared to tube drainage, first-line aspiration in PSP reduces the number of people requiring hospital admission, without increasing the risk of complications.Aspiration may also be considered in secondary pneumothorax of moderate size (air rim 1–2 cm) without breathlessness, with the difference that ongoing observation in hospital is required even after a successful procedure. American professional guidelines state that all large pneumothoraces – even those due to PSP – should be treated with a chest tube. Moderately sized iatrogenic traumatic pneumothoraces (due to medical procedures) may initially be treated with aspiration.
Chest tube
A chest tube (or intercostal drain) is the most definitive initial treatment of a pneumothorax. These are typically inserted in an area under the axilla (armpit) called the "safe triangle", where damage to internal organs can be avoided; this is delineated by a horizontal line at the level of the nipple and two muscles of the chest wall (latissimus dorsi and pectoralis major). Local anesthetic is applied. Two types of tubes may be used. In spontaneous pneumothorax, small-bore (smaller than 14 F, 4.7 mm diameter) tubes may be inserted by the Seldinger technique, and larger tubes do not have an advantage. In traumatic pneumothorax, larger tubes (28 F, 9.3 mm) are used. When chest tubes are placed due to either blunt or penetrating trauma, antibiotics decrease the risks of infectious complications.Chest tubes are required in PSPs that have not responded to needle aspiration, in large SSPs (>50%), and in cases of tension pneumothorax. They are connected to a one-way valve system that allows air to escape, but not to re-enter, the chest. This may include a bottle with water that functions like a water seal, or a Heimlich valve. They are not normally connected to a negative pressure circuit, as this would result in rapid re-expansion of the lung and a risk of pulmonary edema ("re-expansion pulmonary edema"). The tube is left in place until no air is seen to escape from it for a period of time, and X-rays confirm re-expansion of the lung.If after 2–4 days there is still evidence of an air leak, various options are available. Negative pressure suction (at low pressures of –10 to –20 cmH2O) at a high flow rate may be attempted, particularly in PSP; it is thought that this may accelerate the healing of the leak. Failing this, surgery may be required, especially in SSP.Chest tubes are used first-line when pneumothorax occurs in people with AIDS, usually due to underlying pneumocystis pneumonia (PCP), as this condition is associated with prolonged air leakage. Bilateral pneumothorax (pneumothorax on both sides) is relatively common in people with pneumocystis pneumonia, and surgery is often required.It is possible for a person with a chest tube to be managed in an ambulatory care setting by using a Heimlich valve, although research to demonstrate the equivalence to hospitalization has been of limited quality.
Pleurodesis and surgery
Pleurodesis is a procedure that permanently eliminates the pleural space and attaches the lung to the chest wall. No long-term study (20 years or more) has been performed on its consequences. Good results in the short term are achieved with a thoracotomy (surgical opening of the chest) with identification of any source of air leakage and stapling of blebs followed by pleurectomy (stripping of the pleural lining) of the outer pleural layer and pleural abrasion (scraping of the pleura) of the inner layer. During the healing process, the lung adheres to the chest wall, effectively obliterating the pleural space. Recurrence rates are approximately 1%. Post-thoracotomy pain is relatively common.
A less invasive approach is thoracoscopy, usually in the form of a procedure called video-assisted thoracoscopic surgery (VATS). The results from VATS-based pleural abrasion are slightly worse than those achieved using thoracotomy in the short term, but produce smaller scars in the skin. Compared to open thoracotomy, VATS offers a shorter in-hospital stays, less need for postoperative pain control, and a reduced risk of lung problems after surgery. VATS may also be used to achieve chemical pleurodesis; this involves insufflation of talc, which activates an inflammatory reaction that causes the lung to adhere to the chest wall.If a chest tube is already in place, various agents may be instilled through the tube to achieve chemical pleurodesis, such as talc, tetracycline, minocycline or doxycycline. Results of chemical pleurodesis tend to be worse than when using surgical approaches, but talc pleurodesis has been found to have few negative long-term consequences in younger people.
Aftercare
If pneumothorax occurs in a smoker, this is considered an opportunity to emphasize the markedly increased risk of recurrence in those who continue to smoke, and the many benefits of smoking cessation. It may be advisable for someone to remain off work for up to a week after a spontaneous pneumothorax. If the person normally performs heavy manual labor, several weeks may be required. Those who have undergone pleurodesis may need two to three weeks off work to recover.Air travel is discouraged for up to seven days after complete resolution of a pneumothorax if recurrence does not occur. Underwater diving is considered unsafe after an episode of pneumothorax unless a preventive procedure has been performed. Professional guidelines suggest that pleurectomy be performed on both lungs and that lung function tests and CT scan normalize before diving is resumed. Aircraft pilots may also require assessment for surgery.
Neonatal period
For newborn infants with pneumothorax, different management strategies have been suggested including careful observation, thoracentesis (needle aspiration), or insertion of a chest tube. Needle aspiration may reduce the need for a chest tube, however, the effectiveness and safety of both invasive procedures have not been fully studied.
Prevention
A preventative procedure (thoracotomy or thoracoscopy with pleurodesis) may be recommended after an episode of pneumothorax, with the intention to prevent recurrence. Evidence on the most effective treatment is still conflicting in some areas, and there is variation between treatments available in Europe and the US. Not all episodes of pneumothorax require such interventions; the decision depends largely on estimation of the risk of recurrence. These procedures are often recommended after the occurrence of a second pneumothorax. Surgery may need to be considered if someone has experienced pneumothorax on both sides ("bilateral"), sequential episodes that involve both sides, or |
Pneumothorax | if an episode was associated with pregnancy.
Epidemiology
The annual age-adjusted incidence rate (AAIR) of PSP is thought to be three to six times as high in males as in females. Fishman cites AAIRs of 7.4 and 1.2 cases per 100,000 person-years in males and females, respectively. Significantly above-average height is also associated with increased risk of PSP – in people who are at least 76 inches (1.93 meters) tall, the AAIR is about 200 cases per 100,000 person-years. Slim build also seems to increase the risk of PSP.The risk of contracting a first spontaneous pneumothorax is elevated among male and female smokers by factors of approximately 22 and 9, respectively, compared to matched non-smokers of the same sex. Individuals who smoke at higher intensity are at higher risk, with a "greater-than-linear" effect; men who smoke 10 cigarettes per day have an approximate 20-fold increased risk over comparable non-smokers, while smokers consuming 20 cigarettes per day show an estimated 100-fold increase in risk.In secondary spontaneous pneumothorax, the estimated annual AAIR is 6.3 and 2.0 cases per 100,000 person-years for males and females, respectively, with the risk of recurrence depending on the presence and severity of any underlying lung disease. Once a second episode has occurred, there is a high likelihood of subsequent further episodes. The incidence in children has not been well studied, but is estimated to be between 5 and 10 cases per 100,000 person-years.Death from pneumothorax is very uncommon (except in tension pneumothoraces). British statistics show an annual mortality rate of 1.26 and 0.62 deaths per million person-years in men and women, respectively. A significantly increased risk of death is seen in older patients and in those with secondary pneumothoraces.
History
An early description of traumatic pneumothorax secondary to rib fractures appears in Imperial Surgery by Turkish surgeon Şerafeddin Sabuncuoğlu (1385–1468), which also recommends a method of simple aspiration.Pneumothorax was described in 1803 by Jean Marc Gaspard Itard, a student of René Laennec, who provided an extensive description of the clinical picture in 1819. While Itard and Laennec recognized that some cases were not due to tuberculosis (then the most common cause), the concept of spontaneous pneumothorax in the absence of tuberculosis (primary pneumothorax) was reintroduced by the Danish physician Hans Kjærgaard in 1932. In 1941, the surgeons Tyson and Crandall introduced pleural abrasion for the treatment of pneumothorax.Prior to the advent of anti-tuberculous medications, pneumothoraces were intentionally caused by healthcare providers in people with tuberculosis in an effort to collapse a lobe, or entire lung, around a cavitating lesion. This was known as "resting the lung". It was introduced by the Italian surgeon Carlo Forlanini in 1888 and publicized by the American surgeon John Benjamin Murphy in the early 20th century (after discovering the same procedure independently). Murphy used the (then) recently discovered X-ray technology to create pneumothoraces of the correct size.
Etymology
The word pneumothorax is from the Greek pneumo- meaning air and thorax meaning chest. Its plural is pneumothoraces.
Other animals
Non-human animals may experience both spontaneous and traumatic pneumothorax. Spontaneous pneumothorax is, as in humans, classified as primary or secondary, while traumatic pneumothorax is divided into open and closed (with or without chest wall damage). The diagnosis may be apparent to the veterinary physician because the animal exhibits difficulty breathing in, or has shallow breathing. Pneumothoraces may arise from lung lesions (such as bullae) or from trauma to the chest wall. In horses, traumatic pneumothorax may involve both hemithoraces, as the mediastinum is incomplete and there is a direct connection between the two halves of the chest. Tension pneumothorax – the presence of which may be suspected due to rapidly deteriorating heart function, absent lung sounds throughout the thorax, and a barrel-shaped chest – is treated with an incision in the animals chest to relieve the pressure, followed by insertion of a chest tube. For spontaneous pneumothorax the use of CT for diagnosis has been described for dogs and Kunekune pigs.
== References == |
Subglottic stenosis | Subglottic stenosis is a congenital or acquired narrowing of the subglottic airway. It can be congenital, acquired, iatrogenic, or very rarely, idiopathic. It is defined as the narrowing of the portion of the airway that lies between the vocal cords and the lower part of the cricoid cartilage. In a normal infant, the subglottic airway is 4.5-5.5 millimeters wide, while in a premature infant, the normal width is 3.5 millimeters. Subglottic stenosis is defined as a diameter of under 4 millimeters in an infant. Acquired cases are more common than congenital cases due to prolonged intubation being introduced in the 1960s. It is most frequently caused by certain medical procedures or external trauma, although infections and systemic diseases can also cause it.
Signs and symptoms
Symptoms may range from stridor during exercise to complete obstruction of the airway. In idiopathic cases, symptoms may be mistaken for asthma. In congenital cases, symptoms occur soon after birth, and include difficulty breathing, stridor, and air hunger. If the vocal cords are affected, symptoms may include inability to make sound, and an unusual cry.
Causes
Most commonly, acquired cases are caused by trauma or certain medical procedures. The condition is more often caused by external trauma in adults. External injuries occur from vehicular accidents or clothesline injuries. Iatrogenic cases can occur from intubation, tracheostomy, and an endotracheal tube cuff pressure that is too high. 17 hours of intubation in adults and 1 week of intubation in neonates can cause the injury. Infants born prematurely can be intubated for a longer amount of time due to the fact that they have more flexible cartilage and a larynx located high in the airway. 90% of acquired cases in children are due to intubation, due to the ring of cartilage in the upper airway. Less commonly, infections, such as bacterial tracheitis, tuberculosis, histoplasmosis, diphtheria, and laryngeal papillomatosis can cause it. Systemic diseases, such as amyloidosis, granulomatosis with polyangiitis, sarcoidosis, inflammatory bowel disease, scleroderma, relapsing polychondritis, and polyarthritis, can also cause it. Other causes may include aspiration of foreign bodies, burns, and exposure to occupational hazards. Very rarely, the condition may also have no known cause, in which case it is known as idiopathic subglottic stenosis.
Mechanism
High cuff pressure or long-term intubation can cause damage to the tracheal mucosa, causing inflammation, ulceration, and breakdown of cartilage. When the injury heals, scarring occurs, narrowing the airway. Treatment-related risk factors include repeated intubation, the presence of a nasogastric tube, and size of an endotracheal tube. Person-related risk factors include systemic diseases, the likelihood of infection, and inadequate perfusion. Acid reflux may cause narrowing due to scarring resulting from stomach acid damaging the tracheal mucosa. 10-23% of causes result due to narrowing arising from granulomatosis with polyangiitis. In these cases, it is believed that this is more common in people under the age of 20. Around 66% of sarcoidosis cases involve the airway.
Diagnosis
CT scans and MRI (magnetic resonance imaging) can help in diagnosis. X-rays can determine the location and size of the narrowed airway portion. Optical coherence tomography (OCT) can help observe the progression of the injury. Esophageal pH monitoring can help detect any acid reflux, which can worsen the condition. An endoscope can be inserted and used to see the vocal cords, airway, and esophagus. Spirometry is a useful way to measure respiratory function. People affected by subglottic stenosis have a FEV1 of over 10.
Subglottic stenosis is graded according to the Cotton-Myer classification system from one to four based on the severity of the blockage. Grade 1 is up to 50% obstruction, Grade 2 is 50-70% obstruction, Grade 3 is 70-99% obstruction, and Grade 4 is with no visible lumen.
Treatment
The goal of treatment is to relieve any breathing difficulty and to ensure that the airway remains open in the long term. In mild cases, the disease can be treated with endoscopic balloon dilation. In severe cases, open surgery is done. Owing to the risk of complications, tracheostomy is avoided if possible.
Surgery
In severe cases, the condition frequently recurs after dilation, and the main treatment is open surgery. There are three main surgical procedures that are used when treating subglottic stenosis. These include endoscopy, open neck surgery, and tracheotomy. Endoscopic procedures include dilation via balloon or rigid, incision via laser, and stent placement.
Other
In mild cases, such as cases with only granuloma or thin, web-like tissue, dilation is able to remove the lesion. In severe cases, dilation and laser treatment only works temporarily, and the condition frequently recurs. Repeated procedures, especially stents, come with the risk of increasing the damaged area. Also, laser resection has a risk of damaging the cartilage underneath. For this reason, surgery is typically done. In addition to surgery, mitomycin can be applied topically and glucocorticoids can be injected.Idiopathic cases are usually treated via endoscopic balloon dilation, and dilation may be improved by injecting corticosteroids. It is also the safest and main treatment in pregnant women. It allows dilation via noninvasive measures such as expanding a balloon catheter via ventilation.
Prognosis
The condition frequently recurs after dilation. The prognosis after surgery is good if it is done carefully to avoid complications.
Epidemiology
The condition has decreased in frequency over time, due to improved management of people on a ventilator. The condition occurs in around 1% of endotracheal tube users.
References
== External links == |
Arrhythmogenic cardiomyopathy | Arrhythmogenic cardiomyopathy (ACM), arrhythmogenic right ventricular dysplasia (ARVD), or arrhythmogenic right ventricular cardiomyopathy (ARVC), most commonly is an inherited heart disease.ACM is caused by genetic defects of the parts of heart muscle (also called myocardium or cardiac muscle) known as desmosomes, areas on the surface of heart muscle cells which link the cells together. The desmosomes are composed of several proteins, and many of those proteins can have harmful mutations.
ARVC can also develop in intense endurance athletes in the absence of desmosomal abnormalities. Exercise-induced ARVC cause possibly is a result of excessive right ventricular wall stress during high intensity exercise.The disease is a type of non-ischemic cardiomyopathy that primarily involves the right ventricle, though cases of exclusive left ventricular disease have been reported. It is characterized by hypokinetic areas involving the free wall of the ventricle, with fibrofatty replacement of the myocardium, with associated arrhythmias often originating in the right ventricle. The nomenclature ARVD is currently thought to be inappropriate and misleading as ACM does not involve dysplasia of the ventricular wall. Cases of ACM originating from the left ventricle led to the abandonment of the name ARVC.
ACM can be found in association with diffuse palmoplantar keratoderma, and woolly hair, in an autosomal recessive condition called Naxos disease, because this genetic abnormality can also affect the integrity of the superficial layers of the skin most exposed to pressure stress.: 513 ACM is an important cause of ventricular arrhythmias in children and young adults. It is seen predominantly in males, and 30–50% of cases have a familial distribution.
Signs and symptoms
Those affected by arrhythmogenic cardiomyopathy may not have any symptoms at all despite having significant abnormalities in the structure of their hearts. If symptoms do occur, the initial presentation is often due to abnormal heart rhythms (arrhythmias) which in arrhythmogenic cardiomyopathy may take the form of palpitations, or blackouts. Sudden death may be the first presentation of ACM without any preceding symptoms. These symptoms often occur during adolescence and early adulthood, but signs of ACM may rarely be seen in infants.
As ACM progresses, the muscle tissue within the ventricles may dilate and weaken. The right ventricle typically weakens first, leading to fatigue and ankle swelling. In the later stages of the disease in which both ventricles are involved shortness of breath may develop, especially when lying flat.The first clinical signs of ACM are usually during adolescence and early adulthood. However, rarely, signs of ACM have been demonstrated in infants.
Causes
Genetics
ACM is usually inherited in an autosomal dominant pattern, with variable expression. Only 30% to 50% of individuals affected by ACM will test positive to one of the known genetic mutations in chromosomal loci associated with the disease. Novel studies showed that mutations (point mutations) in genes encoding for desmosomal proteins (see intercalated disc) are the main causatives for the development of this disease. Recently it has been shown, that mutations in the desmin DES gene could cause ACM. Desmin is an intermediate filament protein, which is linked to the desmosomes. Different DES mutations cause an abnormal aggregation of desmin and associated proteins. The penetrance is 20–35% in general, but significantly higher in Italy. Seven gene loci have been implicated in ACM. It is unclear whether the pathogenesis varies with the different loci involved. Standard genetic screening test are currently tested and evaluated in different state of the art cardiovascular research centres and hospitals. Types include:
Exercise-induced ARVC
In recent years, several studies have found excessive long-term sports activity to be a cause of exercise-induced arrhythmogenic right ventricular cardiomyopathy (EIARVC). For some athletes ARVC might develop due to high-endurance exercise and it most often develops without an underlying desmosomal abnormalities, possibly only as a result of excessive right ventricular (RV) wall stress during very high volumes of training, which is known to be causing a disproportionate remodeling of RV.In a 2003 study, 46 endurance athletes (mostly cyclists) presented with various symptoms suggestive of arrhythmia of RV origin. 59% of participants testing met criteria for ARVC and another 30% for possible ARVC. And only 1 athlete of the group had a family history of hereditable ARVC.Exercise-induced ARVC and athletes heart has an overlapping features.
Pathogenesis
The pathogenesis of ACM is largely unknown. Apoptosis (programmed cell death) appears to play a large role. It was previously thought that only the right ventricle is involved, but recent cohorts have shown many cases of left ventricular disease and biventricular disease. The disease process starts in the subepicardial region and works its way towards the endocardial surface, leading to transmural involvement (possibly accounting for the aneurysmal dilatation of the ventricles). Residual myocardium is confined to the subendocardial region and the trabeculae of the ventricles. These trabeculae may become hypertrophied.
Aneurysmal dilatation is seen in 50% of cases at autopsy. It usually occurs in the diaphragmatic, apical, and infundibular regions (known as the triangle of dysplasia). The left ventricle is involved in 50–67% of individuals. If the left ventricle is involved, it is usually late in the course of disease, and confers a poor prognosis.
There are two pathological patterns seen in ACM, Fatty infiltration and fibro-fatty infiltration.
Fatty infiltration
The first, fatty infiltration, is confined to the right ventricle. This involves a partial or near-complete substitution of myocardium with fatty tissue without wall thinning. It involves predominantly the apical and infundibular regions of the RV. The left ventricle and ventricular septum are usually spared. No inflammatory infiltrates are seen in fatty infiltration. There is evidence of myocyte (myocardial cell) degeneration and death seen in 50% of cases of fatty infiltration.
Fibro-fatty infiltration
The second, fibro-fatty infiltration, involves replacement of myocytes with fibrofatty tissue. A patchy myocarditis is involved in up to 2/3 of cases, with inflammatory infiltrates (mostly T cells) seen on microscopy. Myocardial atrophy is due to injury and apoptosis. This leads to thinning of the RV free wall (to < 3 mm thickness) Myocytes are replaced with fibrofatty tissue. The regions preferentially involved include the RV inflow tract, the RV outflow tract, and the RV apex. However, the LV free wall may be involved in some cases. Involvement of the ventricular septum is rare. The areas involved are prone to aneurysm formation.
The Role of Exercise
Recently, some studies have identified strenuous exercise as a novel risk for accelerated progression of the disease. One retrospective study on 301 patients conclusively demonstrated that the subpopulations participating in strenuous physical activity (professional athletes for example) had an earlier onset of symptoms and earlier mortality compared to other populations.
Ventricular arrhythmias
Ventricular arrhythmias due to ACM typically arise from the diseased right ventricle. The type of arrhythmia ranges from frequent premature ventricular complexes (PVCs) to ventricular tachycardia (VT) to ventricular fibrillation (VF).
While the initiating factor of the ventricular arrhythmias is unclear, it may be due to triggered activity or reentry.
Ventricular arrhythmias are usually exercise-related, suggesting that they are sensitive to catecholamines. The ventricular beats typically have a right axis deviation. Multiple morphologies of ventricular tachycardia may be present in the same individual, suggesting multiple arrhythmogenic foci or pathways.
Right ventricular outflow tract (RVOT) tachycardia is the most common VT seen in individuals with ACM. In this case, the EKG shows a left bundle branch block (LBBB) morphology with an inferior axis.
Diagnosis
The differential diagnosis for the ventricular tachycardia due to ACM include:
Congenital heart disease
Repaired tetralogy of Fallot
Ebsteins anomaly
Uhls anomaly
Atrial septal defect
Partial anomalous venous return
Acquired heart disease
Tricuspid valve disease
Pulmonary hypertension
Right ventricular infarction
Bundle-branch re-entrant tachycardia
Miscellaneous
Pre-excited AV re-entry tachycardia
Idiopathic RVOT tachycardia
SarcoidosisIn order to make the diagnosis of ACM, a number of clinical tests are employed, including the electrocardiogram (EKG), echocardiography, right ventricular angiography, cardiac MRI, and genetic testing.
Electrocardiogram
90% of individuals with ARVD have some EKG abnormality. The most common EKG abnormality seen in ACM is T wave inversion in leads V1 to V3. However, this is a non-specific finding, and may be considered a normal variant in right bundle branch block (RBBB), women, and children under 12 years old.
RBBB itself is seen frequently in individuals with ACM. This may be due to delayed activation of the right ventricle, rather than any intrinsic abnormality in the right bundle branch.
The epsilon wave is found in about 50% of those with ACM. This is described as a terminal notch in the QRS complex. It is due to slowed intraventricular conduction. The epsilon wave may be seen on a surface EKG; however, it is more commonly seen on signal averaged EKGs.
Ventricular ectopy seen on a surface EKG in the setting of ACM is typically of left bundle branch block (LBBB) morphology, with a QRS axis of −90 to +110 degrees. The origin of the ectopic beats is usually from one of the three regions of fatty degeneration (the "triangle of dysplasia"): the RV outflow tract, the RV inflow tract, and the RV apex.
Signal averaged ECG (SAECG) is used to detect late potentials and epsilon waves in individuals with ACM.
Echocardiography
Echocardiography may reveal an enlarged, hypokinetic right ventricle with a paper-thin RV free wall. The dilatation of the RV will cause dilatation of the tricuspid valve annulus, with subsequent tricuspid regurgitation. Paradoxical septal motion may also be present.
MRI
Fatty infiltration of the RV free wall can be visible on cardiac MRI. Fat has increased intensity in T1-weighted images. However, it may be difficult to differentiate intramyocardial fat and the epicardial fat that is commonly seen adjacent to the normal heart. Also, the sub-tricuspid region may be difficult to distinguish from the atrioventricular sulcus, which is rich in fat.
Cardiac MRI can visualize the extreme thinning and akinesis of the RV free wall. However, the normal RV free wall may be about 3 mm thick, making the test less sensitive.
Angiography
Right ventricular angiography is considered the gold standard for the diagnosis of ACM. Findings consistent with ACM are an akinetic or dyskinetic bulging localized to the infundibular, apical, and subtricuspid regions of the RV. The specificity is 90%; however, the test is observer dependent.
Biopsy
Transvenous biopsy of the right ventricle can be highly specific for ACM, but it has low sensitivity. False positives include other conditions with fatty infiltration of the ventricle, such as long-term excessive alcohol use and Duchenne or Becker muscular dystrophy.
False negatives are common, however, because the disease progresses typically from the epicardium to the endocardium (with the biopsy sample coming from the endocardium), and the segmental nature of the disease. Also, due to the paper-thin right ventricular free wall that is common in this disease process, most biopsy samples are taken from the ventricular septum, which is commonly not involved in the disease process.
A biopsy sample that is consistent with ACM would have > 3% fat, >40% fibrous tissue, and <45% myocytes.
A post mortem histological demonstration of full thickness substitution of the RV myocardium by fatty or fibro-fatty tissue is consistent with ACM.
Genetic testing
ACM is an autosomal dominant trait with reduced penetrance. Approximately 40–50% of ACM patients have a mutation identified in one of several genes encoding components of the desmosome, which can help confirm a diagnosis of ACM. Since ACM is an autosomal dominant trait, children of an ACM patient have a 50% chance of inheriting the disease-causing mutation. Whenever a mutation is identified by genetic testing, family-specific genetic testing can be used to differentiate between relatives who are at-risk for the disease and those who are not. ACM genetic testing is clinically available.
Diagnostic criteria
There is no pathognomonic feature of ACM. The diagnosis of ACM is based on a combination of major and minor criteria. To make a diagnosis of ACM requires either 2 major criteria or 1 major and 2 minor criteria or 4 minor criteria.Major criteria
Right ventricular dysfunction
Severe dilatation and reduction of RV ejection fraction with little or no LV impairment
Localized RV aneurysms
Severe segmental dilatation of the RV
Tissue characterization
Fibrofatty replacement of myocardium on endomyocardial biopsy
Electrocardiographical abnormalities
Epsilon waves in V1 – V3
Localized prolongation (>110 ms) of QRS in V1 – V3
Inverted T waves in V1 -V3 in an individual over 12 years old, in the absence of a right bundle branch block (RBBB)
Ventricular tachycardia with a left bundle branch block (LBBB) morphology, with superior axis
Family history
Familial disease confirmed either clinically or on autopsy or surgeryMinor criteria
Right ventricular dysfunction
Mild global RV dilatation and/or reduced ejection fraction with normal LV.
Mild segmental dilatation of the RV
Regional RV hypokinesis
Tissue characterization
Electrocardiographical abnormalities
Late potentials on signal averaged EKG.
Ventricular tachycardia with a left bundle branch block (LBBB) morphology, with inferior or unknown axis
Frequent PVCs (> 500 PVCs / 24 hours)
Management
The goal of management of ACM is to decrease the incidence of sudden cardiac death. This raises a clinical dilemma: How to prophylactically treat the asymptomatic patient who was diagnosed during family screening.
A certain subgroup of individuals with ACM are considered at high risk for sudden cardiac death. Associated characteristics include:
Young age
Competitive sports activity
Malignant familial history
Extensive RV disease with decreased right ventricular ejection fraction.
Left ventricular involvement
Syncope
Episode of ventricular arrhythmiaManagement options include pharmacological, surgical, catheter ablation, and placement of an implantable cardioverter-defibrillator.
Prior to the decision of the treatment option, programmed electrical stimulation in the electrophysiology laboratory may be performed for additional prognostic information. Goals of programmed stimulation include:
Assessment of the diseases arrhythmogenic potential
Evaluate the hemodynamic consequences of sustained VT
Determine whether the VT can be interrupted via antitachycardia pacing (ATP).Regardless of the management option chosen, the individual is typically advised to undergo lifestyle modification, including avoidance of strenuous exercise, cardiac stimulants (i.e.: caffeine, nicotine, pseudoephedrine) and alcohol.
Regarding physical activity and exercise, ARVC patients, as well as gene carriers of pathogenic ARVC-associated desmosomal mutations, should not participate in competitive sports. These patients should be advised to limit their exercise programmes to leisure-time activities and remain under clinical surveillance.
Medications
Pharmacologic management of ACM involves arrhythmia suppression and prevention of thrombus formation.
Sotalol, a beta blocker and a class III antiarrhythmic agent, is the most effective antiarrhythmic agent in ACM. Other antiarrhythmic agents used include amiodarone and conventional beta blockers (i.e.: metoprolol). If antiarrhythmic agents are used, their efficacy should be guided by series ambulatory Holter monitoring, to show a reduction in arrhythmic events.
While angiotensin converting enzyme inhibitors (ACE Inhibitors) are well known for slowing progression in other cardiomyopathies, they have not been proven to be helpful in ACM.
Individuals with decreased RV ejection fraction with dyskinetic portions of the right ventricle may benefit from long term anticoagulation with warfarin to prevent thrombus formation and subsequent pulmonary embolism.
Catheter ablation
Catheter ablation may be used to treat intractable ventricular tachycardia.
It has a 60–90% success rate. Unfortunately, due to the progressive nature of the disease, recurrence is common (60% recurrence rate), with the creation of new arrhythmogenic foci. Indications for catheter ablation include drug-refractory VT and frequent recurrence of VT after ICD placement, causing frequent discharges of the ICD.
Implantable cardioverter-defibrillator
An ICD is the most effective prevention against sudden cardiac death. Due to the prohibitive cost of ICDs, they are not routinely placed in all individuals with ACM.
Indications for ICD placement in the setting of ACM include:
Cardiac arrest due to VT or VF
Symptomatic VT that is not inducible during programmed stimulation
Failed programmed stimulation-guided drug therapy
Severe RV involvement with poor tolerance of VT
Sudden death of immediate family memberSince ICDs are typically placed via a transvenous approach into the right ventricle, there are complications associated with ICD placement and follow-up.
Due to the extreme thinning of the RV free wall, it is possible to perforate the RV during implantation, potentially causing pericardial tamponade. Because of this, every attempt is made at placing the defibrillator lead on the ventricular septum.
After a successful implantation, the progressive nature of the disease may lead to fibro-fatty replacement of the myocardium at the site of lead placement. This may lead to undersensing of the individuals electrical activity (potentially causing inability to sense VT or VF), and inability to pace the ventricle.
Heart transplant
Heart transplant may be performed in ACM. It may be indicated if the arrhythmias associated with the disease are uncontrollable or if there is severe bi-ventricular heart failure that is not manageable with pharmacological therapy.
Family screening
All first degree family members of the affected individual should be screened for ACM. This is used to establish the pattern of inheritance. Screening should begin during the teenage years unless otherwise indicated. Screening tests include:
Echocardiogram
EKG
Signal averaged EKG
Holter monitoring
Cardiac MRI
Exercise stress test
Prognosis
There is a long asymptomatic lead-time in individuals with ACM. While this is a genetically transmitted disease, individuals in their teens may not have any characteristics of ACM on screening tests.
Many individuals have symptoms associated with ventricular tachycardia, such as palpitations, light-headedness, or syncope. Others may have symptoms and signs related to right ventricular failure, such as lower extremity edema, or liver congestion with elevated hepatic enzymes.
ACM is a progressive disease. Over time, the right ventricle becomes more involved, leading to right ventricular failure. The right ventricle will fail before there is left ventricular dysfunction. However, by the time the individual has signs of overt right ventricular failure, there will be histological involvement of the left ventricle. Eventually, the left ventricle will also become involved, leading to bi-ventricular failure. Signs and symptoms of left ventricular failure may become evident, including congestive heart failure, atrial fibrillation, and an increased incidence of thromboembolic events.
Epidemiology
The prevalence of ACM is about 1/10,000 in the general population in the United States, although some studies have suggested that it may be as common as 1/1,000. Recently, 1/200 were found to be carriers of mutations that predispose to ACM. Based on these findings and other evidence, it is thought that in most patients, additional factors such as other genes, athletic lifestyle, exposure to certain viruses, etc. may be required for a patient to eventually develop signs and symptoms of ACM. It accounts for up to 17% of all sudden cardiac deaths in the young. In Italy, the prevalence is 40/10,000, making it the most common cause of sudden cardiac death in the young population.
Society and culture
Notable cases
Columbus Crew midfielder Kirk Urso collapsed out with friends on August 5, 2012, and was pronounced dead an hour later. An autopsy later revealed the disease to be the likely culprit.
Sevilla FC and Spanish international left wing-back Antonio Puerta died from the condition, at the age of 22, on 28 August 2007, three days after suffering several cardiac arrests, while disputing a La Liga game against Getafe CF.
Englishman Matt Gadsby also died from the condition after collapsing on the pitch on 9 September 2006, while playing for Hinckley United in a Conference North game against Harrogate Town.
Suzanne Crough, an American child actress best known for her role on The Partridge Family, died suddenly from the condition in 2015 at age 52.
James Taylor English international cricketer, retired April 2016.
Krissy Taylor, an American model, died at the age of 17 on July 2, 1995, in the family home in Florida. Her official cause of death was cardiac arrhythmia and severe asthma, the latter of which she had never been diagnosed with. Her family had independent experts examine tissue samples of her heart muscle and they concluded that the most likely cause of death was a missed diagnosis of ACM.
Jordan Boyd (1997-2013), Canadian junior hockey player. He was posthumously diagnosed with the ailment after passing away from a collapse from training camp in 2013.
See also
Woolly hair nevus
List of conditions caused by problems with junctional proteins
References
External links
GeneReviews/NCBI/NIH/UW entry on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant
OMIM entries on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant |
Mastocytosis | Mastocytosis, a type of mast cell disease, is a rare disorder affecting both children and adults caused by the accumulation of functionally defective mast cells (also called mastocytes) and CD34+ mast cell precursors.People affected by mastocytosis are susceptible to a variety of symptoms, including itching, hives, and anaphylactic shock, caused by the release of histamine and other pro-inflammatory substances from mast cells.
Signs and symptoms
When mast cells undergo degranulation, the substances that are released can cause a number of symptoms that can vary over time and can range in intensity from mild to severe. Because mast cells play a role in allergic reactions, the symptoms of mastocytosis often are similar to the symptoms of an allergic reaction. They may include, but are not limited to
Fatigue
Skin lesions (urticaria pigmentosa), itching, and dermatographic urticaria (skin writing)
"Dariers Sign", a reaction to stroking or scratching of urticaria lesions.
Abdominal discomfort
Nausea and vomiting
Diarrhea
Olfactive intolerance
Ear/nose/throat inflammation
Anaphylaxis (shock from allergic or immune causes)
Episodes of very low blood pressure (including shock) and faintness
Bone or muscle pain
Decreased bone density or increased bone density (osteoporosis or osteosclerosis)
Headache
Depression
Ocular discomfort
Increased stomach acid production causing peptic ulcers (increased stimulation of enterochromaffin cell and direct histamine stimulation on parietal cell)
Malabsorption (due to inactivation of pancreatic enzymes by increased acid)
HepatosplenomegalyThere are few qualitative studies about the effects of mastocytosis on daily life. However, a Danish study from 2018 describes the multidimensional impact of the disease on everyday life.
Pathophysiology
Mast cells are located in connective tissue, including the skin, the linings of the stomach and intestine, and other sites. They play an important role in the immune defence against bacteria and parasites. By releasing chemical "alarms" such as histamine, mast cells attract other key players of the immune defense system to areas of the body where they are needed.Mast cells seem to have other roles as well. Because they gather together around wounds, mast cells may play a part in wound healing. For example, the typical itching felt around a healing scab may be caused by histamine released by mast cells. Researchers also think mast cells may have a role in the growth of blood vessels (angiogenesis). No one with too few or no mast cells has been found, which indicates to some scientists we may not be able to survive with too few mast cells.Mast cells express a cell surface receptor, c-kit (CD117), which is the receptor for stem cell factor (scf). In laboratory studies, scf appears to be important for the proliferation of mast cells. Mutations of the gene coding for the c-kit receptor (mutation KIT(D816V)), leading to constitutive signalling through the receptor is found in >90% of patients with systemic mastocytosis.
Diagnosis
Diagnosis of urticaria pigmentosa (cutaneous mastocytosis, see above) can often be done by seeing the characteristic lesions that are dark brown and fixed. A small skin sample (biopsy) may help confirm the diagnosis.In case of suspicion of systemic disease the level of serum tryptase in the blood can be of help. If the base level of s-tryptase is elevated, this implies that the mastocytosis can be systemic. In cases of suspicion of SM help can also be drawn from analysis of mutation in KIT(D816V) in peripheral blood using sensitive PCR-technologyTo set the diagnosis of systemic mastocytosis, certain criteria must be met. Either one major + one minor criterium or 3 minor criteria has to be fulfilled:
Major criterion
Dense infiltrates of >15 mast cells in the bone marrow or an extracutaneous organ
Minor criteria
Aberrant phenotype on the mast cells (pos. for CD2 and/or CD25)
Aberrant mast cell morphology (spindle-shaped)
Finding of mutation in KIT(D816V)
S-tryptase >20 ng/ml
Other mast cell diseases
Other types of mast cell disease include:
Monoclonal mast cell activation, defined by the World Health Organization definitions 2010, also has increased mast cells but insufficient to be systemic mastocytosis (in World Health Organization Definitions)
Mast cell activation syndrome – has normal number of mast cells, but all the symptoms and in some cases the genetic markers of systemic mastocytosis
Another known but rare mast cell proliferation disease is mast cell sarcoma.
Classification
Mastocytosis can occur in a variety of forms:
Cutaneous mastocytosis (CM)
The most common cutaneous mastocytosis is maculopapular cutaneous mastocytosis, previously named papular urticaria pigmentosa (UP), more common in children, although also seen in adults. Telangiectasia macularis eruptiva perstans (TMEP) is a much rarer form of cutaneous mastocytosis that affects adults.[2] MPCM and TMEP can be a part of indolent systemic mastocytosis. This should be considered if patients develop any systemic symptoms
Generalized eruption of cutaneous mastocytosis (adult type) is the most common pattern of mastocytosis presenting to the dermatologist, with the most common lesions being macules, papules, or nodules that are disseminated over most of the body but especially on the upper arms, legs, and trunk
Diffuse cutaneous mastocytosis has diffuse involvement in which the entire integument may be thickened and infiltrated with mast cells to produce a peculiar orange color, giving rise to the term "homme orange."Cutaneous mastocytosis in children usually presents in the first year after birth and in most cases vanishes during adolescence.
Systemic mastocytosis (SM)
Systemic mastocytosis involves the bone marrow in the majority of cases and in some cases other internal organs, usually in addition to involving the skin. Mast cells collect in various tissues and can affect organs where mast cells do not normally inhabit such as the liver, spleen and lymph nodes, and organs which have normal populations but where numbers are increased. In the bowel, it may manifest as mastocytic enterocolitis. However, normal ranges for mast cell counts in the gastrointestinal tract mucosa are not well established in the literature, and depend upon the exact location (e.g. right versus left colon), gender, and patient populations (such as asymptomatic patients versus patients with chronic diarrhea of unknown etiology). Quantitative mast cell stains may yield little diagnostic information, and further research studies are warranted to determine whether "mastocytic enterocolitis" truly represents a distinct entity.There are five types of systemic mastocytosis:
Indolent systemic mastocytosis (ISM). The most common SM (>90%)
Smouldering systemic mastocytosis (SSM)
Systemic mastocytosis with associated hematological neoplasm (SM-AHN)
Aggressive systemic mastocytosis (ASM)
Mast cell leukemia (MCL)
Treatment
There is no cure for mastocytosis, but there are a number of medicines to help treat the symptoms:
Anti-mediator therapy
Antihistamines block receptors targeted by histamine released from mast cells. Both H1 and H2 blockers may be helpful, often in combination.
Leukotriene antagonists block receptors targeted by leukotrienes released from mast cells.
Mast cell stabilizers help prevent mast cells from releasing their chemical contents. Cromoglicic acid is the only medicine specifically approved by the FDA for the treatment of mastocytosis. Ketotifen is available in Canada and Europe and more recently in the U.S. It is also available as eyedrops (Zaditor).
Proton-pump inhibitors help reduce production of gastric acid, which is often increased in patients with mastocytosis. Excess gastric acid can harm the stomach, esophagus, and small intestine.
Epinephrine constricts blood vessels and opens airways to maintain adequate circulation and ventilation when excessive mast cell degranulation has caused anaphylaxis.
Salbutamol and other beta-2 agonists open airways that can constrict in the presence of histamine.
Corticosteroids can be used topically, inhaled, or systemically to reduce inflammation associated with mastocytosis.
Drugs to prevent/treat osteoporosis include Calcium-Vitamine D, bisphosphonates and in rare cases inhibitors of RANK-LAntidepressants are an important and often overlooked tool in the treatment of mastocytosis. Depression and other neurological symptoms have been noted in mastocytosis. Some antidepressants, such as doxepin and mirtazapine, are themselves potent antihistamines and can help relieve physical as well as cognitive symptoms.
Cytoreductive therapy
In cases of advanced systemic mastocytosis or rare cases with indolent systemic mastocytosis with very troublesome symptoms, cytoreductive therapy can be indicated.
ɑ-interferon. Given as subcutaneous injections. Side effects include fatigue and influenza-like symptoms
Cladribine (CdA). Chemotherapy which is given as subcutaneous injections. Side effects include immunodeficiency and infections.
Tyrosine kinase inhibitors (TKI)
Midostaurin. TKI acting on many different tyrosine kinases, approved by FDA and EMA for advanced mastocytosis
Imatinib. Can have effect in rare cases without mutation in KIT(D816V)
Masitinib. Is being tested in trials. Not approved.
Midostaurin - 60% respond.
Avapritinib in trials; currently being tested but showing promise in reduction of tryptase levels.Allogeneic stem cell transplantation has been used in rare cases with aggressive systemic mastocytosis in patients deemed to be fit for the procedure.
Other
Treatment with ultraviolet light can relieve skin symptoms, but may increase the risk of skin cancer.
Prognosis
Patients with indolent systemic mastocytosis have a normal life expectancy. The prognosis for patients with advanced systemic mastocytosis differs depending on type of disease with MCL being the most serious form with short survival.
Epidemiology
The true incidence and prevalence of mastocytosis is unknown, but mastocytosis generally has been considered to be an "orphan disease"; orphan diseases affect 200,000 or fewer people in the United States. Mastocytosis, however, often may be misdiagnosed, as it typically occurs secondary to another condition, and thus may occur more frequently than assumed.[
Research
National Institute of Allergy and Infectious Diseases scientists have been studying and treating patients with mastocytosis for several years at the National Institutes of Health (NIH) Clinical Center.Some of the most important research advances for this rare disorder include improved diagnosis of mast cell disease and identification of growth factors and genetic mechanisms responsible for increased mast cell production. Researchers are currently evaluating approaches to improve ways to treat mastocytosis.Scientists also are focusing on identifying disease-associated mutations (changes in genes). NIH scientists have identified some mutations, which may help researchers understand the causes of mastocytosis, improve diagnosis, and develop better treatments.In Europe the European Competence Network on Mastocytosis (ECNM) coordinates studies, registries and education on mastocytosis.
History
Urticaria pigmentosa was first described in 1869. The first report of a primary mast cell disorder is attributed to Unna, who in 1887 reported that skin lesions of urticaria pigmentosa contained numerous mast cells. Systemic mastocytosis was first reported by French scientists in 1936.
See also
Mastocytoma
References
Further reading
Gruchalla, Rebecca S. (June 1995). "Mastocytosis: Developments During the Past Decade". The American Journal of the Medical Sciences. 309 (6): 328–338. doi:10.1097/00000441-199506000-00007. PMID 7771504. |
Arthrofibrosis | Arthrofibrosis (from Greek: arthro- joint, fibrosis – scar tissue formation) has been described in most joints like knee, hip, ankle, foot joints, shoulder (frozen shoulder, adhesive capsulitis), elbow (stiff elbow), wrist, hand joints as well as spinal vertebrae. It can occur after injury or surgery or may arise without an obvious cause. There is excessive scar tissue formation within the joint and/or surrounding soft tissues leading to painful restriction of joint motion that persists despite physical therapy and rehabilitation. The scar tissue may be located inside the knee joint or may involve the soft tissue structures around the knee joint, or both locations.
The pathology that causes arthrofibrosis also causes other forms of fibrosis. Injury and inflammation activates fibroblasts and other cell types, turning them into myofibroblasts which create scar tissue and more inflammation.
Arthrofibrosis of the knee (frozen knee)
Arthrofibrosis of the knee, also known as "frozen knee", has been one of the more studied joints as a result of its frequency of occurrence. Arthrofibrosis can follow knee injury and knee surgeries like arthroscopic knee surgery or knee replacement. Scar tissue can cause structures of the knee to become contracted, restricting normal motion. Depending on the site of scarring, knee cap mobility and/or joint range of motion (i.e. flexion, extension, or both) may be affected. Symptoms experienced as a result of arthrofibrosis of the knee include stiffness, pain, limping, heat, swelling, crepitus, and/or weakness. Clinical diagnosis may also include the use of magnetic resonance imaging (or MRI) to visualize the knee compartments affected. The consequent pain may lead to the cascade of quadriceps weakness, patellar tendon shortening and scarring in the tissues around the knee cap—with an end stage of permanent patella infera—where the knee cap is pulled down into an abnormal position where it becomes vulnerable to joint surface damage.
Arthrofibrosis after knee injury, knee arthroscopy or other surgeries
The first step in treating arthrofibrosis is appropriately directed physical therapy with a focus on icing and elevating and passive stretching exercises such as continuous passive motion (CPM). Passive stretching can increase range of motion if conducted frequently and carefully so that tissues are not torn. There are a number of treatment options and treatment varies depending on the knowledge of the treating clinician and on the cause and duration of the fibrosis. Often physical therapy is used as an attempt at conservative management. Knowledge of the role of inflammation in arthrofibrosis has led a cautionary approach to exercise, because exercise increases inflammation. Advice to AF patients now typically consists of "listen to your knee" and stop, or reduce, activities that increase pain during and after exercise. Aggressive exercise of the affected limb may cause permanent damage.
If physical therapy fails options include manipulation under anaesthesia (MUA), arthroscopic lysis of adhesions and open lysis of adhesions. Although MUA and surgery can be successful, the resulting increase in inflammation may cause scar tissue to rapidly return and symptoms can worsen.Pharmacological interventions such as anti-inflammatory medications and supplements are increasingly used to treat arthrofibrosis. Biologics that reduce the signalling of the major inflammatory cytokines TNF-α (Simponi, Humira) and IL-1β (anakinra) are promising treatments. Consultation with a rheumatologist can help to determine appropriate medications.
After knee replacement
Arthrofibrosis can occur after total knee replacement or partial knee replacement, when excessive scar tissue (collagen fibril) deposition occurs in and around the knee. This can be accompanied by shortening of the patellar tendon (patella baja/infera) which can also contribute to limited flexion. The rates of AF after TKA vary widely in the literature as there is no standard definition. One studys definition is a total range of motion (ROM) <90 degrees constitutes AF, another definition is flexion contracture >10 degrees, or inability to flex the knee >100 degrees. AF is a diagnosis of exclusion; before making a final diagnosis of arthrofibrosis, other causes of stiffness following knee replacement should be excluded (ex: infection, malposition of the implants, or mechanical block to motion).
In the case of AF after total knee arthroplasty (TKA) management traditionally consisted of aggressive physical therapy, and in the case that failed, manipulation under anesthesia (MUA). As discussed above, aggressive exercise is now avoided. The rates of MUA after TKA vary widely. There are several reasons for this: there is no definite consensus to when a MUA is required (different surgeons follow different indications), there is no standardized definition of arthrofibrosis (see above), and MUA is not always a reliable treatment. MUAs can lead to adverse outcomes, including fractures, rupture of tendons, damage to the prosthesis, heterotrophic ossification, muscle tears and bleeding and the return of scar tissue. For these reasons treatment patterns vary widely. MUA after TKA is more likely to be to be successful if performed in the first 8–12 weeks after surgery. After 12 weeks manipulation is much less likely to have an acceptable outcome.
If the fibrosis is chronic (more than 12 weeks) there is a decreased likelihood of success with MUA, and open lysis of adhesions is sometime performed. However, this carries with it the attendant risks of another open procedure (i.e., infection, blood clots, blood loss, etc.) and the return of scar tissue.
References
External links
https://arthrofibrosis.info
http://kneearthrofibrosis.com
http://www.kneeguru.co.uk/KNEEnotes/primers/complications-rehabilitation/key-arthrofibrosis-resources-kneeguru-site |
Oil acne | Oil acne is an occupational skin condition caused by exposure to oils used in industry.
See also
Soot tattoo
List of cutaneous conditions
References
== External links == |
Pulmonary alveolar microlithiasis | Pulmonary alveolar microlithiasis (PAM) is a rare, inherited disorder of lung phosphate balance that is associated with small stone formation in the airspaces of the lung. Mutations in the gene SLC34A2 result in loss of a key sodium, phosphate co-transporter (called Npt2b), known to be expressed in distal alveolar type II cells, as well as in the mammary gland, and to a lesser extent in intestine, kidney, skin, prostate and testes. As the disease progresses, the lung fields become progressively more dense (white) on the chest xray, and low oxygen level, lung inflammation and fibrosis, elevated pressures in the lung blood vessels, and respiratory failure ensue, usually in middle age. The clinical course of PAM can be highly variable, with some patients remaining asymptomatic for decades, and others progressing more rapidly. There is no effective treatment, and the mechanisms of stone formation, inflammation and scarring are not known.
Signs and symptoms
Patients typically have no symptoms until the third or fourth decade of life. In most cases, the disease is discovered incidentally on routine chest Xray. The most common symptoms include the following:
dyspnea
dry cough
chest pain
sporadic hemoptysis
asthenia
pneumothoraces
Genetics
PAM is hereditary and another involved family member can be identified in 36% to 61% of cases. Impaired activity of the SLC34A2 gene is responsible for PAM.The SLC34A2 gene encodes a membrane protein that is expressed primarily in the apical portions of alveolar type II cells and is the most abundant phosphate carrier in the lungs.
Pathogenesis
Type II alveolar cells have many important functions in the lung, including the production of pulmonary surfactant, maintenance of fluid balance and composition in the airspace. Phospholipids that make up pulmonary surfactant are broken down by macrophages, releasing phosphate into the alveolar lining fluid. The loss of the Npt2b phosphate transported eliminates the ability of alveolar type II cells to pump phosphorus ions from the alveolar space back into the bloodstream, and leads to microlith formation.Epithelial deletion of Npt2b in mice results in an authentic mimic of the human condition, including accumulation of calcium phosphate microliths in the lung tissue and progressive diffuse radiographic opacities. The mouse model provides a useful platform for preclinical studies, including therapeutic trials of EDTA lavage and low phosphate diet/phosphate binders.
Pathology
PAM may be confined to certain areas or show diffuse distribution through the lungs. Lung biopsy and autopsy specimens demonstrate characteristic intra-alveolar lamellar microliths. Calcium deposits in the alveoli begin in the lower lobes and spread over a period of years throughout the lungs.
Diagnosis
PAM is usually diagnosed on the basis of a typical radiological pattern, namely a very fine, sand-like micronodulation of calcific density diffusely involving both lungs, with basal predominance. Many authors argue that this pattern precludes the need for a lung biopsy in most cases. After PAM is diagnosed in a given patient, family members should be screened by chest radiography, and parents should be counseled that future children are also at risk of developing the disease.
Radiology
Chest radiographs of patients with PAM usually reveal bilateral diffuse micronodular calcifications, producing a "sandstorm” appearance that first involves the inferior portions and then the middle and upper portions of the lungs.
High-resolution computed tomography
The most common findings on HRCT are diffuse hyperdense ground-glass attenuation and subpleural linear calcifications, often most predominant in the inferior and posterior portions of the lungs. Additionally, the medial aspects of the lungs appear to be more heavily involved than the lateral aspects. Ground-glass opacities, probably due to small calculi in the air space, are the most common finding in children and in patients with early-stage PAM.
Magnetic resonance imaging
On magnetic resonance imaging (MRI), the calcific lesions usually show hypointensity or a signal void on T1- and T2-weighted images.
Pulmonary function studies
Pulmonary function tests, arterial blood gases, ventilation perfusion relationships, and O2 diffusing capacity are normal in the initial stages of PAM. As the disease progresses, pulmonary function tests reveal typical features of a restrictive defect with reduced forced vital capacity (FVC) and elevated forced expiratory volume in FEV1/FVC.
Treatment
To date, no treatment has been proven to effectively reverse or prevent the progression of PAM. Lung transplantation is an option for end stage disease, but is typically only recommended as a last resort when quality of life is significantly impaired.Etidronate is a bisphosphonate and can reduce the formation of calcium hydroxyapatite crystals. It has led to clinical and radiological improvements in few cases.
Epidemiology
Since the disease was first described in 1918, over 500 case reports have appeared in the literature. PAM is associated with consanguinity. The incidence is higher in Turkey, Japan, India and Italy. The disease affects both men and women equally, and it has been associated with intermarriage within families. The mean age at diagnosis is 35 years based on the cases reported in the literature.
Society
PAM is one of the rare lung diseases currently being studied by the Rare Lung Diseases Consortium (RLDC). Pulmonary Alveolar Microlithiasis patients, families, and caregivers are encouraged to join the NIH Rare Lung Diseases Consortium Contact Registry. This is a privacy protected site that provides up-to-date information for individuals interested in the latest scientific news, trials, and treatments related to rare lung diseases.
References
== External links == |
Gastrocutaneous syndrome | Gastrocutaneous syndrome is a rare autosomal dominant cutaneous condition characterized by multiple lentigines.
See also
Gardners syndrome
List of cutaneous conditions
References
== External links == |
Arthritis | Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some types of arthritis, other organs are also affected. Onset can be gradual or sudden.There are over 100 types of arthritis. The most common forms are osteoarthritis (degenerative joint disease) and rheumatoid arthritis. Osteoarthritis usually occurs with age and affects the fingers, knees, and hips. Rheumatoid arthritis is an autoimmune disorder that often affects the hands and feet. Other types include gout, lupus, fibromyalgia, and septic arthritis. They are all types of rheumatic disease.Treatment may include resting the joint and alternating between applying ice and heat. Weight loss and exercise may also be useful. Recommended medications may depend on the form of arthritis. These may include pain medications such as ibuprofen and paracetamol (acetaminophen). In some circumstances, a joint replacement may be useful.Osteoarthritis affects more than 3.8% of people, while rheumatoid arthritis affects about 0.24% of people. Gout affects about 1–2% of the Western population at some point in their lives. In Australia about 15% of people are affected by arthritis, while in the United States more than 20% have a type of arthritis. Overall the disease becomes more common with age. Arthritis is a common reason that people miss work and can result in a decreased quality of life. The term is derived from arthr- (meaning joint) and -itis (meaning inflammation).
Classification
There are several diseases where joint pain is primary, and is considered the main feature. Generally when a person has "arthritis" it means that they have one of these diseases, which include:
Osteoarthritis
Rheumatoid arthritis
Gout and pseudo-gout
Septic arthritis
Ankylosing spondylitis
Juvenile idiopathic arthritis
Stills disease
Psoriatic arthritisJoint pain can also be a symptom of other diseases. In this case, the arthritis is considered to be secondary to the main disease; these include:
Psoriasis
Reactive arthritis
Ehlers–Danlos syndrome
Iron overload
Hepatitis
Lyme disease
Sjögrens disease
Hashimotos thyroiditis
Celiac disease
Non-celiac gluten sensitivity
Inflammatory bowel disease (including Crohns disease and ulcerative colitis)
Henoch–Schönlein purpura
Hyperimmunoglobulinemia D with recurrent fever
Sarcoidosis
Whipples disease
TNF receptor associated periodic syndrome
Granulomatosis with polyangiitis (and many other vasculitis syndromes)
Familial Mediterranean fever
Systemic lupus erythematosus
An undifferentiated arthritis is an arthritis that does not fit into well-known clinical disease categories, possibly being an early stage of a definite rheumatic disease.
Signs and symptoms
Pain, which can vary in severity, is a common symptom in virtually all types of arthritis. Other symptoms include swelling, joint stiffness, redness, and aching around the joint(s). Arthritic disorders like lupus and rheumatoid arthritis can affect other organs in the body, leading to a variety of symptoms. Symptoms may include:
Inability to use the hand or walk
Stiffness in one or more joints
Rash or itch
Malaise and fatigue
Weight loss
Poor sleep
Muscle aches and pains
Tenderness
Difficulty moving the jointIt is common in advanced arthritis for significant secondary changes to occur. For example, arthritic symptoms might make it difficult for a person to move around and/or exercise, which can lead to secondary effects, such as:
Muscle weakness
Loss of flexibility
Decreased aerobic fitnessThese changes, in addition to the primary symptoms, can have a huge impact on quality of life.
Disability
Arthritis is the most common cause of disability in the United States. More than 20 million individuals with arthritis have severe limitations in function on a daily basis. Absenteeism and frequent visits to the physician are common in individuals who have arthritis. Arthritis can make it difficult for individuals to be physically active and some become home bound.
It is estimated that the total cost of arthritis cases is close to $100 billion of which almost 50% is from lost earnings. Each year, arthritis results in nearly 1 million hospitalizations and close to 45 million outpatient visits to health care centers.Decreased mobility, in combination with the above symptoms, can make it difficult for an individual to remain physically active, contributing to an increased risk of obesity, high cholesterol or vulnerability to heart disease. People with arthritis are also at increased risk of depression, which may be a response to numerous factors, including fear of worsening symptoms.
Risk factors
There are common risk factors that increase a persons chance of developing arthritis later in adulthood. Some of these are modifiable while others are not. Smoking has been linked to an increased susceptibility of developing arthritis, particularly rheumatoid arthritis.
Diagnosis
Diagnosis is made by clinical examination from an appropriate health professional, and may be supported by other tests such as radiology and blood tests, depending on the type of suspected arthritis. All arthritides potentially feature pain. Pain patterns may differ depending on the arthritides and the location. Rheumatoid arthritis is generally worse in the morning and associated with stiffness lasting over 30 minutes. However, in the early stages, patients may have no symptoms after a warm shower. Osteoarthritis, on the other hand, tends to be associated with morning stiffness which eases relatively quickly with movement and exercise. In the aged and children, pain might not be the main presenting feature; the aged patient simply moves less, the infantile patient refuses to use the affected limb.
Elements of the history of the disorder guide diagnosis. Important features are speed and time of onset, pattern of joint involvement, symmetry of symptoms, early morning stiffness, tenderness, gelling or locking with inactivity, aggravating and relieving factors, and other systemic symptoms. Physical examination may confirm the diagnosis or may indicate systemic disease. Radiographs are often used to follow progression or help assess severity.Blood tests and X-rays of the affected joints often are performed to make the diagnosis. Screening blood tests are indicated if certain arthritides are suspected. These might include: rheumatoid factor, antinuclear factor (ANF), extractable nuclear antigen, and specific antibodies.
Osteoarthritis
Osteoarthritis is the most common form of arthritis. It affects humans and other animals, notably dogs, but also occurs in cats and horses. It can affect both the larger and the smaller joints of the body. In humans, this includes the hands, wrists, feet, back, hip, and knee. In dogs, this includes the elbow, hip, stifle (knee), shoulder, and back. The disease is essentially one acquired from daily wear and tear of the joint; however, osteoarthritis can also occur as a result of injury. Osteoarthritis begins in the cartilage and eventually causes the two opposing bones to erode into each other. The condition starts with minor pain during physical activity, but soon the pain can be continuous and even occur while in a state of rest. The pain can be debilitating and prevent one from doing some activities. In dogs, this pain can significantly affect quality of life and may include difficulty going up and down stairs, struggling to get up after lying down, trouble walking on slick floors, being unable to hop in and out of vehicles, difficulty jumping on and off furniture, and behavioral changes (e.g., aggression, difficulty squatting to toilet). Osteoarthritis typically affects the weight-bearing joints, such as the back, knee and hip. Unlike rheumatoid arthritis, osteoarthritis is most commonly a disease of the elderly. The strongest predictor of osteoarthritis is increased age, likely due to the declining ability of chondrocytes to maintain the structural integrity of cartilage. More than 30 percent of women have some degree of osteoarthritis by age 65. Other risk factors for osteoarthritis include prior joint trauma, obesity, and a sedentary lifestyle.
Rheumatoid arthritis
Rheumatoid arthritis (RA) is a disorder in which the bodys own immune system starts to attack body tissues. The attack is not only directed at the joint but to many other parts of the body. In rheumatoid arthritis, most damage occurs to the joint lining and cartilage which eventually results in erosion of two opposing bones. RA often affects joints in the fingers, wrists, knees and elbows, is symmetrical (appears on both sides of the body), and can lead to severe deformity in a few years if not treated. RA occurs mostly in people aged 20 and above. In children, the disorder can present with a skin rash, fever, pain, disability, and limitations in daily activities. With earlier diagnosis and aggressive treatment, many individuals can lead a better quality of life than if going undiagnosed for long after RAs onset. The risk factors with the strongest association for developing rheumatoid arthritis are the female sex, a family history of rheumatoid arthritis, age, obesity, previous joint damage from an injury, and exposure to tobacco smoke.Bone erosion is a central feature of rheumatoid arthritis. Bone continuously undergoes remodeling by actions of bone resorbing osteoclasts and bone forming osteoblasts. One of the main triggers of bone erosion in the joints in rheumatoid arthritis is inflammation of the synovium, caused in part by the production of pro-inflammatory cytokines and receptor activator of nuclear factor kappa B ligand (RANKL), a cell surface protein present in Th17 cells and osteoblasts. Osteoclast activity can be directly induced by osteoblasts through the RANK/RANKL mechanism.
Lupus
Lupus is a common collagen vascular disorder that can be present with severe arthritis. Other features of lupus include a skin rash, extreme photosensitivity, hair loss, kidney problems, lung fibrosis and constant joint pain.
Gout
Gout is caused by deposition of uric acid crystals in the joints, causing inflammation. There is also an uncommon form of gouty arthritis caused by the formation of rhomboid crystals of calcium pyrophosphate known as pseudogout. In the early stages, the gouty arthritis usually occurs in one joint, but with time, it can occur in many joints and be quite crippling. The joints in gout can often become swollen and lose function. Gouty arthritis can become particularly painful and potentially debilitating when gout cannot successfully be treated. When uric acid levels and gout symptoms cannot be controlled with standard gout medicines that decrease the production of uric acid (e.g., allopurinol) or increase uric acid elimination from the body through the kidneys (e.g., probenecid), this can be referred to as refractory chronic gout.
Comparison of types
Other
Infectious arthritis is another severe form of arthritis. It presents with sudden onset of chills, fever and joint pain. The condition is caused by bacteria elsewhere in the body. Infectious arthritis must be rapidly diagnosed and treated promptly to prevent irreversible joint damage.Psoriasis can develop into psoriatic arthritis. With psoriatic arthritis, most individuals develop the skin problem first and then the arthritis. The typical features are continuous joint pains, stiffness and swelling. The disease does recur with periods of remission but there is no cure for the disorder. A small percentage develop a severely painful and destructive form of arthritis which destroys the small joints in the hands and can lead to permanent disability and loss of hand function.
Treatment
There is no known cure for arthritis and rheumatic diseases. Treatment options vary depending on the type of arthritis and include physical therapy, exercise and diet, orthopedic bracing, and oral and topical medications. Joint replacement surgery may be required to repair damage, restore function, or relieve pain.
Physical therapy
In general, studies have shown that physical exercise of the affected joint can noticeably improve long-term pain relief. Furthermore, exercise of the arthritic joint is encouraged to maintain the health of the particular joint and the overall body of the person.Individuals with arthritis can benefit from both physical and occupational therapy. In arthritis the joints become stiff and the range of movement can be limited. Physical therapy has been shown to significantly improve function, decrease pain, and delay the need for surgical intervention in advanced cases. Exercise prescribed by a physical therapist has been shown to be more effective than medications in treating osteoarthritis of the knee. Exercise often focuses on improving muscle strength, endurance and flexibility. In some cases, exercises may be designed to train balance. Occupational therapy can provide assistance with activities. Assistive technology is a tool used to aid a persons disability by reducing their physical barriers by improving the use of their damaged body part, typically after an amputation. Assistive technology devices can be customized to the patient or bought commercially.
Medications
There are several types of medications that are used for the treatment of arthritis. Treatment typically begins with medications that have the fewest side effects with further medications being added if insufficiently effective.Depending on the type of arthritis, the medications that are given may be different. For example, the first-line treatment for osteoarthritis is acetaminophen (paracetamol) while for inflammatory arthritis it involves non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen. Opioids and NSAIDs may be less well tolerated. However, topical NSAIDs may have better safety profiles than oral NSAIDs. For more severe cases of osteoarthritis, intra-articular corticosteroid injections may also be considered.The drugs to treat rheumatoid arthritis (RA) range from corticosteroids to monoclonal antibodies given intravenously. Due to the autoimmune nature of RA, treatments may include not only pain medications and anti-inflammatory drugs, but also another category of drugs called disease-modifying antirheumatic drugs (DMARDs). Treatment with DMARDs is designed to slow down the progression of RA by initiating an adaptive immune response, in part by CD4+ T helper (Th) cells, specifically Th17 cells. Th17 cells are present in higher quantities at the site of bone destruction in joints and produce inflammatory cytokines associated with inflammation, such as interleukin-17 (IL-17).
Surgery
A number of rheumasurgical interventions have been incorporated in the treatment of arthritis since the 1950s. Arthroscopic surgery for osteoarthritis of the knee provides no additional benefit to optimized physical and medical therapy.
Adaptive aids
People with hand arthritis can have trouble with simple activities of daily living tasks (ADLs), such as turning a key in a lock or opening jars, as these activities can be cumbersome and painful. There are adaptive aids or assistive devices (ADs) available to help with these tasks, but they are generally more costly than conventional products with the same function. It is now possible to 3-D print adaptive aids, which have been released as open source hardware to reduce patient costs. Adaptive aids can significantly help arthritis patients and the vast majority of those with arthritis need and use them.
Alternative medicine
Further research is required to determine if transcutaneous electrical nerve stimulation (TENS) for knee osteoarthritis is effective for controlling pain.Low level laser therapy may be considered for relief of pain and stiffness associated with arthritis. Evidence of benefit is tentative.Pulsed electromagnetic field therapy (PEMFT) has tentative evidence supporting improved functioning but no evidence of improved pain in osteoarthritis. The FDA has not approved PEMFT for the treatment of arthritis. In Canada, PEMF devices are legally licensed by Health Canada for the treatment of pain associated with arthritic conditions.
Epidemiology
Arthritis is predominantly a disease of the elderly, but children can also be affected by the disease. Arthritis is more common in women than men at all ages and affects all races, ethnic groups and cultures. In the United States a CDC survey based on data from 2013 to 2015 showed 54.4 million (22.7%) adults had self-reported doctor-diagnosed arthritis, and 23.7 million (43.5% of those with arthritis) had arthritis-attributable activity limitation (AAAL). With an aging population, this number is expected to increase. Adults with co-morbid conditions, such as heart disease, diabetes, and obesity, were seen to have a higher than average prevalence of doctor-diagnosed arthritis (49.3%, 47.1%, and 30.6% respectively).Disability due to musculoskeletal disorders increased by 45% from 1990 to 2010. Of these, osteoarthritis is the fastest increasing major health condition. Among the many reports on the increased prevalence of musculoskeletal conditions, data from Africa are lacking and underestimated. A systematic review assessed the prevalence of arthritis in Africa and included twenty population-based and seven hospital-based studies. The majority of studies, twelve, were from South Africa. Nine studies were well-conducted, eleven studies were of moderate quality, and seven studies were conducted poorly. The results of the systematic review were as follows:
Rheumatoid arthritis: 0.1% in Algeria (urban setting); 0.6% in Democratic Republic of Congo (urban setting); 2.5% and 0.07% in urban and rural settings in South Africa respectively; 0.3% in Egypt (rural setting), 0.4% in Lesotho (rural setting)
Osteoarthritis: 55.1% in South Africa (urban setting); ranged from 29.5 to 82.7% in South Africans aged 65 years and older
Knee osteoarthritis has the highest prevalence from all types of osteoarthritis, with 33.1% in rural South Africa
Ankylosing spondylitis: 0.1% in South Africa (rural setting)
Psoriatic arthritis: 4.4% in South Africa (urban setting)
Gout: 0.7% in South Africa (urban setting)
Juvenile idiopathic arthritis: 0.3% in Egypt (urban setting)
History
Evidence of osteoarthritis and potentially inflammatory arthritis has been discovered in dinosaurs. The first known traces of human arthritis date back as far as 4500 BC. In early reports, arthritis was frequently referred to as the most common ailment of prehistoric peoples. It was noted in skeletal remains of Native Americans found in Tennessee and parts of what is now Olathe, Kansas. Evidence of arthritis has been found throughout history, from Ötzi, a mummy (c. 3000 BC) found along the border of modern Italy and Austria, to the Egyptian mummies circa 2590 BC.In 1715, William Musgrave published the second edition of his most important medical work, De arthritide symptomatica, which concerned arthritis and its effects. Augustin Jacob Landré-Beauvais, a 28-year-old resident physician at Saltpêtrière Asylum in France was the first person to describe the symptoms of rheumatoid arthritis. Though Landré-Beauvais classification of rheumatoid arthritis as a relative of gout was inaccurate, his dissertation encouraged others to further study the disease.
Terminology
The term is derived from arthr- (from Ancient Greek: ἄρθρον, romanized: árthron, lit. joint) and -itis (from -ῖτις, -îtis, lit. pertaining to), the latter suffix having come to be associated with inflammation.
The word arthritides is the plural form of arthritis, and denotes the collective group of arthritis-like conditions.
See also
Antiarthritics
Arthritis Care (charity in the UK)
Arthritis Foundation (US not-for-profit)
Knee arthritis
Osteoimmunology
Weather pains
References
External links
Arthritis at Curlie
American College of Rheumatology – US professional society of rheumatologists
National Institute of Arthritis and Musculoskeletal and Skin Diseases - US National Institute of Arthritis and Musculoskeletal and Skin Diseases |
Pesticide poisoning | A pesticide poisoning occurs when pesticides, chemicals intended to control a pest, affect non-target organisms such as humans, wildlife, plant, or bees. There are three types of pesticide poisoning. The first of the three is a single and short-term very high level of exposure which can be experienced by individuals who commit suicide, as well as pesticide formulators. Type two poisoning is long-term high-level exposure, which can occur in pesticide formulators and manufacturers. The third type of poisoning is a long-term low-level exposure, which individuals are exposed to from sources such as pesticide residues in food as well as contact with pesticide residues in the air, water, soil, sediment, food materials, plants and animals.In developing countries, such as Sri Lanka, pesticide poisonings from short-term very high level of exposure (acute poisoning) is the most worrisome type of poisoning. However, in developed countries, such as Canada, it is the complete opposite: acute pesticide poisoning is controlled, thus making the main issue long-term low-level exposure of pesticides.
Cause
The most common exposure scenarios for pesticide-poisoning cases are accidental or suicidal poisonings, occupational exposure, by-stander exposure to off-target drift, and the general public who are exposed through environmental contamination.
Accidental or suicidal
Self-poisoning with agricultural pesticides represents a major hidden public health problem accounting for approximately one-third of all suicides worldwide. It is one of the most common forms of self-injury in the Global South. The World Health Organization estimates that 300,000 people die from self-harm each year in the Asia-Pacific region alone. Most cases of intentional pesticide poisoning appear to be impulsive acts undertaken during stressful events, and the availability of pesticides strongly influences the incidence of self poisoning. Pesticides are the agents most frequently used by farmers and students in India to commit suicide.
Occupational
Pesticide poisoning is an important occupational health issue because pesticides are used in a large number of industries, which puts many different categories of workers at risk. Extensive use puts agricultural workers in particular at increased risk for pesticide illnesses. Exposure can occur through inhalation of pesticide fumes, and often occurs in settings including greenhouse spraying operations and other closed environments like tractor cabs or while operating rotary fan mist sprayers in facilities or locations with poor ventilation systems.
Workers in other industries are at risk for exposure as well. For example, commercial availability of pesticides in stores puts retail workers at risk for exposure and illness when they handle pesticide products. The ubiquity of pesticides puts emergency responders such as fire-fighters and police officers at risk, because they are often the first responders to emergency events and may be unaware of the presence of a poisoning hazard. The process of aircraft disinsection, in which pesticides are used on inbound international flights for insect and disease control, can also make flight attendants sick.Different job functions can lead to different levels of exposure. Most occupational exposures are caused by absorption through exposed skin such as the face, hands, forearms, neck, and chest. This exposure is sometimes enhanced by inhalation in settings including spraying operations in greenhouses and other closed environments, tractor cabs, and the operation of rotary fan mist sprayers.
Residential
The majority of households in Canada use pesticides while taking part in activities such as gardening. In Canada, 96 percent of households report having a lawn or a garden. 56 percent of the households who have a lawn or a garden utilize fertilizer or pesticide. This form of pesticide use may contribute to the third type of poisoning, which is caused by long-term low-level exposure. As mentioned before, long-term low-level exposure affects individuals from sources such as pesticide residues in food as well as contact with pesticide residues in the air, water, soil, sediment, food materials, plants and animals.
Pathophysiology
Organochlorines
The organochlorine pesticides, like DDT, aldrin, and dieldrin, are extremely persistent and accumulate in fatty tissue. Through the process of bioaccumulation (lower amounts in the environment get magnified sequentially up the food chain), large amounts of organochlorines can accumulate in top species like humans. There is substantial evidence to suggest that DDT, and its metabolite DDE, act as endocrine disruptors, interfering with hormonal function of estrogen, testosterone, and other steroid hormones.
Anticholinesterase compounds
Cholinesterase-inhibiting pesticides, also known as organophosphates, carbamates, and anticholinesterases, are most commonly reported in occupationally related pesticide poisonings globally. Besides acute symptoms including cholinergic crisis, certain organophosphates have long been known to cause a delayed-onset toxicity to nerve cells, which is often irreversible. Several studies have shown persistent deficits in cognitive function in workers chronically exposed to pesticides.
Diagnosis
Most pesticide-related illnesses have signs and symptoms that are similar to common medical conditions, so a complete and detailed environmental and occupational history is essential for correctly diagnosing a pesticide poisoning. A few additional screening questions about the patients work and home environment, in addition to a typical health questionnaire, can indicate whether there was a potential pesticide poisoning.If one is regularly using carbamate and organophosphate pesticides, it is important to obtain a baseline cholinesterase test. Cholinesterase is an important enzyme of the nervous system, and these chemical groups kill pests and potentially injure or kill humans by inhibiting cholinesterase. If one has had a baseline test and later suspects a poisoning, one can identify the extent of the problem by comparison of the current cholinesterase level with the baseline level.
Prevention
Accidental poisonings can be avoided by proper labeling and storage of containers. When handling or applying pesticides, exposure can be significantly reduced by protecting certain parts of the body where the skin shows increased absorption, such as the scrotal region, underarms, face, scalp, and hands. Safety protocols to reduce exposure include the use of personal protective equipment, washing hands and exposed skin during as well as after work, changing clothes between work shifts, and having first aid trainings and protocols in place for workers.Personal protective equipment for preventing pesticide exposure includes the use of a respirator, goggles, and protective clothing, which have all have been shown to reduce risk of developing pesticide-induced diseases when handling pesticides. A study found the risk of acute pesticide poisoning was reduced by 55% in farmers who adopted extra personal protective measures and were educated about both protective equipment and pesticide exposure risk. Exposure can be significantly reduced when handling or applying pesticides by protecting certain parts of the body where the skin shows increased absorption, such as the scrotal region, underarms, face, scalp, and hands. Using chemical-resistant gloves has been shown to reduce contamination by 33–86%.Use of genetically modified crops led to significant reduction of pesticide poisoning as these require significantly less pesticide application. In India alone reduction of 2.4–9 million cases per year was observed after widespread adoption of Bt cotton, with similar reductions reported in China, Pakistan and other countries.
Treatment
Specific treatments for acute pesticide poisoning are often dependent on the pesticide or class of pesticide responsible for the poisoning. However, there are basic management techniques that are applicable to most acute poisonings, including skin decontamination, airway protection, gastrointestinal decontamination, and seizure treatment.Decontamination of the skin is performed while other life-saving measures are taking place. Clothing is removed, the patient is showered with soap and water, and the hair is shampooed to remove chemicals from the skin and hair. The eyes are flushed with water for 10–15 minutes. The patient is intubated and oxygen administered, if necessary. In more severe cases, pulmonary ventilation must sometimes be supported mechanically. Seizures are typically managed with lorazepam, phenytoin and phenobarbitol, or diazepam (particularly for organochlorine poisonings).Gastric lavage is not recommended to be used routinely in pesticide poisoning management, as clinical benefit has not been confirmed in controlled studies; it is indicated only when the patient has ingested a potentially life-threatening amount of poison and presents within 60 minutes of ingestion. An orogastric tube is inserted and the stomach is flushed with saline to try to remove the poison. If the patient is neurologically impaired, a cuffed endotracheal tube inserted beforehand for airway protection. Studies of poison recovery at 60 minutes have shown recovery of 8–32%. However, there is also evidence that lavage may flush the material into the small intestine, increasing absorption. Lavage is contra-indicated in cases of hydrocarbon ingestion.Activated charcoal is sometimes administered as it has been shown to be successful with some pesticides. Studies have shown that it can reduce the amount absorbed if given within 60 minutes, though there is not enough data to determine if it is effective if time from ingestion is prolonged. Syrup of ipecac is not recommended for most pesticide poisonings because of potential interference with other antidotes and regurgitation increasing exposure of the esophagus and oral area to the pesticide.Urinary alkalinisation has been used in acute poisonings from chlorophenoxy herbicides (such as 2,4-D, MCPA, 2,4,5-T and mecoprop); however, evidence to support its use is poor.
Epidemiology
Acute pesticide poisoning is a large-scale problem, especially in developing countries.
"Most estimates concerning the extent of acute pesticide poisoning have been based on data from hospital admissions which would include only the more serious cases. The latest estimate by a WHO task group indicates that there may be 1 million serious unintentional poisonings each year and in addition 2 million people hospitalized for suicide attempts with pesticides. This necessarily reflects only a fraction of the real problem. On the basis of a survey of self-reported minor poisoning carried out in the Asian region, it is estimated that there could be as many as 25 million agricultural workers in the developing world suffering an episode of poisoning each year." In Canada in 2007 more than 6000 cases of acute pesticide poisoning occurred.Estimating the numbers of chronic poisonings worldwide is more difficult.
Society and culture
Rachel Carsons 1962 environmental science book Silent Spring brought about the first major wave of public concern over the chronic effects of pesticides.
Other animals
An obvious side effect of using a chemical meant to kill is that one is likely to kill more than just the desired organism. Contact with a sprayed plant or "weed" can have an effect upon local wildlife, most notably insects. A cause for concern is how pests, the reason for pesticide use, are building up a resistance. Phytophagous insects are able to build up this resistance because they are easily capable of evolutionary diversification and adaptation. The problem this presents is that in order to obtain the same desired effect of the pesticides they have to be made increasingly stronger as time goes on. Repercussions of the use of stronger pesticides on vegetation has a negative result on the surrounding environment, but also would contribute to consumers long-term low-level exposure.
See also
Health effects of pesticides
SENSOR-Pesticides program
WHO Pesticide Evaluation Scheme
Notes
References
Cited texts
== External links == |
Scleroderma | Scleroderma is a group of autoimmune diseases that may result in changes to the skin, blood vessels, muscles, and internal organs. The disease can be either localized to the skin or involve other organs, as well. Symptoms may include areas of thickened skin, stiffness, feeling tired, and poor blood flow to the fingers or toes with cold exposure. One form of the condition, known as CREST syndrome, classically results in calcium deposits, Raynauds syndrome, esophageal problems, thickening of the skin of the fingers and toes, and areas of small, dilated blood vessels.The cause is unknown, but it may be due to an abnormal immune response. Risk factors include family history, certain genetic factors, and exposure to silica. The underlying mechanism involves the abnormal growth of connective tissue, which is believed to be the result of the immune system attacking healthy tissues. Diagnosis is based on symptoms, supported by a skin biopsy or blood tests.While no cure is known, treatment may improve symptoms. Medications used include corticosteroids, methotrexate, and non-steroidal anti-inflammatory drugs (NSAIDs). Outcome depends on the extent of disease. Those with localized disease generally have a normal life expectancy. In those with systemic disease, life expectancy can be affected, and this varies based on subtype. Death is often due to lung, gastrointestinal, or heart complications.About three per 100,000 people per year develop the systemic form. The condition most often begins in middle age. Women are more often affected than men. Scleroderma symptoms were first described in 1753 by Carlo Curzio and then well documented in 1842. The term is from the Greek skleros meaning "hard" and derma meaning "skin".
Signs and symptoms
Potential signs and symptoms include:
Cardiovascular: Raynauds phenomenon (is the presenting symptom in 30% of affected persons, occurs in 95% of affected individuals at some time during their illness); healed pitting ulcers on the fingertips; skin and mucosal telangiectasis; palpitations, irregular heart rate and fainting due to conduction abnormalities, hypertension, and congestive heart failure
Digestive: gastroesophageal reflux disease, bloating, indigestion, loss of appetite, diarrhoea alternating with constipation, sicca syndrome and its complications, loosening of teeth, and hoarseness (due to acid reflux).
Pulmonary: progressive worsening of shortness of breath, chest pain (due to pulmonary artery hypertension) and dry, persistent cough due to interstitial lung disease
Musculoskeletal: joint, muscle aches, loss of joint range of motion, carpal tunnel syndrome, and muscle weakness
Genitourinary: erectile dysfunction, dyspareunia, kidney problems, or kidney failure
Other: facial pain due to trigeminal neuralgia, hand paresthesias, headache, stroke, fatigue, calcinosis, and weight loss
Cause
Scleroderma is caused by genetic and environmental factors. Mutations in HLA genes seem to play a crucial role in the pathogenesis of some cases; likewise silica, aromatic and chlorinated solvents, ketones, trichloroethylene, welding fumes, and white spirits exposure seems to contribute to the condition in a small proportion of affected persons.
Pathophysiology
It is characterised by increased synthesis of collagen (leading to the sclerosis), damage to small blood vessels, activation of T lymphocytes, and production of altered connective tissue. Its proposed pathogenesis is the following:
It begins with an inciting event at the level of the vasculature, probably the endothelium. The inciting event is yet to be elucidated, but may be a viral agent, oxidative stress, or autoimmune. Endothelial cell damage and apoptosis ensue, leading to the vascular leakiness that manifests in early clinical stages as tissue oedema. At this stage, it is predominantly a Th1- and Th17-mediated disease.
After this, the vasculature is further compromised by impaired angiogenesis and impaired vasculogenesis (fewer endothelial progenitor cells), likely related to the presence of antiendothelinal cell antibodies (AECA). Despite this impaired angiogenesis, elevated levels of pro-angiogenic growth factors such as PDGF and VEGF is often seen in persons with the condition. The balance of vasodilation and vasoconstriction becomes askew, and the net result is vasoconstriction. The damaged endothelium then serves as a point of origin for blood-clot formation and further contributes to ischaemia-reperfusion injury and the generation of reactive oxygen species. These later stages are characterised by Th2 polarity.
The damaged endothelium upregulates adhesion molecules and chemokines to attract leucocytes, which enables the development of innate and adaptive immune responses, including loss of tolerance to various oxidised antigens, which includes topoisomerase I. B cells mature into plasma cells, which furthers the autoimmune component of the condition. T cells differentiate into subsets, including Th2 cells, which play a vital role in tissue fibrosis. Anti–topoisomerase 1 antibodies, in turn, stimulate type I interferon production.
Fibroblasts are recruited and activated by multiple cytokines and growth factors to generate myofibroblasts. Dysregulated transforming growth factor β (TGF-β) signalling in fibroblasts and myofibroblasts has been observed in multiple studies of scleroderma-affected individuals. Activation of fibroblasts and myofibroblasts leads to excessive deposition of collagen and other related proteins, leading to fibrosis. B cells are implicated in this stage, IL-6 and TGF-β produced by the B cells decrease collagen degradation and increase extracellular matrix production. Endothelin signalling is implicated in the pathophysiology of fibrosis.Vitamin D is implicated in the pathophysiology of the disease. An inverse correlation between plasma levels of vitamin D and scleroderma severity has been noted, and vitamin D is known to play a crucial role in regulating (usually suppressing) the actions of the immune system.
Diagnosis
Typical scleroderma is classically defined as symmetrical skin thickening, with about 70% of cases also presenting with Raynauds phenomenon, nail-fold capillary changes, and antinuclear antibodies. Affected individuals may experience systemic organ involvement. No single test for scleroderma works all of the time, hence diagnosis is often a matter of exclusion. Atypical scleroderma may show any variation of these changes without skin changes or with finger swelling only.Laboratory testing can show antitopoisomerase antibodies, like anti-scl70 (causing a diffuse systemic form), or anticentromere antibodies (causing a limited systemic form and the CREST syndrome). Other autoantibodies can be seen, such as anti-U3 or anti-RNA polymerase.
Antidouble-stranded DNA autoantibodies are likely to be present in serum.
Differential
Diseases that are often in the differential include:
Eosinophilia is a condition in which too many eosinophils (a type of immune cell that attacks parasites and is involved in certain allergic reactions) are present in the blood.
Eosinophilia-myalgia syndrome is a form of eosinophilia caused by L-tryptophan supplements.
Eosinophilic fasciitis affects the connective tissue surrounding skeletal muscles, bones, blood vessels, and nerves in the arms and legs.
Graft-versus-host disease is an autoimmune condition that occurs as a result of bone-marrow transplants in which the immune cells from the transplanted bone marrow attack the hosts body.
Mycosis fungoides is a type of cutaneous T cell lymphoma, a rare cancer that causes rashes all over the body.
Nephrogenic systemic fibrosis is a condition usually caused by kidney failure that results in fibrosis (thickening) of the tissues.
Primary biliary cirrhosis is an autoimmune disease of the liver.
Primary pulmonary hypertension
Complex regional pain syndrome
Classification
Scleroderma is characterised by the appearance of circumscribed or diffuse, hard, smooth, ivory-colored areas that are immobile and which give the appearance of hidebound skin, a disease occurring in both localised and systemic forms:
Treatment
No cure for scleroderma is known, although relief of symptoms is often achieved; these include the:
Raynauds phenomenon with vasodilators such as calcium channel blockers, alpha blockers, serotonin receptor antagonists, angiotensin II receptor inhibitors, statins, local nitrates or iloprost
Digital ulcers with phosphodiesterase 5 inhibitors (e.g., sildenafil) or iloprost
Prevention of new digital ulcers with bosentan
Malnutrition, secondary to intestinal flora overgrowth with tetracycline antibiotics such as tetracycline
Interstitial lung disease with cyclophosphamide, azathioprine with or without corticosteroids
Pulmonary arterial hypertension with endothelin receptor antagonists, phosphodiesterase 5 inhibitors, and prostanoids
Gastrooesophageal reflux disease with antacids or prokinetics
Kidney crises with angiotensin converting enzyme inhibitors and angiotensin II receptor antagonistsSystemic disease-modifying treatment with immunosuppressants is often used. Immunosuppressants used in its treatment include azathioprine, methotrexate, cyclophosphamide, mycophenolate, intravenous immunoglobulin, rituximab, sirolimus, alefacept, and the tyrosine kinase inhibitors, imatinib, nilotinib, and dasatinib.Experimental therapies under investigation include endothelin receptor antagonists, tyrosine kinase inhibitors, beta-glycan peptides, halofuginone, basiliximab, alemtuzumab, abatacept, and haematopoietic stem cell transplantation.
Prognosis
As of 2012, the five-year survival rate for systemic scleroderma was about 85%, whereas the 10-year survival rate was just under 70%. This varies according to the subtype; while localized scleroderma rarely results in death, the systemic form can, and the diffuse systemic form carries a worse prognosis than the limited form. The major scleroderma-related causes of death are: pulmonary hypertension, pulmonary fibrosis, and scleroderma renal crisis. People with scleroderma are also at a heightened risk for contracting cancers (especially liver, lung, haematologic, and bladder cancers), and perhaps, cardiovascular disease.According to a study of an Australian cohort, between 1985 and 2015, the average life expectancy of a person with scleroderma increased from 66 years to 74 years (around 8 years less than the average Australian life expectancy of 82 years).
Epidemiology
Scleroderma most commonly first presents between the ages of 20 and 50 years, although any age group can be affected. Women are four to nine times more likely to develop scleroderma than men.This disease is found worldwide. In the United States, prevalence is estimated at 240 per million and the annual incidence of scleroderma is 19 per million people. Likewise in the United States, it is slightly more common in African Americans than in their White counterparts. Choctaw Native Americans are more likely than Americans of European descent to develop the type of scleroderma that affects internal organs. In Germany, the prevalence is between 10 and 150 per million people, and the annual incidence is between three and 28 per million people. In South Australia, the annual incidence is 23 per million people, and the prevalence 233 per million people. Scleroderma is less common in the Asian population.
Pregnancy
Scleroderma in pregnancy is a complex situation; it increases the risk to both mother and child. Overall, scleroderma is associated with reduced fetal weight for gestational age. The treatment for scleroderma often includes known teratogens such as cyclophosphamide, methotrexate, mycophenolate, etc., so careful avoidance of such drugs during pregnancy is advised. In these cases hydroxychloroquine and low-dose corticosteroids might be used for disease control.
See also
Congenital fascial dystrophy
Chi Chi DeVayne, (developed scleroderma in the years leading up to her death)
References
External links
Handout on Health: Scleroderma – US National Institute of Arthritis and Musculoskeletal and Skin Diseases |
Pulmonary hyalinizing granuloma | Pulmonary hyalinizing granuloma is a lesional pattern of pulmonary inflammatory pseudotumor.
Pathology
Pulmonary hyalinizing granuloma is characterized by localized changes in lung architecture determined by deposition of hyaline collagenous fibrosis accompanied by sparse lymphocytic infiltrate that compresses and distorts the remaining bronchioles. A higher magnification, the mass is composed by hypocellular collagen lamellae.
Associations
HIV/AIDS
Posterior uveitis
Castlemans disease
== References == |
Netherton syndrome | Netherton syndrome is a severe, autosomal recessive form of ichthyosis associated with mutations in the SPINK5 gene. It is named after Earl W. Netherton (1910–1985), an American dermatologist who discovered it in 1958.
Signs and symptoms
Netherton syndrome is characterized by chronic skin inflammation, universal pruritus (itch), severe dehydration, and stunted growth. Patients with this disorder tend to have a hair shaft defect (trichorrhexis invaginata), also known as "bamboo hair". The disrupted skin barrier function in affected individuals also presents a high susceptibility to infection and allergy, leading to the development of scaly, reddish skin similar to atopic dermatitis. In severe cases, these atopic manifestations persist throughout the individuals life, and consequently post-natal mortality rates are high. In less severe cases, this develops into the milder ichthyosis linearis circumflexa.Netherton syndrome has recently been characterised as a primary immunodeficiency, which straddles the innate and acquired immune system, much as does Wiskott–Aldrich syndrome. A group of Netherton patients have been demonstrated to have altered immunoglobulin levels (typically high IgE and low to normal IgG) and immature natural killer cells. These Natural Killer cells have a reduced lytic function; which can be improved with regular infusions of immunoglobulin (see Treatment); although the mechanism for this is not clear.Patients are more prone than healthy people to infections of all types, especially recurrent skin infections with staphylococcus. They may have more severe infections; but are not as vulnerable to opportunistic pathogens as patients with true Natural Killer cell deficiency-type SCID.
Cause
Netherton syndrome is an autosomal recessive disorder associated with mutations in the SPINK5 gene, which encodes the serine protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI). These mutations result in a dysfunctional protein that has a reduced capacity to inhibit serine proteases expressed in the skin. Potential endogenous targets of LEKTI include KLK5, KLK7 and KLK14. These enzymes are involved in various aspects of epidermal remodelling, including desquamation, PAR-2 activation and degradation of lipid hydrolases, suggesting a potential mechanism for the development of atopic manifestations characteristic of Netherton syndrome.Disease severity is determined by the level of LEKTI expression and, consequently, serine protease activity. Complete SPINK5 gene deletions have been linked to severe cases, while mutations which induce alternate splicing or create premature stop codons may lead to varying levels of severity. Furthermore, LEKTI-knockout mice exhibit a phenotype similar to Netherton syndrome in humans.
Diagnosis
Treatment
There is no known cure at the moment but there are several things that can be done to relieve the symptoms. Moisturising products are very helpful to minimize the scaling/cracking, and anti-infective treatments are useful when appropriate because the skin is very susceptible to infection. Extra protein in the diet during childhood is also beneficial, to replace that which is lost through the previously mentioned "leaky" skin.Steroid and retinoid products have been proven ineffective against Netherton syndrome, and may in fact make things worse for the affected individual.Intravenous immunoglobulin has become established as the treatment of choice in Nethertons syndrome. This therapy reduces infection; enables improvement and even resolution of the skin and hair abnormalities, and dramatically improves quality of life of the patients; although exactly how it achieves this is not known. Given this; it is possible that the reason Nethertons usually is not very severe at or shortly after birth is due to a protective effect of maternal antibodies; which cross the placenta but wane by four to six months.
See also
List of skin conditions
References
Yang T, Liang D, Koch PJ, Hohl D, Kheradmand F, Overbeek PA (October 2004). "Epidermal detachment, desmosomal dissociation, and destabilization of corneodesmosin in Spink5-/- mice". Genes Dev. 18 (19): 2354–8. doi:10.1101/gad.1232104. PMC 522985. PMID 15466487.{{cite journal}}: CS1 maint: multiple names: authors list (link)
External links
DermAtlas 1194463137 |
Congenital hepatic fibrosis | Congenital hepatic fibrosis is an inherited fibrocystic liver disease associated with proliferation of interlobular bile ducts within the portal areas and fibrosis that do not alter hepatic lobular architecture. The fibrosis would affect resistance in portal veins leading to portal hypertension.
Cause
The condition is usually congenital, but sporadic cases have also been reported. It may be associated with other congenital defects, commonly with autosomal recessive polycystic kidney disease, the most severe form of PKD. Some suggest that these two conditions are one disorder with different presentation.
Mechanism
Embryogenically, congenital hepatic fibrosis is due to malformation of the duct plate, a round structure appearing in the eighth week of gestation that is formed by primitive hepatocytes, which differentiate into cholangiocytes. Congenital hepatic fibrosis usually presents in adolescent or young adulthood, but onset of signs and symptoms can range from early childhood through mid-life. Clinical features may vary but commonly include cholangitis, hepatomegaly and signs of portal hypertension.
Diagnosis
Liver biopsy is diagnostic. In biopsy there is diffuse periportal and perilobular fibrosis in broad bands, containing distorted duct like structure or microcyst formation.
Management
Management includes control of esophageal bleeding/varices and treatment of associated renal disease if present.
See also
Caroli disease
Polycystic kidney disease
Von Meyenburg complex
Biliary hamartomas
References
External links
GeneReviews/NCBI/NIH/UW entry on Congenital Hepatic Fibrosis Overview |
Polycythemia | Polycythemia (also known as polycythaemia, polyglobulia and Erythrocytosis) is a disease state in which the hematocrit (the volume percentage of red blood cells in the blood) and/or hemoglobin concentration are elevated in peripheral blood.
It can be due to an increase in the number of red blood cells ("absolute polycythemia") or to a decrease in the volume of plasma ("relative polycythemia"). Polycythemia is sometimes called erythrocytosis, but the terms are not synonymous, because polycythemia describes any increase in red blood mass (whether due to an erythrocytosis or not), whereas erythrocytosis is a documented increase of red cell count.
The emergency treatment of polycythemia (e.g., in hyperviscosity or thrombosis) is by phlebotomy (removal of blood from the circulation). Depending on the underlying cause, phlebotomy may also be used on a regular basis to reduce the hematocrit. Myelosuppressive medications such as hydroxyurea are sometimes used for long-term management of polycythemia.
Absolute polycythemia
The overproduction of red blood cells may be due to a primary process in the bone marrow (a so-called myeloproliferative syndrome), or it may be a reaction to chronically low oxygen levels or, rarely, a malignancy. Alternatively, additional red blood cells may have been received through another process—for example, being over-transfused (either accidentally or, as blood doping, deliberately) or being the recipient twin in a pregnancy, undergoing twin-to-twin transfusion syndrome.
Primary polycythemia
Primary polycythemias are due to factors intrinsic to red cell precursors. Polycythemia vera (PCV), polycythemia rubra vera (PRV), or erythremia, occurs when excess red blood cells are produced as a result of an abnormality of the bone marrow. Often, excess white blood cells and platelets are also produced. PCV is classified as a myeloproliferative disease. Symptoms include headaches and vertigo, and signs on physical examination include an abnormally enlarged spleen and/or liver. In some cases, affected individuals may have associated conditions including high blood pressure or formation of blood clots. Transformation to acute leukemia is rare. Phlebotomy is the mainstay of treatment. A hallmark of polycythemia is an elevated hematocrit, with Hct > 55% seen in 83% of cases. A somatic (non-hereditary) mutation (V617F) in the JAK2 gene, also present in other myeloproliferative disorders, is found in 95% of cases.Primary familial polycythemia, also known as primary familial and congenital polycythemia (PFCP), exists as a benign hereditary condition, in contrast with the myeloproliferative changes associated with acquired PCV. In many families, PFCP is due to an autosomal dominant mutation in the EPOR erythropoietin receptor gene. PFCP can cause an increase of up to 50% in the oxygen-carrying capacity of the blood; skier Eero Mäntyranta had PFCP, which is considered to have given him a large advantage in endurance events.
Secondary polycythemia
Secondary polycythemia is caused by either natural or artificial increases in the production of erythropoietin, hence an increased production of erythrocytes. In secondary polycythemia, 6 to 8 million and occasionally 9 million erythrocytes may occur per cubic millimeter of blood. Secondary polycythemia resolves when the underlying cause is treated.Secondary polycythemia in which the production of erythropoietin increases appropriately is called physiologic polycythemia.
Conditions which may result in a physiologically appropriate polycythemia include:
Altitude related – This physiologic polycythemia is a normal adaptation to living at high altitudes (see altitude sickness). Many athletes train at high altitude to take advantage of this effect, which can be considered a legal form of blood doping. Some individuals believe athletes with primary polycythemia may have a competitive advantage due to greater stamina. However, this has yet to be proven due to the multifaceted complications associated with this condition.
Hypoxic disease-associated – for example in cyanotic heart disease where blood oxygen levels are reduced significantly, may also occur as a result of hypoxic lung disease such as COPD and as a result of chronic obstructive sleep apnea.
Iatrogenic – Secondary polycythemia can be induced directly by phlebotomy (blood letting) to withdraw some blood, concentrate the erythrocytes, and return them to the body.
Genetic – Heritable causes of secondary polycythemia also exist and are associated with abnormalities in hemoglobin oxygen release. This includes patients who have a special form of hemoglobin known as Hb Chesapeake, which has a greater inherent affinity for oxygen than normal adult hemoglobin. This reduces oxygen delivery to the kidneys, causing increased erythropoietin production and a resultant polycythemia. Hemoglobin Kempsey also produces a similar clinical picture. These conditions are relatively uncommon.Conditions where the secondary polycythemia is not caused by physiologic adaptation, and occurs irrespective of body needs include:
Neoplasms – Renal cell carcinoma or liver tumors, von Hippel-Lindau disease, and endocrine abnormalities including pheochromocytoma and adrenal adenoma with Cushings syndrome.
People whose testosterone levels are high because of the use of anabolic steroids, including athletes who abuse steroids, or people on testosterone replacement for hypogonadism or transgender hormone replacement therapy, may develop secondary polycythemia.
Blood doping - Secondary polycythemia can be induced by endurance athletes that take erythropoietin-stimulating agents, receive blood transfusions, and take other measures to increase their red blood cell mass in an effort to increase oxygen transport capacity.
Altered oxygen sensing
Inherited mutations in three genes which all result in increased stability of hypoxia-inducible factors, leading to increased erythropoietin production, have been shown to cause erythrocytosis:
Chuvash erythrocytosis is an autosomal recessive form of erythrocytosis which is endemic in patients from the Chuvash Republic in Russia. Chuvash erythrocytosis is associated with homozygosity for a C598T mutation in the von Hippel-Lindau gene (VHL), which is needed for the destruction of hypoxia-inducible factors in the presence of oxygen. Clusters of patients with Chuvash erythrocytosis have been found in other populations, such as on the Italian island of Ischia, located in the Bay of Naples.
PHD2 erythrocytosis: Heterozygosity for loss-of-function mutations of the PHD2 gene are associated with autosomal dominant erythrocytosis and increased hypoxia-inducible factors activity.
HIF2α erythrocytosis: Gain-of-function mutations in HIF2α are associated with autosomal dominant erythrocytosis and pulmonary hypertension.
Relative polycythemia
Relative polycythemia is an apparent rise of the erythrocyte level in the blood; however, the underlying cause is reduced blood plasma (hypovolemia, cf. dehydration). Relative polycythemia is often caused by loss of body fluids, such as through burns, dehydration, and stress. A specific type of relative polycythemia is Gaisböck syndrome. In this syndrome, primarily occurring in obese men, hypertension causes a reduction in plasma volume, resulting in (amongst other changes) a relative increase in red blood cell count.
Symptoms
Doctors say that patients may not experience in any notable symptom of PV until the late stages. Although vague, these symptoms might help patients get help in the early years of the progression.
Severe headache
Dizziness, fatigue, and tiredness
Unusual bleeding, nosebleeds
Pain
Itchiness
Numbness or tingling in different body parts
Notable people
Polycythemia is linked to increased performance in endurance sports due to the blood being able to store more oxygen. It can also be linked to damage from smoking.
Eero Mäntyranta, Finnish cross-country skier
Bob Newhart, American comedian
See also
Cytopenia, a decrease in blood cell count
Capillary leak syndrome, another cause of hemoconcentration
References
== External links == |
Velopharyngeal insufficiency | Velopharyngeal insufficiency is a disorder of structure that causes a failure of the velum (soft palate) to close against the posterior pharyngeal wall (back wall of the throat) during speech in order to close off the nose (nasal cavity) during oral speech production. This is important because speech requires sound (from the vocal folds) and airflow (from the lungs) to be directed into the oral cavity (mouth) for the production of all speech sound with the exception of nasal sounds (m, n, and ng). If complete closure does not occur during speech, this can cause hypernasality (a resonance disorder) and/or audible nasal emission during speech (a speech sound disorder). In addition, there may be inadequate airflow to produce most consonants, making them sound weak or omitted.The terms "velopharyngeal insufficiency" "velopharyngeal incompetence, "velopharyngeal inadequacy" and "velopharyngeal dysfunction" have often been used interchangeably, although they do not mean the same thing. "Velopharyngeal dysfunction" now refers to abnormality of the velopharyngeal valve, regardless of cause. Velopharyngeal insufficiency includes any structural defect of the velum or mechanical interference with closure. Causes include a history of
cleft palate, adenoidectomy, irregular adenoids, cervical spine anomalies, or oral/pharyngeal tumor removal. In contrast, "velopharyngeal incompetence" refers to a neurogenic cause of inadequate velopharyngeal closure. Causes may include stroke, traumatic brain injury, cerebral palsy, or neuromuscular disorders. It is important that the term "velopharyngeal insufficiency" is used if it is an anatomical defect and not a neurological problem.
Anatomy
Diagnosis
Speech analysis
Velopharyngeal insufficiency can be diagnosed by a speech pathologist through a perceptual speech assessment. Speech characteristics of VPI include hypernasality (too much sound in the nasal cavity during speech) and/or audible nasal emission of air during speech. Nasal emission can also cause the consonants to be very weak in intensity and pressure. The patient may develop compensatory productions for consonants, where the sounds are produced in the pharynx (throat area) where there is adequate airflow.
Nasometry
Nasometry is a method of measuring the acoustic correlates of resonance and velopharyngeal function through a computer-based instrument. Nasometry testing gives the speech pathologist a nasalance score, which is the percentage of nasal sound of the total (nasal plus oral) sound during speech. This score can be compared to normative values for the speech passage. Nasometry is useful in the evaluation of hypernasality because it provides objective measurements of the function of the velopharyngeal valve. As such, it is often used for pre-and post-surgical comparisons and to determine speech outcomes as a result of certain surgical interventions.
Nasopharyngoscopy
Nasopharyngoscopy is endoscopic technique in which the physician or speech pathologist passes a small scope through the patients nose to the nasopharynx. The nasal cavity is typically numbed before the procedure, so there is minimal discomfort. Nasopharyngoscopy provides a view of the velum (soft palate) and pharyngeal walls (walls of the throat) during nasal breathing and during speech. The advantage of this technique over videofluoroscopy is that the examiner can see the size, location, and cause of the velopharyngeal opening very clearly and without harm (e.g., radiation) to the patient. Even very small openings can be visualized. This information is helpful in determining appropriate surgical or prosthetic management for the patient. The disadvantage of this technique is that the vertical level velar elevation is less obvious than with videofluoroscopy, although this is not a big concern.
Videofluoroscopy
Multiview videofluoroscopy is a radiographic technique to view the length and movement of the velum (soft palate) and the posterior and lateral pharyngeal (throat) walls during speech. The advantage of this technique is that the entire posterior pharyngeal wall can be visualized. Disadvantages include the following: 1. This procedure requires radiation, which is a particular concern for children. 2. It is not well tolerated by some children because it requires injection of barium into the nasopharynx through a nasal catheter. 3. The resolution (clarity of the image) is not nearly as good as nasopharyngoscopy. 4. Small or unilateral openings cannot be seen because the X-ray beam takes a sum of all the parts. 5. It only provides a two-dimensional view, and therefore, multiple views are needed to see the entire velopharyngeal mechanism. Comparison between multiview videofluoroscopy and nasoendoscopy of velopharyngeal movements."/> This diagnosis method is useful in assessing velopharyngeal (VP) closure in healthy individuals vs individuals who experience velar backed articulation (BA); given that it was found that healthy individuals had VP closure occur before tongue movement, whereas individuals with BA had VP closure occur after tongue movement when articulating words.
Magnetic resonance imaging
A relatively new approach in the diagnosis is magnetic resonance imaging (MRI), which is noninvasive. MRI uses the property of nuclear magnetic resonance to image nuclei of atoms inside the body. MRI is non-radiographic and therefore can be repeated more often in short periods of time. In addition, different studies show that the MRI is better as an imaging tool than videofluoroscopy for visualizing the anatomy of the velopharynx. There are some limitations of the MRI however. Unlike videofluoroscopy and nasopharyngoscopy, MRI does not show the movement of the velopharyngeal structures during speech. In addition, artifacts can be shown on the images when the patient moves while imaging or if the patient has orthodontic appliances. MRI is limited in children who are claustrophobic. Finally, MRI is much more expensive than videofluoroscopy or nasopharyngoscopy. Because of these limits, MRI is currently not widely used for clinical diagnostic purposes.
Treatment
Speech pathology
Speech therapy will not correct velopharyngeal insufficiency. The condition results from abnormal structure and requires physical management (surgery, or a prosthetic device if surgery cannot be done). Speech therapy is appropriate to correct the compensatory articulation productions that develop as a result of velopharyngeal insufficiency. Speech therapy is most successful after correction of velopharyngeal insufficiency. Speech pathologists who are associated with a cleft palate/craniofacial team are most qualified for this type of therapy.
Operation techniques
In patients with cleft palate, the palate must be repaired through a palatoplasty for normal velopharyngeal function. Despite the palatoplasty, 20-30% of these patients will still have some degree of velopharyngeal insufficiency, which will require surgical (or prosthetic) management for correction. Therefore, a secondary operation is necessary.
There is not one single operative approach to surgical correction of VPI. The surgical approach typically depends on the size of the velopharyngeal opening, its location, and the cause. With diagnostic tools the surgeon is able to decide which technique should be used based on the anatomical situation of the individual. The goal of every operation is to achieve the best possible result with the technique assigned to each individual case, without causing upper airway obstruction and sleep apnea.Nowadays the procedure that is chosen the most from the palatoplasties is the pharyngeal flap or sphincter palatoplasty.
Pharyngeal flap
When a pharyngeal flap is used, a flap of the posterior wall is attached to the posterior border of the soft palate. The flap consists of mucosa and the superior pharyngeal constrictor muscle. The muscle stays attached to the pharyngeal wall at the upper side (superior flap) or at the lower side (inferior flap). The function of the muscle is to obstruct the pharyngeal port at the moment that the pharyngeal lateral walls move towards each other. It is important that the width and the level of insertion of the flap are properly constructed, because if the flap is too wide, the patient can have problems with breathing through the nose, which can result in sleep apnea. Alternatively, a postoperative situation can be created with the same symptoms as before surgery. Some complications are possible; for example, the flaps width can change because of contraction of the flap. This results in a situation with the same symptoms of hypernasality after a few weeks of surgery. Also a fistula can occur in 2.4% of the cases.
Sphincter palatoplasty
When the sphincter pharyngoplasty is used, both sides of the superior-based palatopharyngeal mucosa and muscle flaps are elevated. Because the distal parts (posterior tonsillar pillars, which the palatopharyngeal muscles are attached to) are sutured to the other side of the posterior wall, the pharyngeal port will become smaller. As a result, the tissue flaps cross each other, leading to a smaller port in the middle and a shorter distance between the palate and posterior pharyngeal wall.There are a few advantages with using this technique. First of all the procedure is relatively easy to execute. This makes the operation cheaper, also because of a reduced anesthesia time. Secondly the dynamic sphincter can be moved as result of a remaining neuromuscular innervation, which gives a better function of the velopharyngeal port. Finally there is a lower complication rate, although obstructive sleep apnoea syndrome (OSAS) is associated.Both techniques are used often, but there is no standard operation. Pharyngeal flap surgery is not better than sphincter palatoplasty. It is more upon the surgeons experience, knowledge and preference which operation will be done. Also the patient’s age, and the size and nature of the velopharyngeal defect, contribute to which technique is used.
Posterior wall augmentation
Another option for diminishing the velopharyngeal port is posterior wall augmentation. This technique is not often used. Additionally this technique can only be used for small gaps. When this operation is performed there are several advantages. It is possible to narrow down the velopharyngeal port without modifying the function of the velum or lateral walls. Furthermore, the chance of obstructing the airway is lower, because the port can be closed more precisely. Many materials have been used for this closure: petroleum jelly, paraffin, cartilage, adjacent soft tissue, silastic, fat, Teflon and proplast. But results in the long term are very unpredictable. There are problems with tissue incompatibility and migration of the implant. Even migration to the brain is noticed.
Non-operative techniques
Prosthesis
Prostheses are used for nonsurgical closure in a situation of velopharyngeal dysfunction. There are two types of prosthesis: the speech bulb and the palatal lift prosthesis. The speech bulb is an acrylic body that can be placed in the velopharyngeal port and can achieve obstruction. The palatal lift prosthesis is comparable with the speech bulb, but with a metal skeleton attached to the acrylic body. This will also obstruct the velopharyngeal port. It is a good option for patients that have enough tissue but a poor control of the coordination and timing of velopharyngeal movement. It is also used in patients with contraindications for surgery. It has also been used as a reversible test to confirm whether a surgical intervention would help.
Etymology
The word velopharyngeal uses combining forms of velo- + pharyng-, referring to the soft palate (velum palatinum) and the pharynx.
== References == |
Emphysema | Emphysema, or pulmonary emphysema, is a lower respiratory tract disease, characterised by air-filled spaces (pneumatoses) in the lungs, that can vary in size and may be very large. The spaces are caused by the breakdown of the walls of the alveoli and they replace the spongy lung parenchyma. This reduces the total alveolar surface available for gas exchange leading to a reduction in oxygen supply for the blood. Emphysema usually affects the middle aged or older population because it takes time to develop with the effects of tobacco smoking, and other risk factors. Alpha-1 antitrypsin deficiency is a genetic risk factor that may lead to the condition presenting earlier.When associated with significant airflow limitation, emphysema is a major subtype of chronic obstructive pulmonary disease (COPD), a progressive lung disease characterized by long-term breathing problems and poor airflow. Without COPD, the finding of emphysema on a CT lung scan still confers a higher mortality risk in tobacco smokers. In 2016 in the United States there were 6,977 deaths from emphysema – 2.2 per 100,000 of the population. Globally it accounts for 5% of all deaths. A study on the effects of tobacco and cannabis smoking showed that a possibly cumulative toxic effect could be a risk factor for developing emphysema, and spontaneous pneumothorax.There are four types of emphysema, three of which are related to the anatomy of the lobules of the lung – centrilobular or centriacinar, panlobular or panacinar, and paraseptal or distal acinar emphysema, and are not associated with fibrosis (scarring). The fourth type is known as paracicatricial emphysema or irregular emphysema that involves the acinus irregularly and is associated with fibrosis. Though the different types can be seen on imaging they are not well-defined clinically. There are also a number of associated conditions including bullous emphysema, focal emphysema, and Ritalin lung. Only the first two types of emphysema – centrilobular, and panlobular are associated with significant airflow obstruction, with that of centrilobular emphysema around 20 times more common than panlobular. Centrilobular emphysema is the only type associated with smoking.Osteoporosis is often a comorbidity of emphysema. The use of systemic corticosteroids for treating exacerbations is a significant risk factor for osteoporosis, and their repeated use is recommended against.
Signs and symptoms
Emphysema is a respiratory disease of the lower respiratory tract. It is commonly caused by tobacco smoking but a significant number of people are affected who either do not smoke, or have never smoked. The presence of emphysema is a clear risk factor for the development of lung cancer, made stronger in those who smoke.Early symptoms of emphysema may vary from person to person. Symptoms can include a cough (with or without sputum), wheezing, a fast breathing rate, breathlessness on exertion, and a feeling of tightness in the chest. There may be frequent cold or flu infections. Other symptoms may include anxiety, depression, fatigue, sleep problems and weight loss. Since these symptoms could also relate to other lung conditions or other health problems, emphysema is often under diagnosed. The shortness of breath caused by emphysema can increase over time and develop into chronic obstructive pulmonary disease.
A sign of emphysema in smokers is the finding of a higher number of alveolar macrophages sampled from the bronchoalveolar lavage (BAL) in the lungs. The number can be four to six times greater in those who smoke than in non-smokers.
Types
There are four main types of emphysema, three of which are related to the anatomy of the lobules of the lung – centrilobular or centriacinar, panlobular or panacinar, and paraseptal or distal acinar and are not associated with fibrosis (scarring). Although fibrosis is not a normal feature of these subtypes, repair strategies in end-stage emphysema may lead to pulmonary fibrosis. The fourth subtype is known as paracicatricial emphysema or irregular emphysema, involves the acinus irregularly and is associated with fibrosis.Only the first two types of emphysema – centrilobular, and panlobular are associated with significant airflow obstruction, with that of centrilobular emphysema around 20 times more common than panlobular. The subtypes can be seen on imaging but are not well-defined clinically.
There are also a number of associated conditions including bullous emphysema, focal emphysema, and Ritalin lung.
Centrilobular
Centrilobular emphysema also called centriacinar emphysema, affects the centre of a pulmonary lobule (centrilobular) in the lung, the area around the terminal bronchiole, and the first respiratory bronchiole, and can be seen on imaging as an area around the tip of the visible pulmonary artery. Centrilobular emphysema is the most common type usually associated with smoking, and with chronic bronchitis. The disease progresses from the centrilobular portion, leaving the lung parenchyma in the surrounding (perilobular) region preserved. Usually the upper lobes of the lungs are affected.
Panlobular
Panlobular emphysema also called panacinar emphysema affects all of the alveoli in a lobule and can involve the whole lung or mainly the lower lobes. This type of emphysema is associated with alpha-1 antitrypsin deficiency (A1AD or AATD), and Ritalin lung, and is not related to smoking.
Complications
Likely complications of centrilobular, and panlobular emphysema, some of which are life-threatening, include: respiratory failure, pneumonia, respiratory infections, pneumothorax, interstitial emphysema, pulmonary heart disease, and respiratory acidosis.
Paraseptal
Paraseptal emphysema also called distal acinar emphysema relates to emphysematous change next to a pleural surface, or to a fissure. The cystic spaces known as blebs or bullae that form in paraseptal emphysema typically occur in just one layer beneath the pleura. This distinguishes it from the honeycombing of small cystic spaces seen in fibrosis that typically occurs in layers. This type of emphysema is not associated with airflow obstruction.
Bullous
When the subpleural bullae are significant, the emphysema is called bullous emphysema. Bullae can become extensive and combine to form giant bullae. These can be large enough to take up a third of a hemithorax, compress the lung parenchyma, and cause displacement. The emphysema is now termed giant bullous emphysema, more commonly called vanishing lung syndrome due to the compressed parenchyma. A bleb or bulla may sometimes rupture and cause a pneumothorax.
Paracicatricial
Paracicatricial emphysema, also known as irregular emphysema, is seen next to areas of fibrosis (scarring) as large spaces. The scarring is most often a result of silicosis, granulomatous infection, tuberculosis, or pulmonary infarction. It can be difficult to differentiate from the honeycombing of pulmonary fibrosis.
HIV associated
Classic lung diseases are a complication of HIV/AIDS with emphysema being a source of disease. HIV is cited as a risk factor for the development of emphysema, and COPD regardless of smoking status. Around 20 percent of those with HIV have increased emphysematous changes. This has suggested that an underlying mechanism related to HIV is a contributory factor in the development of emphysema. HIV associated emphysema occurs over a much shorter time than that associated with smoking; an earlier presentation is also seen in emphysema caused by alpha-1 antitrypsin deficiency. Both of these conditions predominantly show damage in the lower lungs which suggests a similarity between the two mechanisms.
Alpha-1 related
Emphysema may develop in some people with alpha-1 antitrypsin deficiency, the only genotype of chronic obstructive pulmonary disease. This usually occurs a lot earlier, as does HIV associated emphysema than other types.
Ritalin lung
The intravenous use of methylphenidate, commonly marketed as Ritalin and widely used as a stimulant drug in the treatment of attention deficit hyperactivity disorder, can lead to emphysematous changes known as Ritalin lung. The mechanism underlying this link is not clearly understood. Ritalin tablets contain talc as a filler, and these need to be crushed and dissolved for injecting. It has been suggested that the talc exposure causes granulomatosis leading to alveolar destruction. However, other intravenous drugs also contain talc and there is no associated emphysematous change. High resolution CT scanning shows the emphysema to be panlobular.
CPFE
Combined pulmonary fibrosis and emphysema (CPFE) is a rare syndrome that shows upper-lobe emphysema, together with lower-lobe interstitial fibrosis. This is diagnosed by CT scan. This syndrome presents a marked susceptibility for the development of pulmonary hypertension.
Congenital lobar
Congenital lobar emphysema (CLE), also known as congenital lobar overinflation and infantile lobar emphysema, is a neonatal condition associated with enlarged air spaces in the lungs of newborn infants. It is diagnosed around the time of birth or in the first 6 months of life, occurring more often in boys than girls. CLE affects the upper lung lobes more than the lower lobes, and the left lung more often than the right lung. CLE is defined as the hyperinflation of one or more lobes of the lung due to the partial obstruction of the bronchus. This causes symptoms of pressure on the nearby organs. It is associated with several cardiac abnormalities such as patent ductus arteriosus, atrial septal defect, ventricular septal defect, and tetralogy of Fallot. Although CLE may be caused by the abnormal development of bronchi, or compression of airways by nearby tissues, no cause is identified in half of cases. CT scan of the lungs is useful in assessing the anatomy of the lung lobes and status of the neighbouring lobes on whether they are hypoplastic or not. Contrast-enhanced CT is useful in assessing vascular abnormalities and mediastinal masses.
Focal
Focal emphysema, is a localized region of emphysema in the lung that is larger than alveoli, and often associated with coalworkers pneumoconiosis. This is also known as localized pulmonary emphysema. Blebs and bullae may also be included as focal emphysema. These can be differentiated from the other type of enclosed air space known as a lung cyst by their size and wall thickness. A bleb or bulla has a wall thickness of less than 1 mm, and are smaller.
Occupational
A number of occupations are associated with the development of emphysema due to the inhalation of varied gases and particles. In the US uranium mining that releases radon gas and particles has been shown to be a cause of emphysema deaths; the figures in the study included some miners who also smoked. Uranium mining and milling was found to create environmental pollution.The inhalation of coal mine dust that can result in coalworkers pneumoconiosis is an independent risk factor for the development of emphysema. Focal emphysema is associated with the coal macule, and this extends into progressive centrilobular emphysema. Less commonly a variant of panlobular emphysema develops.Silicosis results from the inhalation of silica particles, and the formation of large silica nodules is associated with paracicatricial emphysema, with or without bullae.
Ozone-induced emphysema
Ozone is another pollutant that can affect the respiratory system. Long-term exposure to ozone can result in emphysema.
Osteoporosis
Osteoporosis is a major comorbidity of emphysema. Both conditions are associated with a low body mass index. There is an association between treating emphysema, and osteoporosis; the use of systemic corticosteroids for treating exacerbations is a significant risk factor for osteoporosis, and their repeated use is not recommended.
Other terms
Compensatory emphysema, is overinflation of part of a lung in response to either removal by surgery of another part of the lung or decreased size of another part of the lung.Pulmonary interstitial emphysema (PIE) is a collection of air outside of the normal air space of the alveoli, found as pneumatoses inside the connective tissue of the peribronchovascular sheaths, interlobular septa, and visceral pleura.
Lung volume reduction
Lung volume reduction may be offered to those with advanced emphysema. When other treatments fail, and the emphysema is located in the upper lobes a surgical option may be possible. A number of minimally invasive bronchoscopic procedures are increasingly used to reduce lung volume.
Surgical
Where there is severe emphysema with significant hyperinflation that has proved unresponsive to other therapies lung volume reduction surgery (LVRS) may be an option. LVRS involves the removal of tissue from the lobe most damaged by emphysema, which allows the other lobes to expand and give improved function. The procedure appears to be particularly effective if the emphysema primarily involves the upper lobes; however, the procedure increases the risk of adverse events and early death in people who have diffuse emphysema.
Bronchoscopic
Minimally invasive bronchoscopic procedures may be carried out to reduce lung volume. These include the use of valves, coils, or thermal ablation. Endobronchial valves are one-way valves that may be used in those with severe hyperinflation resulting from advanced emphysema; a suitable target lobe, and no collateral ventilation are required for this procedure. The placement of one or more valves in the lobe induces a partial collapse of the lobe that ensures a reduction in residual volume that improves lung function, the capacity for exercise, and quality of life.The placement of nitinol coils instead of valves is recommended where there is collateral ventilation that would prevent the use of valves. Nitinol is a biocompatible shape-memory alloy.
Both of these techniques are associated with adverse effects including persistent air leaks and cardiovascular complications. Bronchoscopic thermal vapor ablation has an improved profile. Heated water vapor is used to target affected lobe regions which leads to permanent fibrosis and volume reduction. The procedure is able to target individual lobe segments, can be carried out regardless of collateral ventilation, and can be repeated with the natural advance of emphysema.
Other surgeries
Lung transplantation – the replacement of either a single lung or both (bilateral) may be considered in end-stage disease. A bilateral transplant is the preferred choice as complications can arise in a remaining single native lung; complications can include hyperinflation, pneumonia, and the development of lung cancer. Careful selection as recommended by the National Emphysema Treatment Trial (NETT) for transplant surgeries is needed as in some cases there will be an increased risk of mortality. Several factors including age, and poor exercise tolerance, using the BODE index need to be taken into account. A transplant is only considered where there are no serious comorbidites. A CT scan or a ventilation/perfusion scan may be useful in surgery considerations to evaluate cases for surgical interventions, and also to evaluate post-surgery responses. A bullectomy may be carried out when a giant bulla occupies more than a third of a hemithorax.
History
The terms emphysema, and chronic bronchitis were formally defined in 1959 at the CIBA guest symposium, and in 1962 at the American Thoracic Society Committee meeting on Diagnostic Standards. The word emphysema is derived from Ancient Greek ἐμφύσημα inflation, swelling (referring to a lung inflated by air-filled spaces), itself from ἐμφυσάω emphysao to blow in, to inflate, composed of ἐν en, meaning "in", and φυσᾶ physa, meaning "wind, blast".René Laennec, the physician who invented the stethoscope, used the term emphysema in his book A Treatise on the Diseases of the Chest and of Mediate Auscultation (1837) to describe lungs that did not collapse when he opened the chest during an autopsy. He noted that they did not collapse as usual because they were full of air and the airways were filled with mucus. Early descriptions of probable emphysema include: in 1679 by T. Bonet of a condition of "voluminous lungs" and in 1769 by Giovanni Morgagni of lungs which were "turgid particularly from air". In 1721 the first drawings of emphysema were made by Ruysh. These were followed the illustrations of Matthew Baillie in 1789 and descriptions of the destructive nature of the condition.
References
Bibliography
== External links == |
Essential fatty acid | Essential fatty acids, or EFAs, are fatty acids that humans and other animals must ingest because the body requires them for good health but cannot synthesize them.The term "essential fatty acid" refers to fatty acids required for biological processes but does not include the fats that only act as fuel. Essential fatty acids should not be confused with essential oils, which are "essential" in the sense of being a concentrated essence.
Only two fatty acids are known to be essential for humans: alpha-linolenic acid (an omega-3 fatty acid) and linoleic acid (an omega-6 fatty acid). Some other fatty acids are sometimes classified as "conditionally essential", meaning that they can become essential under some developmental or disease conditions; examples include docosahexaenoic acid (an omega-3 fatty acid) and gamma-linolenic acid (an omega-6 fatty acid).
When the two EFAs were discovered in 1923, they were designated "vitamin F", but in 1929, research on rats showed that the two EFAs are better classified as fats rather than vitamins.
Functions
The biological effects of the ω-3 and ω-6 fatty acids are mediated by their mutual interactions, see Essential fatty acid interactions for detail.In the body, essential fatty acids serve multiple functions. In each of these, the balance between dietary ω-3 and ω-6 strongly affects function.
They are modified to make
the classic eicosanoids (affecting inflammation and many other cellular functions)
the endocannabinoids (affecting mood, behavior and inflammation)
the lipoxins which are a group of eicosanoid derivatives formed via the lipoxygenase pathway from ω-6 EFAs and resolvins from ω-3 (in the presence of acetylsalicylic acid, downregulating inflammation)
the isofurans, neurofurans, isoprostanes, hepoxilins, epoxyeicosatrienoic acids (EETs) and neuroprotectin D
They form lipid rafts (affecting cellular signaling)
They act on DNA (activating or inhibiting transcription factors such as NF-κB, which is linked to pro-inflammatory cytokine production)
Fatty acids comprise an aliphatic hydrocarbon chain plus a carboxyl group (–COOH) group at one end, and terminated by a methyl group (–CH3) at the other end. They are almost always straight-chained. The carbon next to the carboxylate is known as α, the next carbon β, and so forth. Since biological fatty acids can be of diverse lengths, the last position is often labelled as a "ω", the last letter in the Greek alphabet. Thus, the ω-3 indicates that the first unsaturated carbon-carbon bond from the terminal end (ω) of then chain is the third one. Typically, the number of carbons and the number of double bonds are also listed in short descriptions of unsaturated fatty acids. For instance, ω-3 18:4, or 18:4 ω-3, or 18:4 n−3 indicates stearidonic acid, an 18-carbon chain with 4 double bonds, and with a double bond between the third and fourth carbon atoms from the CH3 end. Double bonds are cis and separated by a single methylene (CH2) group unless otherwise noted. In free fatty acid form, the chemical structure of stearidonic acid is:
Examples
Polyunsaturated fatty acids with 16- and 18-carbon chains are sometimes classified as short chain polyunsaturated fatty acids (SC-PUFA), as opposed to long-chain polyunsaturated fatty acids (LC-PUFA), which have more than 18 carbon atoms.Both the essential fatty acids are SC-PUFA with an 18-carbon chain:
ω-3 fatty acid:
α-linolenic acid or ALA (18:3n-3)
ω-6 fatty acid:
linoleic acid or LA (18:2n-6)These two fatty acids cannot be synthesized by humans because humans lack the desaturase enzymes required for their production.
They form the starting point for the creation of more desaturated fatty acids, most of which also have a longer carbon chain:
ω-3 fatty acids:
eicosapentaenoic acid or EPA (20:5n-3)
docosahexaenoic acid or DHA (22:6n-3)
ω-6 fatty acids:
gamma-linolenic acid or GLA (18:3n-6)
dihomo-gamma-linolenic acid or DGLA (20:3n-6)
arachidonic acid or AA (20:4n-6)Except for GLA, which has a short 18-carbon chain, these fatty acids have more than 18 carbon atoms and are typically classified as LC-PUFA.ω-9 fatty acids are not essential in humans because they can be synthesized from carbohydrates or other fatty acids.
Essentiality in human diet
Mammals lack the ability to introduce double bonds in fatty acids beyond carbon 9 and 10, hence the omega-6 linoleic acid (18:2n-6; LA) and the omega-3 Alpha-linolenic acid (18:3n-3; ALA) are essential for humans in the diet. However, humans can convert both LA and ALA to fatty acids with longer carbon chains and a larger number of double bonds, by alternative desaturation and chain elongation.
In humans, arachidonic acid (20:4n-6; AA) can be synthesized from LA. In turn, AA can be converted to an even longer fatty acid, the docosapentaenoic acid (22:5n-6; DPA). Similarly, ALA can be converted to docosahexaenoic acid (22:6n-3; DHA), although the latter conversion is limited, resulting in lower blood levels of DHA than through direct ingestion. This is illustrated by studies in vegans and vegetarians. If there is relatively more LA than ALA in the diet it favors the formation of DPA from LA rather than DHA from ALA. This effect can be altered by changing the relative ratio of LA:ALA, but is more effective when total intake of polyunsaturated fatty acids is low.
In preterm infants, the capacity to convert LA to AA and ALA to DHA is limited, and preformed AA and DHA may be required to meet the needs of the developing brain. Both AA and DHA are present in breastmilk and contribute along with the parent fatty acids LA and ALA to meeting the requirements of the newborn infant. Many infant formulas have AA and DHA added to them with an aim to make them more equivalent to human milk.
Essential nutrients are defined as those that cannot be synthesized de novo in sufficient quantities for normal physiological function. This definition is met for LA and ALA but not the longer chain derivatives in adults. The longer chain derivatives particularly, however, have pharmacological properties that can modulate disease processes, but this should not be confused with dietary essentiality.
Between 1930 and 1950, arachidonic acid and linolenic acid were termed essential because each was more or less able to meet the growth requirements of rats given fat-free diets. In the 1950s Arild Hansen showed that in humans: infants fed skimmed milk developed the essential fatty acid deficiency. It was characterized by an increased food intake, poor growth, and a scaly dermatitis, and was cured by the administration of corn oil.
Later work by Hansen randomized 426 children to four treatments: modified cows milk formula, skimmed milk formula, skimmed milk formula with coconut oil, or cows milk formula with corn oil. The infants who received the skimmed milk formula or the formula with coconut oil developed essential fatty acid deficiency signs and symptoms. This could be cured by administration of ethyl linoleate (the ethyl ester of linoleic acid) with about 1% of the energy intake.Collins et al. 1970 were the first to demonstrate linoleic acid deficiency in adults. They found that patients undergoing intravenous nutrition with glucose became isolated from their fat supplies and rapidly developed biochemical signs of essential fatty acid deficiency (an increase in 20:3n-9/20:4n-6 ratio in plasma) and skin symptoms. This could be treated by infusing lipids, and later studies showed that topical application of sunflower oil would also resolve the dermal symptoms. Linoleic acid has a specific role in maintaining the skin water-permeability barrier, probably as constituents of acylglycosylceramides. This role cannot be met by any ω-3 fatty acids or by arachidonic acid.
The main physiological requirement for ω-6 fatty acids is attributed to arachidonic acid. Arachidonic acid is the major precursor of prostaglandins, leukotrienes that play a vital role in cell signaling, and an endogenous cannabinoid anandamide. Metabolites from the ω-3 pathway, mainly from eicosapentaenoic acid, are mostly inactive, and this explains why ω-3 fatty acids do not correct the reproductive failure in rats where arachidonic is needed to make active prostaglandins that cause uterine contraction. To some extent, any ω-3 or ω-6 can contribute to the growth-promoting effects of EFA deficiency, but only ω-6 fatty acids can restore reproductive performance and correct the dermatitis in rats. Particular fatty acids are still needed at critical life stages (e.g. lactation) and in some disease states.
In nonscientific writing, common usage is that the term essential fatty acid comprises all the ω-3 or -6 fatty acids. Conjugated fatty acids like calendic acid are not considered essential. Authoritative sources include the whole families, but generally only make dietary recommendations for LA and ALA with the exception of DHA for infants under the age of 6 months. Recent reviews by WHO/FAO in 2009 and the European Food Safety Authority have reviewed the evidence and made recommendations for minimal intakes of LA and ALA and have also recommended intakes of longer chain ω-3 fatty acids based on the association of oily fish consumption with a lower risk of cardiovascular disease. Some earlier review lumped all polyunsaturated fatty acids together without qualification whether they were short or long-chain PUFA or whether they were ω-3 and ω-6 PUFA.
Conditional essentiality
Traditionally speaking, the LC-PUFAs are not essential to healthy adults. Because the LC-PUFA are sometimes required, they may be considered conditionally essential fatty acids.
== Food sources == |
Toxic shock syndrome | Toxic shock syndrome (TSS) is a condition caused by bacterial toxins. Symptoms may include fever, rash, skin peeling, and low blood pressure. There may also be symptoms related to the specific underlying infection such as mastitis, osteomyelitis, necrotising fasciitis, or pneumonia.TSS is typically caused by bacteria of the Streptococcus pyogenes or Staphylococcus aureus type, though others may also be involved. Streptococcal toxic shock syndrome is sometimes referred to as toxic-shock-like syndrome (TSLS). The underlying mechanism involves the production of superantigens during an invasive streptococcus infection or a localized staphylococcus infection. Risk factors for the staphylococcal type include the use of very absorbent tampons, and skin lesions in young children characterized by fever, low blood pressure, rash, vomiting and/or diarrhea, and multiorgan failure. Diagnosis is typically based on symptoms.Treatment includes intravenous fluids, antibiotics, incision and drainage of any abscesses, and possibly intravenous immunoglobulin. The need for rapid removal of infected tissue via surgery in those with a streptococcal cause, while commonly recommended, is poorly supported by the evidence. Some recommend delaying surgical debridement. The overall risk of death is about 50% in streptococcal disease, and 5% in staphylococcal disease. Death may occur within 2 days.In the United States, streptococcal TSS occurs in about 3 per 100,000 per year, and staphylococcal TSS in about 0.5 per 100,000 per year. The condition is more common in the developing world. It was first described in 1927. Due to the association with very absorbent tampons, these products were removed from sale.
Signs and symptoms
Symptoms of toxic shock syndrome (TSS) vary depending on the underlying cause. TSS resulting from infection with the bacterium Staphylococcus aureus typically manifests in otherwise healthy individuals via signs and symptoms including high fever, accompanied by low blood pressure, malaise and confusion, which can rapidly progress to stupor, coma, and multiple organ failure. The characteristic rash, often seen early in the course of illness, resembles a sunburn (conversely, streptococcal TSS will rarely involve a sunburn-like rash), and can involve any region of the body including the lips, mouth, eyes, palms and soles of the feet. In patients who survive, the rash desquamates (peels off) after 10–21 days.STSS caused by the bacterium Streptococcus pyogenes, or TSLS, typically presents in people with pre-existing skin infections with the bacteria. These individuals often experience severe pain at the site of the skin infection, followed by rapid progression of symptoms as described above for TSS.
Pathophysiology
In both TSS (caused by S. aureus) and TSLS (caused by S. pyogenes), disease progression stems from a superantigen toxin. The toxin in S. aureus infections is TSS Toxin-1, or TSST-1. The TSST-1 is secreted as a single polypeptide chain. The gene encoding toxic shock syndrome toxin is carried by a mobile genetic element of S. aureus in the SaPI family of pathogenicity islands. The toxin causes the non-specific binding of MHC II, on professional antigen presenting cells, with T-cell receptors, on T cells.
In typical T-cell recognition, an antigen is taken up by an antigen-presenting cell, processed, expressed on the cell surface in complex with class II major histocompatibility complex (MHC) in a groove formed by the alpha and beta chains of class II MHC, and recognized by an antigen-specific T-cell receptor. This results in polyclonal T-cell activation. Superantigens do not require processing by antigen-presenting cells but instead, interact directly with the invariant region of the class II MHC molecule. In patients with TSS, up to 20% of the bodys T-cells can be activated at one time. This polyclonal T-cell population causes a cytokine storm, followed by a multisystem disease.
Risk factors
A few possible causes of toxic shock syndrome are:
Cuts or open wounds on the skin
Surgical wounds
Viral infections (e.g. Chicken Pox)
Contraceptive sponges
History of a recent birth, miscarriage, or abortion
Using super-absorbent tampons
Previously having TSS
Diagnosis
For staphylococcal toxic shock syndrome, the diagnosis is based upon CDC criteria defined in 2011, as follows:
Body temperature > 38.9 °C (102.02 °F)
Systolic blood pressure < 90 mmHg
Diffuse macular erythroderma
Desquamation (especially of the palms and soles) 1–2 weeks after onset
Involvement of three or more organ systems:
Gastrointestinal (vomiting, diarrhea)
Muscular: severe myalgia or creatine phosphokinase level at least twice the upper limit of normal for laboratory
Mucous membrane hyperemia (vaginal, oral, conjunctival)
Kidney failure (serum creatinine > 2 times normal)
Liver inflammation (bilirubin, AST, or ALT > 2 times normal)
Low platelet count (platelet count < 100,000 / mm3)
Central nervous system involvement (confusion without any focal neurological findings)
Negative results of:
Blood, throat, and CSF cultures for other bacteria (besides S. aureus)
Negative serology for Rickettsia infection, leptospirosis, and measlesCases are classified as confirmed or probable as follows:
Confirmed: All six of the criteria above are met (unless the patient dies before desquamation can occur)
Probable: Five of the six criteria above are met
Treatment
The severity of this disease frequently warrants hospitalization. Admission to the intensive care unit is often necessary for supportive care (for aggressive fluid management, ventilation, renal replacement therapy and inotropic support), particularly in the case of multiple organ failure. Treatment includes removal or draining of the source of infection—often a tampon—and draining of abscesses. Outcomes are poorer in patients who do not have the source of infection removed.Antibiotic treatment should cover both S. pyogenes and S. aureus. This may include a combination of cephalosporins, penicillins or vancomycin. The addition of clindamycin or gentamicin reduces toxin production and mortality.
In some cases doctors will prescribe other treatments such as blood pressure medications (to stabilize blood pressure if it is too low), dialysis, oxygen mask (to stabilize oxygen levels), and sometimes a ventilator. These will sometimes be used to help treat side affects of contracting TSS.
Prognosis
With proper treatment, people usually recover in two to three weeks. The condition can, however, be fatal within hours. TSS has a mortality rate of 30%–70%. Children who are affected by TSS tend to recover easier than adults do.
Complications
Amputation of fingers, toes, and sometimes limbs
Death
Liver or Kidney failure
Heart problems
Respiratory distress
Septic shock
Other abnormalities may occur depending on the case
Prevention
During menstruation:
Use pads at night instead of tampons
Try to keep up with changing a tampon every 4 to 8 hours
Use low absorbent tampons
Follow directions when using vaginal contraceptives (sponges or diaphragms)
Make sure to maintain good hygiene during a menstrual cycleFor anyone:
Keep open wounds clean
Watch wounds and cuts for signs of infection (e.g. pus, redness, and warm to touch)
Keep personal items personal (e.g.towels, sheets, razors)
Wash clothing and bedding in hot water
Epidemiology
Staphylococcal toxic shock syndrome is rare and the number of reported cases has declined significantly since the 1980s. Patrick Schlievert, who published a study on it in 2004, determined incidence at three to four out of 100,000 tampon users per year; the information supplied by manufacturers of sanitary products such as Tampax and Stayfree puts it at one to 17 of every 100,000 menstruating females per year.TSS was considered a sporadic disease that occurred in immunocompromised people. It was not a more well-known disease until the 1980s, when high-absorbency tampons were in use by menstruating women. Due to the idea of the tampons having a high absorbency this led women to believe that they could leave a tampon in for several hours. Doing this allowed the bacteria to grow and infect women. This resulted in a spike of cases of TSS.Philip M. Tierno Jr. helped determine that tampons were behind TSS cases in the early 1980s. Tierno blames the introduction of higher-absorbency tampons in 1978. A study by Tierno also determined that all-cotton tampons were less likely to produce the conditions in which TSS can grow; this was done using a direct comparison of 20 brands of tampons including conventional cotton/rayon tampons and 100% organic cotton tampons from Natracare. In fact, Dr Tierno goes as far to state, "The bottom line is that you can get TSS with synthetic tampons, but not with an all-cotton tampon."A rise in reported cases occurred in the early 2000s: eight deaths from the syndrome in California in 2002 after three successive years of four deaths per year, and Schlieverts study found cases in part of Minnesota more than tripled from 2000 to 2003. Schlievert considers earlier onset of menstruation to be a cause of the rise; others, such as Philip M. Tierno and Bruce A. Hanna, blame new high-absorbency tampons introduced in 1999 and manufacturers discontinuing warnings not to leave tampons in overnight.TSS is more common during the winter and spring and occurs most often in the young and old.Toxic shock syndrome is commonly known to be an issue for females who menstruate. TSS although can occur in people of all ages and genders. Around fifty percent of Toxic Shock Syndrome cases are in non menstruating cases. TSS in these cases can be caused by skin wounds, surgical sites, nasal packing, and burns.
History
Initial description
The term "toxic shock syndrome" was first used in 1978 by a Denver pediatrician, James K. Todd, to describe the staphylococcal illness in three boys and four girls aged 8–17 years. Even though S. aureus was isolated from mucosal sites in the patients, bacteria could not be isolated from the blood, cerebrospinal fluid, or urine, raising suspicion that a toxin was involved. The authors of the study noted reports of similar staphylococcal illnesses had appeared occasionally as far back as 1927, but the authors at the time failed to consider the possibility of a connection between toxic shock syndrome and tampon use, as three of the girls who were menstruating when the illness developed were using tampons. Many cases of TSS occurred after tampons were left in after they should have been removed.
Rely tampons
Following controversial test marketing in Rochester, New York, and Fort Wayne, Indiana, in August 1978, Procter and Gamble introduced superabsorbent Rely tampons to the United States market in response to womens demands for tampons that could contain an entire menstrual flow without leaking or replacement. Rely used carboxymethylcellulose (CMC) and compressed beads of polyester for absorption. This tampon design could absorb nearly 20 times its own weight in fluid. Further, the tampon would "blossom" into a cup shape in the vagina to hold menstrual fluids without leakage.In January 1980, epidemiologists in Wisconsin and Minnesota reported the appearance of TSS, mostly in those menstruating, to the CDC. S. aureus was successfully cultured from most of the subjects. The Toxic Shock Syndrome Task Force was created and investigated the epidemic as the number of reported cases rose throughout the summer of 1980. In September 1980, CDC reported users of Rely were at increased risk for developing TSS.On 22 September 1980, Procter and Gamble recalled Rely following release of the CDC report. As part of the voluntary recall, Procter and Gamble entered into a consent agreement with the FDA "providing for a program for notification to consumers and retrieval of the product from the market". However, it was clear to other investigators that Rely was not the only culprit. Other regions of the United States saw increases in menstrual TSS before Rely was introduced.It was shown later that higher absorbency of tampons was associated with an increased risk for TSS, regardless of the chemical composition or the brand of the tampon. The sole exception was Rely, for which the risk for TSS was still higher when corrected for its absorbency. The ability of carboxymethylcellulose to filter the S. aureus toxin that causes TSS may account for the increased risk associated with Rely.
Notable cases
Clive Barker, fully recovered, contracted the syndrome after visiting the dentist.
Lana Coc-Kroft, fully recovered, contracted the syndrome due to group A streptococcal infection.
Jim Henson, d. 1990, contracted the syndrome due to group A streptococcal infection and subsequently died from it.
Nan C. Robertson, d. 2009, the 1983 winner of the Pulitzer Prize for Feature Writing for her medically detailed account of her struggle with toxic shock syndrome, a cover story for The New York Times Magazine which at that time became the most widely syndicated article in Times history.
Barbara Robison, lead vocalist for the psychedelic rock band the Peanut Butter Conspiracy, was performing in Butte, Montana on April 6, 1988; during the concert, she fell ill and was transported to a hospital. She did not recover, and died sixteen days later on April 22 from toxic shock poisoning at the age of 42.
Mike Von Erich, d. 1987, developed the syndrome after shoulder surgery: he made an apparent recovery but experienced brain damage and weight loss as a result of the condition; he died by suicide later.
References
External links
Stevens DL (1995). "Streptococcal toxic-shock syndrome: spectrum of disease, pathogenesis, and new concepts in treatment". Emerging Infectious Diseases. 1 (3): 69–78. doi:10.3201/eid0103.950301. PMC 2626872. PMID 8903167.
"Toxic Shock Syndrome (TSS): The Facts". Toxic Shock Syndrome information service. tssis.com. |
Biliary dyskinesia | Biliary dyskinesia is a disorder of some component of biliary part of the digestive system in which bile cannot physically move in the proper direction through the tubular biliary tract. It most commonly involves abnormal biliary tract peristalsis muscular coordination within the gallbladder in response to dietary stimulation of that organ to squirt the liquid bile through the common bile duct into the duodenum. Ineffective peristaltic contraction of that structure produces postprandial (after meals) right upper abdominal pain (cholecystodynia) and almost no other problem. When the dyskinesia is localized at the biliary outlet into the duodenum just as increased tonus of that outlet sphincter of Oddi, the backed-up bile can cause pancreatic injury with abdominal pain more toward the upper left side. In general, biliary dyskinesia is the disturbance in the coordination of peristaltic contraction of the biliary ducts, and/or reduction in the speed of emptying of the biliary tree into the duodenum.
Mechanism
Normally, the downstream gallbladder stores and concentrates the bile which originates in liver hepatocyte cells and is released into the microscopic component of the biliary system by the liver. Through aggregating tubules of increasing diameter, the bile leaves the liver and reaches the upstream (proximal) component of the common bile duct. Apparently, the common bile duct beyond (distal to) the gallbladder tends to normally have a greater tone so that the bile backs up into the gallbladder. When bile enters the duodenum (the first part of the small intestine), it aids in digesting the fat within food leaving the stomach. When the bile can not be properly propelled from the not-mechanically-obstructed gallbladder or can not flow out of the end of the common bile duct properly, there is a state of biliary dyskinesia.
So, biliary dyskinesia is a dynamically (functional...not fixed mechanical) obstructive, pain-producing disorder. Obstruction by a stone or tumor is a static, mechanical obstruction and tends to produce a more intense pain known as biliary colic.
Failure of the biliary sphincter of Oddi can be distinguished from failure of the pancreatic sphincter.
Diagnosis
Diagnosis may or may not be determined by an ultrasound, but most likely the disease and other biliary diseases of the liver, gallbladder, and bile duct are found by what is most commonly referred to as a hepatobiliary or HIDA scan. This type of imaging is known as cholescintigraphy.
Cholescintigraphy
Cholescintigraphy or hepatobiliary scintigraphy is scintigraphy of the hepatobiliary tract, including the gallbladder and bile ducts. The image produced by this type of medical imaging, called a cholescintigram, is also known by other names depending on which radiotracer is used, such as HIDA scan, PIPIDA scan, DISIDA scan, or BrIDA scan. Cholescintigraphic scanning is a nuclear medicine procedure to evaluate the health and function of the gallbladder and biliary system. A radioactive tracer is injected through any accessible vein and then allowed to circulate to the liver and starts accumulating in the gall bladder which can take up to an hour. A standard fatty meal (usually a high fat milk shake) is then given and more imaging is performed for another hour so that the response to the fatty meal by the gall bladder can be shown. The gall bladder should respond and begin emptying into the duodenum, the amount of bile ejected can then be calculated as an ejection fraction (EF). An EF < 35% is considered to be diagnostic of biliary dyskinesia and suitable for cholecystectomy to be considered.
Treatment
Laparoscopic cholecystectomy has been used to treat the condition when due to dyskinesia of the gallbladder.
Prognosis
Symptoms may persist after cholecystectomy, and have been linked to the use of proton pump inhibitors.
See also
Bile acid malabsorption, an entry of the bile acid into a large intestine due to malabsorption the bile in the ileum, which may cause chronic diarrhea.
References
== External links == |
Maturity-onset diabetes of the young | Maturity-onset diabetes of the young (MODY) refers to any of several hereditary forms of diabetes mellitus caused by mutations in an autosomal dominant gene disrupting insulin production. MODY is often referred to as monogenic diabetes to distinguish it from the more common types of diabetes (especially type 1 and type 2), which involve more complex combinations of causes involving multiple genes and environmental factors. MODY 2 and MODY 3 are the most common forms.Robert Tattersall and Stefan Fajans initially identified the phenomenon known as maturity onset diabetes of the young in a classic study published in the journal Diabetes in 1975.
Signs and symptoms
MODY is the final diagnosis in 1%–2% of people initially diagnosed with diabetes. The prevalence is 70–110 per million people. 50% of first-degree relatives will inherit the same mutation, giving them a greater than 95% lifetime risk of developing MODY themselves. For this reason, correct diagnosis of this condition is important. Typically patients present with a strong family history of diabetes (any type) and the onset of symptoms is in the second to fifth decade.
There are two general types of clinical presentation.
Some forms of MODY produce significant hyperglycemia and the typical signs and symptoms of diabetes: increased thirst and urination (polydipsia and polyuria).
In contrast, many people with MODY have no signs or symptoms and are diagnosed either by accident, when a high glucose is discovered during testing for other reasons, or screening of relatives of a person discovered to have diabetes. Discovery of mild hyperglycemia during a routine glucose tolerance test for pregnancy is particularly characteristic.MODY cases may make up as many as 5% of presumed type 1 and type 2 diabetes cases in a large clinic population. While the goals of diabetes management are the same no matter what type, there are two primary advantages of confirming a diagnosis of MODY.
Insulin may not be necessary and it may be possible to switch a person from insulin injections to oral agents without loss of glycemic control.
It may prompt screening of relatives and so help identify other cases in family members.As it occurs infrequently, many cases of MODY are initially assumed to be more common forms of diabetes: type 1 if the patient is young and not overweight, type 2 if the patient is overweight, or gestational diabetes if the patient is pregnant. Standard diabetes treatments (insulin for type 1 and gestational diabetes, and oral hypoglycemic agents for type 2) are often initiated before the doctor suspects a more unusual form of diabetes.
Genetics
Some sources make a distinction between two forms of monogenetic diabetes: MODY and neonatal diabetes. However, they have much in common and are often studied together.
Heterozygous
MODY is inherited in an autosomal dominant fashion, and most patients therefore have other members of the family with diabetes; penetrance differs between the types (from 40% to 90%).
Homozygous
By definition, the forms of MODY are autosomal dominant, requiring only one abnormal gene to produce the disease; the severity of the disease is moderated by the presence of a second, normal allele which presumably functions normally. However, conditions involving people carrying two abnormal alleles have been identified. Unsurprisingly, combined (homozygous) defects of these genes are much rarer and much more severe in their effects.
MODY2: Homozygous glucokinase deficiency causes severe congenital insulin deficiency resulting in persistent neonatal diabetes mellitus. About 6 cases have been reported worldwide. All have required insulin treatment from shortly after birth. The condition does not seem to improve with age.
MODY4: Homozygous IPF1 results in failure of the pancreas to form. Congenital absence of the pancreas, termed pancreatic agenesis, involves deficiency of both endocrine and exocrine functions of the pancreas.Homozygous mutations in the other forms have not yet been described. Those mutations for which a homozygous form has not been described may be extremely rare, may result in clinical problems not yet recognized as connected to the monogenic disorder, or may be lethal for a fetus and not result in a viable child.
Pathophysiology
The recognised forms of MODY are all due to ineffective insulin production or release by pancreatic beta cells. Several of the defects are mutations of transcription factor genes. One form is due to mutations of the glucokinase gene. For each form of MODY, multiple specific mutations involving different amino acid substitutions have been discovered. In some cases, there are significant differences in the activity of the mutant gene product that contribute to variations in the clinical features of the diabetes (such as degree of insulin deficiency or age of onset).
Diagnosis
The following characteristics suggest the possibility of a diagnosis of MODY in hyperglycemic and diabetic patients:
Mild to moderate hyperglycemia (typically 130–250 mg/dL, or 7–14 mmol/L) discovered before 30 years of age. However, anyone under 50 can develop MODY.
A first-degree relative with a similar degree of diabetes.
Absence of positive antibodies or other autoimmunity (e.g., thyroiditis) in patient and family. However, Urbanova et al. found that about one quarter of Central European MODY patients are positive for islet cell autoantibodies (GABA and IA2A). Their expression is transient but highly prevalent. The autoantibodies were found in patients with delayed diabetes onset, and in times of insufficient diabetes control. The islet cell autoantibodies are absent in MODY in at least some populations (Japanese, Britons).
Persistence of a low insulin requirement (e.g., less than 0.5 u/kg/day) past the usual "honeymoon" period.
Absence of obesity (although overweight or obese people can get MODY) or other problems associated with type 2 diabetes or metabolic syndrome (e.g., hypertension, hyperlipidemia, polycystic ovary syndrome).
Insulin resistance very rarely happens.
Cystic kidney disease in patient or close relatives.
Non-transient neonatal diabetes, or apparent type 1 diabetes with onset before six months of age.
Liver adenoma or hepatocellular carcinoma in MODY type 3
Renal cysts, rudimentary or bicornuate uterus, vaginal aplasia, absence of the vas deferens, epidymal cysts in MODY type 5The diagnosis of MODY is confirmed by specific gene testing available through commercial laboratories.
Classification
Common or well-established forms of MODY (1% of MODY or greater) - HNF1A-(MODY3), HNF4A-(MODY1) and GCK-(MODY2), HNF1B-(MODY5), ABCC8-(MODY12), KCNJ11-(MODY13), INS-(MODY10)
Rare forms of MODY (Few families described but reasonable generic evidence for causing MODY) - NEUROD1-(MODY6), IPF1/PDX1-(MODY4), CEL-(MODY8), WSF1 and RFX6
Genes reported as causal for MODY but evidence not compelling - BLK-(MODY11), PAX4-(MODY9) and KLF11-(MODY7), APPL1-(MODY14), NKX6-1
Treatment
In some forms of MODY, standard treatment is appropriate, though exceptions occur:
In MODY2, oral agents are relatively ineffective, however most patients are managed conservatively through diet and exercise.
In MODY1 and MODY3, sulfonylureas are usually very effective, delaying the need for insulin treatment.
Sulfonylureas are effective in the KATP channel forms of neonatal-onset diabetes. The mouse model of MODY diabetes suggested that the reduced clearance of sulfonylureas stands behind their therapeutic success in human MODY patients, but Urbanova et al. found that human MODY patients respond differently to the mouse model and that there was no consistent decrease in the clearance of sulfonylureas in randomly selected HNF1A-MODY and HNF4A-MODY patients.Chronic hyperglycemia due to any cause can eventually cause blood vessel damage and the microvascular complications of diabetes. The principal treatment goals for people with MODY — keeping the blood sugars as close to normal as possible ("good glycemic control"), while minimizing other vascular risk factors — are the same for all known forms of diabetes.
The tools for management are similar for all forms of diabetes: blood testing, changes in diet, physical exercise, oral hypoglycemic agents, and insulin injections. In many cases these goals can be achieved more easily with MODY than with ordinary types 1 and 2 diabetes. Some people with MODY may require insulin injections to achieve the same glycemic control that another person may attain with careful eating or an oral medication.
When oral hypoglycemic agents are used in MODY, the sulfonylureas remain the oral medication of first resort. When compared to patients with type 2 diabetes, MODY patients are often more sensitive to sulphonylureas, such that a lower dose should be used to initiate treatment to avoid hypoglycaemia. Patients with MODY less often suffer from obesity and insulin resistance than those with ordinary type 2 diabetes (for whom insulin sensitizers like metformin or the thiazolidinediones are often preferred over the sulfonylureas).
Epidemiology
According to data from Saxony, Germany, MODY was responsible for 2.4% of diabetes incidence in children younger than 15 years.
History
The term MODY dates back to 1964, when diabetes mellitus was considered to have two main forms: juvenile-onset and maturity-onset, which roughly corresponded to what we now call type 1 and type 2. MODY was originally applied to any child or young adult who had persistent, asymptomatic hyperglycemia without progression to diabetic ketosis or ketoacidosis. In retrospect we can now recognize that this category covered a heterogeneous collection of disorders which included cases of dominantly inherited diabetes (the topic of this article, still called MODY today), as well as cases of what we would now call type 2 diabetes occurring in childhood or adolescence, and a few even rarer types of hyperglycemia (e.g., mitochondrial diabetes or mutant insulin). Many of these patients were treated with sulfonylureas with varying degrees of success.The current usage of the term MODY dates from a case report published in 1974.Since the 1990s, as the understanding of the pathophysiology of diabetes has improved, the concept and usage of MODY have become refined and narrower. It is now used as a synonym for dominantly inherited, monogenic defects of insulin secretion occurring at any age, and no longer includes any forms of type 2 diabetes.
Miscellaneous
MODY should not be confused with latent autoimmune diabetes of adults (LADA) — a form of type 1 DM, with slower progression to insulin dependence than child-onset type 1 DM, and which occurs later in life.
References
== External links == |
Syringofibroadenoma | Syringofibroadenoma is a cutaneous condition characterized by a hyperkeratotic nodule or plaque involving the extremities.: 668 It is considered of eccrine origin.
See also
Syringadenoma papilliferum
Skin lesion
References
== External links == |
Encephalitis lethargica | Encephalitis lethargica is an atypical form of encephalitis. Also known as "sleeping sickness" or "sleepy sickness" (distinct from tsetse fly-transmitted sleeping sickness), it was first described in 1917 by the neurologist Constantin von Economo and the pathologist Jean-René Cruchet. The disease attacks the brain, leaving some victims in a statue-like condition, speechless and motionless. Between 1915 and 1926, an epidemic of encephalitis lethargica spread around the world. The exact number of people infected is unknown, but it is estimated that more than one million people contracted the disease during the epidemic, which directly caused more than 500,000 deaths. Most of those who survived never returned to their pre-morbid vigour.
In the words of the famed neurologist and writer Oliver Sacks: They would be conscious and aware – yet not fully awake; they would sit motionless and speechless all day in their chairs, totally lacking energy, impetus, initiative, motive, appetite, affect or desire; they registered what went on about them without active attention, and with profound indifference. They neither conveyed nor felt the feeling of life; they were as insubstantial as ghosts, and as passive as zombies.No recurrence of the epidemic has since been reported, though isolated cases continue to occur.
Signs and symptoms
Encephalitis lethargica is characterized by high fever, sore throat, headache, lethargy, double vision, delayed physical and mental response, sleep inversion and catatonia. In severe cases, patients may enter a coma-like state (akinetic mutism). Patients may also experience abnormal eye movements ("oculogyric crises"), Parkinsonism, upper body weakness, muscular pains, tremors, neck rigidity, and behavioral changes including psychosis. Klazomania (a vocal tic) is sometimes present.
Cause
The causes of encephalitis lethargica are uncertain. Some studies have explored its origins in an autoimmune response, and, separately or in relation to an immune response, links to pathologies of infectious disease—viral and bacterial, such as in the case of influenza, where a link with encephalitis is clear. Postencephalitic Parkinsonism was clearly documented to have followed an outbreak of encephalitis lethargica following the 1918 influenza pandemic; evidence for viral causation of the Parkinsons symptoms is circumstantial (epidemiologic, and finding influenza antigens in encephalitis lethargica patients), while evidence arguing against this cause is of the negative sort (for example, lack of viral RNA in postencephalitic Parkinsonian brain material). In reviewing the relationship between influenza and encephalitis lethargica (EL), McCall and coworkers conclude, as of 2008, that "the case against influenza [is] less decisive than currently perceived… there is little direct evidence supporting influenza in the etiology of EL," and that "[a]lmost 100 years after the EL epidemic, its etiology remains enigmatic." Hence, while opinions on the relationship of encephalitis lethargica to influenza remain divided, the preponderance of literature appears skeptical.The German neurologist Felix Stern, who examined hundreds of encephalitis lethargica patients during the 1920s, noted that their encephalitis lethargica typically evolved over time. The early symptoms would be dominated by sleepiness or wakefulness. A second symptom would lead to an oculogyric crisis. The third symptom would be recovery, followed by a Parkinson-like syndrome. If patients of Stern followed this course of disease, he diagnosed them with encephalitis lethargica. Stern suspected encephalitis lethargica to be close to poliomyelitis, without evidence. Nevertheless, he experimented with the convalescent serum of survivors of the first acute syndrome. He vaccinated patients with early-stage symptoms, telling them that it might be successful. Stern is author of the definitive 1920s book, Die Epidemische Encephalitis.In 2010, in a substantial Oxford University Press compendium reviewing the historic and contemporary views on EL, its editor, Joel Vilensky, of the Indiana University School of Medicine, quotes another researcher, writing in 1930, who states, "we must confess that etiology is still obscure, the causative agent still unknown, the pathological riddle still unsolved…", and goes on to offer the following conclusion, as of that publication date:
Does the present volume solve the "riddle" of EL, which… has been referred to as the greatest medical mystery of the 20th century? Unfortunately, no: but inroads are certainly made here pertaining to diagnosis, pathology, and even treatment."
Subsequent to publication of this compendium, an enterovirus was discovered in encephalitis lethargica cases from the epidemic. In 2012, Oliver Sacks, the author of the book Awakenings, about institutionalized survivors, acknowledged this virus as the probable cause of the disease. Other sources have suggested Streptococcus pneumoniae as a cause.
Diagnosis
There have been several proposed diagnostic criteria for encephalitis lethargica. One, which has been widely accepted, includes an acute or subacute encephalitic illness where all other known causes of encephalitis have been excluded. Another diagnostic criterion, suggested more recently, says that the diagnosis of encephalitis lethargica "may be considered if the patients condition cannot be attributed to any other known neurological condition and that they show the following signs: influenza-like signs; hypersomnolence (hypersomnia), wakeability, ophthalmoplegia (paralysis of the muscles that control the movement of the eye), and psychiatric changes."
Treatment
Modern treatment approaches to encephalitis lethargica include immunomodulating therapies, and treatments to remediate specific symptoms.There is little evidence so far of a consistent effective treatment for the initial stages, though some patients given steroids have seen improvement. The disease becomes progressive, with evidence of brain damage similar to that of Parkinsons disease.Treatment is then symptomatic. L-DOPA (Levodopa) and other anti-Parkinson drugs often produce dramatic responses; however, most people given L-DOPA experience improvements that are short lived.
History
Occurrences
Retrospective diagnosis tentatively suggests various historical outbreaks of encephalitis lethargica:
In 1580, Europe was swept by a serious febrile and lethargic illness that led to Parkinsonism and other neurological sequelae.
In 1673–1675, a similar serious epidemic occurred in London, which Thomas Sydenham described as "febris comatosa".
In 1695, a 20-year-old woman in Germany experienced oculogyric crises, Parkinsonism, diplopia, strabismus, and other symptoms following an attack of somnolent brain fever, as described by Albrecht of Hildesheim.
In 1712–1713, a severe epidemic of Schlafkrankheit (sleep sickness) occurred in Tübingen, Germany, followed in many cases by persistent slowness of movement and lack of initiative (aboulia).
Between 1750 and 1800, France and Germany experienced minor epidemics of "coma somnolentum" with features of Parkinsonism, including hyperkinetic hiccup, myoclonus, chorea, and tics.
Between 1848 and 1882, Paris-based neurologist Jean-Martin Charcot documented many isolated cases of juvenile Parkinsonism, associated with diplopia, oculogyria, tachypnoea, retropulsion, and obsessional disorders, which were almost certainly post-encephalitic in origin.
In 1890 in Italy, following the influenza epidemic of 1889–1890, a severe epidemic of somnolent illnesses (nicknamed the "Nona") appeared. For the few survivors of the Nona, Parkinsonism and other sequelae developed in almost all cases.
Between 1915 and 1926, a world-wide encephalitis lethargica pandemic occurred, impacting nearly 5 million people and killing an estimated 1.6 million people.
Pandemic of 1915–1926
In the winter of 1916–1917, a "new" illness suddenly appeared in Vienna and other cities, and rapidly spread world-wide over the next three years. Earlier reports appeared throughout Europe as early as the winter of 1915–1916, but communication about the disease was slow and chaotic, given the varied manifestation of symptoms and difficulties disseminating information in wartime. Until Constantin von Economo identified a unique pattern of damage among the brains of deceased patients and introduced the unifying name encephalitis lethargica, reports of the protean disease came in under a range of names: botulism, toxic ophthalmoplegia, epidemic stupor, epidemic lethargic encephalitis, acute polioencephalitis, Heine-Medin disease, bulbar paralysis, hystero-epilepsy, acute dementia, and sometimes just "an obscure disease with cerebral symptoms." Just 10 days before von Economos breakthrough in Vienna, Jean-René Cruchet described 40 cases of "subacute encephalomyelitis" in France.The number of people infected during the ten years of the pandemic is unknown, but it is estimated that more than 1 million people contracted the disease, which directly caused more than 500,000 deaths. Encephalitis lethargica assumed its most virulent form between October 1918 and January 1919. The pandemic disappeared in 1927, as abruptly and mysteriously as it first appeared. The great encephalitis pandemic coincided with the 1918 influenza pandemic, and it is likely that the influenza virus potentiated the effects of the causative agent of the encephalitis or lowered resistance to it in a catastrophic way.
Aftermath
Many surviving patients of the 1915–1926 pandemic seemed to make a complete recovery and return to their normal lives. However, the majority of survivors subsequently developed neurological or psychiatric disorders, often after years or decades of seemingly perfect health. Post-encephalitic syndromes varied widely: sometimes they proceeded rapidly, leading to profound disability or death; sometimes very slowly; sometimes they progressed to a certain point and then stayed at this point for years or decades; and sometimes, following their initial onslaught, they remitted and disappeared. Postencephalitic Parkinsonism is perhaps the most widely recognized of such syndromes.
Notable cases
Notable cases include:
Muriel "Kit" Richardson (née Hewitt), first wife of actor Sir Ralph Richardson, died of the condition in October 1942, having first shown symptoms in 1927–28.
There is speculation that Adolf Hitler may have had encephalitis lethargica when he was a young adult (in addition to the more substantial case for Parkinsonism in his later years).
Mervyn Peake (1911–1968), author of the Gormenghast books, began his decline towards death which was initially attributed to encephalitis lethargica with Parkinsons disease–like symptoms, although others have later suggested his decline in health and eventual death may have been due to Lewy body dementia.
Those described in the book Awakenings by the British neurologist Oliver Sacks.
Jane Norton Grew Morgan, wife of J. P. Morgan Jr., died of encephalitis lethargica in 1925. At the time, doctors attributed her encephalitis to having contracted influenza during the 1918 pandemic.
References
Further reading
Crosby, Molly Caldwell (2010). Asleep: The Forgotten Epidemic that Remains One of Medicines Greatest Mysteries. New York: Penguin/Berkley. – Describes the history of the disease, and the epidemic of the 1920s.
Reid, A.H.; McCall, S.; Henry, J.M.; Taubenberger, J.K. (2001). "Experimenting on the Past: The Enigma of von Economos Encephalitis Lethargica". J. Neuropathol. Exp. Neurol. 60 (7): 663–670. doi:10.1093/jnen/60.7.663. PMID 11444794.
Sacks, Oliver (1990). Awakenings. Vintage Books. ISBN 978-0-375-70405-5. OCLC 21910570.
Sacks O (1983). "The origin of Awakenings". Br. Med. J. (Clin. Res. Ed.). 287 (6409): 1968–1969. doi:10.1136/bmj.287.6409.1968. PMC 1550182. PMID 6418286.
Vilensky, J.A.; Foley, P.; Gilman, S. (2007). "Children and Encephalitis Lethargica: A Historical Review". Pediatr. Neurol. 37 (2, August): 79–84. doi:10.1016/j.pediatrneurol.2007.04.012. PMID 17675021.
Vilensky, Joel A., ed. (2010). Encephalitis Lethargica: During and After the Epidemic. Oxford, UK: Oxford University Press. ISBN 978-0190452209.
External links
National Institute of Neurological Disorders and Stroke
Mystery of the Forgotten Plague: BBC news item about the tracing of the infectious agent in encephalitis lethargica |
Phaeohyphomycosis | Phaeohyphomycosis is a diverse group of fungal infections, caused by dematiaceous fungi whose morphologic characteristics in tissue include hyphae, yeast-like cells, or a combination of these.: 324 It can be associated an array of melanistic filamentous fungi including Alternaria species, Exophiala jeanselmei, and Rhinocladiella mackenziei.The term “phaeohyphomycosis” was introduced to determine infections caused by dematiaceous (pigmented) filamentous fungi which contain melanin in their cell walls. Phaeohyphomycosis is an uncommon infection, but the number of cases reported has been increasing in recent years. Fungal melanin is thought to be a virulence factor. The outcome of antifungal treatment is poor, and mortality is almost 80%. Phaeohyphomycosis has been attributed to more than 100 species and 60 genera of fungi over the past several decades. The pathogens are considered opportunistic. Almost all cases of widely disseminated infection have occurred in immunosuppressed people.
Clinical signs of phaeohyphomycosis
Wildlife
Phaeohyphomycosis is found throughout the animal kingdom. From molluscs to humans, different strains of this fungus affect animals differently, based on how severely the fungus has infected the animal. The clinical signs depend on the species of animal that is infected as well as the strain of fungus it is infected with. This disease is usually found more often in stressed animals after removal from their habitat.
Invertebrates
Invertebrates, such as crabs and mollusks, show a variety of clinical signs.
Crabs had increasingly weak motor control, especially in legs and claws, and were lethargic. They had poor balance and tetany, or muscle spasms, in the claws. Finally, they had tissue necrosis, which caused deterioration of the epidermis, connective tissue, heart, hepatopancreas, nervous system, and gills. In severe cases, there was congestion of hemal sinuses, two principal empty areas along the digestive tube and vessels. Mass amounts of yeast-like cells compressed nerve fibers and the gill lamellae were destroyed.
Mollusks clinical signs vary from scattered spots of brownish discoloration on the mantle tissues to general deterioration of mussel condition. In severe cases, there were black-bodied mussels with a distinct odor and black yeast-cells infected the connective tissues around the gonads and the digestive tract.
Cold-blooded vertebrates
Cold-blooded vertebrates exhibited an assortment of clinical signs.
Amphibians showed signs of anorexia. Ulcers or nodules in the skin were found, as well as swelling and lesions of internal organs, including the spleen, liver, and kidney. In extreme cases, neurological disorders and multifocal dermatitis (swelling caused by irritation of the fungus) occurred.
Fish demonstrated signs of lethargy and disoriented swimming. There were ulcerative lesions, multiple dark foci in the gills, and non-ulcerative dermal masses found. In critical cases, some fish showed a variety of inflammatory responses including the formation of microabscesses. Lesions in the brain and kidneys were also found. These fish had abnormal swimming behavior, bulging eyes, and abdominal swelling.
Warm-blooded vertebrates
From birds to equines, Phaeohyphomycosis persists and has a massive range of clinical signs throughout differing species. Poultry and wild birds had neurological disorders and a loss of movement control. They experienced severe torticollis, which are severe muscle spasms that compromise the bird’s ability to hold up its head. The birds exhibited a loss of balance due to the rigidity of their legs.
Cats showed signs of difficulty breathing due to excessive swelling of the nose. There were also lesions found throughout the body, including the brain. Common lesions include ulcerated cutaneous nodules of the digits, pinnae, nasal planum, and nasal/paranasal tissues.In extreme cases dogs exhibited vision impairment and had deep infections in the nasal cavity, kidneys, and the cerebellum. In dogs, brain infections were found similar to infections that were found in humans. Other clinical signs were lesions, abscesses, and severe inflammation throughout the dog’s body.
Ruminants and equines were affected the same way from Phaeohyphomycosis. They showed respiratory distress through constant coughing and a fever. They demonstrated signs of anorexia, lethargy, and hypothermia. There was inflammation, hair loss, scaling, and damage to their cerebellum.
Humans
Human’s clinical signs consisted of swelling and eye infections. There were nodules underneath the skin, abscesses or cysts, and lesions running throughout the body. There were papules, plaques and granulomatous damages on the body. In extreme cases there were deep infections within the eyes, bones, heart and central nervous system.
Treatment
Extensive treatments have been used on domestic animals more than on wild animals, probably because infected domestic animals are easier to identify and treat than infected wildlife. Treatment plans and management vary across taxa because this disease tends to affect each species differently. Antifungal drugs are the first line of defense to kill the agents causing phaeohyphomycosis, but despite the significant progress made in the last two decades and a 30% increase in available antifungal drugs since 2000, many drugs are not effective against black fungi. Diseases caused by black fungi are hard to treat because the fungi are very difficult to kill. This high resilience may be contributed to the presence of melanin in their cell walls, as well as the greater similarity to host cells which are both eukaryotes than other pathogens such as bacteria or viruses. Current antifungal agents the fungi are not resistant to are posaconazole, voriconazole, and azole isavuconazole.In 2006, a free-living Eastern box turtle, Terrapene carolina carolina, was found with a form of phaeohyphomycosis and was brought in the Wildlife Center of Virginia. Its symptom was swelling of the right hindfoot; it was diagnosed as having chromomycosis by histopathology. The center provided a series of antimicrobial treatments and a one-month course of 1 mg itraconazole, administered orally once a day. The eastern box turtle was euthanized due to further complications and the caretakers’ belief that the turtle would not be able to survive if placed back in the wild.
A recent case of a form of phaeohyphomycosis infection was found in a dog in 2011. The Journal of the American Veterinary Medical Association published a case study in which researchers successfully managed an intracranial phaeohyphomycotic fungal granuloma in a one-year-old male Boxer dog. Veterinarians of the Department of Veterinary Clinical Sciences at Tufts University surgically removed the granuloma in the right cerebral hemisphere. The patient was treated with fluconazole for 4 months, and was followed with voriconazole for 10 months. Both are medications used to treat fungal infections. Based on magnetic resonance imaging and cerebrospinal fluid (CSF) analysis 8 months after the surgery, the male Boxer’s outcome was considered excellent.
Emphasis has been placed on how to manage this disease through careful management practices including: proper handling, preventing crowding situation with animals, and transportation. Both the animals and the environment should be treated thoroughly to hinder the spread and control the fungal infection. This is especially important since humans can also contract this disease.
Research projects and implications
Phaeohyphomycosis is a disease caused by this fungus. If given the opportunity, this disease can spread to the brain and cause a painful death. There have been multiple reports of this host of fungi, but by the time the disease is recognized, it is usually too late for the animal to be successfully treated. Recent searches of databases show that there are no current projects studying the spread of this fungus in wild animals, though there are documented cases of its occurrence.
In 2005, a five-month-old snow leopard (Uncia uncia) in Europe was diagnosed with phaeohyphomycosis due to Cladophalophora bantiana. This fungus caused spastic paralysis as well as the inability to defecate or urinate. Because of this finding, more researchers are aware of this disease and the fact that it does not just infect the brain, as previously thought, but also other organs and other parts of the nervous system. A Purdue University study in 2011 showed a Huacaya alpaca (Vicugna pacos) with the same fungus affected by cerebral phaeohyphomycosis. The eight-year-old animal was the first report of this disease in a camelid ruminant.Conclusively, phaeohyphomycosis is a highly prolific disease that is caused by multiple genera of fungi. The disease is transmissible through several mediums, including air, wind, and water. Both individual animals and whole populations can be affected by it. Although it does not seem to be an epidemic, it is nonetheless an area of concern and requires much more active research rather than simply reports of terminal or already-dead animals.
See also
Skin lesion
== References == |
Birth weight | Birth weight is the body weight of a baby at its birth. The average birth weight in babies of European descent is 3.5 kilograms (7.7 lb), with the normative range between 2.5 and 4.5 kilograms (5.5 and 9.9 lb). On average, babies of South Asian and Chinese descent weigh about 3.26 kilograms (7.2 lb). As far as low birth weight prevalence rates changing over time, there has been a slight decrease from 7.9% (1970) to 6.8% (1980), then a slight increase to 8.3% (2006), to the current levels of 8.2% (2016). The prevalence of low birth weights has trended slightly upward from 2012 to the present.There have been numerous studies that have attempted, with varying degrees of success, to show links between birth weight and later-life conditions, including diabetes, obesity, tobacco smoking, and intelligence. Low birth weight is associated with neonatal infection and infant mortality.
Abnormalities
A low birth weight can be caused either by a preterm birth (low gestational age at birth) or of the infant being small for gestational age (slow prenatal growth rate), or a combination of both. Potential causes of low birth weight can also be cause by health issues in the person giving birth, genetic factors, or problems in the placenta.
A very large birth weight is usually caused by the infant having been large for gestational age. Infants that are large for gestational age have been associated with significantly higher rates of neonatal morbidity.
Determinants
Genetics
There are two genetic loci that have been strongly linked to birth weight, ADCY5 and CCNL1, as well four that show some evidence (CDKAL1, HHEX-IDE, GCK, and TCF7L2). The heritability of birth weight ranges from 25 to 40%. There is a complex relationship between a babys genes and the maternal environment that the child is developing in. Foetal genes influence how the fetus grows in utero, and the maternal genes influence how the environment affects the growing fetus.
Maternal health
The health of the mother during the pregnancy can affect birth weight. A pre-existing disease or acquired disease in pregnancy is sometimes associated with decreased birth weight. For example, celiac disease confers an odds ratio of low birth weight of approximately 1.8. Certain medications (e.g. for high blood pressure or epilepsy) can put a mother at a higher risk for delivering a low birth weight baby. Women younger than 15 or older than 35 are at a higher risk to have a low-birth weight baby. Multiple births, where a mother has more than one child at one time, can also be a determinant in birth weight as each baby is likely to be outside the AGA (appropriate for gestational age). Multiple births put children at a higher rate to have low birth weight (56.6%) compared to children born in a single birth ( 6.2%). Low birth weight can also vary by maternal age. In 2008 the rate of low birth weight was the highest in babies born to women younger than 15 years old (12.4%). Women aged 40–54 had a rate of low birth weight at 11.8 percent. The lowest rates of low birth weight happened among babies whose mothers were between the ages of 25–29 years (4.4%) and 30–34 years (7.6%).
Stress
Stressful events have been demonstrated to produce significant effects on birth weight. Those mothers who have stressful events during pregnancy, especially during the first and second trimester, are at higher risk to deliver low-birth weight babies. Researchers furthered this study and found that maternal stressful events that occur prior to conception have a negative impact on birth weight as well, and can result in a higher risk for preterm and lower birth weight babies. Women who experienced abuse (physical, sexual, or emotional) during pregnancy are also at increased risk of delivering a low-birth weight baby. For example, in a study completed by Witt et al., those women who experienced a stressful event (i.e. death of close family member, infertility issues, separation from partner) prior to conception had 38% more of a chance to have a very low birth weight baby compared to those who had not experienced a stressful life event. The theory is that stress can impact a baby based on two different mechanisms: neuroendocrine pathway or immune/inflammatory pathway. Stress causes the body to produce stress hormones called glucocorticoids that can suppress the immune system., as well as raises levels of placental corticotropin-releasing hormone (CRH) which can lead to preterm labor. These findings can pose evidence for future prevention efforts for low birth weight babies. One way to decrease rates of low birth weight and premature delivery is to focus on the health of women prior to conception through reproductive education, screening and counseling regarding mental health issues and stress, and access to primary care.
Racial stress
Non-Hispanic Blacks have the highest infant mortality rate in the United States (11.4 deaths per 1,000 live births compared to the national average of 5.9 deaths per 1,000 live births). Subsequently, there has been growing research supporting the idea of racial discrimination as a risk factor for low birth weight. In one study by Collins et al., evidence suggested that African American mothers who experienced high levels of racial discrimination were at significantly higher risk of delivering a very low-birth weight baby compared to African American mothers who had not experienced racial discrimination. Black infants (13.2%) are more likely to have low birth weight compared to Asian and Pacific Islander (8.1%), American Indian and Alaska Native (7.6%), Non-Hispanic White (7.0%), and Hispanic Infants (7.1%).
Environmental factors
Environmental factors, including exposure of the mother to secondhand smoke can be a factor in determining the birth weight of child. In 2014, 13% of children exposed to smoke were born with low birth weight compared with 7.5% of those children born to nonsmokers. Children born to mothers who smoked or were exposed to secondhand smoke are more likely to develop health problems earlier in life such as neurodevelopmental delays. When mothers actively smoke during pregnancy, their child is at a higher risk of being born with a low birth weight. Smoking can also be a stress management tool used by expecting mothers. There is some support for lower socioeconomic status of the parents being a determinant of low birth weight, but there is conflicting evidence, as socioeconomic status is tied to many other factors.
Neonatal care
Most babies admitted to the NICU are born before 37 weeks of pregnancy or have low birth weight which is less than 5.5 pounds (2.5 kg). They could also have a medical condition that requires special care. In the United States nearly half a million babies are born preterm. Because of this, many of these babies also have low birth weights. There are four levels of care in the neonatal care units. Intensive Care, High Dependency Care, Low Dependency, and Transitional Care are the four levels:
Intensive Care: For babies with serious problems. This includes babies born three months early and have extremely low birth weight.
High Dependency Care: For babies with less serious problem, but who still may not to be looked after or babies that are recovering from a critical illness.
Low Dependency Care: For babies that do not need a continuous supervision.
Transitional Care: For babies that still need medical treatment, but are well enough to be called for at their mothers bedside.
Influence on the first few years of life
Children born with an abnormally low birth weight can have significant problems within the first few years of life. They may have trouble gaining weight, obtaining adequate nutrition, and supporting a strong immune system. They also have higher risks for mortality, behavior problems, and mental deficiencies. Low birth weight babies are more likely to develop the following conditions after birth compared to normal birth weight babies:
Breathing problems (infant respiratory distress syndrome)
Bleeding in the brain (intraventricular hemorrhage)
Patent ductus arteriosus (PDA)
Necrotizing enterocolitis
Retinopathy of prematurity
Jaundice
InfectionsThat said, the effects of low birth weight on a childs first few years of life are often intertwined with other maternal, environmental, and genetic factors and most effects of low birth weight are only slightly negatively significant on a childs life when these factors are controlled for. When these factors are controlled, the only significant effect low birth weight has on a childs development is physical growth in the early years and the likelihood of being underweight compared to normal birth weight babies.
Influence on adult life
Studies have been conducted to investigate how a persons birth weight can influence aspects of their future life. This includes theorised links with obesity, diabetes and intelligence.
Obesity and diabetes
A baby born small or large for gestational age (either of the two extremes) is thought to have an increased risk of obesity in later life, but it was also shown that this relationship is fully explained by maternal weight. Middle aged adults with low birth weight present with a higher chance of obesity and diabetes. Children that are born under six pounds were 1.27 times more likely to develop diabetes compared to babies born at a healthy weight over six pounds.
Growth hormone (GH) therapy at a certain dose induced catch-up of lean body mass (LBM). However percentage body fat decreased in the GH-treated subjects. Bone mineral density SDS measured by DEXA increased significantly in the GH-treated group compared to the untreated subjects, though there is much debate over whether or not SGA (small for gestational age) is significantly adverse to children to warrant inducing catch-up.
Babies that have a low birth weight are thought to have an increased risk of developing type 2 diabetes in later life. Low birth weight is linked with increase rates of obesity, insulin resistance, and type 2 diabetes and it is shown that children with the low birth weights have increased leptin levels after they catch up growth during childhood. Adiponectin levels are positively related with birth weight and BMI in babies with an increase of risk of type 2 diabetes. The leptin and adiponection mechanisms are still being studied when involving low birth weight.
Around the world
There is much variation regarding birth weight within continents, countries, and cities. Even though over 20 million babies are born each year with low birth weight, it is hard to know the exact number as more than half of babies born in the world are not weighed at birth. The babys weight is an indicator of the mother and babys health. In 2013, 22 million newborns had low birth weight, around 16 percent of all babies globally. Data on low birth weight is adjusted to account for under reporting. South Asia has the highest rate of babies not weighed at birth with 66 percent, but also have the highest low birth weight at 28 percent worldwide. West and Central Africa and least developed countries are next with 14 percent low birth weight worldwide.More than 96.5% of low birth weight babies are born in developing countries around the world. Because low birth weight babies can require more extensive care, it places a financial burden on communities.
Prevention
The World Health Organization (WHO) recently announced an initiative to have a thirty percent reduction in low birth weight worldwide. This is public health priority, as birth weight can have short and long term effects. WHO estimates that worldwide, 15-20 % of all births each year are considered low birth weight, which is about 20 million births.The start of prenatal care is very important to help prevent low birth weight and early medical problems. Going to regular doctors visits is very important for the health of the mother and the baby. At the visits the OB/GYN will be checking maternal nutrition and weight gain because that is linked with the babys weight gain. The mother having a healthy diet is essential for the baby. Maintaining good nutrition by taking folic acid, which can be found in fruits and vegetables, is linked to the prevention of premature births and low birth weight. Alcohol, cigarettes, and drugs should also be avoided during pregnancy because they can also lead to poor growth and other complications. By seeing the doctor they are also able to monitor pre-existing medical illnesses to make sure they are under control during pregnancy. Mothers with high blood pressure and type 2 diabetes are more likely to have infants with low birth weights. One essential action to increase normal birth weights is to have affordable, accessible, and culturally sensitive prenatal care worldwide. This is essential not just for treating low birth weight, but also preventing it. Other prevention efforts include: smoking cessation programs, food-distribution systems, stress reduction and social service supports.
See also
Infant mortality
Low birth-weight paradox
MOMO syndrome
Prenatal nutrition
Thrifty phenotype
References
Further reading
External links
MedlinePlus Encyclopedia: Intrauterine growth restriction
Fetal Growth Restriction at eMedicine |
Subsets and Splits