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Affects of Pityriasis Rosea
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Some reports in the medical literature state that pityriasis rosea affects females more often than males; others state that the disorder affects males and females in equal numbers. The disorder most commonly affects individuals between the ages of 10 and 35, but has been reported in all age groups including infants and the elderly. Pityriasis rosea occurs with greater frequency in the spring and autumn months.
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Affects of Pityriasis Rosea. Some reports in the medical literature state that pityriasis rosea affects females more often than males; others state that the disorder affects males and females in equal numbers. The disorder most commonly affects individuals between the ages of 10 and 35, but has been reported in all age groups including infants and the elderly. Pityriasis rosea occurs with greater frequency in the spring and autumn months.
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Pityriasis Rosea
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Related disorders of Pityriasis Rosea
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Symptoms of the following disorders can be similar to those of pityriasis rosea. Comparisons may be useful for a differential diagnosis.Psoriasis is a chronic, inflammatory skin disease characterized by dry, reddish (erythematous), thickened patches of skin that are covered with silvery-gray scales. These patches may be referred to as papules or plaques and most often affect the scalp, elbows, knees, hands, feet and/or lower back. The plaques may be intensely itchy (pruritic) or sore. In some cases, individuals with psoriasis may experience abnormalities affecting the fingernails, toenails, and the soft tissues inside the mouth. The severity of psoriasis varies from case to case. Psoriasis may be classified as mild, moderate or severe depending upon the amount of skin involved and the effect on an individual’s quality of life. In approximately one-third of cases a family history of psoriasis is present. (For more information on this disorder, choose “psoriasis” as your search term in the Rare Disease Database.)Syphilis is a chronic infectious disease caused by the bacterium (microorganism) treponema pallidum. It is transmitted by direct contact with an infected lesion, usually through sexual intercourse. When untreated, syphilis progresses through primary, secondary and latent stages. The early stages of syphilis may not have any detectable symptoms. In some cases, symptoms can remain dormant for years. Eventually any tissue or vascular organ in the body may be affected. Secondary syphilis usually presents itself within two weeks to six months after the appearance of the primary lesions. This stage of the disorder is characterized by lesions of the skin and mucous membranes that may be pink or coppery in color, widespread, symmetrical, and follow the lines of skin cleavage. Often the palms and soles are affected. The skin lesions of secondary syphilis are infectious. Symptoms such as loss of appetite, sore throat, headache, low-grade fever, muscle aches, nasal discharge, and swollen lymph nodes may occur. There is a relapse in 25 percent of the untreated cases, occurring most often in the first year. Secondary syphilis usually lasts two to six weeks and some of the lesions may leave scarring. (For more information on this disorder, choose “syphilis” as your search term in the Rare Disease Database.)Certain drugs can potentially cause a rash extremely similar to pityriasis rosea as a side effect of their use. These drugs include barbiturates, bismuth, clonidine, captopril, gold, imatinib mesylate, interferon, arsenic compounds and gold.
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Related disorders of Pityriasis Rosea. Symptoms of the following disorders can be similar to those of pityriasis rosea. Comparisons may be useful for a differential diagnosis.Psoriasis is a chronic, inflammatory skin disease characterized by dry, reddish (erythematous), thickened patches of skin that are covered with silvery-gray scales. These patches may be referred to as papules or plaques and most often affect the scalp, elbows, knees, hands, feet and/or lower back. The plaques may be intensely itchy (pruritic) or sore. In some cases, individuals with psoriasis may experience abnormalities affecting the fingernails, toenails, and the soft tissues inside the mouth. The severity of psoriasis varies from case to case. Psoriasis may be classified as mild, moderate or severe depending upon the amount of skin involved and the effect on an individual’s quality of life. In approximately one-third of cases a family history of psoriasis is present. (For more information on this disorder, choose “psoriasis” as your search term in the Rare Disease Database.)Syphilis is a chronic infectious disease caused by the bacterium (microorganism) treponema pallidum. It is transmitted by direct contact with an infected lesion, usually through sexual intercourse. When untreated, syphilis progresses through primary, secondary and latent stages. The early stages of syphilis may not have any detectable symptoms. In some cases, symptoms can remain dormant for years. Eventually any tissue or vascular organ in the body may be affected. Secondary syphilis usually presents itself within two weeks to six months after the appearance of the primary lesions. This stage of the disorder is characterized by lesions of the skin and mucous membranes that may be pink or coppery in color, widespread, symmetrical, and follow the lines of skin cleavage. Often the palms and soles are affected. The skin lesions of secondary syphilis are infectious. Symptoms such as loss of appetite, sore throat, headache, low-grade fever, muscle aches, nasal discharge, and swollen lymph nodes may occur. There is a relapse in 25 percent of the untreated cases, occurring most often in the first year. Secondary syphilis usually lasts two to six weeks and some of the lesions may leave scarring. (For more information on this disorder, choose “syphilis” as your search term in the Rare Disease Database.)Certain drugs can potentially cause a rash extremely similar to pityriasis rosea as a side effect of their use. These drugs include barbiturates, bismuth, clonidine, captopril, gold, imatinib mesylate, interferon, arsenic compounds and gold.
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Pityriasis Rosea
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Diagnosis of Pityriasis Rosea
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A diagnosis of pityriasis rosea is made based upon identification of characteristic symptoms, a detailed patient history, and a thorough clinical evaluation. In the earlier stages of the disorder, additional tests such as blood tests or a biopsy may be necessary to distinguish pityriasis rosea from similar skin disorders.
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Diagnosis of Pityriasis Rosea. A diagnosis of pityriasis rosea is made based upon identification of characteristic symptoms, a detailed patient history, and a thorough clinical evaluation. In the earlier stages of the disorder, additional tests such as blood tests or a biopsy may be necessary to distinguish pityriasis rosea from similar skin disorders.
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Therapies of Pityriasis Rosea
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Treatment
The treatment is symptomatic and supportive. Many individuals may not require treatment and the rash usually clears up on its own within 1-3 months. Most treatment is geared to controlling or reducing itching. Such therapies include antihistamines, steroid creams or ointments.A variety of therapies have been used to try to shorten the duration of the rash associated with pityriasis rosea. Such therapies include systemic corticosteroids, certain antiviral drugs such as acyclovir and famciclovir, and the antibiotic erythromycin. There is limited evidence to support any of these treatments.Phototherapy is used for individuals with inflammatory skin disorders such as pityriasis rosea. Phototherapy may be administered by itself or in conjunction with topical treatments. Some affected individuals may be treated by greater exposure to sunlight.
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Therapies of Pityriasis Rosea. Treatment
The treatment is symptomatic and supportive. Many individuals may not require treatment and the rash usually clears up on its own within 1-3 months. Most treatment is geared to controlling or reducing itching. Such therapies include antihistamines, steroid creams or ointments.A variety of therapies have been used to try to shorten the duration of the rash associated with pityriasis rosea. Such therapies include systemic corticosteroids, certain antiviral drugs such as acyclovir and famciclovir, and the antibiotic erythromycin. There is limited evidence to support any of these treatments.Phototherapy is used for individuals with inflammatory skin disorders such as pityriasis rosea. Phototherapy may be administered by itself or in conjunction with topical treatments. Some affected individuals may be treated by greater exposure to sunlight.
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Overview of Pityriasis Rubra Pilaris
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SummaryPityriasis rubra pilaris (PRP) is a rare skin disorder that causes inflammation of the skin, thickening of the nails and at times shedding of the hair. The name means scaling (pityriasis), redness (rubra), and involvement of the hair follicles (pilaris).4Typically, PRP appears first as a small spot somewhere on the face and then spreads to the back and the rest of the body.5It may impact different parts of the body in different ways for unpredictable periods of time.5 The inflammation may cover the entire body or just parts of the body such as the elbows, knees, palms, and soles.6 The disease may progress and leave distinct areas of uninvolved skin, the so-called “islands of sparing” or “skip areas”.7The classic adult type, the most prevalent subcategory, had previously been reported to resolve within three years. The largest case series to date, however, demonstrated that courses are often much longer than this. The pediatric type tends to be a more protracted course.36The peak onset years of PRP are in the first, sixth and seventh decades of life. While it most commonly affects adults, there is a significant proportion of pediatric patients affected. The disorder favors no gender.8There are five types of PRP, which are classified based on age of onset and body areas affected. The sixth type of PRP, or HIV associated, has been more recently described but is still debated. PRP usually occurs at random, but some forms may be hereditary.9While the exact prevalence and incidence are unknown, there are an estimated 800+ “active” patients in the U.S. and less than 1900 patients in Europe. PRP is an ultra-rare skin disorder. In fact, it is considered an orphan disease. The rarity of PRP notwithstanding, the signs and symptoms of PRP often mimic those of eczema (31.6 million patients) and psoriasis (8 million patients).10-11PRP patients and their caregivers quickly learn that every case of PRP is unique.4 Unfortunately, there is no specific or consistently effective therapy for PRP. In fact, there are no treatments approved by the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA) for use in PRP.12 Nevertheless, experts tend to use a multimodal approach including topical and systemic therapies to control the symptoms of the disorder. Topical therapies can reduce skin (cutaneous) inflammation and aid with itch (pruritus) and dryness/flaking (xerosis). Systemic therapy can reduce inflammation and is generally required in the majority of patients with large body surface areas of involvement.12IntroductionWhen James Shooter was admitted to St. Bartholomew’s Hospital in London, England in 1828, he unwittingly became the world’s first recorded patient with what the medical community would eventually call pityriasis rubra pilaris. In 1828, however, Mr. Shooter’s skin disorder did not yet have a name. Seven years passed before Claudius Tarral, a French dermatologist, wrote about the case in Traite theorique et pratique des maladies de la peau (Treatise on Skin Diseases) in 1835. Tarral saw it as a variant of psoriasis.13-14It would take another 21 years for Marie Guillaume Alphonse Devergie, a dermatologist and forensic doctor at St. Louis Hospital in Paris, to publish the most complete description of PRP. In fact, it is considered to be the “original description” of PRP by the medical community. Devergie’s article was published in the Gazette Hebdomadaire de Medecine et de Chirurgie in 1856.14While Devergie saw the skin disorder as a combination of “follicular lesions and psoriasis palmaris, pityriasis capillitii and pityriasis rubra”, it would take yet another 21 years before another Frenchman and dermatologist by the name of Richaud to recognize PRP as a distinct entity. Richaud published his paper “Etude sur le pityriasis pilaris” in 1877.15When Ernest Besnier presented nine cases in a 120-page article published in 1889 — 12 years after Richaud, 43 years after Devergie, and 54 years after Tarral, he forever fixed the name of the disease as pityriasis rubra pilaris. Besnier too, was a Frenchman and dermatologist. He was also the medical director of the St. Louis Hospital in Paris — the same hospital as Devergie.16 The name comes from three Latin words: pityriasis (scale-like), rubra (red) and pilaris (hair follicles).2Like many rare disease, the PRP community laments the snail’s pace at which PRP research progresses. What should we expect — it took 61 years just to pick the name.Recently, the Research Group from Thomas Jefferson University’s PRP Center of Excellence has compiled the world’s largest cohort of PRP patients. With each day, new understanding of the diagnosis and management of PRP are gained; yet much work remains to be accomplished.
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Overview of Pityriasis Rubra Pilaris. SummaryPityriasis rubra pilaris (PRP) is a rare skin disorder that causes inflammation of the skin, thickening of the nails and at times shedding of the hair. The name means scaling (pityriasis), redness (rubra), and involvement of the hair follicles (pilaris).4Typically, PRP appears first as a small spot somewhere on the face and then spreads to the back and the rest of the body.5It may impact different parts of the body in different ways for unpredictable periods of time.5 The inflammation may cover the entire body or just parts of the body such as the elbows, knees, palms, and soles.6 The disease may progress and leave distinct areas of uninvolved skin, the so-called “islands of sparing” or “skip areas”.7The classic adult type, the most prevalent subcategory, had previously been reported to resolve within three years. The largest case series to date, however, demonstrated that courses are often much longer than this. The pediatric type tends to be a more protracted course.36The peak onset years of PRP are in the first, sixth and seventh decades of life. While it most commonly affects adults, there is a significant proportion of pediatric patients affected. The disorder favors no gender.8There are five types of PRP, which are classified based on age of onset and body areas affected. The sixth type of PRP, or HIV associated, has been more recently described but is still debated. PRP usually occurs at random, but some forms may be hereditary.9While the exact prevalence and incidence are unknown, there are an estimated 800+ “active” patients in the U.S. and less than 1900 patients in Europe. PRP is an ultra-rare skin disorder. In fact, it is considered an orphan disease. The rarity of PRP notwithstanding, the signs and symptoms of PRP often mimic those of eczema (31.6 million patients) and psoriasis (8 million patients).10-11PRP patients and their caregivers quickly learn that every case of PRP is unique.4 Unfortunately, there is no specific or consistently effective therapy for PRP. In fact, there are no treatments approved by the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA) for use in PRP.12 Nevertheless, experts tend to use a multimodal approach including topical and systemic therapies to control the symptoms of the disorder. Topical therapies can reduce skin (cutaneous) inflammation and aid with itch (pruritus) and dryness/flaking (xerosis). Systemic therapy can reduce inflammation and is generally required in the majority of patients with large body surface areas of involvement.12IntroductionWhen James Shooter was admitted to St. Bartholomew’s Hospital in London, England in 1828, he unwittingly became the world’s first recorded patient with what the medical community would eventually call pityriasis rubra pilaris. In 1828, however, Mr. Shooter’s skin disorder did not yet have a name. Seven years passed before Claudius Tarral, a French dermatologist, wrote about the case in Traite theorique et pratique des maladies de la peau (Treatise on Skin Diseases) in 1835. Tarral saw it as a variant of psoriasis.13-14It would take another 21 years for Marie Guillaume Alphonse Devergie, a dermatologist and forensic doctor at St. Louis Hospital in Paris, to publish the most complete description of PRP. In fact, it is considered to be the “original description” of PRP by the medical community. Devergie’s article was published in the Gazette Hebdomadaire de Medecine et de Chirurgie in 1856.14While Devergie saw the skin disorder as a combination of “follicular lesions and psoriasis palmaris, pityriasis capillitii and pityriasis rubra”, it would take yet another 21 years before another Frenchman and dermatologist by the name of Richaud to recognize PRP as a distinct entity. Richaud published his paper “Etude sur le pityriasis pilaris” in 1877.15When Ernest Besnier presented nine cases in a 120-page article published in 1889 — 12 years after Richaud, 43 years after Devergie, and 54 years after Tarral, he forever fixed the name of the disease as pityriasis rubra pilaris. Besnier too, was a Frenchman and dermatologist. He was also the medical director of the St. Louis Hospital in Paris — the same hospital as Devergie.16 The name comes from three Latin words: pityriasis (scale-like), rubra (red) and pilaris (hair follicles).2Like many rare disease, the PRP community laments the snail’s pace at which PRP research progresses. What should we expect — it took 61 years just to pick the name.Recently, the Research Group from Thomas Jefferson University’s PRP Center of Excellence has compiled the world’s largest cohort of PRP patients. With each day, new understanding of the diagnosis and management of PRP are gained; yet much work remains to be accomplished.
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Symptoms of Pityriasis Rubra Pilaris
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The terms “sign” and “symptom” are not redundant. SIGN is an indication of a medical condition that can be objectively observed by others, including healthcare professionals. In contrast, a SYMPTOM is subjective, information that is shared by the PRP patient with the healthcare provider such as pain, itching, fatigue. The following is a list of signs and symptoms that define PRP.Pre-onset Signs
Mild signs include dandruff and crusty scalp, as well as limited red patches or scaling of the skin, (e.g., a “dime-sized red spot” on the forehead). The duration varies from patient to patient. At some point the patient determines that intervention of a healthcare professional is warranted, (eg, a red spot has doubled in size in less than two weeks).Progression of Signs
Depending on the advancement of inflammation, a general practitioner or dermatologist will see signs including pink, red, or orange-red scaly patches on the skin. These patches are usually itchy. Initially, PRP patients may have the scaly patches only on some parts of the body. Patches most often occur on the elbows, knees, hands, feet, and ankles. Skin on the palms and soles may also become red or waxy and thickened with a classic orange hue (palmoplantar keratoderma). The scaly patches may eventually spread over the entire body.17 Islands of sparing can occur within the salmon-colored patches of inflammation.Cracks (fissures) may develop within thickened skin which can be painful and make walking and using one’s hands difficult. Nails may become thickened, discolored, ridged, cluttered with debris under the free-edge and may even shed. Hair may shed considerably due to the disorder itself or some treatments used. Heat intolerance, protein loss and fluid imbalance can occur when the rash becomes widespread (erythroderma).4Diagnosis is often delayed by the prolonged course of evolution of the disease and its ability to masquerade as other disorders, particularly eczema and psoriasis. Fortunately, many of the treatments for eczema, psoriasis and PRP are shared.5Acute Stage Signs and Symptoms
A dermatologist will be able to see the signs of a body engulfed by dry, red, and flaking skin, swollen feet and legs, and cracked and bleeding hands and feet. There may be serious issues related to impaired mobility, eyes and vision (caused by tightness and pulling of the eyelids), and dexterity. The PRP patient will see symptoms of PRP from a different perspective, e.g., pain of motion, unrelenting itch (pruritus), and heat intolerance. Pruritus, pain, and sleep disturbance are common with this disorder. The acute stage poses the greatest challenge to body, mind, and spirit and can last anywhere from less than a month or many months longer. This is the time in the PRP journey that PRP patients and caregivers should seek support from patient support groups. It is also a time to address issues of depression.5Management Stage
After the acute stage, the journey of a PRP patient takes on a new focus — mitigating and managing symptoms. Potential irritants are waiting on the roadside, such as joint pain, clogged ears, and disability claims, to name a few. While 90% of the PRP patient population can look forward to full remission within one to five years, the timetable is not certain. Those diagnosed with atypical adult onset and atypical juvenile onset, the chronic versions of PRP, must develop long-term coping skills. For everyone, the daily routine associated with medications, moisturizing, and dealing with the challenges of body, mind and spirit of this skin disorder cannot be ignored.Remission & Healing Milestones
The medical community defines remission as the disappearance of signs and symptoms of disease, whether through the use of medication or naturally with time. Recovery is considered the restoration of health or function. The PRP community has adopted a more celebratory approach to disease recovery with recognition of healing milestones. The return of sweat, the first trip out of the house for groceries, and dark hardwood floors that don’t need hourly vacuuming are all cause to celebrate. These milestones are symptoms of healing that PRP patients and caregivers feel and signs that everyone else observes.
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Symptoms of Pityriasis Rubra Pilaris. The terms “sign” and “symptom” are not redundant. SIGN is an indication of a medical condition that can be objectively observed by others, including healthcare professionals. In contrast, a SYMPTOM is subjective, information that is shared by the PRP patient with the healthcare provider such as pain, itching, fatigue. The following is a list of signs and symptoms that define PRP.Pre-onset Signs
Mild signs include dandruff and crusty scalp, as well as limited red patches or scaling of the skin, (e.g., a “dime-sized red spot” on the forehead). The duration varies from patient to patient. At some point the patient determines that intervention of a healthcare professional is warranted, (eg, a red spot has doubled in size in less than two weeks).Progression of Signs
Depending on the advancement of inflammation, a general practitioner or dermatologist will see signs including pink, red, or orange-red scaly patches on the skin. These patches are usually itchy. Initially, PRP patients may have the scaly patches only on some parts of the body. Patches most often occur on the elbows, knees, hands, feet, and ankles. Skin on the palms and soles may also become red or waxy and thickened with a classic orange hue (palmoplantar keratoderma). The scaly patches may eventually spread over the entire body.17 Islands of sparing can occur within the salmon-colored patches of inflammation.Cracks (fissures) may develop within thickened skin which can be painful and make walking and using one’s hands difficult. Nails may become thickened, discolored, ridged, cluttered with debris under the free-edge and may even shed. Hair may shed considerably due to the disorder itself or some treatments used. Heat intolerance, protein loss and fluid imbalance can occur when the rash becomes widespread (erythroderma).4Diagnosis is often delayed by the prolonged course of evolution of the disease and its ability to masquerade as other disorders, particularly eczema and psoriasis. Fortunately, many of the treatments for eczema, psoriasis and PRP are shared.5Acute Stage Signs and Symptoms
A dermatologist will be able to see the signs of a body engulfed by dry, red, and flaking skin, swollen feet and legs, and cracked and bleeding hands and feet. There may be serious issues related to impaired mobility, eyes and vision (caused by tightness and pulling of the eyelids), and dexterity. The PRP patient will see symptoms of PRP from a different perspective, e.g., pain of motion, unrelenting itch (pruritus), and heat intolerance. Pruritus, pain, and sleep disturbance are common with this disorder. The acute stage poses the greatest challenge to body, mind, and spirit and can last anywhere from less than a month or many months longer. This is the time in the PRP journey that PRP patients and caregivers should seek support from patient support groups. It is also a time to address issues of depression.5Management Stage
After the acute stage, the journey of a PRP patient takes on a new focus — mitigating and managing symptoms. Potential irritants are waiting on the roadside, such as joint pain, clogged ears, and disability claims, to name a few. While 90% of the PRP patient population can look forward to full remission within one to five years, the timetable is not certain. Those diagnosed with atypical adult onset and atypical juvenile onset, the chronic versions of PRP, must develop long-term coping skills. For everyone, the daily routine associated with medications, moisturizing, and dealing with the challenges of body, mind and spirit of this skin disorder cannot be ignored.Remission & Healing Milestones
The medical community defines remission as the disappearance of signs and symptoms of disease, whether through the use of medication or naturally with time. Recovery is considered the restoration of health or function. The PRP community has adopted a more celebratory approach to disease recovery with recognition of healing milestones. The return of sweat, the first trip out of the house for groceries, and dark hardwood floors that don’t need hourly vacuuming are all cause to celebrate. These milestones are symptoms of healing that PRP patients and caregivers feel and signs that everyone else observes.
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Causes of Pityriasis Rubra Pilaris
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The specific underlying cause of PRP is unknown, although a combination of a genetic predisposition, environmental trigger, and other unknown causes is believed to play key roles. Vitamin A deficiency was once believed to be related to the disorder, however, this theory lacks sufficient evidence and treatment with Vitamin A has been less than effective.36, 38
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Causes of Pityriasis Rubra Pilaris. The specific underlying cause of PRP is unknown, although a combination of a genetic predisposition, environmental trigger, and other unknown causes is believed to play key roles. Vitamin A deficiency was once believed to be related to the disorder, however, this theory lacks sufficient evidence and treatment with Vitamin A has been less than effective.36, 38
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Affects of Pityriasis Rubra Pilaris
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Based on conversations within the PRP community, we can say with metaphysical certitude that PRP isn’t a punishment for misbehavior or forgetting to put the toilet seat down. There are thousands of perfectly wonderful people who have — or had — PRP. Moreover, there are many very bad people who don’t have it. Who then gets the short end of this rare disease stick?Prevalence: In March 2003, Dr. Andrew Griffiths delivered a “Dowling Oration” to members of the British Association of Dermatology assembled in Liverpool, England. Dr. Griffiths reflected on 35 years of diagnosing, treating and researching pityriasis rubra pilaris. He unilaterally guessed the PRP prevalence rate at one in 400,000 persons. While the methodology used by Dr Griffiths is subject to debate, dermatologists worldwide have used his estimate due to a lack of evidence-based studies of how often diseases occur in different groups of people and why (epidemiology).1Age: Pityriasis rubra pilaris is a rare disorder that may develop during childhood or adulthood. Juvenile onset accounts for 45% of the “active” patient population while adult onset accounts for 55%.6 Although PRP may occur at any age10, it most commonly affects those in their first, second, fifth, and sixth decades of life.24, 2Gender: PRP appears to occur in males and females in relatively equal numbers. However, in childhood, the male to female ratio is 3:2.25Race: Persons of any race may be affected.2, 7
Acquired or Inherited: PRP is usually sporadic (occurring randomly) but some forms may be herediatry.6, 2
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Affects of Pityriasis Rubra Pilaris. Based on conversations within the PRP community, we can say with metaphysical certitude that PRP isn’t a punishment for misbehavior or forgetting to put the toilet seat down. There are thousands of perfectly wonderful people who have — or had — PRP. Moreover, there are many very bad people who don’t have it. Who then gets the short end of this rare disease stick?Prevalence: In March 2003, Dr. Andrew Griffiths delivered a “Dowling Oration” to members of the British Association of Dermatology assembled in Liverpool, England. Dr. Griffiths reflected on 35 years of diagnosing, treating and researching pityriasis rubra pilaris. He unilaterally guessed the PRP prevalence rate at one in 400,000 persons. While the methodology used by Dr Griffiths is subject to debate, dermatologists worldwide have used his estimate due to a lack of evidence-based studies of how often diseases occur in different groups of people and why (epidemiology).1Age: Pityriasis rubra pilaris is a rare disorder that may develop during childhood or adulthood. Juvenile onset accounts for 45% of the “active” patient population while adult onset accounts for 55%.6 Although PRP may occur at any age10, it most commonly affects those in their first, second, fifth, and sixth decades of life.24, 2Gender: PRP appears to occur in males and females in relatively equal numbers. However, in childhood, the male to female ratio is 3:2.25Race: Persons of any race may be affected.2, 7
Acquired or Inherited: PRP is usually sporadic (occurring randomly) but some forms may be herediatry.6, 2
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Related disorders of Pityriasis Rubra Pilaris
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Symptoms of the following disorders can be similar to those of pityriasis rubra pilaris. Comparisons may be useful for a differential diagnosis:Psoriasis: According to the National Psoriasis Foundation (NPF), “Psoriasis is an immune-mediated disease that causes raised, red, scaly patches to appear on the skin. It typically affects the outside of the elbows, knees or scalp, though it can appear on any location. Some people report that psoriasis is itchy, burns and stings. Psoriasis is associated with other serious health conditions, such as diabetes, heart disease and depression.” More information is available at the NPF website.26Atopic dermatitis (eczema & dermatitis): There are different types of eczema that collectively affect more than 30 million Americans: atopic dermatitis, contact dermatitis, dyshidrotic eczema, hand eczema, neurodermatitis, nummular eczema and stasis dermatitis. For more information, contact the National Eczema Foundation.27Allergic reaction: Most skin allergic reactions are minor, such as an eczema-like rash from poison ivy, or mosquito or other bug bites, or sneezing from hay fever. The type of reaction depends on the person’s immune system response, which is sometimes unpredictable. For more information about allergic reactions, go to eMedicineHealth.28Pityriasis rosea: Pityriasis rosea (PR) is a benign rash, a common skin disorder observed in otherwise healthy people, most frequently found in children and young adults, that is thought to be caused by a mild viral infection. It usually goes away without treatment after a few months. It can easily mimic types of similar skin eruptions including lichen planus, psoriasis, and pityriasis rubra pilaris. Pityriasis rosea has a very specific and recognizable rash. It does, however, begin with a “herald mark”. Follow the link listed in the reference section for additional information at Medscape.29Fungal infection: Mycoses are fungal infections of the skin. They are common and generally mild. However, in very sick or otherwise immunosuppressed people, fungi can sometimes cause serious disease.30Lupus: Lupus is a chronic autoimmune disease that can damage any part of the body including skin, joints and organs. “Chronic” means that the signs and symptoms tend to last longer than six weeks and often for a lifetime. In lupus, something goes wrong with the immune system. Normally our immune systems produce proteins called “antibodies” which protect the body from invaders. “Autoimmunity” means your immune system cannot tell the difference between these foreign invaders and your body’s healthy tissues. As a result, it creates autoantibodies that attack and destroy healthy tissue. When someone has lupus, these autoantibodies cause inflammation, pain, and damage in various parts of the body.31Cutaneous T-cell lymphoma: On occasion, the diagnosis of a PRP patient has been changed to cutaneous T-cell lymphoma (CTCL). Chronic inflammation in the skin occurs in PRP and other inflammatory skin diseases like psoriasis and eczema and can even trigger CTCL after many years. The PRP community recommends that appropriate tests which may include skin biopsy and blood work be performed to rule out CTCL. 32
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Related disorders of Pityriasis Rubra Pilaris. Symptoms of the following disorders can be similar to those of pityriasis rubra pilaris. Comparisons may be useful for a differential diagnosis:Psoriasis: According to the National Psoriasis Foundation (NPF), “Psoriasis is an immune-mediated disease that causes raised, red, scaly patches to appear on the skin. It typically affects the outside of the elbows, knees or scalp, though it can appear on any location. Some people report that psoriasis is itchy, burns and stings. Psoriasis is associated with other serious health conditions, such as diabetes, heart disease and depression.” More information is available at the NPF website.26Atopic dermatitis (eczema & dermatitis): There are different types of eczema that collectively affect more than 30 million Americans: atopic dermatitis, contact dermatitis, dyshidrotic eczema, hand eczema, neurodermatitis, nummular eczema and stasis dermatitis. For more information, contact the National Eczema Foundation.27Allergic reaction: Most skin allergic reactions are minor, such as an eczema-like rash from poison ivy, or mosquito or other bug bites, or sneezing from hay fever. The type of reaction depends on the person’s immune system response, which is sometimes unpredictable. For more information about allergic reactions, go to eMedicineHealth.28Pityriasis rosea: Pityriasis rosea (PR) is a benign rash, a common skin disorder observed in otherwise healthy people, most frequently found in children and young adults, that is thought to be caused by a mild viral infection. It usually goes away without treatment after a few months. It can easily mimic types of similar skin eruptions including lichen planus, psoriasis, and pityriasis rubra pilaris. Pityriasis rosea has a very specific and recognizable rash. It does, however, begin with a “herald mark”. Follow the link listed in the reference section for additional information at Medscape.29Fungal infection: Mycoses are fungal infections of the skin. They are common and generally mild. However, in very sick or otherwise immunosuppressed people, fungi can sometimes cause serious disease.30Lupus: Lupus is a chronic autoimmune disease that can damage any part of the body including skin, joints and organs. “Chronic” means that the signs and symptoms tend to last longer than six weeks and often for a lifetime. In lupus, something goes wrong with the immune system. Normally our immune systems produce proteins called “antibodies” which protect the body from invaders. “Autoimmunity” means your immune system cannot tell the difference between these foreign invaders and your body’s healthy tissues. As a result, it creates autoantibodies that attack and destroy healthy tissue. When someone has lupus, these autoantibodies cause inflammation, pain, and damage in various parts of the body.31Cutaneous T-cell lymphoma: On occasion, the diagnosis of a PRP patient has been changed to cutaneous T-cell lymphoma (CTCL). Chronic inflammation in the skin occurs in PRP and other inflammatory skin diseases like psoriasis and eczema and can even trigger CTCL after many years. The PRP community recommends that appropriate tests which may include skin biopsy and blood work be performed to rule out CTCL. 32
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Diagnosis of Pityriasis Rubra Pilaris
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A medical diagnosis is based on information from sources such as findings from a physical examination, an interview with the patient, family or both, a medical history of the patient and family, and clinical findings as reported by laboratory tests and radiologic studies.A differential diagnosis is a process of weighing the probability of one disease versus that of other diseases. It represents an alternative diagnosis based on the clinical and pathologic features of the patient.Pityriasis rubra pilaris is not easy to diagnose. In March 2003, English dermatologist Dr. Andrew Griffiths reinforced that fact when he titled his Dowling Oration to the British Association of Dermatologists “Pityriasis Rubra Pilaris — The Scarlet Pimpernel”. Griffiths quoted author Baroness Orczy’s character who says: “They seek him here, they seek him there, that damned elusive Pimpernel.” We agree with Griffiths, “This disease remains an enigma.”1The Diagnostic Role of the Dermatologist
Clinical observation is where it all begins. What symptoms are visible to the dermatologist during the examination? A dime-sized red spot on a forehead can reasonably be diagnosed as seborrheic dermatitis. Similarly, a patient “in full bloom” presenting with 90% of the skin covered with redness and scale, islands of sparing, and other key indicators might be more than enough to awaken a memory of a grand rounds experience years earlier in medical school.The Diagnostic Role of the Dermatopathologist
The microscope is where the clinical observations are either supported or not. Biopsies sent to a dermatopathologist are often used to “rule out” specific skin maladies or causes. The PRP community has learned from shared experiences — albeit anecdotal — that when the dermatologist suspects PRP and instructs the dermatopathologist to “consider PRP,” that the findings support the clinical observations. Special tests can be performed on the skin biopsy to rule out the possibility of cutaneous lymphoma which can mimic PRP at the microscopic level (histology).Nevertheless, the signs of PRP under the microscope are neither sensitive (the ability to pick up a diagnosis when using a test) nor specific (not shared by many other disorders as well) to PRP. As such, the diagnosis of PRP remains largely a clinicopathologic correlation, that is to say piecing together the clinical and pathologic features to make the “best fit” of a diagnosis based on the patient’s presentation.Differential Diagnosis
A differential diagnosis is the method by which a physician determines what disease process has caused a patient’s symptoms. The physician considers all relevant potential causes of the symptoms and then eliminates alternative causes based on a physical examination, clinical tests and a thorough case history.33The International Center for Toxicology and Medicine states, “A differential diagnosis is a quest for a diagnosis. What is wrong with the patient internally? It is not, inherently, a search for the ultimate cause (critical to liability) of that disease process or disorder.”34 It is “the process of weighing the probability of one disease versus that of other diseases possibly accounting for a patient’s illness.”35
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Diagnosis of Pityriasis Rubra Pilaris. A medical diagnosis is based on information from sources such as findings from a physical examination, an interview with the patient, family or both, a medical history of the patient and family, and clinical findings as reported by laboratory tests and radiologic studies.A differential diagnosis is a process of weighing the probability of one disease versus that of other diseases. It represents an alternative diagnosis based on the clinical and pathologic features of the patient.Pityriasis rubra pilaris is not easy to diagnose. In March 2003, English dermatologist Dr. Andrew Griffiths reinforced that fact when he titled his Dowling Oration to the British Association of Dermatologists “Pityriasis Rubra Pilaris — The Scarlet Pimpernel”. Griffiths quoted author Baroness Orczy’s character who says: “They seek him here, they seek him there, that damned elusive Pimpernel.” We agree with Griffiths, “This disease remains an enigma.”1The Diagnostic Role of the Dermatologist
Clinical observation is where it all begins. What symptoms are visible to the dermatologist during the examination? A dime-sized red spot on a forehead can reasonably be diagnosed as seborrheic dermatitis. Similarly, a patient “in full bloom” presenting with 90% of the skin covered with redness and scale, islands of sparing, and other key indicators might be more than enough to awaken a memory of a grand rounds experience years earlier in medical school.The Diagnostic Role of the Dermatopathologist
The microscope is where the clinical observations are either supported or not. Biopsies sent to a dermatopathologist are often used to “rule out” specific skin maladies or causes. The PRP community has learned from shared experiences — albeit anecdotal — that when the dermatologist suspects PRP and instructs the dermatopathologist to “consider PRP,” that the findings support the clinical observations. Special tests can be performed on the skin biopsy to rule out the possibility of cutaneous lymphoma which can mimic PRP at the microscopic level (histology).Nevertheless, the signs of PRP under the microscope are neither sensitive (the ability to pick up a diagnosis when using a test) nor specific (not shared by many other disorders as well) to PRP. As such, the diagnosis of PRP remains largely a clinicopathologic correlation, that is to say piecing together the clinical and pathologic features to make the “best fit” of a diagnosis based on the patient’s presentation.Differential Diagnosis
A differential diagnosis is the method by which a physician determines what disease process has caused a patient’s symptoms. The physician considers all relevant potential causes of the symptoms and then eliminates alternative causes based on a physical examination, clinical tests and a thorough case history.33The International Center for Toxicology and Medicine states, “A differential diagnosis is a quest for a diagnosis. What is wrong with the patient internally? It is not, inherently, a search for the ultimate cause (critical to liability) of that disease process or disorder.”34 It is “the process of weighing the probability of one disease versus that of other diseases possibly accounting for a patient’s illness.”35
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Therapies of Pityriasis Rubra Pilaris
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Treatment
Treatment of pityriasis rubra pilaris is mainly anecdotal, based on case reports and case series, a feature shared by many disorders in dermatology due to their rarity. The fleeting nature of the large proportion of PRP symptoms also makes it difficult to study in standardized, long-term therapeutic studies. As controlled trials are lacking, the effectiveness and safety of treatments is unclear. Thus, there is low quality evidence supporting treatment strategies of PRP. Currently there are no treatments approved by the US Food and Drug Administration or the European Medicines Agency for use in PRP.9PRP tends to follow a natural waxing and waning course, with episodes in which there is periodic worsening (exacerbation) or cessation (remission) of symptoms. Thus, according to many researchers, it may be difficult to evaluate the effectiveness of particular therapies.9The value of treatment is difficult to assess, as the clinical course is so variable for each of the different types of PRP. Patients with classical adult onset PRP, for example, may present with intense and widespread reddening of the entire skin surface (erythroderma). Hospital admission for skin care, fluid replacement and other supportive care may be warranted.6From the patient perspective, there are two major objectives in the treatment of pityriasis rubra pilaris:• relieving symptoms as they present
• achieving long-term remission, if possible. The mantra heard within the PRP community is simple but deafening: What works for one doesn’t work for all.Treatment Options
Management of PRP often involves systemic and topical therapies combined. Topical therapies can help with the symptoms and may be enough for people with mild PRP. Topical treatments are usually combined with systemic therapy for PRP that affects a large part of the body. Most PRP patients need systemic therapy to control the condition.9Treatment options will vary based on age, geography, and cost to the patient. Moreover, laboratory tests are important to monitor the effects of medications on the body — especially the liver — and to manage and monitor the side effects of drugs.Some of the medications used to treat PRP can harm a developing fetus and are not recommended for use right before or during pregnancy.9
People seeking information about specific treatment options for themselves or family members should speak with their health care provider.9RETINOIDS
Oral retinoids are derivatives of vitamin A that slow the growth and shedding of skin cells. Treatment options include acitretin / Soriatane® and isotretinoin / Accutane®, though researchers at the PRP Center of Excellence prefer acitretin over isotretinoin and etretinate. Oral retinoids (synthetic vitamin A derivatives) are the first line systemic treatment for PRP.9 A scientific survey of patients with PRP performed by researchers at Thomas Jefferson University published that oral retinoids were helpful in approximately 60% of patients with PRP.36IMMUNOSUPPRESSANTS
Immunosuppressants slow down the body’s immune system. These can be used in combination when oral retinoids are ineffective. Treatment options (oral and injection) include methotrexate, cyclosporine, TNF-alpha inhibitors, IL-12/23 inhibitors, among others. Methotrexate was reported to be helpful in approximately 50% of patients with PRP.36BIOLOGICALS
Biologicals are also immunosuppressants. Biologicals are injectable or intravenous (IV) medications that target various pathways of inflammation in the body. With generally fewer side effects, biologicals are targeted to reduce inflammation. Treatment options include adalimumab / Humira®, etanercept / Enbrel®, infliximab / Remicade®, ustekinumab / Stelara®, secukinumab / Cosentyx®, ixekizumab / Taltz®, brodalumab / Siliq®, guselkumab / Tremfya®, and apremilast / Otezla®. These biologic medications are FDA-approved for psoriasis but improvement or remission for some patients with PRP have been published in the medical literature.OTHER THERAPIES
• Topical creams that contain urea or ammonium lactate decrease scaling and flaking of the skin. Topical corticosteroid creams decrease skin inflammation. These are applied directly to the skin.8
• Oral vitamin A. This may be helpful in some people, but only in very high doses that may cause toxicity. Retinoids (synthetic derivatives of vitamin A) are safer and more effective and more commonly used than high-dose vitamin A.8
• Traditional Chinese Medicine and other Alternative Medicines with varying degrees of success.REFERRALS
Depending on the severity, duration and array of signs and symptoms, PRP patients seek the expertise of specialized healthcare professionals:
• Opthamologist: ectropion (eyelids are turned outward) and impaired vision
• Podiatrist: impaired mobility
• Otorhinolaryngologist (ENT specialist): impaired hearing, removal of ear wax (cerumen) from ear canal.
• Hepatologist: monitor impact of PRP treatment on the liver.
• Psychiatrists/Clinical Psychologist: depression and mental wellness
PRP patient support resources: (see Resources) further information on patient care and tools see http://prpalliance.com/survival-guide/.
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Therapies of Pityriasis Rubra Pilaris. Treatment
Treatment of pityriasis rubra pilaris is mainly anecdotal, based on case reports and case series, a feature shared by many disorders in dermatology due to their rarity. The fleeting nature of the large proportion of PRP symptoms also makes it difficult to study in standardized, long-term therapeutic studies. As controlled trials are lacking, the effectiveness and safety of treatments is unclear. Thus, there is low quality evidence supporting treatment strategies of PRP. Currently there are no treatments approved by the US Food and Drug Administration or the European Medicines Agency for use in PRP.9PRP tends to follow a natural waxing and waning course, with episodes in which there is periodic worsening (exacerbation) or cessation (remission) of symptoms. Thus, according to many researchers, it may be difficult to evaluate the effectiveness of particular therapies.9The value of treatment is difficult to assess, as the clinical course is so variable for each of the different types of PRP. Patients with classical adult onset PRP, for example, may present with intense and widespread reddening of the entire skin surface (erythroderma). Hospital admission for skin care, fluid replacement and other supportive care may be warranted.6From the patient perspective, there are two major objectives in the treatment of pityriasis rubra pilaris:• relieving symptoms as they present
• achieving long-term remission, if possible. The mantra heard within the PRP community is simple but deafening: What works for one doesn’t work for all.Treatment Options
Management of PRP often involves systemic and topical therapies combined. Topical therapies can help with the symptoms and may be enough for people with mild PRP. Topical treatments are usually combined with systemic therapy for PRP that affects a large part of the body. Most PRP patients need systemic therapy to control the condition.9Treatment options will vary based on age, geography, and cost to the patient. Moreover, laboratory tests are important to monitor the effects of medications on the body — especially the liver — and to manage and monitor the side effects of drugs.Some of the medications used to treat PRP can harm a developing fetus and are not recommended for use right before or during pregnancy.9
People seeking information about specific treatment options for themselves or family members should speak with their health care provider.9RETINOIDS
Oral retinoids are derivatives of vitamin A that slow the growth and shedding of skin cells. Treatment options include acitretin / Soriatane® and isotretinoin / Accutane®, though researchers at the PRP Center of Excellence prefer acitretin over isotretinoin and etretinate. Oral retinoids (synthetic vitamin A derivatives) are the first line systemic treatment for PRP.9 A scientific survey of patients with PRP performed by researchers at Thomas Jefferson University published that oral retinoids were helpful in approximately 60% of patients with PRP.36IMMUNOSUPPRESSANTS
Immunosuppressants slow down the body’s immune system. These can be used in combination when oral retinoids are ineffective. Treatment options (oral and injection) include methotrexate, cyclosporine, TNF-alpha inhibitors, IL-12/23 inhibitors, among others. Methotrexate was reported to be helpful in approximately 50% of patients with PRP.36BIOLOGICALS
Biologicals are also immunosuppressants. Biologicals are injectable or intravenous (IV) medications that target various pathways of inflammation in the body. With generally fewer side effects, biologicals are targeted to reduce inflammation. Treatment options include adalimumab / Humira®, etanercept / Enbrel®, infliximab / Remicade®, ustekinumab / Stelara®, secukinumab / Cosentyx®, ixekizumab / Taltz®, brodalumab / Siliq®, guselkumab / Tremfya®, and apremilast / Otezla®. These biologic medications are FDA-approved for psoriasis but improvement or remission for some patients with PRP have been published in the medical literature.OTHER THERAPIES
• Topical creams that contain urea or ammonium lactate decrease scaling and flaking of the skin. Topical corticosteroid creams decrease skin inflammation. These are applied directly to the skin.8
• Oral vitamin A. This may be helpful in some people, but only in very high doses that may cause toxicity. Retinoids (synthetic derivatives of vitamin A) are safer and more effective and more commonly used than high-dose vitamin A.8
• Traditional Chinese Medicine and other Alternative Medicines with varying degrees of success.REFERRALS
Depending on the severity, duration and array of signs and symptoms, PRP patients seek the expertise of specialized healthcare professionals:
• Opthamologist: ectropion (eyelids are turned outward) and impaired vision
• Podiatrist: impaired mobility
• Otorhinolaryngologist (ENT specialist): impaired hearing, removal of ear wax (cerumen) from ear canal.
• Hepatologist: monitor impact of PRP treatment on the liver.
• Psychiatrists/Clinical Psychologist: depression and mental wellness
PRP patient support resources: (see Resources) further information on patient care and tools see http://prpalliance.com/survival-guide/.
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Overview of PLA2G6-Associated Neurodegeneration
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SummaryPLA2G6-associated neurodegeneration (PLAN) is an extremely rare, inherited degenerative disorder of the nervous system characterized by abnormalities of nerve endings within the brain, spinal cord and peripheral nerves. PLAN is inherited as an autosomal recessive genetic condition caused by changes (variants) in the PLA2G6 gene. PLA2G6 tells the body’s cells how to make the enzyme A2 phospholipase, an enzyme that breaks down certain fats known as lipids. Symptoms of PLAN may start as early as 3 months through 3 years. Based on an individual’s age of onset and symptoms, their disease may be classified as one of three types of PLAN: infantile neuroaxonal dystrophy (INAD), a juvenile onset form called atypical neuroaxonal dystrophy (aNAD) or an adult-onset type called PLA2G6-related dystonia-parkinsonism. However, there is a broad spectrum of symptoms with people falling between these three categories.IntroductionPLAN is classified as a form of neurodegeneration with brain iron accumulation (NBIA), a group of disorders marked by progressive abnormal involuntary movements, alterations in muscle tone, and eye disease. These disorders usually show evidence of iron accumulation on brain MRI.
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Overview of PLA2G6-Associated Neurodegeneration. SummaryPLA2G6-associated neurodegeneration (PLAN) is an extremely rare, inherited degenerative disorder of the nervous system characterized by abnormalities of nerve endings within the brain, spinal cord and peripheral nerves. PLAN is inherited as an autosomal recessive genetic condition caused by changes (variants) in the PLA2G6 gene. PLA2G6 tells the body’s cells how to make the enzyme A2 phospholipase, an enzyme that breaks down certain fats known as lipids. Symptoms of PLAN may start as early as 3 months through 3 years. Based on an individual’s age of onset and symptoms, their disease may be classified as one of three types of PLAN: infantile neuroaxonal dystrophy (INAD), a juvenile onset form called atypical neuroaxonal dystrophy (aNAD) or an adult-onset type called PLA2G6-related dystonia-parkinsonism. However, there is a broad spectrum of symptoms with people falling between these three categories.IntroductionPLAN is classified as a form of neurodegeneration with brain iron accumulation (NBIA), a group of disorders marked by progressive abnormal involuntary movements, alterations in muscle tone, and eye disease. These disorders usually show evidence of iron accumulation on brain MRI.
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Symptoms of PLA2G6-Associated Neurodegeneration
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INAD
INAD is characterized by abnormalities of nerve endings (axons) within the brain and spinal cord (central nervous system) and outside the central nervous system (peripheral nerves), resulting in loss of proper nerve function.The symptoms of INAD usually start to appear between the ages of 3 months and 3 years of age. The common pattern in young children with INAD is slowing of their development, followed by loss of skills and progression of the disorder over time. Common symptoms include regression or delay:
-Loss of previously acquired milestones, such as the ability to sit, stand, or vocalize sounds and words
-Delayed walking or gait disturbance
-Loss of muscle control (ataxia)
-Low muscle tone in the trunk more than the limbs (truncal hypotonia)
-Later development of muscle tightness and weakness in both arms and legs (spastic tetraparesis)
-Abnormal reflexesCommon eye features include:
-Crossed eyes (strabismus) and rapid uncontrolled eye movements (nystagmus) seen early in disease
-Deterioration of the nerve that connects the eye to the brain (optic atrophy) seen later in diseaseCommon symptoms of cranial nerve dysfunction:
-Speech problems including poor articulation (dysarthria), poor use of voice (dysphonia) and poor understanding of words (dysphasia)
-Difficulty swallowing and chewing (dysphagia) causing nutritional problems
-Choking and nasal regurgitationLater in the disease, seizures may develop and cognitive decline occurs with progression. Progression of INAD is usually rapid and many affected children never learn to walk or lose this ability shortly after learning it. During the last stages of disease, severe stiff muscles, progressive cognitive decline and vision loss have a large impact on daily life. Many children with INAD do not live beyond age 10, but some do survive into their teens and early twenties. Death usually occurs due to secondary problems, such as aspiration pneumonia or other infections. aNAD
The symptoms of aNAD are more variable than those of INAD with symptoms developing usually by 4 years of age. Delayed speech and autistic features may be the first evidence of disease with regression or slowed development of milestones.Common muscle symptoms:
-Involuntary muscle contractions (dystonia)
-Poor articulation and speech (dysarthria)
-Muscle tightness and weakness in both arms and legs
-Reduced joint mobility due to muscle tightness
-Overactive reflexes developing early disease
-Absent reflexes developing late in diseaseCommon neuropsychiatric symptoms:
-Poor attention span
-Impulsivity
-Hyperactivity
-Emotional labilityaNAD shares common eye symptoms with INAD. Seizures are rare but may occur later in the disease. Individuals with aNAD are fairly stable during their early childhood but start declining between the ages of 7 and 12. aNAD patients are very rare so the average life span is not known. However, the life span is expected to be longer than that of classic INAD since initial symptoms develop at a later age.PLA2G6-related dystonia-parkinsonism
There have been only a small number of PLA2G6-related dystonia-parkinsonism cases reported. The age of onset of symptoms varies from 4 to 37 years.Common symptoms include:
-Tremors
-Decreased muscle movement (hypokinesia)
-Stiffness
-Loss of balance
-Walking difficulties: shuffling, freezing or getting stuck while walking
-Involuntary muscles contractions and spasms (dystonia)
– Poor articulation and speech (dysarthria)
-Cold/blue hands and feet, difficulty regulating core body temperature
-ConstipationCommon neuropsychiatric changes (often the first symptoms seen in young adults)
-Depression
-Personality changes
-Aggression
-Delusions
-ParanoiaAs PLA2G6-related dystonia-parkinsonism is very rare, the long-term progression and average life span are difficult to predict. Once symptoms begin, the progression typically moves rapidly.
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Symptoms of PLA2G6-Associated Neurodegeneration. INAD
INAD is characterized by abnormalities of nerve endings (axons) within the brain and spinal cord (central nervous system) and outside the central nervous system (peripheral nerves), resulting in loss of proper nerve function.The symptoms of INAD usually start to appear between the ages of 3 months and 3 years of age. The common pattern in young children with INAD is slowing of their development, followed by loss of skills and progression of the disorder over time. Common symptoms include regression or delay:
-Loss of previously acquired milestones, such as the ability to sit, stand, or vocalize sounds and words
-Delayed walking or gait disturbance
-Loss of muscle control (ataxia)
-Low muscle tone in the trunk more than the limbs (truncal hypotonia)
-Later development of muscle tightness and weakness in both arms and legs (spastic tetraparesis)
-Abnormal reflexesCommon eye features include:
-Crossed eyes (strabismus) and rapid uncontrolled eye movements (nystagmus) seen early in disease
-Deterioration of the nerve that connects the eye to the brain (optic atrophy) seen later in diseaseCommon symptoms of cranial nerve dysfunction:
-Speech problems including poor articulation (dysarthria), poor use of voice (dysphonia) and poor understanding of words (dysphasia)
-Difficulty swallowing and chewing (dysphagia) causing nutritional problems
-Choking and nasal regurgitationLater in the disease, seizures may develop and cognitive decline occurs with progression. Progression of INAD is usually rapid and many affected children never learn to walk or lose this ability shortly after learning it. During the last stages of disease, severe stiff muscles, progressive cognitive decline and vision loss have a large impact on daily life. Many children with INAD do not live beyond age 10, but some do survive into their teens and early twenties. Death usually occurs due to secondary problems, such as aspiration pneumonia or other infections. aNAD
The symptoms of aNAD are more variable than those of INAD with symptoms developing usually by 4 years of age. Delayed speech and autistic features may be the first evidence of disease with regression or slowed development of milestones.Common muscle symptoms:
-Involuntary muscle contractions (dystonia)
-Poor articulation and speech (dysarthria)
-Muscle tightness and weakness in both arms and legs
-Reduced joint mobility due to muscle tightness
-Overactive reflexes developing early disease
-Absent reflexes developing late in diseaseCommon neuropsychiatric symptoms:
-Poor attention span
-Impulsivity
-Hyperactivity
-Emotional labilityaNAD shares common eye symptoms with INAD. Seizures are rare but may occur later in the disease. Individuals with aNAD are fairly stable during their early childhood but start declining between the ages of 7 and 12. aNAD patients are very rare so the average life span is not known. However, the life span is expected to be longer than that of classic INAD since initial symptoms develop at a later age.PLA2G6-related dystonia-parkinsonism
There have been only a small number of PLA2G6-related dystonia-parkinsonism cases reported. The age of onset of symptoms varies from 4 to 37 years.Common symptoms include:
-Tremors
-Decreased muscle movement (hypokinesia)
-Stiffness
-Loss of balance
-Walking difficulties: shuffling, freezing or getting stuck while walking
-Involuntary muscles contractions and spasms (dystonia)
– Poor articulation and speech (dysarthria)
-Cold/blue hands and feet, difficulty regulating core body temperature
-ConstipationCommon neuropsychiatric changes (often the first symptoms seen in young adults)
-Depression
-Personality changes
-Aggression
-Delusions
-ParanoiaAs PLA2G6-related dystonia-parkinsonism is very rare, the long-term progression and average life span are difficult to predict. Once symptoms begin, the progression typically moves rapidly.
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Causes of PLA2G6-Associated Neurodegeneration
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INAD and other forms of PLAN are inherited in an autosomal recessive pattern. Variants of the PLA2G6 gene cause PLAN.Researchers believe that the PLA2G6 gene carries instructions to create (encode) an enzyme that breaks down certain fats known as lipids. When the PLA2G6 gene is changed, the breakdown of lipids is affected, which may result in the excess accumulation of membranes in the nerve axons.Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one working gene and one non-working gene, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive working genes from both parents is 25 percent. The risk is the same for males and females.All individuals carry a few recessive genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
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Causes of PLA2G6-Associated Neurodegeneration. INAD and other forms of PLAN are inherited in an autosomal recessive pattern. Variants of the PLA2G6 gene cause PLAN.Researchers believe that the PLA2G6 gene carries instructions to create (encode) an enzyme that breaks down certain fats known as lipids. When the PLA2G6 gene is changed, the breakdown of lipids is affected, which may result in the excess accumulation of membranes in the nerve axons.Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one working gene and one non-working gene, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive working genes from both parents is 25 percent. The risk is the same for males and females.All individuals carry a few recessive genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
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Affects of PLA2G6-Associated Neurodegeneration
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PLAN is an extremely rare genetic disorder, and the incidence and prevalence are not known with any certainty. It is estimated to occur in about 1-2/million children.
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Affects of PLA2G6-Associated Neurodegeneration. PLAN is an extremely rare genetic disorder, and the incidence and prevalence are not known with any certainty. It is estimated to occur in about 1-2/million children.
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Related disorders of PLA2G6-Associated Neurodegeneration
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Symptoms of the following disorders may be similar to those of PLAN. Comparisons may be useful while investigating diagnoses. Pantothenate kinase associated neurodegeneration (PKAN) is a rare, inherited neurological movement disorder characterized by the progressive degeneration of specific regions in the central nervous system and the most common type of NBIA. PKAN is inherited as an autosomal recessive genetic condition and is described as being classical or atypical. Classic PKAN typically appears in early childhood with symptoms that worsen rapidly. Atypical PKAN, which progresses more slowly, appears later in childhood or early adolescence. Some people have been diagnosed in infancy or adulthood, and some of those affected have characteristics that are between the two categories. (For more information about this condition, search for “PKAN” in the Rare Disease Database.)Late infantile metachromatic leukodystrophy is usually diagnosed in the second year of life, most commonly before the age of 30 months. The initial signs of the late infantile form include irritability, diminished muscle tone, and gait disturbance. (For more information about this condition, search for “metachromatic leukodystrophy ” in the Rare Disease Database.)
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Related disorders of PLA2G6-Associated Neurodegeneration. Symptoms of the following disorders may be similar to those of PLAN. Comparisons may be useful while investigating diagnoses. Pantothenate kinase associated neurodegeneration (PKAN) is a rare, inherited neurological movement disorder characterized by the progressive degeneration of specific regions in the central nervous system and the most common type of NBIA. PKAN is inherited as an autosomal recessive genetic condition and is described as being classical or atypical. Classic PKAN typically appears in early childhood with symptoms that worsen rapidly. Atypical PKAN, which progresses more slowly, appears later in childhood or early adolescence. Some people have been diagnosed in infancy or adulthood, and some of those affected have characteristics that are between the two categories. (For more information about this condition, search for “PKAN” in the Rare Disease Database.)Late infantile metachromatic leukodystrophy is usually diagnosed in the second year of life, most commonly before the age of 30 months. The initial signs of the late infantile form include irritability, diminished muscle tone, and gait disturbance. (For more information about this condition, search for “metachromatic leukodystrophy ” in the Rare Disease Database.)
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Diagnosis of PLA2G6-Associated Neurodegeneration
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PLAN is diagnosed by means of a thorough clinical evaluation, brain MRI, a detailed history, and a variety of specialized tests including molecular genetic testing to sequence the PLA2G6 gene. A diagnosis of PLAN is confirmed by finding two changes in the PLA2G6 gene that are predicted to affect how it works or have been documented in other patients with PLAN. If no gene variant or only one gene variant is found through sequencing analysis of the PLA2G6 gene, then genetic testing may proceed to deletion/duplication analysis. This looks for large pieces of the gene that may be extra or missing, which sequencing can miss. Among individuals who go forward with deletion/duplication analysis, a gene change may be found in ~ 12.5 % of patients. Brain imaging techniques may also be used to detect, confirm, and/or characterize specific abnormalities of the central nervous system that may be associated with PLAN. Magnetic resonance imaging (MRI), which uses a magnetic field and radio waves to create cross-sectional images of the brain, often reveals progressive, generalized degeneration (diffuse atrophy) of tissue of the outer portion of the cerebellum (cerebellar cortex). Images may reveal areas of iron accumulation, although this is only observed about half the time and usually occurs later in disease. In addition, microscopic examination (i.e., light and electron microscopy) of samples (biopsies) of peripheral nerve tissue from the skin or the transparent membrane covering the whites of the eyes (conjunctivae) may reveal swelling and degeneration of nerve endings (dystrophic axonal swellings or “spheroids”).In infants and children with INAD, specialized testing may also be conducted to evaluate electrical activity (electrophysiological studies) of certain areas of the body. For example, electromyograms (EMG), tests that record electrical activity in skeletal muscles at rest and during muscle contraction, may indicate that, although nerve signals may be transmitted at normal speed to muscles (normal nerve conduction velocities [NCV]), there is failed communication of such signals to the muscles (denervation). Electroencephalography (EEG), which records the brain's electrical impulses, may reveal abnormally high amplitude and fast activity within brain wave patterns. INAD may result in a decreased or absent response when the eye is stimulated by light (visually evoked potential [VEP]), confirming degeneration in optic pathways in the brain.
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Diagnosis of PLA2G6-Associated Neurodegeneration. PLAN is diagnosed by means of a thorough clinical evaluation, brain MRI, a detailed history, and a variety of specialized tests including molecular genetic testing to sequence the PLA2G6 gene. A diagnosis of PLAN is confirmed by finding two changes in the PLA2G6 gene that are predicted to affect how it works or have been documented in other patients with PLAN. If no gene variant or only one gene variant is found through sequencing analysis of the PLA2G6 gene, then genetic testing may proceed to deletion/duplication analysis. This looks for large pieces of the gene that may be extra or missing, which sequencing can miss. Among individuals who go forward with deletion/duplication analysis, a gene change may be found in ~ 12.5 % of patients. Brain imaging techniques may also be used to detect, confirm, and/or characterize specific abnormalities of the central nervous system that may be associated with PLAN. Magnetic resonance imaging (MRI), which uses a magnetic field and radio waves to create cross-sectional images of the brain, often reveals progressive, generalized degeneration (diffuse atrophy) of tissue of the outer portion of the cerebellum (cerebellar cortex). Images may reveal areas of iron accumulation, although this is only observed about half the time and usually occurs later in disease. In addition, microscopic examination (i.e., light and electron microscopy) of samples (biopsies) of peripheral nerve tissue from the skin or the transparent membrane covering the whites of the eyes (conjunctivae) may reveal swelling and degeneration of nerve endings (dystrophic axonal swellings or “spheroids”).In infants and children with INAD, specialized testing may also be conducted to evaluate electrical activity (electrophysiological studies) of certain areas of the body. For example, electromyograms (EMG), tests that record electrical activity in skeletal muscles at rest and during muscle contraction, may indicate that, although nerve signals may be transmitted at normal speed to muscles (normal nerve conduction velocities [NCV]), there is failed communication of such signals to the muscles (denervation). Electroencephalography (EEG), which records the brain's electrical impulses, may reveal abnormally high amplitude and fast activity within brain wave patterns. INAD may result in a decreased or absent response when the eye is stimulated by light (visually evoked potential [VEP]), confirming degeneration in optic pathways in the brain.
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Therapies of PLA2G6-Associated Neurodegeneration
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TreatmentThe treatment of PLAN is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who diagnose and treat neurological disorders (neurologists), eye specialists (ophthalmologists), and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment. Treatment will likely eventually include a combination of medications and other therapies, like physical or occupational therapy. With progression, treatments like a feeding tube or pulmonary hygiene to help prevent infections may be added.
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Therapies of PLA2G6-Associated Neurodegeneration. TreatmentThe treatment of PLAN is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who diagnose and treat neurological disorders (neurologists), eye specialists (ophthalmologists), and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment. Treatment will likely eventually include a combination of medications and other therapies, like physical or occupational therapy. With progression, treatments like a feeding tube or pulmonary hygiene to help prevent infections may be added.
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Overview of Plague
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Plague is an acute, severe infectious disease caused by the bacterium Yersinia pestis. The bacterium is found in fleas and wild rodents such as rats, squirrels, chipmunks or prairie dogs. Plague is a zoonotic disease, which means it can be transmitted to humans through animals, most often through the bites of fleas or through direct contact with infected animal tissue. The disease is most common in parts of Africa, Asia and South America, but it also occurs in some areas of the western United States. Symptoms can include an abrupt onset of chills, fever, and enlarged, painful lymph nodes (buboes). Most cases of plague resolve with effective treatment, though treatment must be started immediately to avoid life-threatening complications. Although plague is extremely rare in the United States, interest in the infection has heightened in recent years because of its potential use as an agent of biological warfare.
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Overview of Plague. Plague is an acute, severe infectious disease caused by the bacterium Yersinia pestis. The bacterium is found in fleas and wild rodents such as rats, squirrels, chipmunks or prairie dogs. Plague is a zoonotic disease, which means it can be transmitted to humans through animals, most often through the bites of fleas or through direct contact with infected animal tissue. The disease is most common in parts of Africa, Asia and South America, but it also occurs in some areas of the western United States. Symptoms can include an abrupt onset of chills, fever, and enlarged, painful lymph nodes (buboes). Most cases of plague resolve with effective treatment, though treatment must be started immediately to avoid life-threatening complications. Although plague is extremely rare in the United States, interest in the infection has heightened in recent years because of its potential use as an agent of biological warfare.
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Symptoms of Plague
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The symptoms of plague vary greatly depending upon the specific form that develops. The main clinical forms of plague are bubonic, septicemic, and pneumonic.Bubonic Plague
Bubonic plague is the most common form of the disease. Symptoms usually develop 2-6 days after exposure to the bacterium and include the sudden onset of fever, chills, weakness, headaches, muscle pain and a general feeling of discomfort or ill health (malaise). An infected individual develops a bubo – a tender, inflamed swelling of a lymph node. Buboes are firm and often very painful. The lymph nodes of the groin, armpit (axilla) or neck are most often involved. If untreated, the bacteria can spread from the affected lymph node to the bloodstream (septicemia) and the lungs (pneumonia) and cause toxicity, shock, and other life-threatening complications.Septicemic Plague
This form of plague is characterized by massive growth of bacteria in the blood. It can occur as bacteria in the lymph nodes (bubonic plague) spread to the bloodstream, or as a primary infection (no swollen lymph nodes). Affected individuals may develop prominent gastrointestinal symptoms such as diarrhea, nausea, vomiting and abdominal pain. Other general symptoms may include high fever, chills, exhaustion, headache and muscle pain (myalgia). Septicemic plague progresses rapidly and can quickly cause life-threatening complications if not diagnosed and treated promptly.Pneumonic Plague
Pneumonic plague is infection of the lungs by the Yersinia pestis bacterium. It can occur as a complication of bubonic or septicemic plague in which the bacteria spread to the lungs through the bloodstream, or as a primary infection in which the bacterium is inhaled directly into the lungs. If inhaled, disease develops rapidly, usually within 1-3 days Affected individuals can develop a wide variety of symptoms including fever, chills, a rapid heartbeat, difficulty breathing, cough, chest pain, severe headaches and the coughing up of bloody sputum (hemoptysis). If untreated within the first 24-36 hours, this form of plague can rapidly progress to multiple organ failure, adult respiratory distress syndrome and ultimately death.
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Symptoms of Plague. The symptoms of plague vary greatly depending upon the specific form that develops. The main clinical forms of plague are bubonic, septicemic, and pneumonic.Bubonic Plague
Bubonic plague is the most common form of the disease. Symptoms usually develop 2-6 days after exposure to the bacterium and include the sudden onset of fever, chills, weakness, headaches, muscle pain and a general feeling of discomfort or ill health (malaise). An infected individual develops a bubo – a tender, inflamed swelling of a lymph node. Buboes are firm and often very painful. The lymph nodes of the groin, armpit (axilla) or neck are most often involved. If untreated, the bacteria can spread from the affected lymph node to the bloodstream (septicemia) and the lungs (pneumonia) and cause toxicity, shock, and other life-threatening complications.Septicemic Plague
This form of plague is characterized by massive growth of bacteria in the blood. It can occur as bacteria in the lymph nodes (bubonic plague) spread to the bloodstream, or as a primary infection (no swollen lymph nodes). Affected individuals may develop prominent gastrointestinal symptoms such as diarrhea, nausea, vomiting and abdominal pain. Other general symptoms may include high fever, chills, exhaustion, headache and muscle pain (myalgia). Septicemic plague progresses rapidly and can quickly cause life-threatening complications if not diagnosed and treated promptly.Pneumonic Plague
Pneumonic plague is infection of the lungs by the Yersinia pestis bacterium. It can occur as a complication of bubonic or septicemic plague in which the bacteria spread to the lungs through the bloodstream, or as a primary infection in which the bacterium is inhaled directly into the lungs. If inhaled, disease develops rapidly, usually within 1-3 days Affected individuals can develop a wide variety of symptoms including fever, chills, a rapid heartbeat, difficulty breathing, cough, chest pain, severe headaches and the coughing up of bloody sputum (hemoptysis). If untreated within the first 24-36 hours, this form of plague can rapidly progress to multiple organ failure, adult respiratory distress syndrome and ultimately death.
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Causes of Plague
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Plague is caused by infection with the bacterium Yersinia pestis. This bacterium is found in wild rodents and their fleas. Some of the most commonly infected rodents are rats, squirrels, chipmunks or prairie dogs. Rabbits and hares (lagomorphs) may also carry the bacteria. The disease is most often transmitted to humans by the bite of infected fleas. Less frequently, direct contact with infectious animal tissue can also result in infection.Pneumonic plague is the only manifestation of plague that can be transmitted from one person to another. This transmission occurs when a person breathes in (inhales) droplets from a coughing pneumonic plague patient. However, human-to-human transmission is extremely rare and has not been demonstrated in the United States since 1924. Domestic cats and dogs can become ill with pneumonic plague and transmit the infection to their owners or attending veterinarians in the same manner. The source of a recent human plague outbreak in Colorado was a dog with pneumonic plague.In recent years, plague has regained notoriety as a potential agent of bioterrorism. Most researchers believe that if used in such a manner, the bacteria would most likely be released as an aerosol with the intent of causing an outbreak of pneumonic plague.
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Causes of Plague. Plague is caused by infection with the bacterium Yersinia pestis. This bacterium is found in wild rodents and their fleas. Some of the most commonly infected rodents are rats, squirrels, chipmunks or prairie dogs. Rabbits and hares (lagomorphs) may also carry the bacteria. The disease is most often transmitted to humans by the bite of infected fleas. Less frequently, direct contact with infectious animal tissue can also result in infection.Pneumonic plague is the only manifestation of plague that can be transmitted from one person to another. This transmission occurs when a person breathes in (inhales) droplets from a coughing pneumonic plague patient. However, human-to-human transmission is extremely rare and has not been demonstrated in the United States since 1924. Domestic cats and dogs can become ill with pneumonic plague and transmit the infection to their owners or attending veterinarians in the same manner. The source of a recent human plague outbreak in Colorado was a dog with pneumonic plague.In recent years, plague has regained notoriety as a potential agent of bioterrorism. Most researchers believe that if used in such a manner, the bacteria would most likely be released as an aerosol with the intent of causing an outbreak of pneumonic plague.
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Affects of Plague
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Plague affects both males and females of all ages; however, historically it is slightly more common among men. Men may be more likely to become infected with plague because they are more likely to engage in outdoor activities that put them at risk (http://www.cdc.gov/plague/maps/index.html). Seven human plague cases are reported on average in the United States each year. Most cases in the United States occur in the Western and Southwestern part of the country, especially in New Mexico, Colorado, Arizona and California (http://www.cdc.gov/plague/maps/index.html). Plague has a scattered worldwide distribution. Most cases occur in sub-Saharan Africa, but plague still occurs on most continents. Historically, plague has caused massive pandemics most notably the Black Death of the Middle Ages.
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Affects of Plague. Plague affects both males and females of all ages; however, historically it is slightly more common among men. Men may be more likely to become infected with plague because they are more likely to engage in outdoor activities that put them at risk (http://www.cdc.gov/plague/maps/index.html). Seven human plague cases are reported on average in the United States each year. Most cases in the United States occur in the Western and Southwestern part of the country, especially in New Mexico, Colorado, Arizona and California (http://www.cdc.gov/plague/maps/index.html). Plague has a scattered worldwide distribution. Most cases occur in sub-Saharan Africa, but plague still occurs on most continents. Historically, plague has caused massive pandemics most notably the Black Death of the Middle Ages.
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Related disorders of Plague
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Symptoms of the following disorders can be similar to those of the plague. Comparisons may be useful for a differential diagnosis.Tularemia is a rare infectious disease, caused by the bacterium Francisella tularensis, which most often affects small mammals such as rabbits, rodents and hares. It is highly infectious and is most often transmitted to humans by handling infected animal tissues or through the bite of an infected tick or deer fly. Direct human-to-human transmission has not been documented. The severity of tularemia varies greatly. Some cases are mild and self-limiting; others may have serious complications, and a small percentage (about 2 percent) may become life-threatening. (For more information on this disorder, choose “tularemia” as your search term in the Rare Disease Database.)Cat-scratch disease (also commonly known as cat-scratch fever) is a self-limiting infectious disease characterized by swelling and pain in the lymph nodes (regional lymphadenitis). Symptoms can vary from mild to severe, and may include achiness and discomfort (malaise), and/or loss of appetite (anorexia). The disease is caused by the bacterium Bartonella henselae and, in most cases, occurs as a result of a scratch, bite, or lick from a cat or kitten. Symptoms may not appear for several days after exposure and may last for several weeks. Although cat-scratch disease usually subsides without treatment, antibiotics and/or antimicrobial therapy may speed recovery. (For more information on this disorder, choose “bartonellosis” as your search term in the Rare Disease Database.)There are numerous other infections that cause similar symptoms to plague including Rocky Mountain spotted fever, lymphatic filariasis, brucellosis, dengue virus disease, and streptococcal lymphadenitis. (For more information on this disorder, choose the specific disorder name as your search term in the Rare Disease Database.)
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Related disorders of Plague. Symptoms of the following disorders can be similar to those of the plague. Comparisons may be useful for a differential diagnosis.Tularemia is a rare infectious disease, caused by the bacterium Francisella tularensis, which most often affects small mammals such as rabbits, rodents and hares. It is highly infectious and is most often transmitted to humans by handling infected animal tissues or through the bite of an infected tick or deer fly. Direct human-to-human transmission has not been documented. The severity of tularemia varies greatly. Some cases are mild and self-limiting; others may have serious complications, and a small percentage (about 2 percent) may become life-threatening. (For more information on this disorder, choose “tularemia” as your search term in the Rare Disease Database.)Cat-scratch disease (also commonly known as cat-scratch fever) is a self-limiting infectious disease characterized by swelling and pain in the lymph nodes (regional lymphadenitis). Symptoms can vary from mild to severe, and may include achiness and discomfort (malaise), and/or loss of appetite (anorexia). The disease is caused by the bacterium Bartonella henselae and, in most cases, occurs as a result of a scratch, bite, or lick from a cat or kitten. Symptoms may not appear for several days after exposure and may last for several weeks. Although cat-scratch disease usually subsides without treatment, antibiotics and/or antimicrobial therapy may speed recovery. (For more information on this disorder, choose “bartonellosis” as your search term in the Rare Disease Database.)There are numerous other infections that cause similar symptoms to plague including Rocky Mountain spotted fever, lymphatic filariasis, brucellosis, dengue virus disease, and streptococcal lymphadenitis. (For more information on this disorder, choose the specific disorder name as your search term in the Rare Disease Database.)
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Diagnosis of Plague
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The diagnosis of plague may be confirmed by specialized laboratory tests in addition to characteristic clinical findings. Yersinia pestis can be identified in blood samples, tissue taken from enlarged lymph nodes (buboes) and sputum. All suspected cases of plague in the United States must be reported to the appropriate local and/or state health department, which in turn notifies the Centers for Disease Control and Prevention (CDC).
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Diagnosis of Plague. The diagnosis of plague may be confirmed by specialized laboratory tests in addition to characteristic clinical findings. Yersinia pestis can be identified in blood samples, tissue taken from enlarged lymph nodes (buboes) and sputum. All suspected cases of plague in the United States must be reported to the appropriate local and/or state health department, which in turn notifies the Centers for Disease Control and Prevention (CDC).
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Therapies of Plague
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TreatmentThe treatment of plague must begin as soon as possible to avoid serious life-threatening complications.
Doxycycline (and other tetracyclines) and fluoroquinolones levofloxacin, ciprofloxacin, and moxifloxacin are approved by the U.S. Food and Drug Administration (FDA) to treat plague. Gentamicin is not FDA approved for this purpose, but has been used successfully to treat plague, and is recommended therapy. Streptomycin is FDA approved and highly effective, but rarely available in many countries. In addition, doxycycline, ciprofloxacin, levofloxacin and moxifloxacin are approved by the FDA to prevent plague in exposed individuals (http://www.cdc.gov/plague/healthcare/clinicians.html).When pneumonia has developed, droplet precautions should be taken by health care providers to prevent transmission. There is no commercially available vaccine against plague in the United States.Individuals living in plague endemic areas should take preventive measures such as avoiding contact with rodents and fleas.
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Therapies of Plague. TreatmentThe treatment of plague must begin as soon as possible to avoid serious life-threatening complications.
Doxycycline (and other tetracyclines) and fluoroquinolones levofloxacin, ciprofloxacin, and moxifloxacin are approved by the U.S. Food and Drug Administration (FDA) to treat plague. Gentamicin is not FDA approved for this purpose, but has been used successfully to treat plague, and is recommended therapy. Streptomycin is FDA approved and highly effective, but rarely available in many countries. In addition, doxycycline, ciprofloxacin, levofloxacin and moxifloxacin are approved by the FDA to prevent plague in exposed individuals (http://www.cdc.gov/plague/healthcare/clinicians.html).When pneumonia has developed, droplet precautions should be taken by health care providers to prevent transmission. There is no commercially available vaccine against plague in the United States.Individuals living in plague endemic areas should take preventive measures such as avoiding contact with rodents and fleas.
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Overview of Pleuropulmonary Blastoma
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Summary Pleuropulmonary blastoma (PPB) is a rare childhood cancer occurring in the chest, specifically in the lungs or in the coverings of the lungs called “pleura”. Four subtypes of PPB exist: type Ir, type I, type II, and type III PPB. Type I, II, and III PPB are usually found in children under the age of approximately 7-8 years; PPB occurs rarely in older children or teenagers, and even more rarely in adults, but type Ir PPB may be found at any age.Type I PPB takes the form of one or more cysts in the lungs (air-filled pockets) and may be found in very young children (from birth to about 3 years of age). Type III PPB is an entirely solid tumor. Type II PPB includes both cystic and solid parts. Types II and III PPB tend to be found more often after 2 years of age. Type Ir (the “r” stands for regressed/regressing) is a type of PPB that is similar to type I PPB in terms of how the cells appear under the microscope, but cancerous cells are not present.Children with type I PPB have a better outlook (“prognosis”) than children with types II and III PPB. Most children with type I PPB are cured (89%) but type I PPB can sometimes recur (“come back”) as type II or III PPB. Treatment for type I consists of surgery and sometimes chemotherapy. Treatment for types II and III PPB consists of surgery and chemotherapy and possibly radiation therapy. At present, about 50-70% of children with types II and III PPB are cured. Introduction PPB is a childhood cancer in the family of cancers called soft tissue cancers, which are scientifically called sarcomas. PPB is, therefore, a soft tissue sarcoma. Physicians classify diseases this way in order to compare features and to compare treatments. PPB occurs in the lungs and is the most common lung cancer of childhood but PPB has no connection to lung cancers in adults that are often related to tobacco use or asbestos exposure. Like many cancers, PPB can spread through the blood to other areas of the body. When a cancer spreads to another part of the body it is called a “metastasis” of the cancer. Types II and III PPB can metastasize. The most common location for a PPB metastasis is the brain. PPB may also spread to remaining part of the lung, bones, liver and rarely to other organs. PPB can also spread by growing directly into tissues next to the lung like the diaphragm.
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Overview of Pleuropulmonary Blastoma. Summary Pleuropulmonary blastoma (PPB) is a rare childhood cancer occurring in the chest, specifically in the lungs or in the coverings of the lungs called “pleura”. Four subtypes of PPB exist: type Ir, type I, type II, and type III PPB. Type I, II, and III PPB are usually found in children under the age of approximately 7-8 years; PPB occurs rarely in older children or teenagers, and even more rarely in adults, but type Ir PPB may be found at any age.Type I PPB takes the form of one or more cysts in the lungs (air-filled pockets) and may be found in very young children (from birth to about 3 years of age). Type III PPB is an entirely solid tumor. Type II PPB includes both cystic and solid parts. Types II and III PPB tend to be found more often after 2 years of age. Type Ir (the “r” stands for regressed/regressing) is a type of PPB that is similar to type I PPB in terms of how the cells appear under the microscope, but cancerous cells are not present.Children with type I PPB have a better outlook (“prognosis”) than children with types II and III PPB. Most children with type I PPB are cured (89%) but type I PPB can sometimes recur (“come back”) as type II or III PPB. Treatment for type I consists of surgery and sometimes chemotherapy. Treatment for types II and III PPB consists of surgery and chemotherapy and possibly radiation therapy. At present, about 50-70% of children with types II and III PPB are cured. Introduction PPB is a childhood cancer in the family of cancers called soft tissue cancers, which are scientifically called sarcomas. PPB is, therefore, a soft tissue sarcoma. Physicians classify diseases this way in order to compare features and to compare treatments. PPB occurs in the lungs and is the most common lung cancer of childhood but PPB has no connection to lung cancers in adults that are often related to tobacco use or asbestos exposure. Like many cancers, PPB can spread through the blood to other areas of the body. When a cancer spreads to another part of the body it is called a “metastasis” of the cancer. Types II and III PPB can metastasize. The most common location for a PPB metastasis is the brain. PPB may also spread to remaining part of the lung, bones, liver and rarely to other organs. PPB can also spread by growing directly into tissues next to the lung like the diaphragm.
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Symptoms of Pleuropulmonary Blastoma
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Two different sets of symptoms are found in children with PPB, based generally on the child’s age and the type of PPB:Respiratory Distress Respiratory distress or breathing difficulty (dyspnea) may be mild to severe. Large pockets of air in the chest may prevent normal breathing. The air may be in large pockets in the lung (cysts) that compress the normal lung. Air also sometimes escapes from cysts into the chest cavity (pneumothorax). A chest x-ray or computed tomography (CT) scan will discover these air pockets and further investigations will lead to surgery to remove them.Pneumonia/General Illness These symptoms tend to be found in children with types II and III PPB. These children PPB may present with signs of pneumonia or another general illness including cough, fever, difficulty breathing, fatigue, loss of energy and decreased appetite. Chest or abdominal pain may also occur. Occasionally there is weight loss. A chest x-ray will show a problem that may look like pneumonia (lung infection). Because PPB is rare and other conditions of the lung are more common, PPB may not be initially suspected when a child has these symptoms. Children are often treated with antibiotics for 2-3 weeks, but when these symptoms are caused by PPB, they generally do not improve with antibiotics. Further investigations are done, such as a chest CT scan; these tests raise the possibility of a tumor in the chest/lung.
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Symptoms of Pleuropulmonary Blastoma. Two different sets of symptoms are found in children with PPB, based generally on the child’s age and the type of PPB:Respiratory Distress Respiratory distress or breathing difficulty (dyspnea) may be mild to severe. Large pockets of air in the chest may prevent normal breathing. The air may be in large pockets in the lung (cysts) that compress the normal lung. Air also sometimes escapes from cysts into the chest cavity (pneumothorax). A chest x-ray or computed tomography (CT) scan will discover these air pockets and further investigations will lead to surgery to remove them.Pneumonia/General Illness These symptoms tend to be found in children with types II and III PPB. These children PPB may present with signs of pneumonia or another general illness including cough, fever, difficulty breathing, fatigue, loss of energy and decreased appetite. Chest or abdominal pain may also occur. Occasionally there is weight loss. A chest x-ray will show a problem that may look like pneumonia (lung infection). Because PPB is rare and other conditions of the lung are more common, PPB may not be initially suspected when a child has these symptoms. Children are often treated with antibiotics for 2-3 weeks, but when these symptoms are caused by PPB, they generally do not improve with antibiotics. Further investigations are done, such as a chest CT scan; these tests raise the possibility of a tumor in the chest/lung.
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Causes of Pleuropulmonary Blastoma
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Sometimes PPB occurs without any other conditions in the individual or family but PPB may also be an indication of an underlying variation in a gene called DICER1 (see Related Disorders).
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Causes of Pleuropulmonary Blastoma. Sometimes PPB occurs without any other conditions in the individual or family but PPB may also be an indication of an underlying variation in a gene called DICER1 (see Related Disorders).
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Affects of Pleuropulmonary Blastoma
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PPB occurs in boys and girls approximately equally. Children under the age of 7-8 years are most often affected, but rarely teenagers or young adults may be diagnosed with PPB. Other conditions sometimes associated with PPB may be seen in individuals throughout the life span (see Related Disorders).
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Affects of Pleuropulmonary Blastoma. PPB occurs in boys and girls approximately equally. Children under the age of 7-8 years are most often affected, but rarely teenagers or young adults may be diagnosed with PPB. Other conditions sometimes associated with PPB may be seen in individuals throughout the life span (see Related Disorders).
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Related disorders of Pleuropulmonary Blastoma
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In about 40% of children with PPB, there are other childhood cancers or abnormalities in the PPB patient or in their immediate or extended family. Individuals with PPB may have variation in the DICER1 gene. When this variation alters the function of the gene, there is an increased risk for PPB and a variety of other conditions including lung cysts, kidney cysts or tumors, ovarian tumors in children or adults, thyroid nodules or cancers, certain childhood brains and rarely, tumors in the eye or nose/sinuses. All of these are in the DICER1– related spectrum of diseases and conditions. It should be emphasized that many children and adults in these families have no medical problems. When a DICER gene mutation is found, specific screening studies may be recommended to look for PPB and other conditions known to be related to DICER1. Chest screening (by chest x-ray or chest CT) for young children known to have the DICER1 gene mutation but no symptoms have in some cases lead to a PPB diagnosis at the earliest and most curable stage. Likewise, when found early, the ovarian tumors associated with DICER1 may be removed with surgery alone and are associated with a favorable prognosis.
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Related disorders of Pleuropulmonary Blastoma. In about 40% of children with PPB, there are other childhood cancers or abnormalities in the PPB patient or in their immediate or extended family. Individuals with PPB may have variation in the DICER1 gene. When this variation alters the function of the gene, there is an increased risk for PPB and a variety of other conditions including lung cysts, kidney cysts or tumors, ovarian tumors in children or adults, thyroid nodules or cancers, certain childhood brains and rarely, tumors in the eye or nose/sinuses. All of these are in the DICER1– related spectrum of diseases and conditions. It should be emphasized that many children and adults in these families have no medical problems. When a DICER gene mutation is found, specific screening studies may be recommended to look for PPB and other conditions known to be related to DICER1. Chest screening (by chest x-ray or chest CT) for young children known to have the DICER1 gene mutation but no symptoms have in some cases lead to a PPB diagnosis at the earliest and most curable stage. Likewise, when found early, the ovarian tumors associated with DICER1 may be removed with surgery alone and are associated with a favorable prognosis.
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Diagnosis of Pleuropulmonary Blastoma
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When a child presents with symptoms of PPB, a chest x-ray may show an air filled pocket (cyst) or a solid mass. Chest CT may be performed to look at the lungs in more detail. Surgery, either a biopsy or removal of the cyst or mass, is performed to diagnose and often remove the tumor. Microscopic examination of the specimen is needed. Review by the International PPB/DICER1 Registry pathology specialists is often helpful in confirming the diagnosis. This is offered at no cost to families or hospitals.
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Diagnosis of Pleuropulmonary Blastoma. When a child presents with symptoms of PPB, a chest x-ray may show an air filled pocket (cyst) or a solid mass. Chest CT may be performed to look at the lungs in more detail. Surgery, either a biopsy or removal of the cyst or mass, is performed to diagnose and often remove the tumor. Microscopic examination of the specimen is needed. Review by the International PPB/DICER1 Registry pathology specialists is often helpful in confirming the diagnosis. This is offered at no cost to families or hospitals.
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Therapies of Pleuropulmonary Blastoma
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TreatmentAfter surgery to remove type I PPB, some physicians recommend use of chemotherapy to attempt to remove any remaining small collections of malignant cells; some physicians recommend watchful waiting. Whether chemotherapy or observation is chosen depends on very specific factors for each individual child. Radiation therapy is not used for type I PPB. If type I PPB recurs in a child as type II or type III PPB, then the treatments for types II and III disease must be used.Type II and III PPB are both serious (aggressive) malignancies. Surgery is the first step in treatment but sometimes due to the size and location of the tumor, only biopsy can be performed. In these situations, chemotherapy is given to shrink the remaining tumor and remove the malignant cells left behind after surgery. Sometimes radiation therapy is also used. All children with type II or III PPB require additional treatment after tumor removal. The medications usually used for treatment of PPB are the same or similar to drugs used for more common childhood cancers. Even though PPB is rare, pediatric cancer specialists have experience using these drugs. Their use in children with PPB is guided by their use in other children.The use of radiation therapy is highly individualized in PPB patients. In general if there is a small area of tumor which could not be removed by surgery and which does not seem to disappear with chemotherapy, then radiation may be considered. Radiation can damage lung tissue so the doses and locations of radiation therapy are limited by the radiation oncology team. When PPB spreads to the brain, surgery followed by radiation therapy is often advised.Another possible therapy for PPB is high dose chemotherapy followed by autologous stem cell transplantation. This overall approach may be useful in cases where PPB has not been eliminated by more standard therapy.When standard treatments are not successful at eliminating PPB other therapies are often tried. Research is ongoing to find more effective therapies for PPB
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Therapies of Pleuropulmonary Blastoma. TreatmentAfter surgery to remove type I PPB, some physicians recommend use of chemotherapy to attempt to remove any remaining small collections of malignant cells; some physicians recommend watchful waiting. Whether chemotherapy or observation is chosen depends on very specific factors for each individual child. Radiation therapy is not used for type I PPB. If type I PPB recurs in a child as type II or type III PPB, then the treatments for types II and III disease must be used.Type II and III PPB are both serious (aggressive) malignancies. Surgery is the first step in treatment but sometimes due to the size and location of the tumor, only biopsy can be performed. In these situations, chemotherapy is given to shrink the remaining tumor and remove the malignant cells left behind after surgery. Sometimes radiation therapy is also used. All children with type II or III PPB require additional treatment after tumor removal. The medications usually used for treatment of PPB are the same or similar to drugs used for more common childhood cancers. Even though PPB is rare, pediatric cancer specialists have experience using these drugs. Their use in children with PPB is guided by their use in other children.The use of radiation therapy is highly individualized in PPB patients. In general if there is a small area of tumor which could not be removed by surgery and which does not seem to disappear with chemotherapy, then radiation may be considered. Radiation can damage lung tissue so the doses and locations of radiation therapy are limited by the radiation oncology team. When PPB spreads to the brain, surgery followed by radiation therapy is often advised.Another possible therapy for PPB is high dose chemotherapy followed by autologous stem cell transplantation. This overall approach may be useful in cases where PPB has not been eliminated by more standard therapy.When standard treatments are not successful at eliminating PPB other therapies are often tried. Research is ongoing to find more effective therapies for PPB
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Overview of PMM2-CDG
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SummaryPMM2-CDG, formerly known as congenital disorder of glycosylation type 1a, is a rare multisystem disorder that involves a normal, but complex, chemical process known as glycosylation. Glycosylation is the process by which sugar chains (glycans) are created, altered and chemically attached to certain proteins or fats (lipids). When these sugar molecules are attached to proteins, they form glycoproteins. Glycoproteins have varied important functions within the body and are essential for the normal growth and function of numerous tissues and organs. PMM2-CDG can affect virtually any part of the body, although most cases usually have an important neurological component. PMM2-CDG is associated with a broad and highly variable range of symptoms and can vary in severity from mild cases to severe, disabling or life-threatening cases. Most cases are apparent in infancy. PMM2-CDG is caused by mutations of the phosphomannomutase-2 (PMM2) gene and is inherited as an autosomal recessive condition.IntroductionPMM2-CDG belongs to a group of disorders known as the congenital disorders of glycosylation (CDG). CDG were first reported in the medical literature in 1980 by Dr. Jaak Jaeken, et al. More than 100 different forms of CDG have been reported in the ensuing years. PMM2-CDG is the most common form. Several different names have been used to describe these disorders including carbohydrate-deficient glycoprotein syndromes. Recently, researchers have proposed a classification system that names each subtype by the official abbreviation of its defective gene followed by a dash and CDG. Congenital disorder of glycosylation type 1a is now known as PMM2-CDG. CDG are a rapidly growing disease family and information about these disorders is constantly changing.
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Overview of PMM2-CDG. SummaryPMM2-CDG, formerly known as congenital disorder of glycosylation type 1a, is a rare multisystem disorder that involves a normal, but complex, chemical process known as glycosylation. Glycosylation is the process by which sugar chains (glycans) are created, altered and chemically attached to certain proteins or fats (lipids). When these sugar molecules are attached to proteins, they form glycoproteins. Glycoproteins have varied important functions within the body and are essential for the normal growth and function of numerous tissues and organs. PMM2-CDG can affect virtually any part of the body, although most cases usually have an important neurological component. PMM2-CDG is associated with a broad and highly variable range of symptoms and can vary in severity from mild cases to severe, disabling or life-threatening cases. Most cases are apparent in infancy. PMM2-CDG is caused by mutations of the phosphomannomutase-2 (PMM2) gene and is inherited as an autosomal recessive condition.IntroductionPMM2-CDG belongs to a group of disorders known as the congenital disorders of glycosylation (CDG). CDG were first reported in the medical literature in 1980 by Dr. Jaak Jaeken, et al. More than 100 different forms of CDG have been reported in the ensuing years. PMM2-CDG is the most common form. Several different names have been used to describe these disorders including carbohydrate-deficient glycoprotein syndromes. Recently, researchers have proposed a classification system that names each subtype by the official abbreviation of its defective gene followed by a dash and CDG. Congenital disorder of glycosylation type 1a is now known as PMM2-CDG. CDG are a rapidly growing disease family and information about these disorders is constantly changing.
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Symptoms of PMM2-CDG
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In order to help characterize and clarify this disorder, researchers have divided PMM2-CDG into three stages. These stages are based upon the symptoms at different periods of life. They are: the infantile multisystem stage; the late-infantile and childhood ataxia-intellectual disability stage; and the adult stable disability stage.The symptoms associated with PMM2-CDG are broad and highly variable. The specific symptoms present, severity and prognosis can vary greatly from one person to another depending upon several factors such as the specific organ system involved. Therefore, it is important to note that affected individuals will not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.INFANTILE MULTISYSTEM STAGE
This phase is primarily characterized by feeding problems, neuromuscular abnormalities, severe developmental delay, symptoms resulting from episodes of internal organ failure, and/or additional physical abnormalities (e.g., squinting facial appearance, inverted nipples, fat pads above the buttocks).Some researchers break down the infantile multisystem stage into two distinct clinical presentations. One presentation is a non-fatal neurological form characterized by psychomotor retardation, underdevelopment (hypoplasia) of the cerebellum, and crossed eyes. Later on, symptoms of abnormal nerve development may occur as could problems with eyesight. The second presentation is potentially fatal as it affects the neurological system and various internal organs. All organs except the lungs can become affected. Mortality is approximately 20% in the first 5 years.Most infants with PMM2-CDG exhibit normal birth weight. However, they may be slightly smaller than normal. Newborns may also appear sluggish and have an abnormally weak sucking response. Throughout their first year of life, affected infants may demonstrate little interest in nursing or bottle-feeding, have repeated episodes of diarrhea, vomit frequently, and/or fail to gain weight or grow at the expected rate (failure to thrive). In many cases, growth is significantly impaired. Infants and children may have also an increased (sometimes pronounced) susceptibility to infection.Newborns with PMM2-CDG may also exhibit many neuromuscular abnormalities. Their arms and legs (limbs) may appear abnormally thin and weak and may fail to extend normally. In addition, affected infants may exhibit severely diminished muscle tone (generalized hypotonia), so that they appear “floppy,” have little or no control of head movements, and/or exhibit decreased reflexes (hyporeflexia).Most infants with PMM2-CDG also exhibit additional physical abnormalities. Some have a distinctive facial appearance (minor facial dysmorphism) characterized by an abnormally prominent jaw; a nose with an unusually high bridge; an unequal, inward deviation of both eyes (bilateral internal strabismus and esotropia); a squinting facial appearance; large ears; and/or other facial abnormalities. Additional characteristic physical abnormalities may include inverted nipples; abnormally thick, dimpled skin, particularly on the thighs and buttocks (“peau d’orange” meaning “skin of orange”); an abnormal fat distribution on the body including prominent pads of fat under the skin (subcutaneous) above the buttocks; fat deposits around the external genitals (e.g., penis and scrotum in males, labia majora in females); and/or abnormal streaks of fat on the lower limbs.From the age of approximately four months, most affected infants begin to exhibit delays in the acquisition of skills requiring the coordination of mental and muscular activity (psychomotor developmental delay). Throughout infancy and early childhood, affected children may be severely delayed in achieving certain developmental milestones (e.g., sitting with minimal support, grasping objects, etc.). Although hand coordination may improve during late infancy, skills requiring the coordination of large muscles (gross motor abilities), such as those necessary for crawling, may continue to be delayed.In most cases, individuals with PMM2-CDG exhibit underdevelopment (hypoplasia) of certain portions of the brain (e.g., the cerebellum). Symptoms indicating such underdevelopment usually become apparent during infancy and may include poor sucking response, abnormal eye movements, lack of coordination, and/or low muscle tone. Hypoplasia of certain portions of the brain may also play a role in the other neuromuscular abnormalities and developmental delays apparent during infancy and childhood.In many cases, newborns and infants with PMM2-CDG may also have episodes of organ system failure, potentially resulting in life-threatening complications. For example, malfunction of the liver (hepatic dysfunction) may occur. Hepatic abnormalities include increased levels of certain liver enzymes (e.g., aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and/or abnormal enlargement of the liver (hepatomegaly), possibly in association with unusual enlargement of the spleen (splenomegaly). Affected infants may also have abnormal deposits of fat (hepatic steatosis) and/or unusual accumulations of scar tissue (fibrosis) within the liver.Because the liver creates many glycoproteins that function in the blood, liver malfunction may lead to problems with blood clotting and, in some cases, heart problems. For example, in some affected infants, abnormally increased amounts of fluid may accumulate between the two layers (pericardial space) of the membranous bag (pericardium) that surrounds the heart (pericardial effusion). The pericardial space normally contains a few small drops of fluid to help lubricate the contractions of the heart. However, if excess fluid accumulates in the pericardial space, the tough outermost layer of the pericardium (fibrous pericardium) may not be able to stretch normally, causing abnormal pressure to build up around the heart (cardiac tamponade). As a result, the heart may not be able to pump blood efficiently to the lungs and the rest of the body (cardiac failure). In most cases, in individuals with PMM2-CDG, such pericardial effusions do not result in life-threatening complications and tend to resolve over time.Some affected infants may experience episodes of severe gastrointestinal bleeding and/or abnormal accumulation of body fluids in the abdominal cavity (ascites). Symptoms associated with these findings may include shortness of breath, difficulty breathing, chest pain, bloating, and/or cramping. As mentioned above, it is believed that episodes of pericardial effusion, ascites, and/or gastrointestinal bleeding may be due in part to certain blood factor deficiencies exhibited by some infants with PMM2-CDG. Many affected infants periodically exhibit low levels of certain substances in the blood (e.g., factor XI) that help the blood clot (coagulation factors) as well as deficient levels of albumin, a protein that helps regulate the movement of fluid between the bloodstream and tissues.Some infants with PMM2-CDG may also exhibit kidney (renal) abnormalities. Such abnormalities may include enlarged kidneys (nephromegaly) and/or the presence of numerous small cysts within the kidneys (renal microcysts). Nephrotic syndrome, a condition in which the body secretes too much protein, has also been reported. Nephrotic syndrome can cause swelling (edema) especially of the feet and increase the risk of additional health problems.Some children with PMM2-CDG may have an underactive thyroid (hypothyroidism). Disease of the heart muscle (cardiomyopathy) and congenital heart anomalies have also been reported. Osteopenia, a condition in characterized by decreased bone mineralization and bone loss, is common and persistent. Some newborns experience abnormal accumulation of fluid in various tissues of the body (hydrops fetalis).LATE-INFANTILE AND CHILDHOOD ATAXIA-INTELLECTUAL DISABILITY PHASE
In PMM2-CDG, episodes of internal organ failure (e.g., hepatopathy, pericardial effusion, gastrointestinal bleeding, etc.) tend to decline during late infancy and early childhood. However, during this stage of development, several additional symptoms and characteristics may become apparent including varying degrees of intellectual disability, further physical signs of cerebellar hypoplasia, visual impairment, signs of impaired nerve impulse transmission to the legs (peripheral neuropathy), and/or additional abnormalities.During this second phase of PMM2-CDG, most affected children exhibit intellectual disability, ranging from moderate to severe. The degree of intellectual disability tends to remain stable at this point unless secondary events, such as stroke-like episodes, cause regression in a child’s previous mental capabilities. Although most children have some form of intellectual disability, children have been reported with normal intellectual development or only extremely mild deficiencies.Language and motor development can be affected and significantly delayed. Most affected children do not develop normal speech patterns. Intellectual disability, severe development delays, cerebellar ataxia, and/or other abnormalities contribute to communication limitations. In most cases, however, affected children may begin to develop their own communication methods through the use of signs, expressions, and gestures. Most children with this disorder tend to be outgoing and sociable.Additional symptoms associated with underdevelopment (hypoplasia) of certain portions of the brain (e.g., the cerebellum) also become apparent during this stage of PMM2-CDG. The cerebellum is the part of the brain that plays a role in maintaining balance and posture as well as coordinating voluntary movement. Such symptoms may include progressive balance problems (disequilibrium) and further impairment of the ability to coordinate voluntary movements (cerebellar ataxia). Cerebellar ataxia and other symptoms due to such hypoplasia tend to stabilize during later childhood or early adolescence.Individuals with PMM2-CDG continue to exhibit severe psychomotor developmental delays throughout childhood. For example, although some children may learn toilet habits, they tend to do so much later than expected. In addition, although some affected children may learn to feed themselves, most require regular assistance. Many affected children are unable to walk without assistance.In approximately 50 percent of children with PMM2-CDG, infections and fevers may trigger stroke-like episodes characterized by sluggishness (lethargy) and unresponsiveness to the environment (stupor), sudden unconsciousness, seizures, temporary blindness, paralysis on one side of the body (hemiplegia), and/or coma. In most cases, recovery may occur from such episodes within a few hours or days. However, in other cases, such episodes may be characterized by tissue damage and loss (necrosis) in part of the brain due to a lack of blood supply (cerebral infarction). Cerebral infarction may sometimes result in permanent damage, causing regression in a child's previous mental capabilities.In addition, many infants and children with PMM2-CDG periodically exhibit low levels of certain substances in the blood that help the blood clot (coagulation factors, such as factor XI) or prevent abnormal blood clotting (coagulation inhibitors, such as antithrombin III, protein C, protein S, and heparin cofactor II). The stroke-like episodes and cerebral infarctions sometimes occurring in children with PMM2-CDG may be due in part to coagulation factor and coagulation inhibitor deficiencies. In addition, some affected children may be predisposed to the development of clots within blood vessels (thromboses).Approximately half of affected children experience seizures during such stroke-like episodes. However, in some cases, affected children may also experience seizures outside of these episodes (epilepsy). Epilepsy is a condition characterized by recurrent episodes of uncontrolled electrical disturbances in the brain that may cause spasms, convulsions, and/or other symptoms. In some cases, seizures may develop as early as the second or third month. Seizures usually respond to anti-seizure medications.During this stage of development, children with PMM2-CDG may also begin to exhibit abnormalities of the peripheral nervous system (i.e., the motor and sensory nerves outside the brain and spinal cord). Due to loss or deficiency of the fatty coverings (myelin) around these nerve fibers (demyelination), nerve impulses may not be appropriately conducted from the brain and spinal cord to the extremities (peripheral neuropathy). Myelin, a substance made up of fatty materials and protein, enables effective transmission of nerve impulses from the brain and spinal cord by serving as an electrical insulator. As a result, the muscles in the arms and, in particular, the legs may become progressively weak and thin (atrophied).Infants and children with PMM2-CDG may also exhibit various abnormalities of the eyes during this stage. In addition to the bilateral inward deviation present during early infancy, affected children may also exhibit wandering eye movements and progressive degeneration of the colored (pigmented) layer of the nerve-rich membrane lining the eyes (progressive tapetoretinal degeneration, retinitis pigmentosa type). Progressive tapetoretinal degeneration may lead to poor night vision, restriction of visual fields, and/or difficulty with glare. Nearsightedness (myopia) and cataracts may also occur. The degree of visual impairment may vary from case to case, depending upon the combination and severity of various visual abnormalities present.Additional symptoms that may develop during this stage include skeletal malformations and abnormally fixed joints that occur when thickening and shortening of tissue such as muscle fibers cause deformity and restrict the movement an affected area (joint contractures).Adult Stable Disability Stage
Most individuals with PMM2-CDG enter a period of general stabilization and adaptation. According to the medical literature, at this phase of development, the coordination and balance difficulties (cerebellar ataxia) due to cerebellar hypoplasia generally have stabilized; stroke-like episodes typically have ceased; and convulsive episodes in those who exhibit epilepsy may begin to decrease. In addition, in most cases, episodes of internal organ failure have not occurred for some time, liver function has stabilized, and fat pads and other subcutaneous abnormalities (lipodystrophic accumulations) may have diminished or disappeared.Intellectual disability stabilizes in this phase. But for many affected adolescents, abnormalities involving the peripheral nervous system (peripheral neuropathy) may worsen. Impaired transmission of nerve impulses from the brain and spinal cord to muscle tissue, particularly in the legs, causes further weakening and wasting away (atrophy) of the muscles. In addition, atrophy, weakness, and shortening of muscle fibers may cause certain joints, particularly in the legs and feet, to become fixed in a permanently flexed position (joint contractures). In addition, all individuals with PMM2-CDG exhibit various skeletal abnormalities that may become apparent during this stage. Some abnormalities include short stature with long limbs and a compressed body. Others are reduced bone mass, a barrel-shaped rib cage, and abnormal curvature of the spine (kyphosis). Many of the spinal malformations occurring in PMM2-CDG may contribute to mobility impairment.Because many hormones are glycoproteins, both males and females with PMM2-CDG exhibit certain hormonal abnormalities. However, the range of such symptoms may be greater and more apparent in affected females.Affected females may not develop secondary sexual development (such as the growth of pubic hair and hair under the arms [axillary hair], breast enlargement, and an increase in body fat around the hips and other areas); in addition, they do not menstruate (amenorrhea) and are infertile. In such cases, it appears that the ovaries, the pair of female sex glands (gonads) in which eggs develop, fail to respond appropriately to hormones (gonadotropins such as follicle-stimulating hormone [FSH]) that normally stimulate their function. As a result, many affected females may exhibit abnormally high levels of such gonadotropic hormone (elevated serum FSH).Although males with PMM2-CDG experience puberty and develop secondary sexual characteristics (e.g., enlargement of the penis and testes; growth of pubic, facial, and other body hair), they tend to exhibit low levels of an important hormone that helps to stimulate sexual development (testosterone). Levels of gonadotrophin hormones (e.g., FSH), which stimulate cellular activity in the male sex glands (testes), may be normal or slightly elevated (elevated serum FSH).At this stage of development, individuals with PMM2-CDG exhibit stable (nonprogressive) cerebellar ataxia and varying degrees of peripheral neuropathy. Some individuals may continue to exhibit epileptic episodes; however, such episodes tend to occur randomly and are generally mild.Some adults with PMM2-CDG continue to have difficulty with verbalization and communication. Some are able to read and/or write simple sentences; however, they generally continue to communicate through their own basic telegraphic language. Although affected adolescents and adults require ongoing assistance with daily functions and mobility, many are able to complete special educational classes, and some are able to maintain employment with special supervision and support.In recent years, more and more adults have been diagnosed with a mild form of PMM2-CDG. Some of these individuals have normal intellectual development. Therefore, the complete clinical spectrum of PMM2-CDG is still being defined.
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Symptoms of PMM2-CDG. In order to help characterize and clarify this disorder, researchers have divided PMM2-CDG into three stages. These stages are based upon the symptoms at different periods of life. They are: the infantile multisystem stage; the late-infantile and childhood ataxia-intellectual disability stage; and the adult stable disability stage.The symptoms associated with PMM2-CDG are broad and highly variable. The specific symptoms present, severity and prognosis can vary greatly from one person to another depending upon several factors such as the specific organ system involved. Therefore, it is important to note that affected individuals will not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.INFANTILE MULTISYSTEM STAGE
This phase is primarily characterized by feeding problems, neuromuscular abnormalities, severe developmental delay, symptoms resulting from episodes of internal organ failure, and/or additional physical abnormalities (e.g., squinting facial appearance, inverted nipples, fat pads above the buttocks).Some researchers break down the infantile multisystem stage into two distinct clinical presentations. One presentation is a non-fatal neurological form characterized by psychomotor retardation, underdevelopment (hypoplasia) of the cerebellum, and crossed eyes. Later on, symptoms of abnormal nerve development may occur as could problems with eyesight. The second presentation is potentially fatal as it affects the neurological system and various internal organs. All organs except the lungs can become affected. Mortality is approximately 20% in the first 5 years.Most infants with PMM2-CDG exhibit normal birth weight. However, they may be slightly smaller than normal. Newborns may also appear sluggish and have an abnormally weak sucking response. Throughout their first year of life, affected infants may demonstrate little interest in nursing or bottle-feeding, have repeated episodes of diarrhea, vomit frequently, and/or fail to gain weight or grow at the expected rate (failure to thrive). In many cases, growth is significantly impaired. Infants and children may have also an increased (sometimes pronounced) susceptibility to infection.Newborns with PMM2-CDG may also exhibit many neuromuscular abnormalities. Their arms and legs (limbs) may appear abnormally thin and weak and may fail to extend normally. In addition, affected infants may exhibit severely diminished muscle tone (generalized hypotonia), so that they appear “floppy,” have little or no control of head movements, and/or exhibit decreased reflexes (hyporeflexia).Most infants with PMM2-CDG also exhibit additional physical abnormalities. Some have a distinctive facial appearance (minor facial dysmorphism) characterized by an abnormally prominent jaw; a nose with an unusually high bridge; an unequal, inward deviation of both eyes (bilateral internal strabismus and esotropia); a squinting facial appearance; large ears; and/or other facial abnormalities. Additional characteristic physical abnormalities may include inverted nipples; abnormally thick, dimpled skin, particularly on the thighs and buttocks (“peau d’orange” meaning “skin of orange”); an abnormal fat distribution on the body including prominent pads of fat under the skin (subcutaneous) above the buttocks; fat deposits around the external genitals (e.g., penis and scrotum in males, labia majora in females); and/or abnormal streaks of fat on the lower limbs.From the age of approximately four months, most affected infants begin to exhibit delays in the acquisition of skills requiring the coordination of mental and muscular activity (psychomotor developmental delay). Throughout infancy and early childhood, affected children may be severely delayed in achieving certain developmental milestones (e.g., sitting with minimal support, grasping objects, etc.). Although hand coordination may improve during late infancy, skills requiring the coordination of large muscles (gross motor abilities), such as those necessary for crawling, may continue to be delayed.In most cases, individuals with PMM2-CDG exhibit underdevelopment (hypoplasia) of certain portions of the brain (e.g., the cerebellum). Symptoms indicating such underdevelopment usually become apparent during infancy and may include poor sucking response, abnormal eye movements, lack of coordination, and/or low muscle tone. Hypoplasia of certain portions of the brain may also play a role in the other neuromuscular abnormalities and developmental delays apparent during infancy and childhood.In many cases, newborns and infants with PMM2-CDG may also have episodes of organ system failure, potentially resulting in life-threatening complications. For example, malfunction of the liver (hepatic dysfunction) may occur. Hepatic abnormalities include increased levels of certain liver enzymes (e.g., aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and/or abnormal enlargement of the liver (hepatomegaly), possibly in association with unusual enlargement of the spleen (splenomegaly). Affected infants may also have abnormal deposits of fat (hepatic steatosis) and/or unusual accumulations of scar tissue (fibrosis) within the liver.Because the liver creates many glycoproteins that function in the blood, liver malfunction may lead to problems with blood clotting and, in some cases, heart problems. For example, in some affected infants, abnormally increased amounts of fluid may accumulate between the two layers (pericardial space) of the membranous bag (pericardium) that surrounds the heart (pericardial effusion). The pericardial space normally contains a few small drops of fluid to help lubricate the contractions of the heart. However, if excess fluid accumulates in the pericardial space, the tough outermost layer of the pericardium (fibrous pericardium) may not be able to stretch normally, causing abnormal pressure to build up around the heart (cardiac tamponade). As a result, the heart may not be able to pump blood efficiently to the lungs and the rest of the body (cardiac failure). In most cases, in individuals with PMM2-CDG, such pericardial effusions do not result in life-threatening complications and tend to resolve over time.Some affected infants may experience episodes of severe gastrointestinal bleeding and/or abnormal accumulation of body fluids in the abdominal cavity (ascites). Symptoms associated with these findings may include shortness of breath, difficulty breathing, chest pain, bloating, and/or cramping. As mentioned above, it is believed that episodes of pericardial effusion, ascites, and/or gastrointestinal bleeding may be due in part to certain blood factor deficiencies exhibited by some infants with PMM2-CDG. Many affected infants periodically exhibit low levels of certain substances in the blood (e.g., factor XI) that help the blood clot (coagulation factors) as well as deficient levels of albumin, a protein that helps regulate the movement of fluid between the bloodstream and tissues.Some infants with PMM2-CDG may also exhibit kidney (renal) abnormalities. Such abnormalities may include enlarged kidneys (nephromegaly) and/or the presence of numerous small cysts within the kidneys (renal microcysts). Nephrotic syndrome, a condition in which the body secretes too much protein, has also been reported. Nephrotic syndrome can cause swelling (edema) especially of the feet and increase the risk of additional health problems.Some children with PMM2-CDG may have an underactive thyroid (hypothyroidism). Disease of the heart muscle (cardiomyopathy) and congenital heart anomalies have also been reported. Osteopenia, a condition in characterized by decreased bone mineralization and bone loss, is common and persistent. Some newborns experience abnormal accumulation of fluid in various tissues of the body (hydrops fetalis).LATE-INFANTILE AND CHILDHOOD ATAXIA-INTELLECTUAL DISABILITY PHASE
In PMM2-CDG, episodes of internal organ failure (e.g., hepatopathy, pericardial effusion, gastrointestinal bleeding, etc.) tend to decline during late infancy and early childhood. However, during this stage of development, several additional symptoms and characteristics may become apparent including varying degrees of intellectual disability, further physical signs of cerebellar hypoplasia, visual impairment, signs of impaired nerve impulse transmission to the legs (peripheral neuropathy), and/or additional abnormalities.During this second phase of PMM2-CDG, most affected children exhibit intellectual disability, ranging from moderate to severe. The degree of intellectual disability tends to remain stable at this point unless secondary events, such as stroke-like episodes, cause regression in a child’s previous mental capabilities. Although most children have some form of intellectual disability, children have been reported with normal intellectual development or only extremely mild deficiencies.Language and motor development can be affected and significantly delayed. Most affected children do not develop normal speech patterns. Intellectual disability, severe development delays, cerebellar ataxia, and/or other abnormalities contribute to communication limitations. In most cases, however, affected children may begin to develop their own communication methods through the use of signs, expressions, and gestures. Most children with this disorder tend to be outgoing and sociable.Additional symptoms associated with underdevelopment (hypoplasia) of certain portions of the brain (e.g., the cerebellum) also become apparent during this stage of PMM2-CDG. The cerebellum is the part of the brain that plays a role in maintaining balance and posture as well as coordinating voluntary movement. Such symptoms may include progressive balance problems (disequilibrium) and further impairment of the ability to coordinate voluntary movements (cerebellar ataxia). Cerebellar ataxia and other symptoms due to such hypoplasia tend to stabilize during later childhood or early adolescence.Individuals with PMM2-CDG continue to exhibit severe psychomotor developmental delays throughout childhood. For example, although some children may learn toilet habits, they tend to do so much later than expected. In addition, although some affected children may learn to feed themselves, most require regular assistance. Many affected children are unable to walk without assistance.In approximately 50 percent of children with PMM2-CDG, infections and fevers may trigger stroke-like episodes characterized by sluggishness (lethargy) and unresponsiveness to the environment (stupor), sudden unconsciousness, seizures, temporary blindness, paralysis on one side of the body (hemiplegia), and/or coma. In most cases, recovery may occur from such episodes within a few hours or days. However, in other cases, such episodes may be characterized by tissue damage and loss (necrosis) in part of the brain due to a lack of blood supply (cerebral infarction). Cerebral infarction may sometimes result in permanent damage, causing regression in a child's previous mental capabilities.In addition, many infants and children with PMM2-CDG periodically exhibit low levels of certain substances in the blood that help the blood clot (coagulation factors, such as factor XI) or prevent abnormal blood clotting (coagulation inhibitors, such as antithrombin III, protein C, protein S, and heparin cofactor II). The stroke-like episodes and cerebral infarctions sometimes occurring in children with PMM2-CDG may be due in part to coagulation factor and coagulation inhibitor deficiencies. In addition, some affected children may be predisposed to the development of clots within blood vessels (thromboses).Approximately half of affected children experience seizures during such stroke-like episodes. However, in some cases, affected children may also experience seizures outside of these episodes (epilepsy). Epilepsy is a condition characterized by recurrent episodes of uncontrolled electrical disturbances in the brain that may cause spasms, convulsions, and/or other symptoms. In some cases, seizures may develop as early as the second or third month. Seizures usually respond to anti-seizure medications.During this stage of development, children with PMM2-CDG may also begin to exhibit abnormalities of the peripheral nervous system (i.e., the motor and sensory nerves outside the brain and spinal cord). Due to loss or deficiency of the fatty coverings (myelin) around these nerve fibers (demyelination), nerve impulses may not be appropriately conducted from the brain and spinal cord to the extremities (peripheral neuropathy). Myelin, a substance made up of fatty materials and protein, enables effective transmission of nerve impulses from the brain and spinal cord by serving as an electrical insulator. As a result, the muscles in the arms and, in particular, the legs may become progressively weak and thin (atrophied).Infants and children with PMM2-CDG may also exhibit various abnormalities of the eyes during this stage. In addition to the bilateral inward deviation present during early infancy, affected children may also exhibit wandering eye movements and progressive degeneration of the colored (pigmented) layer of the nerve-rich membrane lining the eyes (progressive tapetoretinal degeneration, retinitis pigmentosa type). Progressive tapetoretinal degeneration may lead to poor night vision, restriction of visual fields, and/or difficulty with glare. Nearsightedness (myopia) and cataracts may also occur. The degree of visual impairment may vary from case to case, depending upon the combination and severity of various visual abnormalities present.Additional symptoms that may develop during this stage include skeletal malformations and abnormally fixed joints that occur when thickening and shortening of tissue such as muscle fibers cause deformity and restrict the movement an affected area (joint contractures).Adult Stable Disability Stage
Most individuals with PMM2-CDG enter a period of general stabilization and adaptation. According to the medical literature, at this phase of development, the coordination and balance difficulties (cerebellar ataxia) due to cerebellar hypoplasia generally have stabilized; stroke-like episodes typically have ceased; and convulsive episodes in those who exhibit epilepsy may begin to decrease. In addition, in most cases, episodes of internal organ failure have not occurred for some time, liver function has stabilized, and fat pads and other subcutaneous abnormalities (lipodystrophic accumulations) may have diminished or disappeared.Intellectual disability stabilizes in this phase. But for many affected adolescents, abnormalities involving the peripheral nervous system (peripheral neuropathy) may worsen. Impaired transmission of nerve impulses from the brain and spinal cord to muscle tissue, particularly in the legs, causes further weakening and wasting away (atrophy) of the muscles. In addition, atrophy, weakness, and shortening of muscle fibers may cause certain joints, particularly in the legs and feet, to become fixed in a permanently flexed position (joint contractures). In addition, all individuals with PMM2-CDG exhibit various skeletal abnormalities that may become apparent during this stage. Some abnormalities include short stature with long limbs and a compressed body. Others are reduced bone mass, a barrel-shaped rib cage, and abnormal curvature of the spine (kyphosis). Many of the spinal malformations occurring in PMM2-CDG may contribute to mobility impairment.Because many hormones are glycoproteins, both males and females with PMM2-CDG exhibit certain hormonal abnormalities. However, the range of such symptoms may be greater and more apparent in affected females.Affected females may not develop secondary sexual development (such as the growth of pubic hair and hair under the arms [axillary hair], breast enlargement, and an increase in body fat around the hips and other areas); in addition, they do not menstruate (amenorrhea) and are infertile. In such cases, it appears that the ovaries, the pair of female sex glands (gonads) in which eggs develop, fail to respond appropriately to hormones (gonadotropins such as follicle-stimulating hormone [FSH]) that normally stimulate their function. As a result, many affected females may exhibit abnormally high levels of such gonadotropic hormone (elevated serum FSH).Although males with PMM2-CDG experience puberty and develop secondary sexual characteristics (e.g., enlargement of the penis and testes; growth of pubic, facial, and other body hair), they tend to exhibit low levels of an important hormone that helps to stimulate sexual development (testosterone). Levels of gonadotrophin hormones (e.g., FSH), which stimulate cellular activity in the male sex glands (testes), may be normal or slightly elevated (elevated serum FSH).At this stage of development, individuals with PMM2-CDG exhibit stable (nonprogressive) cerebellar ataxia and varying degrees of peripheral neuropathy. Some individuals may continue to exhibit epileptic episodes; however, such episodes tend to occur randomly and are generally mild.Some adults with PMM2-CDG continue to have difficulty with verbalization and communication. Some are able to read and/or write simple sentences; however, they generally continue to communicate through their own basic telegraphic language. Although affected adolescents and adults require ongoing assistance with daily functions and mobility, many are able to complete special educational classes, and some are able to maintain employment with special supervision and support.In recent years, more and more adults have been diagnosed with a mild form of PMM2-CDG. Some of these individuals have normal intellectual development. Therefore, the complete clinical spectrum of PMM2-CDG is still being defined.
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Causes of PMM2-CDG
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PMM2-CDG is caused by mutations of the PMM2 gene and is inherited as an autosomal recessive genetic trait. The malfunctioning PMM2 gene has been tracked to gene map locus chromosome 16p13.3-p13.2.Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 16p13.3-p13.2” refers to a region on the short arm of chromosome 16 between band 13.3 and band 13.2. The numbered bands specify the location of the thousands of genes that are present on each chromosome.Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.Congenital disorders of glycosylation can be further subdivided. PMM2-CDG is further classified as a disorder of N-glycosylation, which involves carbohydrates called N-linked oligosaccharides. These oligosaccharides are created in a specific order to create specific sugar chain patterns, which are then attached to proteins on various cells. Disorders of N-glycosylation develop due to an enzyme deficiency or malfunction somewhere along the N-glycosylation pathway. Researchers have determined that the PMM2 gene encodes for the enzyme phosphomannomutase-2 (PMM2), which is required for the proper synthesis of N-linked oligosaccharides. Mutations in the PMM2 gene lead to deficient levels of functional phosphomannomutase-2 in the body, which, in turn, prevents proper glycosylation. Improper glycosylation is the underlying defect in individuals with PMM2-CDG.
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Causes of PMM2-CDG. PMM2-CDG is caused by mutations of the PMM2 gene and is inherited as an autosomal recessive genetic trait. The malfunctioning PMM2 gene has been tracked to gene map locus chromosome 16p13.3-p13.2.Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 16p13.3-p13.2” refers to a region on the short arm of chromosome 16 between band 13.3 and band 13.2. The numbered bands specify the location of the thousands of genes that are present on each chromosome.Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.Congenital disorders of glycosylation can be further subdivided. PMM2-CDG is further classified as a disorder of N-glycosylation, which involves carbohydrates called N-linked oligosaccharides. These oligosaccharides are created in a specific order to create specific sugar chain patterns, which are then attached to proteins on various cells. Disorders of N-glycosylation develop due to an enzyme deficiency or malfunction somewhere along the N-glycosylation pathway. Researchers have determined that the PMM2 gene encodes for the enzyme phosphomannomutase-2 (PMM2), which is required for the proper synthesis of N-linked oligosaccharides. Mutations in the PMM2 gene lead to deficient levels of functional phosphomannomutase-2 in the body, which, in turn, prevents proper glycosylation. Improper glycosylation is the underlying defect in individuals with PMM2-CDG.
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Affects of PMM2-CDG
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PMM2-CDG is the most common of a growing family of more than 100 extremely rare inherited metabolic disorders. More than 800 cases of this specific disorder have been reported worldwide. Two other disorders in this family are each represented by more than 20 cases. The remaining disorders in this family have fewer than 20 cases with several earning a place in the medical literature based on the report of one or two cases. The exact incidence and prevalence of these disorders in the general population is unknown. It is difficult to determine the true frequency of PMM2-CDG in the general population since the disorder may still be under-recognized and under-diagnosed in many parts of the world.
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Affects of PMM2-CDG. PMM2-CDG is the most common of a growing family of more than 100 extremely rare inherited metabolic disorders. More than 800 cases of this specific disorder have been reported worldwide. Two other disorders in this family are each represented by more than 20 cases. The remaining disorders in this family have fewer than 20 cases with several earning a place in the medical literature based on the report of one or two cases. The exact incidence and prevalence of these disorders in the general population is unknown. It is difficult to determine the true frequency of PMM2-CDG in the general population since the disorder may still be under-recognized and under-diagnosed in many parts of the world.
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nord_976_4
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Related disorders of PMM2-CDG
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Symptoms of the following disorders can be similar to those of PMM2-CDG. Comparisons may be useful for a differential diagnosis.Numerous different metabolic disorders share similar signs and symptoms to PMM2-CDG. Such disorders include congenital muscle disorders (myopathies), urea cycle disorders, inborn errors of bile metabolism, fatty acid oxidation disorders, organic acidurias, and peroxisome biogenesis disorders. Additional disorders that have similar signs and symptoms include cerebral palsy, congenital coagulation disorders, and ataxia-telangiectasia and other hereditary ataxias. (For more information on these disorders, choose the specific disorder or umbrella group name as your search term in the Rare Disease Database.).Prader-Willi syndrome is a genetic disorder characterized in infancy by diminished muscle tone (hypotonia), feeding difficulties, and failure to grow and gain weight. In childhood, features of the disorder include short stature, genital abnormalities and an excessive appetite. Progressive obesity results because of a lack of feeling satisfied after completing a meal (satiety) that leads to overeating. Without appropriate treatment, individuals with severe obesity may have an increased risk of cardiac insufficiency, diabetes or other serious conditions that can lead to potentially life-threatening complications. All individuals with Prader-Willi syndrome have some cognitive impairment that ranges from learning disabilities to mild mental retardation. Behavior problems are common and can include temper tantrums, obsessive/compulsive behavior, and skin picking. Prader-Willi syndrome occurs when the genes in a specific region of chromosome 15 do not function. The abnormal genes usually result from random errors in development, but are sometimes inherited. (For more information on this disorder, choose “Prader-Willi” as your search term in the Rare Disease Database.)
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Related disorders of PMM2-CDG. Symptoms of the following disorders can be similar to those of PMM2-CDG. Comparisons may be useful for a differential diagnosis.Numerous different metabolic disorders share similar signs and symptoms to PMM2-CDG. Such disorders include congenital muscle disorders (myopathies), urea cycle disorders, inborn errors of bile metabolism, fatty acid oxidation disorders, organic acidurias, and peroxisome biogenesis disorders. Additional disorders that have similar signs and symptoms include cerebral palsy, congenital coagulation disorders, and ataxia-telangiectasia and other hereditary ataxias. (For more information on these disorders, choose the specific disorder or umbrella group name as your search term in the Rare Disease Database.).Prader-Willi syndrome is a genetic disorder characterized in infancy by diminished muscle tone (hypotonia), feeding difficulties, and failure to grow and gain weight. In childhood, features of the disorder include short stature, genital abnormalities and an excessive appetite. Progressive obesity results because of a lack of feeling satisfied after completing a meal (satiety) that leads to overeating. Without appropriate treatment, individuals with severe obesity may have an increased risk of cardiac insufficiency, diabetes or other serious conditions that can lead to potentially life-threatening complications. All individuals with Prader-Willi syndrome have some cognitive impairment that ranges from learning disabilities to mild mental retardation. Behavior problems are common and can include temper tantrums, obsessive/compulsive behavior, and skin picking. Prader-Willi syndrome occurs when the genes in a specific region of chromosome 15 do not function. The abnormal genes usually result from random errors in development, but are sometimes inherited. (For more information on this disorder, choose “Prader-Willi” as your search term in the Rare Disease Database.)
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PMM2-CDG
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nord_976_5
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Diagnosis of PMM2-CDG
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A diagnosis of PMM2-CDG may be suspected based upon the identification of characteristic symptoms, a detailed patient history and a thorough clinical evaluation. A variety of specialized tests may be necessary to confirm a diagnosis of PMM2-CDG.According to the medical literature, a diagnosis of PMM2-CDG should be considered if infants or young children exhibit intellectual disability and severe psychomotor developmental delay in association with prominent fat pads on the buttocks, inverted nipples, squinting, cerebellar hypoplasia (as indicated by special imaging tests such as computed tomography (CT) scanning or magnetic resonance imaging (MRI), feeding difficulties and poor weight gain, hypotonia, liver abnormalities, pericardial effusion, stroke-like episodes, and/or eye abnormalities such as strabismus or retinal pigmentary degeneration. In general, CDG should be ruled out in any unexplained syndrome.Clinical Testing and Work-Up
A simple blood test to analyze the glycosylation status of transferrin can diagnose CDG due to N-glycosylation such as PMM2-CDG. Transferrin is a glycoprotein found in the blood plasma and that is essential for the proper transport of iron within the body. Abnormal transferrin patterns can be detected through a test known as isoelectric focusing (IEF). IEF allows physicians to separate molecules such as proteins or enzymes based upon their electrical charge. This allows physicians to detect abnormal serum transferrin. IEF is the standard test for diagnosing CDG due to N-glycosylation. However, a more accurate and sensitive method known as electrospray ionization-mass spectrometry is highly preferred to detect abnormal transferrin. Because this method is more sensitive it is able, in the case of type II CDG, to determine which individual sugars are missing from transferrin.Once a defect of N-linked glycosylation is diagnosed, further testing is required to determine the specific subtype. PMM2-CDG can be diagnosed by an enzyme assay, a tests that measures the activity of a specific type of enzyme (e.g., phosphomannomutase-2) in certain cells or tissues of the body.Molecular genetic testing can confirm a diagnosis of PMM2-CDG. Molecular genetic testing can detect mutations of the PMM2 gene that cause the disorder. However, it is only available on a clinical basis.In many cases, advanced imaging techniques may be used to confirm specific clinical features that may be associated with PMM2-CDG. For example, a complete neurological evaluation may be conducted including MRI, CT scanning, and electroencephalography (EEG). MRI and CT scanning may reveal underdevelopment (hypoplasia) of certain parts of the brain (e.g., the cerebellum).Nerve conduction velocity (NCV) testing may be performed to evaluate the peripheral neuropathy associated with PMM2-CDG. In NCV testing, an electric stimulator placed in the skin over a peripheral nerve evaluates the time that it takes for a nerve impulse to travel over a certain, measured portion of the nerve. In most cases, in individuals with PMM2-CDG who exhibit peripheral neuropathy, such nerve conduction time is only moderately decreased; however, such a reduction may become more pronounced with age.In many individuals with PMM2-CDG, x-ray studies may be used to reveal abnormally reduced bone mass (osteopenia) and to confirm certain skeletal malformations (e.g., scoliosis and/or kyphosis) often associated with the disorder.Visual abnormalities associated with progressive retinal pigmentary degeneration may be detected and measured through electroretinography (ERG). Through the use of a special instrument, ERG measures the retina’s electrical response to light stimulation.Liver abnormalities associated with PMM2-CDG may be detected through a number of specialized tests. Abnormally high levels of certain liver enzymes (i.e., aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) may be confirmed through laboratory tests conducted on the fluid portion of the blood (serum assays). Imaging studies, including ultrasound, may reveal hepatomegaly or hepatosplenomegaly. In ultrasonography, reflected sound waves create an image of the organs in question. In addition, in some cases, examination of samples of liver tissue (biopsy) under a microscope (light microscopy) may reveal fatty infiltration (steatosis) and/or abnormal accumulations of scar tissue (fibrosis) within the liver.In some individuals with PMM2-CDG, imaging tests such as ultrasonography may also reveal kidney (renal) abnormalities such as enlargement of the kidneys (nephromegaly) and/or the presence of numerous small cysts (renal microcysts). In addition, urine tests often reveal abnormally increased levels of protein in the urine (proteinuria).In many cases of PMM2-CDG, routine blood tests may reveal periodically low levels of certain substances in the blood that interact to help the blood clot (coagulation factors, such as Factor XI) or to help prevent abnormal blood clotting (coagulation inhibitors, such as antithrombin III, protein C, protein S, and heparin cofactor II). In addition, laboratory tests (assays) conducted on the fluid portion of the blood (serum) may reveal abnormal levels of certain hormones. For example, in affected females, unusually elevated levels of follicle-stimulating hormone (FSH) may become apparent during early childhood or adolescence. Adolescent males tend to exhibit low levels of testosterone; in addition, their FSH levels may also be slightly elevated in some cases.
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Diagnosis of PMM2-CDG. A diagnosis of PMM2-CDG may be suspected based upon the identification of characteristic symptoms, a detailed patient history and a thorough clinical evaluation. A variety of specialized tests may be necessary to confirm a diagnosis of PMM2-CDG.According to the medical literature, a diagnosis of PMM2-CDG should be considered if infants or young children exhibit intellectual disability and severe psychomotor developmental delay in association with prominent fat pads on the buttocks, inverted nipples, squinting, cerebellar hypoplasia (as indicated by special imaging tests such as computed tomography (CT) scanning or magnetic resonance imaging (MRI), feeding difficulties and poor weight gain, hypotonia, liver abnormalities, pericardial effusion, stroke-like episodes, and/or eye abnormalities such as strabismus or retinal pigmentary degeneration. In general, CDG should be ruled out in any unexplained syndrome.Clinical Testing and Work-Up
A simple blood test to analyze the glycosylation status of transferrin can diagnose CDG due to N-glycosylation such as PMM2-CDG. Transferrin is a glycoprotein found in the blood plasma and that is essential for the proper transport of iron within the body. Abnormal transferrin patterns can be detected through a test known as isoelectric focusing (IEF). IEF allows physicians to separate molecules such as proteins or enzymes based upon their electrical charge. This allows physicians to detect abnormal serum transferrin. IEF is the standard test for diagnosing CDG due to N-glycosylation. However, a more accurate and sensitive method known as electrospray ionization-mass spectrometry is highly preferred to detect abnormal transferrin. Because this method is more sensitive it is able, in the case of type II CDG, to determine which individual sugars are missing from transferrin.Once a defect of N-linked glycosylation is diagnosed, further testing is required to determine the specific subtype. PMM2-CDG can be diagnosed by an enzyme assay, a tests that measures the activity of a specific type of enzyme (e.g., phosphomannomutase-2) in certain cells or tissues of the body.Molecular genetic testing can confirm a diagnosis of PMM2-CDG. Molecular genetic testing can detect mutations of the PMM2 gene that cause the disorder. However, it is only available on a clinical basis.In many cases, advanced imaging techniques may be used to confirm specific clinical features that may be associated with PMM2-CDG. For example, a complete neurological evaluation may be conducted including MRI, CT scanning, and electroencephalography (EEG). MRI and CT scanning may reveal underdevelopment (hypoplasia) of certain parts of the brain (e.g., the cerebellum).Nerve conduction velocity (NCV) testing may be performed to evaluate the peripheral neuropathy associated with PMM2-CDG. In NCV testing, an electric stimulator placed in the skin over a peripheral nerve evaluates the time that it takes for a nerve impulse to travel over a certain, measured portion of the nerve. In most cases, in individuals with PMM2-CDG who exhibit peripheral neuropathy, such nerve conduction time is only moderately decreased; however, such a reduction may become more pronounced with age.In many individuals with PMM2-CDG, x-ray studies may be used to reveal abnormally reduced bone mass (osteopenia) and to confirm certain skeletal malformations (e.g., scoliosis and/or kyphosis) often associated with the disorder.Visual abnormalities associated with progressive retinal pigmentary degeneration may be detected and measured through electroretinography (ERG). Through the use of a special instrument, ERG measures the retina’s electrical response to light stimulation.Liver abnormalities associated with PMM2-CDG may be detected through a number of specialized tests. Abnormally high levels of certain liver enzymes (i.e., aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) may be confirmed through laboratory tests conducted on the fluid portion of the blood (serum assays). Imaging studies, including ultrasound, may reveal hepatomegaly or hepatosplenomegaly. In ultrasonography, reflected sound waves create an image of the organs in question. In addition, in some cases, examination of samples of liver tissue (biopsy) under a microscope (light microscopy) may reveal fatty infiltration (steatosis) and/or abnormal accumulations of scar tissue (fibrosis) within the liver.In some individuals with PMM2-CDG, imaging tests such as ultrasonography may also reveal kidney (renal) abnormalities such as enlargement of the kidneys (nephromegaly) and/or the presence of numerous small cysts (renal microcysts). In addition, urine tests often reveal abnormally increased levels of protein in the urine (proteinuria).In many cases of PMM2-CDG, routine blood tests may reveal periodically low levels of certain substances in the blood that interact to help the blood clot (coagulation factors, such as Factor XI) or to help prevent abnormal blood clotting (coagulation inhibitors, such as antithrombin III, protein C, protein S, and heparin cofactor II). In addition, laboratory tests (assays) conducted on the fluid portion of the blood (serum) may reveal abnormal levels of certain hormones. For example, in affected females, unusually elevated levels of follicle-stimulating hormone (FSH) may become apparent during early childhood or adolescence. Adolescent males tend to exhibit low levels of testosterone; in addition, their FSH levels may also be slightly elevated in some cases.
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Therapies of PMM2-CDG
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TreatmentThe treatment of PMM2-CDG is directed toward the specific symptoms that are apparent in each individual. Treatment requires the efforts of a team of specialists working together to agree on a comprehensive treatment plan. Such specialists may include pediatricians and/or internists; physicians who diagnose and treat disorders of the nervous system (neurologists), the eyes (ophthalmologists), the skeletal system (orthopedists), the gastrointestinal system (gastroenterologists), and the endocrine system (endocrinologists); physicians specializing in blood disorders (hematologists); those who specialize in abnormalities of speech and language development (speech-language pathologists); physical therapists; surgeons; dietitians; and/or other health care professionals.The specific therapeutic procedures and interventions for individuals with PMM2-CDG will vary, depending upon numerous factors including the specific symptoms present, the extent of the disorder, an individual’s age and overall health, tolerance of certain medications or procedures, personal preference and other factors. Decisions concerning the use of particular therapeutic interventions should be made by physicians and other members of the healthcare team in careful consultation with the patient and/or parents based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks including possible side effects and long-term effects; patient preference; and other appropriate factors.Some general therapies are common for infants and children with PMM2-CDG including nutritional supplements to ensure maximum caloric intake. In addition, in some cases, children may require the insertion of a tube through a small surgical opening in the stomach (gastrostomy) or a tube through the nose, down the esophagus and into the stomach (nasogastric tube). Many children develop persistent vomiting and dysfunction of oral motor skills, which involve the muscles of the face and throat. A variety of therapies may be necessary to ensure proper feeding including agents to thicken food, antacids, and maintaining an upright position when eating. Maintaining proper nutrition and caloric intake is critical for infants with chronic disorders and often a particular challenge for infants and children with PMM2-CDG.Early developmental intervention is important to ensure that affected children reach their potential. Most affected children will benefit from occupational, physical and speech therapy. Additional medical, social, and/or vocational services including special remedial education may also be beneficial. Ongoing counseling and support for parents is beneficial as well. Genetic counseling will also be of benefit for affected individuals and their families.Other treatment is symptomatic and supportive. Additional therapies for PMM2-CDG depend upon the specific abnormalities present and generally follow standard guidelines.Because infections and fevers may trigger stroke-like episodes, physicians may closely monitor affected infants and children, recommend preventive measures, and institute immediate antibiotic and/or other appropriate treatment should such infections and fevers occur. Stroke-like episodes may be treated intravenous (IV) hydration if necessary and physical therapy afterward.Physicians may also monitor affected infants and children for other potentially serious findings often associated with the disorder (e.g., signs of hepatic dysfunction, pericardial and/or pleural effusion, ascites) to ensure that appropriate preventive and/or treatment measures are taken.Regular ophthalmological exams may also be necessary to monitor and characterize the level of visual impairment and to ensure that affected children receive the benefit of early, appropriate supportive measures such as glasses, patching or surgery to correct strabismus.In some cases, various orthopedic measures may be used to help treat skeletal and/or neuromuscular abnormalities associated with PMM2-CDG such as joint contractures, scoliosis and/or kyphosis, etc. Treatments may include a combination of various supportive techniques, splints, braces, casts, and/or other orthopedic measures. Few affected individuals can walk unsupported and therefore require wheelchairs or other mobility equipment.In addition, for those affected individuals who have epilepsy, treatment with anti-seizure (anticonvulsant) drugs may help prevent, reduce, or control seizure activity. Hypothyroidism may be treated by hormone replacement therapy.Blood clotting abnormalities (coagulopathies) require special attention if affected individuals need surgery, but rarely pose problems during normal daily activities.
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Therapies of PMM2-CDG. TreatmentThe treatment of PMM2-CDG is directed toward the specific symptoms that are apparent in each individual. Treatment requires the efforts of a team of specialists working together to agree on a comprehensive treatment plan. Such specialists may include pediatricians and/or internists; physicians who diagnose and treat disorders of the nervous system (neurologists), the eyes (ophthalmologists), the skeletal system (orthopedists), the gastrointestinal system (gastroenterologists), and the endocrine system (endocrinologists); physicians specializing in blood disorders (hematologists); those who specialize in abnormalities of speech and language development (speech-language pathologists); physical therapists; surgeons; dietitians; and/or other health care professionals.The specific therapeutic procedures and interventions for individuals with PMM2-CDG will vary, depending upon numerous factors including the specific symptoms present, the extent of the disorder, an individual’s age and overall health, tolerance of certain medications or procedures, personal preference and other factors. Decisions concerning the use of particular therapeutic interventions should be made by physicians and other members of the healthcare team in careful consultation with the patient and/or parents based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks including possible side effects and long-term effects; patient preference; and other appropriate factors.Some general therapies are common for infants and children with PMM2-CDG including nutritional supplements to ensure maximum caloric intake. In addition, in some cases, children may require the insertion of a tube through a small surgical opening in the stomach (gastrostomy) or a tube through the nose, down the esophagus and into the stomach (nasogastric tube). Many children develop persistent vomiting and dysfunction of oral motor skills, which involve the muscles of the face and throat. A variety of therapies may be necessary to ensure proper feeding including agents to thicken food, antacids, and maintaining an upright position when eating. Maintaining proper nutrition and caloric intake is critical for infants with chronic disorders and often a particular challenge for infants and children with PMM2-CDG.Early developmental intervention is important to ensure that affected children reach their potential. Most affected children will benefit from occupational, physical and speech therapy. Additional medical, social, and/or vocational services including special remedial education may also be beneficial. Ongoing counseling and support for parents is beneficial as well. Genetic counseling will also be of benefit for affected individuals and their families.Other treatment is symptomatic and supportive. Additional therapies for PMM2-CDG depend upon the specific abnormalities present and generally follow standard guidelines.Because infections and fevers may trigger stroke-like episodes, physicians may closely monitor affected infants and children, recommend preventive measures, and institute immediate antibiotic and/or other appropriate treatment should such infections and fevers occur. Stroke-like episodes may be treated intravenous (IV) hydration if necessary and physical therapy afterward.Physicians may also monitor affected infants and children for other potentially serious findings often associated with the disorder (e.g., signs of hepatic dysfunction, pericardial and/or pleural effusion, ascites) to ensure that appropriate preventive and/or treatment measures are taken.Regular ophthalmological exams may also be necessary to monitor and characterize the level of visual impairment and to ensure that affected children receive the benefit of early, appropriate supportive measures such as glasses, patching or surgery to correct strabismus.In some cases, various orthopedic measures may be used to help treat skeletal and/or neuromuscular abnormalities associated with PMM2-CDG such as joint contractures, scoliosis and/or kyphosis, etc. Treatments may include a combination of various supportive techniques, splints, braces, casts, and/or other orthopedic measures. Few affected individuals can walk unsupported and therefore require wheelchairs or other mobility equipment.In addition, for those affected individuals who have epilepsy, treatment with anti-seizure (anticonvulsant) drugs may help prevent, reduce, or control seizure activity. Hypothyroidism may be treated by hormone replacement therapy.Blood clotting abnormalities (coagulopathies) require special attention if affected individuals need surgery, but rarely pose problems during normal daily activities.
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Overview of Pneumocystis Pneumonia
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Pneumocystis pneumonia is a type of infection of the lungs (pneumonia) in people with a weak immune system. It is caused by a yeast-like fungus called Pneumocystis jirovecii (PJP). People with a healthy immune system don't usually get infected with PCP. It becomes a problem only for people with a weak immune system that allows the fungus to cause infection. The immune system can be weakened by cancer, HIV infection or AIDS, high dose corticosteroids, or from medicine taken after having a bone marrow or organ transplant. It is the most common opportunistic infection found in HIV infected people and may cause mild symptoms. However, in individuals who do not have HIV infection it is typically characterized by severe respiratory failure coupled with fever and dry cough much like most pneumonias. Nearly all individual with PJP will have either low levels of oxygen in their blood (hypoxemia) at rest or with exertion, or an increase in the alveolar-arterial oxygen tension gradient which makes it difficult for an individual to breathe.
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Overview of Pneumocystis Pneumonia. Pneumocystis pneumonia is a type of infection of the lungs (pneumonia) in people with a weak immune system. It is caused by a yeast-like fungus called Pneumocystis jirovecii (PJP). People with a healthy immune system don't usually get infected with PCP. It becomes a problem only for people with a weak immune system that allows the fungus to cause infection. The immune system can be weakened by cancer, HIV infection or AIDS, high dose corticosteroids, or from medicine taken after having a bone marrow or organ transplant. It is the most common opportunistic infection found in HIV infected people and may cause mild symptoms. However, in individuals who do not have HIV infection it is typically characterized by severe respiratory failure coupled with fever and dry cough much like most pneumonias. Nearly all individual with PJP will have either low levels of oxygen in their blood (hypoxemia) at rest or with exertion, or an increase in the alveolar-arterial oxygen tension gradient which makes it difficult for an individual to breathe.
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Pneumocystis Pneumonia
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Symptoms of Pneumocystis Pneumonia
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Pneumocystis pneumonia is characterized by a gradual onset with shortness of breath and/or difficulty breathing. This disorder may be accompanied with fevers, night sweats, weight loss and dry cough. Dry cough is one distinction from typical pneumonia because spit (sputum) is too thick to become productive, therefore productive cough is not as common in PJP. Uncommonly, the PJP fungus can spread to other body organs such as the liver, kidney and spleen as the disease progresses.
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Symptoms of Pneumocystis Pneumonia. Pneumocystis pneumonia is characterized by a gradual onset with shortness of breath and/or difficulty breathing. This disorder may be accompanied with fevers, night sweats, weight loss and dry cough. Dry cough is one distinction from typical pneumonia because spit (sputum) is too thick to become productive, therefore productive cough is not as common in PJP. Uncommonly, the PJP fungus can spread to other body organs such as the liver, kidney and spleen as the disease progresses.
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Pneumocystis Pneumonia
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Causes of Pneumocystis Pneumonia
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Pneumocystis pneumonia is caused by the yeast-like fungus Pneumocystis jirovecii that most commonly presents as an opportunistic infection in HIV infected patients, but may present in a variety of people with weak immune systems. Most individuals infected are unaware of their HIV infection at the time of presentation and thus are not receiving PJP prophylaxis and are more prone to acquire PJP.
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Causes of Pneumocystis Pneumonia. Pneumocystis pneumonia is caused by the yeast-like fungus Pneumocystis jirovecii that most commonly presents as an opportunistic infection in HIV infected patients, but may present in a variety of people with weak immune systems. Most individuals infected are unaware of their HIV infection at the time of presentation and thus are not receiving PJP prophylaxis and are more prone to acquire PJP.
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Affects of Pneumocystis Pneumonia
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PJP is a frequent AIDS-defining diagnosis in the United States and in Europe. Pneumocystis pneumonia is commonly seen in HIV infected people with a CD4 count of less than 200 cells/mm3. People receiving high doses of glucocorticoids or other immunosuppressive drugs after an organ transplant or to treat cancer are at risk for PJP. People with other inflammatory conditions such as granulomatosis with polyangiitis (Wegener’s), polymyositis or dermatomyositis can also have an increased risk of acquiring PJP.
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Affects of Pneumocystis Pneumonia. PJP is a frequent AIDS-defining diagnosis in the United States and in Europe. Pneumocystis pneumonia is commonly seen in HIV infected people with a CD4 count of less than 200 cells/mm3. People receiving high doses of glucocorticoids or other immunosuppressive drugs after an organ transplant or to treat cancer are at risk for PJP. People with other inflammatory conditions such as granulomatosis with polyangiitis (Wegener’s), polymyositis or dermatomyositis can also have an increased risk of acquiring PJP.
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Related disorders of Pneumocystis Pneumonia
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Symptoms of the following disorders can be similar to those of Pneumocystis pneumonia:Bacterial pneumonia is a lung infection caused by bacterial. The most common bacteria likely to cause bacterial pneumonia are: Streptococcus pneumoniae, Haemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila. Pneumonias of these types are quite common and are often called community-acquired pneumonia (CAP). There are also other categories of pneumonia depending on the likelihood of where they acquired. Health-care-associated pneumonia (HAP) can occur in healthcare facilities with bacteria that are much more dangerous. The type of pneumonia and severity will determine the choice of treatment. Pneumonia can also be caused by endemic fungal pathogens such as Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Sporothrix schenckii, Cryptococcus neoformans and infect both healthy and immunocompromised persons. Fungal infection occurs following the inhalation of fungal spores, or by the reactivation of a latent infection.Respiratory failure occurs when not there is enough oxygen that passes from the lungs into the blood. Respiratory failure also can occur if the lungs cannot remove carbon dioxide (a waste gas) from the blood. If there is too much carbon dioxide in the blood it can lead to damage to other organs. This makes it difficult to breathe to compensate for the low oxygen exchange or abundance of carbon dioxide.Heart failure occurs when the heart cannot pump (systolic) or fill (diastolic) the heart back with enough blood. Symptoms include shortness of breath, fatigue, swollen legs, and rapid heartbeat.Pulmonary edema is usually caused by a heart condition or exposure to certain toxins and drugs, and being at high elevations. It may occur suddenly or develop over time with symptoms including difficulty breathing, cough, chest pain, or fatigue.
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Related disorders of Pneumocystis Pneumonia. Symptoms of the following disorders can be similar to those of Pneumocystis pneumonia:Bacterial pneumonia is a lung infection caused by bacterial. The most common bacteria likely to cause bacterial pneumonia are: Streptococcus pneumoniae, Haemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila. Pneumonias of these types are quite common and are often called community-acquired pneumonia (CAP). There are also other categories of pneumonia depending on the likelihood of where they acquired. Health-care-associated pneumonia (HAP) can occur in healthcare facilities with bacteria that are much more dangerous. The type of pneumonia and severity will determine the choice of treatment. Pneumonia can also be caused by endemic fungal pathogens such as Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Sporothrix schenckii, Cryptococcus neoformans and infect both healthy and immunocompromised persons. Fungal infection occurs following the inhalation of fungal spores, or by the reactivation of a latent infection.Respiratory failure occurs when not there is enough oxygen that passes from the lungs into the blood. Respiratory failure also can occur if the lungs cannot remove carbon dioxide (a waste gas) from the blood. If there is too much carbon dioxide in the blood it can lead to damage to other organs. This makes it difficult to breathe to compensate for the low oxygen exchange or abundance of carbon dioxide.Heart failure occurs when the heart cannot pump (systolic) or fill (diastolic) the heart back with enough blood. Symptoms include shortness of breath, fatigue, swollen legs, and rapid heartbeat.Pulmonary edema is usually caused by a heart condition or exposure to certain toxins and drugs, and being at high elevations. It may occur suddenly or develop over time with symptoms including difficulty breathing, cough, chest pain, or fatigue.
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Diagnosis of Pneumocystis Pneumonia
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The diagnosis of Pneumocystis pneumonia requires multiple tests such as a chest X-ray and a sample of sputum collected by a procedure called bronchoalveolar lavage to differentiate PJP between from other causes of pneumonia. To further confirm PJP, a test to amplify trace amounts of DNA (polymerase chain reaction or PCR) is used and a blood test to detect β-D-glucan is used.
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Diagnosis of Pneumocystis Pneumonia. The diagnosis of Pneumocystis pneumonia requires multiple tests such as a chest X-ray and a sample of sputum collected by a procedure called bronchoalveolar lavage to differentiate PJP between from other causes of pneumonia. To further confirm PJP, a test to amplify trace amounts of DNA (polymerase chain reaction or PCR) is used and a blood test to detect β-D-glucan is used.
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Pneumocystis Pneumonia
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Therapies of Pneumocystis Pneumonia
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Treatment
PJP infection can be serious, but many people can be treated at home with antibiotics such as Bactrim (trimethoprim and sulfamethoxazole). There are also different alternative therapies such as atovaquone, dapsone, primaquine w/ clindamycin, and pentamidine. Oxygen therapy may be needed to help get more oxygen into your lungs and bloodstream.
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Therapies of Pneumocystis Pneumonia. Treatment
PJP infection can be serious, but many people can be treated at home with antibiotics such as Bactrim (trimethoprim and sulfamethoxazole). There are also different alternative therapies such as atovaquone, dapsone, primaquine w/ clindamycin, and pentamidine. Oxygen therapy may be needed to help get more oxygen into your lungs and bloodstream.
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Overview of POEMS Syndrome
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SummaryPOEMS syndrome is an extremely rare paraneoplastic syndrome. Paraneoplastic syndromes are caused by an abnormal immune response to a cancerous tumor (neoplasm) where the body accidently attacks normal cells in the nervous system. POEMS is an acronym that stands for the disorder’s five major signs and symptoms, which include Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin abnormalities. Common symptoms include progressive weakness of the nerves in the arms and legs (sensorimotor polyneuropathy), an abnormally enlarged liver and/or spleen (hepatosplenomegaly), enlarged lymph nodes (lymphadenitis), darkening of the skin (hyperpigmentation), thickening of the skin and excessive hair growth (hypertrichosis).POEMS syndrome occurs 1.5 times more frequently among men than women, and the typical age of onset is adults in their 50s. The exact cause of POEMS syndrome is unknown, but research suggests that a chemical called VEGF (vascular endothelial growth factor) plays an important role in this disease.POEMS syndrome is a chronic disorder and the prognosis depends on the extent of the disease and an individual’s response to treatment. There is no standard treatment for POEMS syndrome. Treatment options for patients diagnosed with POEMS syndrome include radiation therapy, chemotherapy, and/or hematopoietic cell transplantation. The median survival for patients with POEMS syndrome is more than14 years.
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Overview of POEMS Syndrome. SummaryPOEMS syndrome is an extremely rare paraneoplastic syndrome. Paraneoplastic syndromes are caused by an abnormal immune response to a cancerous tumor (neoplasm) where the body accidently attacks normal cells in the nervous system. POEMS is an acronym that stands for the disorder’s five major signs and symptoms, which include Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin abnormalities. Common symptoms include progressive weakness of the nerves in the arms and legs (sensorimotor polyneuropathy), an abnormally enlarged liver and/or spleen (hepatosplenomegaly), enlarged lymph nodes (lymphadenitis), darkening of the skin (hyperpigmentation), thickening of the skin and excessive hair growth (hypertrichosis).POEMS syndrome occurs 1.5 times more frequently among men than women, and the typical age of onset is adults in their 50s. The exact cause of POEMS syndrome is unknown, but research suggests that a chemical called VEGF (vascular endothelial growth factor) plays an important role in this disease.POEMS syndrome is a chronic disorder and the prognosis depends on the extent of the disease and an individual’s response to treatment. There is no standard treatment for POEMS syndrome. Treatment options for patients diagnosed with POEMS syndrome include radiation therapy, chemotherapy, and/or hematopoietic cell transplantation. The median survival for patients with POEMS syndrome is more than14 years.
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POEMS Syndrome
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Symptoms of POEMS Syndrome
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POEMS syndrome is a rare, multisystem paraneoplastic syndrome. POEMS stands for some of the major signs and symptoms associated with the disease. The major criteria for POEMS syndrome include polyneuropathy, monoclonal gammopathy and either osteosclerotic lesion, Castleman disease, or elevated levels of vascular endothelial growth factor (VEGF) in addition to at least one minor criterion listed below.Summary of symptoms identified in patients with POEMS syndrome:PolyneuropathyPolyneuropathy is a disease affecting nerves throughout the body. Symptoms of polyneuropathy include: OrganomegalyOrganomegaly is the abnormal enlargement of an organ or organs in the body. Symptoms of organomegaly in patients with POEMS syndrome include: EndocrinopathyEndocrinopathy is when abnormal hormone levels are produced by the endocrine system (system of glands that secrete hormones into the blood). Symptoms of endocrinopathy in POEMS syndrome patients include: Monoclonal gammopathy Monoclonal gammopathy is when abnormal bone marrow cells (plasma cells) that produce a protein (monoclonal protein) can be found in the bloodstream. Plasma cells are a key component of the immune system but overproduction of these cells in individuals with POEMS syndrome may result in these symptoms: Skin abnormalities Additional blood abnormalities Breathing problems Other Symptoms
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Symptoms of POEMS Syndrome. POEMS syndrome is a rare, multisystem paraneoplastic syndrome. POEMS stands for some of the major signs and symptoms associated with the disease. The major criteria for POEMS syndrome include polyneuropathy, monoclonal gammopathy and either osteosclerotic lesion, Castleman disease, or elevated levels of vascular endothelial growth factor (VEGF) in addition to at least one minor criterion listed below.Summary of symptoms identified in patients with POEMS syndrome:PolyneuropathyPolyneuropathy is a disease affecting nerves throughout the body. Symptoms of polyneuropathy include: OrganomegalyOrganomegaly is the abnormal enlargement of an organ or organs in the body. Symptoms of organomegaly in patients with POEMS syndrome include: EndocrinopathyEndocrinopathy is when abnormal hormone levels are produced by the endocrine system (system of glands that secrete hormones into the blood). Symptoms of endocrinopathy in POEMS syndrome patients include: Monoclonal gammopathy Monoclonal gammopathy is when abnormal bone marrow cells (plasma cells) that produce a protein (monoclonal protein) can be found in the bloodstream. Plasma cells are a key component of the immune system but overproduction of these cells in individuals with POEMS syndrome may result in these symptoms: Skin abnormalities Additional blood abnormalities Breathing problems Other Symptoms
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Causes of POEMS Syndrome
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The exact cause of POEMS syndrome is unknown. POEMS syndrome is associated with an overproduction of molecules that promote inflammation through cell-to-cell communication (pro-inflammatory cytokines). Studies have demonstrated abnormally high levels of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines, interleukin-6, interleukin-1 and TNF-alpha in the blood of individuals with POEMS syndrome. Cytokines are proteins that are produced by the body’s immune system in response to inflammation. More research is needed to determine the exact role cytokines and VEGF play in the development of POEMS syndrome.
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Causes of POEMS Syndrome. The exact cause of POEMS syndrome is unknown. POEMS syndrome is associated with an overproduction of molecules that promote inflammation through cell-to-cell communication (pro-inflammatory cytokines). Studies have demonstrated abnormally high levels of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines, interleukin-6, interleukin-1 and TNF-alpha in the blood of individuals with POEMS syndrome. Cytokines are proteins that are produced by the body’s immune system in response to inflammation. More research is needed to determine the exact role cytokines and VEGF play in the development of POEMS syndrome.
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POEMS Syndrome
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Affects of POEMS Syndrome
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POEMS syndrome affects 1.5 times more men than women, and disease onset usually occurs during a patient’s 40s to 60s. POEMS syndrome often goes unrecognized, making it difficult to determine the number of people afflicted with the disease.
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Affects of POEMS Syndrome. POEMS syndrome affects 1.5 times more men than women, and disease onset usually occurs during a patient’s 40s to 60s. POEMS syndrome often goes unrecognized, making it difficult to determine the number of people afflicted with the disease.
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Related disorders of POEMS Syndrome
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Symptoms of the following disorders can be similar to those of POEMS syndrome. Comparisons may be useful for a differential diagnosis:Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare neurological disorder in which there is swelling of nerve roots and peripheral nerves as well as destruction of the fatty protective covering (myelin sheath) of the nerves. This disorder causes weakness, paralysis and/or impairment in motor function, especially of the arms and legs. Sensory loss may also be present causing numbness, tingling or prickling sensations in affected areas. The motor and sensory impairments are usually on both sides of the body (symmetrical) and the degree of severity and disease course may vary. Some affected individuals may follow a slow steady pattern of symptoms while others may have symptoms that stabilize and relapse. A distinct feature of CIDP is that most patients cannot identify a preceding viral infection or illness. (For more information on this disorder, choose “chronic inflammatory demyelinating polyneuropathy” as your search term in the Rare Disease Database.)Amyloid light chains (AL) amyloidosis is a systematic disorder caused by an abnormality in white blood cells (plasma cells) of the bone marrow. As a result of this bone marrow disorder, misfolded, amyloid proteins are formed and deposited in and around tissues, nerves and organs. A gradual build-up of these amyloid proteins in tissues, nerves, and organs can damage and impair their function over time. Common symptoms include protein in the urine, blood pressures changes, stiffening of the heart and kidney issues. Other symptoms include fatigue, weight loss, diarrhea/constipation, dizziness, shortness of breath and general pain. (For more information on this disorder, choose “amyloidosis” as your search term in Rare Disease Database.)Guillain-Barré syndrome is a rare disorder in which the body’s immune system attacks the peripheral nervous system, the system carrying signals from the brain to muscles throughout the body. Symptoms associated with Guillain-Barré syndrome include muscle weakness, numbness and tingling sensation that begins in the arms and legs then spreads to the upper body. Loss of muscle function can occur overtime (paralysis). The exact cause of Guillain-Barré syndrome is unknown. (For more information on this disorder, choose “Guillain-Barré syndrome” as your search term in Rare Disease Database.)Monoclonal gammopathy of undetermined significance (MGUS) is a condition in which an abnormal protein (monoclonal protein) is detected in the blood. Traditionally MGUS does not cause any problems, but some symptoms can include numbness, tingling or weakness. In some patients, MGUS has progressed into different forms of blood cancer overtime (multiple myeloma, macroglobulinemia or B-cell lymphoma).Chronic ataxic neuropathy with ophthalmoplegia (CANOMAD) is an antibody-associated neuropathy that is caused by a certain type of antibody (IgM). The origin of the IgM antibodies is not known. This disease is more common in males than females, and the typical age of onset is during a patient’s 60s. The muscle pain and weakness is often severe but progresses more slowly than POEMS syndrome.The following disorders may occur in association with POEMS syndrome:Castleman disease (CD) is a rare disorder that involves overgrowth of cells in the lymph nodes and related tissues. There are two main types: unicentric CD and multicentric CD. Unicentric CD is a “localized” condition that is confined to a single set of lymph nodes, while multicentric CD is a “systemic” disease that affects multiple sets of lymph nodes. Most often, the enlarged lymph nodes occur in the chest, stomach and/or neck. Less common sites include the armpit (axilla), pelvis and pancreas. Most individuals with unicentric CD exhibit no symptoms (asymptomatic). Multicentric Castleman disease may be associated with fever, weight loss, skin rash, peripheral neuropathy and enlarged lymph nodes. Many individuals with multicentric Castleman disease may exhibit an abnormally large liver and spleen (hepatosplenomegaly). It is not clear what causes Castleman disease. (For more information on this disorder, choose “Castleman” as your search term in the Rare Disease Database.)Osteosclerotic myeloma is a variant of multiple myeloma, a rare condition characterized by excessive production (proliferation) and improper function of certain cells (plasma cells) of the bone marrow. If there are symptoms other than CRAB (hypercalcemia, renal dysfunction, anemia, or sclerotic bone lesions, a diagnosis of POEMS syndrome could be considered. These patients have symptoms akin to regular multiple myeloma but for reasons that are unknown, instead of lytic (thin and holey bones), there is osteosclerosis, which is a condition marked by abnormal density and hardening of bone. The exact cause of osteosclerotic myeloma is not known. (For more information on this disorder, choose “multiple myeloma” as your search term in the Rare Disease Database.)
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Related disorders of POEMS Syndrome. Symptoms of the following disorders can be similar to those of POEMS syndrome. Comparisons may be useful for a differential diagnosis:Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare neurological disorder in which there is swelling of nerve roots and peripheral nerves as well as destruction of the fatty protective covering (myelin sheath) of the nerves. This disorder causes weakness, paralysis and/or impairment in motor function, especially of the arms and legs. Sensory loss may also be present causing numbness, tingling or prickling sensations in affected areas. The motor and sensory impairments are usually on both sides of the body (symmetrical) and the degree of severity and disease course may vary. Some affected individuals may follow a slow steady pattern of symptoms while others may have symptoms that stabilize and relapse. A distinct feature of CIDP is that most patients cannot identify a preceding viral infection or illness. (For more information on this disorder, choose “chronic inflammatory demyelinating polyneuropathy” as your search term in the Rare Disease Database.)Amyloid light chains (AL) amyloidosis is a systematic disorder caused by an abnormality in white blood cells (plasma cells) of the bone marrow. As a result of this bone marrow disorder, misfolded, amyloid proteins are formed and deposited in and around tissues, nerves and organs. A gradual build-up of these amyloid proteins in tissues, nerves, and organs can damage and impair their function over time. Common symptoms include protein in the urine, blood pressures changes, stiffening of the heart and kidney issues. Other symptoms include fatigue, weight loss, diarrhea/constipation, dizziness, shortness of breath and general pain. (For more information on this disorder, choose “amyloidosis” as your search term in Rare Disease Database.)Guillain-Barré syndrome is a rare disorder in which the body’s immune system attacks the peripheral nervous system, the system carrying signals from the brain to muscles throughout the body. Symptoms associated with Guillain-Barré syndrome include muscle weakness, numbness and tingling sensation that begins in the arms and legs then spreads to the upper body. Loss of muscle function can occur overtime (paralysis). The exact cause of Guillain-Barré syndrome is unknown. (For more information on this disorder, choose “Guillain-Barré syndrome” as your search term in Rare Disease Database.)Monoclonal gammopathy of undetermined significance (MGUS) is a condition in which an abnormal protein (monoclonal protein) is detected in the blood. Traditionally MGUS does not cause any problems, but some symptoms can include numbness, tingling or weakness. In some patients, MGUS has progressed into different forms of blood cancer overtime (multiple myeloma, macroglobulinemia or B-cell lymphoma).Chronic ataxic neuropathy with ophthalmoplegia (CANOMAD) is an antibody-associated neuropathy that is caused by a certain type of antibody (IgM). The origin of the IgM antibodies is not known. This disease is more common in males than females, and the typical age of onset is during a patient’s 60s. The muscle pain and weakness is often severe but progresses more slowly than POEMS syndrome.The following disorders may occur in association with POEMS syndrome:Castleman disease (CD) is a rare disorder that involves overgrowth of cells in the lymph nodes and related tissues. There are two main types: unicentric CD and multicentric CD. Unicentric CD is a “localized” condition that is confined to a single set of lymph nodes, while multicentric CD is a “systemic” disease that affects multiple sets of lymph nodes. Most often, the enlarged lymph nodes occur in the chest, stomach and/or neck. Less common sites include the armpit (axilla), pelvis and pancreas. Most individuals with unicentric CD exhibit no symptoms (asymptomatic). Multicentric Castleman disease may be associated with fever, weight loss, skin rash, peripheral neuropathy and enlarged lymph nodes. Many individuals with multicentric Castleman disease may exhibit an abnormally large liver and spleen (hepatosplenomegaly). It is not clear what causes Castleman disease. (For more information on this disorder, choose “Castleman” as your search term in the Rare Disease Database.)Osteosclerotic myeloma is a variant of multiple myeloma, a rare condition characterized by excessive production (proliferation) and improper function of certain cells (plasma cells) of the bone marrow. If there are symptoms other than CRAB (hypercalcemia, renal dysfunction, anemia, or sclerotic bone lesions, a diagnosis of POEMS syndrome could be considered. These patients have symptoms akin to regular multiple myeloma but for reasons that are unknown, instead of lytic (thin and holey bones), there is osteosclerosis, which is a condition marked by abnormal density and hardening of bone. The exact cause of osteosclerotic myeloma is not known. (For more information on this disorder, choose “multiple myeloma” as your search term in the Rare Disease Database.)
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POEMS Syndrome
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Diagnosis of POEMS Syndrome
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Patients suspected of having POEMS syndrome should undergo a thorough clinical evaluation to include a physical exam, medical history review and laboratory testing. The detailed physical exam includes examination of the eyes, skin and neurological status as well as overall function of organs and body.Confirmation of certain immunologic abnormalities plays an essential role in establishing the diagnosis of POEMS syndrome. Laboratory tests conducted on the blood (serum) or cerebrospinal fluid (CSF) may reveal elevated levels of M-proteins and blood plasma may show high levels of vascular endothelial growth factor (VEGF). Skeletal imaging may be performed to detect osteosclerotic lesions characteristic of POEMS syndrome. In many patients, surgical removal (biopsy) and microscopic examination of small samples of tissue from an osteosclerotic lesion or a bone marrow biopsy will reveal the abnormal presence of monoclonal plasma cells.In order to be diagnosed with POEMS syndrome, a person must present both polyneuropathy and monoclonal plasma cell proliferative disorder in addition to one major criterion and one minor criterion. The other major criteria for POEMS syndrome include osteosclerotic lesion, Castleman disease, and elevated levels of vascular endothelial growth factor (VEGF). Minor criteria for POEMS syndrome include enlargement of organs (organomegaly), extracellular fluid accumulation (peripheral edema, ascites, or pleural effusion), endocrinopathy, skin changes, swelling of the optic disc (papilledema) and elevated blood cell count (polycythemia or thrombocytosis).
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Diagnosis of POEMS Syndrome. Patients suspected of having POEMS syndrome should undergo a thorough clinical evaluation to include a physical exam, medical history review and laboratory testing. The detailed physical exam includes examination of the eyes, skin and neurological status as well as overall function of organs and body.Confirmation of certain immunologic abnormalities plays an essential role in establishing the diagnosis of POEMS syndrome. Laboratory tests conducted on the blood (serum) or cerebrospinal fluid (CSF) may reveal elevated levels of M-proteins and blood plasma may show high levels of vascular endothelial growth factor (VEGF). Skeletal imaging may be performed to detect osteosclerotic lesions characteristic of POEMS syndrome. In many patients, surgical removal (biopsy) and microscopic examination of small samples of tissue from an osteosclerotic lesion or a bone marrow biopsy will reveal the abnormal presence of monoclonal plasma cells.In order to be diagnosed with POEMS syndrome, a person must present both polyneuropathy and monoclonal plasma cell proliferative disorder in addition to one major criterion and one minor criterion. The other major criteria for POEMS syndrome include osteosclerotic lesion, Castleman disease, and elevated levels of vascular endothelial growth factor (VEGF). Minor criteria for POEMS syndrome include enlargement of organs (organomegaly), extracellular fluid accumulation (peripheral edema, ascites, or pleural effusion), endocrinopathy, skin changes, swelling of the optic disc (papilledema) and elevated blood cell count (polycythemia or thrombocytosis).
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POEMS Syndrome
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Therapies of POEMS Syndrome
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TreatmentCurrent treatments for POEMS syndrome focus on improvement of symptoms and can lead to good prognosis in patients.The use of ionizing radiation (radiotherapy) or surgical removal (excision) of osteosclerotic lesions that are localized (not spread throughout the body) may temporarily or permanently lead to remission of symptoms associated with POEMS syndrome.In many patients, including those with widespread unusual hardening of bone (osteosclerotic lesions) or diffuse bone marrow involvement, therapy with certain anticancer drugs (alkylating chemotherapy agents) may alleviate symptoms associated with POEMS syndrome.Some patients with widespread disease may also receive high doses of chemotherapy followed by infusion of healthy blood stem cells from their own body (autologous stem cell transplant). Additional therapies used to treat POEMS syndrome include lenalidomide, thalidomide and bortezomib depending on a patient’s disease course. Other treatment such as physical therapy and medications to relieve swelling can help with improving mobility and other symptoms of POEMS syndrome.
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Therapies of POEMS Syndrome. TreatmentCurrent treatments for POEMS syndrome focus on improvement of symptoms and can lead to good prognosis in patients.The use of ionizing radiation (radiotherapy) or surgical removal (excision) of osteosclerotic lesions that are localized (not spread throughout the body) may temporarily or permanently lead to remission of symptoms associated with POEMS syndrome.In many patients, including those with widespread unusual hardening of bone (osteosclerotic lesions) or diffuse bone marrow involvement, therapy with certain anticancer drugs (alkylating chemotherapy agents) may alleviate symptoms associated with POEMS syndrome.Some patients with widespread disease may also receive high doses of chemotherapy followed by infusion of healthy blood stem cells from their own body (autologous stem cell transplant). Additional therapies used to treat POEMS syndrome include lenalidomide, thalidomide and bortezomib depending on a patient’s disease course. Other treatment such as physical therapy and medications to relieve swelling can help with improving mobility and other symptoms of POEMS syndrome.
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POEMS Syndrome
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nord_979_0
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Overview of Poland Syndrome
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Poland Syndrome is a rare condition that is evident at birth (congenital). Associated features may be extremely variable from case to case. However, it is classically characterized by absence (aplasia) of chest wall muscles on one side of the body (unilateral) and abnormally short, webbed fingers (symbrachydactyly) of the hand on the same side (ipsilateral).In those with the condition, there is typically unilateral absence of the pectoralis minor and the sternal or breastbone portion of the pectoralis major. The pectoralis minor is a thin, triangular muscle of the upper chest wall; the pectoralis major is a large, fanlike muscle that covers most of the upper, front part of the chest.Affected individuals may have variable associated features, such as underdevelopment or absence of one nipple (including the darkened area around the nipple [areola]) and/or patchy absence of hair under the arm (axilla). In females, there may be underdevelopment or absence (aplasia) of one breast and underlying (subcutaneous) tissues. In some cases, associated skeletal abnormalities may also be present, such as underdevelopment or absence of upper ribs; elevation of the shoulder blade (Sprengel deformity); and/or shortening of the arm, with underdevelopment of the forearm bones (i.e., ulna and radius).Poland Syndrome affects males more commonly than females and most frequently involves the right side of the body. The exact cause of the condition is unknown.
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Overview of Poland Syndrome. Poland Syndrome is a rare condition that is evident at birth (congenital). Associated features may be extremely variable from case to case. However, it is classically characterized by absence (aplasia) of chest wall muscles on one side of the body (unilateral) and abnormally short, webbed fingers (symbrachydactyly) of the hand on the same side (ipsilateral).In those with the condition, there is typically unilateral absence of the pectoralis minor and the sternal or breastbone portion of the pectoralis major. The pectoralis minor is a thin, triangular muscle of the upper chest wall; the pectoralis major is a large, fanlike muscle that covers most of the upper, front part of the chest.Affected individuals may have variable associated features, such as underdevelopment or absence of one nipple (including the darkened area around the nipple [areola]) and/or patchy absence of hair under the arm (axilla). In females, there may be underdevelopment or absence (aplasia) of one breast and underlying (subcutaneous) tissues. In some cases, associated skeletal abnormalities may also be present, such as underdevelopment or absence of upper ribs; elevation of the shoulder blade (Sprengel deformity); and/or shortening of the arm, with underdevelopment of the forearm bones (i.e., ulna and radius).Poland Syndrome affects males more commonly than females and most frequently involves the right side of the body. The exact cause of the condition is unknown.
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Poland Syndrome
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Symptoms of Poland Syndrome
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Associated symptoms and findings are extremely variable, including in rare cases in which more than one family member has been affected. For example, in some reported cases, one sibling has had all major features of the condition, while the other sibling has had only absence of pectoral muscle or hand involvement.However, as noted above, Poland Syndrome is most commonly characterized by absence of chest wall muscles on one side of the body (unilateral) as well as involvement of the hand on the same side (ipsilateral). In approximately 75 percent of cases, such abnormalities affect the right side of the body.In most affected individuals, there is absence of the sternal portion of the pectoralis major as well as absence of the pectoralis minor. The pectoralis major, a large muscle of the upper chest wall, arises from the breastbone (sternum), the collarbone (clavicle), and cartilages of the second to the sixth ribs; it acts on the joint of the shoulder, functioning to move the arm across the body. The pectoralis minor is a thin, triangular muscle beneath the pectoralis major. This muscle arises from the third to fifth ribs and functions to rotate the shoulder blade (scapula) and move it forward and down.In some individuals with Poland Syndrome, there may also be unilateral absence of other regional muscles, such as certain large muscles of the back (latissimus dorsi) and/or a thin muscle of the chest wall that extends from ribs under the arm to the scapula (serratus anterior).In some cases, associated abnormalities may include underdevelopment or absence of the darkened area around the nipple (areola) and the nipple and/or abnormal patchy hair growth under the arm (axilla). In addition, in affected females, there may be underdevelopment or absence of the breast and subcutaneous tissues.Additional, variable bone defects may also be present in some individuals with Poland Syndrome. These may include underdevelopment or absence of certain upper ribs and the bars of cartilage (costal cartilages) by which the ribs are attached to the sternum. In addition, in some cases, there may be abnormal elevation and/or underdevelopment of the shoulder blade (scapula), limited movement of the arm on the affected side, and the development of a lump at the base of the neck due to elevation of the scapula (a condition known as Sprengel deformity). (For more information, please choose “Sprengel” as your search term in the Rare Disease Database.)As noted above, most individuals with Poland Syndrome also have involvement of the hand on the affected side of the body. Certain bones of the fingers (phalanges) are underdeveloped or absent, resulting in abnormally short fingers (brachydactyly). In addition, in most cases, there is webbing (syndactyly) of certain fingers, particularly the index and middle fingers. In addition, in some cases, affected individuals may have abnormal shortening of the arm, with underdevelopment of the bones on the thumb and pinky sides of the forearm (i.e., radius and ulna).
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Symptoms of Poland Syndrome. Associated symptoms and findings are extremely variable, including in rare cases in which more than one family member has been affected. For example, in some reported cases, one sibling has had all major features of the condition, while the other sibling has had only absence of pectoral muscle or hand involvement.However, as noted above, Poland Syndrome is most commonly characterized by absence of chest wall muscles on one side of the body (unilateral) as well as involvement of the hand on the same side (ipsilateral). In approximately 75 percent of cases, such abnormalities affect the right side of the body.In most affected individuals, there is absence of the sternal portion of the pectoralis major as well as absence of the pectoralis minor. The pectoralis major, a large muscle of the upper chest wall, arises from the breastbone (sternum), the collarbone (clavicle), and cartilages of the second to the sixth ribs; it acts on the joint of the shoulder, functioning to move the arm across the body. The pectoralis minor is a thin, triangular muscle beneath the pectoralis major. This muscle arises from the third to fifth ribs and functions to rotate the shoulder blade (scapula) and move it forward and down.In some individuals with Poland Syndrome, there may also be unilateral absence of other regional muscles, such as certain large muscles of the back (latissimus dorsi) and/or a thin muscle of the chest wall that extends from ribs under the arm to the scapula (serratus anterior).In some cases, associated abnormalities may include underdevelopment or absence of the darkened area around the nipple (areola) and the nipple and/or abnormal patchy hair growth under the arm (axilla). In addition, in affected females, there may be underdevelopment or absence of the breast and subcutaneous tissues.Additional, variable bone defects may also be present in some individuals with Poland Syndrome. These may include underdevelopment or absence of certain upper ribs and the bars of cartilage (costal cartilages) by which the ribs are attached to the sternum. In addition, in some cases, there may be abnormal elevation and/or underdevelopment of the shoulder blade (scapula), limited movement of the arm on the affected side, and the development of a lump at the base of the neck due to elevation of the scapula (a condition known as Sprengel deformity). (For more information, please choose “Sprengel” as your search term in the Rare Disease Database.)As noted above, most individuals with Poland Syndrome also have involvement of the hand on the affected side of the body. Certain bones of the fingers (phalanges) are underdeveloped or absent, resulting in abnormally short fingers (brachydactyly). In addition, in most cases, there is webbing (syndactyly) of certain fingers, particularly the index and middle fingers. In addition, in some cases, affected individuals may have abnormal shortening of the arm, with underdevelopment of the bones on the thumb and pinky sides of the forearm (i.e., radius and ulna).
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Poland Syndrome
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Causes of Poland Syndrome
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According to reports in the medical literature, an overwhelming majority of cases appear to occur randomly for unknown reasons (sporadically) in the absence of a family history. However, in some very rare cases, familial patterns have been reported, including occurrence of the condition in a parent and child and in siblings born to unaffected parents. Some researchers suggest that apparently familial cases may result from inherited susceptibility to a certain event or anomaly (such as early interruption of blood flow) that may predispose to the syndrome (see directly below).Poland Syndrome is sometimes referred to as Poland sequence. A “sequence” (or anomalad) refers to a pattern of malformations derived from a single anomaly. According to some investigators, the primary defect in Poland Syndrome may be impaired development of a certain artery or other mechanical factors that may result in diminished or interrupted blood flow during early embryonic growth. The term “Subclavian Artery Supply Disruption Sequence” has been suggested for a group of conditions that may occur due to disruption of blood flow through particular arteries (i.e., subclavian artery, vertebral artery, and/or their branches) at or around the sixth week of embryonic development. Such conditions include Poland Syndrome, Moebius Syndrome, Klippel-Feil Syndrome, and Sprengel deformity. The specific pattern of defects that results is thought to depend on the particular site and degree of the diminished blood flow. (For further information on Moebius Syndrome, see the “Related Disorders” section below. For more on Klippel-Feil Syndrome and Sprengel deformity, choose “Klippel” or “Sprengel” as your search term in the Rare Disease Database.)
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Causes of Poland Syndrome. According to reports in the medical literature, an overwhelming majority of cases appear to occur randomly for unknown reasons (sporadically) in the absence of a family history. However, in some very rare cases, familial patterns have been reported, including occurrence of the condition in a parent and child and in siblings born to unaffected parents. Some researchers suggest that apparently familial cases may result from inherited susceptibility to a certain event or anomaly (such as early interruption of blood flow) that may predispose to the syndrome (see directly below).Poland Syndrome is sometimes referred to as Poland sequence. A “sequence” (or anomalad) refers to a pattern of malformations derived from a single anomaly. According to some investigators, the primary defect in Poland Syndrome may be impaired development of a certain artery or other mechanical factors that may result in diminished or interrupted blood flow during early embryonic growth. The term “Subclavian Artery Supply Disruption Sequence” has been suggested for a group of conditions that may occur due to disruption of blood flow through particular arteries (i.e., subclavian artery, vertebral artery, and/or their branches) at or around the sixth week of embryonic development. Such conditions include Poland Syndrome, Moebius Syndrome, Klippel-Feil Syndrome, and Sprengel deformity. The specific pattern of defects that results is thought to depend on the particular site and degree of the diminished blood flow. (For further information on Moebius Syndrome, see the “Related Disorders” section below. For more on Klippel-Feil Syndrome and Sprengel deformity, choose “Klippel” or “Sprengel” as your search term in the Rare Disease Database.)
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Poland Syndrome
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Affects of Poland Syndrome
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Poland Syndrome was named for the investigator (Poland A) who initially described the condition in 1841. According to reports in the medical literature, Poland Syndrome appears to be three times as common in males as females. Estimates of its incidence have ranged from approximately one in 10,000 to one in 100,000 individuals. (Incidence refers to the number of new cases in a particular period.)As noted above, Poland Syndrome affects the right side of the body in approximately 75 percent of cases. In 1998, investigators reported what was thought to be the first known case in which both sides of the body have been affected (bilateral). Researchers described a young girl with bilateral absence of pectoralis muscle, symmetric chest wall deformity, and bilateral hand involvement.
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Affects of Poland Syndrome. Poland Syndrome was named for the investigator (Poland A) who initially described the condition in 1841. According to reports in the medical literature, Poland Syndrome appears to be three times as common in males as females. Estimates of its incidence have ranged from approximately one in 10,000 to one in 100,000 individuals. (Incidence refers to the number of new cases in a particular period.)As noted above, Poland Syndrome affects the right side of the body in approximately 75 percent of cases. In 1998, investigators reported what was thought to be the first known case in which both sides of the body have been affected (bilateral). Researchers described a young girl with bilateral absence of pectoralis muscle, symmetric chest wall deformity, and bilateral hand involvement.
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Poland Syndrome
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Related disorders of Poland Syndrome
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Symptoms of the following disorders may be similar to those of Poland Syndrome. Comparisons may be useful for a differential diagnosis:Several investigators have reported cases in which the features of Poland Syndrome occur in association with Moebius Syndrome. Known as “Poland-Moebius Syndrome,” such cases are characterized by facial paralysis due to impairment of the sixth and seventh cranial nerves (i.e., Moebius Syndrome) associated with the chest wall defects and/or hand malformations (symbrachydactyly) typically seen in Poland Syndrome. Moebius Syndrome may be characterized by a “masklike”, expressionless face; inability to conduct certain eye movements; drooping of the upper eyelids (ptosis); underdevelopment and/or limited mobility of the tongue; poor sucking and swallowing; and speech impairment. Additional features may include a deformity in which the foot is twisted out of shape or position (clubfoot); various other limb defects; mild mental retardation; and/or other abnormalities. Moebius Syndrome typically appears to occur randomly for unknown reasons (sporadically). As mentioned above (see “Causes”), some investigators suggest that the condition may result from early disruption of blood flow through particular arteries during embryonic development (i.e., Subclavian Artery Supply Disruption Sequence). (For more information on this condition, choose “Moebius” as your search term in the Rare Disease Database.)Oromandibular-Limb Hypogenesis Syndromes is a term sometimes used to describe a group of rare conditions characterized by underdevelopment (hypogenesis) of the mouth and jaw (oromandibular) areas; parts of the embryo that eventually develop into the arms, legs, hands, and feet (the limb buds); and possibly other areas in the developing embryo. This “community” of so-called face-limb malformation syndromes includes Moebius Syndrome, Charlie M Syndrome (see below), Hanhart Syndrome, and others. (For more on Hanhart Syndrome, use “Hanhart” as your search term in the Rare Disease Database.) Such conditions typically appear to occur randomly for unknown reasons (sporadically) and may be characterized by extremely variable clinical features. Some researchers believe that these are overlapping syndromes or disease variants representing a spectrum of malformations caused by environmental and/or other factors. As noted earlier, some experts suggest that certain Oromandibular-Limb Hypogenesis Syndromes, such as Moebius Syndrome, may be due to early disruption of blood flow in certain arteries due to various mechanical factors (i.e., Subclavian Artery Supply Disruption Sequence).Charlie M Syndrome is a rare condition characterized by certain distinctive facial and limb malformations. According to reports in the medical literature, there may be disagreement differentiating between Charlie M Syndrome and various other face-limb malformation syndromes. The syndrome is characterized by widely spaced eyes (ocular hypertelorism); a broad nose and small mouth; incomplete closure of the roof of the mouth (cleft palate); an abnormally small jaw (micrognathia); facial nerve paralysis in some cases; absent or cone-shaped front teeth (incisors); and variable, asymmetric abnormalities of the fingers and toes. The condition typically appears to occur randomly for unknown reasons.A number of other conditions may be characterized by certain chest wall defects, hand malformations, and/or other findings similar to those associated with Poland Syndrome. (For further information on such disorders, use the exact disease name in question as your search term in the Rare Disease Database.)
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Related disorders of Poland Syndrome. Symptoms of the following disorders may be similar to those of Poland Syndrome. Comparisons may be useful for a differential diagnosis:Several investigators have reported cases in which the features of Poland Syndrome occur in association with Moebius Syndrome. Known as “Poland-Moebius Syndrome,” such cases are characterized by facial paralysis due to impairment of the sixth and seventh cranial nerves (i.e., Moebius Syndrome) associated with the chest wall defects and/or hand malformations (symbrachydactyly) typically seen in Poland Syndrome. Moebius Syndrome may be characterized by a “masklike”, expressionless face; inability to conduct certain eye movements; drooping of the upper eyelids (ptosis); underdevelopment and/or limited mobility of the tongue; poor sucking and swallowing; and speech impairment. Additional features may include a deformity in which the foot is twisted out of shape or position (clubfoot); various other limb defects; mild mental retardation; and/or other abnormalities. Moebius Syndrome typically appears to occur randomly for unknown reasons (sporadically). As mentioned above (see “Causes”), some investigators suggest that the condition may result from early disruption of blood flow through particular arteries during embryonic development (i.e., Subclavian Artery Supply Disruption Sequence). (For more information on this condition, choose “Moebius” as your search term in the Rare Disease Database.)Oromandibular-Limb Hypogenesis Syndromes is a term sometimes used to describe a group of rare conditions characterized by underdevelopment (hypogenesis) of the mouth and jaw (oromandibular) areas; parts of the embryo that eventually develop into the arms, legs, hands, and feet (the limb buds); and possibly other areas in the developing embryo. This “community” of so-called face-limb malformation syndromes includes Moebius Syndrome, Charlie M Syndrome (see below), Hanhart Syndrome, and others. (For more on Hanhart Syndrome, use “Hanhart” as your search term in the Rare Disease Database.) Such conditions typically appear to occur randomly for unknown reasons (sporadically) and may be characterized by extremely variable clinical features. Some researchers believe that these are overlapping syndromes or disease variants representing a spectrum of malformations caused by environmental and/or other factors. As noted earlier, some experts suggest that certain Oromandibular-Limb Hypogenesis Syndromes, such as Moebius Syndrome, may be due to early disruption of blood flow in certain arteries due to various mechanical factors (i.e., Subclavian Artery Supply Disruption Sequence).Charlie M Syndrome is a rare condition characterized by certain distinctive facial and limb malformations. According to reports in the medical literature, there may be disagreement differentiating between Charlie M Syndrome and various other face-limb malformation syndromes. The syndrome is characterized by widely spaced eyes (ocular hypertelorism); a broad nose and small mouth; incomplete closure of the roof of the mouth (cleft palate); an abnormally small jaw (micrognathia); facial nerve paralysis in some cases; absent or cone-shaped front teeth (incisors); and variable, asymmetric abnormalities of the fingers and toes. The condition typically appears to occur randomly for unknown reasons.A number of other conditions may be characterized by certain chest wall defects, hand malformations, and/or other findings similar to those associated with Poland Syndrome. (For further information on such disorders, use the exact disease name in question as your search term in the Rare Disease Database.)
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Poland Syndrome
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Diagnosis of Poland Syndrome
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The diagnosis of Poland Syndrome is usually made at birth based upon characteristic physical findings, a thorough clinical evaluation, and a variety of specialized tests. Such tests may include advanced imaging techniques, such as a CT scan that can determine the extent to which the muscles may be affected. During CT scanning, a computer and X-rays are used to create a film showing cross-sectional images particular organs or structures within the body. X-ray studies may be used to help identify and characterize specific abnormalities in the hands, forearms, ribs, and/or shoulder blades.
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Diagnosis of Poland Syndrome. The diagnosis of Poland Syndrome is usually made at birth based upon characteristic physical findings, a thorough clinical evaluation, and a variety of specialized tests. Such tests may include advanced imaging techniques, such as a CT scan that can determine the extent to which the muscles may be affected. During CT scanning, a computer and X-rays are used to create a film showing cross-sectional images particular organs or structures within the body. X-ray studies may be used to help identify and characterize specific abnormalities in the hands, forearms, ribs, and/or shoulder blades.
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Poland Syndrome
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Therapies of Poland Syndrome
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TreatmentThe treatment of Poland Syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Plastic surgery may be performed to rebuild the chest wall and to graft ribs into their proper places. In females, plastic surgery may also be performed to construct a breast mound. In some cases, surgery may also be performed to help correct skeletal abnormalities affecting other areas of the body such as the hands. Physical therapy may also be prescribed to help improve any limitations of motion.Genetic counseling will be of benefit for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.
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Therapies of Poland Syndrome. TreatmentThe treatment of Poland Syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Plastic surgery may be performed to rebuild the chest wall and to graft ribs into their proper places. In females, plastic surgery may also be performed to construct a breast mound. In some cases, surgery may also be performed to help correct skeletal abnormalities affecting other areas of the body such as the hands. Physical therapy may also be prescribed to help improve any limitations of motion.Genetic counseling will be of benefit for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.
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Poland Syndrome
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Overview of Polyarteritis Nodosa
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Polyarteritis nodosa is a rare multi-system disorder characterized by widespread inflammation, weakening, and damage to small and medium-sized arteries. Blood vessels in any organ or organ system may be affected, including those supplying the kidneys, heart, intestine, nervous system, and/or skeletal muscles. Damage to affected arteries may result in abnormally increased blood pressure (hypertension), “ballooning” (aneurysm) of an arterial wall, the formation of blood clots (thrombosis), obstruction of blood supply to certain tissues, and/or tissue damage and loss (necrosis) in certain affected areas.The disorder is more common among men, and is more likely to present during early middle age, between 40 and 50 years.Although the exact cause of polyarteritis nodosa is not known, it is clear that an attack may be triggered by any of several drugs or vaccines or by a reaction to infections (either bacterial or viral) such as strep or staph infections or hepatitis B virus. Many researchers suspect that the disorder is due to disturbances of the body’s immune system. Confirming the diagnosis required either a biopsy showing small or medium sized arteries with alternating areas of stenosis (constriction or block) and dilation.
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Overview of Polyarteritis Nodosa. Polyarteritis nodosa is a rare multi-system disorder characterized by widespread inflammation, weakening, and damage to small and medium-sized arteries. Blood vessels in any organ or organ system may be affected, including those supplying the kidneys, heart, intestine, nervous system, and/or skeletal muscles. Damage to affected arteries may result in abnormally increased blood pressure (hypertension), “ballooning” (aneurysm) of an arterial wall, the formation of blood clots (thrombosis), obstruction of blood supply to certain tissues, and/or tissue damage and loss (necrosis) in certain affected areas.The disorder is more common among men, and is more likely to present during early middle age, between 40 and 50 years.Although the exact cause of polyarteritis nodosa is not known, it is clear that an attack may be triggered by any of several drugs or vaccines or by a reaction to infections (either bacterial or viral) such as strep or staph infections or hepatitis B virus. Many researchers suspect that the disorder is due to disturbances of the body’s immune system. Confirming the diagnosis required either a biopsy showing small or medium sized arteries with alternating areas of stenosis (constriction or block) and dilation.
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Polyarteritis Nodosa
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Symptoms of Polyarteritis Nodosa
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Polyarteritis nodosa mainly affects small and medium-sized arteries. Blood vessels in any organ or organ system may be affected, including arteries supplying the kidneys, heart, intestine, nervous system, and/or skeletal muscles. Damage to affected arteries may result in abnormally increased blood pressure (hypertension), “ballooning” (aneurysm) of an arterial wall, the formation of blood clots (thrombosis), obstruction of blood supply to certain tissues, and/or tissue damage and loss (necrosis) in certain affected areas. Joint, muscle, abdominal and testicular pain may occur. The small and medium-sized arteries of the kidneys are most often involved. The lungs are much less commonly affected.
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Symptoms of Polyarteritis Nodosa. Polyarteritis nodosa mainly affects small and medium-sized arteries. Blood vessels in any organ or organ system may be affected, including arteries supplying the kidneys, heart, intestine, nervous system, and/or skeletal muscles. Damage to affected arteries may result in abnormally increased blood pressure (hypertension), “ballooning” (aneurysm) of an arterial wall, the formation of blood clots (thrombosis), obstruction of blood supply to certain tissues, and/or tissue damage and loss (necrosis) in certain affected areas. Joint, muscle, abdominal and testicular pain may occur. The small and medium-sized arteries of the kidneys are most often involved. The lungs are much less commonly affected.
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Polyarteritis Nodosa
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Causes of Polyarteritis Nodosa
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The exact cause of polyarteritis nodosa is not known. In the majority of patients no predisposing cause has been found. Unidentified bacterial and/or viral infections may be a cause. Polyarteritis nodosa has been observed in drug abusers, particularly those using amphetamines, and in patients with hepatitis B (infection of the liver). (For more information on this disorder, choose “Hepatitis B” as your search term in the Rare Disease Database.) This disorder has also been linked to an allergic reaction to some drugs and vaccines.Most scientists believe that polyarteritis nodosa is an autoimmune disease. Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons. Recent research suggests that a bacterial infection may initially trigger onset of polyarteritis nodosa causing an abnormal immune response to infection. Treatment of polyarteritis nodosa usually involves drugs that alter the immune system.
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Causes of Polyarteritis Nodosa. The exact cause of polyarteritis nodosa is not known. In the majority of patients no predisposing cause has been found. Unidentified bacterial and/or viral infections may be a cause. Polyarteritis nodosa has been observed in drug abusers, particularly those using amphetamines, and in patients with hepatitis B (infection of the liver). (For more information on this disorder, choose “Hepatitis B” as your search term in the Rare Disease Database.) This disorder has also been linked to an allergic reaction to some drugs and vaccines.Most scientists believe that polyarteritis nodosa is an autoimmune disease. Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons. Recent research suggests that a bacterial infection may initially trigger onset of polyarteritis nodosa causing an abnormal immune response to infection. Treatment of polyarteritis nodosa usually involves drugs that alter the immune system.
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Affects of Polyarteritis Nodosa
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Polyarteritis nodosa usually affects people between 40 and 50 years of age, but it may occur in any age group. It affects approximately 1 in 100,000 people. Men appear to be affected two to three times more often than women.
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Affects of Polyarteritis Nodosa. Polyarteritis nodosa usually affects people between 40 and 50 years of age, but it may occur in any age group. It affects approximately 1 in 100,000 people. Men appear to be affected two to three times more often than women.
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Related disorders of Polyarteritis Nodosa
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Symptoms of the following disorders can be similar to those of polyarteritis nodosa. Comparisons may be useful for a differential diagnosis:Microscopic polyangiitis (formerly known as microscopic polyarteritis) can have inflammation of arteries that is clinically and pathologically indistinguishable from polyarteritis nodosa, but, unlike polyarteritis nodosa, this form of systemic vasculitis also has inflammation of vessels smaller than arteries, including arterioles, capillaries and venules. This small vessel involvement often involvers the venules in the skin (causing hemorrhage called purpura), capillaries in the lungs (causing pulmonary hemorrhage) and capillaries in the filters of the kidneys (causing glomerulonephritis). Microscopic polyangiitis is closely related to Wegener’s granulomatosis and Churg-Strauss syndrome; and all three are associated with anti-neutrophil cytoplasmic autoantibodies (ANCA) in the blood.Wegener's granulomatosis occurs in the 4th or 5th decade of life and has a slight male preponderance. It typically involves the upper and lower respiratory tracts and kidney. This disorder usually progresses into a generalized inflammation of the blood vessels and kidney. (For more information on this disorder, choose “Wegener” as your search term in the Rare Disease Database.)Churg-Strauss syndrome is a lung disorder often occurring as a complication of other disorders that affect the arteries. Allergenic blood vessel inflammation, (angiitis or vasculitis), is usually accompanied by many inflammatory nodular lesions. (For more information on this disorder, choose “Churg-Strauss” as your search term in the Rare Disease Database.)Takayasu arteritis (aortic arch syndrome) is an inflammation of the walls of large and mid-sized arteries followed by fibrosis and thickening. It affects mainly women. (For more information on this disorder, choose “Takayasu” as your search term in the Rare Disease Database.)Giant cell arteritis is a disease that affects the large arteries and occasionally the small ones. Cranial arteries are often affected causing headaches, and scalp tenderness. (For more information on this disorder, choose “Giant Cell Arteritis” as your search term in the Rare Disease Database.)Cogan's syndrome is a very rare polyarteritis-type disorder. It is characterized by interstitial keratitis, vertigo, tinnitus, and hearing loss. This is often associated with other systemic disease symptoms such as: congestive heart failure, intestinal hemorrhage, enlarged spleen, high blood pressure, and muscle and bone symptoms. Treatment may consist of the use of corticosteroid drug therapy and when started early in the disease can result in clearing of inflamed eyes and in hearing recovery. Other symptoms may respond to treatment specific to that disorder. Cogan's syndrome can occur at any age and affects men and women equally.
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Related disorders of Polyarteritis Nodosa. Symptoms of the following disorders can be similar to those of polyarteritis nodosa. Comparisons may be useful for a differential diagnosis:Microscopic polyangiitis (formerly known as microscopic polyarteritis) can have inflammation of arteries that is clinically and pathologically indistinguishable from polyarteritis nodosa, but, unlike polyarteritis nodosa, this form of systemic vasculitis also has inflammation of vessels smaller than arteries, including arterioles, capillaries and venules. This small vessel involvement often involvers the venules in the skin (causing hemorrhage called purpura), capillaries in the lungs (causing pulmonary hemorrhage) and capillaries in the filters of the kidneys (causing glomerulonephritis). Microscopic polyangiitis is closely related to Wegener’s granulomatosis and Churg-Strauss syndrome; and all three are associated with anti-neutrophil cytoplasmic autoantibodies (ANCA) in the blood.Wegener's granulomatosis occurs in the 4th or 5th decade of life and has a slight male preponderance. It typically involves the upper and lower respiratory tracts and kidney. This disorder usually progresses into a generalized inflammation of the blood vessels and kidney. (For more information on this disorder, choose “Wegener” as your search term in the Rare Disease Database.)Churg-Strauss syndrome is a lung disorder often occurring as a complication of other disorders that affect the arteries. Allergenic blood vessel inflammation, (angiitis or vasculitis), is usually accompanied by many inflammatory nodular lesions. (For more information on this disorder, choose “Churg-Strauss” as your search term in the Rare Disease Database.)Takayasu arteritis (aortic arch syndrome) is an inflammation of the walls of large and mid-sized arteries followed by fibrosis and thickening. It affects mainly women. (For more information on this disorder, choose “Takayasu” as your search term in the Rare Disease Database.)Giant cell arteritis is a disease that affects the large arteries and occasionally the small ones. Cranial arteries are often affected causing headaches, and scalp tenderness. (For more information on this disorder, choose “Giant Cell Arteritis” as your search term in the Rare Disease Database.)Cogan's syndrome is a very rare polyarteritis-type disorder. It is characterized by interstitial keratitis, vertigo, tinnitus, and hearing loss. This is often associated with other systemic disease symptoms such as: congestive heart failure, intestinal hemorrhage, enlarged spleen, high blood pressure, and muscle and bone symptoms. Treatment may consist of the use of corticosteroid drug therapy and when started early in the disease can result in clearing of inflamed eyes and in hearing recovery. Other symptoms may respond to treatment specific to that disorder. Cogan's syndrome can occur at any age and affects men and women equally.
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Diagnosis of Polyarteritis Nodosa
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Since there are no blood or other chemical tests to indicate the presence of this disorder, the diagnosis is based upon physical examination and the exclusion of other likely candidates for diagnosis. In suspected cases, biopsy of the blood vessel wall (lumen) is necessary to confirm the presence of the typical lesions. Biopsies of the kidney or liver may also be required.
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Diagnosis of Polyarteritis Nodosa. Since there are no blood or other chemical tests to indicate the presence of this disorder, the diagnosis is based upon physical examination and the exclusion of other likely candidates for diagnosis. In suspected cases, biopsy of the blood vessel wall (lumen) is necessary to confirm the presence of the typical lesions. Biopsies of the kidney or liver may also be required.
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Therapies of Polyarteritis Nodosa
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TreatmentTreatment of polyarteritis nodosa usually consists of the use of corticosteroid drugs, such as prednisone, to suppress the immune system and relieve inflammation. Cyclophosphamide has also been used for this purpose. Treatment for control of hypertension may also be indicated. Surgical intervention is sometimes required in cases of gastrointestinal involvement. Other treatment is symptomatic and supportive.
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Therapies of Polyarteritis Nodosa. TreatmentTreatment of polyarteritis nodosa usually consists of the use of corticosteroid drugs, such as prednisone, to suppress the immune system and relieve inflammation. Cyclophosphamide has also been used for this purpose. Treatment for control of hypertension may also be indicated. Surgical intervention is sometimes required in cases of gastrointestinal involvement. Other treatment is symptomatic and supportive.
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Overview of Polycystic Liver Disease
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SummaryPolycystic liver disease, also called autosomal dominant polycystic liver disease (ADPLD) is an inherited disorder estimated to affect less than 1 in 10,000 people. It is characterized by the progressive growth of cysts of various sizes scattered throughout the liver. People affected by this condition tend to have more and larger cysts as they age and usually start to have symptoms as early as age 30. However, many affected individuals do not have symptoms. Enlargement of the liver (hepatomegaly) can cause abdominal pain and discomfort, shortness of breath (dyspnea), early satiety and gastro-esophageal reflux. Rare complications are hepatic cyst hemorrhage, infection or rupture. Surgical and medical treatment is available to manage the symptoms, but the only definitive treatment for this condition is liver transplant. Most cases are inherited in an autosomal dominant pattern, but some occur in families with no family history of the condition. Sometimes, cysts are found in the liver in association with ADPKD. In fact, most people who have ADPKD have liver cysts.
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Overview of Polycystic Liver Disease. SummaryPolycystic liver disease, also called autosomal dominant polycystic liver disease (ADPLD) is an inherited disorder estimated to affect less than 1 in 10,000 people. It is characterized by the progressive growth of cysts of various sizes scattered throughout the liver. People affected by this condition tend to have more and larger cysts as they age and usually start to have symptoms as early as age 30. However, many affected individuals do not have symptoms. Enlargement of the liver (hepatomegaly) can cause abdominal pain and discomfort, shortness of breath (dyspnea), early satiety and gastro-esophageal reflux. Rare complications are hepatic cyst hemorrhage, infection or rupture. Surgical and medical treatment is available to manage the symptoms, but the only definitive treatment for this condition is liver transplant. Most cases are inherited in an autosomal dominant pattern, but some occur in families with no family history of the condition. Sometimes, cysts are found in the liver in association with ADPKD. In fact, most people who have ADPKD have liver cysts.
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Symptoms of Polycystic Liver Disease
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Polycystic liver disease is characterized by the growth of more than 10 cysts in the liver, ranging in size from a few millimeters to over 15 cm in diameter. Symptoms usually begin to show in the third decade, as cysts grow and increase in number with age. Some people begin to have symptoms in early adulthood, but many affected individuals do not have symptoms. The growth and accumulation of cysts can cause enlargement of the liver (hepatomegaly) and compression of adjacent anatomical structures, leading to abdominal pain and discomfort, shortness of breath (dyspnea), indigestion (dyspepsia), gastro-esophageal reflux and limited mobility. More rarely, liver cysts can also compress the bile duct and lead to yellowing of the skin (jaundice). Compression of the blood vessels of the liver by cysts can lead to accumulation of fluid in the abdomen (ascites), bleeding and high blood pressure in the blood flow from intestines to the liver (portal hypertension). In rare cases, patients can suffer from cyst bleeding (hepatic cyst hemorrhage) or a cyst can be infected by bacteria (hepatic cyst infection), causing pain and fever. Infrequently, large liver cysts may rupture, causing severe abdominal pain. Even with the presence of many cysts, the liver of individuals with polycystic liver disease functions normally.
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Symptoms of Polycystic Liver Disease. Polycystic liver disease is characterized by the growth of more than 10 cysts in the liver, ranging in size from a few millimeters to over 15 cm in diameter. Symptoms usually begin to show in the third decade, as cysts grow and increase in number with age. Some people begin to have symptoms in early adulthood, but many affected individuals do not have symptoms. The growth and accumulation of cysts can cause enlargement of the liver (hepatomegaly) and compression of adjacent anatomical structures, leading to abdominal pain and discomfort, shortness of breath (dyspnea), indigestion (dyspepsia), gastro-esophageal reflux and limited mobility. More rarely, liver cysts can also compress the bile duct and lead to yellowing of the skin (jaundice). Compression of the blood vessels of the liver by cysts can lead to accumulation of fluid in the abdomen (ascites), bleeding and high blood pressure in the blood flow from intestines to the liver (portal hypertension). In rare cases, patients can suffer from cyst bleeding (hepatic cyst hemorrhage) or a cyst can be infected by bacteria (hepatic cyst infection), causing pain and fever. Infrequently, large liver cysts may rupture, causing severe abdominal pain. Even with the presence of many cysts, the liver of individuals with polycystic liver disease functions normally.
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Causes of Polycystic Liver Disease
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Changes (mutations or pathogenic variants) in many different genes can cause ADPLD. Mutations in PRKCSH cause about 20% of cases and mutations in SEC6 cause about 15% of cases. Other genes associated with ADPLD include ALG8, GANAB, LRP5, PKHD and SEC61B3. However, less than 50% of individuals with polycystic liver disease have a mutation in one of these genes, so other genes may be involved in this condition.Pathogenic variants in SEC63 and PRKCSH lead to defects in processing, folding and translocation of newly synthesized glycoproteins. This is associated with embryological malformations which contributes to the formation of fluid-filled cysts throughout the liver.Most cases of polycystic liver disease are inherited in an autosomal dominant pattern. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
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Causes of Polycystic Liver Disease. Changes (mutations or pathogenic variants) in many different genes can cause ADPLD. Mutations in PRKCSH cause about 20% of cases and mutations in SEC6 cause about 15% of cases. Other genes associated with ADPLD include ALG8, GANAB, LRP5, PKHD and SEC61B3. However, less than 50% of individuals with polycystic liver disease have a mutation in one of these genes, so other genes may be involved in this condition.Pathogenic variants in SEC63 and PRKCSH lead to defects in processing, folding and translocation of newly synthesized glycoproteins. This is associated with embryological malformations which contributes to the formation of fluid-filled cysts throughout the liver.Most cases of polycystic liver disease are inherited in an autosomal dominant pattern. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
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Affects of Polycystic Liver Disease
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Polycystic liver disease is estimated to affect less than 1 in 10,000 people. This is likely an underestimate because many people with the condition do not have symptoms. Males and females are affected in equal numbers, but most patients with symptoms and with severe disease are women. The suggested cause of this difference is that female sex hormones, such as estrogen, contribute to growth of liver cysts. Oral contraceptives and estrogen replacement therapy are also associated with more severe disease]. Cysts can begin to grow at any age but are rare in childhood and more common with age. The age at which symptoms begin to occur varies with individuals but is usually after 30 years old.
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Affects of Polycystic Liver Disease. Polycystic liver disease is estimated to affect less than 1 in 10,000 people. This is likely an underestimate because many people with the condition do not have symptoms. Males and females are affected in equal numbers, but most patients with symptoms and with severe disease are women. The suggested cause of this difference is that female sex hormones, such as estrogen, contribute to growth of liver cysts. Oral contraceptives and estrogen replacement therapy are also associated with more severe disease]. Cysts can begin to grow at any age but are rare in childhood and more common with age. The age at which symptoms begin to occur varies with individuals but is usually after 30 years old.
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Related disorders of Polycystic Liver Disease
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Symptoms of the following disorders can be similar to those of polycystic liver disease. Comparisons may be useful for a differential diagnosis:Caroli syndrome is a rare congenital liver disorder characterized by enlargement (dilation) of the small branches of the bile ducts inside the liver. If symptoms occur, the most common are abdominal pain, fever and jaundice. Caroli syndrome is often associated with autosomal recessive polycystic kidney disease (ARPKD). (For more information on this disorder, choose “Caroli” as your search term in the Rare Disease Database.).Congenital hepatic fibrosis is a rare inherited disorder that is associated with autosomal recessive polycystic kidney disease (AR-PKD). (For more information on this disorder, choose “hepatic fibrosis” as your search term in the Rare Disease Database.)Bile duct (choledochal) cysts may develop if the common bile duct is malformed, leading to the formation of a cyst. This condition typically appears between the ages of two or three years and adolescence. Bile backs up into the liver causing jaundice. If the cyst becomes infected, surgical removal is necessary. If untreated, cysts in the common bile duct may cause extensive scarring (cirrhosis) of the liver.Neoplastic cysts are abnormal tissue growths that may be benign or malignant. Benign tumors may cause abdominal discomfort or bleeding within the sac that lines the abdominal cavity (peritoneum). Liver function is usually normal with benign tumors. Malignant tumors may cause loss of appetite, weight loss, pain and fever. The liver may be enlarged, tender and hard. Excess watery fluid in the spaces between the tissues and organs in the abdomen (ascites) may also occur. Jaundice is usually absent or mild but may worsen with time.Hydatid cyst disease is transmitted to humans by animals via the ingestion of tapeworm eggs of the echinococcus species. The eggs enter the blood by penetrating the intestinal walls. They then develop into larvae that form cysts, most commonly in the liver, but also in the lungs, brain and visceral organs. Hydatid cysts in the liver cause symptoms similar to cysts from polycystic liver disease including hepatomegaly, abdominal pain, indigestion (dyspepsia), and jaundice.
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Related disorders of Polycystic Liver Disease. Symptoms of the following disorders can be similar to those of polycystic liver disease. Comparisons may be useful for a differential diagnosis:Caroli syndrome is a rare congenital liver disorder characterized by enlargement (dilation) of the small branches of the bile ducts inside the liver. If symptoms occur, the most common are abdominal pain, fever and jaundice. Caroli syndrome is often associated with autosomal recessive polycystic kidney disease (ARPKD). (For more information on this disorder, choose “Caroli” as your search term in the Rare Disease Database.).Congenital hepatic fibrosis is a rare inherited disorder that is associated with autosomal recessive polycystic kidney disease (AR-PKD). (For more information on this disorder, choose “hepatic fibrosis” as your search term in the Rare Disease Database.)Bile duct (choledochal) cysts may develop if the common bile duct is malformed, leading to the formation of a cyst. This condition typically appears between the ages of two or three years and adolescence. Bile backs up into the liver causing jaundice. If the cyst becomes infected, surgical removal is necessary. If untreated, cysts in the common bile duct may cause extensive scarring (cirrhosis) of the liver.Neoplastic cysts are abnormal tissue growths that may be benign or malignant. Benign tumors may cause abdominal discomfort or bleeding within the sac that lines the abdominal cavity (peritoneum). Liver function is usually normal with benign tumors. Malignant tumors may cause loss of appetite, weight loss, pain and fever. The liver may be enlarged, tender and hard. Excess watery fluid in the spaces between the tissues and organs in the abdomen (ascites) may also occur. Jaundice is usually absent or mild but may worsen with time.Hydatid cyst disease is transmitted to humans by animals via the ingestion of tapeworm eggs of the echinococcus species. The eggs enter the blood by penetrating the intestinal walls. They then develop into larvae that form cysts, most commonly in the liver, but also in the lungs, brain and visceral organs. Hydatid cysts in the liver cause symptoms similar to cysts from polycystic liver disease including hepatomegaly, abdominal pain, indigestion (dyspepsia), and jaundice.
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Diagnosis of Polycystic Liver Disease
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Magnetic resonance imaging (MRI) computed tomography (CT) scan and ultrasound (US) are used to take pictures of the liver to see if cysts are present. The images are used for diagnosis and monitoring of cysts growth. Molecular genetic testing is available to look for mutations in the SEC63, LRP5 and PRKCSH genes and may be particularly helpful in individuals that inherited the disease from one of their parents. It is also possible to test for blood levels of two markers of liver and bile duct disease: gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP). These two markers might be elevated in patients with severe polycystic liver disease.
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Diagnosis of Polycystic Liver Disease. Magnetic resonance imaging (MRI) computed tomography (CT) scan and ultrasound (US) are used to take pictures of the liver to see if cysts are present. The images are used for diagnosis and monitoring of cysts growth. Molecular genetic testing is available to look for mutations in the SEC63, LRP5 and PRKCSH genes and may be particularly helpful in individuals that inherited the disease from one of their parents. It is also possible to test for blood levels of two markers of liver and bile duct disease: gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP). These two markers might be elevated in patients with severe polycystic liver disease.
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Therapies of Polycystic Liver Disease
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Treatment
Treatment may not be necessary in many cases of polycystic liver disease and is only indicated in severely affected or symptomatic patients. Large cysts (>5 cm) can be treated with aspiration sclerotherapy, which includes puncture of the cyst, removal of the fluid and treatment of the cyst wall with a chemical allowing tissues to harden, (sclerosing agent) such as ethanol. When multiple large cysts are causing symptoms, keyhole surgery can be a treatment option. The surgeon punctures and then removes the ‘roof’ of the cysts. This procedure is called laparoscopic fenestration. It is also possible to remove parts of the liver (hepatic resection) to reduce symptoms related to hepatomegaly. The only definitive treatment of PLD, used in only the most severe cases, is liver transplant.Medication to slow down cyst growth and fluid secretion in the liver (somatostatin analogs, namely octreotide and lanreotide) is also useful in reducing liver volume. Because they are very expensive, these medications are typically reserved for patients with moderate to severe disease with reduced quality of life. Referral to a specialized center is recommended. As estrogen promotes cysts growth, it is recommended for women diagnosed with polycystic liver disease to stop hormonal contraceptives or estrogen replacement therapy.Genetic counseling is recommended for patients and their families.
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Therapies of Polycystic Liver Disease. Treatment
Treatment may not be necessary in many cases of polycystic liver disease and is only indicated in severely affected or symptomatic patients. Large cysts (>5 cm) can be treated with aspiration sclerotherapy, which includes puncture of the cyst, removal of the fluid and treatment of the cyst wall with a chemical allowing tissues to harden, (sclerosing agent) such as ethanol. When multiple large cysts are causing symptoms, keyhole surgery can be a treatment option. The surgeon punctures and then removes the ‘roof’ of the cysts. This procedure is called laparoscopic fenestration. It is also possible to remove parts of the liver (hepatic resection) to reduce symptoms related to hepatomegaly. The only definitive treatment of PLD, used in only the most severe cases, is liver transplant.Medication to slow down cyst growth and fluid secretion in the liver (somatostatin analogs, namely octreotide and lanreotide) is also useful in reducing liver volume. Because they are very expensive, these medications are typically reserved for patients with moderate to severe disease with reduced quality of life. Referral to a specialized center is recommended. As estrogen promotes cysts growth, it is recommended for women diagnosed with polycystic liver disease to stop hormonal contraceptives or estrogen replacement therapy.Genetic counseling is recommended for patients and their families.
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Overview of Polycythemia Vera
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Summary Polycythemia vera is a rare, chronic disorder involving the overproduction of blood cells in the bone marrow (myeloproliferation). The overproduction of red blood cells is most dramatic, but the production of white blood cells and platelets are also elevated in most cases. Since red blood cells are overproduced in the marrow, this leads to abnormally high numbers of circulating red blood cells (red blood mass) within the blood. Consequently, the blood thickens and increases in volume, a condition called hyperviscosity. Thickened blood may not flow through smaller blood vessels properly. A variety of symptoms can occur in individuals with polycythemia vera including nonspecific symptoms such as headaches, fatigue, weakness, dizziness or itchy skin; an enlarged spleen (splenomegaly); a variety of gastrointestinal issues; and the risk of blood clot formation, which may prevent blood flow to vital organs. More than 90 percent of individuals with polycythemia vera have a variation (mutation) in the JAK2 gene. The exact role that this variation plays in the development of polycythemia vera is not yet known. Introduction Polycythemia vera was first reported in the medical literature in 1892. The term “myeloproliferative disorder” (MPD) was first used to described polycythemia vera and related disorders in 1951. In 2008, the World Health Organization reclassified MPDs to “myeloproliferative neoplasms” (MPNs) to reflect the consensus that these diseases are blood cancers (neoplasms). This group of disorders is characterized by the overproduction (proliferation) of one or more of the three main blood cell lines – red or white blood cells or platelets. Red blood cells carry oxygen to the body. White blood cells fight infection. Platelets are involved in clotting of the blood in response to injury. Three other disorders are commonly classified as MPNs: chronic myeloid leukemia, essential thrombocythemia and idiopathic myelofibrosis. Because MPNs are characterized by uncontrolled cell growth, they may also be classified as blood cancers.
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Overview of Polycythemia Vera. Summary Polycythemia vera is a rare, chronic disorder involving the overproduction of blood cells in the bone marrow (myeloproliferation). The overproduction of red blood cells is most dramatic, but the production of white blood cells and platelets are also elevated in most cases. Since red blood cells are overproduced in the marrow, this leads to abnormally high numbers of circulating red blood cells (red blood mass) within the blood. Consequently, the blood thickens and increases in volume, a condition called hyperviscosity. Thickened blood may not flow through smaller blood vessels properly. A variety of symptoms can occur in individuals with polycythemia vera including nonspecific symptoms such as headaches, fatigue, weakness, dizziness or itchy skin; an enlarged spleen (splenomegaly); a variety of gastrointestinal issues; and the risk of blood clot formation, which may prevent blood flow to vital organs. More than 90 percent of individuals with polycythemia vera have a variation (mutation) in the JAK2 gene. The exact role that this variation plays in the development of polycythemia vera is not yet known. Introduction Polycythemia vera was first reported in the medical literature in 1892. The term “myeloproliferative disorder” (MPD) was first used to described polycythemia vera and related disorders in 1951. In 2008, the World Health Organization reclassified MPDs to “myeloproliferative neoplasms” (MPNs) to reflect the consensus that these diseases are blood cancers (neoplasms). This group of disorders is characterized by the overproduction (proliferation) of one or more of the three main blood cell lines – red or white blood cells or platelets. Red blood cells carry oxygen to the body. White blood cells fight infection. Platelets are involved in clotting of the blood in response to injury. Three other disorders are commonly classified as MPNs: chronic myeloid leukemia, essential thrombocythemia and idiopathic myelofibrosis. Because MPNs are characterized by uncontrolled cell growth, they may also be classified as blood cancers.
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Symptoms of Polycythemia Vera
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The symptoms of polycythemia vera usually develop slowly over many years. Often, the disorder is found incidentally on a blood test as part of a routine exam before noticeable symptoms occur. Occasionally, affected individuals may report vague, nonspecific symptoms that eventually lead to diagnosis of the disorder.Many individuals with polycythemia vera slowly development a variety of general, nonspecific symptoms that are common to many disorders such as headaches, fatigue, weakness, dizziness, excessive sweating especially at night, and itchy skin that, in severe cases, may be worse after taking a shower or a warm bath. Additional symptoms may occur in some affected individuals including blurred vision, ringing in the ears (tinnitus), and abnormal redness of the skin especially on the face.Eventually, the spleen becomes involved. The spleen is an organ located in upper left part of the abdomen that filters out worn out blood cells. It often becomes abnormally enlarged in individuals with polycythemia vera as it attempts to clear a greater number of blood cells than normal – a condition called splenomegaly. Splenomegaly may cause an affected individual to have a bloated or full feeling in the abdomen.Less common symptoms associated with polycythemia vera include a tendency to bruise easily, frequent nosebleeds or bleeding from the gums, enlargement of the liver (hepatomegaly), and erythromelalgia, a condition characterized by a reddened or purplish appearance to the skin of the hands and feet. The skin may feel warm to the touch. Erythromelalgia can also cause a painful, burning sensation or swelling of the affected areas.Some individuals with polycythemia vera may develop symptoms secondary to reduced blood flow (due to thickening of the blood) and abnormalities affecting the platelets, which can increase a person’s risk of developing blood clots. Complications that occur due to blood clots may be referred as thrombotic events and, in rare cases, can be the first obvious sign of polycythemia vera. Specific symptoms depend upon where a blood clot forms. A blood clot can cause a stroke, chest pain (angina), a heart attack, deep vein thrombosis (DVT) or a pulmonary embolism. DVT occurs when a blood clot forms in the legs may cause the legs to become painful and swollen. A pulmonary embolism occurs when a clot forms in the lungs or when a piece of a DVT breaks off and travels through the bloodstream eventually becoming stuck in the pulmonary artery. A pulmonary embolism can cause breathlessness, a sudden pain the chest, exhaustion, or life-threatening complications such as high blood pressure of the pulmonary artery.Some individuals with polycythemia vera have developed Budd-Chiari syndrome, a condition in which a blood clot forms in the main blood vessel leading to the liver (hepatic vein thrombosis). Symptoms of Budd-Chiari syndrome include pain in the upper right part of the abdomen, an abnormally enlarged liver (hepatomegaly), yellowing of the skin and the whites of the eyes (jaundice), and/or accumulation of fluid in the space (peritoneal cavity) between the two layers of the membrane that line the stomach (ascites).The abnormal proliferation of red blood cells may also cause peptic ulcers, gout, and kidney stones. Peptic ulcers are open sores on the lining of the gastrointestinal tract, which may cause bleeding (hemorrhaging) within the gastrointestinal tract. Gout is an inflammation of the joints caused by a build-up of uric acid. Abnormally high levels of uric acid can also cause kidney stones. Gout and kidney stone associated with polycythemia vera occur due to the high turnover of red blood cells, which results in higher-than-normal uric acid production.Polycythemia vera may eventually “burn out” so that scar tissue replaces the marrow and the disorder resembles idiopathic myelofibrosis. This may also be referred to as the “spent phase” of polycythemia vera. When this occurs, the marrow can no longer produce blood cells resulting in low levels of healthy, functioning red blood cells (anemia), platelets (thrombocytopenia) and white blood cells (leukopenia). In rare cases, polycythemia vera may eventually progress into a form of leukemia known as acute myeloid leukemia.
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Symptoms of Polycythemia Vera. The symptoms of polycythemia vera usually develop slowly over many years. Often, the disorder is found incidentally on a blood test as part of a routine exam before noticeable symptoms occur. Occasionally, affected individuals may report vague, nonspecific symptoms that eventually lead to diagnosis of the disorder.Many individuals with polycythemia vera slowly development a variety of general, nonspecific symptoms that are common to many disorders such as headaches, fatigue, weakness, dizziness, excessive sweating especially at night, and itchy skin that, in severe cases, may be worse after taking a shower or a warm bath. Additional symptoms may occur in some affected individuals including blurred vision, ringing in the ears (tinnitus), and abnormal redness of the skin especially on the face.Eventually, the spleen becomes involved. The spleen is an organ located in upper left part of the abdomen that filters out worn out blood cells. It often becomes abnormally enlarged in individuals with polycythemia vera as it attempts to clear a greater number of blood cells than normal – a condition called splenomegaly. Splenomegaly may cause an affected individual to have a bloated or full feeling in the abdomen.Less common symptoms associated with polycythemia vera include a tendency to bruise easily, frequent nosebleeds or bleeding from the gums, enlargement of the liver (hepatomegaly), and erythromelalgia, a condition characterized by a reddened or purplish appearance to the skin of the hands and feet. The skin may feel warm to the touch. Erythromelalgia can also cause a painful, burning sensation or swelling of the affected areas.Some individuals with polycythemia vera may develop symptoms secondary to reduced blood flow (due to thickening of the blood) and abnormalities affecting the platelets, which can increase a person’s risk of developing blood clots. Complications that occur due to blood clots may be referred as thrombotic events and, in rare cases, can be the first obvious sign of polycythemia vera. Specific symptoms depend upon where a blood clot forms. A blood clot can cause a stroke, chest pain (angina), a heart attack, deep vein thrombosis (DVT) or a pulmonary embolism. DVT occurs when a blood clot forms in the legs may cause the legs to become painful and swollen. A pulmonary embolism occurs when a clot forms in the lungs or when a piece of a DVT breaks off and travels through the bloodstream eventually becoming stuck in the pulmonary artery. A pulmonary embolism can cause breathlessness, a sudden pain the chest, exhaustion, or life-threatening complications such as high blood pressure of the pulmonary artery.Some individuals with polycythemia vera have developed Budd-Chiari syndrome, a condition in which a blood clot forms in the main blood vessel leading to the liver (hepatic vein thrombosis). Symptoms of Budd-Chiari syndrome include pain in the upper right part of the abdomen, an abnormally enlarged liver (hepatomegaly), yellowing of the skin and the whites of the eyes (jaundice), and/or accumulation of fluid in the space (peritoneal cavity) between the two layers of the membrane that line the stomach (ascites).The abnormal proliferation of red blood cells may also cause peptic ulcers, gout, and kidney stones. Peptic ulcers are open sores on the lining of the gastrointestinal tract, which may cause bleeding (hemorrhaging) within the gastrointestinal tract. Gout is an inflammation of the joints caused by a build-up of uric acid. Abnormally high levels of uric acid can also cause kidney stones. Gout and kidney stone associated with polycythemia vera occur due to the high turnover of red blood cells, which results in higher-than-normal uric acid production.Polycythemia vera may eventually “burn out” so that scar tissue replaces the marrow and the disorder resembles idiopathic myelofibrosis. This may also be referred to as the “spent phase” of polycythemia vera. When this occurs, the marrow can no longer produce blood cells resulting in low levels of healthy, functioning red blood cells (anemia), platelets (thrombocytopenia) and white blood cells (leukopenia). In rare cases, polycythemia vera may eventually progress into a form of leukemia known as acute myeloid leukemia.
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Polycythemia Vera
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Causes of Polycythemia Vera
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Polycythemia vera is caused by a malignant change in the genetic material (DNA) within a single cell of the bone marrow (clonal disorder). Bone marrow is the soft, spongy material found inside bone where most blood cell production occurs. The underlying reason why this malignant change occurs is unknown.This change is acquired meaning that it occurs after conception and is not inherited. Researchers have determined that approximately 90 percent of individuals with polycythemia vera have a variation in the JAK2 gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, absent, or overproduced. Depending upon the functions of the particular protein, this can affect many organ systems of the body.The JAK2 gene produces a protein called a kinase, specifically Janus kinase 2. Kinases are very powerful drivers of cell growth. In people with polycythemia vera, the JAK2 gene is overactive because of the underlying genetic change.The original defective cell in the bone marrow of individuals with polycythemia vera is a hematopoietic stem cell – a specialized cell that grows and eventually develops into one of the three main types of blood cells: red blood cells, white blood cells or platelets. A change in the DNA of a single hematopoietic stem cell causes the abnormal cell to continually reproduce itself eventually becoming the predominant hematopoietic stem cell in the bone marrow. Normally, the kidneys produce a hormone called erythropoietin. This hormone binds to receptors found on hematopoietic stem cells. Because the JAK2 gene is overactive, these cells derived from the original defective hematopoietic stem cell continue to grow and divide even in the absence of erythropoietin. These rapidly growing cells clog the bone marrow and when the break down and die cause scar tissue to form.Polycythemia vera and some similar disorders have, in rare cases, affected multiple members of the same family suggesting that genetic factors in addition to a JAK2 gene mutation may play a role in the development of the disorder. However, researchers have not established a strong familial predisposition in association with polycythemia vera.The symptoms of polycythemia vera occur because of abnormalities affecting the formation of blood cells that result in an overproduction of red blood cells and, to a lesser extent, the overproduction of white blood cells and platelets.
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Causes of Polycythemia Vera. Polycythemia vera is caused by a malignant change in the genetic material (DNA) within a single cell of the bone marrow (clonal disorder). Bone marrow is the soft, spongy material found inside bone where most blood cell production occurs. The underlying reason why this malignant change occurs is unknown.This change is acquired meaning that it occurs after conception and is not inherited. Researchers have determined that approximately 90 percent of individuals with polycythemia vera have a variation in the JAK2 gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, absent, or overproduced. Depending upon the functions of the particular protein, this can affect many organ systems of the body.The JAK2 gene produces a protein called a kinase, specifically Janus kinase 2. Kinases are very powerful drivers of cell growth. In people with polycythemia vera, the JAK2 gene is overactive because of the underlying genetic change.The original defective cell in the bone marrow of individuals with polycythemia vera is a hematopoietic stem cell – a specialized cell that grows and eventually develops into one of the three main types of blood cells: red blood cells, white blood cells or platelets. A change in the DNA of a single hematopoietic stem cell causes the abnormal cell to continually reproduce itself eventually becoming the predominant hematopoietic stem cell in the bone marrow. Normally, the kidneys produce a hormone called erythropoietin. This hormone binds to receptors found on hematopoietic stem cells. Because the JAK2 gene is overactive, these cells derived from the original defective hematopoietic stem cell continue to grow and divide even in the absence of erythropoietin. These rapidly growing cells clog the bone marrow and when the break down and die cause scar tissue to form.Polycythemia vera and some similar disorders have, in rare cases, affected multiple members of the same family suggesting that genetic factors in addition to a JAK2 gene mutation may play a role in the development of the disorder. However, researchers have not established a strong familial predisposition in association with polycythemia vera.The symptoms of polycythemia vera occur because of abnormalities affecting the formation of blood cells that result in an overproduction of red blood cells and, to a lesser extent, the overproduction of white blood cells and platelets.
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Polycythemia Vera
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Affects of Polycythemia Vera
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Polycythemia vera affects slightly more men than women. The disorder is estimated to affect approximately 44 to 57 per 100,000 people in the US. It occurs most often in individuals more than 60 years old, but can affect individuals of any age. It is extremely rare in individuals under 20.
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Affects of Polycythemia Vera. Polycythemia vera affects slightly more men than women. The disorder is estimated to affect approximately 44 to 57 per 100,000 people in the US. It occurs most often in individuals more than 60 years old, but can affect individuals of any age. It is extremely rare in individuals under 20.
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Polycythemia Vera
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nord_982_4
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Related disorders of Polycythemia Vera
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Symptoms of the following disorders can be similar to those of polycythemia vera. Comparisons may be useful for a differential diagnosis.Secondary polycythemia is a general term for the overproduction of red blood cells that occurs as a result of (secondary to) a known cause. Such causes include genetic disorders, certain tumors that may secrete erythropoietin (a hormone that stimulates red blood cell production), conditions that deprive the body of oxygen such as certain lung or heart diseases. Some people living in high altitudes may develop secondary polycythemia in response to poor oxygenation of tissue. Certain kidney disorders can result in the excessive production of erythropoietin and, in turn, overproduction of red blood cells. Therapy in individuals with secondary polycythemia involves treating the underlying disorder or cause of the polycythemia.Primary myelofibrosis is a rare bone marrow disorder that is characterized by abnormalities in blood cell production (hematopoiesis) and scarring (formation of fibrous tissue) within the bone marrow. Bone marrow is the soft, spongy tissue that fills the center of most bones. Bone marrow contains specialized cells called hematopoietic stem cells that grow and eventually develop into one of the three main types of blood cells: red blood cells, white blood cells or platelets. In primary myelofibrosis, a change in the DNA of a single hematopoietic stem cell causes the abnormal cell to continually reproduce itself. Eventually, these abnormal cells crowd out normal, healthy cells in the marrow and, along with scarring within the marrow, disrupt the production of red and white blood cells and platelets. The symptoms associated with primary myelofibrosis vary and are related to the abnormalities affecting blood cell production. Affected individuals may not have symptoms at the time of diagnosis (asymptomatic) may remain symptom-free for many years. Eventually, affected individuals may develop fatigue, fever, frequent infections, pale skin, night sweats and unexplained weight loss. An enlarged (spleen) is a common finding. An enlarged liver (hepatomegaly) may also occur. (For more information on this disorder, choose “primary myelofibrosis” as your search term in the Rare Disease Database.)Essential thrombocythemia (ET) is one of four rare MPNs. Myeloproliferative means uncontrolled production of cells by the bone marrow. Each of the four myeloproliferative neoplasms is characterized by over-production of a different, but essential, type of blood cell resulting in a high concentration of these cells in the blood. Essential thrombocythemia is characterized by overproduction of the precursor cells to blood platelets (megakaryocytes) which, in turn, leads to a vastly increased number of platelets in the blood. Platelets are specialized cells in blood essential for the normal process of clotting. In addition to over-production of platelets, other symptoms and signs of ET may include an enlarged spleen (splenomegaly); bleeding from the gut, gums and/or nose (hemorrhaging); and constricted or blocked arteries (thrombosis). As many as two-thirds of patients are without symptoms (asymptomatic) upon initial examination. Most patients present with symptoms related to small or large vessel thrombosis or minor bleeding. Presentation with a major bleeding episode is very unusual. Clots may occur in the small arteries of the toes and fingers, leading to pain, warmth, tissue death (gangrene) and/or classic erythromelalgia. Erythromelalgia refers to a syndrome of redness and burning pain in the extremities. The incidence of the thrombotic and bleeding episodes is minimized, but not eliminated, with reduction of the platelet count to normal. In some instances, this chronic disorder may be progressive, evolving in relatively rare cases into acute leukemia or myelofibrosis. (For more information on this disorder, choose “essential thrombocythemia” as your search term in the Rare Disease Database.)Chronic myelogenous leukemia is a rare myeloproliferative neoplasm characterized by the excessive development of white blood cells in the spongy tissue found inside large bones of the body (bone marrow), spleen, liver and blood. As the disease progresses, the leukemic cells invade other areas of the body including the intestinal tract, kidneys, lungs, gonads and lymph nodes. There are two phases to chronic myelogenous leukemia. The first phase, or chronic phase, is characterized by a slow, progressive overproduction of white blood cells. An advanced phase is called the acute phase or blast crisis. At this point, over 50 percent of the cells in the bone marrow are immature malignant cells (blast cells or promelocytes). In the acute phase, the leukemia is very aggressive and does not respond well to therapy. Approximately 85 percent of all individuals with chronic myelogenous leukemia enter the acute phase.
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Related disorders of Polycythemia Vera. Symptoms of the following disorders can be similar to those of polycythemia vera. Comparisons may be useful for a differential diagnosis.Secondary polycythemia is a general term for the overproduction of red blood cells that occurs as a result of (secondary to) a known cause. Such causes include genetic disorders, certain tumors that may secrete erythropoietin (a hormone that stimulates red blood cell production), conditions that deprive the body of oxygen such as certain lung or heart diseases. Some people living in high altitudes may develop secondary polycythemia in response to poor oxygenation of tissue. Certain kidney disorders can result in the excessive production of erythropoietin and, in turn, overproduction of red blood cells. Therapy in individuals with secondary polycythemia involves treating the underlying disorder or cause of the polycythemia.Primary myelofibrosis is a rare bone marrow disorder that is characterized by abnormalities in blood cell production (hematopoiesis) and scarring (formation of fibrous tissue) within the bone marrow. Bone marrow is the soft, spongy tissue that fills the center of most bones. Bone marrow contains specialized cells called hematopoietic stem cells that grow and eventually develop into one of the three main types of blood cells: red blood cells, white blood cells or platelets. In primary myelofibrosis, a change in the DNA of a single hematopoietic stem cell causes the abnormal cell to continually reproduce itself. Eventually, these abnormal cells crowd out normal, healthy cells in the marrow and, along with scarring within the marrow, disrupt the production of red and white blood cells and platelets. The symptoms associated with primary myelofibrosis vary and are related to the abnormalities affecting blood cell production. Affected individuals may not have symptoms at the time of diagnosis (asymptomatic) may remain symptom-free for many years. Eventually, affected individuals may develop fatigue, fever, frequent infections, pale skin, night sweats and unexplained weight loss. An enlarged (spleen) is a common finding. An enlarged liver (hepatomegaly) may also occur. (For more information on this disorder, choose “primary myelofibrosis” as your search term in the Rare Disease Database.)Essential thrombocythemia (ET) is one of four rare MPNs. Myeloproliferative means uncontrolled production of cells by the bone marrow. Each of the four myeloproliferative neoplasms is characterized by over-production of a different, but essential, type of blood cell resulting in a high concentration of these cells in the blood. Essential thrombocythemia is characterized by overproduction of the precursor cells to blood platelets (megakaryocytes) which, in turn, leads to a vastly increased number of platelets in the blood. Platelets are specialized cells in blood essential for the normal process of clotting. In addition to over-production of platelets, other symptoms and signs of ET may include an enlarged spleen (splenomegaly); bleeding from the gut, gums and/or nose (hemorrhaging); and constricted or blocked arteries (thrombosis). As many as two-thirds of patients are without symptoms (asymptomatic) upon initial examination. Most patients present with symptoms related to small or large vessel thrombosis or minor bleeding. Presentation with a major bleeding episode is very unusual. Clots may occur in the small arteries of the toes and fingers, leading to pain, warmth, tissue death (gangrene) and/or classic erythromelalgia. Erythromelalgia refers to a syndrome of redness and burning pain in the extremities. The incidence of the thrombotic and bleeding episodes is minimized, but not eliminated, with reduction of the platelet count to normal. In some instances, this chronic disorder may be progressive, evolving in relatively rare cases into acute leukemia or myelofibrosis. (For more information on this disorder, choose “essential thrombocythemia” as your search term in the Rare Disease Database.)Chronic myelogenous leukemia is a rare myeloproliferative neoplasm characterized by the excessive development of white blood cells in the spongy tissue found inside large bones of the body (bone marrow), spleen, liver and blood. As the disease progresses, the leukemic cells invade other areas of the body including the intestinal tract, kidneys, lungs, gonads and lymph nodes. There are two phases to chronic myelogenous leukemia. The first phase, or chronic phase, is characterized by a slow, progressive overproduction of white blood cells. An advanced phase is called the acute phase or blast crisis. At this point, over 50 percent of the cells in the bone marrow are immature malignant cells (blast cells or promelocytes). In the acute phase, the leukemia is very aggressive and does not respond well to therapy. Approximately 85 percent of all individuals with chronic myelogenous leukemia enter the acute phase.
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Polycythemia Vera
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Diagnosis of Polycythemia Vera
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Diagnosis of polycythemia vera may be made based upon a thorough clinical evaluation, detailed patient history, and various specialized tests. In many cases, the disorder may be detected from blood tests conducted during a routine examination. A complete blood count (CBC) may demonstrate elevated numbers of red blood cells and sometimes platelets and white blood cells.Blood tests may also measure hemoglobulin and hematocrit. Hemoglobin is the protein within red blood cells that carry oxygen. Hematocrit is the percentage of red blood cells in the total blood volume. If these measures are elevated it may indicate polycythemia vera.Physicians may also measure the levels of erythropoietin (EPO), a hormone that causes the bone marrow to produce red blood cells. In individuals with polycythemia vera, EPO levels are abnormally low. This test is usually done to distinguish polycythemia vera from secondary polycythemia, in which EPO levels are not affected.In some cases, surgical removal and microscopic examination of bone marrow tissue (biopsy) may also be used to diagnose of polycythemia vera. The sample tissue is tested to determine whether the marrow is functioning properly.A variety of specialized tests can be used to identify the JAK2 mutation in blood cells, which is also diagnostic of polycythemia vera.
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Diagnosis of Polycythemia Vera. Diagnosis of polycythemia vera may be made based upon a thorough clinical evaluation, detailed patient history, and various specialized tests. In many cases, the disorder may be detected from blood tests conducted during a routine examination. A complete blood count (CBC) may demonstrate elevated numbers of red blood cells and sometimes platelets and white blood cells.Blood tests may also measure hemoglobulin and hematocrit. Hemoglobin is the protein within red blood cells that carry oxygen. Hematocrit is the percentage of red blood cells in the total blood volume. If these measures are elevated it may indicate polycythemia vera.Physicians may also measure the levels of erythropoietin (EPO), a hormone that causes the bone marrow to produce red blood cells. In individuals with polycythemia vera, EPO levels are abnormally low. This test is usually done to distinguish polycythemia vera from secondary polycythemia, in which EPO levels are not affected.In some cases, surgical removal and microscopic examination of bone marrow tissue (biopsy) may also be used to diagnose of polycythemia vera. The sample tissue is tested to determine whether the marrow is functioning properly.A variety of specialized tests can be used to identify the JAK2 mutation in blood cells, which is also diagnostic of polycythemia vera.
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Polycythemia Vera
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Therapies of Polycythemia Vera
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Treatment
The treatment of polycythemia vera is aimed at reducing the levels of red blood cells and preventing the complications of the disorder especially blood clot (thrombosis) formation. Treatment options include phlebotomy and drug therapy.Most individuals with polycythemia vera will have their blood drawn (similar to as is done when donating blood) usually at regular intervals over several months. Phlebotomy is used to reduce the volume of circulating red blood cells so that blood can flow and function properly. Phlebotomy may resolve symptoms associated with thickened blood and increased red blood cell production. Phlebotomy may be the only treatment necessary for some people, for many years. However, this procedure does not treat elevated platelet levels (thrombocythemia), elevated white blood cell levels (leukocytosis), itchy skin or gout. In some cases, phlebotomy may contribute to elevated platelet levels. Phlebotomy is also known as venesection.Many individuals with polycythemia vera will also receive treatment with certain drugs that suppress the formation of blood cells by the marrow (myelosuppressive drugs). A chemotherapy drug known as hydroxyurea is most often used. Another chemotherapy drug used is busulfan. Other drugs such as chlorambucil and radioactive phosphorous have been used in the past, but these drugs, especially in individuals requiring long-term therapy, have been associated with increased risk of developing leukemia.
Anagrelide is a drug used to lower the number of platelets and reduce the risk of blood clot formation. Another drug, called interferon alfa, stimulates the immune system to suppress blood cell production.Additional therapies used for polycythemia vera include low-dose aspirin to decrease the risk of blood clot formation, a drug called allopurinol to treat high uric acid levels, and antihistamines or ultraviolet light therapy to treat severe, persistent itchiness.Individuals who enter the “spent phase” of polycythemia vera, in which the bone marrow no longer produces healthy, functioning blood cells, may require periodic blood transfusions to maintain sufficient levels of blood cells. During the spent phase, the spleen may become significantly enlarged and painful, potentially requiring its removal through surgery (splenectomy).Jakafi (ruxolitinib) was approved by the FDA in 2011 for treatment of patients with intermediate or high risk myelofibrosis, including post-polycythemia vera myelofibrosis. In 2014, Jakafi was approved for PV patients who have had an inadequate response to or are intolerant of hydroxyurea. This medication inhibits the JAK 1 and 2 enzymes that are involved in regulating blood and immunological functioning. Jakafi is manufactured by Incyte Corp.
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Therapies of Polycythemia Vera. Treatment
The treatment of polycythemia vera is aimed at reducing the levels of red blood cells and preventing the complications of the disorder especially blood clot (thrombosis) formation. Treatment options include phlebotomy and drug therapy.Most individuals with polycythemia vera will have their blood drawn (similar to as is done when donating blood) usually at regular intervals over several months. Phlebotomy is used to reduce the volume of circulating red blood cells so that blood can flow and function properly. Phlebotomy may resolve symptoms associated with thickened blood and increased red blood cell production. Phlebotomy may be the only treatment necessary for some people, for many years. However, this procedure does not treat elevated platelet levels (thrombocythemia), elevated white blood cell levels (leukocytosis), itchy skin or gout. In some cases, phlebotomy may contribute to elevated platelet levels. Phlebotomy is also known as venesection.Many individuals with polycythemia vera will also receive treatment with certain drugs that suppress the formation of blood cells by the marrow (myelosuppressive drugs). A chemotherapy drug known as hydroxyurea is most often used. Another chemotherapy drug used is busulfan. Other drugs such as chlorambucil and radioactive phosphorous have been used in the past, but these drugs, especially in individuals requiring long-term therapy, have been associated with increased risk of developing leukemia.
Anagrelide is a drug used to lower the number of platelets and reduce the risk of blood clot formation. Another drug, called interferon alfa, stimulates the immune system to suppress blood cell production.Additional therapies used for polycythemia vera include low-dose aspirin to decrease the risk of blood clot formation, a drug called allopurinol to treat high uric acid levels, and antihistamines or ultraviolet light therapy to treat severe, persistent itchiness.Individuals who enter the “spent phase” of polycythemia vera, in which the bone marrow no longer produces healthy, functioning blood cells, may require periodic blood transfusions to maintain sufficient levels of blood cells. During the spent phase, the spleen may become significantly enlarged and painful, potentially requiring its removal through surgery (splenectomy).Jakafi (ruxolitinib) was approved by the FDA in 2011 for treatment of patients with intermediate or high risk myelofibrosis, including post-polycythemia vera myelofibrosis. In 2014, Jakafi was approved for PV patients who have had an inadequate response to or are intolerant of hydroxyurea. This medication inhibits the JAK 1 and 2 enzymes that are involved in regulating blood and immunological functioning. Jakafi is manufactured by Incyte Corp.
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Polycythemia Vera
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nord_983_0
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Overview of Polymorphous Low-Grade Adenocarcinoma
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Polymorphous low-grade adenocarcinoma (PLGA) is a rare tumor of the salivary glands that is limited, to a great extent, to the minor salivary glands and commonly, but not exclusively, localized in the palate of the mouth. The major salivary glands are the parotid glands (at the side of the face, below the ears), the sublingual glands (below the tongue), and the submandibular glands (below the lower jaw). As the name suggests, each of the major salivary glands is of substantial size and visible to the naked eye. There are about 600 to 1,000 minor salivary glands that are microscopic in size. These minor salivary glands are found in the lining (mucosa) of the lips, tongue, and hard and soft palate, as well as inside the nose, cheeks, and sinuses.Less than one (1%) per cent of all cancers reported in the USA are salivary cancers and, of these, 80% begin in the parotid glands, and about 15% begin in the submandibular glands, leaving only 5% that begin in the sublingual and minor salivary glands. Most of the tumors that start in the major salivary glands turn out to be benign, while most, but not all, of the cancers that start in the minor salivary glands turn out to be malignant.
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Overview of Polymorphous Low-Grade Adenocarcinoma. Polymorphous low-grade adenocarcinoma (PLGA) is a rare tumor of the salivary glands that is limited, to a great extent, to the minor salivary glands and commonly, but not exclusively, localized in the palate of the mouth. The major salivary glands are the parotid glands (at the side of the face, below the ears), the sublingual glands (below the tongue), and the submandibular glands (below the lower jaw). As the name suggests, each of the major salivary glands is of substantial size and visible to the naked eye. There are about 600 to 1,000 minor salivary glands that are microscopic in size. These minor salivary glands are found in the lining (mucosa) of the lips, tongue, and hard and soft palate, as well as inside the nose, cheeks, and sinuses.Less than one (1%) per cent of all cancers reported in the USA are salivary cancers and, of these, 80% begin in the parotid glands, and about 15% begin in the submandibular glands, leaving only 5% that begin in the sublingual and minor salivary glands. Most of the tumors that start in the major salivary glands turn out to be benign, while most, but not all, of the cancers that start in the minor salivary glands turn out to be malignant.
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Polymorphous Low-Grade Adenocarcinoma
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Symptoms of Polymorphous Low-Grade Adenocarcinoma
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A lump or mass in the palate or near any of the salivary glands should be seen by a physician as soon as possible. A lingering pain in the area of the salivary glands is a signal to see a physician. A change in the size and/or shape of one of the salivary glands (asymmetry) may be a sufficient reason to see a doctor. Unexplained bleeding in the mouth is also a symptom warranting attention, and any persistent numbness on any part of the face or a weakening of the muscles on one side of the face should be brought to the attention of a physician. Early diagnosis and treatment are important.
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Symptoms of Polymorphous Low-Grade Adenocarcinoma. A lump or mass in the palate or near any of the salivary glands should be seen by a physician as soon as possible. A lingering pain in the area of the salivary glands is a signal to see a physician. A change in the size and/or shape of one of the salivary glands (asymmetry) may be a sufficient reason to see a doctor. Unexplained bleeding in the mouth is also a symptom warranting attention, and any persistent numbness on any part of the face or a weakening of the muscles on one side of the face should be brought to the attention of a physician. Early diagnosis and treatment are important.
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Polymorphous Low-Grade Adenocarcinoma
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Causes of Polymorphous Low-Grade Adenocarcinoma
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Why a normal cell becomes malignant is not yet fully understood.
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Causes of Polymorphous Low-Grade Adenocarcinoma. Why a normal cell becomes malignant is not yet fully understood.
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Polymorphous Low-Grade Adenocarcinoma
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Affects of Polymorphous Low-Grade Adenocarcinoma
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In most instances PLGA affects people in their middle age. The median age at which patients are diagnosed is 57 years, with a range of from 22 to 71 years. For reasons that are unknown, this disease affects slightly more women than men.
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Affects of Polymorphous Low-Grade Adenocarcinoma. In most instances PLGA affects people in their middle age. The median age at which patients are diagnosed is 57 years, with a range of from 22 to 71 years. For reasons that are unknown, this disease affects slightly more women than men.
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Polymorphous Low-Grade Adenocarcinoma
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Related disorders of Polymorphous Low-Grade Adenocarcinoma
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Acinic cell carcinomaAcinic cell carcinoma is a rare salivary gland cancer that represents approximately 6-10% of all salivary gland cancers. The National Cancer Institute reported 1,353 cases of acinic cell carcinoma of the head and neck in the U.S. from 1985 to 1995 or about 135 cases per year. They make up approximately 4% of all minor and 2-4% of all major salivary gland tumors. Acinic cell carcinomas arise most frequently in the parotid gland (86.3% in largest study). Other sites of primary tumors have included the submandibular gland and other major and minor salivary glands.
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Related disorders of Polymorphous Low-Grade Adenocarcinoma. Acinic cell carcinomaAcinic cell carcinoma is a rare salivary gland cancer that represents approximately 6-10% of all salivary gland cancers. The National Cancer Institute reported 1,353 cases of acinic cell carcinoma of the head and neck in the U.S. from 1985 to 1995 or about 135 cases per year. They make up approximately 4% of all minor and 2-4% of all major salivary gland tumors. Acinic cell carcinomas arise most frequently in the parotid gland (86.3% in largest study). Other sites of primary tumors have included the submandibular gland and other major and minor salivary glands.
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Polymorphous Low-Grade Adenocarcinoma
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nord_983_5
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Diagnosis of Polymorphous Low-Grade Adenocarcinoma
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The diagnosis of PLGA may be suspected on history and clinical examination, but can be confirmed only by biopsy of the affected tissue.
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Diagnosis of Polymorphous Low-Grade Adenocarcinoma. The diagnosis of PLGA may be suspected on history and clinical examination, but can be confirmed only by biopsy of the affected tissue.
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Polymorphous Low-Grade Adenocarcinoma
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nord_983_6
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Therapies of Polymorphous Low-Grade Adenocarcinoma
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TreatmentThe primary mode of treatment for low-grade stage I tumors of the salivary gland is surgery (resection). Radiation therapy may be prescribed as a supplement in some cases. Palate rehabilitation may be needed depending on the size of the tumor.
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Therapies of Polymorphous Low-Grade Adenocarcinoma. TreatmentThe primary mode of treatment for low-grade stage I tumors of the salivary gland is surgery (resection). Radiation therapy may be prescribed as a supplement in some cases. Palate rehabilitation may be needed depending on the size of the tumor.
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Polymorphous Low-Grade Adenocarcinoma
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nord_984_0
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Overview of Polymyalgia Rheumatica
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Polymyalgia rheumatica is a rare inflammatory disease characterized by muscle pain (myalgia), stiffness, and additional generalized systemic symptoms such as fatigue, low-grade fever, and/or a general feeling of ill health (malaise). Polymyalgia rheumatica can be a relatively benign condition that is extremely responsive to treatment. In some rare cases, permanent muscle weakness, degeneration and loss (atrophy) of muscle mass, and disability may occur. The exact cause of polymyalgia rheumatica is unknown, although immunological factors and familial tendencies (genetic predisposition) have been mentioned in the medical literature.Polymyalgia rheumatica is closely related to giant cell arteritis, another inflammatory disorder. Giant cell arteritis is characterized by progressive inflammation of many arteries of the body. These two disorders have been described in the medical literature as possible variants of the same disease process. Some researchers believe they represent different ends of a disease continuum. The exact nature of the association is not fully understood.
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Overview of Polymyalgia Rheumatica. Polymyalgia rheumatica is a rare inflammatory disease characterized by muscle pain (myalgia), stiffness, and additional generalized systemic symptoms such as fatigue, low-grade fever, and/or a general feeling of ill health (malaise). Polymyalgia rheumatica can be a relatively benign condition that is extremely responsive to treatment. In some rare cases, permanent muscle weakness, degeneration and loss (atrophy) of muscle mass, and disability may occur. The exact cause of polymyalgia rheumatica is unknown, although immunological factors and familial tendencies (genetic predisposition) have been mentioned in the medical literature.Polymyalgia rheumatica is closely related to giant cell arteritis, another inflammatory disorder. Giant cell arteritis is characterized by progressive inflammation of many arteries of the body. These two disorders have been described in the medical literature as possible variants of the same disease process. Some researchers believe they represent different ends of a disease continuum. The exact nature of the association is not fully understood.
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Polymyalgia Rheumatica
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Symptoms of Polymyalgia Rheumatica
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In most cases, the symptoms of polymyalgia rheumatica begin abruptly (acutely). However, symptoms may develop slowly (insidiously) during a period of several weeks or months. Symptoms may include muscle pain (myalgia) and stiffness in the neck, shoulders, upper arms, lower back, hips, and/or thighs. The lower arms, hands, lower legs, and feet (distal extremities) are not usually affected by this disorder. Stiffness and pain, which typically occur on both sides of the body (bilateral), are most severe in the morning (morning stiffness) and after long periods of rest or inactivity (gel phenomenon). In most cases, the shoulder girdle is the first area affected. However, in other cases, the neck or hips may show the first signs of the disorder. Pain or discomfort usually begins on one side of the body before affecting the other side as well.Additional symptoms of polymyalgia rheumatica may include muscle tenderness and weakness, low-grade fever, loss of appetite, weight loss, fatigue, a general feeling of ill health (malaise), and/or depression. In some cases, fever or weight loss may be the initial symptoms of polymyalgia rheumatica. About 30 percent of people with polymyalgia rheumatica develop symptoms that are characteristic of rheumatoid-like arthritis including joint swelling, pain (arthralgia), and degenerative changes in some joints. Low levels of circulating red blood cells (anemia, nonhemolytic type) may also develop in some people with this disorder.The symptoms associated with polymyalgia rheumatica often disappear for periods of time (remission) and then reappear (exacerbation). These episodes may continue for about six months or up to six years. However, severe impairment or permanent disability, even after months or years, is rare. In most cases, individuals with polymyalgia rheumatica do not experience loss of muscle strength.
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Symptoms of Polymyalgia Rheumatica. In most cases, the symptoms of polymyalgia rheumatica begin abruptly (acutely). However, symptoms may develop slowly (insidiously) during a period of several weeks or months. Symptoms may include muscle pain (myalgia) and stiffness in the neck, shoulders, upper arms, lower back, hips, and/or thighs. The lower arms, hands, lower legs, and feet (distal extremities) are not usually affected by this disorder. Stiffness and pain, which typically occur on both sides of the body (bilateral), are most severe in the morning (morning stiffness) and after long periods of rest or inactivity (gel phenomenon). In most cases, the shoulder girdle is the first area affected. However, in other cases, the neck or hips may show the first signs of the disorder. Pain or discomfort usually begins on one side of the body before affecting the other side as well.Additional symptoms of polymyalgia rheumatica may include muscle tenderness and weakness, low-grade fever, loss of appetite, weight loss, fatigue, a general feeling of ill health (malaise), and/or depression. In some cases, fever or weight loss may be the initial symptoms of polymyalgia rheumatica. About 30 percent of people with polymyalgia rheumatica develop symptoms that are characteristic of rheumatoid-like arthritis including joint swelling, pain (arthralgia), and degenerative changes in some joints. Low levels of circulating red blood cells (anemia, nonhemolytic type) may also develop in some people with this disorder.The symptoms associated with polymyalgia rheumatica often disappear for periods of time (remission) and then reappear (exacerbation). These episodes may continue for about six months or up to six years. However, severe impairment or permanent disability, even after months or years, is rare. In most cases, individuals with polymyalgia rheumatica do not experience loss of muscle strength.
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Polymyalgia Rheumatica
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nord_984_2
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Causes of Polymyalgia Rheumatica
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The exact cause of polymyalgia rheumatica is not known. The immune system has been implicated in some studies, but a direct relationship has not been established. Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons. In addition, because the disorder occurs in older individuals, polymyalgia rheumatica may be related to the aging process.A small percentage of cases of polymyalgia rheumatica seem to run in families (familial aggregation), and some people may inherit a genetic predisposition (possibly HLA-DR4) to this disorder. A genetic predisposition means that a person may carry a gene for a disease but it may not be expressed unless something in the environment triggers the disease. Although HLA-DR4 is associated with more cases of polymyalgia rheumatica than chance alone would explain, the exact nature of the relationship is not fully understood.
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Causes of Polymyalgia Rheumatica. The exact cause of polymyalgia rheumatica is not known. The immune system has been implicated in some studies, but a direct relationship has not been established. Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons. In addition, because the disorder occurs in older individuals, polymyalgia rheumatica may be related to the aging process.A small percentage of cases of polymyalgia rheumatica seem to run in families (familial aggregation), and some people may inherit a genetic predisposition (possibly HLA-DR4) to this disorder. A genetic predisposition means that a person may carry a gene for a disease but it may not be expressed unless something in the environment triggers the disease. Although HLA-DR4 is associated with more cases of polymyalgia rheumatica than chance alone would explain, the exact nature of the relationship is not fully understood.
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Polymyalgia Rheumatica
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nord_984_3
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Affects of Polymyalgia Rheumatica
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Polymyalgia rheumatica is a rare disorder that affects twice as many females as males. Affected individuals are usually over the age of 50 years. This disorder occurs at the rate of about 50 per 100,000 in people over 50 years of age. Polymyalgia rheumatica is estimated to affect 450,000 individuals in the United States. The disease occurs with greater frequency in Caucasians and has higher incidence rates in the United States and northern Europe than in the rest of the world. Most individuals with this disorder eventually experience total recovery from the symptoms of polymyalgia rheumatica.
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Affects of Polymyalgia Rheumatica. Polymyalgia rheumatica is a rare disorder that affects twice as many females as males. Affected individuals are usually over the age of 50 years. This disorder occurs at the rate of about 50 per 100,000 in people over 50 years of age. Polymyalgia rheumatica is estimated to affect 450,000 individuals in the United States. The disease occurs with greater frequency in Caucasians and has higher incidence rates in the United States and northern Europe than in the rest of the world. Most individuals with this disorder eventually experience total recovery from the symptoms of polymyalgia rheumatica.
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Polymyalgia Rheumatica
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nord_984_4
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Related disorders of Polymyalgia Rheumatica
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Symptoms of the following disorders can be similar to those of polymyalgia rheumatica. Comparisons may be useful for a differential diagnosis:Giant cell arteritis, also known as temporal arteritis, is a chronic inflammatory disorder characterized by the progressive inflammation of many arteries of the body (panarteritis). Granular material and abnormally large cells (giant cells) accumulate in the elastic lining of the arteries. Symptoms of giant cell arteritis vary widely from case to case. In some cases, chronic inflammation is confined to the different branches of the heart's main artery (aorta), resulting in many large arteries becoming inflamed. However, the temporal arteries in the head are most frequently affected, causing symptoms such as headaches and stabbing pain on both sides of the head. The scalp of some affected individuals may also become red, swollen, and/or tender. Some affected individuals may also feel rhythmic pulsations on either side of the head. Additional symptoms may include fever, muscles weakness, a general feeling of ill health (malaise), muscle pain, weight loss, and stiffness. Some individuals with giant cell arteritis may develop polymyalgia rheumatica. (For more information on this disorder, choose “Giant Cell Arteritis” as your search term in the Rare Disease Database.)Polymyositis is a rare inflammatory disease characterized by degenerative changes in muscles and supporting connective tissue. Muscle weakness may occur rapidly and affect the neck, trunk, and upper arms and legs. Joint pain, swelling, and tenderness may be present. Eventually, it becomes difficult for affected individuals to rise from a sitting position. In some cases, individuals may have difficulty climbing stairs, lifting objects, and reaching overhead. The exact cause of polymyositis is unknown, although the interaction of inherited, viral, and environmental factors may play a role. (For more information on this disorder, choose “Polymyositis” as your search term in the Rare Disease Database.)Fibromyalgia is a chronic disorder characterized by pain throughout the muscles of the body and abnormally persistent episodes of fatigue. The pain may begin gradually or have a sudden onset. Additional symptoms may include muscle spasms and stiffness. The parts of the body most frequently affected are the back of the neck, shoulders, lower back, elbows, hips, and/or knees. In addition, small specific areas known as “tender points” are typically painful when pressure is applied to them. Some people with fibromyalgia may also experience chest pain, difficulty concentrating, headaches, painful and/or frequent urination, diarrhea, constipation, numbness of the mouth, and/or unrefreshing (non-restorative) sleep. (For more information on this disorder, choose “Fibromyalgia” as your search term in the Rare Disease Database.)
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Related disorders of Polymyalgia Rheumatica. Symptoms of the following disorders can be similar to those of polymyalgia rheumatica. Comparisons may be useful for a differential diagnosis:Giant cell arteritis, also known as temporal arteritis, is a chronic inflammatory disorder characterized by the progressive inflammation of many arteries of the body (panarteritis). Granular material and abnormally large cells (giant cells) accumulate in the elastic lining of the arteries. Symptoms of giant cell arteritis vary widely from case to case. In some cases, chronic inflammation is confined to the different branches of the heart's main artery (aorta), resulting in many large arteries becoming inflamed. However, the temporal arteries in the head are most frequently affected, causing symptoms such as headaches and stabbing pain on both sides of the head. The scalp of some affected individuals may also become red, swollen, and/or tender. Some affected individuals may also feel rhythmic pulsations on either side of the head. Additional symptoms may include fever, muscles weakness, a general feeling of ill health (malaise), muscle pain, weight loss, and stiffness. Some individuals with giant cell arteritis may develop polymyalgia rheumatica. (For more information on this disorder, choose “Giant Cell Arteritis” as your search term in the Rare Disease Database.)Polymyositis is a rare inflammatory disease characterized by degenerative changes in muscles and supporting connective tissue. Muscle weakness may occur rapidly and affect the neck, trunk, and upper arms and legs. Joint pain, swelling, and tenderness may be present. Eventually, it becomes difficult for affected individuals to rise from a sitting position. In some cases, individuals may have difficulty climbing stairs, lifting objects, and reaching overhead. The exact cause of polymyositis is unknown, although the interaction of inherited, viral, and environmental factors may play a role. (For more information on this disorder, choose “Polymyositis” as your search term in the Rare Disease Database.)Fibromyalgia is a chronic disorder characterized by pain throughout the muscles of the body and abnormally persistent episodes of fatigue. The pain may begin gradually or have a sudden onset. Additional symptoms may include muscle spasms and stiffness. The parts of the body most frequently affected are the back of the neck, shoulders, lower back, elbows, hips, and/or knees. In addition, small specific areas known as “tender points” are typically painful when pressure is applied to them. Some people with fibromyalgia may also experience chest pain, difficulty concentrating, headaches, painful and/or frequent urination, diarrhea, constipation, numbness of the mouth, and/or unrefreshing (non-restorative) sleep. (For more information on this disorder, choose “Fibromyalgia” as your search term in the Rare Disease Database.)
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Polymyalgia Rheumatica
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nord_984_5
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Diagnosis of Polymyalgia Rheumatica
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The diagnosis of polymyalgia rheumatica may be confirmed by a thorough clinical examination including a detailed patient history and specialized blood testing that demonstrates an abnormally elevated sedimentation rate. Other substances in the blood, such as serum albumin, globulins, and fibronogen, may also be elevated. Microscopic and laboratory examination of muscle tissue samples (biopsy) from affected individuals does not usually reveal any muscle abnormality. Some people with this disorder may also be anemic. Rheumatoid factor is not present in the blood of people with this disorder.
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Diagnosis of Polymyalgia Rheumatica. The diagnosis of polymyalgia rheumatica may be confirmed by a thorough clinical examination including a detailed patient history and specialized blood testing that demonstrates an abnormally elevated sedimentation rate. Other substances in the blood, such as serum albumin, globulins, and fibronogen, may also be elevated. Microscopic and laboratory examination of muscle tissue samples (biopsy) from affected individuals does not usually reveal any muscle abnormality. Some people with this disorder may also be anemic. Rheumatoid factor is not present in the blood of people with this disorder.
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Polymyalgia Rheumatica
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nord_984_6
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Therapies of Polymyalgia Rheumatica
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TreatmentNonsteroidal antiinflammatory drugs (NSAIDs) may be used to treat those people with polymyalgia rheumatica who do not have vascular symptoms or signs (e.g., recurring headaches indicative of giant cell arteritis). Some affected individuals respond well to treatment with aspirin, which relieves pain and reduces inflammation.If these medications are not effective, low to moderate doses of corticosteroid drugs (e.g., prednisone) may be prescribed. Most affected individuals treated with corticosteroids experience rapid improvement within a few days. After the symptoms resolve, the dosage may then be lowered and a maintenance dose may be prescribed for a few months or up to several years. Periodic medical evaluation is essential to screen for potential side effects of corticosteroid drugs.Individuals with polymyalgia rheumatica who also have other symptoms such as recurring headaches that may be suggestive of giant-cell arteritis, are usually placed on high-doses of corticosteroid drugs (e.g., prednisone). Other treatment for polymyalgia rheumatica is symptomatic and supportive.
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Therapies of Polymyalgia Rheumatica. TreatmentNonsteroidal antiinflammatory drugs (NSAIDs) may be used to treat those people with polymyalgia rheumatica who do not have vascular symptoms or signs (e.g., recurring headaches indicative of giant cell arteritis). Some affected individuals respond well to treatment with aspirin, which relieves pain and reduces inflammation.If these medications are not effective, low to moderate doses of corticosteroid drugs (e.g., prednisone) may be prescribed. Most affected individuals treated with corticosteroids experience rapid improvement within a few days. After the symptoms resolve, the dosage may then be lowered and a maintenance dose may be prescribed for a few months or up to several years. Periodic medical evaluation is essential to screen for potential side effects of corticosteroid drugs.Individuals with polymyalgia rheumatica who also have other symptoms such as recurring headaches that may be suggestive of giant-cell arteritis, are usually placed on high-doses of corticosteroid drugs (e.g., prednisone). Other treatment for polymyalgia rheumatica is symptomatic and supportive.
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Polymyalgia Rheumatica
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nord_985_0
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Overview of Polymyositis and Necrotizing Myopathy
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SummaryPolymyositis (PM) and necrotizing myopathy (NM) are two types of inflammatory myopathy characterized by characteristic features on a muscle biopsy. PM has more inflammatory changes in the muscle tissue, while NM has more necrosis and degeneration of the muscle fibers. Both lead to symmetric weakness and some degree of muscle wasting (atrophy). The muscles that are principally affected include those closest to and within the trunk of the body such as the hip, shoulders, arms, pharynx and neck. PM occurs most often in women over 20 years of age, but men can also be affected. NM can occur in all age groups and is very rarely seen as a complication of the statin drugs used to lower the serum cholesterol. Muscle weakness usually happens over days, weeks or months. Some affected people have muscle pain, breathing problems, and trouble swallowing.IntroductionThe inflammatory myopathies are a group of diseases that involve chronic muscle inflammation and weakness. They are thought to be autoimmune diseases, meaning the body’s natural defenses (antibodies, lymphocytes, etc.) against invading organisms begin to attack perfectly healthy tissue for unknown reasons, leading to inflammation or swelling. Over the past several years, PM has been less frequently diagnosed as more patients are being classified as having necrotizing myopathy (NM) or an overlap of myositis with another autoimmune disease. NM has similar clinical features compared to PM and is distinguished by the characteristic histopathological findings noted above. Further, NM patients often have characteristic autoantibodies in their blood that can be detected using specialized laboratory testing.
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Overview of Polymyositis and Necrotizing Myopathy. SummaryPolymyositis (PM) and necrotizing myopathy (NM) are two types of inflammatory myopathy characterized by characteristic features on a muscle biopsy. PM has more inflammatory changes in the muscle tissue, while NM has more necrosis and degeneration of the muscle fibers. Both lead to symmetric weakness and some degree of muscle wasting (atrophy). The muscles that are principally affected include those closest to and within the trunk of the body such as the hip, shoulders, arms, pharynx and neck. PM occurs most often in women over 20 years of age, but men can also be affected. NM can occur in all age groups and is very rarely seen as a complication of the statin drugs used to lower the serum cholesterol. Muscle weakness usually happens over days, weeks or months. Some affected people have muscle pain, breathing problems, and trouble swallowing.IntroductionThe inflammatory myopathies are a group of diseases that involve chronic muscle inflammation and weakness. They are thought to be autoimmune diseases, meaning the body’s natural defenses (antibodies, lymphocytes, etc.) against invading organisms begin to attack perfectly healthy tissue for unknown reasons, leading to inflammation or swelling. Over the past several years, PM has been less frequently diagnosed as more patients are being classified as having necrotizing myopathy (NM) or an overlap of myositis with another autoimmune disease. NM has similar clinical features compared to PM and is distinguished by the characteristic histopathological findings noted above. Further, NM patients often have characteristic autoantibodies in their blood that can be detected using specialized laboratory testing.
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Polymyositis and Necrotizing Myopathy
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nord_985_1
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Symptoms of Polymyositis and Necrotizing Myopathy
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The symptoms of PM and NM may start gradually or suddenly and often wax and wane for no apparent reason.The major symptom of the disorder is muscle weakness, most often in the hip and shoulder areas, eventually making it difficult for patients to lift their arms, get out of a chair or to climb steps. Other muscles which may be affected are the neck and throat muscles, which may result in difficulty swallowing and cause changes in the voice due to muscle weakness. Rarely, chest muscles are affected.The muscle weakness may appear suddenly and progress over weeks to months. Additionally, the degree of muscle weakness may fluctuate over time as well. The muscles of the hands, feet and face are rarely involved in PM or NM, but generalized muscle pain may occur. Atrophy (loss of bulk) of muscle and contractures of the muscle around larger joints may develop late in the chronic stage.Other symptoms of PM and NM may include weight loss and fatigue, and patients with PM or the overlap syndrome noted above may also have fever, joint pain and Raynaud phenomenon which is a sensitivity to the cold that is most often felt in the fingers. Raynaud phenomenon is caused by constriction (narrowing) of the blood vessels in the fingers upon exposure to the cold. Cracking of the fingers, termed “mechanic’s hands” may also develop in PM and overlap disorders and this skin problem is associated with certain autoantibodies which circulate in the blood of affected patients.The joint pain seen in PM (called polyarthralgia) may be accompanied by swelling and mimic the findings seen in patients with rheumatoid arthritis but generally these rheumatic complaints are mild and respond well to glucocorticoids (i.e. prednisone). Gastrointestinal involvement in both PM and NM can lead to difficulty swallowing as the muscles involved in swallowing can become inflamed and weak, and the esophagus can be affected leading to heartburn but lower GI involvement is uncommon. Involvement of the heart, detected chiefly by irregularities in the electrocardiogram (ECG), has been reported but inflammation and weakening of the heart muscle (myocarditis) is rare.Interstitial lung disease is a serious complication seen in PM and the overlap myositis disorders but is uncommon in NM and leads to cough with shortness of breath as inflammation occurs in the lung tissue. This may progress to scarring (fibrosis) of the lung tissue making the lungs stiff and inelastic. In some patients, lung disease may precede myositis and dominate the clinical picture.Symptoms in both PM and NM may worsen during pregnancy in women whose disease is active increasing the risk of premature birth or stillbirth.As noted above, PM can occur in overlap with other autoimmune or rheumatic diseases, including Sjogren syndrome or scleroderma (systemic sclerosis). In addition, malignancy may complicate the course and presentation of PM or NM but is more common in dermatomyositis. This is more common in males and females over the age of 50.Abdominal symptoms, more common in children with juvenile dermatomyositis (JDM), may be associated with the passage of dark stools or the vomiting of blood from gastrointestinal ulcerations that may progress to perforation and require surgical intervention. Calcinosis (the deposition of calcium deposits in the skin and soft tissue or muscle) is also more frequent in JDM.
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Symptoms of Polymyositis and Necrotizing Myopathy. The symptoms of PM and NM may start gradually or suddenly and often wax and wane for no apparent reason.The major symptom of the disorder is muscle weakness, most often in the hip and shoulder areas, eventually making it difficult for patients to lift their arms, get out of a chair or to climb steps. Other muscles which may be affected are the neck and throat muscles, which may result in difficulty swallowing and cause changes in the voice due to muscle weakness. Rarely, chest muscles are affected.The muscle weakness may appear suddenly and progress over weeks to months. Additionally, the degree of muscle weakness may fluctuate over time as well. The muscles of the hands, feet and face are rarely involved in PM or NM, but generalized muscle pain may occur. Atrophy (loss of bulk) of muscle and contractures of the muscle around larger joints may develop late in the chronic stage.Other symptoms of PM and NM may include weight loss and fatigue, and patients with PM or the overlap syndrome noted above may also have fever, joint pain and Raynaud phenomenon which is a sensitivity to the cold that is most often felt in the fingers. Raynaud phenomenon is caused by constriction (narrowing) of the blood vessels in the fingers upon exposure to the cold. Cracking of the fingers, termed “mechanic’s hands” may also develop in PM and overlap disorders and this skin problem is associated with certain autoantibodies which circulate in the blood of affected patients.The joint pain seen in PM (called polyarthralgia) may be accompanied by swelling and mimic the findings seen in patients with rheumatoid arthritis but generally these rheumatic complaints are mild and respond well to glucocorticoids (i.e. prednisone). Gastrointestinal involvement in both PM and NM can lead to difficulty swallowing as the muscles involved in swallowing can become inflamed and weak, and the esophagus can be affected leading to heartburn but lower GI involvement is uncommon. Involvement of the heart, detected chiefly by irregularities in the electrocardiogram (ECG), has been reported but inflammation and weakening of the heart muscle (myocarditis) is rare.Interstitial lung disease is a serious complication seen in PM and the overlap myositis disorders but is uncommon in NM and leads to cough with shortness of breath as inflammation occurs in the lung tissue. This may progress to scarring (fibrosis) of the lung tissue making the lungs stiff and inelastic. In some patients, lung disease may precede myositis and dominate the clinical picture.Symptoms in both PM and NM may worsen during pregnancy in women whose disease is active increasing the risk of premature birth or stillbirth.As noted above, PM can occur in overlap with other autoimmune or rheumatic diseases, including Sjogren syndrome or scleroderma (systemic sclerosis). In addition, malignancy may complicate the course and presentation of PM or NM but is more common in dermatomyositis. This is more common in males and females over the age of 50.Abdominal symptoms, more common in children with juvenile dermatomyositis (JDM), may be associated with the passage of dark stools or the vomiting of blood from gastrointestinal ulcerations that may progress to perforation and require surgical intervention. Calcinosis (the deposition of calcium deposits in the skin and soft tissue or muscle) is also more frequent in JDM.
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Polymyositis and Necrotizing Myopathy
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nord_985_2
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Causes of Polymyositis and Necrotizing Myopathy
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The exact cause of PM and NM is unknown. Like other autoimmune diseases, the body’s natural immune defense mechanisms attack its own tissue. Exposure to certain drugs has been shown to increase the likelihood of developing myositis and a common drug known to induce NM are the statin agents and a specific autoantibody (anti-HMGCR) has been found to be associated with statin-associated NM. In PM and overlap myositis disorders, the autoimmune attack on muscle tissue can occur through a T-cell mediated destructive process directed against unidentified muscle antigens, but the finding of myositis-specific autoantibodies in many PM and overlap myositis patients also supports disorders associated with B cells.The injection of collagen for cosmetic use has been implicated in the onset of a polymyositis-like syndrome. Injectable bovine collagen has been used to reduce wrinkles and facial scars, usually in women. The onset of PM in such patients is felt to result from an autoimmune reaction to the collagen.
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Causes of Polymyositis and Necrotizing Myopathy. The exact cause of PM and NM is unknown. Like other autoimmune diseases, the body’s natural immune defense mechanisms attack its own tissue. Exposure to certain drugs has been shown to increase the likelihood of developing myositis and a common drug known to induce NM are the statin agents and a specific autoantibody (anti-HMGCR) has been found to be associated with statin-associated NM. In PM and overlap myositis disorders, the autoimmune attack on muscle tissue can occur through a T-cell mediated destructive process directed against unidentified muscle antigens, but the finding of myositis-specific autoantibodies in many PM and overlap myositis patients also supports disorders associated with B cells.The injection of collagen for cosmetic use has been implicated in the onset of a polymyositis-like syndrome. Injectable bovine collagen has been used to reduce wrinkles and facial scars, usually in women. The onset of PM in such patients is felt to result from an autoimmune reaction to the collagen.
| 985 |
Polymyositis and Necrotizing Myopathy
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nord_985_3
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Affects of Polymyositis and Necrotizing Myopathy
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PM and NM may appear at any time from infancy through the age of 80 years, but most commonly occurs in adults over 20 years of age, especially those aged 45 to 60 years. Juvenile PM is very rare (much less common than juvenile DM) and the symptoms usually appear between the ages of five to 15 years. Females are affected twice as often as males and PM is more common in African Americans than in Caucasians.
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Affects of Polymyositis and Necrotizing Myopathy. PM and NM may appear at any time from infancy through the age of 80 years, but most commonly occurs in adults over 20 years of age, especially those aged 45 to 60 years. Juvenile PM is very rare (much less common than juvenile DM) and the symptoms usually appear between the ages of five to 15 years. Females are affected twice as often as males and PM is more common in African Americans than in Caucasians.
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Polymyositis and Necrotizing Myopathy
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nord_985_4
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Related disorders of Polymyositis and Necrotizing Myopathy
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Related disorders of Polymyositis and Necrotizing Myopathy.
| 985 |
Polymyositis and Necrotizing Myopathy
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