Yao syndrome (formerly called NOD2 -associated autoinflammatory disease) is a disorder involving episodes of fever and abnormal inflammation affecting many parts of the body, particularly the skin, joints, and gastrointestinal system. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). In people with Yao syndrome, part of the immune system called the innate immune response is turned on (activated) abnormally, which causes fevers and inflammation-related damage to tissues and organs. Based on this process, Yao syndrome is classified as an autoinflammatory disease. Autoinflammatory diseases are distinct from autoimmune diseases; these two groups of diseases involve abnormalities in different parts of the immune system.

A number sign (#) is used with this entry because of evidence that susceptibility to Yao syndrome (YAOS) is conferred by variation in the NOD2 gene (605956) on chromosome 16q12. Description Yao syndrome is an autoinflammatory disease characterized by periodic fever, dermatitis, arthritis, and swelling of the distal extremities, as well as gastrointestinal and sicca-like symptoms. The disorder is associated with specific NOD2 variants (Yao and Shen, 2017). Clinical Features Yao et al. (2011) described 7 unrelated patients with apparent autoinflammatory disease with multisystem involvement. Mean age at disease onset was 40.7 years, and the patients characteristically presented with periodic fever, dermatitis, and inflammatory polyarthritis.

A number sign (#) is used with this entry because of evidence that microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma, can be caused by homozygous mutation in the LTBP2 gene (602091) on chromosome 14q24. Description Microspherophakia (MSP) is a rare disease characterized by smaller and more spherical lenses than normal bilaterally, an increased anteroposterior thickness of the lens, and highly myopic eyes. Lens dislocation or subluxation may occur, leading to defective accommodation (summary by Ben Yahia et al., 2009). Microspherophakia may occur in association with ectopia lentis and glaucoma, Marfan syndrome (MFS; 154700), and Weill-Marchesani syndrome (WMS; 277600). Clinical Features Ben Yahia et al. (2009) studied a sister and brother with isolated microspherophakia from a consanguineous Tunisian family.

Glaucoma secondary to spherophakia/ectopia lentis and megalocornea is a rare, genetic, non-syndromic developmental defect of the eye disorder characterized by congenital megalocornea associated with spherophakia and/or ectopia lentis leading to pupillary block and secondary glaucoma. Additional features may include flat irides, iridodonesis, axial myopia, very deep anterior chambers, miotic, oval pupils without well-defined borders, ocular pain and irritability manifesting as conjunctival injection, corneal edema and central scarring, as well as a high arched palate.

In a 2-stage genomewide scan of 71 multicase leprosy families (365 individuals) in Brazil, Miller et al. (2004) found suggestive evidence for linkage to chromosomes 6p21.32, 17q22, and 20p13.

A number sign (#) is used with this entry because this form of susceptibility to leprosy (LPRS5) is associated with a polymorphism in the TLR1 gene (601194). A polymorphism in the TLR1 gene is also associated with protection against leprosy. See 609888 for a discussion of leprosy susceptibility in general and information on genetic heterogeneity. Mapping LPRS5 is associated with a polymorphism in the TLR1 gene, which Taguchi et al. (1996) mapped to chromosome 4p14. Molecular Genetics Schuring et al. (2009) studied association of an asn248-to-ser (N248S; 601194.0002) SNP in the TLR1 gene and leprosy in a Bangladeshi population consisting of 842 patients and 543 controls.

See 609888 for a discussion of leprosy susceptibility in general and information on genetic heterogeneity. Mapping In a study in a Vietnamese population, Mira et al. (2003) found significant evidence for a susceptibility gene for leprosy on chromosome region 6q25; maximum likelihood binomial (MLB) lod score was 4.31. They confirmed this by family-based association analysis in an independent panel of 208 Vietnamese leprosy simplex families (i.e., families with 2 unaffected parents and 1 affected child). Mira et al. (2003) confirmed the linkage of paucibacillary leprosy to 10p13 (LPRS1; 609888), as reported by Siddiqui et al. (2001). Their evidence suggested that the 6q25 locus is involved in leprosy of both the paucibacillary and multibacillary types.

A number sign (#) is used with this entry because this form of susceptibility to leprosy (LPRS3) is associated with a polymorphism in the TLR2 gene (603028) on chromosome 4q32. See 609888 for a discussion of leprosy susceptibility in general and information on genetic heterogeneity. Mapping LPRS3 is associated with a polymorphism in the TLR2 gene, which Rock et al. (1998) mapped to chromosome 4q32. Molecular Genetics Kang and Chae (2001) identified an arg677-to-trp polymorphism (R677W; 603028.0001) in the intracellular domain of TLR2 in 10 (22%) of 45 Korean lepromatous leprosy patients, but not in any of 41 Korean tuberculoid patients or 45 Korean controls. They concluded that the R677W polymorphism in TLR2 has a role in susceptibility to lepromatous leprosy.

See 609888 for a discussion of leprosy susceptibility in general and information on genetic heterogeneity. Mapping Zhang et al. (2009) performed a genomewide association study to identify leprosy susceptibility loci in 706 patients and 1,225 controls, all of whom were self-identified Han Chinese from eastern China. Diagnosis was made on the basis of the consensus of at least 2 dermatologists. Patients and controls reported an absence of M. tuberculosis and other chronic infections. Controls lacked a history of leprosy in themselves and their families, as well as autoimmune and systemic disorders.

A chronic infectious disease affecting primarily the skin and peripheral nervous system. Epidemiology Worldwide annual incidence is estimated at 250,000 cases, with a large majority in India and Brazil. Clinical description A wide clinical spectrum has been described from a polar tuberculoid (localized) form (TT) to a polar lepromatous (disseminated) one (LL). Borderline forms exist: borderline tuberculoid, borderline borderline and borderline lepromatous (BT, BB, BL). Tuberculoid leprosy (TLep) or paucibacillary form includes TT and BT and lepromatous leprosy (LLep) or multibacillary form includes LL, BL and BB.

Chronic infection caused by bacteria Mycobacteria lepræ and lepromatosis For other uses, see Leprosy (disambiguation) . Leprosy Other names Hansen's disease (HD) [1] Rash on the chest and abdomen due to leprosy Pronunciation / ˈ l ɛ p r ə s i / [2] Specialty Infectious disease Symptoms Decreased ability to feel pain [3] Causes Mycobacterium leprae or Mycobacterium lepromatosis [4] [5] Risk factors Close contact with a case of leprosy, living in poverty [3] [6] Treatment Multidrug therapy [4] Medication Rifampicin , dapsone , clofazimine [3] Frequency 209,000 (2018) [7] Leprosy , also known as Hansen's disease ( HD ), is a long-term infection by the bacteria Mycobacterium leprae or Mycobacterium lepromatosis . [4] [8] Infection can lead to damage of the nerves , respiratory tract , skin, and eyes. [4] This nerve damage may result in a lack of ability to feel pain, which can lead to the loss of parts of a person's extremities from repeated injuries or infection due to unnoticed wounds. [3] An infected person may also experience muscle weakness and poor eyesight. [3] Leprosy symptoms may begin within one year, but for some people symptoms may take 20 years or more to occur. [4] Leprosy is spread between people, although extensive contact is necessary. [3] [9] About 95% of people who contract M. leprae do not develop the disease. [10] Spread is thought to occur through a cough or contact with fluid from the nose of a person infected by leprosy. [9] [10] Genetic factors and immune function play a role in how easily a person catches the disease. [10] [11] Leprosy does not spread during pregnancy to the unborn child, or through sexual contact. [9] Leprosy occurs more commonly among people living in poverty. [3] There are two main types of the disease – paucibacillary and multibacillary, which differ in the number of bacteria present. [3] A person with paucibacillary disease has five or fewer poorly pigmented numb skin patches while a person with multibacillary disease has more than five skin patches. [3] The diagnosis is confirmed by finding acid-fast bacilli in a biopsy of the skin. [3] Leprosy is curable with multidrug therapy. [4] Treatment of paucibacillary leprosy is with the medications dapsone , rifampicin , and clofazimine for six months. [10] Treatment for multibacillary leprosy uses the same medications for 12 months. [10] A number of other antibiotics may also be used. [3] These treatments are provided free of charge by the World Health Organization . [4] People with leprosy can live with their families and go to school and work. [12] In 2018, there were 209,000 leprosy cases globally, down from 5.2 million in the 1980s. [7] [13] [14] The number of new cases in 2016 was 216,000. [4] Most new cases occur in 14 countries, with India accounting for more than half. [3] [4] In the 20 years from 1994 to 2014, 16 million people worldwide were cured of leprosy. [4] About 200 cases per year are reported in the United States. [15] Leprosy has affected humanity for thousands of years. [3] The disease takes its name from the Greek word λέπρᾱ ( léprā ), from λεπῐ́ς ( lepís ; "scale"), while the term "Hansen's disease" is named after the Norwegian physician Gerhard Armauer Hansen . [3] Leprosy has historically been associated with social stigma , which continues to be a barrier to self-reporting and early treatment. [4] Separating people affected by leprosy by placing them in leper colonies still occurs in some areas of India, [16] China, [17] Africa, [18] and Thailand. [19] Most colonies have closed, as leprosy is not very contagious. [18] Some consider the word "leper" offensive, preferring the phrase "person affected with leprosy". [20] Leprosy is classified as a neglected tropical disease . [21] World Leprosy Day was started in 1954 to draw awareness to those affected by leprosy. [22] Contents 1 Signs and symptoms 2 Cause 2.1 M. leprae and M. lepromatosis 2.2 Risk factors 2.3 Transmission 2.4 Genetics 3 Mechanism 4 Diagnosis 4.1 Classification 5 Prevention 6 Treatment 6.1 Anti-leprosy medication 6.2 Skin changes 7 Epidemiology 7.1 Disease burden 8 History 9 Society and culture 9.1 India 9.2 Treatment cost 9.3 Historical texts 9.4 Middle Ages 9.5 19th century 9.5.1 Norway 9.5.2 Colonialism and imperialism 9.6 Stigma 9.7 Programs and treatment 10 Notable cases 11 Coverage in the media 12 Other animals 13 See also 14 References 15 Further reading 16 External links Signs and symptoms [ edit ] Common symptoms present in the different types of leprosy include a runny nose; dry scalp; eye problems; skin lesions; muscle weakness; reddish skin; smooth, shiny, diffuse thickening of facial skin, ear, and hand; loss of sensation in fingers and toes; thickening of peripheral nerves; a flat nose due to destruction of nasal cartilage; and changes in phonation and other aspects of speech production. [23] [24] In addition, atrophy of the testes and impotence may occur. [25] Leprosy can affect people in different ways. [10] The average incubation period is 5 years. [4] People may begin to notice symptoms within the first year or up to 20 years after infection. [4] The first noticeable sign of leprosy is often the development of pale or pink coloured patches of skin that may be insensitive to temperature or pain. [26] Patches of discolored skin are sometimes accompanied or preceded by nerve problems including numbness or tenderness in the hands or feet. [26] [27] Secondary infections (additional bacterial or viral infections) can result in tissue loss, causing fingers and toes to become shortened and deformed, as cartilage is absorbed into the body. [28] [29] A person's immune response differs depending on the form of leprosy. [30] Approximately 30% of people affected with leprosy experience nerve damage. [31] The nerve damage sustained is reversible when treated early, but becomes permanent when appropriate treatment is delayed by several months. Damage to nerves may cause loss of muscle function, leading to paralysis. It may also lead to sensation abnormalities or numbness , which may lead to additional infections, ulcerations, and joint deformities. [31] Paucibacillary leprosy (PB): Pale skin patch with loss of sensation Skin lesions on the thigh of a person with leprosy Hands deformed by leprosy Cause [ edit ] M. leprae and M. lepromatosis [ edit ] Main articles: Mycobacterium leprae and Mycobacterium lepromatosis M. leprae , one of the causative agents of leprosy: As an acid-fast bacterium, M. leprae appears red when a Ziehl-Neelsen stain is used. M. leprae and M. lepromatosis are the mycobacteria that cause leprosy. [31] M. lepromatosis is a relatively newly identified mycobacterium isolated from a fatal case of diffuse lepromatous leprosy in 2008. [5] [32] M. lepromatosis is indistinguishable clinically from M. leprae . [33] M. leprae is an intracellular, acid-fast bacterium that is aerobic and rod-shaped. [34] M. leprae is surrounded by the waxy cell envelope coating characteristic of the genus Mycobacterium . [34] Genetically, M. leprae and M. lepromatosis lack the genes that are necessary for independent growth. [35] M. leprae and M. lepromatosis are obligate intracellular pathogens , and can not be grown ( cultured ) in the laboratory. [35] The inability to culture M. leprae and M. lepromatosis has resulted in a difficulty definitively identifying the bacterial organism under a strict interpretation of Koch's postulates . [5] [35] While the causative organisms have to date been impossible to culture in vitro , it has been possible to grow them in animals such as mice and armadillos . [36] [37] Naturally occurring infection has been reported in nonhuman primates (including the African chimpanzee , the sooty mangabey , and the cynomolgus macaque), armadillos, [38] and red squirrels . [39] Multilocus sequence typing of the armadillo M. leprae strains suggests that they were of human origin for at most a few hundred years. [40] Thus, it is suspected that armadillos first acquired the organism incidentally from early American explorers. [41] This incidental transmission was sustained in the armadillo population, and it may be transmitted back to humans, making leprosy a zoonotic disease (spread between humans and animals). [41] Red squirrels ( Sciurus vulgaris ) , a threatened species in Great Britain , were found to carry leprosy in November 2016. [42] It has been suggested that the trade in red squirrel fur, highly prized in the medieval period and intensively traded, may have been responsible for the leprosy epidemic in medieval Europe. [43] A pre-Norman-era skull excavated in Hoxne, Suffolk , in 2017 was found to carry DNA from a strain of Mycobacterium leprae, which closely matched the strain carried by modern red squirrels on Brownsea Island , UK. [43] [44] Risk factors [ edit ] The greatest risk factor for developing leprosy is contact with another person infected by leprosy. [4] People who are exposed to a person who has leprosy are 5–8 times more likely to develop leprosy than members of the general population. [6] Leprosy also occurs more commonly among those living in poverty. [3] Not all people who are infected with M. leprae develop symptoms. [45] [46] Conditions that reduce immune function, such as malnutrition, other illnesses, or genetic mutations, may increase the risk of developing leprosy. [6] Infection with HIV does not appear to increase the risk of developing leprosy. [47] Certain genetic factors in the person exposed have been associated with developing lepromatous or tuberculoid leprosy. [48] Transmission [ edit ] Transmission of leprosy occurs during close contact with those who are infected. [4] Transmission of leprosy is not well understood, but the upper respiratory tract is thought to be the most likely entry route. [10] [49] Older research suggested the skin as the main route of transmission, but recent research has increasingly favored the respiratory route. [50] Leprosy is not sexually transmitted and is not spread through pregnancy to the unborn child. [4] [9] The majority (95%) of people who are exposed to M.

Hansen's disease (also known as leprosy) is a rare bacterial infection that affects the skin, nerves and mucous membranes . After exposure, it may take anywhere from 2 to 10 years to develop features of the condition. Once present, common signs and symptoms include skin lesions ; muscle weakness or paralysis; eye problems that may lead to blindness; nosebleeds; severe pain; and/or numbness in the hands, feet, arms and legs. Hansen's disease is caused by the bacterium Mycobacterium leprae; however, the way in which the bacterium is transmitted (spread) is poorly understood. It appears that only about 5% of people are susceptible to the condition.

Pancreatic endocrine tumor, also known as pancreatic neuroendocrine tumor (PNET), describes a group of endocrine tumors originating in the pancreas that are usually indolent and benign, but may have the potential to be malignant. They can be functional, exhibiting a hormonal hypersecretion syndrome, but can be non-functional presenting with non-specific symptoms and include insulinoma, glucagonoma, VIPoma, somatostatinoma (SSoma), PPoma and Zollinger-Ellison syndrome (ZES, or gastrinoma) and other ectopic hormone producing tumors (such as GRFoma) (see these terms). Epidemiology Prevalence in the U.S. is estimated at 1/4,000-1/3,300 and 1/37,000 in Japan, but this is likely an underestimate due to a low detection rate. Clinical description PNETs, when functional, usually present in the 5th decade of life as various hypersecretion syndromes. These include insulinoma presenting with hyperinsulinemic hypoglycemia; glucagonoma with necrolytic migratory erythema, diabetes mellitus, and thomboembolisms; VIPoma with watery diarrhea, hypokalemia and or hypo/achlorhydia; SSoma with diabetes mellitus, cholelithiasis, steatorrhea and hypochlorhydria; and ZES with severe peptic ulcer disease.

Multiple myeloma is a cancer that develops in the bone marrow , the spongy tissue found in the center of most bones. The bone marrow produces red blood cells, which carry oxygen throughout the body; white blood cells, which form the body's defenses (immune system); and platelets, which are necessary for blood clotting . Multiple myeloma is characterized by abnormalities in plasma cells, a type of white blood cell. These abnormal cells multiply out of control, increasing from about one percent of cells in the bone marrow to the majority of bone marrow cells. The abnormal cells form tumors within the bone, causing bone pain and an increased risk of fractures.

A plasma cell disorder characterized by the aggregation and deposition of insoluble amyloid fibrils derived from misfolding of monoclonal immunoglobulin light chains usually produced by a plasma cell tumor. It usually presents as primary systemic amyloidosis (PSA) with multiple organ involvement and less frequently as primary localized amyloidosis (PLA) restricted to a single organ.

AL amyloidosisis the most common form of amyloidosis, a group of disorders in which an abnormal protein called amyloid builds up in tissues and organs. The signs and symptoms of AL amyloidosis vary among patients because the build up may occur in the tongue, intestines, muscles, joints, nerves, skin, ligaments, heart, liver, spleen, or kidneys. To diagnose AL amyloidosis, healthcare professionals use blood or urine tests to identify signs of amyloid protein and a biopsy to confirm the diagnosis. Treatment may include chemotherapy directed at the abnormal plasma cells, stem cell transplantation , or other treatments based on which symptoms have developed.

Primary systemic amyloidosis (PSA) is a form of AL amyloidosis (see this term) caused by the aggregation and deposition of insoluble amyloid fibrils derived from misfolded monoclonal immunoglobulin light chains usually produced by a plasma cell tumor (see this term) and characterized by multiple organ involvement.

Endocrine gland neoplasm Specialty Oncology , endocrinology An endocrine gland neoplasm is a neoplasm affecting one or more glands of the endocrine system . Examples include: Adrenal tumor Pituitary adenoma The most common form is thyroid cancer . [1] Condition such as pancreatic cancer or ovarian cancer can be considered endocrine tumors, or classified under other systems. Pinealoma is often grouped with brain tumors because of its location. [ citation needed ] See also [ edit ] Multiple endocrine neoplasia References [ edit ] ^ "Thyroid cancer" . Archived from the original on 2007-12-20 . Retrieved 2007-12-22 . External links [ edit ] Classification D ICD - 10 : C73 - C75 D34 - D35 MeSH : D00470 v t e Overview of tumors , cancer and oncology Conditions Benign tumors Hyperplasia Cyst Pseudocyst Hamartoma Malignant progression Dysplasia Carcinoma in situ Cancer Metastasis Primary tumor Sentinel lymph node Topography Head and neck ( oral , nasopharyngeal ) Digestive system Respiratory system Bone Skin Blood Urogenital Nervous system Endocrine system Histology Carcinoma Sarcoma Blastoma Papilloma Adenoma Other Precancerous condition Paraneoplastic syndrome Staging / grading TNM Ann Arbor Prostate cancer staging Gleason grading system Dukes classification Carcinogenesis Cancer cell Carcinogen Tumor suppressor genes / oncogenes Clonally transmissible cancer Oncovirus Carcinogenic bacteria Misc. Research Index of oncology articles History Cancer pain Cancer and nausea v t e Tumours of endocrine glands Pancreas Pancreatic cancer Pancreatic neuroendocrine tumor α : Glucagonoma β : Insulinoma δ : Somatostatinoma G : Gastrinoma VIPoma Pituitary Pituitary adenoma : Prolactinoma ACTH-secreting pituitary adenoma GH-secreting pituitary adenoma Craniopharyngioma Pituicytoma Thyroid Thyroid cancer (malignant): epithelial-cell carcinoma Papillary Follicular / Hurthle cell Parafollicular cell Medullary Anaplastic Lymphoma Squamous-cell carcinoma Benign Thyroid adenoma Struma ovarii Adrenal tumor Cortex Adrenocortical adenoma Adrenocortical carcinoma Medulla Pheochromocytoma Neuroblastoma Paraganglioma Parathyroid Parathyroid neoplasm Adenoma Carcinoma Pineal gland Pinealoma Pinealoblastoma Pineocytoma MEN 1 2A 2B This article about a neoplasm is a stub .

Overview Neuroendocrine tumors are cancers that begin in specialized cells called neuroendocrine cells. Neuroendocrine cells have traits similar to those of nerve cells and hormone-producing cells. Neuroendocrine tumors are rare and can occur anywhere in the body. Most neuroendocrine tumors occur in the lungs, appendix, small intestine, rectum and pancreas. There are many types of neuroendocrine tumors. Some grow slowly and some grow very quickly. Some neuroendocrine tumors produce excess hormones (functional neuroendocrine tumors).

TEMPI syndrome is a rare multi-systemic disease characterized by the presence of Telangiectasias, Erythrocytosis with elevated erythropoietin levels, Monoclonal gammopathy, Perinephric-fluid collections, and Intrapulmonary shunting. Epidemiology Less than 10 cases have been described in the literature. Clinical description TEMPI syndrome manifests in mid-adulthood with the development of telangiectasias mostly on the face, trunk and arms, as well as with erythrocytosis which may cause a red facies and occasionally, headaches. The increased serum erythropoietin levels precede the intrapulmonary shunting. The intrapulmonary shunts cause hypoxia which slowly progresses until the person needs continuous supplemental oxygen.

TEMPI syndrome is a newly discovered, multisystem condition named for 5 characteristics that affected individuals have: T elangiectasias , E rythrocytosis with elevated erythropoietin level , M onoclonal gammopathy , P erinephric-fluid collections (fluid around the kidney), and I ntrapulmonary shunting (when a region of the lungs is supplied with blood but with little or no ventilation). Signs and symptoms of TEMPI syndrome have appeared in mid-adulthood in all known affected individuals. The telangiectasias develop mostly on the face, trunk and arms. The intrapulmonary shunt causes hypoxia (not enough oxygen supply), which slowly progresses until the person needs continuous supplemental oxygen to support their breathing. Blood clots and bleeding in the brain have also been reported in some affected individuals. The cause of TEMPI syndrome is currently unknown. Treatment has reportedly been completely or partially successful with the medication bortezomib .

Eosinophilic pustular folliculitis (EPF) affects the skin causing itchy, red or skin-colored bumps and pustules (bumps containing pus). The papules mostly appear on the face, scalp, neck and trunk and may last for weeks or months. EPF affects males more than females. There are several forms of EPF. Classic eosinophilic pustular folliculitis mainly occurs in Japan. Immunosuppression-associated EPF is mainly associated with HIV infection, but has also been associated with certain cancers and medications.[16046] The infantile form of EPF is seen in infants from birth or within the first year of life. The underlying cause of EFP is unknown. All of these forms have similar skin findings.

Human disease Orthostatic intolerance ( OI ) is the development of symptoms when standing upright which are relieved when reclining . [1] There are many types of orthostatic intolerance. OI can be a subcategory of dysautonomia , a disorder of the autonomic nervous system [2] occurring when an individual stands up. [3] There is a substantial overlap between syndromes of orthostatic intolerance on the one hand, and either chronic fatigue syndrome (CFS) or fibromyalgia (FM) on the other. [4] It affects more women than men (female-to-male ratio is at least 4:1), usually under the age of 35. [5] Orthostatic intolerance occurs in humans because standing upright is a fundamental stressor and requires rapid and effective circulatory and neurologic compensations to maintain blood pressure , cerebral blood flow , and consciousness . When a human stands, approximately 750 mL of thoracic blood is abruptly translocated downward. People who suffer from OI lack the basic mechanisms to compensate for this deficit. [1] Changes in heart rate , blood pressure, and cerebral blood flow that produce OI may be caused by abnormalities in the interactions between blood volume control, the cardiovascular system , the nervous system and circulation control system . [6] Contents 1 Signs and symptoms 1.1 Acute OI 1.2 Chronic OI 2 Causes 3 Diagnosis 4 Management 5 Notable case 6 See also 7 References 8 External links Signs and symptoms [ edit ] Orthostatic intolerance is divided, roughly based on patient history, in two variants: acute and chronic . Acute OI [ edit ] Patients who suffer from acute OI usually manifest the disorder by a temporary loss of consciousness and posture , with rapid recovery (simple faints , or syncope ), as well as remaining conscious during their loss of posture.

Not to be confused with Pott disease . Condition in which a change from lying to standing causes an abnormally large increase in heart rate Postural orthostatic tachycardia syndrome Other names Postural tachycardia syndrome (POTS) Specialty Cardiology , Neurology Symptoms More often with standing: lightheadedness , trouble thinking , tachycardia , weakness, [1] palpitations , heat intolerance , acrocyanosis Usual onset Most common (modal) age of onset is 14 years [2] Duration > 6 months [3] Causes Antibodies against the Alpha 1 adrenergic receptor [4] [5] [6] Risk factors Family history [1] Diagnostic method An increase in heart rate by 30 beats/min with standing [1] Differential diagnosis Dehydration , heart problems, adrenal insufficiency , epilepsy , parkinson disease [7] Treatment Avoiding factors that bring on symptoms, increasing dietary salt and water, compression stockings , exercise, medications [1] Medication Beta blockers , Ivabradine , midodrine , and fludrocortisone . [1] Prognosis ~90% improve with treatment, [8] 25% of patients unable to work [9] Frequency ~ 500,000 (US) [7] Postural orthostatic tachycardia syndrome ( POTS ) is a condition in which a change from lying to standing causes an abnormally large (or higher than normal) increase in heart beat rate . [1] This occurs with symptoms that may include lightheadedness , trouble thinking, blurred vision , or weakness. [1] Other commonly associated conditions include Ehlers–Danlos syndrome , mast cell activation syndrome , irritable bowel syndrome , insomnia , chronic headaches , chronic fatigue syndrome , and fibromyalgia . [1] Contents 1 Causation 2 Signs and symptoms 2.1 Brain fog 3 Causes 3.1 Autoimmunity 3.2 Secondary 4 COVID-19 5 Diagnosis 5.1 Diagnostic criteria 5.2 Autoantibodies against G-protein coupled receptor 5.3 Orthostatic intolerance 5.4 Differential diagnoses 6 Treatment 6.1 Medication 7 Prognosis 8 Epidemiology 9 History 10 Notable cases 11 References 12 Further reading 13 External links Causation [ edit ] The causes of POTS are varied. [10] Often, it begins after a viral infection, surgery, or pregnancy. [8] Risk factors include a family history of the condition. [1] Diagnosis in adults is based on an increase in heart rate of more than 30 beats per minute within ten minutes of standing up that is accompanied by symptoms. [1] Low blood pressure with standing , however, does not occur. [1] Other conditions which can cause similar symptoms, such as dehydration , heart problems, adrenal insufficiency , epilepsy , and parkinson disease , must not be present. [7] Treatment may include avoiding factors that bring on symptoms, increasing dietary salt and water, small and frequent meals, [11] avoidance of immobilization, [11] compression stockings , exercise program, and medications. [12] [13] [1] [14] Medications used may include beta blockers , [15] pyridostigmine , [16] midodrine [17] or fludrocortisone . [1] More than 50% of people whose condition was triggered by a viral infection get better within five years. [8] About 80% have symptomatic improvement with treatment, but 25 percent of patients are still unable to work. [9] [8] Retrospective studies has shown that five years after diagnosis 19% had a full resolution of symptom. [18] It is estimated that 500,000 people are affected in the United States. [19] The average age of onset is 20 years old, and it occurs about five times more frequently in females. [1] Signs and symptoms [ edit ] In adults the primary symptom is an increase in heart rate of more than 30 beats per minute within ten minutes of standing up. [1] [20] The resulting heart rate is typically more than 120 beats per minute. [1] For people aged between 12 and 19, the minimum increase for diagnosis is 40 beats per minute. [21] This symptom is known as orthostatic (upright) tachycardia (fast heart rate). It occurs without any coinciding drop in blood pressure, as that would indicate orthostatic hypotension . [20] Certain medications to treat POTS may cause orthostatic hypotension. It is accompanied by other features of orthostatic intolerance —symptoms that develop in an upright position and are relieved by reclining. [20] These orthostatic symptoms include palpitations , light-headedness , chest discomfort, shortness of breath , [20] nausea, weakness or "heaviness" in the lower legs, blurred vision , and cognitive difficulties. [1] Symptoms may be exacerbated with prolonged sitting, prolonged standing, alcohol, heat, exercise, or eating a large meal. [ citation needed ] In up to one third of people with POTS, [1] fainting occurs in response to postural changes or exercise. [22] Migraine -like headaches are common, sometimes with symptoms worsening in an upright position ( orthostatic headache ). [22] 40-50% of patients with POTS develop acrocyanosis of extremities, a reddish-purple color in the legs and/or hands when they stand (indicative of blood pooling). [23] [22] [24] 48% of people with POTS report chronic fatigue and 32% report sleep disturbances . [25] [26] [27] [28] Others exhibit only the cardinal symptom of orthostatic tachycardia. [22] Additional symptoms are varied, and may include excessive sweating, a lack of sweating, heat intolerance, digestive issues such as bloating, nausea, indigestion, constipation, and diarrhea, a flu-like feeling, coat-hanger pain, forgetfulness, brain fog, and presyncope . [29] Brain fog [ edit ] One of the most disabling and prevalent symptoms in POTS is " brain fog ", [30] a term used by patient to describe the cognitive difficulties they experience. In one survey of 138 POTS patients, brain fog was defined as “forgetful” (91%), “difficulty thinking” (89%), and “difficulty focusing” (88%). Other common description was "Difficulty processing what others say" (80%), Confusion (71%), Lost (64 %), and "Thoughts moving too quickly" (40%) [31] The same survey described the most common triggers of brain fog to be fatigue (91%), lack of sleep (90%), prolonged standing (87%) and dehydration (86%). [ citation needed ] Neuropsychological testing has shown that a POTS-patient has reduced attention (Ruff 2&7 speed and WAIS-III digits forward), short-term memory ( WAIS-III digits back), cognitive processing speed ( Symbol digits modalities test ) and executive function ( Stroop word color and trails B ). [32] [33] [34] A potential cause for brain fog is a decrease in cerebral blood flow (CBF), especially in upright position. [35] [36] [37] Another theory is that interoception of excessive autonomic activity causes interoceptive prediction errors (PE) to occur. [38] A prediction error is the mismatch between a prior expectation and reality. [39] This would cause anxiety which then overwhelms the consciousness of pots-patient causing cognitive-affective symptoms.

A number sign (#) is used with this entry because of evidence that orthostatic intolerance is caused by heterozygous mutation in the gene encoding the norepinephrine transporter (SLC6A2; 163970) on chromosome 16q12. One such family has been reported. Clinical Features Orthostatic intolerance is a syndrome characterized by adrenergic symptoms that occur when an upright posture is assumed: the heart rate increases by at least 30 beats per minute, without orthostatic hypotension (Jacob et al., 1997). Most patients with orthostatic intolerance are women between the ages of 20 and 50 years (Low et al., 1995). This syndrome, first described by Da Costa (1871), has been called soldiers heart (Fraser and Wilson, 1918), neurocirculatory asthenia (Wooley, 1976), and mitral valve prolapse syndrome (Boudoulas et al., 1980). It is similar in many respects to chronic fatigue syndrome (Schondorf and Freeman, 1999).

Garrod's pads (also known as violinist's pads [1] ) are a cutaneous condition characterized by calluses on the dorsal aspect of the interphalangeal joints , [2] i.e. the back side of the finger joints. They are often seen in violin , viola , and cello players, along with fiddler's neck and other dermatologic conditions peculiar to string musicians. [2] Although Garrod's pads are conventionally described as appearing on the proximal interphalangeal joint, distal interphalangeal joint involvement has also been described. [2] Garrod's pads are named after Archibald Garrod who first documented them in 1904 in association with Dupuytren's contracture . [3] H.A. Bird described them as an incidental finding in a professional violinist and proposed that they arise in such cases due to repeated extreme tension of the extensor tendons over the interphalangeal joints. [4] Bird noted that violin players use the left hand for a markedly different task than the right hand, with the extensor tendons in the left hand subjected to considerable tension, and that Garrod's pads only arise on the left hand in such cases. This unilateral finding differentiates the occupational hazard of Garrod's pads from more significant disorders. Among violinists and violists, Garrod's pads apparently arise as a protective mechanism for the skin and subcutaneous tissues above the tendons; Bird notes that they do not protect against external trauma unlike most calluses. [4] Patients with Dupuytren's contracture are four times more likely to have coexisting Garrod's pads. [5] [6] See also [ edit ] Knuckle pads Harpist's finger Fiddler's neck Cellist's chest Cello scrotum Paget-Schroetter syndrome List of cutaneous conditions List of eponymously named medical signs References [ edit ] ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007).

A number sign (#) is used with this entry because knuckle pads are associated with certain genetic disorders such as epidermolytis palmoplantar keratoderma (144200) or Dupuytren contractures (126900), both of which are autosomal dominant. Knuckle pads are sometimes associated with Dupuytren contractures and it is not completely certain that a different gene is involved. Camptodactyly (114200) also has an uncertain relationship. Skoog (1948) defined knuckle pads as 'subcutaneous nodules on the dorsal aspect of the proximal interphalangeal joints.' Lu et al. (2003) reported association of knuckle pads with epidermolytic palmoplantar keratoderma in a Chinese family and identified a novel leu160-to-phe mutation in the keratin-9 gene (L160F; 607606.0012) as the presumed cause. They presented evidence that both the hyperkeratosis and the knuckle pads were friction-related.