sarcoidosis sarcoidosis sarcoidosis (also known as besnier-boeck-schaumann disease) is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. the disease usually begins in the lungs, skin, or lymph nodes. less commonly affected are the eyes, liver, heart, and brain, though any organ can be affected. the signs and symptoms depend on the organ involved. often, no, or only mild, symptoms are seen. when it affects the lungs, wheezing, coughing, shortness of breath, or chest pain may occur. some may have löfgren syndrome with fever, large lymph nodes, arthritis, and a rash known as erythema nodosum. sarcoidosisother namessarcoïdosis, sarcoid, besnier-boeck-schaumann diseasechest x-ray showing the typical nodularity of sarcoidosis, predominantly in the bases of the lungs.pronunciationsar-koy-doh-sis specialtyrheumatology, immunologysymptomsdepends on the organ involvedlungs: wheezing, cough, shortness of breath, chest painskin: lumps, ulcers, discolored skinchildren: weight loss, bone pain, feeling tiredusual onset20–50 years old more common in womendurationfew years to long termcausesunknownrisk factorsfamily historydiagnostic methodbased on symptoms and tissue biopsydifferential diagnosistuberculosis, lymphoma, infectious mononucleosis, pulmonary eosinophiliatreatmentibuprofen, prednisone, methotrexateprognosismortality 1–7%frequency1.9 million with interstitial lung disease (2015)deaths122,000 with interstitial lung disease (2015) the cause of sarcoidosis is unknown. some believe it may be due to an immune reaction to a trigger such as an infection or chemicals in those who are genetically predisposed. those with affected family members are at greater risk. diagnosis is partly based on signs and symptoms, which may be supported by biopsy. findings that make it likely include large lymph nodes at the root of the lung on both sides, high blood calcium with a normal parathyroid hormone level, or elevated levels of angiotensin-converting enzyme in the blood. the diagnosis should only be made after excluding other possible causes of similar symptoms such as tuberculosis. sarcoidosis may resolve without any treatment within a few years. however, some people may have long-term or severe disease. some symptoms may be improved with the use of anti-inflammatory drugs such as ibuprofen. in cases where the condition causes significant health problems, steroids such as prednisone are indicated. medications such as methotrexate, chloroquine, or azathioprine may occasionally be used in an effort to decrease the side effects of steroids. the risk of death is 1–7%. the chance of the disease returning in someone who has had it previously is less than 5%. in 2015, pulmonary sarcoidosis and interstitial lung disease affected 1.9 million people globally and they resulted in 122,000 deaths. it is most common in scandinavians, but occurs in all parts of the world. in the united states, risk is greater among black people as opposed to white people. it usually begins between the ages of 20 and 50. it occurs more often in women than men. sarcoidosis was first described in 1877 by the english doctor jonathan hutchinson as a non-painful skin disease. signs and symptoms signs and symptoms of sarcoidosis sarcoid affecting the skin sarcoidosis is a systemic inflammatory disease that can affect any organ, although it can be asymptomatic and is discovered by accident in about 5% of cases. common symptoms, which tend to be vague, include fatigue (unrelieved by sleep; occurs in up to 85% of cases ), lack of energy, weight loss, joint aches and pains (which occur in about 70% of cases), arthritis (14–38% of cases), dry eyes, swelling of the knees, blurry vision, shortness of breath, a dry, hacking cough, or skin lesions. less commonly, people may cough up blood. sarcoidosis is also accompanied by psychological distress and symptoms of anxiety and depression, which are also associated with fatigue. the cutaneous symptoms vary, and range from rashes and noduli (small bumps) to erythema nodosum, granuloma annulare, or lupus pernio. sarcoidosis and cancer may mimic one another, making the distinction difficult. the combination of erythema nodosum, bilateral hilar lymphadenopathy, and joint pain is called löfgren syndrome, which has a relatively good prognosis. this form of the disease occurs significantly more often in scandinavian patients than in those of non-scandinavian origin. respiratory tract localization to the lungs is by far the most common manifestation of sarcoidosis. at least 90% of those affected experience lung involvement. overall, about 50% develop permanent pulmonary abnormalities, and 5 to 15% have progressive fibrosis of the lung parenchyma. sarcoidosis of the lung is primarily an interstitial lung disease in which the inflammatory process involves the alveoli, small bronchi, and small blood vessels. in acute and subacute cases, physical examination usually reveals dry crackles. at least 5% of cases include pulmonary arterial hypertension. the upper respiratory tract (including the larynx, pharynx, and sinuses) may be affected, which occurs in between 5 and 10% of cases. the four stages of pulmonary involvement are based on radiological stage of the disease, which is helpful in prognosis: stage i: bilateral hilar lymphadenopathy (bhl) alone stage ii: bhl with pulmonary infiltrates stage iii: pulmonary infiltrates without bhl stage iv: fibrosis use of the scadding scale only provides general information regarding the prognosis of the pulmonary disease over time. caution is recommended, as it only shows a general relation with physiological markers of the disease and the variation is such that it has limited applicability in individual assessments, including treatment decisions. skin main article: skin manifestations of sarcoidosis sarcoidosis involves the skin in between 9 and 37% of cases and is more common in african americans than in european americans. the skin is the second-most commonly affected organ after the lungs. the most common lesions are erythema nodosum, plaques, maculopapular eruptions, subcutaneous nodules, and lupus pernio. treatment is not required, since the lesions usually resolve spontaneously in 2–4 weeks. although it may be disfiguring, cutaneous sarcoidosis rarely causes major problems. sarcoidosis of the scalp presents with diffuse or patchy hair loss. heart histologically, sarcoidosis of the heart is an active granulomatous inflammation surrounded by reactive oedema. the distribution of affected areas is patchy with localised enlargement of heart muscles. this causes scarring and remodelling of the heart, which leads to dilatation of heart cavities and thinning of heart muscles. as the situation progresses, it leads to aneurysm of heart chambers. when the distribution is diffuse, there would be dilatation of both ventricles of the heart, causing heart failure and arrhythmia. when the conduction system in the intraventricular septum is affected, it would lead to heart block, ventricular tachycardia and ventricular arrhythmia, causing sudden death. nevertheless, the involvement of pericardium and heart valves are uncommon. the frequency of cardiac involvement varies and is significantly influenced by race; in japan, more than 25% of those with sarcoidosis have symptomatic cardiac involvement, whereas in the us and europe, only about 5% of cases present with cardiac involvement. autopsy studies in the us have revealed a frequency of cardiac involvement of about 20–30%, whereas autopsy studies in japan have shown a frequency of 60%. the presentation of cardiac sarcoidosis can range from asymptomatic conduction abnormalities to fatal ventricular arrhythmia. conduction abnormalities are the most common cardiac manifestations of sarcoidosis in humans and can include complete heart block. second to conduction abnormalities, in frequency, are ventricular arrhythmias, which occurs in about 23% of cases with cardiac involvement. sudden cardiac death, either due to ventricular arrhythmias or complete heart block is a rare complication of cardiac sarcoidosis. cardiac sarcoidosis can cause fibrosis, granuloma formation, or the accumulation of fluid in the interstitium of the heart, or a combination of the former two. cardiac sarcoidosis may also cause congestive heart failure when granulomas cause myocardial fibrosis and scarring. congestive heart failure affects 25-75% of those with cardiac sarcoidosis. diabetes mellitus and sarcoidosis-related arrhythmias are believed to be strong risk factors of heart failure in sarcoidosis. a small (20-40%) increased risk of acute myocardial infarction has also been described. pulmonary arterial hypertension occurs by two mechanisms in cardiac sarcoidosis: reduced left heart function due to granulomas weakening the heart muscle or from impaired blood flow. eye eye involvement occurs in about 10–90% of cases. manifestations in the eye include uveitis, uveoparotitis, and retinal inflammation, which may result in loss of visual acuity or blindness. the most common ophthalmologic manifestation of sarcoidosis is uveitis. the combination of anterior uveitis, parotitis, vii cranial nerve paralysis and fever is called uveoparotid fever or heerfordt syndrome (d86.8). development of scleral nodule associated with sarcoidosis has been observed. nervous system main article: neurosarcoidosis any of the components of the nervous system can be involved. sarcoidosis affecting the nervous system is known as neurosarcoidosis. cranial nerves are most commonly affected, accounting for about 5–30% of neurosarcoidosis cases, and peripheral facial nerve palsy, often bilateral, is the most common neurological manifestation of sarcoidosis. it occurs suddenly and is usually transient. the central nervous system involvement is present in 10–25% of sarcoidosis cases. other common manifestations of neurosarcoidosis include optic nerve dysfunction, papilledema, palate dysfunction, neuroendocrine changes, hearing abnormalities, hypothalamic and pituitary abnormalities, chronic meningitis, and peripheral neuropathy. myelopathy, that is spinal cord involvement, occurs in about 16–43% of neurosarcoidosis cases and is often associated with the poorest prognosis of the neurosarcoidosis subtypes. whereas facial nerve palsies and acute meningitis due to sarcoidosis tend to have the most favourable prognosis, another common finding in sarcoidosis with neurological involvement is autonomic or sensory small-fiber neuropathy. neuroendocrine sarcoidosis accounts for about 5–10% of neurosarcoidosis cases and can lead to diabetes insipidus, changes in menstrual cycle and hypothalamic dysfunction. the latter can lead to changes in body temperature, mood, and prolactin (see the endocrine and exocrine section for details). endocrine and exocrine prolactin is frequently increased in sarcoidosis, between 3 and 32% of cases have hyperprolactinemia this frequently leads to amenorrhea, galactorrhea, or nonpuerperal mastitis in women. it also frequently causes an increase in 1,25-dihydroxy vitamin d, the active metabolite of vitamin d, which is usually hydroxylated within the kidney, but in sarcoidosis patients, hydroxylation of vitamin d can occur outside the kidneys, namely inside the immune cells found in the granulomas the condition produces. 1,25-dihydroxy vitamin d is the main cause for hypercalcemia in sarcoidosis and is overproduced by sarcoid granulomata. gamma-interferon produced by activated lymphocytes and macrophages plays a major role in the synthesis of 1 alpha, 25(oh)2d3. hypercalciuria (excessive secretion of calcium in one's urine) and hypercalcemia (an excessively high amount of calcium in the blood) are seen in <10% of individuals and likely results from the increased 1,25-dihydroxy vitamin d production. thyroid dysfunction is seen in 4.2–4.6% of cases. parotid enlargement occurs in about 5–10% of cases. bilateral involvement is the rule. the gland is usually not tender, but firm and smooth. dry mouth can occur; other exocrine glands are affected only rarely. the eyes, their glands, or the parotid glands are affected in 20–50% of cases. gastrointestinal and genitourinary symptomatic gastrointestinal (gi) involvement occurs in less than 1% of cases (if one excludes the liver), and most commonly the stomach is affected, although the small or large intestine may also be affected in a small portion of cases. studies at autopsy have revealed gi involvement in less than 10% of people. these cases would likely mimic crohn's disease, which is a more commonly intestine-affecting granulomatous disease. about 1–3% of people have evidence of pancreatic involvement at autopsy. symptomatic kidney involvement occurs in just 0.7% of cases, although evidence of kidney involvement at autopsy has been reported in up to 22% of people and occurs exclusively in cases of chronic disease. symptomatic kidney involvement is usually nephrocalcinosis, although granulomatous interstitial nephritis that presents with reduced creatinine clearance and little proteinuria is a close second. less commonly, the epididymis, testicles, prostate, ovaries, fallopian tubes, uterus, or the vulva may be affected, the latter may cause vulva itchiness. testicular involvement has been reported in about 5% of people at autopsy. in males, sarcoidosis may lead to infertility. around 70% of people have granulomas in their livers, although only in about 20–30% of cases, liver function test anomalies reflecting this fact are seen. about 5–15% of patients exhibit hepatomegaly. only 5–30% of cases of liver involvement are symptomatic. usually, these changes reflect a cholestatic pattern and include raised levels of alkaline phosphatase (which is the most common liver function test anomaly seen in those with sarcoidosis), while bilirubin and aminotransferases are only mildly elevated. jaundice is rare. blood abnormal blood tests are frequent, accounting for over 50% of cases, but are not diagnostic. lymphopenia is the most common blood anomaly in sarcoidosis. anemia