Sarcoidosis
[24] The cutaneous symptoms vary, and range from rashes and noduli (small bumps) to erythema nodosum, granuloma annulare, or lupus pernio.[25] The combination of erythema nodosum, bilateral hilar lymphadenopathy, and joint pain is called Löfgren syndrome, which has a relatively good prognosis.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.[19][22][56] Symptomatic kidney involvement is usually nephrocalcinosis, although granulomatous interstitial nephritis that presents with reduced creatinine clearance and little proteinuria is a close second.[68] 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.[19] In the absence of splenomegaly, leukopenia may reflect bone marrow involvement, but the most common mechanism is a redistribution of blood T cells to sites of disease.[69] Other nonspecific findings include monocytosis, occurring in the majority of sarcoidosis cases,[70] increased hepatic enzymes or alkaline phosphatase.[72] The arthritis symptoms of Löfgren syndrome occur most frequently in the ankles, followed by the knees, wrists, elbows, and metacarpophalangeal joints.[72] Even when erythema nodosum is absent, it is believed that the combination of hilar lymphadenopathy and ankle periarthritis can be considered as a variant of Löfgren syndrome.[72] Soft-tissue swelling of the ankles can be prominent, and biopsy of this soft tissue reveals no granulomas, but does show panniculitis similar to erythema nodosum.[72] Dactylitis similar to that seen in psoriatic arthritis, that is associated with pain, swelling, overlying skin erythema, and underlying bony changes may also occur.[2] The current working hypothesis is, in genetically susceptible individuals, sarcoidosis is caused through alteration to the immune response after exposure to an environmental, occupational, or infectious agent.[84] A meta-analysis investigating the role of mycobacteria in sarcoidosis found it was present in 26.4% of cases, but they also detected a possible publication bias, so the results need further confirmation.[84][92] Sarcoidosis has paradoxical effects on inflammatory processes; it is characterized by increased macrophage and CD4 helper T-cell activation, resulting in accelerated inflammation, but immune response to antigen challenges such as tuberculin is suppressed.[citation needed] The regulatory T-lymphocytes in the periphery of sarcoid granulomas appear to suppress IL-2 secretion, which is hypothesized to cause the state of anergy by preventing antigen-specific memory responses.[26] Likewise the ratio of CD4/CD8 T cells in bronchoalveolar lavage is usually higher in people with pulmonary sarcoidosis (usually >3.5), although it can be normal or even abnormally low in some cases.The presence of a noncaseating epithelioid granuloma in a gastrocnemius specimen is definitive evidence of sarcoidosis, as other tuberculoid and fungal diseases extremely rarely present histologically in this muscle.[28] Major categories of drug interventions include glucocorticoids, antimetabolites, biologic agents especially monoclonal anti-tumor necrosis factor antibodies.[19] Methotrexate can also lead to pulmonary toxicity (lung damage), although this is fairly uncommon and more commonly it can confound the leukopenia caused by sarcoidosis.[116] Likewise chlorambucil and cyclophosphamide are seldom used in the treatment of sarcoidosis due to their high degree of toxicity, especially their potential for causing malignancies.[114][116][127] Case reports have supported the efficacy of rituximab, an anti-CD20 monoclonal antibody and a clinical trial investigating atorvastatin as a treatment for sarcoidosis is under-way.[135] Antimycobacterial treatment (drugs that kill off mycobacteria, the causative agents behind tuberculosis and leprosy) has also proven itself effective in treating chronic cutaneous (that is, it affects the skin) sarcoidosis in one clinical trial.[138] Physical therapy, rehabilitation, and counseling can help avoid deconditioning,[138]: 733 and improve social participation, psychological well-being, and activity levels.[147] The risk for premature death was markedly (2.3-fold) increased compared to the general population for a smaller group of cases with severe disease at diagnosis.The first cases of sarcoïdosis, which were recognised as a new pathological entity, in Scandinavia, at the end of the 19th century exhibited skin nodules resembling cutaneous sarcomas, hence the name initially given.[178] American football player Reggie White died in 2004, with pulmonary and cardiac sarcoidosis being contributing factors to his fatal heart arrhythmia.[180] Manning Marable, a professor of public policy at Columbia University, died of pneumonia in 2011, less than a year after undergoing a double lung transplant following a diagnosis of sarcoidosis.In a 2014 letter to the British medical journal The Lancet, it was suggested that the French Revolution leader Maximilien Robespierre may have had sarcoidosis, causing him impairment during his time as head of the Reign of Terror.[185] Increased risks associated with sarcoidosis ranging from 30 to 70% have been reported for preeclampsia/eclampsia, cesarian or preterm delivery as well as (non-cardiac) birth defects in first singleton pregnancies.[186] In absolute numbers, birth defects and other complications such as maternal death, cardiac arrest, placental abruption or venous thromboembolism are extremely rare in sarcoidosis pregnancies.
SpecialtyRheumatologyimmunologySymptomswheezingshortness of breathRisk factorsDiagnostic methodtissue biopsyDifferential diagnosisTuberculosislymphomainfectious mononucleosispulmonary eosinophiliaIbuprofenprednisonemethotrexatePrognosisinterstitial lung diseaseinflammatory cellsgranulomatalymph nodesLöfgren syndromeenlarged hilar lymph nodesarthritiserythema nodosuminfectionbiopsylarge lymph nodesroot of the lunghigh blood calciumparathyroid hormoneangiotensin-converting enzymechloroquineazathioprineJonathan Hutchinsonasymptomaticfatiguelack of energyweight lossdry eyesrasheslupus perniodistinctionbilateral hilar lymphadenopathyjoint painparenchymacracklespulmonary arterial hypertensionlarynxpharynxsinusespulmonary infiltratesSkin manifestations of sarcoidosisAfrican Americansmaculopapularaneurysmventricular tachycardiaventricular arrhythmiasudden deathpericardiumheart blockcongestive heart failureDiabetes mellitusacute myocardial infarctionuveitisuveoparotitisparotitisHeerfordt syndromeNeurosarcoidosispapilledemaperipheral neuropathyMyelopathydiabetes insipidusProlactinhyperprolactinemiaamenorrheagalactorrheanonpuerperal mastitisvitamin DhypercalcemiaParotidDry mouthCrohn's diseasenephrocalcinosiscreatinineproteinuriaepididymistesticlesprostateovariesfallopian tubesuterusTesticular involvementhepatomegalycholestaticalkaline phosphatasebilirubinaminotransferasesLymphopeniaAnemiaLeukopeniaThrombocytopeniahemolytic anemiasplenomegalymonocytosisCandidapurified protein derivativehypergammaglobulinemiaLymphadenopathycervicalhilar lymphadenopathyEnthesitispanniculitisDactylitispsoriatic arthritisJaccoud arthropathyPeriostitistumor necrosis factoretanerceptethnicityEuropean AmericansHLA-DRHLA-B7HLA DR3-DQ2tumor necrosis factor alpha