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A rare multisystemic, autoinflammatory disorder of unknown etiology characterized by the formation of immune, non-caseating granulomas in any organ(s), leading to variable clinical symptoms and severity. Clinical presentation is typically with persistent dry cough, eye or skin manifestations, peripheral lymph nodes, fatigue, weight loss, fever or night sweats, and Löfgren syndrome.
ORPHA:797Classification level: Disorder
Sarcoidosis is a ubiquitous disease with incidence varying according to age, sex, race and geographic origin. The highest rates are reported in Northern Europe and in African-American individuals, the lowest rates in Asia. In Europe, incidence ranges between 1/625 to 500,000 inhabitants. There is a slight predominance in females.
Presentation, severity and evolution of sarcoidosis is highly variable. Diagnosis typically occurs in the fourth and fifth decade of life with a second peak of incidence occurring in women older than 50 years of age, but presentation may occur anywhere between childhood and elderly age. The disease is classed as either acute, resolving within 2 years, or chronic, persisting for 3-5 years or longer. The lung and the lymphatic system are predominantly affected, but virtually every organ may be involved. Other severe manifestations result from cardiac, neurological, ocular, kidney or laryngeal localizations. In most cases, sarcoidosis is revealed by persistent dry cough, eye or skin manifestations, peripheral lymph nodes, fatigue, weight loss, fever or night sweats, and Löfgren syndrome (an acute form characterized by fever, bilateral ankle arthritis and/or erythema nodosum and bilateral hilar lymphadenopathy). Abnormal metabolism of vitamin D3 within granulomatous lesions and hypercalcemia are possible. Chest radiography is abnormal in about 90% of cases and shows lymphadenopathy and/or pulmonary infiltrates (without or with fibrosis), defining sarcoidosis stages from I to IV. African-Americans present a more severe disease, and in Scandinavian countries, about one third of cases have Löfgren syndrome.
The etiology remains unknown. The prevailing hypothesis is that various, unidentified antigens of either infectious or environmental origin could trigger an exaggerated immune reaction in genetically susceptible hosts.
Diagnosis relies on compatible clinical and radiographic manifestations, biopsy showing non-caseating granulomas and exclusion of all other causes of granulomatous disease. Some situations do not require biopsy such as Lofgren's syndrome or the presence of typical asymptomatic bilateral mediastino-hilar adenopathies. Biopsies from easily accessible areas (skin, peripheral lymphadenopathies, conjunctival nodules) should be considered. However, bronchoscopy with bronchial and transbronchial biopsies has a good diagnostic performance. Endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA) provide a high yield in case of mediastino-hilar lymphadenopathies.
Differential diagnosis includes infections, chronic beryllium disease, common variable immunodeficiency, hypersensitivity pneumonitis, granulomatous polyangiitis, Crohn disease, sarcoid-like reactions (cancer or lymphomas), as well as drug-induced granulomatosis.
Sarcoidosis results from a complex interaction of multiple genes and thus does not require genetic counseling.
Management and treatment
Depending on the evolution and severity of sarcoidosis, patients may not require systemic therapy. Therapy is considered where there is a possibility of severe complications (i.e. functional organ failure) or to reduce persistent symptoms of discomfort that impact on quality of life. Discomfort may be due to fibrosis, para-sarcoidosis syndrome or comorbidities as well as active disease. Treatment is principally with systemic corticosteroids, and generally maintained for 12 months; however, the duration and minimal efficient dose should be adapted to each patient. Patients with repeated relapses may require long-term, low-dose corticosteroid therapy. Other treatments including immunosuppressive drugs (methotrexate, azathioprine, or leflunomide) and aminoquinolins may be useful in case of unsatisfactory response to corticosteroids, poor tolerance or as sparing agents. In some strictly selected cases refractory to standard therapy, specific anti-TNF-alpha agents (infliximab or adalimumab) may offer improvement. Some patients benefit from topical corticosteroids.
In at least half of cases, sarcoidosis resolves spontaneously within 2 years. Remission is less likely where diseases persists for five years after presentation. Mortality is estimated at 6-8% and typically due to organ failure (typically respiratory or cardiac). The extent of pulmonary fibrosis and pulmonary hypertension are predictive of mortality.