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Background: Sarcoidosis is a multiorgan granulomatous inflammatory disease of unknown aetiology. Familial clustering of cases and ethnic variation in the epidemiology suggests a genetic influence on susceptibility to the disease. This paper reports twin concordance and heritability estimates of sarcoidosis in order to assess the overall contribution of genetic factors to the disease susceptibility., Methods: Monozygotic and dizygotic twins enrolled in the Danish and the Finnish population-based national twin cohorts (61,662 pairs in total) were linked to diagnostic information on sarcoidosis obtained from the Danish National Patient Registry or the Social Insurance Institution, Finland registry of reimbursed medication using the 8th and 10th editions of the International Classification of Diseases. The Fisher exact test was used to compare probandwise concordance rates in different zygosity groups. Heritability was estimated based on a multifactorial threshold liability model., Results: A total of 210 twin pairs with at least one proband with a diagnosis of sarcoidosis were identified. The probandwise concordance rate was higher in monozygotic than in dizygotic twins (0.148 vs 0.012). Compared with the general population there was an 80-fold increased risk of developing sarcoidosis in co-twins of affected monozygotic brothers or sisters. The increased risk in dizygotic twins was only 7-fold. Aetiological model fitting gave a heritability of sarcoidosis of 0.66 (95% CI 0.45 to 0.80)., Conclusions: This study suggests that genetic factors play an important role in the susceptibility to sarcoidosis. This result should encourage the search for molecular genetic markers of susceptibility to the disease.

The review is based on studies of pulmonary sarcoidosis from Denmark, Finland and Sweden during 1950-1982, focusing on the course and prognosis of the disease. Cases with acute onset with chest X-ray stage I, fever, arthritis and erythema nodosum had a 85-90% remission rate during the first two years. The overall 5 year remission rate for stage I was 82%, stage II 66% and stage III 30%. Among cases with stage I, 2-5%, and among cases with stage II and III, 6-10% developed chronic pulmonary disease. Patients with stage I had a normal mortality rate, whereas those with stage II, III and IV had a rate threefold higher than expected due to sarcoidosis-related cardiopulmonary complications.