Sarcoidosis is a multisystem granulomatous disease of unknown cause. Although the lung is most commonly affected, sarcoidosis may occur in any organ. The severity of pulmonary sarcoidosis may range from an abnormal screening chest radiograph finding in a patient free of symptoms, to end-stage lung disease with respiratory failure. Some patients have clinical disease that is most prominent in extrapulmonary organs. The prognosis of sarcoidosis is highly variable with a tendency to wax and wane, and may resolve either spontaneously or in response to therapy. The clinical course is chronic or progressive in 10 to 30% of patients.
Sarcoidosis is more common in first-degree relatives of an affected patient than in the general population. In the A Case Controlled Etiology of Sarcoidosis Study (ACCESS), the odds ratios (ORs) for a sarcoidosis patient having an affected parent or sibling were 16.6 (95% confidence interval [CI], 2.2 to 126.1) and 3.1 (95% CI, 1.4 to 7.1) for white and African-American patients, respectively. It has been estimated that approximately 19% of African Americans with sarcoidosis have an affected first-degree relative with the disease, compared to 6% in whites. It is not known if affected relatives have similar phenotypic expression of the disease. It is thought that sarcoidosis is caused by an abnormal host response to an unknown exposure in genetically susceptible individuals. Conceivably, first-degree relatives who are likely to share genes and environmental exposures might also have similar phenotypic disease expression.
The Sarcoidosis Genetic Analysis (SAGA) study was a multicenter study that enrolled African-American sibling pairs with sarcoidosis plus unaffected siblings to perform a genome scan to identify chromosomally linked regions. Affected sibling pairs were phenotypically characterized, gave detailed exposure histories, and were subjected to genetic analysis. The purpose of this article is to describe the phenotypic expression of sarcoidosis in SAGA sibling pairs, and to determine if there was significant similarity in phenotypic expression between sibling pairs,