Chapter 12

• • Sarcoidosis is a systemic granulomatous disorder of unknown etiology, primarily affecting the lung.
• • Diagnostic criteria:
• • Compatible clinical and radiographic presentation (see specifics below).
• • Histopathological demonstration of noncaseating granulomatous inflammation.
• • Exclusion of other diseases capable of producing a similar clinical/radiographic/histopathological picture.

In 1899, Boeck used the term “multiple benign sarkoid of the skin” to describe a disorder characterized by multiple raised skin lesions. Subsequently, similar pathological findings were seen in other organ systems, including the lung and lymph nodes, and the term “sarcoidosis” was derived from these descriptions. Sarcoidosis occurs worldwide, affecting individuals of all races, all ages, and both sexes, although with a slight female predominance. Most patients are diagnosed between the ages of 20 and 40 years, with a peak incidence in the 20–29 year age group. Estimates of disease prevalence in the United States range from <1 to 40 per 100,000 with certain ethnic and racial groups having an increased incidence of disease. For example, age-adjusted incidence rates in the United States are 35.5 per 100,000 for African-Americans and 10.9 per 100,000 for whites. African-Americans also tend to present with more severe disease.

Newman LS, Rose CS, Maier LA: Sarcoidosis. N Engl J Med 1997;336:1224.   [PubMed: 9110911] (Good general review of clinical manifestations, diagnosis, and treatment of sarcoidosis.)

Although the cause(s) of sarcoidosis is unknown, evidence suggests that the immune response occurs following a specific environmental exposure in genetically susceptible individuals. Whether an infectious or noninfectious environmental agent is responsible for initiation of the inflammatory response remains unknown. Several epidemiological studies of disease clusters support the existence of shared environmental exposures. These include a case–control study of a sarcoidosis cluster on the Isle of Man, which revealed that a significantly greater percentage of cases as compared to control subjects had previous contact with a sarcoidosis patient. In addition, clusters of disease have been found among nurses, firefighters, and individuals exposed to pine pollen.

Large numbers of activated macrophages and T-lymphocytes accumulate at sites of ongoing inflammation. The T cells express a CD4+ phenotype and secrete Th1-type cytokines such as interleukin-2 and interferon-γ. CD4+ T cell alveolitis likely represents the earliest event in generation of the noncaseating granuloma. The CD4+ T cells result from oligoclonal expansion, suggesting development of a conventional antigen-stimulated immune response.

The variation in incidence, severity, and manifestations of disease among different racial and ethnic groups suggests a genetic predisposition to disease development. Another observation that supports genetic susceptibility is familial clustering of disease. For example, sarcoidosis occurs two to four times more frequently in monozygotic than in dizygotic twins. Similarly, up to 19% of affected African-American families and 5% of white families have more than one affected family member. Results from a case–control etiological study of sarcoidosis (ACCESS) further support these observations. This study enrolled over 700 case–control pairs in the United States matched for age, gender, race, and ethnicity. Analysis of nearly 11,000 first-degree and over 17,000 second-degree relatives of these groups demonstrated an overall adjusted familial relative risk of developing sarcoidosis of 4.7 (95% CI = 2.3–9.7). In this study whites had a much higher familial relative risk compared to African-Americans (18.0 ...

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