- • 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
- • Exclusion of other diseases capable of producing
a similar clinical/radiographic/histopathological
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.
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 ...