Shortfalls in imputing sarcoidosis to occupational exposures.

The cause of sarcoidosis remains elusive. Reports of elevated sarcoidosis incidence in New York City firefighters and World Trade Center disaster responders have been advanced to support a causal relationship. This inference is open to question due to methodological differences in assessing and computing sarcoidosis incidence in populations versus putative occupational exposures. The magnitude of the odds ratio (OR; ca. 1.5) of causal candidates in the ACCESS case-control study of occupational and environmental exposures is sufficiently small that it might easily be attributable to confounders. Additionally, multiplicity of comparisons, difficulty in assembling a valid control population and the potential for recall bias critically limit causal inferences. A possible explanation for etiological elusiveness and multiplicity of elevated OR is that individuals with sarcoidosis, lacking components of efficient cellular immunity, respond with systemic granulomas to a variety of ubiquitous, frequently unidentifiable environmental antigens. Epidemiological methods for the identification of sarcoidosis causal candidates are potentially misleading and are unlikely to prove useful.