The cause of sarcoidosis is unknown. It is likely that both environmental factors and genetic susceptibility play an important role in the pathogenesis (1).
Genetic factors
- observations of familial clustering have indicated an increase in incidence of sarcoidosis among monozygotic twins over dizygotic or non-twin siblings (1)
- a questionnaire based study carried out on sarcoidosis patients in UK reported that 5.9% had at least one other relative (first, second, or third degree) with biopsy confirmed disease (2)
- furthermore a difference in the populations can be observed in various clinical presentations as well as absolute disease prevalence e.g. - African- Americans are more predisposed to a prolong and more severe form of sarcoidosis (4)
- a major linkage between sarcoidosis and class II major histocompatibility complex (MHC) region of the 6th chromosome has been suggested e.g. – erythema nodosum or Löfgren syndrome is strongly associated with H LA DQB1*0201 in British and Dutch patients (2)
Environmental factors
- person to person transmission or shared exposure to an environmental agent has been suggested as causes for geographical clusters reported in epidemiological studies (4)
- since lungs, eyes, and skin are commonly involved in sarcoidosis, an air born cause has been suggested by some
- earlier studies have shown an associations with exposures to irritants seen in rural settings, such as emissions from wood-burning stoves and tree pollen
- more recently, exposure to inorganic particles, insecticides and moldy environments have been shown to have a positive association
- clustering of cases have been reported in winter and early spring as well
- micro-organisms (such as mycobacteria and propionibacterium acnes) or organic/inorganic substances have also been suggested as a possible trigger of sarcoidosis (2,3)
There is defective cell mediated immunity in sarcoidosis which may be demonstrated by a negative tuberculin test in a patient with a previous positive result.
Despite the reduced response to tests of cellular mediated hypersensitivity, the lungs appear to be a site of intense lymphocyte activity and contain a large number of T lymphocytes (mostly T helper lymphocytes). Many have taken this pulmonary lymphocyte activity as an indication of infection, however no infective agent has been isolated.
Others suggest the pulmonary lymphocyte activity is secondary to reaction against very small foreign particles ("the nanoparticulate theory") (5):
- reason the particles are not seen microscopically is that they are nanoparticles (less than a micrometer in largest dimension); larger particles are cleared from the lung efficiently by mucociliary transport.
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