The Role of Environmental Factors in the Pathogenesis of Anti-Neutrophil Antibody Associated Vasculitis

Abstract

This review seeks to critically examine the environmental factors reported to be associated with anti-neutrophil antibody associated systemic vasculitis. The published literature was searched in a systematic fashion. From this emerges strong evidence for a latitude gradient in the case of granulomatous polyangiitis and eosinophilic granulomatous polyangiitis; both appear more common at high latitudes. Microscopic polyangiitis does not demonstrate this. Latitude affects ultraviolet radiation exposure and the relationship of increased incidence of granulomatous polyangiitis and eosinophilic polyangiitis with decreased ultraviolet radiation exposure is much stronger. The most plausible explanation is vitamin D levels, a hormone known to be vital for normal immune function and largely synthesised in humans secondary to ultraviolet radiation exposure. Case control studies demonstrate a consistent relationship to silica exposure a substance well known to have profound immunological effects. The genetic risk factors for these diseases will be considered and a model of how genes and environment may interact to produce these diseases discussed. Low vitamin D levels, silica exposure, other environmental triggers may interact with genes that influence the immune and inflammatory response to initiate and sustain these diseases. As such, the broad concepts developed about the etiopathogenesis of the anti-neutrophil antibody associated vasculitides shows many parallels to other autoimmune diseases. Much more information is required about both genes and the environment, but the model helps define the questions that need to be answered.