Anti-neutrophil cytoplasmic antibody-associated systemic vasculitis: nature or nurture?

This review examines the environmental and genetic contributions to the anti-neutrophil cytoplasmic antibody-associated systemic vasculitides. The dominant environmental risk factors appear to be silica exposure for all three syndromes, and vitamin D deficiency is strongly suggested by the latitude and ultraviolet radiation gradient observed for Wegener's granulomatosis and Churg-Strauss syndrome. Genetic factors are generally not very strong, consistent with the rarity of these conditions in children. However, multiple genetic factors, each with a relatively small effect, may combine to create a state of susceptibility towards autoimmunity. With infection as a triggering agent, it is possible to synthesise a pathogenetic hypothesis that accounts for both environmental and genetic effects in regard to both necrotising vasculitis and granuloma formation.