Antineutrophil Cytoplasmic Antibody - Associated Vasculitides: Could Geographic Patterns Be Explained by Ambient Ultraviolet Radiation?

Abstract

Objective. This ecological study describes and quantifies the association between ambient ultraviolet (UV) radiation levels, including daily winter vitamin D effective UV radiation levels and the incidence of the 3 antineutrophil cytoplasmic antibody-associated vasculitides (AAVs): Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), and Churg-Strauss syndrome (CSS). Latitudinal variation in occurrence of the AAVs, especially WG, has been previously reported. For other autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus, inverse associations with latitude are hypothesized to indicate a causative role for low UV radiation exposure, possibly acting via vitamin D status. Methods. Published epidemiologic studies provided data on incident cases, total population of study regions, age-specific incidence rates, and study location. From these data and online age-specific population data, we calculated crude incidence rates, the expected number of cases (to control for possible age confounding), and measures of ambient UV radiation. Negative binomial regression models were used to calculate the incidence rate ratio (IRR) for a 1,000 joules/m2 increase in ambient UV radiation. Results. The incidence of WG and CSS increased with increasing latitude and decreasing ambient UV radiation, with a stronger and more consistent effect across different UV radiation measures for WG, e.g., for average daily ambient clear sky erythemal UV radiation (WG: IRR 0.64 [95% confidence interval (95% CI) 0.44-0.94], P = 0.02; CSS: IRR 0.67 [95% CI 0.43-1.05], P = 0.08; MPA: IRR 1.16 [95% CI 0.92-1.47], P = 0.22). There was no apparent latitudinal variation in MPA incidence. Conclusion. Our findings are consistent with a protective immunomodulatory effect of ambient UV radiation on the onset of WG and CSS. We discuss possible mechanisms, including the effect of vitamin D on the immune system.