Seasonal and residential clustering at disease onset of anti-MDA5-associated interstitial lung disease

Objectives To investigate whether the onset of polymyositis (PM)/dermatomyositis (DM)-associated interstitial lung disease (ILD) is influenced by season and residence in the context of myositis-specific autoantibodies. Methods For patients with PM/DM-associated ILD enrolled in a multicentre cohort, 365 and 481 patients were eligible for seasonal and geographical analysis, respectively, based on the availability of reliable clinical information. The patients were divided into three groups: (1) anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive patients, (2) anti-aminoacyl tRNA synthetase (anti-ARS) antibody-positive patients and (3) patients negative for those antibodies. Seasonality was assessed by the Rayleigh test. Distance from residence to the nearest waterfront was measured on Google Map and was compared between groups by the exact Wilcoxon rank-sum test. Results In anti-MDA5-positive patients, the disease developed more frequently in October-March (p=0.03), whereas a seasonal relationship was not found in the remaining two patient groups. Residence at disease onset in anti-MDA5-positive patients was significantly closer to the waterfront, especially to freshwater, compared with that in anti-ARS-positive or anti-MDA5-/ARS-negative patients (p=0.003 and 0.006, respectively). Conclusions Anti-MDA5-associated ILD occurred predominantly from October to March in individuals residing near freshwater, suggesting an environmental influence on the onset of this disease subset.