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

Abstract

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.

Keywords: Autoantibodies; Cytokines; Dermatomyositis; Rheumatoid arthritis; Systemic sclerosis.

Figure 1

Seasonality analysis. Rose diagrams of the Rayleigh test showing the number of patients categorised by months of disease onset. The radius of each sector of the circle indicates the number of patients. Inside and outside circles represent 10 and 20 cases, respectively. An arrow indicates the mean direction of the circular data for significant seasonality. (A) Anti-MDA5-positive patients. (B) Anti-ARS-positive patients. Black sectors indicate numbers of patients with anti-Jo-1 antibody. (C) Anti-MDA5-/ARS-negative patients. ARS, aminoacyl tRNA synthetase; MDA5, melanoma differentiation-associated gene 5.

Figure 2

Distance from residential place to the nearest waterfront. Histograms showing the number of patients hierarchised by the distance from the residential place at disease onset to the nearest waterfront. The distance was categorised by multiplication of 1.75 km. Zone 0 covers the distance from 0 to 1.75 km, while Zone 1 covers the distance from 1.75 to 3.50 km. P values were calculated by exact Wilcoxon rank-sum test. (A) Distance to any waterfront. (B) Distance to seawater. (C) Distance to freshwater (river, lake or pond).