Seasonal Variations in Drug-Related Erythema Multiforme: A Time Series Analysis Using the JADER Database

Abstract

Erythema multiforme (EM) is a rare, immune-mediated skin condition triggered primarily by infections, drugs, and autoimmune diseases. Although its seasonal variations have been reported, with peaks in spring and summer, comprehensive analyses remain limited. In this study, we aimed to investigate the seasonal patterns and drug associations of EM using the Japanese Adverse Drug Event Report database. A time series analysis was performed using EM-related adverse event onset dates reported between January 2005 and December 2019. The periodic patterns and residual autocorrelation were evaluated by applying seasonal and trend decomposition using loess (STL) and autocorrelation function (ACF) analyses to the time series data of monthly EM reports. A total of 3843 cases of EM were analyzed, with 43.1% being male and 56.3% female. STL decomposition identified June as the peak month for EM cases, with a higher incidence observed from spring to summer than in winter. Male patients exhibited greater seasonal variations, with a higher incidence in summer. Reports of anti-infective and antineoplastic drugs increased from spring to summer and declined in winter in male patients with EM, suggesting a potential seasonal trend. Female patients with EM also showed seasonal variations, albeit less pronounced than in male patients. The current study identified seasonal variations in drug-related EM, with reports peaking in June, which is consistent with previous observations of higher EM incidence in spring and summer. The findings indicated potential sex-related disparities in drug-related EM, underscoring the necessity for additional research to elucidate its mechanisms and patterns.