Long-term Particulate Matter Exposure and Risk of Alopecia Areata: A Nationwide Epidemiological Study with Preliminary In Vitro Evidence

BACKGROUND: Although particulate matter (PM) has been implicated in various systemic and cutaneous diseases, large-scale evidence on whether PM exposure affects the risk of alopecia areata (AA) remains limited. OBJECTIVES: To assess the epidemiologic association between long-term PM exposure and incident AA risk with exploration of potential biological mechanisms. METHODS: In the epidemiologic study, annual average concentrations of fine (PM2.5) and coarse (PM10) PM were linked to individuals who underwent national health screening between 2006 and 2022, and the risk of incident AA, defined as ≥3 outpatient claims with relevant diagnostic codes within a 1-year period, was evaluated. In the preliminary in vitro experiment, human hair outer root sheath (ORS) cells were exposed to varying concentrations of PM10-like fine dust for 24 hours. The expression of inflammatory cytokines was evaluated using quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence analyses. RESULTS: Higher long-term PM2.5 and PM10 exposures were associated with increased risk of incident AA (per 10μg/m3 increase, adjusted HR 1.45, 95% CI 1.39-1.52 for PM2.5 and adjusted HR 1.32, 95% CI 1.28-1.36 for PM10) with the strongest association for alopecia universalis subtype (per 10μg/m3 increase, adjusted HR 2.23, 95% CI 1.83-2.63 for PM2.5 and adjusted HR 1.82, 95% CI 1.58-2.07 for PM10). PM10 exposure increased reactive oxygen species generation, expression of IL-1β, IL-6, IL-8, and IL-15RA, and phosphorylation of p38 and STAT3 in ORS cells. CONCLUSIONS: This study suggests that ambient PM may be a modifiable environmental risk factor for AA through activation of selective inflammatory pathways, underscoring the need for public health efforts to reduce PM exposure and potentially mitigate AA risk.