Physical Activity and Risk of Autoimmune Bullous Skin Diseases: A Prospective Cohort Study

Physical activity has been linked to immunee regulation in several autoimmune diseases, but its association with autoimmune bullous skin diseases (AIBD), mainly pemphigus and pemphigoid, has not been adequately evaluated. We examined the association between regular physical activity and incident AIBD in 476,057 UK Biobank participants. Multivariable-adjusted Cox models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for AIBD risk according to habitual physical activity. We also assessed joint associations with polygenic risk and performed mediation analysis. During a median follow-up of 15.21 years, 272 incident AIBD cases were documented, including 61 pemphigus and 211 pemphigoid cases. Physically active participants had a 31% lower risk of AIBD than inactive participants (adjusted HR 0.69, 95% CI 0.54-0.88). Similar associations were observed for pemphigus (HR 0.53) and pemphigoid (HR 0.72). Individuals with high genetic risk who were physically inactive had a higher risk than physically active individuals with low genetic risk (HR 2.12, 95% CI 1.47-3.07). In an exploratory mediation analysis, BMI accounted for 8.86 % of the association. These findings suggest that regular physical activity is associated with a lower risk of AIBD after adjustment for genetic susceptibility and other risk factors.