Association of herpes simplex virus infection and vitiligo: a nationwide retrospective cohort study

Background: Several studies have proposed viral infection with herpes simplex virus (HSV) as a probable cause of vitiligo. We aimed to examine the association between HSV infection and vitiligo.

Methods: We used the National Health Insurance Research Database of Taiwan to perform a comparative analysis of the study population with or without a diagnosis of HSV infection. The study period was from January 1st, 2008, to December 31st, 2019. The primary outcome was the date of first vitiligo diagnosis, death, withdrawal from the National Health Insurance Program, or end of the study.

Results: We performed 1:1 propensity score matching based on age, sex, and comorbidities, resulting in 1,009,445 matched pairs of patients with and without HSV infections. The adjusted hazard ratio for developing vitiligo in the HSV cohort was 1.71 (95% confidence interval, 1.59 - 1.83; P < 0.001). An age-dependent pattern was also observed among HSV-infected patients with vitiligo (P for interaction < 0.001). Both sexes exhibited a significantly higher risk of developing vitiligo in the presence of HSV infection. The HSV cohort significantly increased cumulative vitiligo risk compared to the non-HSV cohort in a 12-year follow-up (log-rank P < 0.001). The result of sensitivity analysis was compatible with that of primary analysis. Patients with HSV infection had a considerably increased vitiligo risk within the 1-year follow-up than the non-HSV cohort (adjusted hazard ratio, 4.83; 95% confidence interval, 4.04 - 5.77, P < 0.001).

Conclusion: This nationwide population-based study demonstrated an association between HSV infection and an increased risk of vitiligo. Further investigation of HSV DNA in the affected regions of vitiligo lesions may help to establish causality.