Atopic Dermatitis as an Independent Risk Factor for Herpes Simplex Virus Infection Irrespective of Treatment: A Nationwide Population-Based Cohort Study

Abstract Background: Atopic dermatitis (AD) is characterized by chronic skin inflammation, impaired barrier function, and immune dysregulation. Although patients with AD are known to be susceptible to infections, the long-term risk of herpes simplex virus (HSV) infection and the influence of treatment modalities remain unclear. Objectives: To evaluate the risk of HSV infection among adults with AD compared with non-AD individuals and to determine whether systemic immunomodulatory treatments modify this risk. Methods: A retrospective nationwide cohort study was conducted using the Taiwan National Health Insurance Research Database (2000–2015), which included 140,775 individuals comprising 28,155 adults with AD and 112,620 matched controls. Adjusted hazard ratios (aHRs) for HSV infection were estimated using Cox proportional hazards models. Because subtype-specific coding was unavailable, HSV-1 and HSV-2 were analyzed collectively. Results: Adults with AD had a significantly higher risk of HSV infection than those without AD (aHR 2.243; 95% confidence interval (CI): 1.101–3.402; P < 0.001), a finding consistent across all age and sex subgroups. Elevated HSV risk was also observed in AD patients who did not receive systemic treatment. In contrast, systemic therapy was not associated with additional HSV risk. Kaplan–Meier analysis demonstrated a significantly higher cumulative HSV incidence in the AD cohort ( P < 0.001). Conclusion: AD is independently associated with an increased risk of HSV infection, irrespective of systemic treatment. These findings suggest that immune dysregulation and barrier impairment intrinsic to AD contribute to heightened susceptibility and highlight the importance of awareness and prevention in clinical management.