The Association Between Repeated Lip Augmentation With Hyaluronic Acid Filler and Recurrence of Herpes Labialis: A Longitudinal Self-controlled Study

Background Recurrent herpes labialis is a common condition characterized by episodic viral reactivation triggered by local or systemic factors. Hyaluronic acid lip augmentation is widely performed for aesthetic purposes, yet its potential association with changes in herpes labialis recurrence has not been systematically evaluated. Objectives To investigate whether repeated lip augmentation with hyaluronic acid filler is associated with changes in the incidence of recurrent herpes labialis episodes over time. Methods A self-controlled longitudinal observational study was conducted in adult patients with a documented history of recurrent herpes labialis undergoing lip augmentation with hyaluronic acid filler between 2016 and 2025. Each participant served as their own control, with recurrence rates compared across predefined baseline and post-treatment intervals. The primary outcome was the incidence of clinically typical herpes labialis episodes, expressed as episodes per person-year. Recurrent events were analyzed using generalized estimating equations with a negative binomial distribution. Results Ninety patients were included in the final analysis. Baseline incidence was 5.22 episodes per person-year. No significant change in recurrence rate was observed after the first filler session. A statistically significant reduction emerged after the second session (incidence rate ratio [IRR] 0.81; 95% CI 0.72–0.91; p<0.001) and became more pronounced after subsequent sessions. After four sessions, the IRR was 0.55 (95% CI 0.45–0.66; p<0.001). Recurrence rates stabilized after multiple treatments. Conclusions In this longitudinal self-controlled cohort, repeated lip augmentation with hyaluronic acid filler was associated with a progressive reduction in recurrent herpes labialis incidence after multiple sessions. The clinical relevance of this observed reduction was not predefined. While causality cannot be established, the temporal pattern and statistical robustness of the findings warrant further investigation.