Background: Vitiligo is an autoimmune condition characterized by melanocyte loss and depigmented patches. Cytokines, especially those in the Th1 and Th17 pathways, play pivotal roles in its pathogenesis. Interleukin (IL)-38, a cytokine involved in immune regulation, may influence vitiligo progression and treatment outcomes, particularly in response to narrowband ultraviolet B (NB-UVB) therapy.

Aim: This study aimed to assess serum IL-38 levels in vitiligo patients compared to healthy controls and evaluate correlations between IL-38 levels, disease severity indices, and treatment response to NB-UVB.

Methods: A case-control study was conducted on 45 participants from the Dermatology Clinic at Benha University Hospitals. Group I included 15 patients with active vitiligo, Group II included 15 patients with stable vitiligo, and Group III included 15 healthy controls. Disease severity was assessed using Vitiligo Area Scoring Index (VASI) and Vitiligo Disease Activity (VIDA) scores, while quality of life was evaluated with the Dermatological Life Quality Index (DLQI). Serum IL-38 levels were measured pre- and post-NB-UVB therapy.

Results: IL-38 levels were significantly elevated in vitiligo patients compared to controls (P < 0.001), with generalized vitiligo showing the highest levels. Post-treatment, IL-38 levels decreased significantly (P = 0.003), correlating with improvements in VASI scores (P < 0.001). IL-38 demonstrated strong sensitivity and specificity for predicting vitiligo (AUC = 0.891).

Conclusion: Serum IL-38 is a potential biomarker for disease activity and treatment efficacy in vitiligo. Its role in modulating inflammation suggests therapeutic and diagnostic implications.