Drug-associated vitiligo: A systematic review of therapies, clinical patterns and mechanisms.

BACKGROUND: Vitiligo is an acquired depigmenting disorder resulting from melanocyte loss. Although drug-associated vitiligo has been increasingly reported following exposure to immunomodulatory, oncological and other pharmacological therapies, implicated drug classes, clinical patterns and underlying mechanisms remain incompletely characterised. OBJECTIVES: To systematically review reported cases of drug-associated vitiligo, identify implicated therapies, characterise clinical features and evaluate proposed pathogenic mechanisms. METHODS: A systematic review was conducted according to PRISMA guidelines and a prospectively registered protocol (PROSPERO: CRD42025648719). Pubmed, Embase Classic + Embase and Ovid MEDLINE ALL were searched from January 1975 to April 2025, with an updated PubMed search performed to January 2026. Studies reporting new-onset vitiligo following exposure to a pharmacological agent were included. Demographic, clinical, treatment and outcome data were extracted and synthesised narratively. RESULTS: A total of 184 publications comprising 258 individual cases were included. The most frequently implicated drug classes were immune checkpoint inhibitors (72/258, 27.9%), topical immune modifiers and sensitisers (46/258, 17.8%), biologic immunomodulators (44/258, 17.1%) and targeted therapies (43/258, 16.7%). The most commonly reported agents were imiquimod 5% cream (n=30), nivolumab (n=30), diphenylcyclopropenone (n=18), pembrolizumab (n=17), interferon-α (n=17) and ribociclib (n=16). Vitiligo most commonly involved the upper extremities (n=127), face (n=119) and trunk (n=101). Among 256 cases with reported latency, vitiligo most frequently developed between 3 and 6 months following treatment initiation (66/256, 25.8%), although distinct temporal patterns were observed between therapeutic classes. Among malignancy-associated cases with available outcome data, favourable oncological outcomes were reported in 74/95 patients (77.9%), including 38/42 melanoma-associated cases (90.5%). Recurrent mechanistic themes included immune-mediated melanocyte destruction, direct melanocyte toxicity and local inflammatory triggering. CONCLUSIONS: Drug-associated vitiligo represents a heterogeneous spectrum of disorders spanning multiple therapeutic classes. While recurrent clinical patterns and biologically plausible mechanisms support a contributory role for several drug classes, causality remains uncertain for many reported associations. Recognition of characteristic clinical and temporal patterns may improve patient counselling, inform treatment decisions and guide future pharmacovigilance and mechanistic research.