Topical Ruxolitinib for Immune Checkpoint Inhibitor–Induced Vitiligo

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) or its ligand have transformed the prognosis of advanced melanoma but may induce a spectrum of cutaneous immune-related adverse events (irAEs) [1]. Among these, vitiligo-like depigmentation is a well-recognized manifestation, and is often associated with favorable tumor response, but management of extensive or cosmetically distressing nonsegmental vitiligo arising during anti–PD-1 therapy remains challenging [2]. We report a case of anti–PD-1–induced nonsegmental vitiligo successfully treated with topical ruxolitinib, a Janus kinase (JAK)1/2 inhibitor, while continuing nivolumab without oncologic compromise. A 62-year-old man with stage IV metastatic melanoma developed progressive depigmented macules on the face and trunk after 10 months of nivolumab monotherapy. Cutaneous examination revealed sharply demarcated, milky-white macules coalescing into larger patches on highly visible facial areas and on the trunk (Figure 1A,B). Wood's lamp examination showed bright chalk-white accentuation, consistent with active depigmentation. The estimated baseline Vitiligo Extent Score (VES) was 2.08. The patient had a history of localized genital vitiligo that had remained stable for several years, without other involvement. Given the rapid extension and psychosocial impact of facial lesions, treatment with topical ruxolitinib 1.5% cream twice daily was initiated on the affected areas, while nivolumab was continued due to sustained oncologic benefit. No systemic corticosteroids or additional immunosuppressive agents were administered. After 12 weeks of treatment, partial perifollicular repigmentation was observed on the face and trunk, with a reduction in VES to 1.6 and clear cosmetic improvement (Figure 1C,D). Continued application led to further gradual repigmentation over 5 months of total follow-up. Treatment was well tolerated, with no local irritation or systemic adverse events reported. The pathogenesis of anti–PD-1–induced vitiligo involves enhanced cytotoxic CD8+ T-cell responses directed against shared melanocytic antigens. PD-1 blockade amplifies interferon-gamma (IFN-γ) production and CXCL10-mediated T-cell recruitment, leading to activation of the Janus kinase/signal transducer and activator of transcription (JAK–STAT) signaling pathway, a central driver of melanocyte destruction in both idiopathic and ICI-induced vitiligo. Topical ruxolitinib, a selective JAK1/2 inhibitor, blocks downstream IFN-γ signaling locally, thereby reducing T-cell–mediated melanocyte apoptosis and enabling repigmentation [3, 4]. While its efficacy in nonsegmental vitiligo has been established in phase III trials, evidence specifically addressing ICI-induced vitiligo has not been reported. Importantly, topical JAK inhibition provides localized immunomodulation with minimal systemic absorption, theoretically reducing the risk of interfering with systemic antitumor immunity [5]. In our patient, continuation of PD-1 blockade alongside topical ruxolitinib was not associated with diminished oncologic response during follow-up, supporting the feasibility of this approach in carefully selected cases. Vitiligo arising during immunotherapy should be recognized not only as a biomarker of immune activation but also as a treatable condition when cosmetically or psychologically impactful. This case highlights the potential role of targeted JAK inhibition as a mechanism-based therapeutic approach for anti–PD-1–induced nonsegmental vitiligo, allowing preservation of life-prolonging immunotherapy while effectively addressing pigmentary toxicity. The authors have nothing to report. The patient in this manuscript has given written informed consent to publication of their case details. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.