Neurological Sciences, cilt.47, sa.4, 2026 (SCI-Expanded, Scopus)
Immune checkpoint inhibitors (ICIs), particularly pembrolizumab, have significantly improved outcomes in carcinomas; however, they may trigger immune-related adverse events (irAEs) across multiple organ systems. Vitiligo and central nervous system (CNS) demyelination are individually recognized irAEs, yet their simultaneous occurrence is rare and may offer mechanistic insights. Here, we report a 63-year-old male with metastatic urothelial carcinoma who developed new-onset vitiligo after four cycles of enfortumab-vedotin plus pembrolizumab combination therapy. Despite continuation of treatment due to favorable tumor response, the patient subsequently presented with rapidly progressive ataxia, muscle weakness, and seizures. Brain MRI demonstrated contrast-enhancing patchy demyelinating plaques involving both grey and white matter, and EMG supported demyelinating pathology. High-dose corticosteroids and intravenous immunoglobulin (IVIG) resulted in partial neurological improvement. The temporal association between immunotherapy exposure, cutaneous depigmentation, and CNS demyelination suggests a shared neurocutaneous susceptibility. This case reinforces the hypothesis that ICIs can activate immune mechanisms simultaneously affecting melanocytic and myelin-forming cells. Awareness of this spectrum is clinically important, as vitiligo may correlate with favorable oncologic outcomes, but demyelination poses potentially severe neurologic risks requiring prompt recognition and multidisciplinary management.