Immune checkpoint inhibitors (ICIs) have transformed the management of melanoma, but immune activation can also trigger cutaneous immune-related adverse events (cirAEs), among the earliest and most frequent treatment toxicities. This narrative review critically examines the mechanisms, clinical spectrum, assessment, management and prognostic significance of cirAEs, highlighting their implications for melanoma care.
Literature was identified through structured searches of PubMed, Ovid (Embase), and Google Scholar conducted between February and August 2026, supplemented by guideline review and citation chaining, yielding 112 sources.
Reported cirAE incidence varies from approximately 20–60%, reflecting differences in regimen, tumour type, and ascertainment. Combined CTLA-4/PD-1 blockade, an important strategy in melanoma, is associated with particularly frequent and early cutaneous toxicity. The phenotypic spectrum is broad, extending from common inflammatory eruptions to autoimmune blistering disease, severe cutaneous adverse reactions, and a growing list of rare entities defined largely by case reports. Recent consensus disease definitions have begun to replace the non-specific term "rash" with phenotype-specific diagnoses.
Severity grading remains dependent on Common Terminology Criteria for Adverse Events (CTCAE), which relies heavily on body surface area and incompletely captures symptom burden, anatomical site, and psychosocial impact. Most low-grade cirAEs can be managed without ICI interruption, whereas severe or refractory disease may require systemic therapy and coordinated oncology–dermatology input. Management is increasingly phenotype-directed, with targeted biologics emerging as steroid-sparing options for refractory cases, although the supporting evidence remains largely anecdotal.
Vitiligo-like depigmentation is of particular relevance in melanoma: reactivated cytotoxic T cells may recognise antigens shared by melanoma cells and normal melanocytes. Its development has been associated with improved progression-free and overall survival, although observational analyses remain vulnerable to immortal-time bias and confounding.
These findings support phenotype-specific diagnosis, judicious immunosuppression, and avoidance of unnecessary ICI interruption. Prospective studies are needed to refine management and establish whether cirAEs can serve as reliable biomarkers of treatment response in melanoma.