Introduction
Immune checkpoint inhibitors (ICIs) have emerged as key anti-tumor drugs that leverage the immune system to promote anti-tumor activity. Monoclonal antibodies directed against programmed cell death 1 (PD-1; e.g., nivolumab, pembrolizumab), programmed cell death ligand 1 (PD-L1; e.g., avelumab, atezolizumab, durvalumab), and cytotoxic T-lymphocyte associated protein 4 (CTLA-4; e.g., ipilimumab) have been approved for treating multiple solid tumor types, including melanoma, Merkel cell carcinoma, head and neck squamous cell carcinoma, non-small cell lung cancer, urothelial carcinoma, renal cell carcinoma, and gastrointestinal cancers. Sustained anti-tumor responses can be elicited, but immune-related adverse events (irAEs) affecting multiple organs may also be triggered.1–3 Cutaneous irAEs are the most frequent and usually the earliest irAEs arising in patients receiving ICIs. Dermatologists play an important role in evaluating and managing these cutaneous toxicities.
Cutaneous irAEs include a diverse group of inflammatory eruptions. Nonspecific maculopapular rash, pruritus, and lichenoid reactions are the most prevalent subtypes.4–6 Other frequent cutaneous irAEs include erythema multiforme, psoriasiform reactions, bullous pemphigoid, dermatomyositis, and oral mucosal changes.7, 8 Severe inflammatory eruptions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been also reported.7–11 Vitiligo-like depigmentation occurs frequently in patients who receive anti–PD-1 agents for melanoma.7, 8
Clinical trials have demonstrated that cutaneous irAEs are more likely to develop during combination anti–CTLA-4 and anti–PD-1 therapy (i.e., 40.3% of patients with melanoma receiving nivolumab and ipilimumab) than during monotherapy with anti–PD-1 (25.9% of patients with melanoma receiving nivolumab) or anti–CTLA-4 (32.8% of patients with melanoma receiving ipilimumab).12 Previous studies identified different rash types of irAEs and reported their characteristics, therapeutic impact, and response to treatment.4, 5 However, no report has described the clinical and histopathological findings of cutaneous irAEs in Asian populations. This study analyzed cutaneous irAEs to better characterize the features of each rash.