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.