Skin Manifestation Induced by Immune Checkpoint Inhibitors

In accordance with recent therapeutic progress of immune checkpoint inhibitors for certain cancers, various disorders are induced as immune-related adverse events (irAEs) affecting the skin, gut, thyroid gland, lung, and liver. Among such irAEs, mucocutaneous manifestation is the most common. Cutaneous manifestations are categorized into several groups, ie, inflammatory reactions, immunobullous reactions, alterations of epidermal keratinocytes, and alterations of epidermal melanocytes; however, there are additionally various cutaneous toxicities, unclassified into those groups. Blocking of programmed cell death 1 (PD-1)/programmed cell death ligand 1(PDL1) can lead to the induction of autoimmune reaction, via activation of cytotoxic T cells, inhibition of regulatory T cell function, and alteration of cytokine balance. Similarly, blockade of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) reduces the suppressive function of regulatory T cells. Due to those mechanisms, various autoimmune conditions can be induced, in addition to nonspecific drug eruptions. Dermatologists should be aware of various types of those mucocutaneous manifestations, either common or rare, as well as the management of such conditions. Herein, various mucocutaneous manifestations of irAEs and cases involving Japanese patients have been described, based on a single institute's experience.