Immune checkpoint inhibitor–related dermatologic adverse events

• Published in: Journal of the American Academy of Dermatology Vol. 83; no. 5; pp. 1255 - 1268
• Main Authors: Geisler, Amaris N., Phillips, Gregory S., Barrios, Dulce M., Wu, Jennifer, Leung, Donald Y.M., Moy, Andrea P., Kern, Jeffrey A., Lacouture, Mario E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2020
• Subjects: checkpoint inhibitor; CTLA-4 inhibitor; dermatologic adverse event; Drug Eruptions - epidemiology; Drug Eruptions - etiology; Drug Eruptions - immunology; Drug Eruptions - pathology; Humans; Immune Checkpoint Inhibitors - adverse effects; immune-related cutaneous adverse event; lichenoid eruption; maculopapular rash; Neoplasms - drug therapy; PD-1 inhibitor; PD-L1 inhibitor; pruritus; vitiligo; pruritus; LP; TCS; BP; MPR; BSA; PD-L1; immune-related cutaneous adverse event; PD-L1 inhibitor; CTLA-4; dermatologic adverse event; SJS; checkpoint inhibitor; DIF; irCAE; AE; SCAR; vitiligo; PD-1 inhibitor; DRESS; CTLA-4 inhibitor; maculopapular rash; lichenoid eruption; irAE; TEN; CPI; PD-1
• ISSN: 0190-9622; 1097-6787
• DOI: 10.1016/j.jaad.2020.03.132

Immune checkpoint inhibitors have emerged as a pillar in the management of advanced malignancies. However, nonspecific immune activation may lead to immune-related adverse events, wherein the skin and its appendages are the most frequent targets. Cutaneous immune-related adverse events include a diverse group of inflammatory reactions, with maculopapular rash, pruritus, psoriasiform and lichenoid eruptions being the most prevalent subtypes. Cutaneous immune-related adverse events occur early, with maculopapular rash presenting within the first 6 weeks after the initial immune checkpoint inhibitor dose. Management involves the use of topical corticosteroids for mild to moderate (grades 1-2) rash, addition of systemic corticosteroids for severe (grade 3) rash, and discontinuation of immunotherapy with grade 4 rash. Bullous pemphigoid eruptions, vitiligo-like skin hypopigmentation/depigmentation, and psoriasiform rash are more often attributed to programmed cell death-1/programmed cell death ligand-1 inhibitors. The treatment of bullous pemphigoid eruptions is similar to the treatment of maculopapular rash and lichenoid eruptions, with the addition of rituximab in grade 3-4 rash. Skin hypopigmentation/depigmentation does not require specific dermatologic treatment aside from photoprotective measures. In addition to topical corticosteroids, psoriasiform rash may be managed with vitamin D3 analogues, narrowband ultraviolet B light phototherapy, retinoids, or immunomodulatory biologic agents. Stevens–Johnson syndrome and other severe cutaneous immune-related adverse events, although rare, have also been associated with checkpoint blockade and require inpatient care as well as urgent dermatology consultation.