Immune checkpoint inhibitor-induced cutaneous toxicities: a review of histopathologic and clinical features

Julianna Martel; Hannah L Hanania; Anisha B Patel

doi:10.1016/j.humpath.2023.04.016

Immune checkpoint inhibitor-induced cutaneous toxicities: a review of histopathologic and clinical features

Hum Pathol. 2023 Oct:140:144-172. doi: 10.1016/j.humpath.2023.04.016. Epub 2023 May 2.

Authors

Julianna Martel¹, Hannah L Hanania², Anisha B Patel³

Affiliations

¹ Department of Dermatology, The University of Texas, MD Anderson Cancer Center, Houston, TX, 77030, USA.
² Baylor College of Medicine, Houston, TX, 77030, USA.
³ Department of Dermatology, The University of Texas, MD Anderson Cancer Center, Houston, TX, 77030, USA. Electronic address: Apatel11@mdanderson.org.

PMID: 37141978
DOI: 10.1016/j.humpath.2023.04.016

Abstract

Immune checkpoint inhibitors (ICIs) represent an emerging treatment option for a variety of cancer types. Through inhibition of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), and/or cytotoxic lymphocyte-associated antigen-4 (CTLA-4), ICIs activate the host's immune system causing a heightened anti-tumor response. However, off-target effects of ICIs can result in numerous different immune-related cutaneous adverse events (irCAEs). Beyond impacting quality of life, irCAEs can lead to dose limitations or discontinuation of anti-cancer therapies. Correct diagnosis is necessary for expedient and appropriate management. Skin biopsies are often performed to increase diagnostic accuracy and guide clinical management. An extensive literature review was performed using the PubMed database to identify the reported clinical and histopathologic features of irCAEs. This comprehensive review primarily details the histopathologic features of various irCAEs reported to date. Clinical presentation and immunopathogenesis are also discussed in relation to histopathology.

Keywords: CTLA-4; Checkpoint inhibitor; Cutaneous; Drug rash; Immunotherapy; PD-1; PD-L1.