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World J Exp Med. Dec 30, 2021; 11(6): 79-92
Published online Dec 30, 2021. doi: 10.5493/wjem.v11.i6.79
Differential diagnosis and management of immune checkpoint inhibitor-induced colitis: A comprehensive review
Hua Li, Zhi-Yan Fu, Mustafa Erdem Arslan, Daniel Cho, Hwajeong Lee
Hua Li, Zhi-Yan Fu, Mustafa Erdem Arslan, Hwajeong Lee, Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
Daniel Cho, Schenectady Pathology Associates, Ellis Hospital, Schenectady, NY 12308, United States
Author contributions: Li H carried out the study including review of the literature, data analysis, and drafted the manuscript, gave final approval of the version to be published; Fu ZY, Arslan ME and Cho D contributed to the editing and critical review of the manuscript, as well as final approval of the version to be published; Lee H provided cases for microscopic images, edited and critically reviewed the manuscript, and approved the final version to be published; all authors are agreeable to be accountable for all aspects of the work.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hwajeong Lee, MD, Associate Professor, Department of Pathology and Laboratory Medicine, Albany Medical Center, 47 New Scotland Ave. MC81, Albany, NY 12208, United States. leeh5@amc.edu
Received: February 19, 2021
Peer-review started: February 19, 2021
First decision: July 29, 2021
Revised: August 8, 2021
Accepted: December 23, 2021
Article in press: December 23, 2021
Published online: December 30, 2021
Abstract

Immune checkpoint inhibitors (ICIs) are a new class of cancer pharmacotherapy consisting of antibodies that block inhibitory immune regulators such as cytotoxic T lymphocyte antigen 4, programmed cell death 1 and programmed death-ligand 1. Checkpoint blockade by ICIs reactivates a tumor-specific T cell response. Immune-related adverse events can occur in various organs including skin, liver, and gastrointestinal tract. Mild to severe colitis is the most common side effect with some experiencing rapid progression to more serious complications including bowel perforation and even death. Prompt diagnosis and management of ICI-induced colitis is crucial for optimal outcome. Unfortunately, its clinical, endoscopic and histopathologic presentations are non-specific and overlap with those of colitis caused by other etiologies, such as infection, medication, graft-versus-host disease and inflammatory bowel disease. Thus, a definitive diagnosis can only be rendered after these other possible etiologies are excluded. Sometimes an extensive clinical, laboratory and radiologic workup is required, making it challenging to arrive at a prompt diagnosis. Most patients experience full resolution of symptoms with corticosteroids and/or infliximab. For ICI-induced colitis that is treatment-refractory, small scale studies offer alternative strategies, such as vedolizumab and fecal microbiota transplantation. In this review, we focus on the clinical features, differential diagnosis, and management of ICI-induced colitis with special attention to emerging treatment options for treatment-refractory ICI-induced colitis.

Keywords: Immune checkpoint inhibitor, Immune checkpoint inhibitor-induced colitis, Infliximab, Vedolizumab, Graft-versus-host disease, Inflammatory bowel disease

Core Tip: Colitis is the most common adverse effect associated with immune checkpoint inhibitor (ICI) therapy. Its clinical, endoscopic and histopathologic presentations overlap with those of colitis caused by other etiologies, including infection, other medications and graft-versus-host disease. Patients often present with diarrhea, abdominal pain and variable endoscopic findings ranging from normal or mild inflammation to ulcerations. Microscopically, acute colitis pattern of injury is the most common finding. ICI-induced colitis is a diagnosis of exclusion. Its current first-line treatment is corticosteroids, followed by infliximab for steroid-refractory colitis. Vedolizumab and fecal microbiota transplantation are promising options for treatment-refractory ICI-induced colitis.