Immune Checkpoint Inhibitor Induced Colitis or “Immune Mediated Colitis”

A 70-year-old woman with history of metastatic melanoma on treatment with ipilimumab presented with acute onset abdominal pain and bloody bowel movements.

Figure 1. Immune checkpoint inhibitor induced colitis (“immune mediated colitis”). A. diffuse mucosal edema, loss of light reflex, erythema, granularity. B. Large amount of secretion and pus (“mucopus”). C. “Tubular” colon because of severe inflammation. D. Immune mediated colitis is associated with significant neutrophilic inflammation, hence pus. E. Descending colon stenosis due to massive edema and inflammation. F. IMC is often indistinguishable from inflammatory bowel diseases. G. Typical granularity of mucosa in IMC. NBI views of inflamed crypts (cryptitis, white spots).

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target cancer modulatory cells and immune processes such as cytotoxic T-lymphocyte antigen-4 (ipilimumab), and interaction between PD-1 and the ligands PD-L1 and programmed death ligand 2 (anti–PD-1 agents such as pembrolizumab, nivolumab) (1). Although ICIs have improved the treatment of several malignancies such as melanomas, their severe immune-related adverse events including hepatitis and colitis hamper their use in a significant proportion of patients (1, 2). Indeed, immune-mediated colitis (IMC) can occur in up to 25% (1, 2). On endoscopy, this iatrogenic colitis is very hard to differentiate from classical ulcerative colitis or Crohn’s disease. On histology there is more neutrophilic infiltration without chronic inflammation (1, 2). Therapy consists mainly on reducing or stopping the ICIs. In addition, corticosteroids are recommended for moderate and severe forms of colitis (1-3). Infliximab has also been shown to be beneficial, especially in those patients that do not respond to steroids (1-3. As ICIs are entering practice worldwide it is important to know about immune colitis.

References:

Som A, Mandaliya R, Alsaadi D, Farshidpour M, Charabaty A, Malhotra N, Mattar MC. Immune checkpoint inhibitor-induced colitis: A comprehensive review. World J Clin Cases. 2019 Feb 26;7(4):405-418. doi: 10.12998/wjcc.v7.i4.405. PMID: 30842952; PMCID: PMC6397821.
Hashash JG, Francis FF, Farraye FA. Diagnosis and Management of Immune Checkpoint Inhibitor Colitis. Gastroenterol Hepatol (N Y). 2021 Aug;17(8):358-366. PMID: 34602898; PMCID: PMC8475264.
Dougan M, Wang Y, Rubio-Tapia A, Lim JK. AGA Clinical Practice Update on Diagnosis and Management of Immune Checkpoint Inhibitor Colitis and Hepatitis: Expert Review. Gastroenterology. 2021 Mar;160(4):1384-1393. doi: 10.1053/j.gastro.2020.08.063. Epub 2020 Oct 17. PMID: 33080231.

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About the authors

Hiral Patel, MD

Gastroenterology Fellow, PGY-6

Carilion Clinic / Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA

Hiral Patel, MD, is a senior gastroenterology fellow at Carilion Clinic and Virginia Tech Carilion School of Medicine. She received her medical degree from the Medical College of Georgia School of Medicine and completed her internal medicine residency at Wake Forest School of Medicine. She has contributed cases on Barrett's esophagus and small-bowel bleeding to The Practicing Endoscopist alongside the Carilion endoscopy faculty.

Robert Moylan, MD

Gastroenterologist; Assistant Professor of Medicine

Carilion Clinic / Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA

Robert D. Moylan, MD, is a board-certified gastroenterologist with Carilion Clinic and an Assistant Professor at Virginia Tech Carilion School of Medicine, with more than three decades of clinical experience. He earned his medical degree from the University of Virginia School of Medicine, where he also completed his internal medicine residency and gastroenterology fellowship. His clinical focus includes inflammatory bowel disease, upper GI endoscopy, and chronic liver disease.

Klaus Mönkemüller, MD, PhD, FASGE, FJGES, FESGE

Editor-in-Chief, The Practicing Endoscopist

Professor of Medicine, Carilion Memorial Hospital / Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA

Klaus Mönkemüller, MD, PhD, FASGE, FJGES, FESGE, is the editor-in-chief of The Practicing Endoscopist and the founder of EndoCollab. He is Professor of Medicine at Virginia Tech Carilion School of Medicine and a practicing endoscopist at Carilion Memorial Hospital in Roanoke, Virginia.

Dr. Mönkemüller has published extensively on endoscopic techniques and devices, with a particular focus on therapeutic endoscopy, foreign body removal, GI bleeding, and the use of caps and accessories in everyday practice. He lectures internationally and has contributed to multiple GI endoscopy textbooks and atlases.

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