Immunotherapy‐Induced Colitis: An Emerging Problem for the Hospitalist

Abstract

Since their introduction for melanoma treatment, the use of immune checkpoint inhibitors (ICIs) has rapidly expanded. Though their impact on survival is irrefutable, these medications have been associated with autoimmune-like adverse events related to their ability to induce the immune system. One of the most commonly affected organ systems is the gastrointestinal (GI) tract, in which manifestations range from mild diarrhea to severe colitis with intestinal perforation. Because of the increased use of ICIs, hospitalists are caring for an increasing number of patients experiencing their adverse events. We present a case-oriented review of the GI adverse events associated with the use of ICIs to familiarize the hospitalist with their mechanism of action and potential complications and to emphasize the importance of early diagnosis and treatment to decrease morbidity and mortality.

Management of Gastrointestinal Toxicity from Immune Checkpoint Inhibitor

“…Watery, nonbloody diarrhoea occurs in 19% of patients with anti-PD-1/PD-L1 therapy and 33% receiving anti-CTLA-4 therapy. Diarrhoea and colitis, including severe forms, occur earlier and are more frequent with combined anti-CTLA-4 and anti-PD-1 agents than with either ipilimumab or anti-PD-1 [13]. Other presenting symptoms are abdominal pain, haematochezia, weight loss, fever, and vomiting [1, 7, 13].…”

“…Diarrhoea and colitis, including severe forms, occur earlier and are more frequent with combined anti-CTLA-4 and anti-PD-1 agents than with either ipilimumab or anti-PD-1 [13]. Other presenting symptoms are abdominal pain, haematochezia, weight loss, fever, and vomiting [1, 7, 13]. Anti-CTLA-4-induced enterocolitis may be associated with mouth ulcers, anal lesions (fistulas, abscesses, fissures), and extra-intestinal manifestations [14].…”

“…Colitis can mimic inflammatory bowel disease (IBD) [14]. Diarrhoea and colitis severity can be graded according to the Common Terminology Criteria for Adverse Events (Table 1) [13]. …”

“…Less commonly, the upper gastrointestinal tract is involved and clinical manifestations include aphthous ulcers, esophagitis, and gastritis [13]. Nausea, vomiting, dysphagia, and epigastric pain may be present [1, 17].…”

“…Management of patients with non-severe diarrhoea is mainly supportive, with antidiarrhoeals, fluid, and electrolyte supplementation. Persistence of grade 2 diarrhoea (defined as four to six stools per day for more than 3 days), should prompt initiation of 0.5 to 1 mg/kg/day of oral corticosteroids and ICPIs should be withheld [2, 3, 5, 13, 19, 21, 22]. The use of budesonide seems attractive since it might avoid the systemic effects of corticosteroids, though its effect in this context seems limited.…”