Gastrointestinal Adverse Events Induced by Immune-Checkpoint Inhibitors

Abstract

<b><i>Background:</i></b> As immune-checkpoint inhibitors (ICI) are becoming standard therapies for malignant tumors, increasing attention has been paid to their associated immune-related adverse events (irAEs). The gastrointestinal tract is the major site of irAEs, and it has recently become evident that the large bowel is the most frequently affected region. The aim of this narrative review was to clarify the endoscopic and histopathologic findings of and treatments for ICI-induced colitis. <b><i>Summary:</i></b> Endoscopic findings of ICI-induced colitis include a reddish, edematous mucosa with increased mucous exudate, loss of normal vascularity, and a granular mucosa with or without mucosal breaks. Histopathologic findings of ICI-induced colitis are expansion of the lamina propria, intraepithelial infiltration of neutrophils, crypt architectural distortion, neutrophilic crypt abscess, and prominent apoptosis. The clinical, endoscopic, and histopathologic severity of ICI-induced colitis is diverse, but colonoscopy together with biopsy is necessary for diagnosis. While a certain proportion of patients with ICI-induced colitis have an intractable clinical course, management guidelines are based on retrospective analyses. Prospective studies are needed to assess the efficacy of various medications, including immunosuppressive regimens. <b><i>Key Messages:</i></b> Colonoscopy with biopsy is the gold standard for the diagnosis of ICI-induced colitis. Endoscopists should be aware of the clinical features and pathophysiology of ICI-induced colitis for prompt diagnosis and treatment planning.

Immune-Related Adverse Events Due to Cancer Immunotherapy: Immune Mechanisms and Clinical Manifestations

“…A meta-analysis showed an overall incidence of all-grade colitis of 13.6% in patients treated with a combination therapy of ipilimumab/nivolumab, 9.1% in patients receiving ipilimumab, and 1.3% with anti-PD1/PD-L1 monotherapy [111]. The use of non-steroidal anti-inflammatory drugs can be a relevant risk factor, while inflammatory bowel disease is associated with severe ICI-induced colitis [110,112]. An early clinical and instrumental (colonoscopy) diagnosis of colitis is essential to avoid complications such as dehydration, toxic megacolon, colonic perforation (seen in 1-6.6% of patients), and death [7].…”

Contribution of the Skin–Gut Axis to Immune-Related Adverse Events with Multi-System Involvement

“…Mild to moderate (CTCAE grade 1 or grade 2) diarrhea includes an increase of up to 6 stools per day and grade 2 colitis presents with abdominal pain, or mucus or blood in the stool. Grade 3 diarrhea is defined as an increase in 7 or more stools per day and grade 3 colitis can present with severe abdominal pain, fever, and abdominal signs [ 18 ]. As ircAEs and GI irAEs are among the most frequently observed irAEs, these events may co-occur in many patients.…”