Immune Checkpoint Inhibitor-Related Gastrointestinal Toxicity: Pathogenesis, Diagnosis, and Management

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape across multiple malignancies. However, their expanding use has been accompanied by an increasing spectrum of immune-related adverse events (irAEs), particularly those affecting the gastrointestinal (GI) tract. GI toxicities may involve both the upper and lower GI tract and range from mild, nonspecific symptoms to severe inflammatory complications requiring treatment interruption, hospitalization, or selective immunosuppressive therapy. This review summarizes the current evidence regarding the pathogenesis, clinical presentation, endoscopic and histopathologic findings, and management of GI irAEs associated with ICIs. Upper GI involvement, including esophagitis, gastritis, and duodenitis, is relatively uncommon and typically presents with nonspecific symptoms and heterogeneous endoscopic findings, which may occur despite a macroscopically normal-appearing mucosa. Lower GI toxicity, particularly diarrhea and colitis, is more common and clinically significant, especially in patients receiving anti-CTLA-4-based and combination regimens. Endoscopic evaluation with mucosal biopsy remains central to diagnosis because clinical severity does not always correlate with endoscopic or histopathologic activity. Histopathologic patterns are heterogeneous and may overlap with those of other inflammatory or infectious GI disorders, making clinicopathologic correlation essential. Current management is largely guided by expert consensus and includes supportive care, corticosteroids, and biologic rescue therapy with agents such as infliximab or vedolizumab for steroid-refractory disease. Early recognition, appropriate grading, exclusion of alternative etiologies, and multidisciplinary collaboration among oncologists and gastroenterologists are critical to optimize outcomes while preserving the benefits of cancer immunotherapy.