Case Report: Immune checkpoint inhibitor-induced gastrointestinal toxicity: the diagnostic challenge of sequential...

Immune checkpoint inhibitors can cause diverse immune-related adverse events, the early recognition of which is critical. Intestinal pseudo-obstruction caused by immune-mediated gastrointestinal dysautonomia is a rare, potentially fatal, and under-recognized toxicity that may be difficult to distinguish from more common gastrointestinal complications.

We describe the clinical course, investigation, and management of a patient with metastatic esophageal mucosal melanoma who developed sequential gastrointestinal toxicities following combination ipilimumab and nivolumab therapy, focusing on early recognition and the diagnostic challenges associated with recognizing immune-mediated intestinal dysmotility.

Following four cycles of immunotherapy, the patient developed intractable nausea, vomiting, and constipation. Computed tomography demonstrated diffuse small bowel dilatation without a mechanical transition point, raising suspicion of immune checkpoint inhibitor-induced ileus. Despite intravenous corticosteroids, the clinical phenotype evolved over the following week to high-frequency diarrhea, with repeat imaging and endoscopy supporting superimposed enterocolitis. Following an initial response to prolonged corticosteroid treatment, diarrhea recurred and ultimately improved after infliximab therapy. The sequential presentation of dysmotility and inflammatory colitis complicated the assessment of disease evolution and decisions regarding the escalation of immunosuppression.

This case highlights intestinal pseudo-obstruction as an important but easily overlooked immune-related adverse event and demonstrates how rare gastrointestinal dysautonomia may precede, coexist with, or be masked by more familiar immune-mediated colitis. Recognition of the contrasting clinical phenotypes, particularly otherwise unexplained nausea, vomiting, constipation, and bowel dilatation without mechanical obstruction, is essential because the underlying mechanisms and therapeutic responses may differ. Greater awareness of these early warning features, coupled with prompt investigation and multidisciplinary assessment, may reduce diagnostic delays and enable earlier treatment of this potentially life-threatening toxicity.