Checkpoint Inhibitor-Induced Colitis: A Case Series

Abstract Introduction/Objective Checkpoint inhibitors are novel immune-stimulating antibodies that have revolutionized the management and prognosis of several malignancies. The primary targets are cytotoxic T-lymphocyte–associated antigen-4 (anti-CTLA-4; e.g. pembrolizumab) and programmed cell death-1 receptor (anti-PD-1; e.g. ipilimumab and nivolumab). In spite of the significant advantages, many immune-related adverse effects have been identified. One of which is checkpoint inhibitor-induced colitis (CIC). Although there is awareness of the histopathologic features of anti- CTLA-4 induced colitis, there is much to be discovered about the pathologic features of anti-PD-1 colitis. Methods We herein report three cases of CIC. There were two women and 1 male (age range, 50 to 73-years-old, mean 64-years-old) who presented with diarrhea and/or hematochezia after multiple cycles of pembrolizumab or ipilimumab/ nivolumab combination therapy. Endoscopic examination was abnormal in all of these cases. Results The histologic features were similar in two cases, with moderate active chronic colitis and one case with focal active colitis. Two of the three patient were given steroids in addition to their regular medications with symptom improvement. One patient was removed off all medications and enrolled into hospice due to disease progression. CIC has been an increasingly recognized immune-related adverse effect that has a wide spectrum of clinical presentations ranging from mild diarrhea and abdominal pain to severe colitis and intestinal perforation. However, it is thought to be underestimated. Histologically, CIC can mimic inflammatory bowel disease, microscopic colitis and active colitis. Our cases showed histopathologic features mimicking those of ulcerative colitis. Conclusion Awareness of CIC is crucial for the multidisciplinary management essential for these patients. The histopathologic pattern coupled with the clinical history can allow pathologists to confirm the diagnosis of CIC and facilitate timely diagnosis and treatment.