An Unusual Case of Colitis

Abstract

Purpose: A 65 year old man with a history of metastatic prostate cancer was being treated in a clinical trial with ipilimumab when he presented to the hospital with fever and 10–12 episodes of bloody diarrhea. The patient had recently received a course of antibiotics for bronchitis. His stool cultures were positive for C. difficile and he was begun on treatment with metronidazole. However, over the next few days his diarrhea did not improve with appropriate therapy. His physical exam revealed him to be afebrile with moderate diffuse abdominal tenderness without any evidence of peritoneal signs. Laboratory evaluation revealed normal blood count and chemistry except for an elevated ESR of 65. A CT of his abdomen revealed evidence of diffuse colonic thickening. With his lack of improvement, a colonoscopy was performed which revealed severe erythema and ulceration throughout the entire colon consistent with diffuse colitis without any evidence of pseudo- membranes. Histopathology of the colonic biopsy showed a severe acute and chronic colitis with features essentially identical to and indistinguishable from those of active inflammatory bowel disease. It was determined that ipilimumab which results in stimulation of the immune system can precipitate a colitis which mimics inflammatory bowel disease in presentation both clinically, endoscopically and histologically. Ipilimumab is a human monoclonal antibody that binds to CTLA-4 (cytotoxic T lymphocyte-associated antigen 4), a molecule on T-cells that plays a critical role in regulating immune responses. Ipilimumab is designed to block the activity of CTLA-4, thereby sustaining an active immune response. Ipilimumab is currently being used in clinical trials for patients with melanoma and prostate cancer with known gastrointestinal side effects of colitis. Through protocol the colitis has been treated with high dose intravenous steroids, with failures requiring treatment with infliximab and colectomy. Our patient was started on high dose steroids with significant improvement in his symptoms. Overall this presentation demonstrates a case of colitis due to immune stimulation from a medication perfectly imitating inflammatory bowel disease both clinically, endoscopically and histologically. It is important to be aware of the gastrointestinal complications of this medication so as not to confuse with IBD. The long-term ramifications of this medication are unknown. It may be possible that this medication could result in chronic IBD secondary to initiation of the immune cascade. Also, it is important to consider that this immune pathway may hold potential future immunological treatment options for IBD patients.