Ipilimumab-Induced Colonic Perforation: 1425

Introduction: Ipilimumab is an antigen-4-blocking monoclonal antibody that enhances the antitumor T-cell response in metastatic melanoma. The activated T-cell immune response can lead to varied adverse side effects including colitis. We report a case of ipilimumab-induced colonic perforation in a 50-year-old female. She initially presented with a stage IIIC ulcerated, primary cutaneous melanoma. Sentinel lymph node biopsy was negative, and she underwent a wide local excision with clear margins. One year later, her melanoma recurred as a left groin mass with no metastatic disease. She was subsequently started ipilimumab therapy. After the second dose, she developed nausea, vomiting, and grade-III diarrhea. Stool cultures were negative. She did not respond to steroids, and was started on Infliximab with immediate response. After the third dose of ipilimumab, she had recurrent vomiting, bloody diarrhea, and abdominal cramping. A gentle, limited flexible sigmoidoscopy revealed severe hemorrhagic, ulcerated inflammation of the sigmoid colon (Figure 1). Pathology confirmed chronic inflammation, ulceration, and granulation tissue. Despite corticosteroids, supportive management, and infliximab, she continued to experience abdominal cramping and bloody diarrhea. Computed tomography of the abdomen revealed free air and presumed colonic perforation (Figure 2). Explorative laparotomy revealed splenic flexure perforation and she underwent total colectomy with ileostomy. Colitis can develop in 20% of ipilimumab-treated patients. To our knowledge, there have been only 5 reported cases of ipilimumab-associated colonic perforation. Perforation occurs in <1%, and should be strongly considered in patients with refractory abdominal pain not responding to steroid and infliximab therapy.Figure 1: Flexible sigmoidoscopy.Figure 2: Colonic perforation.