Ipilimumab-induced Colitis with Concomitant Clostridium difficile Infection

Abstract

Introduction: Ipilimumab (Anti-Cytotoxic T lymphocyte-associated antigen (CTLA)-4 antibody)-induced colitis is a rare immune-mediated adverse event. Prompt diagnosis and treatment can prevent life-threatening complications. We report a case of colitis caused by Ipilimumab with concomitant Clostridium difficile (C. diff) infection and successful treatment with systemic corticosteroids. Case Report: A 32-year-old female who was undergoing Ipilimumab therapy post cycle number four for relapse of malignant melanoma presented with bloody diarrhea for two days. The patient denied fever, nausea, and vomiting. Examination revealed a soft but tender abdomen in the left lower quadrant. Stool studies were positive for C. diff toxin. She was treated with PO Vancomycin. Diarrhea slowly improved with recurrent episodes of bright red blood. Repeat C. diff toxin on day 10 was negative. IV Solumedrol 40 mg q8hrs was started with immediate response and complete resolution of hematochezia and diarrhea. Colonoscopy on day 13 showed severe colitis with erythema, edema, and friability with a plethora of large crated ulcers in the left colon, predominantly the splenic flexure. Biopsy showed mucosal ulceration and granulation tissue with rare cryptitis. She remained asymptomatic for the next few days on IV steroids, and was transitioned to 60-mg prednisone with a slow taper of Vancomycin over three weeks. As an outpatient, she was switched to Budesonide with plan for repeat colonoscopy. Discussion: Colonic toxicity is an immune-mediated adverse event caused by a biological agent. With increased use of Ipilimumab to treat malignant melanoma, the incidence of colitis is rising (recorded in about 20% of the patients receiving this treatment). Typical symptoms include abdominal pain and diarrhea, sometimes bloody. Endoscopy can show segmental or diffuse colitis. Biopsies show nonspecific inflammatory infiltrate with predominant T-cells, cryptitis, and abscess formation. Fatal complications (5%) like perforation (<1%) can occur without prompt appropriate treatment. Systemic steroids are the treatment of choice. Limited or no response to steroids in a week should lead to the use of infliximab. Failure of medical treatment can necessitate partial or complete colectomy with diverting ileostomy. Few cases have been reported of concomitant C. diff colitis, which complicates the course. Our patient was initially treated only for C. diff. Lack of sustained response to antibiotics prompted initiation of corticosteroids. Colonoscopy showed significantly deep ulcerations, suggesting that perforation could have occurred without timely steroids. C. diff infection should not preclude use of systemic steroids if immune mediated colitis is suspected.