A Rare Presentation of Severe Colitis with Ipilimumab Therapy

Abstract

Introduction: Diarrhea is a commonly encountered problem in the inpatient hospital and the outpatient setting as well. We present an interesting case of a female patient whose diarrhea demonstrated GI (Gastrointestinal) toxicity in a setting of immunotherapy. Case: A 67-year-old Caucasian female with malignant melanoma of the right index finger, status post resection, developed recurrence with axillary involvement. She was undergoing systemic chemotherapy with ipilimumab. She presented with severe, non-bloody diarrhea (> 10 times a day) associated with abdominal pain. She did not have any recent hospitalizations, infections, antibiotics, or known gastrointestinal disorders. Initially, she was afebrile without leukocytosis, and negative Clostridium difficile toxin. Stool culture and fecal leukocytes were unremarkable. Despite anti-motility agents, her diarrhea persisted, and she underwent a flexible sigmoidoscopy, which revealed non-specific active transmural colitis with ulceration and necrosis involving the distal ileum, cecum, and descending colon. Given recent treatment with ipilimumab, immune-related enterocolitis was highly suspected. The patient was treated with IV (intravenous) high-dose prednisone, mesalamine, and ioperamide. She continued to have progressively worsening diarrhea, despite therapy. Her clinical condition rapidly declined, requiring surgery for bowel perforation. Recovery was complicated and prolonged, and she decided to forego any further medical treatment, and subsequently died. Discussion: Ipilimumab has recently been found to be an efficacious treatment of malignant melanoma. However, it does present with an array of adverse effects, including enterocolitis in 1% of patients. If suspected, early immune-mediated enterocolitis responds well to systemic steroids, as per recently documented case reports. Other studies concluded that surgery in steroid-resistant cases maybe necessary in order to prevent progression of colitis to intestinal perforation. Although our patient's presentation of diarrhea and colitis was an expected side effect of Ipilimumab, she failed to respond to systemic steroids; this resulted in bowel perforation, rapid decline, and ultimately death. In conclusion, this case report should raise the awareness of ipilimumab GI-related side effects among gastroenterologists. Moreover, steroid therapy, as suggested by our reference studies, may not be sufficient in such severe enterocolitis. Other treatment options should be considered.