A Case of Severe Enterocolitis Secondary to a Novel Biological Agent

Abstract

Introduction: Ipilimumab is a recombinant human IgG1 immunoglobulin monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen, used in the treatment of metastatic melanoma. We present a case of severe enterocolitis associated with the use of ipilimumab in a patient with recurrent metastatic melanoma. Case Presentation: A 67-year-old female with history of recurrent metastatic melanoma presented with a four-week history of loose, non-bloody watery stools, associated nausea, vomiting, and lower abdominal pain, following four cycles of chemotherapy with ipilimumab. Physical examination revealed diffuse lower abdominal wall tenderness with no peritoneal signs. Laboratory testing showed acute pre-renal kidney injury secondary to dehydration. Stool studies ruled out an infectious etiology. Flexible sigmoidoscopy with biopsy revealed a continuous area of ulcerated mucosa in the descending colon with no active bleeding, and biopsies showed moderately active colitis/proctitis with ulceration. The patient was started on prednisone for the colitis. In the interim, an elective chest X-ray showed free air under the diaphragm, and a follow-up CT abdomen/pelvis showed diffusely dilated loops of small and large bowel, with free air in the abdomen. Exploratory laparotomy revealed perforated sigmoid colon and distal ileum, and the patient underwent resection of terminal ileum, cecum, and left colon with end ileostomy and transverse colostomy. Histopathological analysis of the resected bowel showed severe transmural acute inflammation with extensive necrosis. The patient eventually succumbed to her illness, in spite of aggressive supportive management. Discussion: Ipilimumab, a new promising tool for the treatment of metastatic melanoma, is reported to cause new types of toxicities called “immune- related adverse events” due to prolonged activation of cytotoxic T lymphocytes. Gastrointestinal side effects include nausea, vomiting, abdominal pain, and even severe colitis. Treatment includes supportive measures, including fluid and electrolyte replacement, intravenous high dose steroids, infliximab for steroid-resistant cases, and ileostomy or colectomy for cases unresponsive to medical therapy. Conclusion: Even though ipilimumab has emerged as a promising tool in the treatment of metastatic malignant melanoma, clinicians should be aware of its severe side effects, including enterocolitis.