Endoscopic Remission After Infliximab Treatment in a Patient with Ipilimumab-Induced Colitis

Abstract

Biological medications may result in serious side effects. Some effects relate to immunosuppression while others are from immunostimulation. Our case demonstrates severe ipilimumab-induced colitis in a patient being treated for stage 4 malignant melanoma, which responded to treatment with infliximab. A 78 year old man with stage 4 malignant melanoma treated with ipilimumab and radiation was admitted to our hospital with three weeks of abdominal pain and severe refractory bloody diarrhea. Prior to hospitalization he received four infusions of ipilimumab. Stool analysis revealed leukocytosis and no Clostridium difficile toxin, Cryptosporidium, or Giardia. There was a negative serum CMV antigen screen. The patient was started on metronidazole, ciprofloxacin, and prednisone although these did not provide resolution of his symptoms. CT abdomen and pelvis with contrast revealed extensive colonic wall thickening that extended up to the proximal transverse colon. Sigmoidoscopy demonstrated severe colitis with mucosal edema, erythema, and ulceration. Colonic mucosal biopsies were obtained and the results revealed acute colitis with ulceration as well as negative CMV and HSV histochemistries. Despite continued high dose steroids and bowel rest there was no clinical improvement. The patient was started on Infliximab, and he noticed progressive improvement in his diarrhea. The patient was discharged for outpatient GI clinic follow up and continued infusions. The patient's clinical course was complicated by pulmonary embolism and he required anticoagulation. At a three-month follow up sigmoidoscopy, the ulcers showed healing change, normal rectal mucosa, and resolved colitis. The nine-month follow up colonoscopy demonstrated remission. The Infliximab was stopped and patient was followed clinically. Ipilimumab related colitis is the result of hyperactive cytotoxic T lymphocytes. Ensuing necrotizing colitis can cause bloody diarrhea, bowel wall perforation, or toxic megacolon. Aggressive medical management decreases excessive inflammatory reaction in areas of large immunologic cell populations, such as the colon. Infliximab, tacrolimus and corticosteroids have efficacy against the excessive inflammatory side effects of hypersensitivity colitis. Unfortunately, medical management cannot prevent colectomy in all cases which is a last resort for necrotizing colitis. Our case presents the management of complicated colitis with colon-sparing medical management.Figure 1Figure 2