title: Clinical, Endoscopic, and Histologic Characteristics of Ipilimumab-Associated Colitis.
abstract: Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte-associated antigen-4, is a treatment for metastatic melanoma that can induce immune-related adverse effects, such as enterocolitis. We aimed to characterize the clinical, endoscopic, and histologic features of ipilimumab-induced colitis and evaluate the efficacy of therapy for this reaction.
  
  
  
  We performed a retrospective analysis of 27 consecutive patients who developed colitis after treatment with ipilimumab infusion therapy for castration-resistant prostate cancer or metastatic melanoma, from April 2007 through September 2012. Clinical, endoscopic, and histologic information was collected from the database of the VU University Medical Center, Amsterdam, The Netherlands. Selected cases were ascertained by cross-checking with endoscopy reports.
  
  
  
  All patients had diarrhea (range, 3-20 stools per day); 26% had concurrent rectal blood loss and 30% had abdominal pain. These symptoms usually started after 2 infusions of ipilimumab (range, 1-4) and all patients except for 1 (who received no treatment for colitis) were given corticosteroids. Twelve patients had steroid-refractory colitis, for which they received infliximab (5 mg/kg). Diarrhea resolved in all the patients. Colon erythema was detected by endoscopy in 84% of patients, with an absent vascular pattern in all patients. In histologic analyses, colon biopsy specimens ranged from having normal architecture to severe active inflammation. Intraepithelial neutrophilic leucocytes were detected in 72% of samples, cryptitis in 92%, and crypt abscesses in 60%. Crypt irregularities were found in 40% of colon biopsy specimens, indicating chronic disease.
  
  
  
  In a retrospective analysis, we associated ipilimumab-associated colitis diarrhea with a variety of endoscopic and histologic features. Treatment with corticosteroids, followed by infliximab in steroid-refractory patients, was successful for all cases.
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Eduard Cornelis
authors.initials: EC
authors.lastname: Verschuren
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Alfonsus Johannes
authors.initials: AJ
authors.lastname: van den Eertwegh
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Janneke
authors.initials: J
authors.lastname: Wonders
authors.affiliation: Department of Gastroenterology and Hepatology, HagaZiekenhuis Teaching Hospital, The Hague, The Netherlands.
authors.forename: Rob Michel
authors.initials: RM
authors.lastname: Slangen
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Foke
authors.initials: F
authors.lastname: van Delft
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands; Department of Internal Medicine, Gastroenterology and Geriatrics, Zuyderland Medical Center, Sittard-Geleen, The Netherlands.
authors.forename: Adriaan
authors.initials: A
authors.lastname: van Bodegraven
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Andra
authors.initials: A
authors.lastname: Neefjes-Borst
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: KHN.deBoer@vumc.nl.
authors.forename: Nanne Klaas
authors.initials: NK
authors.lastname: de Boer
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects*; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology*; D003106:Colon / Q000473:pathology; D003113:Colonoscopy; D003967:Diarrhea / Q000139:chemically induced / Q000473:pathology; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects*; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000556:secondary; D008875:Middle Aged; D009426:Netherlands; D011471:Prostatic Neoplasms / Q000188:drug therapy; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D000074324:Ipilimumab
keywords: Adverse Event; Autoimmunity; IBD; Liquid Stool