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Case report
peer-reviewed

Ipilimumab as a Cause of Severe Pan-Colitis and Colonic Perforation



Abstract

Ipilimumab is a human monoclonal antibody that functions as a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor that is used to treat malignant melanoma. Due to ipilimumab’s removal of immune regulation, specifically through the inactivation of CTLA-4, it is commonly associated with inflammatory and autoimmune events. Gastrointestinal (GI) related immune-related adverse events such as diarrhea occur in 29% of patients with 7.6% of patients specifically suffering from colitis. We describe a case of colonic perforation with ipilimumab use. Our goal is to raise awareness and alert practicing gastroenterologists of this particular adverse effect.​

A 74-year-old male patient presented to the emergency department with complaints of hematochezia, abdominal pain and decreased appetite. The patient’s past medical history included desmoplastic BRAF mutation negative melanoma with metastatic disease to the face, liver, and trigeminal nerve. He underwent his last treatment of ipilimumab three weeks prior to presentation. In total, the patient received four doses of 3 mg/kg of ipilimumab every three weeks. Since the initiation of ipilimumab, he reported diarrhea as its adverse effect, which was treated with tapering doses of prednisone one month at a time. Colonoscopy revealed mucosal ulceration and erosion in the rectum, sigmoid colon, and remaining descending colon up to the splenic flexure and cecum. After the colonoscopy, the patient became tachycardic, hypotensive and complained of sudden abdominal pain. A computed tomographic (CT) scan of the abdomen showed free intraperitoneal air. He was immediately taken to the operating room (OR) for an emergent laparotomy. In the operating room, perforations were noted at the splenic flexure and the cecum with large amounts of succus spilling from the perforations. The majority of the large bowel appeared cyanotic and dusky; consequently, a sub-total colectomy with terminal ileostomy was performed. After the procedure, the patient was started on antibiotics for severe peritonitis and admitted to the intensive care unit (ICU) with septic shock. His clinical status continued to deteriorate due to acute respiratory failure, nosocomial pneumonia, severe protein calorie malnutrition and coagulopathy from disseminated intravascular coagulation (DIC). The patient did not recover from his illness and died a few days later.

It is imperative that physicians caring for patients receiving treatment with CTLA-4 inhibitors frequently monitor for and promptly treat possible immune-related adverse effects. For patients with ipilimumab-related colitis, prompt identification of symptoms and early treatment with steroids are crucial in preventing harmful or possibly fatal immune-related adverse events. Gastroenterologists should be wary of this adverse side effect in this high-risk population when performing colonoscopy and take necessary precautions.



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Case report
peer-reviewed

Ipilimumab as a Cause of Severe Pan-Colitis and Colonic Perforation


Author Information

Raj Shah

Department of Internal Medicine, University of Missouri Kansas City (UMKC)

Danielle Witt

Department of Internal Medicine, University of Missouri Kansas City (UMKC)

Talal Asif Corresponding Author

Department of Internal Medicine, University of Missouri Kansas City (UMKC)

Fahad F. Mir

Department of Gastroenterology, University of Missouri Kansas City (UMKC)


Ethics Statement and Conflict of Interest Disclosures

Human subjects: Consent was obtained by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.


Case report
peer-reviewed

Ipilimumab as a Cause of Severe Pan-Colitis and Colonic Perforation


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Case report
peer-reviewed

Ipilimumab as a Cause of Severe Pan-Colitis and Colonic Perforation

Raj Shah">Raj Shah, Danielle Witt">Danielle Witt, Talal Asif">Talal Asif , Fahad F. Mir">Fahad F. Mir

  • Author Information
    Raj Shah

    Department of Internal Medicine, University of Missouri Kansas City (UMKC)

    Danielle Witt

    Department of Internal Medicine, University of Missouri Kansas City (UMKC)

    Talal Asif Corresponding Author

    Department of Internal Medicine, University of Missouri Kansas City (UMKC)

    Fahad F. Mir

    Department of Gastroenterology, University of Missouri Kansas City (UMKC)


    Ethics Statement and Conflict of Interest Disclosures

    Human subjects: Consent was obtained by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

    Acknowledgements


    Article Information

    Published: April 20, 2017

    DOI

    10.7759/cureus.1182

    Cite this article as:

    Shah R, Witt D, Asif T, et al. (April 20, 2017) Ipilimumab as a Cause of Severe Pan-Colitis and Colonic Perforation. Cureus 9(4): e1182. doi:10.7759/cureus.1182

    Publication history

    Received by Cureus: April 10, 2017
    Peer review began: April 12, 2017
    Peer review concluded: April 18, 2017
    Published: April 20, 2017

    Copyright

    © Copyright 2017
    Shah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 3.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    License

    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Ipilimumab is a human monoclonal antibody that functions as a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor that is used to treat malignant melanoma. Due to ipilimumab’s removal of immune regulation, specifically through the inactivation of CTLA-4, it is commonly associated with inflammatory and autoimmune events. Gastrointestinal (GI) related immune-related adverse events such as diarrhea occur in 29% of patients with 7.6% of patients specifically suffering from colitis. We describe a case of colonic perforation with ipilimumab use. Our goal is to raise awareness and alert practicing gastroenterologists of this particular adverse effect.​

A 74-year-old male patient presented to the emergency department with complaints of hematochezia, abdominal pain and decreased appetite. The patient’s past medical history included desmoplastic BRAF mutation negative melanoma with metastatic disease to the face, liver, and trigeminal nerve. He underwent his last treatment of ipilimumab three weeks prior to presentation. In total, the patient received four doses of 3 mg/kg of ipilimumab every three weeks. Since the initiation of ipilimumab, he reported diarrhea as its adverse effect, which was treated with tapering doses of prednisone one month at a time. Colonoscopy revealed mucosal ulceration and erosion in the rectum, sigmoid colon, and remaining descending colon up to the splenic flexure and cecum. After the colonoscopy, the patient became tachycardic, hypotensive and complained of sudden abdominal pain. A computed tomographic (CT) scan of the abdomen showed free intraperitoneal air. He was immediately taken to the operating room (OR) for an emergent laparotomy. In the operating room, perforations were noted at the splenic flexure and the cecum with large amounts of succus spilling from the perforations. The majority of the large bowel appeared cyanotic and dusky; consequently, a sub-total colectomy with terminal ileostomy was performed. After the procedure, the patient was started on antibiotics for severe peritonitis and admitted to the intensive care unit (ICU) with septic shock. His clinical status continued to deteriorate due to acute respiratory failure, nosocomial pneumonia, severe protein calorie malnutrition and coagulopathy from disseminated intravascular coagulation (DIC). The patient did not recover from his illness and died a few days later.

It is imperative that physicians caring for patients receiving treatment with CTLA-4 inhibitors frequently monitor for and promptly treat possible immune-related adverse effects. For patients with ipilimumab-related colitis, prompt identification of symptoms and early treatment with steroids are crucial in preventing harmful or possibly fatal immune-related adverse events. Gastroenterologists should be wary of this adverse side effect in this high-risk population when performing colonoscopy and take necessary precautions.



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Raj Shah

Department of Internal Medicine, University of Missouri Kansas City (UMKC)

Danielle Witt

Department of Internal Medicine, University of Missouri Kansas City (UMKC)

Talal Asif

Department of Internal Medicine, University of Missouri Kansas City (UMKC)

For correspondence:
asift@umkc.edu

Fahad F. Mir

Department of Gastroenterology, University of Missouri Kansas City (UMKC)

Raj Shah

Department of Internal Medicine, University of Missouri Kansas City (UMKC)

Danielle Witt

Department of Internal Medicine, University of Missouri Kansas City (UMKC)

Talal Asif

Department of Internal Medicine, University of Missouri Kansas City (UMKC)

For correspondence:
asift@umkc.edu

Fahad F. Mir

Department of Gastroenterology, University of Missouri Kansas City (UMKC)