Noninfectious colitis

Ipilimumab associated colitis

Topic Completed: 3 March 2021

Minor changes: 8 March 2021

Copyright: 2016-2021,, Inc.

PubMed Search: Colon colitis Ipilimumab

Raul S. Gonzalez, M.D.
Page views in 2020: 776
Page views in 2021 to date: 889
Cite this page: Gonzalez RS. Ipilimumab associated colitis. website. Accessed October 25th, 2021.
Definition / general
  • Colitis caused by use of the anti-CTLA4 medication, ipilimumab
Essential features
  • Colitis is a somewhat common side effect of ipilimumab
  • Can be mild (diarrhea) or severe (perforation, death)
  • Histology: increased intraepithelial lymphocytes, increased apoptosis, cryptitis
  • Occurs in up to 29% of patients taking ipilimumab, an immunologic agent used for melanoma and other malignancies (Melanoma Res 2015;25:321)
  • Causes dysregulation of gastrointestinal mucosal immunity
Clinical features
  • Diarrhea, colitis
Radiology description
Prognostic factors
Case reports
  • Steroids are usually effective but anti-TNF agents or surgery may be required for severe cases (Dig Dis Sci 2016;61:2132)
Clinical images

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Ipilimumab associated colitis
on colonoscopy

Gross images

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Cecal perforation due to severe colitis

Microscopic (histologic) description
  • Lymphoplasmacytic expansion of lamina propria; increased apoptosis and intraepithelial lymphocytes; cryptitis and crypt elongation (Am J Surg Pathol 2008;32:1130)
  • Severe cases may show ulceration/perforation, pseudopolyp formation and crypt dilation, without lymphocytosis or apoptosis (J Clin Gastroenterol 2013;47:781)
Microscopic (histologic) images

Contributed by Raul S. Gonzalez, M.D.
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Acute inflammation with focal cryptitis

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Broad mucosal ulceration

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Increased apoptosis and lymphocytosis

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Lymphoplasmacytic expansion of lamina propria

Positive stains
  • Immunohistochemistry (CD3, CD4, CD8) shows increase in T cell subsets
Sample pathology report
  • Sigmoid colon, biopsy:
    • Colonic mucosa with mild acute inflammation, expanded lamina propria, increased intraepithelial lymphocytes and focally increased apoptosis (see comment)
    • Comment: The patient's use of ipilimumab is noted. The findings are most consistent with ipilimumab associated colitis.
Differential diagnosis
Board review style question #1
Which of the following is true about gastrointestinal tract injury secondary to ipilimumab use?

  1. It can cause ulceration and perforation
  2. It is an extremely rare side effect
  3. It only occurs in the colon
  4. The main histologic findings are Paneth cell metaplasia and a thickened basement membrane
Board review style answer #1
A. It can cause ulceration and perforation

Comment Here

Reference: Ipilimumab associated colitis
Board review style question #2
Ipilimumab associated colitis Ipilimumab associated colitis

A 55 year old man with a history of metastatic melanoma presents with diarrhea and undergoes colonoscopy, which finds musical erythema. A biopsy is taken, with histology shown above. What is the most likely diagnosis?

  1. Ipilimumab induced colitis
  2. Lymphocytic colitis
  3. Segmental colitis associated with diverticulosis
  4. Ulcerative colitis
Board review style answer #2
A. Ipilimumab induced colitis

Comment Here

Reference: Ipilimumab associated colitis
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