Noninfectious colitis

Mycophenolate mofetil associated colitis

Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.
Catherine E. Hagen, M.D.

Last author update: 12 May 2020
Last staff update: 17 September 2021

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PubMed Search: Mycophenolate mofetil[TI] colitis

Catherine E. Hagen, M.D.
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Cite this page: Hagen CE. Mycophenolate mofetil associated colitis. website. Accessed April 1st, 2023.
Definition / general
  • Gastrointestinal tract toxicity related to mycophenolate therapy
  • Mycophenolate mofetil (CellCept) is a therapeutic immunosuppressant agent that inhibits the proliferation of B and T cells through noncompetitive, reversible inhibition of inosine monophosphate dehydrogenase and is used for (Pharmacotherapy 1997;17:1178):
    • Prevention of acute rejection of solid organ transplants
    • Treatment of various inflammatory and autoimmune disorders
    • Prophylaxis of acute graft versus host disease (GVHD) and treatment of chronic graft versus host disease
Essential features
  • Gastrointestinal tract toxicity commonly seen in transplant patients taking mycophenolate, particularly renal transplant recipients
  • Symptoms resolve with medication withdrawal or dose reduction
  • Histologically characterized by crypt apoptosis, crypt injury, lamina propria eosinophils and architectural distortion
  • Lack of neuroendocrine cell aggregates, presence of eosinophils and paucity of apoptotic microabscesses can help distinguish from graft versus host disease
  • Also called CellCept colitis
ICD coding
  • ICD-10: Z79.899 - other long term (current) drug therapy
  • Anywhere in gastrointestinal tract can be involved:
Clinical features
  • Endoscopy with tissue biopsy
  • Symptom resolution following drug withdrawal / dose reduction
  • Exclusion of other etiologies (e.g. infection, other drugs, etc.)
Prognostic factors
  • Patients universally do well following withdrawal or dose reduction
Case reports
  • Dose reduction or discontinuation of mycophenolate
Clinical images

Images hosted on other servers:

Endoscopic appearance

Microscopic (histologic) description
  • Crypt apoptosis with no or few apoptotic microabscesses
  • Increased eosinophils (> 15/10 high powered fields) present in lamina propria
  • Neutrophilic inflammation may also be present in lamina propria; cryptitis and crypt abscess may be present but usually focal (J Clin Pathol 2013;66:8)
  • Lack of lamina propria endocrine cell aggregates
  • Architectural distortion
  • Pseudopyloric gland metaplasia can be seen (Int J Surg Pathol 2003;11:295)
  • Injured dilated eosinophilic crypts may be present but typically to a lesser degree than graft versus host disease
  • Can have Crohn's-like appearance with patchy inflammation and lymphoid hyperplasia (Int J Surg Pathol 2003;11:295)
  • Cases are not routinely graded but if necessary the Lerner system can be used (Am J Surg Pathol 2013;37:1319)
Microscopic (histologic) images

Contributed by Catherine E. Hagen, M.D.

Architectural distortion

Injured crypt



Negative stains
  • CMV immunostain
Sample pathology report
  • Colon, biopsy:
    • Colonic mucosa with increased crypt apoptosis and mild architectural distortion (see comment)
    • Comment: Given the patient’s reported use of mycophenolate, the histologic features are suggestive of mycophenolate colitis (or give differential diagnosis as appropriate).
Differential diagnosis
Board review style question #1

A 45 year old man who underwent a kidney transplant one year ago presents complaining of watery diarrhea. A colonoscopy and biopsy are performed. CMV immunohistochemistry is negative. Based on the histologic findings, which of the following is the most likely diagnosis?

  1. Graft versus host disease
  2. Infectious colitis
  3. Mycophenolate toxicity
  4. Ulcerative colitis
Board review style answer #1
C. Mycophenolate toxicity

Comment Here

Reference: Mycophenolate mofetil colitis
Board review style question #2
Which of the following histologic features is not helpful in distinguishing mycophenolate toxicity from graft versus host disease?

  1. Apoptotic microabscesses
  2. Architectural distortion
  3. Endocrine cell aggregates
  4. Eosinophilic inflammation
Board review style answer #2
B. Architectural distortion

Comment Here

Reference: Mycophenolate mofetil colitis
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