Crohn's-like changes in the colon due to mycophenolate?

Colorectal Dis. 2005 Jan;7(1):27-34. doi: 10.1111/j.1463-1318.2004.00695.x.

Abstract

Objective: Mycophenolate mofetil (MMF) is used for prevention of allograft rejection in kidney transplant patients. A subset of patients suffers from chronic diarrhoea of unknown origin. The aim of the study was to investigate the effect of MMF on the colonic mucosa.

Materials and methods: Colonic mucosal biopsies from 24 kidney transplant patients receiving MMF and presenting with chronic diarrhoea were analysed using routine stainings and immunohistochemistry for Ki67 and E-cadherin. Results were compared with a control group of 19 kidney transplant patients not receiving MMF. In all patients routine clinical and laboratory investigations were performed in order to explain the diarrhoea.

Results: In 11 patients, the diarrhoea seemed to be of infectious origin. Furthermore, 19/24 of MMF-patients showed characteristic histological alterations of the mucosa that were Crohn's disease-like: discontinuous crypt architectural distortion, increased epithelial mucin secretion, mildly active inflammation and focal presence of dilated and inflamed crypts. Ki67 staining was abnormal in 6/24 MMF patients but also in 4/19 control patients. E-Cadherin staining was normal in most MMF and control patients.

Conclusions: Diarrhoea following MMF treatment is frequently infectious in origin and associated with morphological changes with a Crohn's-like pattern in the colonic mucosa in a subset of patients. MMF does not induce major alteration in the proliferative compartment of colonic epithelium. The diarrhoea is not associated with altered E-cadherin expression in the colonic epithelium.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cadherins / metabolism
  • Case-Control Studies
  • Chronic Disease
  • Colon / drug effects*
  • Colon / metabolism
  • Colon / pathology*
  • Diarrhea / etiology
  • Diarrhea / metabolism
  • Diarrhea / pathology*
  • Female
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Ki-67 Antigen / metabolism
  • Kidney Transplantation / immunology*
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacology*

Substances

  • Cadherins
  • Immunosuppressive Agents
  • Ki-67 Antigen
  • Mycophenolic Acid