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


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.
Dalle
I J
IJ
University Hospitals Leuven, Leuven, Belgium. ignace.dalle@planetinternet.be
Maes
B D
BD
Geboes
K P
KP
Lemahieu
W
W
Geboes
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000378:metabolism; D016022:Case-Control Studies; D002908:Chronic Disease; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D003967:Diarrhea / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*
D015820:Cadherins; D007166:Immunosuppressive Agents; D019394:Ki-67 Antigen; D009173:Mycophenolic Acid