Mycophenolate Mofetil-Related Enterocolitis and Weight Loss: A Pediatric Case Series

Abstract

Mycophenolate mofetil (MMF) is an immunosuppressive medication utilized in the management of both autoimmune and solid organ transplant patients. Diarrhea is a common gastrointestinal side effect of MMF, but more severe forms of GI symptoms are described in renal transplant patients with a distinct pattern of histopathologic change, similar to graft-versus-host disease or Crohn's disease. This rare entity, commonly referred to as “MMF-related enterocolitis,” has been described in adult patients, mostly in renal transplant patients, and in only two pediatric renal transplant patients. In previously reported cases, symptoms and abnormal histopathology improve with dose reduction of MMF. We describe a series of three pediatric patients with varied underlying disease process who presented with severe diarrhea and histopathologic findings characteristic of MMF-related enterocolitis, who share a novel finding of weight loss as a complication of MMF-related enterocolitis in pediatric patients.

An intact microbiota is required for the gastrointestinal toxicity of the immunosuppressant mycophenolate mofetil

“…In 2 wild-type strains (C57BL/6 and BALB/c), and in Rag1-deficient mice, we have shown that MMF treatment leads to rapid and significant weight loss accompanied by gross colonic changes and inflammation, recapitulating the effects seen in humans. 36,37 We also observed that MMF administration prompted alterations in the composition of the microbiota and its associated metagenome. The presence of the microbiota appears to be a critical factor necessary for the toxicity of MMF, as weight loss and colonic pathology were absent in GF mice, and the administration of antibiotics was sufficient to both prevent and reverse the phenotype associated with MMF exposure.…”