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Mycophenolate mofetil (MMF) is a derivative of mycophenolic acid (MPA) that inhibits the control of T and B lymphocytes and the formation of antibodies and is one of the most effective immunosuppressants in kidney transplant recipients. It is known that MMF can directly cause local gastrointestinal toxicity, or that it can determine cell death by apoptosis and damage to the crypts through cytotoxic or immune-mediated mechanisms. We report a case of colitis caused by MMF.
Male patient, 43 years old, recipient of a kidney transplant from a living donor for 9 years, with a history of diarrhea and vomiting associated with weight loss of 16 kg (35 lb) over 8 months. Pangastritis with positive H. Pylori and chronic colitis with signs of activity were identified in biopsies, and empirical treatment for inflammatory bowel disease (IBD) was initiated by a gastroenterologist. He was hospitalized due to abdominal distension and leukopenia. A surgical abdomen and cytomegalovirus disease were ruled out. Based on the clinical history of prolonged immunosuppression, lack of improvement with empirical treatment for IBD, and exclusion of infectious agents, drug-induced colitis was suspected which was confirmed with the patient's clinical improvement after discontinuation of MMF.
MPA targets fast-growing tissues that depend on purine synthesis. The two main organs dependent on this pathway for regeneration are lymphocytes and intestinal cells. Lymphocytes are more dependent on this pathway, hence the immunosuppression. Thus, patients taking MMF are vulnerable to infections from T- and B-lymphocyte-dependent organisms such as cytomegalovirus, Candida, herpes virus, bacterial pneumonia, and, to a greater extent, sepsis. Enterocytes are included as they are partially pathway dependent and it is estimated that 45% of patients develop gastrointestinal side effects such as esophagitis, enteritis, and colitis like our patient. Gastrointestinal symptoms of MMF include nausea, vomiting, diarrhea, and abdominal pain, particularly in the first six months after starting therapy. However, it has been reported that patients taking MMF can develop mycophenolate-induced colitis between six months and 15 years after first using MMF, with an average of three years. In our patient, symptoms began nine years after the start of MMF. The diagnosis of MMF-induced colitis is based on specific histological features and mainly on the exclusion of an alternative etiology for these histological findings such as infectious colitis and IBD.
Post-transplant colitis represents a challenging complication of kidney transplantation, as data is scarce on why some patients have refractory colitis, why some get it soon after using medications, and while others get it late, in addition to limited data on the management approach.