Case Presentation: A 67-year-old female with a past medical history of hypertension, hyperlipidemia, and systemic lupus erythematosus (SLE) complicated by lupus nephritis requiring a living unrelated donor renal transplant in 1994 and currently on tacrolimus, mycophenolate mofetil (MMF), and prednisone, presented to the Emergency Department with non-bloody, watery diarrhea and weight loss for 3 months. The patient had initially presented to an outside hospital (OSH) where she had been diagnosed with diverticulitis based on CT imaging, and treated with an appropriate antibiotic course. She continued to have non-bloody, watery diarrhea and presented once again to the OSH. While there, she has positive cytomegalovirus (CMV) IgG and IgM, and also had a colonoscopy which showed cells consistent with CMV inclusions and thus it was felt that the patient’s symptoms were related to CMV. She was treated with IV ganciclovir in the hospital and was transitioned to valganciclovir upon discharge. She received a 6-week course of anti-viral therapy but continued to have diarrhea. She presented to our institution for a second opinion. On presentation, the patient had a creatinine of 3.30 mg/dL (from a baseline of 2.8-2.9 mg/dL) and normal electrolytes. Given the patient’s history, valganciclovir was started on admission. Infectious causes of her diarrhea (including Clostridium difficile, E.coli, and gastrointestinal viruses) were ruled out. CMV DNA by PCR was negative and thus antivirals were stopped. The gastroenterology team was consulted and did another colonoscopy. Biopsy results were consistent with mycophenolate mofetil induced colitis. MMF was discontinued and her diarrhea resolved over the next few weeks.
Discussion: Mycophenolate associated colitis generally occurs in the first 6 months after initiating the medication. While diarrhea can be a side of effect of MMF in up to 83% of patients, MMF associated colitis should be considered in cases with prolonged diarrhea. The incidence of biopsy proven MMF associated colitis is roughly 9% and is usually diagnosed in the presence of typical histopathological changes on colonoscopy biopsy. Discontinuation of MMF is the treatment and usually results in resolution of the diarrhea. The mechanism of colonic injury remains unclear. The immunosuppressive effects may indirectly affect lymphocytes in the colon resulting in decreased mucosal protection, although direct MMF colonic cytotoxicity cannot be ruled out. MMF associated colitis should be considered in patients taking this medication (regardless of duration of use) who have persistent diarrhea when alternate causes have been ruled out.
Conclusions: Mycophenolate associated colitis is a rare complication of MMF use in patients who have received an organ transplant. Typically, this occurs within the first 6 months of use, however here we present a case of patient who had been on MMF for more than 25 years without complications, but then developed diarrhea due to mycophenolate induced colitis. As hospitalists commonly manage patients who have had organ transplantation and receive immunosuppressive medications, it is important to consider adverse reactions (both common and rare) from these medications when common etiologies have been ruled out.