Mycophenolate mofetil toxicity mimicking acute cellular rejection in a small intestinal transplant

Abstract

Mycophenolate mofetil (MMF) is an important medication used for maintenance immunosuppression in solid organ transplants. A common gastrointestinal (GI) side effect of MMF is enterocolitis, which has been associated with multiple histological features. There is little data in the literature describing the histological effects of MMF in small intestinal transplant (SIT) recipients. We present a case of MMF toxicity in a SIT recipient, with histological changes in the donor ileum mimicking persistent acute cellular rejection (ACR). Concurrent biopsies of the patient’s native colon showed similar changes to those from the donor small bowel, suggesting a non-graft specific process, raising suspicion for MMF toxicity. The MMF was discontinued and complete resolution of these changes occurred over three weeks. MMF toxicity should therefore be considered as a differential diagnosis for ACR and graft-versus-host disease in SITs.

Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and the International Society for Heart and Lung Transplantation

“…146,193 In intestinal transplantation, in the setting of MPA-associated gastrointestinal toxicities, azathioprine use has been reported in a case series with documented amelioration of gastrointestinal symptoms. 150 Its use was also described in a case series where azathioprine was used along with belatacept and prednisone as a rescue therapy in setting of tacrolimus associated kidney dysfunction. 194 Azathioprine has been associated with less GI side effects compared to MMF in heart transplant.…”

“…109,231,234,235 In intestinal transplantation, corticosteroids are a standard component of early-and long-term M-IMS regimens as illustrated by observational studies that persistently include them as essential components of M-IMS in this population. 51,52,[54][55][56][150][151][152][153]194,[243][244][245][246] In heart transplantation, most patients are either maintained on corticosteroids or withdrawal is attempted at 3-6 months or greater post-transplant. [247][248][249][250][251][252] At 1 and 5 years post-transplant, 89% and 52% of recipients, respectively, continued to be maintained on corticosteroids.…”

“…There are no head to head comparative studies for MPA versus azathiprine. Additionally, there are limited data for mycophenolate use in intestinal transplantation due to gastrointestinal toxicities associated with this medication 150 . However, it continues to remain a standard component in many early M‐IMS regimens with tacrolimus, before transition to alternative therapy or tacrolimus monotherapy as illustrated in case reports and case series 82,151–153 …”

“…In intestinal transplantation , corticosteroids are a standard component of early‐ and long‐term M‐IMS regimens as illustrated by observational studies that persistently include them as essential components of M‐IMS in this population 51,52,54–56,150–153,194,243–246 …”

5-gene differential expression predicts stability of human intestinal allografts

“…Histological findings of intestinal rejection (Ruiz et al, 2004) are not specific and high apoptosis rates can be found in patients receiving mycophenolate mofetil (Apostolov et al, 2017) or during adenovirus infections (Kaufman et al, 2002). As the 5-gene set also identifies RX and IRX biopsies, it could be useful to discriminate those "false rejection" biopsies, avoiding the aggressive anti-rejection therapies.…”