Tacrolimus‐associated Gastrointestinal Ulcers in a Kidney Transplant Recipient

We describe a case of a male in his 40s with recalcitrant gastric and ileal ulceration and significant bleeding after ABO-incompatible living-related kidney transplant for diabetic nephropathy. After induction with rituximab and plasma exchange, maintenance immunosuppression was implemented with tacrolimus, mycophenolate mofetil (MMF) and prednisolone. Four months after the transplant, the patient presented with gastrointestinal (GI) haemorrhage, with endoscopic findings of focally denuded squamous gastric mucosa in gastric ulcers and severe, chronic active ileitis with multiple bleeding ileal ulcers (Fig. 1). Histopathology demonstrated extensive surface ulceration and inflammatory cell infiltration of eosinophils admixed with chronic inflammatory cells. Donor and recipient were Cytomegalovirus (CMV) and Epstein Barr Virus IgG-positive. Gastric – but not ileal –ulcer biopsy specimens demonstrated background CMV staining within vessels – but without convincing strong nuclear staining. However, with concomitant low-level CMV viraemia (<137 IU/mL), the patient was treated empirically for CMV disease with IV ganciclovir, without response. Extensive investigations did not support infective aetiologies such as Helicobacter pylori, Entamoeba histolytica, Strongyloides stercoralis, Cryptosporidium, Microsporidium, Cyclospora, Isospora, Histoplasmosis or mycobacteria. Post transplant lymphoproliferative disorder, bowel cancer, mesenteric ischaemia and vasculitis were also excluded. There was no response or changing MMF to mycophenolate sodium for 2 months or azathioprine for 3 months. Differential diagnoses included de novo inflammatory bowel disease, which has been described with onset in the post-transplant period; the patient did not respond to treatment with infliximab at therapeutic levels. The persistence of ulcers and recurrence of GI bleeding required transfusion of 54 units of packed red blood cells over a 4-month period. Significant morbidity and malnutrition ensued, with 11 kg loss of weight and serum albumin nadir of 14 g/L. Finally, changing tacrolimus to cyclosporin, with the addition of thalidomide 100 mg daily, led to the