Successful treatment of ileal ulcers caused by immunosuppressants in two organ transplant recipients

Abstract

Although gastroduodenal ulcers are common in solid organ transplant patients, there are few reports on multiple giant ulcers in the distal ileum and ileocecal valve caused by immunosuppressants Herein, we report on a liver transplant recipient and a renal transplant recipient with multiple large ulcers in the distal ileum and ileocecal valve who rapidly achieved ulcer healing upon withdrawal of sirolimus or tacrolimus and administration of thalidomide. In case 1, a 56-year-old man with primary hepatocellular carcinoma had received a liver transplantation. Tacrolimus combined with sirolimus and prednisolone was used as the anti-rejection regimen. Colonoscopy was performed because of severe abdominal pain and diarrhea at post-operative month 10. Multiple giant ulcers were found at the ileocecal valve and distal ileum. The ulcers healed rapidly with withdrawal of sirolimus and treatment with thalidomide. There was no recurrence during 2 years of follow-up. In case 2, a 34-year-old man with end-stage kidney disease received kidney transplantation and was put on tacrolimus combined with mycophenolate mofetil and prednisolone as the anti-rejection regimen. Twelve weeks after the operation, the patient presented with hematochezia and severe anemia. Colonoscopy revealed multiple large ulcers in the ileocecal valve and distal ileum, with massive accumulation of fresh blood. The bleeding ceased after treatment with intravenous somatostatin and oral thalidomide. Tacrolimus was withdrawn at the same time. Colonoscopy at week 4 of follow-up revealed remarkable healing of the ulcers, and there was no recurrence of bleeding during 1 year of follow-up. No lymphoma, tuberculosis, or infection of cytomegalovirus, Epstein-Barr virus, or fungus was found in either patient. In post-transplantation cases with ulcers in the distal ileum and ileocecal valve, sirolimus or tacrolimus should be considered a possible risk factor, and withdrawing them or switching to another immunosuppressant might be effective to treat these ulcers.

β-arrestin 2 attenuates lipopolysaccharide-induced liver injuryviainhibition of TLR4/NF-κB signaling pathway-mediated inflammation in mice

“…Hematoxylin and eosin (HE) staining and TUNEL staining were performed to generate a histopathology score of liver injury. H&E staining was performed as described in our previous study[ 8 ] and TUNEL staining was performed using an in-situ cell death detection kit (Roche, Basel, Switzerland) according to the manufacturer’s instructions. Briefly, sections were scored in a blinded manner for apoptosis and hemorrhage in five 200 × magnified fields according to Hoque’s report[ 9 ].…”

Tacrolimus-Induced Esophageal and Colon Ulcers

“…There have been a handful of reported cases of TC inciting the development of diffuse GI ulcers. 5,6 From a histologic perspective, TC-related injury has been associated with regenerative crypts and apoptotic debris; in this case, necroinflammatory debris was appreciated in the biopsies. 7 One possibility is that TC impairs the normal process of wound healing that would otherwise avoid the development of GI ulcers in a person not on this medication.…”

Tacrolimus‐associated gastrointestinal ulcers in a kidney transplant recipient

“…2,3 This is the first reported case of tacrolimus-associated GI ulcers in a kidney transplant recipient from Australia. There have been cases reported of successful treatment of GI ulcers in solid organ transplant recipients by switching tacrolimus to alternative immunosuppression both within and outside drug class, 4,5 and this change, coupled with thalidomide therapy, was effective in treating GI ulcers in this patient. Thalidomide has utility in a variety of chronic GI bleeding pathologies through a combination of anti-angiogenic effects, and its immunomodulatory effects through which it stimulates regulatory T-cells.…”

“…Thalidomide has been used as adjunctive therapy in solid organ transplant recipients with bleeding GI ulcers. 4 It is important to consider iatrogenic causes of GI ulceration. Evidence is circumstantial, and the contribution of thalidomide to ulcer healing in this case is unknown; however this case strongly suggests that idiopathic GI ulceration in a kidney transplant recipient may have been caused by tacrolimus use.…”