tacrolimus and Duodenal-Ulcer

Duodenal ulcers are most often caused by Helicobacter pylori (HP) infection, followed by nonsteroidal anti-inflammatory drugs and hypoperfusion. Posttransplant lymphoproliferative disorder (PTLD) occurs in about 1-6.3% of patients with a heart transplant under immunosuppression therapy. Up to 25% of cases of PTLD have gastrointestinal involvement. Due to a wide spectrum of clinical symptoms and pathological entities, the diagnosis can be challenging. We report the case of a 55-year-old man 12 years after receiving a heart transplant being treated with immunosuppressive agents (tacrolimus) who presented with recurrent bleeding from peptic duodeni. Immunohistochemistry revealed a rare Epstein-Barr-virus-associated polymorphic PTLD. Rarely, PTLD can manifest only with isolated lesions of the duodenal bulb. The course was progressive, going from an incidental finding requiring transfusion anemia to a perforation within 1 month. Repeated endoscopic interventions were unsuccessful. After a surgical intervention the patient died in the course of multiple organ failure. Retrospectively, a reduction of immunosuppression in polymorphic PTLD would have been a treatment option.

Topics: Duodenal Ulcer; Epstein-Barr Virus Infections; Fatal Outcome; Heart Transplantation; Humans; Immunosuppressive Agents; Lymphoproliferative Disorders; Male; Middle Aged; Prognosis; Tacrolimus; Treatment Outcome

Infection due to cytomegalovirus (CMV) is the most frequent opportunistic infection following renal transplantation (RT). It is usually asymptomatic. Cytomegalovirus disease causes fever leucopenia, thrombocytopenia and slightly elevated transaminases. The development of severe invasive forms is uncommon nowadays with post-transplantation monitoring, prophylactic regimens in high-risk patients and early treatment with ganciclovir. We report two renal transplant recipients who presented with severe gastrointestinal bleeding as the first manifestation of CMV disease at 9 and 14 weeks after transplantation. In both patients repeated post-transplantation pp65 antigenemia monitoring was negative. One patient developed hypovolemic shock due to severe rectal bleeding; an atypical bleeding ulcer was detected in the ileocecal valve. The other patient presented with upper gastrointestinal hemorrhage from a bleeding duodenal ulcer. Histological and immunohistochemical study confirmed the diagnosis. Both patients were elderly and on triple therapy with tacrolimus, mycophenolate and prednisone. We discuss the role of mycophenolate and the new immunosuppressant agents as factors favoring a state of enhanced immunosuppression, which may facilitate the onset of severe atypical forms of CMV disease.

Topics: Aged; Cytomegalovirus; Cytomegalovirus Infections; Disease Susceptibility; Duodenal Ulcer; Gastrointestinal Hemorrhage; Humans; Ileal Diseases; Ileocecal Valve; Immunocompromised Host; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Postoperative Complications; Prednisone; Shock; Tacrolimus; Ulcer

The mechanism of nonsteroidal antiinflammatory drug-induced intestinal ulcers is not clearly understood. To evaluate whether immunosuppressants have a preventive effect against indomethacin-induced gastrointestinal damage, we investigated the effects of prednisolone, cyclosporin, and the newly developed immunosuppressant FK-506 in intracolonically indomethacin-treated rats: 24 mg/kg of indomethacin, administered intracolonically for two days, caused gastric ulcers and two types of small intestinal ulcers (longitudinal ulcers and scattered small ulcers). Pretreatment with intraperitoneal immunosuppressants reduced the size of gastric ulcers. Both cyclosporin (10 mg/kg) and FK-506 (1 mg/kg, 2 mg/kg) treatments significantly reduced the incidence and the length of the longitudinal ulcers of the small intestine when compared to the vehicle-treated controls, whereas prednisolone (20 mg/kg) did not show any preventive effect. Furthermore, the number of small scattered ulcers of the small intestine was significantly reduced by the high dose of FK-506 (2 mg/kg), but not by cyclosporin or prednisolone. These findings indicate that immunosuppressants have protective and antiinflammatory effects in indomethacin-induced gastroenteropathy, suggesting that cytokines may be important mediators in the pathogenesis of enteropathy induced by nonsteroidal antiinflammatory drugs.

Topics: Animals; Cyclosporine; Duodenal Ulcer; Immunosuppressive Agents; Indomethacin; Intestine, Small; Male; Prednisolone; Rats; Rats, Wistar; Stomach Ulcer; Tacrolimus