mycophenolic-acid and Ulcer

A 46-year-old man with myelodysplastic syndrome/myeloproliferative neoplasm-unclassifiable underwent myeloablative bone marrow transplantation from an HLA-DR-1-antigen-mismatched related donor while receiving tacrolimus and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. However, grade III acute GVHD of the gut occurred on day 20 and was treated with prednisolone (PSL) and oral beclomethasone dipropionate while continuing MMF. Subsequently, he presented with progressive epigastric pain. Endoscopy demonstrated multiple stomach and duodenal deep ulcers. The ulcers were suspected to be GVHD; thus, the PSL dose was increased and infliximab was administered; however, the ulcers exacerbated, resulting in repeated perforations and hemorrhagic shock. Furthemore, MMF was suspected as the cause of refractory ulcers and was discontinued on day 156, which resolved the ulcers after 6 months. MMF-induced gastrointestinal (GI) injury resembles anti-inflammatory drug-related ulcers and upper and lower GI tract GVHD, respectively. MMF-induced GI injury has been reportedly resolved after discontinuing or reducing the MMF dose. Several reports suggested that refractory upper GI ulcers and rectal sparing colitis were associated with MMF toxicities rather than GVHD in hematopoietic stem cell transplantations. Physicians should be aware that MMF can induce severe GI injury.

Topics: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Tacrolimus; Ulcer

Topics: Anemia, Iron-Deficiency; Diabetic Nephropathies; Humans; Ileitis; Ileum; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Single-Balloon Enteroscopy; Ulcer

Topics: Antirheumatic Agents; Autoantibodies; Child, Preschool; Cyclophosphamide; Dermatomyositis; Diagnosis, Differential; Glucocorticoids; Humans; Male; Muscle Weakness; Mycophenolic Acid; Penis; Scrotum; Ulcer

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized and potentially fatal complication of cardiac transplantation that commonly involves the gastrointestinal tract. Herein, we report a case of life-threatening gastrointestinal bleeding from recurrent terminal ileac ulcers mimicking PTLD in a heart recipient treated with everolimus (EVL). A 40-year-old man underwent heart transplantation for dilated cardiomyopathy 3 years prior to the current admission and was treated with tacrolimus and EVL. He was admitted to a local hospital because of fever, abdominal pain, and diarrhea. His symptoms persisted and, 3 weeks later, hematochezia occurred; thus, he was transferred to our hospital. As computed tomography and

Topics: Adult; Diagnosis, Differential; Everolimus; Graft Rejection; Heart Transplantation; Humans; Ileal Diseases; Immunosuppressive Agents; Lymphoproliferative Disorders; Male; Mycophenolic Acid; Tacrolimus; Ulcer

Systemic sclerosis-related interstitial lung disease (SSc-ILD) is the leading cause of death in SSc. In this study, we aimed to describe the baseline severity and evolution of forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) in patients with SSc-ILD and to assess the baseline clinical, biological and high-resolution CT scan (HRCT) predictors of this evolution. Baseline and serial FVC and DLCO were collected in 75 SSc-ILD patients followed during 6.4±4.2 years (n = 557 individual data). FVC and DLCO evolution was modelled using a linear mixed model with random effect. During follow-up, FVC was stable while DLCO significantly decreased (-1.5±0.3%/year (p<0.0001). Baseline NYHA functional class III/IV, extensive SSc-ILD on HRCT and DLCO<80% were associated with a lower baseline FVC. Absence of digital ulcers extensive SSc-ILD, and FVC<80% and were associated with a lower baseline DLCO. Presence or history of digital ulcers and presence of pulmonary hypertension at baseline or during follow-up were associated with a faster decline of DLCO overtime. Neither age, gender, subtype of SSc nor specificity of autoantibodies were associated with baseline severity or outcome of lung function tests. In this SSc-ILD population, FVC was therefore stable while DLCO significantly declined over time. ILD extension was associated with baseline FVC and DLCO but not with their evolution. Presence or history of digital ulcers and pulmonary hypertension were predictors of a faster decline of DLCO over time.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carbon Monoxide; Cyclophosphamide; Diffusion; Echocardiography; Female; Fingers; Follow-Up Studies; Humans; Hypertension, Pulmonary; Linear Models; Lung; Lung Diseases, Interstitial; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Pulmonary Diffusing Capacity; Respiratory Function Tests; Scleroderma, Systemic; Ulcer; Young Adult

A 54-year-old man was treated with mycophenolate mofetil (MMF) after undergoing living donor renal transplantation. Two years later, he experienced repeated episodes of diarrhea, and his C-reactive protein (CRP) level was found to be 12.63 mg/dL. Ileocolonoscopy showed multiple deep, punched-out ulcers that were similar to Behçet's disease (BD) and cytomegalovirus (CMV) in the ileum. CMV infection was suspected. However, anti-cytomegalovirus agents were ineffective. The patient was subsequently diagnosed with gastrointestinal toxicity of MMF and MMF was switched to mizoribine. His symptoms improved immediately, and his CRP level normalized. Six months later, the patient's mucosa was healed.

Topics: C-Reactive Protein; Graft Rejection; Humans; Ileal Diseases; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Ulcer

Topics: Biopsy; Capsule Endoscopy; Colonoscopy; Drug Substitution; Gastrointestinal Hemorrhage; Humans; Ileal Diseases; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Treatment Outcome; Ulcer

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.

Topics: Adult; Colonoscopy; Deprescriptions; Gastrointestinal Hemorrhage; Graft Rejection; Humans; Ileal Diseases; Immunosuppressive Agents; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Prednisolone; Sirolimus; Tacrolimus; Ulcer

Since first described in the mid 1990s, there has been burgeoning literature on IgG4-related sclerosing disease. The number of sites that may be involved is ever increasing, with the pancreas, salivary glands, and lymph nodes being the most commonly affected organs. There are no well-documented cases arising in the gastrointestinal tract. In this report, we present the first case to our knowledge of IgG4-related sclerosing disease involving the small bowel with a distinctly unusual clinicopathologic presentation. A previously well 46-year-old woman presented with a 2-year history of intermittent abdominal pain with recent worsening due to small bowel obstruction. Following imaging, which showed jejunitis with surrounding mesenteric inflammatory changes, she proceeded to a segmental small bowel resection. The resected jejunum revealed an isolated, stenosing chronic ulcer associated with a necrotizing mesenteric arteritis. A transmural inflammatory infiltrate rich in IgG4 plasma cells was seen in the wall of the bowel and mesenteric artery. Abundant IgG4 interfollicular plasma cells were also identified in a mesenteric lymph node. The serum IgG4 level was elevated at >800 mg/dL (reference range 8 to 140 mg/dL). Although phlebitis is an almost constant feature of this disease, arteritis is not described other than in the lung and aorta. In this report, we also discuss the diagnostic pitfalls and the differential diagnoses that should be considered when this condition arises in the gastrointestinal tract.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Autoimmune Diseases; Biomarkers; Chronic Disease; Diagnosis, Differential; Female; Humans; Immunoglobulin G; Intestinal Obstruction; Jejunal Diseases; Jejunum; Mesenteric Arteries; Middle Aged; Mycophenolic Acid; Plasma Cells; Polyarteritis Nodosa; Prednisolone; Sclerosis; Treatment Outcome; Ulcer

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Cytomegalovirus Infections; Esophageal Diseases; Female; Foscarnet; Humans; Immunocompromised Host; Mycophenolic Acid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Ulcer

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