sirolimus and Gastrointestinal-Hemorrhage

Multifocal lymphangioendotheliomatosis with thrombocytopenia is a rare disease characterized by progressive multiple vascular lesions and is accompanied by thrombocytopenia. The precise diagnosis of this disease is frequently difficult because of the heterogeneity of the clinical symptoms. We report a case of a male infant who presented with severe thrombocytopenia induced by local inflammation. In addition, enlargement of the extremities with soft tissue and bone involvement without gastrointestinal bleeding was observed. The thrombocytopenia resolved after a combination therapy of sirolimus and prednisolone. Our finding that plasma angiopoietin-2 concentrations reflected the disease status suggests its utility as a biomarker of Multifocal lymphangioendotheliomatosis with thrombocytopenia.

Topics: Blood Coagulation Disorders; Gastrointestinal Hemorrhage; Humans; Infant; Male; Prednisolone; Sirolimus; Thrombocytopenia

Blue rubber bleb nevus syndrome (BRBNS) is a rare systemic venous malformation (VM) disease. The characteristic gastrointestinal (GI) bleeding from multiple VM lesions causes severe chronic anemia which renders most patients depend on lifelong blood transfusion and frequent endoscopic treatment with dismayed outcomes. Although recent case reports suggest that oral sirolimus (rapamycin) is effective, a comprehensive evaluation of its efficacy and safety is in need.. A prospective study was conducted for both pediatric and adult BRBNS patients with administration of sirolimus at the dose of 1.0 mg/m2 to maintain a trough concentration of 3-10 ng/mL. Laboratory tests including complete blood count, biochemical profile, D-dimer, and whole-body magnetic resonance imaging were performed at baseline and 3, 6, and 12 months after treatment. Clinical indicators such as hemoglobin level, lesion size, and transfusion need were evaluated. Adverse effects were recorded regularly.. A total of 11 patients (4 males and 7 females) with median age of 14 (range, 5-49) years were recruited. The average lesion size was reduced by 7.4% (P < 0.001), 9.3% (P < 0.001), and 13.0% (P < 0.05) at 3, 6, and 12 months of sirolimus treatment, respectively. Hemoglobin increased significantly after 6- and 12-month treatment (P = 0.006 and 0.019, respectively). Only 1 patient received blood transfusion once during the study. Patients' quality of life and coagulation function were improved. Grade 1-2 adverse effects including oral ulcers (81.8%), acne (27.3%), transient elevation of liver enzymes (18.2%), and hair loss (9.1%) were observed.. Sirolimus reduces the size of VMs, alleviates GI bleeding, and eliminates transfusion dependence of patients with BRBNS. The drug-related adverse effects are mild and mostly self-limited. These findings support sirolimus as a first-line treatment for GI and cutaneous VMs of BRBNS (see Visual abstract, Supplementary Digital Content, http://links.lww.com/AJG/B819).

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Blood Component Transfusion; Child; Child, Preschool; China; Female; Fibrin Fibrinogen Degradation Products; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nevus, Blue; Prospective Studies; Sirolimus; Skin Neoplasms; Whole Body Imaging

An 18-year-old woman was admitted with abdominal pain and hematochezia. She was previously healthy until 15 years of age and was subsequently diagnosed with hypogammaglobulinemia, protein-losing enteropathy, a benign temporal lobe brain lesion/orbital fibroadenoma, autoimmune hepatitis, iron deficiency anaemia and hypothyroidism. She developed respiratory distress and hypoxemia. She was found to have nodules on chest CT scan. She was diagnosed with cytotoxic T-lymphocyte-associated antigen 4 deficiency via genetic testing.

Topics: Abatacept; Abdominal Pain; Adolescent; CTLA-4 Antigen; Diagnosis, Differential; Female; Gastrointestinal Hemorrhage; Humans; Immunosuppressive Agents; Multiple Pulmonary Nodules; Sirolimus; Treatment Outcome

Recently, sirolimus was demonstrated to be effective in treating vascular lesions and lessening the frequency of bleeding and secondary iron deficiency anemia. We present a child with blue rubber bleb nevus syndrome who had prolonged history of iron deficiency anemia secondary to unrecognized gastrointestinal bleeding. Treatment with propranolol, omeprazole and iron had failed. After 2.5 months of sirolimus therapy (trough levels 1 to 5 ng/mL), his hemoglobin concentration improved into the normal range and remained stable. Vascular malformations on both the patient's tongue and in the fundus of his stomach shrank within 5 months of the initiation of sirolimus. In gastrointestinal involvement of blue rubber bleb nevus syndrome sirolimus was found to be effective even in the tongue's vascular lesions.

Topics: Abnormalities, Multiple; Anemia, Iron-Deficiency; Child; Consanguinity; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Heart Septal Defects, Atrial; Humans; Male; Neoplasms, Multiple Primary; Nevus, Blue; Oral Ulcer; Sirolimus; Skin Neoplasms; Tongue Neoplasms

Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a rare disease characterized by congenital and progressive vascular lesions of the skin and gastrointestinal tract that may be associated with thrombocytopenia and possibly life-threatening gastrointestinal bleeding. Reports published on the disease and treatment strategies are scarce. We present two cases of MLT treated with sirolimus.

Topics: Antibiotics, Antineoplastic; Female; Gastrointestinal Hemorrhage; Humans; Infant; Lymphangioma; Sirolimus; Skin; Skin Neoplasms; Thrombocytopenia

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

Topics: Antineoplastic Agents; Everolimus; Gastrointestinal Hemorrhage; Humans; Immunosuppressive Agents; Prognosis; Risk Assessment; Risk Factors; Sirolimus

Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder with characteristic vascular malformations of the skin, gastrointestinal system, and, less often, other organ systems. The characteristic cutaneous lesions consist of deep-blue, soft, rubbery blebs, which are easily compressible. The most serious complication is abundant gastrointestinal bleeding. We describe the case of an 8-year-old girl with diagnosed BRBNS who had multiple venous malformations all over her body, importantly, throughout the gastrointestinal tract, mouth, esophagus, stomach, small bowel, and colon. She presented with recurrent massive gastrointestinal bleeding and soft tissue hematoma despite prednisolone and α-interferon therapy. We started low-dose sirolimus as an antiangiogenic agent. The vascular masses were reduced rapidly and there was no gastrointestinal bleeding and muscular hematoma after sirolimus therapy. There was no drug adverse reaction at 20-month follow-up. To the best of our knowledge, this is the first report related to the use of sirolimus in a patient with BRBNS.

Topics: Biopsy; Child; Diagnosis, Differential; Dose-Response Relationship, Drug; Endoscopy, Gastrointestinal; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Humans; Immunosuppressive Agents; Nevus, Blue; Sirolimus; Skin Neoplasms; Tomography, X-Ray Computed

Radiation-induced gastritis is an infrequent cause of gastrointestinal bleeding. It is a serious complication arising from radiation therapy, and the standard treatment method has not been established. The initial injury is characteristically acute inflammation of gastric mucosa. We presented a 46-year-old male patient with hemorrhagic gastritis induced by external radiotherapy for metastatic retroperitoneal lymph node of hepatocellular carcinoma. The endoscopic examination showed diffuse edematous hyperemicmucosa with telangiectasias in the whole muscosa of the stomach and duodenal bulb. Multiple hemorrhagic patches with active oozing were found over the antrum. Anti-secretary therapy was initiated for hemostasis, but melena still occurred off and on. Finally, he was successfully treated by prednisolone therapy. We therefore strongly argue in favor of perdnisolone therapy to effectively treat patients with radiation-induced hemorrhagic gastritis.

Topics: Carcinoma, Hepatocellular; Endoscopy; Gastritis; Gastrointestinal Hemorrhage; Hemostasis; Humans; Liver Neoplasms; Liver Transplantation; Male; Middle Aged; Neoplasm Metastasis; Prednisolone; Radiation Injuries; Sirolimus