mycophenolic-acid and Thrombotic-Microangiopathies

Despite advances in therapeutic and preventive measures, hematopoietic stem cell transplant recipients remain at risk for a variety of gastrointestinal and liver complications.. To detail the pathologic features of the various gastrointestinal and liver complications occurring after hematopoietic stem cell transplantation in relation to their clinical context. The specific complications covered include graft-versus-host disease, mycophenolate mofetil-induced injury, timeline of infections, neutropenic enterocolitis, gastrointestinal thrombotic microangiopathy, sinusoidal obstruction syndrome, hepatic iron overload, and the controversy around cord colitis syndrome.. The content of this article is based on pertinent peer-reviewed articles in PubMed, relevant textbooks, and on the authors' personal experiences.. The final histopathologic diagnosis requires the integration of clinical and histologic findings and the exclusion of other competing causes of injury. Review of the clinical data, including the original disease pretransplant, the type of transplant, the timing of the gastrointestinal and/or liver manifestations, the timing of the biopsy after transplant, the presence of graft-versus-host disease in other organs and sites, the list of drug regimens, and the clinical and laboratory evidence of infection, is the key to reaching the proper histologic diagnosis.

Topics: Biopsy; Colitis; Enterocolitis, Neutropenic; Gastrointestinal Diseases; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Immunosuppressive Agents; Infections; Liver Diseases; Mucous Membrane; Mycophenolic Acid; Thrombotic Microangiopathies

Topics: Antibodies, Monoclonal; Cyclosporins; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Kidney; Mycophenolic Acid; Prospective Studies; Retrospective Studies; Sirolimus; Thrombotic Microangiopathies; Transplantation, Homologous

Thrombotic microangiopathy (TMA) is generally diagnosed through clinical features characterized as microangiopathic hemolytic anemia, thrombocytopenia, and multiple organ injury, as well as by pathological findings such as vascular damage and endothelial cell injury. Rheumatic and autoimmune diseases could be accompanied by secondary TMA; in fact, systemic lupus erythematosus (SLE) is a common disease associated with secondary TMA, and SLE complicated with TMA has been reported to have a poor prognosis. Although TMA occurs rarely in pediatric SLE patients, it often leads to severe clinical conditions. Here, we report a rare case of severe juvenile-onset SLE complicated with TMA and kidney injury. The 5-year-old patient showed renal dysfunction, thrombocytopenia, hemolytic anemia, nephrotic syndrome, hypocomplementemia, and elevation of anti-dsDNA IgG levels. Kidney biopsy revealed mesangial proliferation and endocapillary proliferation, as well as plumped endothelial cells, with full-house pattern deposits in immunofluorescence study. Combination treatment of methylprednisolone pulse therapy followed by oral prednisolone, mycophenolate mofetil, and plasma exchange was effective, whereas eculizumab did not show therapeutic effects. The patient further showed recurrent deterioration, and we initiated intravenous cyclophosphamide in addition to combination treatment and eventually succeeded in controlling the disease. Genome analysis by whole-exome sequencing revealed no particular gene mutation related to either complement disorders or type-1 interferon. Further elucidations concerning the pathogenic mechanisms causing juvenile-onset SLE are needed to establish an efficient treatment strategy for TMA with SLE.

Topics: Adrenal Cortex Hormones; Anemia, Hemolytic; Antibodies, Antinuclear; Antirheumatic Agents; Biopsy; Child, Preschool; Combined Modality Therapy; Complement Hemolytic Activity Assay; Cyclophosphamide; Enzyme Inhibitors; Humans; Kidney; Lupus Erythematosus, Systemic; Mycophenolic Acid; Nephrotic Syndrome; Plasma Exchange; Recurrence; Thrombocytopenia; Thrombotic Microangiopathies; Treatment Outcome

Thrombotic microangiopathy (TMA) is a pathologic condition characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury due to microvascular endothelial lesions and thrombosis. It occurs in a variety of diseases and, unless recognized and treated, leads to severe morbidity and mortality. We present the case of a 48-year-old woman who underwent lung transplantation, initially under tacrolimus, mycophenolate mofetil (MMF), and prednisolone. Several complications emerged in the following months, including abdominal aortic and left renal artery thrombosis and cutaneous infections, although her renal function remained normal. Six months after transplant, her renal function began to deteriorate, which was assumed to be due to elevated tacrolimus levels and doses were adjusted. Due to leukopenia, MMF was changed to everolimus. One year after, she was admitted with fatigue, anemia, and renal dysfunction. Complementary exams revealed only iron deficiency, leukopenia, normal platelets, and elevated lactate dehydrogenase; her renal ultrasound was normal. A renal biopsy was performed and thrombotic microangiopathy was subsequently identified as the main cause of the renal dysfunction. Tacrolimus was therefore discontinued and MMF restarted with slow improvement of renal function. Only when everolimus was stopped did the patient's renal function show incremental improvement. TMA may be a serious complication after lung transplantation and the risk is higher when a combination of tacrolimus and everolimus is used. Renal biopsy findings are essential to confirm the final diagnosis of TMA, allowing for a change in immunosuppression to prevent permanent and severe renal damage.

Topics: Everolimus; Female; Humans; Immunocompromised Host; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Diseases; Lung Transplantation; Middle Aged; Mycophenolic Acid; Tacrolimus; Thrombotic Microangiopathies

Topics: ADAMTS13 Protein; Adult; Combined Modality Therapy; Female; Humans; Kidney; Lupus Erythematosus, Systemic; Male; Middle Aged; Mycophenolic Acid; Plasma Exchange; Steroids; Thrombotic Microangiopathies; Young Adult

Topics: Acute Disease; Antiviral Agents; Colon; Colonoscopy; DNA, Viral; Enzyme Inhibitors; Ganciclovir; Hepatitis B; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Tacrolimus; Thrombotic Microangiopathies