mycophenolic-acid and Drug-Hypersensitivity

Autoimmune hepatitis (AIH) is a chronic, progressive hepatitis of uncertain cause which has fluctuating activity characterized by periods of flares and remissions. Initial placebo-controlled trials carried out in the 1970s demonstrated that immunosuppression with steroids was extremely effective in reducing flares and progression of disease. The late 1980s-1990s could be described as the 'Dark Ages' of AIH treatment research. Very few clinical studies were performed during this time, although it became increasingly apparent that not all patients tolerated or responded to traditional immunosuppression, and that not all patients were easy to diagnose because of overlapping features with other autoimmune conditions. Fortunately, clinical research in the treatment of AIH has experienced a renaissance in the 21st century.. This review highlights some of the more important recent discoveries, including the creation of the clinically useful short form of the autoimmune hepatitis diagnostic scoring system; accumulation of data supporting the use of mycophenolate and tacrolimus as second-line treatment; and the recent completion of the largest, double-blind, placebo-controlled trial of AIH treatment to date, comparing budesonide to prednisone.. These new findings are pertinent to the everyday clinical management of patients with AIH.

Topics: Azathioprine; Budesonide; Drug Hypersensitivity; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Mycophenolic Acid; Purine-Pyrimidine Metabolism, Inborn Errors; Tacrolimus

Up to now ophthalmologists have only a small number of substances in their therapeutic armamentarium for the treatment of ocular immunological disorders. These are very potent agents, and any rapidly proliferating cells are extremely sensitive to such agents, thus the possibility of severe side effects is great. Mycophenolatemofetil (MMF) has been shown to be effective in preventing acute graft rejection following clinical renal and cardiac transplantation with a low risk of adverse events. Likewise MMF was effective in the treatment of experimental immunological disorders. A review of literature was performed in Medline.. We report on the effective use of MMF in a patient with ocular cicatricial pemphigoid, the switch from Cyclosporin A (CSA) therapy to MMF therapy following high-risk keratoplasty due to CSA allergy and about the combination therapy (CSA/MMF) in a patient following high risk keratoplasty, in whom CSA monotherapy was not sufficient to prevent allograft rejection.. In these three cases MMF has been shown to be a safe and effective agent for the treatment of ocular immunological disorders. Whether these beneficial casuistic experiences will hold true will be depended on the outcome of longterm studies underway.

Topics: Corneal Transplantation; Cyclosporine; Drug Hypersensitivity; Eye Diseases; Female; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Pemphigoid, Benign Mucous Membrane

Rituximab, a chimeric anti-CD20 monoclonal antibody, is an effective treatment in steroid-dependent nephrotic syndrome (SDNS). However, some patients develop adverse reactions.. Patient 1, a 14-year-old boy with SDNS since the age of 2, was treated with oral prednisone, cyclosporine A (CsA) and mycophenolate mofetil. A first infusion of rituximab at age 12 years was well tolerated, but this was followed by a prolonged relapse unresponsive to oral prednisone, mycophenolate mofetil and CsA. A second rituximab infusion was attempted, but treatment was interrupted due to severe dyspnea. Treatment with a humanized anti-CD20 monoclonal antibody, ofatumumab, was then attempted. The patient experienced a mild allergic reaction and maintained remission despite interruption of all treatment at >12 months of follow-up. Patient 2, a 3-year-old boy who presented at 18 months with nephrotic syndrome initially resistant to treatment with oral prednisone, was given with three intravenous boluses of methylprednisolone followed by CsA and achieved remission. Upon steroid discontinuation, the NS relapsed. Prednisone was restarted and treatment with a single dose of rituximab was never completed due to a severe allergic reaction. Ofatumumab infusion was uneventful, and he maintained remission during the follow-up period (>12 months) despite interruption of prednisone therapy. B cells reappeared at 7 months in both patients.. Ofatumumab may be a therapeutic option in severe forms of NS with allergy to rituximab.

Topics: Adolescent; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; B-Lymphocytes; Child, Preschool; Cyclosporine; Drug Hypersensitivity; Drug Resistance; Humans; Immunosuppressive Agents; Male; Methylprednisolone; Mycophenolic Acid; Nephrotic Syndrome; Prednisone; Rituximab; Treatment Outcome

The use of MMF has become standard practice in many solid organ transplant recipients due its efficacy and favorable risk profile compared to other immunosuppressants. There has been a single case report of successful MMF desensitization. However, this protocol did not follow current Drug practice parameters. We report a successful desensitization to MMF in a double heart-kidney transplant recipient.

Topics: Desensitization, Immunologic; Drug Hypersensitivity; Female; Graft Rejection; Graft Survival; Heart Transplantation; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Time Factors; Treatment Outcome

Topics: Adult; Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid

Topics: Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Humans; Immunosuppression Therapy; Insulin; Mycophenolic Acid; Omalizumab; Pancreas Transplantation

Topics: Child; Cyclosporine; Drug Hypersensitivity; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Tacrolimus; Transplantation, Homologous

Despite therapeutic advances in the treatment of systemic lupus erythematosus (SLE), several patients are still afflicted with severe and uncontrolled symptoms. Recently, mycophenolate mofetil (MMF) has been introduced in the treatment of SLE, with a significant therapeutic benefit, and minor side effects have been reported. Data on the adverse effects of MMF in SLE are lacking. We present an SLE patient who developed urticaria during MMF treatment. Rechallenge with MMF established the diagnosis of MMF-induced urticaria. As MMF was considered a necessary therapy, a desensitization protocol was devised, which successfully induced tolerance to MMF. This is the first published protocol for MMF desensitization, which induced tolerance in an SLE patient previously reacting with generalized urticaria.

Topics: Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Middle Aged; Mycophenolic Acid; Urticaria

From 1992 to 2003, 407 kidney transplantations were performed on 403 patients using cyclosporine (CyA) or tacrolimus (Tac), mycophenolate (MMF), and steroid immunosuppression. Patient records examined for adverse events (AE) and MMF dose reductions or discontinuations during 100 days posttransplant were correlated with data on rejections, graft function, and survival. AEs occurred in 79.1% of transplantations. Gastrointestinal (GI) symptoms, infections, and cytopenias were common. Surprisingly, in 50% of all transplantations serum alanine transferase (ALAT) was elevated, among 21% the change was over three times the upper limit of normal. Patients with delayed graft function showed increased incidences of GI symptoms and thrombocytopenias. There were more ALAT increases and thrombocytopenias in patients on CyA and more GI symptoms in patients on Tac. In 34% of transplantations, the MMF dose was reduced or discontinued. In CyA patients with MMF reduction by day 21, rejection incidence during the subsequent 21 days was 10% versus 0.6% in patients with full-dose MMF until day 21 (P < .002). Among Tac patients no increased rejection frequency was seen after reducing MMF.

Topics: Adult; Alanine Transaminase; Drug Hypersensitivity; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Retrospective Studies; Tacrolimus; Treatment Outcome

Topics: Animals; Coronary Thrombosis; Drug Hypersensitivity; Drug Implants; Humans; Male; Middle Aged; Mycophenolic Acid; Rats; Sirolimus; Stents