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Current and future standards in treatment of myasthenia gravis.

Myasthenia gravis (MG) is a prototypic antibody-mediated neurological autoimmune disorder. Herein we characterize modern treatment algorithms that are adapted to disease severity, and introduce the current principles of escalating strategies for MG treatment. In non-thymoma patients younger than about 50 years of age and with generalized weakness, a complete early (but not urgent) thymectomy is considered as state-of-the-art on the basis of circumstantial evidence and expert opinion. In up to 10% of patients, MG is associated with a thymoma (i.e., is of paraneoplastic origin). The best surgical type of procedure is still under debate. Myasthenic crisis is best treated by plasmapheresis, mostly combined with immunoabsorption techniques. Intravenous immunoglobulins are a reasonable alternative, but a shortage in supplies and high prices limit their use. In generalized MG, a wide array of immunosuppressive treatments has been established, although not formally tested in double-blind, prospective trials. With regard to immunosuppression, azathioprine is still the standard baseline treatment, often combined with initial corticosteroids. In rare patients with an inborn hepatic enzyme deficiency of thiomethylation, azathioprine may be substituted by mycophenolate mofetil. Severe cases may benefit from combined immunosuppression with corticosteroids, cyclosporine A, and even with moderate doses of methotrexate or cyclophosphamide. Tacrolimus is under investigation. In refractory cases, immunoablation via high-dose cyclophosphamide followed by trophic factors such as granulocyte colony-stimulating factor has also been suggested. In the future we may face an increased use of novel, B-cell, or T-cell-directed monoclonal antibodies.

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