Myasthenia Gravis – Optimal Treatment in Severe Disease

yasthenia gravis (MG) is an autoimmune disorder, where antibodies bind to the postsynaptic membrane at the neuromuscular junction.These antibodies induce acetylcholine receptor (AChR) dysfunction and destruction, leading to muscle weakness.Fluctuations are typical for the MG weakness, being more prominent after repeated muscle use.Patients with MG are separated into subgroups according to localisation of muscle weakness, age, antibody specificity and thymus pathology.All groups have a minority of patients with severe and therapy-resistant MG.Biomarkers may indicate a more severe prognosis.First-line MG therapy includes pyridostigmine, an acetylcholine esterase inhibitor that gives symptomatic relief, as well as immunosuppressive drugs.European guidelines recommend the combination of prednisolone and azathioprine.Thymectomy is recommended in patients with AChR antibodies, generalised disease and age of onset <65 years, as well as in nearly all patients with a thymoma.Second-line therapies, necessary in many severe cases, include mycophenolate, rituximab, methotrexate, cyclosporine and tacrolimus.Complement inhibitors and FcRn inhibitors represent new therapies that seem to be effective.Their clinical use should depend also on cost-benefit considerations.Intravenous immunoglobulin and plasma exchange are fast-acting therapies used for acute exacerbations and in situations where extra muscle strength is necessary, for example before surgery.Some patients receive this therapy repeatedly.Supportive therapy is important for all patients, and this includes an adapted training programme.In patients with severe MG and an unsatisfactory response to several treatments, the clinician should consider comorbidity.Especially in elderly patients, optimal treatment for several combined conditions may represent a challenge.The MG diagnosis should always be revisited in therapy-resistant cases.