Diagnosis and Treatment of Myasthenia Gravis

Renato Mantegazza; Paola Cavalcante

Disclosures

Curr Opin Rheumatol. 2019;31(6):623-633. 

In This Article

Myasthenia Gravis: Clinical Presentation and Classification

Clinical examination and disease course are crucial in myasthenia gravis diagnosis: muscle weakness upon repetitive exercise and fluctuating over time is suggestive of the disease. Ocular, skeletal, bulbar and respiratory muscles are variably involved. Ocular symptoms are frequently observed at onset and may convert into a generalized form, usually within the first 2–5 years,[7] as described in a recent retrospective population-based study.[8] When myasthenia gravis becomes bulbar and respiratory, the disease can be life-threatening.[1]

Clinical manifestations may vary because of severity and muscle group involvement, and patients can be stratified into disease subgroups (Figure 1),[9,10] according to autoantibodies, age at onset and thymic histology.[1,11,12] Myasthenia gravis stratification may be relevant to prognosis and treatment response, thus becoming functional to a personalized approach. MuSK-MG, predominantly ocular and bulbar, has a high risk of a severe clinical course with a lower chance of achieving complete stable remission than AChR-MG; however, improvement of treatment has induced a reduction of respiratory crisis and a better clinical outcome.[13] MuSK-MG is usually not associated with thymic abnormalities and, after thymectomy, a favorable clinical outcome was not observed, as recently reported by a retrospective multicenter study.[14] On the other hand, a thymic hyperplasia has been detected in 23% of patients in whom anti-MuSK antibodies were identified only by a cell-based assay (CBA).[9] LRP4-MG shows clinical features and response to treatment similar to those of AChR-MG, thymoma is usually absent, and thymic hyperplasia was found in 31% of single LRP4-positive and 67% of double LRP4/AChR-positive patients.[10] A recent report showed an absence of hyperplasia in the thymus of four LRP4-MG patients, and one of them went into clinical remission after thymectomy alone, and another one improved after thymectomy in combination with immunosuppressive therapy.[15] A clinical examination of Chinese LRP4-MG patients reported that symptoms were mild and responses to acetylcholinesterase inhibitors and prednisone were mostly successful.[16]

Figure 1.

Clinical features of myasthenia gravis subgroups classified based on autoantibody status. AChR, acetylcholine receptor; LRP4, low-density lipoprotein receptor-related protein 4; MG, myasthenia gravis; MuSK, muscle-specific tyrosine-kinase; RyR, ryanodine receptor.

Thymoma-associated myasthenia gravis is usually more severe than non-thymomatous disease.[1,17] Such a finding was recently observed in a retrospective study performed in 230 Italian myasthenia gravis patients in which thymoma patients reached higher clinical severity and higher antibody titers than patients without thymoma.[18] In the same study, novel HLA associations were detected: DQB1*05:01 was correlated with thymoma, and DQB1*05:02/DRB1*16 haplotype with late-onset (>60 years) non-thymoma AChR-MG, underlying distinct susceptibility to the disease.[18]

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