Overcoming challenges in the diagnosis and treatment of myasthenia gravis

ABSTRACT

In recent years, the discovery of new autoantigens and the use of sensitive assays have expanded the clinical spectrum of myasthenia gravis (MG). In particular, antibodies binding to clustered acetylcholine receptors and to the low-density lipoprotein receptor-related protein 4 have not only bridged a significant gap in diagnosis but also have relevant clinical implications. MG management includes different therapeutic options, from symptomatic agents as the only therapy in mildly affected cases to combined long-term immunosuppression and thymectomy in patients with severe disabling disease. MG biological diversity can influence the response to therapies and should be taken into account when planning treatment. Biologic agents are promising, though their use is currently limited to patients with refractory disease.

KEYWORDS:

• AChR
• clustered-AChR
• immunosuppressants
• Lrp4
• myasthenia gravis
• MuSK
• thymectomy

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Acetylcholine receptor (AChR) antibodies (Abs) are the first to be tested when myasthenia gravis (MG) is suspected.

• Muscle-specific tyrosine kinase receptor (MuSK) Abs should be tested in all AChR negative patients. MuSK-MG is more likely in young adult women with predominant weakness of bulbar and neck muscles.

• Clustered-AChR Abs seem to be more common in young patients (including children) with ocular or mild generalized disease.

• Further studies are needed to assess the specificity of low-density lipoprotein receptor-related protein 4 Abs for MG. These Abs should be assayed in AChR and MuSK negative patients. The associated phenotype appears to be similar to AChR-MG.

• The frequency of triple-negative (AChR/MuSK/low-density lipoprotein receptor-related protein 4 negative) MG could be estimated at 3–4%.

• Most MuSK-MG patients are unresponsive to or intolerant of acetylcholinesterase inhibitors. 3,4-diaminopyridine and albuterol might be beneficial in these cases.

• In uncontrolled studies, rituximab proved effective in MG, especially in MuSK-MG.