Heterogeneity in myasthenia gravis: considerations for disease management

ABSTRACT

Introduction: Myasthenia gravis is a rare disease of the neuromuscular junction and a prototype of B cell-driven immunopathology. Pathogenic antibodies target post-synaptic transmembrane proteins, most commonly the nicotinic acetylcholine receptor and the muscle-specific tyrosine kinase, inducing end-plate alterations and neuromuscular transmission impairment. Several clinical subtypes are distinct on the basis of associated antibodies, age at symptom onset, thymus pathology, genetic factors, and weakness distribution. These subtypes have distinct pathogenesis that can account for different responses to treatment. Conventional therapy is based on the use of symptomatic agents, steroids, immunosuppressants and thymectomy. Of late, biologics have emerged as effective therapeutic options.

Areas covered: In this review, we will discuss the management of myasthenia gravis in relation to its phenotypic and biological heterogeneity, in the light of recent advances in the disease immunopathology, new diagnostic tools, and results of clinical trials

Expert opinion: Clinical management is shaped on serological subtype, and patient age at onset, lifestyle and comorbidities, balancing therapeutic needs and safety. Although reliable biomarkers predictive of clinical and biologic outcome are still lacking, recent developments promise a more effective and safe treatment. Disease subtyping according to serological testing and immunopathology is crucial to the appropriateness of clinical management.

KEYWORDS:

• Myasthenia gravis
• acetylcholine receptor
• muscle-specific tyrosine kinase
• autoantibodies
• immunotherapy
• rituximab

Highlights

•Myasthenia gravis (MG) subtypes are categorized on the basis of antibody testing, age at onset, thymus pathology, genetic factors and ocular/generalized weakness patterns.

•When MG is suspected on clinical grounds, antibody testing is usually the first step in establishing the diagnosis. In the absence of specific antibodies, MG confirmation should be based on thorough electrophysiological studies.

•MG response to treatment is highly variable and, even though most patients achieve good control of their disease, maintenance immunosuppression is generally required to avoid symptom relapses. Treatment should be as far as possible patient-tailored, counterpoising therapeutic needs and potential adverse events.

•The advent of biologics has started a new era, giving MG patients, particularly those with refractory disease, the opportunity of targeted, well-tolerated treatments.

•Disease subtyping according to serological testing and based on immunopathology is crucial to the appropriateness of clinical management

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Declaration of interest

AE received honoraria from Grifols (scientific award jury member), Alexion (scientific advisory board) and from UCB Pharma (safety monitor). The authors have no other 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.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was not funded.