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 trialsExpert 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; autoantibodies; immunotherapy; muscle-specific tyrosine kinase; rituximab.