Myasthenia gravis: An update for internists

Abstract

Myasthenia gravis (MG) is an uncommon neuromuscular disorder with an estimated prevalence likely under 1 per 10,000. But knowing some of its clinical characteristics and considering it in the differential diagnosis pushes me to probe deeper into the nuances of a patient’s historical narrative when they list fatigue or weakness as a symptom. MG is an autoimmune disease characterized pathobiologically by the presence of antibodies that recognize components of the muscle side of the neuromuscular junction end plate. The initially recognized and most common target for these antibodies is the acetylcholine receptor (AChR). Unlike common autoimmune conditions with their associated antibodies such as lupus (antinuclear antibodies) and rheumatoid arthritis (rheumatoid factor), the antibodies associated with MG are directly pathogenic. Recognition of the pathophysiologic anti-AChR effect of these antibodies led to the still utilized therapeutic strategy of overcoming the antibody-mediated receptor blockade by increasing the concentration of the receptor’s agonist acetylcholine by slowing its metabolism using inhibitors of acetylcholinesterase. But there is more to the effect of these and other pathogenic antibodies on the progression of MG than simply interfering with the binding of acetylcholine to its cognate receptor.