Treatment Strategies in Seronegative and Other Patients With Myasthenia Gravis

Seronegative patients with myasthenia gravis present unique diagnostic and therapeutic challenges, comprising approximately 5% to 10% of cases where conventional antibody testing fails to detect pathogenic autoantibodies. These patients require careful evaluation to exclude alternative diagnoses such as congenital myasthenic syndromes, myopathies, or other neuromuscular disorders through comprehensive clinical assessment, electrodiagnostic studies, and genetic testing. Cell-based assays can detect additional antibodies in some presumed seronegative cases, suggesting that many patients harbor unidentified pathogenic antibodies.

Clinical evidence supports the autoimmune nature of seronegative myasthenia gravis, as these patients typically respond to plasma exchange and immunomodulatory therapies, indicating circulating pathogenic factors. Many seronegative patients demonstrate clinical presentations and treatment responses similar to AChR-positive disease, suggesting shared pathophysiological mechanisms. Recent data from FcRn inhibitor trials in seronegative populations provides hope for expanded treatment options, though no FDA-approved therapies currently exist specifically for this patient subset.

The management approach for seronegative patients relies heavily on clinical judgment, utilizing repetitive nerve stimulation and single-fiber electromyography as diagnostic tools. Treatment decisions must balance the lack of specific biomarkers with the need for effective immunosuppression, often following treatment paradigms established for seropositive patients. Future research into novel autoantibody targets and improved diagnostic techniques will likely reduce the seronegative population and provide more targeted therapeutic approaches for these challenging cases.