What is the initial treatment for myasthenia gravis?

Initial Treatment for Myasthenia Gravis

Pyridostigmine is the first-line treatment for myasthenia gravis, starting at 30 mg orally three times daily and gradually titrating up to a maximum of 120 mg four times daily based on symptom response and tolerability. 1, 2, 3

Stepwise Treatment Algorithm

First-Line: Acetylcholinesterase Inhibitor

• Start pyridostigmine (Mestinon) at 30 mg orally three times daily and increase gradually to a maximum of 120 mg four times daily as tolerated 1, 2, 4
• This is FDA-approved for myasthenia gravis treatment and provides symptomatic relief by enhancing neuromuscular transmission 3
• Patients should take medication at consistent times to optimize strength throughout the day 2
• Important caveat: Approximately 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone and may require escalation 1, 4

Second-Line: Corticosteroids

• Initiate prednisone 1-1.5 mg/kg daily for patients with Grade 2 or higher symptoms who have inadequate response to pyridostigmine 1, 4
• Corticosteroids demonstrate positive response in approximately 66-85% of patients 1, 4
• Taper gradually based on symptom improvement 4
• Can be started directly in patients with Grade 2 symptoms without waiting for pyridostigmine failure 4

Third-Line: Steroid-Sparing Immunosuppression

• Add azathioprine for patients with moderate to severe disease requiring long-term immunosuppression or as adjunctive therapy with corticosteroids 1, 4
• This allows for corticosteroid dose reduction and provides sustained disease control 1

Critical Medications to Avoid

Educate patients to strictly avoid the following medications that can precipitate myasthenic crisis:

• β-blockers 1, 4
• IV magnesium 1, 4
• Fluoroquinolone antibiotics 1, 2, 4
• Aminoglycoside antibiotics 1, 2, 4
• Macrolide antibiotics 1, 2, 4
• Barbiturate-containing medications (e.g., butalbital) 2

Essential Monitoring

• Perform regular pulmonary function assessments, especially in patients with generalized disease, as 50-80% of patients with initial ocular symptoms may progress to generalized myasthenia 1, 2, 4
• Monitor for bulbar symptoms (dysphagia, dysarthria), respiratory difficulties, and diplopia 2
• Patients should seek immediate medical attention for significant increases in muscle weakness 2

Acute Exacerbation Management

For Grade 3-4 myasthenic exacerbations or crisis requiring hospitalization:

• Administer IVIG 2 g/kg IV over 5 days OR plasmapheresis for 5 days 1, 2, 4
• Continue corticosteroids during acute treatment 4
• Do NOT use IVIG for chronic maintenance therapy - it is only indicated for acute exacerbations or in patients resistant to/intolerant of immunosuppressive therapy 2

Common Pitfall

The most significant error is delaying escalation to corticosteroids in patients with inadequate pyridostigmine response. Since approximately half of patients show minimal response to anticholinesterase inhibitors alone, particularly those with ocular symptoms, clinicians should have a low threshold for adding corticosteroids rather than maximizing pyridostigmine doses indefinitely 1, 4.