What is the initial treatment for non-ocular symptoms of myasthenia gravis?

Initial Treatment for Non-Ocular Myasthenia Gravis

Start pyridostigmine at 30 mg orally three times daily and gradually increase to a maximum of 120 mg four times daily based on symptom response, then escalate to prednisone 0.5 mg/kg daily if symptoms interfere with activities of daily living. 1, 2

First-Line Symptomatic Treatment

• Pyridostigmine is the FDA-approved initial treatment for myasthenia gravis and should be started immediately upon diagnosis. 3
• Begin at 30 mg orally three times daily and titrate upward gradually to a maximum dose of 120 mg four times daily as tolerated. 1, 2
• Approximately 50% of patients will show inadequate response to pyridostigmine alone and require escalation to immunosuppressive therapy. 1, 2
• Monitor for common side effects including flatulence (91% of users report side effects), urinary urgency, muscle cramps, blurred vision, and hyperhidrosis. 4
• Be aware that pyridostigmine can cause high-degree AV block and bradycardia; if this occurs, consider hyoscyamine (a muscarinic antagonist) to block cardiac side effects without reducing neuromuscular efficacy. 5

When to Escalate to Immunosuppressive Therapy

For Grade 2 disease (mild generalized weakness) where symptoms interfere with daily activities despite pyridostigmine:

• Add prednisone 0.5 mg/kg orally daily. 2
• Corticosteroids demonstrate superior efficacy with 66-85% positive response rates compared to pyridostigmine's 50% response rate. 1, 6
• Increase prednisone slowly to avoid precipitating myasthenic crisis. 7
• Begin tapering 3-4 weeks after initiation based on symptom improvement. 6

For Grade 3-4 disease (moderate to severe weakness):

• Immediately initiate IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) or plasmapheresis for 3-5 days in addition to pyridostigmine and corticosteroids. 2, 6
• These patients require ICU-level monitoring for rapidly progressive symptoms or respiratory muscle weakness. 2

Essential Concurrent Workup

• Obtain CT chest with contrast after diagnosis confirmation to evaluate for thymoma, which occurs in 10-20% of AChR-positive patients. 2
• Perform pulmonary function testing with negative inspiratory force (NIF) and vital capacity (VC) to assess respiratory muscle involvement. 2
• Regular pulmonary function assessment is crucial as respiratory compromise is a life-threatening complication. 1

Third-Line Steroid-Sparing Agents

• Azathioprine is the first-choice steroid-sparing immunosuppressant for moderate to severe disease when corticosteroids are contraindicated or to reduce steroid burden. 1, 6
• Note that azathioprine requires several months to achieve therapeutic effect. 6

Thymectomy Evaluation

• Always perform thymectomy when thymoma is present. 2, 6
• Evaluate thymectomy in appropriate AChR-positive patients even without thymoma, as it may substantially reduce symptoms. 2

Critical Medication Avoidance

Immediately review and discontinue medications that worsen myasthenia: 1, 2, 6

• β-blockers
• IV magnesium
• Fluoroquinolones
• Aminoglycosides
• Macrolide antibiotics

Common Pitfalls to Avoid

• Do not delay escalation to corticosteroids in patients with inadequate pyridostigmine response, as 50% will require immunosuppression. 1, 2
• Do not increase prednisone rapidly, as this can precipitate myasthenic crisis. 7
• Do not overlook respiratory function monitoring, as 50-80% of patients may develop respiratory compromise. 1, 2
• Do not forget to screen for thymoma with CT chest, as approximately 30-50% of thymoma patients have myasthenia gravis and 20% of thymoma-related mortality is due to myasthenia. 1