What is the initial treatment for a patient diagnosed with myasthenia gravis (MG)?

Initial Treatment for Myasthenia Gravis

Start pyridostigmine at 30 mg orally three times daily and gradually titrate up to a maximum of 120 mg four times daily based on symptom response. 1, 2

Stepwise Treatment Algorithm

First-Line: Symptomatic Treatment with Pyridostigmine

• Pyridostigmine is FDA-approved and recommended as the initial treatment for all newly diagnosed MG patients 1, 2
• Begin at 30 mg orally three times daily and increase gradually to maximum 120 mg four times daily as tolerated 1
• Expect approximately 50% response rate with pyridostigmine monotherapy, particularly in ocular MG 1, 3
• Monitor for common side effects including flatulence (91% of users report some side effects), urinary urgency, muscle cramps, blurred vision, and hyperhidrosis 4
• Critical caveat: Pyridostigmine can rarely precipitate myocardial ischemia through coronary vasospasm, particularly in elderly females—maintain awareness of this risk 5

Second-Line: Add Corticosteroids for Inadequate Response

• Escalate to prednisone 0.5-1.5 mg/kg orally daily if symptoms interfere with activities of daily living (Grade 2 disease or MGFA class I-II) 1, 3
• Corticosteroids demonstrate superior efficacy with 66-85% positive response rates compared to pyridostigmine's 50% 1, 3
• Approximately 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone and require corticosteroid escalation 1, 3
• Early corticosteroid treatment is warranted when ocular motility abnormalities persist despite pyridostigmine 3

Third-Line: Immunosuppressive Therapy for Moderate-to-Severe Disease

• For Grade 3-4 disease (moderate to severe weakness, MGFA class III-V): Add IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) or plasmapheresis for 3-5 days 1, 3
• Consider azathioprine as steroid-sparing immunosuppressive therapy for moderate to severe disease 1, 3
• High-dose corticosteroids (methylprednisolone 1-2 mg/kg/day IV or prednisone 1-1.5 mg/kg/day orally) for severe presentations 6

Essential Baseline Assessments Before Treatment

• Measure acetylcholine receptor (AChR) antibodies and anti-striated muscle antibodies 1, 6
• If AChR antibodies negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 6, 3
• Obtain CT chest with contrast to evaluate for thymoma (present in 10-20% of AChR-positive patients) 3
• Perform pulmonary function testing with negative inspiratory force (NIF) and vital capacity (VC) to assess respiratory muscle involvement 1, 6, 3
• Check CPK, aldolase, ESR, and CRP to evaluate for concurrent myositis 6, 3
• Obtain ECG and consider troponin (with echocardiogram if abnormal) to rule out concomitant myocarditis 6, 3

Critical Medication Avoidance

Immediately discontinue or avoid these medications that worsen myasthenia:

• β-blockers 1, 6, 3
• IV magnesium (absolutely contraindicated) 1, 6, 3
• Fluoroquinolones 1, 6, 3
• Aminoglycosides 1, 6, 3
• Macrolide antibiotics 1, 6, 3

Monitoring Requirements

• Regular pulmonary function assessment is crucial, as 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years 1, 3
• Apply the "20/30/40 rule" to identify respiratory failure risk: vital capacity <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 6
• For stable disease, conduct respiratory function assessments every 6 months 6
• Daily neurologic evaluation and frequent pulmonary function assessment for Grade 3-4 patients 3

Surgical Consideration

• Evaluate for thymectomy in appropriate AChR-positive patients, as it may substantially reduce symptoms 3
• Always perform thymectomy when thymoma is present 3
• Thymectomy is beneficial in AChR antibody-positive generalized MG patients up to age 65 years 7