What are the initial and subsequent treatment options for managing myasthenia gravis?

Management of Myasthenia Gravis

Initial Treatment Approach

Start all myasthenia gravis patients with pyridostigmine 30 mg orally three times daily, gradually titrating to a maximum of 120 mg four times daily based on symptom response. 1, 2

First-Line Symptomatic Therapy

• Pyridostigmine (acetylcholinesterase inhibitor) is FDA-approved and serves as the foundation of symptomatic treatment for all MG patients 2
• Begin at 30 mg orally three times daily and increase gradually as tolerated 1
• Maximum dose is 120 mg orally four times daily 1
• Approximately 50% of patients with ocular myasthenia may show minimal response to pyridostigmine alone and will require escalation 1
• Sustained-release formulations can reduce dosing frequency from 4.3 to 3.6 times daily while improving quality of life scores 3

Baseline Monitoring Requirements

• Perform immediate pulmonary function assessment with negative inspiratory force (NIF) and vital capacity (VC) measurements at diagnosis 4
• 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 4
• Conduct respiratory function assessments every 6 months in stable disease 4
• Regular assessment is crucial as 50-80% of patients with initial ocular symptoms may develop generalized myasthenia within a few years 1

Escalation to Immunosuppressive Therapy

For patients with Grade 2 or higher symptoms who fail to achieve adequate control with pyridostigmine alone, initiate corticosteroids as second-line therapy. 1

Second-Line: Corticosteroids

• Prednisone is the mainstay of immunosuppressive treatment for more than mild MG 5
• Approximately 66-85% of patients show a positive response to corticosteroids 1
• For myasthenic crisis, use methylprednisolone 1-2 mg/kg/day IV or prednisone 1-1.5 mg/kg/day orally 4
• Begin steroid taper 3-4 weeks after initiation, based on symptom improvement 4

Third-Line: Steroid-Sparing Immunosuppressants

• Azathioprine is the preferred third-line option for moderate to severe disease 1
• Consider azathioprine when background comorbidities preclude or restrict steroid use 5
• Alternative agents include mycophenolate mofetil for steroid-sparing effects 6

Acute Crisis Management

Myasthenic crisis requires immediate ICU-level hospitalization with high-dose corticosteroids plus either IVIG or plasmapheresis. 4

Rapid Immunotherapy Options

• Plasmapheresis: 5 sessions over 5 days 4
• IVIG: 2 g/kg total dose over 5 days at 0.4 g/kg/day 4
• Both modalities are equally effective for rapidly reducing antibody levels 4

Critical Medication Avoidance

IMMEDIATELY discontinue these medications that worsen MG: 4, 1

• Beta-blockers 4
• IV magnesium (absolutely contraindicated) 4
• Fluoroquinolones 4
• Aminoglycosides 4
• Macrolide antibiotics 4

Diagnostic Workup During Treatment

Antibody Testing

• Check acetylcholine receptor (AChR) antibodies and anti-striated muscle antibodies 4
• If AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 4
• Measure CPK, aldolase, ESR, and CRP to evaluate for concurrent myositis 4

Cardiac Evaluation

• Perform ECG and transthoracic echocardiogram if respiratory insufficiency or elevated CPK/troponin T present to rule out concurrent myocarditis 4

Treatment-Refractory Disease

For patients failing standard immunosuppression, consider rituximab, high-dose cyclophosphamide, or eculizumab. 6

Advanced Therapies

• Rituximab has an established role in refractory MG 6, 5
• High-dose cyclophosphamide is an option for treatment-refractory cases 6
• Eculizumab (complement inhibitor) may be used in severe refractory disease 6
• Thymectomy (or repeat thymectomy in selected cases) should be evaluated 6

Thymectomy Considerations

• Thymectomy is beneficial in AChR antibody-positive generalized MG up to age 65 years 5
• Should be performed in patients with generalized disease, especially those with detectable anti-AChR antibodies 7
• All patients with suspected thymoma require preoperative anti-AChR antibody measurement to avoid respiratory failure during anesthesia 1
• Approximately 30-50% of thymoma patients have MG, and 20% of thymoma mortality is MG-related 1

Common Pitfalls to Avoid

• Do not rely on pulse oximetry or arterial blood gases as early indicators of respiratory failure—they are unreliable early markers 4
• Do not assume respiratory stability based on lack of dyspnea—respiratory insufficiency may develop without obvious symptoms 4
• Do not administer IV magnesium for hypomagnesemia without mandatory neurology consultation—it is absolutely contraindicated 4
• Do not overlook pupillary examination—pupils are characteristically spared in MG; pupillary involvement suggests alternative diagnoses like third nerve palsy 1