What is the management approach for myasthenia gravis?

Management Approach for Myasthenia Gravis

First-Line Symptomatic Treatment

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

• Pyridostigmine is the cornerstone of initial symptomatic management for all patients with myasthenia gravis, regardless of severity 1, 3
• Approximately 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone and will require escalation to immunosuppressive therapy 1
• The medication should be taken exactly as prescribed, with activities planned around medication timing for optimal strength 2

Critical warning: Overdosage of pyridostigmine can result in cholinergic crisis characterized by increasing muscle weakness that may lead to respiratory failure and death 4. Distinguishing cholinergic crisis from myasthenic crisis requires edrophonium chloride testing and clinical judgment, as both present with severe weakness but require opposite management strategies 4.

Escalation to Immunosuppressive Therapy

For patients with Grade 2 or higher symptoms not adequately controlled by pyridostigmine, initiate prednisone at 1-1.5 mg/kg orally daily. 1, 2

• Corticosteroids are effective in approximately 66-85% of patients with myasthenia gravis 1, 5
• Taper corticosteroids gradually based on symptom improvement rather than following a fixed schedule 2, 5
• The combination of corticosteroids at the lowest effective dose with azathioprine is recommended as the optimal long-term immunosuppressive strategy 3

Long-Term Immunosuppression

Add azathioprine as a steroid-sparing agent for patients requiring chronic immunosuppression. 1, 5

• Azathioprine is an effective third-line treatment option for moderate to severe disease 1
• Rituximab represents an alternative first-line immunosuppressive option, particularly for refractory cases 3
• Second-line immunosuppressive agents include mycophenolate, methotrexate, and tacrolimus 3

Management of Myasthenic Crisis (Grade 3-4)

For patients with respiratory compromise or severe generalized weakness, immediately hospitalize with ICU-level monitoring and initiate IVIG 2 g/kg total dose over 5 days (0.4 g/kg/day × 5 days) or plasmapheresis. 2, 5

• Continue corticosteroids concurrently during IVIG or plasmapheresis treatment 2
• Perform frequent pulmonary function assessments with negative inspiratory force and vital capacity monitoring 2
• Conduct daily neurologic evaluations throughout the crisis period 2, 5

Important: IVIG should not be used for chronic maintenance therapy in myasthenia gravis—it is reserved exclusively for acute exacerbations and crisis situations 2.

Thymectomy Considerations

Perform thymectomy in patients with thymoma at any age, and in non-thymoma AChR antibody-positive patients up to age 50-65 years who do not achieve remission on symptomatic treatment. 3

• All patients suspected of having thymomas must have serum anti-acetylcholine receptor antibody levels measured preoperatively to avoid respiratory failure during anesthesia 1
• Approximately 30-50% of patients with thymomas have myasthenia gravis, and in 20% of thymoma patients, mortality is related to myasthenic complications 1

Critical Medications to Avoid

Strictly avoid β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides in all patients with myasthenia gravis. 1, 2, 5

• These medications can precipitate myasthenic crisis by worsening neuromuscular transmission 1
• Educate patients to inform all healthcare providers about their myasthenia diagnosis before receiving any new medications 2
• Barbiturate-containing medications like Fioricet (butalbital and acetaminophen) also pose significant risks 2

Diagnostic Confirmation Requirements

Obtain acetylcholine receptor (AChR) antibodies and antistriated muscle antibodies in blood; if negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies. 2, 5

• Single-fiber EMG has >90% sensitivity for ocular myasthenia and is considered the gold standard for diagnosis 1, 5
• Repetitive nerve stimulation is positive in only one-third of patients with ocular myasthenia 5
• Perform baseline pulmonary function testing with negative inspiratory force and vital capacity 2

Monitoring and Follow-Up

Regular pulmonary function assessment is crucial in all patients with generalized myasthenia gravis to monitor for respiratory compromise. 1, 2

• Approximately 50-80% of patients presenting with isolated ocular symptoms will develop generalized myasthenia within a few years, making accurate diagnosis and monitoring essential for preventing life-threatening respiratory failure 1
• Plan regular neurology consultation and follow-up to adjust treatment as disease activity fluctuates 2
• Teach patients to monitor for and immediately report worsening bulbar symptoms (changes in speech or swallowing), respiratory difficulties, and diplopia 2

Special Populations

In women of childbearing potential, carefully weigh the drug's potential benefits against possible hazards to mother and child, as the safety of pyridostigmine during pregnancy has not been established. 4

• Planning of pregnancies with optimal treatment, information, and awareness of neonatal MG is necessary 3
• Treatment decisions in elderly patients must account for specific comorbidities 6

Adjunctive Management

Encourage active physical training and implement respiratory physiotherapy techniques for patients with dysfunctional breathing. 6, 3

• Fatigue should be distinguished from fatigable weakness and managed with physical therapy with or without psychological support 6
• Social support and adaptation of work and daily life activities are recommended 3