What is the treatment for Myasthenia Gravis?

Treatment of Myasthenia Gravis

Begin with pyridostigmine 30 mg orally three times daily as first-line symptomatic therapy, titrating up to a maximum of 120 mg four times daily based on clinical response. 1, 2

Initial Symptomatic Management

• Start pyridostigmine immediately for all patients with confirmed myasthenia gravis, as it is FDA-approved and provides rapid symptomatic relief by inhibiting acetylcholine breakdown at the neuromuscular junction. 2
• Titrate the dose gradually from 30 mg three times daily up to 120 mg four times daily, adjusting based on symptom control and tolerability. 1, 3
• Approximately 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone and will require escalation to corticosteroids. 4, 3

Escalation to Immunosuppressive Therapy

For Grade 2 symptoms (mild to moderate generalized weakness) that persist despite optimized pyridostigmine, add corticosteroids directly without delay. 1

• Initiate prednisone at 1 to 1.5 mg/kg orally daily for patients with inadequate response to pyridostigmine. 5, 1
• Expect clinical improvement in 66-85% of patients treated with corticosteroids. 4, 3
• Taper corticosteroids gradually based on symptom improvement, not on a fixed schedule. 5, 1

Management of Severe Disease (Grade 3-4)

For myasthenic crisis with respiratory compromise or severe generalized weakness, immediately hospitalize with ICU-level monitoring and initiate IVIG or plasmapheresis. 5, 1

• Administer IVIG at 2 g/kg total dose over 5 consecutive days (0.4 g/kg/day × 5 days) or plasmapheresis for 5 days. 5, 1, 3
• Continue corticosteroids concurrently during acute crisis management. 5, 1
• Perform frequent pulmonary function assessments with negative inspiratory force and vital capacity monitoring. 5, 1, 3
• Conduct daily neurologic evaluations to assess progression or improvement. 5, 1
• Permanently discontinue immune checkpoint inhibitors if MG is ICPi-associated. 5

Critical Medications to Avoid

Strictly avoid medications that worsen myasthenic symptoms, as they can precipitate life-threatening respiratory failure. 5, 1

• β-blockers can worsen neuromuscular transmission. 5, 1, 3
• Intravenous magnesium blocks acetylcholine release. 5, 1, 3
• Fluoroquinolone antibiotics (e.g., ciprofloxacin, levofloxacin) exacerbate weakness. 5, 1, 3
• Aminoglycoside antibiotics (e.g., gentamicin, tobramycin) impair neuromuscular transmission. 5, 1, 3
• Macrolide antibiotics (e.g., azithromycin, erythromycin) worsen symptoms. 5, 1, 3
• Barbiturate-containing medications like Fioricet (butalbital/acetaminophen) should be avoided. 1

Diagnostic Confirmation Requirements

Before initiating treatment, confirm the diagnosis with the following workup: 5, 3

• Acetylcholine receptor (AChR) antibodies are positive in 80-85% of generalized MG and 40-77% of ocular MG. 4, 3, 6
• Muscle-specific kinase (MuSK) antibodies if AChR antibodies are negative (present in 5-8% of patients). 5, 3, 6
• Lipoprotein-related protein 4 (LRP4) antibodies if both AChR and MuSK are negative (present in <1%). 5, 6
• Electrodiagnostic studies including repetitive nerve stimulation (positive in only one-third of ocular MG) and single-fiber EMG (>90% sensitivity for ocular MG). 4, 3
• Ice pack test for ocular symptoms is highly specific—apply ice pack over closed eyes for 2 minutes and observe for improvement in ptosis. 4
• Pulmonary function testing with negative inspiratory force and vital capacity to assess respiratory involvement. 5, 3

Long-Term Management Considerations

• IVIG should NOT be used for chronic maintenance therapy in myasthenia gravis—reserve it only for acute exacerbations or crisis situations. 1
• Consider thymectomy in all patients with thymoma (present in 10-20% of AChR-positive MG) and in selected patients with generalized MG as it may substantially reduce symptoms. 3, 6
• For steroid-sparing maintenance, consider azathioprine or mycophenolate mofetil as third-line agents. 4, 7
• Newer biologics like efgartigimod alfa-fcab are FDA-approved for AChR-antibody positive patients who remain refractory to standard therapy. 3, 8

Monitoring and Follow-Up

• Regular neurology consultation is essential to adjust treatment as disease activity changes. 1
• Monitor for progression from ocular to generalized disease, as 50-80% of patients with initial ocular symptoms will develop generalized MG within a few years. 4, 3
• Educate patients to seek immediate medical attention for worsening dysphagia, dysarthria, respiratory difficulties, or significant increase in muscle weakness. 1
• Plan activities around medication timing for optimal strength throughout the day. 1

Common Pitfalls to Avoid

• Do not delay corticosteroids in patients with Grade 2 symptoms who have inadequate response to pyridostigmine—early escalation prevents progression to crisis. 1
• Do not use IVIG for chronic maintenance—this represents inappropriate use not supported by guidelines. 1
• Do not overlook respiratory function monitoring—even mild generalized weakness can rapidly progress to respiratory failure. 5, 1
• Pupils are characteristically NOT affected in myasthenia gravis—if pupillary abnormalities are present, immediately consider alternative diagnoses like third nerve palsy. 4