What is the initial treatment for a patient with Myasthenia Gravis?

Initial Treatment for Myasthenia Gravis

The initial treatment for myasthenia gravis should be pyridostigmine (Mestinon), starting at 30 mg three times daily and potentially increasing to a maximum of 120 mg four times daily based on symptoms. 1, 2, 3

Diagnostic Workup

Before initiating treatment, a thorough diagnostic evaluation should include:

• Acetylcholine receptor (AChR) and anti-striated muscle antibodies in blood 4, 5
• If AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 4, 5
• Pulmonary function assessment with negative inspiratory force (NIF) and vital capacity (VC) measurements 4, 5
• Creatine phosphokinase (CPK), aldolase, ESR, and CRP to evaluate for concurrent myositis 4, 5
• Cardiac evaluation with ECG and echocardiogram if respiratory insufficiency or elevated CPK/troponin T is present 4, 5
• Neurology consultation 4, 1
• Electrodiagnostic studies including neuromuscular junction testing 4

Treatment Algorithm

Step 1: Symptomatic Treatment

• Begin with pyridostigmine 30 mg PO three times daily, gradually increasing to a maximum of 120 mg four times daily based on symptom response 4, 1, 6
• Pyridostigmine provides symptomatic relief by inhibiting acetylcholinesterase, thereby increasing acetylcholine availability at the neuromuscular junction 7

Step 2: Immunosuppressive Therapy

• If symptoms persist despite optimal pyridostigmine dosing, add corticosteroids (prednisone 1-1.5 mg/kg PO daily) 4, 1, 6
• Consider early combination with azathioprine to allow for steroid-sparing effect 3, 6

Step 3: Thymectomy Evaluation

• Consider thymectomy in patients under 50-65 years of age, particularly if they have thymoma or are not achieving remission with medication 3, 8

Step 4: Management of Exacerbations

• For acute exacerbations or myasthenic crisis, hospitalize the patient (potentially in ICU) 4, 5
• Administer IVIG (2 g/kg over 5 days) or plasmapheresis (5 sessions over 5 days) 4, 5
• Continue or initiate corticosteroids 4, 5
• Perform frequent pulmonary function assessments 4, 5

Important Precautions

• IMMEDIATELY discontinue medications that can worsen myasthenia gravis: 4, 1, 5

  • Beta-blockers
  • IV magnesium (absolutely contraindicated)
  • Fluoroquinolone antibiotics
  • Aminoglycoside antibiotics
  • Macrolide antibiotics
  • Barbiturate-containing medications like Firocet (butalbital and acetaminophen) 9

• Monitor for respiratory compromise using the "20/30/40 rule": vital capacity <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 5

Special Considerations

• Immune checkpoint inhibitor-associated myasthenia gravis may be monophasic and require less prolonged immunosuppression 4, 5
• For moderate to severe pain requiring medication in MG patients, consult neurology before initiating any new pain medication 9
• Adapted physical training is recommended for patients with stable disease 3
• Regular long-term specialized follow-up is needed due to disease fluctuations, comorbidities, and changes in life conditions 3

Emerging Therapies

For refractory cases not responding to conventional therapy, newer options include:

• Rituximab 3, 6
• Complement inhibitors (eculizumab, ravulizumab, zilucoplan) 10
• FcRn antagonists (efgartigimod, rozanolixizumab) 10

These novel therapies have shown promising results but availability may be limited by cost and access restrictions 3, 10.