What are the guidelines for long-term management of a patient with myasthenia gravis?

Long-Term Management of Myasthenia Gravis: A Guidelines-Based Approach

The long-term management of myasthenia gravis requires a stepwise approach starting with pyridostigmine for symptom control, followed by immunosuppressive therapy with corticosteroids and steroid-sparing agents, with regular monitoring for respiratory compromise and disease progression. 1, 2

Diagnostic Evaluation

• Confirm diagnosis with acetylcholine receptor (AChR) antibodies; if negative, test for muscle-specific kinase (MuSK) and lipoprotein-related 4 (LPR4) antibodies 3
• Perform electrodiagnostic studies including neuromuscular junction testing with repetitive stimulation and/or jitter studies 3, 1
• Assess pulmonary function with negative inspiratory force (NIF) and vital capacity (VC) measurements 3
• Check for concurrent myositis with creatine phosphokinase (CPK), aldolase, ESR, and CRP 3
• Consider MRI of brain/spine to rule out CNS involvement or alternative diagnoses 3
• Evaluate for potential cardiac involvement with ECG and transthoracic echocardiogram if respiratory insufficiency or elevated CPK/troponin is present 3

First-Line Treatment

• Pyridostigmine (acetylcholinesterase inhibitor) is the first-line symptomatic treatment 4, 2, 5
  • Start at 30 mg orally three times daily
  • Gradually increase to maximum of 120 mg orally four times daily as tolerated based on symptoms 3, 1
• For mild disease (ocular symptoms only or mild generalized weakness), pyridostigmine alone may be sufficient 2, 6

Second-Line Treatment

• Corticosteroids are the mainstay of immunosuppressive treatment for patients with more than mild MG 2, 7
  • Prednisone 0.5-1.5 mg/kg orally daily for moderate symptoms (Grade 2) 3
  • Wean based on symptom improvement 3
• Consider early thymectomy in:
  • Patients with thymoma (mandatory)
  • Non-thymoma patients up to age 50-65 years who don't achieve remission on symptomatic treatment 5

Third-Line and Long-Term Immunosuppressive Options

• Azathioprine is commonly used as a steroid-sparing agent, often in combination with corticosteroids 2, 7, 5
• Alternative immunosuppressants include:
  • Mycophenolate mofetil
  • Methotrexate
  • Tacrolimus
  • Cyclosporine
  • Rituximab (particularly for refractory cases) 2, 7, 5, 8

Management of Exacerbations and Crisis

• For severe symptoms (Grade 3-4) or myasthenic crisis:
  • Admit patient, may need ICU-level monitoring 3
  • Continue corticosteroids and initiate IVIG 2 g/kg over 5 days (0.4 g/kg/day) or plasmapheresis for 5 days 3
  • Perform frequent pulmonary function assessment 3
  • Conduct daily neurologic evaluation 3

Emerging Therapies

• Newer treatment options include:
  • Complement inhibitors (eculizumab, ravulizumab, zilucoplan)
  • Neonatal Fc receptor antagonists (efgartigimod, rozanolixizumab) 8
• These novel therapies are promising but may have restricted access due to costs 5, 8

Important Considerations and Pitfalls

• Avoid medications that can worsen myasthenia gravis:
  • β-blockers
  • IV magnesium
  • Fluoroquinolones
  • Aminoglycosides
  • Macrolide antibiotics 3, 1
• Regular pulmonary function assessment is crucial to monitor for respiratory compromise 3, 1
• Physical therapy may help manage fatigue, which is common in MG 2
• For pregnant patients, treatment needs to be adjusted considering potential teratogenicity of certain therapies 2
• Regular long-term specialized follow-up is needed due to disease fluctuations, comorbidities, and changes in life conditions 5