What is the recommended treatment for an acute myasthenia gravis flare‑up?

Treatment for Myasthenia Gravis Flare-Up

For an acute myasthenia gravis flare-up, immediately assess severity and respiratory status, then initiate IVIG (2 g/kg over 5 days) or plasmapheresis for Grade 3-4 exacerbations with severe weakness or respiratory compromise, while continuing or optimizing pyridostigmine and corticosteroids. 1, 2, 3

Severity Assessment and Risk Stratification

First, classify the flare-up severity using the Myasthenia Gravis Foundation of America (MGFA) grading system to guide treatment intensity 3:

• Grade 2 (Mild generalized weakness): Mild weakness beyond ocular muscles with some interference in activities of daily living 3
• Grade 3 (Moderate-severe weakness): Severe weakness limiting self-care, significant bulbar dysfunction (dysphagia, dysarthria), respiratory muscle weakness requiring frequent pulmonary function monitoring 3
• Grade 4 (Myasthenic crisis): Life-threatening respiratory failure requiring intubation, severe bulbar weakness compromising airway protection 3

Critical warning sign: Dysphagia is present in more than 50% of cases that precede myasthenic crisis, making it a key early indicator of impending respiratory failure 1

Immediate Actions for Severe Flare-Ups (Grade 3-4)

Hospitalization and Monitoring

• Admit to ICU with capability for mechanical ventilation 1, 3
• Perform frequent pulmonary function testing with negative inspiratory force (NIF) and vital capacity (VC) measurements 2, 3
• Conduct daily neurologic assessments 2

Acute Immunotherapy (Choose One)

IVIG is the preferred rapid-acting treatment for acute exacerbations:

• Dose: 2 g/kg total over 5 days (0.4 g/kg/day × 5 consecutive days) 1, 2, 3
• Indications: Grade 3-4 exacerbations with severe generalized weakness, dysphagia, facial weakness, or rapidly progressive symptoms 2
• Specific indication: Acute myasthenic crisis with respiratory compromise requiring hospitalization 2, 3

Plasmapheresis (therapeutic plasma exchange) is an alternative:

• Equally effective to IVIG for acute crisis 3
• May be preferred if IVIG is contraindicated or unavailable 3
• Important: Sequential therapy (plasmapheresis followed by IVIG) is no more effective than either alone and should be avoided 3
• IVIG may be preferred in pregnant women due to fewer monitoring requirements 3

Corticosteroids

• Continue or initiate high-dose corticosteroids (prednisone 1-1.5 mg/kg orally daily) concurrently during IVIG or plasmapheresis 2, 3
• Do not delay corticosteroids while awaiting IVIG/plasmapheresis 1, 2

Pyridostigmine Management During Crisis

• May continue pyridostigmine during acute treatment 3
• Can be discontinued or withheld if intubation is required 3
• If unable to take oral medications, convert to IV: 30 mg oral pyridostigmine = 1 mg IV pyridostigmine 3

Treatment for Moderate Flare-Ups (Grade 2)

Optimize Symptomatic Treatment

• Ensure pyridostigmine is optimally dosed: start at 30 mg orally three times daily, titrate up to maximum 120 mg four times daily based on symptoms and tolerability 1, 2, 3, 4
• Time activities around medication dosing for optimal strength 3

Add or Escalate Corticosteroids

• Initiate prednisone 1-1.5 mg/kg orally daily if pyridostigmine provides insufficient control 1, 2, 3
• Taper gradually based on symptom improvement 2, 3
• Approximately 66-85% of patients show positive response to corticosteroids 1

Avoid IVIG for Grade 2

• The American Academy of Neurology explicitly recommends against using IVIG for chronic maintenance therapy 2
• IVIG is reserved exclusively for Grade 3-4 exacerbations or myasthenic crisis requiring hospitalization 2, 3

Critical Medications to Avoid During Flare-Ups

Strictly avoid these medications that can worsen myasthenic symptoms and trigger crisis: 1, 2, 3

• β-blockers
• Intravenous magnesium
• Fluoroquinolone antibiotics (e.g., ciprofloxacin, levofloxacin)
• Aminoglycoside antibiotics (e.g., gentamicin, tobramycin)
• Macrolide antibiotics (e.g., azithromycin, erythromycin)
• Metoclopramide 3

These medications interfere with neuromuscular transmission and can precipitate respiratory failure requiring ICU admission and mechanical ventilation 3

Diagnostic Workup During Flare-Up

Confirm diagnosis and assess for triggers 2, 3:

• Acetylcholine receptor (AChR) antibodies and anti-striated muscle antibodies
• If AChR negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 1, 3
• Pulmonary function testing with NIF and VC 2, 3
• Electrodiagnostic studies (repetitive nerve stimulation, single-fiber EMG) 3

Long-Term Immunosuppression After Acute Flare

For patients with recurrent flare-ups or inadequate control 1, 5, 6:

• Azathioprine: Adjunctive therapy with corticosteroids for moderate to severe disease 1, 2
• Alternative agents: Mycophenolate mofetil, methotrexate, tacrolimus as second-line options 7
• Rituximab: Consider for treatment-refractory disease 8, 7

Common Pitfalls to Avoid

• Do not use IVIG for chronic maintenance therapy—it is only for acute exacerbations 2, 3
• Do not use prophylactic noninvasive ventilation in stable patients, as studies show increased mortality 3
• Do not underdose pyridostigmine—many patients require the full 120 mg four times daily 2, 3
• Do not delay ICU admission if dysphagia or respiratory symptoms are present, as these predict impending crisis 1
• Do not prescribe contraindicated antibiotics (fluoroquinolones, aminoglycosides, macrolides) during infections 1, 2, 3