What is the treatment for a seronegative myasthenia gravis (MG) flare-up?

Treatment of Seronegative Myasthenia Gravis Flare-Up

For seronegative myasthenia gravis flare-ups, treatment should include pyridostigmine as first-line therapy, followed by corticosteroids, and IVIG or plasmapheresis for severe cases, with careful monitoring of respiratory function. 1

Initial Assessment and Grading

The severity of the myasthenia gravis flare-up determines the treatment approach:

Grade 2 (Mild to Moderate Flare-Up)

• Ocular symptoms only or mild generalized weakness
• Some interference with activities of daily living
• MGFA severity class 1-2

Grade 3-4 (Severe Flare-Up)

• Limiting self-care
• Weakness limiting walking
• ANY dysphagia, facial weakness, or respiratory muscle weakness
• Rapidly progressive symptoms
• MGFA severity class 3-5

Treatment Algorithm

First-Line Treatment (All Grades)

1. Pyridostigmine (Mestinon)
   • Starting dose: 30 mg orally three times daily 1
   • Gradually increase to maximum of 120 mg orally four times daily as tolerated 1
   • Titrate based on symptom improvement 1
   • FDA-approved for treatment of myasthenia gravis 2

Second-Line Treatment

1. For Grade 2 (Mild to Moderate)

   • Corticosteroids: Prednisone 0.5-1.5 mg/kg orally daily 1
   • Wean based on symptom improvement

2. For Grade 3-4 (Severe)

   • Hospital admission (may need ICU-level monitoring) 1
   • Continue corticosteroids (methylprednisolone 1-2 mg/kg daily) 1
   • Initiate IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) OR plasmapheresis for 5 days 1
   • Consider adding rituximab if refractory to IVIG or plasmapheresis 1
   • Frequent pulmonary function assessment
   • Daily neurologic review

Monitoring and Precautions

Critical Monitoring

• Pulmonary function assessment with negative inspiratory force (NIF) and vital capacity (VC)
• Daily neurologic evaluation for severe cases
• Monitor for signs of respiratory compromise

Important Precautions

• Avoid medications that can worsen myasthenia 1, 3:

  • β-blockers
  • IV magnesium
  • Fluoroquinolones
  • Aminoglycosides
  • Macrolide antibiotics

• Managing pyridostigmine side effects 4:

  • Common side effects include flatulence, urinary urgency, muscle cramps, blurred vision, and hyperhidrosis
  • For cholinergic side effects (diarrhea, abdominal cramps), consider hyoscyamine 5
  • Up to 91% of patients report side effects, with 26% discontinuing due to side effects 4

Special Considerations for Seronegative MG

Seronegative MG (approximately 15% of MG cases) presents unique challenges 6:

• May have antibodies against muscle-specific kinase (MuSK)
• Often presents with predominantly bulbar muscle weakness (face, tongue, pharynx)
• May have reduced response to conventional immunosuppressive treatments
• Muscle wasting may be present in some cases

Treatment of Concurrent Infections

• Treat infections promptly and aggressively, as they can trigger MG flares 3
• Use penicillins, cephalosporins, or tetracyclines (with normal renal function) as first-line antibiotics 3
• If worsening of MG symptoms occurs after antibiotic administration, discontinue the offending antibiotic immediately 3

Long-Term Management

For patients with recurrent flare-ups, consider:

• Long-term immunosuppressive therapy (azathioprine)
• Regular follow-up with neurology
• Patient education on trigger avoidance and medication adherence

Remember that seronegative MG flare-ups can progress rapidly to respiratory compromise, requiring close monitoring and aggressive treatment, particularly when bulbar or respiratory symptoms are present.