What is the recommended steroid dosing and tapering regimen for a patient with Myasthenia gravis (MG)?

Myasthenia Gravis Steroid Dosing and Tapering

Initial Steroid Dosing by Disease Severity

For Grade 2 myasthenia gravis (mild generalized weakness with some interference in activities of daily living), initiate prednisone at 0.5-1.5 mg/kg orally daily, typically starting at the lower end of this range to minimize risk of steroid-induced exacerbation. 1

Grade 2 (Mild-Moderate Symptoms)

• Start prednisone 0.5 mg/kg orally daily for patients with predominantly ocular symptoms or mild generalized weakness 1
• May increase to 1-1.5 mg/kg orally daily if symptoms are more severe within Grade 2 1
• Administer as single morning dose before 9 am to minimize adrenal suppression 2
• Continue pyridostigmine 30-120 mg orally four times daily as tolerated 1

Grade 3-4 (Severe Symptoms or Crisis)

• Initiate prednisone 1-1.5 mg/kg orally daily (or equivalent IV methylprednisolone 1-2 mg/kg/day) 1
• Requires ICU-level monitoring with frequent pulmonary function assessment 1
• Add IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) or plasmapheresis for 5 days 1
• Continue corticosteroids throughout IVIG or plasmapheresis treatment 1

Critical Warning: Steroid-Induced Exacerbation

Steroid-induced exacerbation occurs in 42-80% of patients, typically within the first 4 weeks of treatment, and is more likely in elderly patients, those with severe bulbar symptoms, and those with lower baseline strength. 3, 4

Risk Factors for Exacerbation

• Age >60 years 3
• Predominantly severe bulbar symptoms (dysphagia, dysarthria) 3
• Low baseline Myasthenia Gravis Severity Scale score (more severe disease) 3
• High initial steroid doses 4

Mitigation Strategies

• Consider starting at lower doses (0.5 mg/kg daily) in high-risk patients rather than jumping to 1.5 mg/kg 1, 3
• Ensure inpatient monitoring for Grade 2 patients at high risk, as they can deteriorate quickly 1
• Do not withhold anticholinesterase medications, as this does not prevent exacerbation 4
• Exacerbation typically begins 1-3 days after steroid initiation and lasts approximately 3 days 5

Steroid Tapering Protocol

Begin tapering 3-4 weeks after initiation once symptoms improve to Grade 1 or resolution, using a slow taper over 4-6 weeks to avoid disease flare. 1, 6

Standard Tapering Schedule

For patients on prednisone 1-1.5 mg/kg daily (approximately 60-100 mg/day for average adult):

1. Weeks 1-4: Maintain initial dose until clinical improvement to Grade 1 1
2. Weeks 5-8: Reduce by 10 mg every week until reaching 30 mg/day 6
3. Weeks 9-12: Reduce by 5 mg every 2 weeks until reaching 20 mg/day 6
4. Weeks 13-16: Reduce by 2.5 mg every 2 weeks until reaching 10 mg/day 6
5. After reaching 10 mg/day: Slow taper by 1 mg every 4 weeks until discontinuation 6

Alternative Tapering for Lower Initial Doses

For patients started on prednisone 0.5 mg/kg daily (approximately 30-40 mg/day):

• Reduce by 5 mg every week until reaching 10 mg/day 6
• Then reduce by 1 mg every 4 weeks until discontinuation 6

Tapering with Azathioprine

If azathioprine has been added and therapeutic levels established (typically after 2-3 months), tapering can be accelerated: 6

• Reduce prednisone by 5 mg every week until reaching 10 mg/day 6
• Then reduce by 2.5 mg every 2-4 weeks 6
• Monitor aminotransferases monthly during accelerated taper 6
• Ensure azathioprine dose is adequate (2 mg/kg/day) before aggressive steroid reduction 6

Managing Relapse During Tapering

If disease flare occurs during tapering, immediately return to the pre-relapse dose and maintain for 4-8 weeks before attempting a slower taper. 6

• Resume the dose at which patient was stable before relapse 6
• Maintain this dose for 4-8 weeks until disease control re-established 6
• Consider adding steroid-sparing agents (azathioprine, mycophenolate) if multiple relapses occur 6
• ICPi-associated myasthenia may be monophasic and not require additional steroid-sparing agents 1

Special Considerations and Monitoring

Medications to Strictly Avoid

Educate patients to avoid medications that worsen myasthenia: 1

• β-blockers 1
• IV magnesium 1
• Fluoroquinolone antibiotics 1
• Aminoglycoside antibiotics 1
• Macrolide antibiotics 1

Adrenal Insufficiency Prevention

Patients on prednisone >7.5 mg daily for >3 weeks require stress dosing during acute illness: 6

• For minor illness: Double current prednisone dose for 3 days 6
• For major illness/surgery: Hydrocortisone 50 mg IV three times daily 6
• Consider medical alert bracelet for patients on chronic therapy 6

Monitoring Requirements

• Daily neurologic evaluation during Grade 3-4 treatment 1
• Frequent pulmonary function assessment (NIF and VC) for all grades 1
• Monitor for steroid side effects: bone density, blood pressure, glucose, ocular pressure 6
• Follow-up visits every 4-8 weeks during first year of tapering 6

Common Pitfalls to Avoid

• Tapering too quickly leads to disease flare or adrenal insufficiency 6
• Starting with excessively high doses (>1.5 mg/kg) increases exacerbation risk without improving outcomes 3, 4
• Failing to provide inpatient monitoring for high-risk Grade 2 patients 1
• Discontinuing anticholinesterase medications does not prevent steroid-induced exacerbation 4
• Using IVIG for chronic maintenance therapy is not recommended 7