When to start rituximab (Rituxan) and Intravenous Immunoglobulin (IVIG) in a patient with myasthenia crisis?

Management of Myasthenia Crisis: Timing of IVIG and Rituximab

In myasthenia crisis, start IVIG (2 g/kg over 5 days) immediately upon ICU admission for respiratory compromise or severe generalized weakness (Grade 3-4), while rituximab should be reserved for refractory cases that fail to respond to IVIG/plasmapheresis and standard immunosuppression, not as acute crisis management. 1

Immediate Crisis Management with IVIG

When to Start IVIG in Crisis

• Initiate IVIG immediately when patients present with myasthenic crisis defined as respiratory failure requiring mechanical ventilation or impending respiratory failure with severe bulbar dysfunction 1, 2
• Start treatment upon ICU admission for Grade 3-4 symptoms: severe generalized weakness limiting self-care activities, respiratory insufficiency, or dysphagia 1
• IVIG dosing: 2 g/kg total dose administered as 0.4 g/kg/day for 5 consecutive days 1, 3

IVIG vs Plasmapheresis Decision

• Plasma exchange provides faster clinical response with reduced ICU stay length (p=0.018) and earlier improvement in quantitative myasthenia gravis scores at one week off-ventilation compared to IVIG 2
• However, clinical efficacy is equivalent between IVIG and plasmapheresis after 1 month, so either can be used based on availability and patient factors 2, 3
• Choose IVIG over plasmapheresis in pregnant women, patients with difficult vascular access, or when plasma exchange is contraindicated 1
• Avoid sequential therapy (plasmapheresis followed by IVIG) as it provides no additional benefit over either treatment alone 1

Critical Timing Consideration

• Do NOT delay IVIG waiting for diagnostic confirmation in patients with life-threatening respiratory compromise—start treatment immediately while continuing diagnostic workup in parallel 1
• Continue pyridostigmine and corticosteroids concurrently during IVIG administration 1
• Perform frequent pulmonary function monitoring with negative inspiratory force and vital capacity measurements 1

Rituximab Timing: NOT for Acute Crisis

When Rituximab is Appropriate

• Rituximab is NOT indicated for acute myasthenic crisis management—it is reserved for refractory disease after standard treatments have failed 4
• Consider rituximab for patients with inadequate response to corticosteroids, azathioprine, mycophenolate, or other immunosuppressants after at least 2-4 weeks of treatment 5
• Rituximab may be considered in impending myasthenic crisis (pre-crisis worsening) as an early intervention in select cases, where 4 of 5 patients improved with rituximab alone 4

Rituximab Dosing and Timing

• Standard dosing: 1000 mg IV repeated on day 15, or 375 mg/m² once weekly for 4 weeks 5
• Peak efficacy occurs after several months with onset of effect beginning sooner, making it inappropriate for acute crisis requiring immediate intervention 5
• In refractory myositis (similar autoimmune mechanism), rituximab is added only if symptoms worsen or show no improvement after 2 weeks of high-dose corticosteroids and IVIG 5

Common Pitfalls to Avoid

IVIG-Specific Pitfalls

• Check serum IgA levels before first IVIG infusion—IgA deficiency can cause severe anaphylaxis; use IgA-reduced preparations if deficient 5, 6
• Never perform plasmapheresis immediately after IVIG—it will remove the immunoglobulin, negating therapeutic benefit 5, 6
• Do not use IVIG for chronic maintenance therapy in myasthenia gravis—it is only indicated for acute exacerbations 1
• Preoperative IVIG to prevent crisis is unnecessary in well-controlled myasthenia gravis patients undergoing surgery, including thymectomy 7

Rituximab-Specific Pitfalls

• Do not use rituximab as first-line treatment in myasthenic crisis—its delayed onset of action (months) makes it unsuitable for acute management 5, 4
• Avoid rituximab in acute crisis when infection risk is elevated, as immunosuppressive effects last 6 months 5
• Do not delay IVIG/plasmapheresis while waiting to start rituximab in crisis situations 1

Algorithmic Approach to Crisis Management

Step 1: Immediate Assessment (Within Minutes)

• Assess respiratory status: negative inspiratory force, vital capacity, oxygen saturation 1
• Grade severity: Grade 3-4 requires immediate ICU admission and IVIG/plasmapheresis 1

Step 2: Acute Treatment (Within Hours)

• Start IVIG 0.4 g/kg/day × 5 days OR plasmapheresis (choose plasmapheresis if faster response needed for severe respiratory compromise) 1, 2
• Continue corticosteroids (prednisone 1-1.5 mg/kg/day) 1
• Maintain pyridostigmine unless intubated 1

Step 3: Post-Crisis Management (After 1-4 Weeks)

• If inadequate response after completing IVIG/plasmapheresis and 2-4 weeks of corticosteroids, consider adding steroid-sparing agents (mycophenolate, azathioprine) 1
• Only consider rituximab if patient remains refractory to standard immunosuppression after appropriate trial duration 5, 4

Step 4: Long-Term Management

• Rituximab may be appropriate for early treatment in select generalized MG cases with impending crisis or frequent exacerbations despite standard therapy 4
• Regular neurology follow-up to adjust immunosuppression and prevent future crises 1