What is the treatment for Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis, EGPA)?

Treatment of Churg-Strauss Syndrome (EGPA)

All patients with EGPA require glucocorticoids as the foundation of therapy, with the addition of cyclophosphamide or rituximab for severe disease, and mepolizumab emerging as the most effective glucocorticoid-sparing agent for maintenance and relapsing disease. 1, 2

Disease Severity Stratification

Treatment must be stratified based on the presence of organ-threatening manifestations 1, 2:

Severe EGPA is defined by any of the following 1, 2:

• Renal insufficiency or proteinuria
• Cardiomyopathy
• Gastrointestinal tract involvement
• Central nervous system involvement
• Peripheral neuropathy
• Alveolar hemorrhage
• Five-Factor Score (FFS) ≥1

Non-severe EGPA has FFS = 0 and lacks organ-threatening manifestations 1, 2

Remission Induction Therapy

For Severe Disease

Initiate high-dose glucocorticoids (0.75-1 mg/kg/day oral prednisone or methylprednisolone 500-1000 mg IV daily for 3 days) PLUS either cyclophosphamide or rituximab 1, 2:

• Cyclophosphamide regimen: 0.6 g/m² IV pulses every 2 weeks for 1 month, then every 4 weeks thereafter 2
• Rituximab regimen: 1-gram IV infusions separated by 2 weeks, with comparable efficacy to cyclophosphamide 2

For Non-Severe Disease

Use glucocorticoids alone or combined with mepolizumab 1, 2

The 2023 Nature Reviews Rheumatology guidelines emphasize that glucocorticoids should be administered as initial therapy in all patients, with the decision to add immunosuppressants based strictly on severity classification 1.

Remission Maintenance Therapy

For Severe EGPA

Use rituximab, mepolizumab, or traditional DMARDs (azathioprine, methotrexate, leflunomide) in combination with low-dose glucocorticoids 1, 2:

• Rituximab maintenance: 500 mg IV every 6 months reduces relapse rates 2
• Mepolizumab maintenance: 300 mg subcutaneously every 4 weeks, particularly effective for controlling asthma and reducing glucocorticoid exposure 2
• Traditional DMARDs: Azathioprine is commonly used for maintenance after cyclophosphamide induction 3

For Non-Severe EGPA

Use glucocorticoids alone or combined with mepolizumab 1

Glucocorticoid Tapering Strategy

Taper glucocorticoids to ≤7.5 mg/day prednisone as the target for remission 1, 2. Mepolizumab is the most effective glucocorticoid-sparing agent, demonstrated in the MIRRA trial 2. This is critical because glucocorticoid-related toxicity is particularly problematic in EGPA due to high cumulative exposure 2.

Management of Relapses

Distinguish between systemic relapses (vasculitis recurrence) and respiratory relapses (isolated asthma/ENT exacerbations) as they require different treatment approaches 1, 2:

Severe Systemic Relapses

Use rituximab or cyclophosphamide with glucocorticoids 1, 2

Non-Severe Systemic and Respiratory Relapses

Increase glucocorticoid dose and/or add mepolizumab 1, 2

Refractory Disease

For relapsing-refractory EGPA without organ- or life-threatening manifestations, use mepolizumab (IL-5 inhibitor) in combination with glucocorticoids 1. Refractory disease is defined as unchanged or increased disease activity after 4 weeks of appropriate remission-induction therapy 1.

Essential Adjunctive Respiratory Management

All patients with asthma or ENT involvement require optimization of topical/inhaled therapies in collaboration with pulmonologists and otolaryngologists 1, 2:

• High-dose inhaled glucocorticoids plus long-acting β2-agonists for asthma control 2
• Nasal rinses and topical therapies for ENT manifestations 2
• Nasal irrigation, topical intranasal corticosteroid sprays or creams (e.g., triamcinolone), and nasal lubricants 1

Special Population Considerations

Young Patients

Prefer rituximab over cyclophosphamide to preserve fertility 2

Elderly Patients

Reduce cyclophosphamide dose to fixed 500 mg (not 500 mg/m²) and shorten glucocorticoid duration to 9 months 2

Pregnant Patients

Use only glucocorticoids, IV immunoglobulins, or azathioprine; discontinue cyclophosphamide, mycophenolate, methotrexate 3-6 months before conception 2

Infection Prophylaxis and Monitoring

Administer Pneumocystis jirovecii prophylaxis with sulfamethoxazole-trimethoprim (800 mg-160 mg on alternate days or 400 mg-80 mg daily) in all patients treated with cyclophosphamide and/or rituximab 1. Screen for hepatitis B virus and HIV before initiating cyclophosphamide or rituximab 1.

Monitor for long-term complications 1:

• Periodic echocardiography and electrocardiography for cardiac involvement
• Lung function monitoring, particularly in overweight patients and those with pulmonary infiltrates
• Neurological assessment for neuropathy sequelae
• Bone density assessment for osteoporosis risk
• Age-appropriate cancer screening; cyclophosphamide-treated patients require screening for bladder cancer, myeloid leukemia, and skin cancer

Critical Monitoring Caveat

Eosinophil count and ANCA titers are unreliable biomarkers for disease activity and should not guide treatment decisions 2. Disease activity must be assessed using validated clinical tools 2.