What's the treatment approach for GPA (Granulomatosis with Polyangiitis) vs EGPA (Eosinophilic Granulomatosis with Polyangiitis) with a 5-point diagnostic difference?

Treatment Approach for GPA vs EGPA: Key Differences

The treatment approach for GPA (Granulomatosis with Polyangiitis) and EGPA (Eosinophilic Granulomatosis with Polyangiitis) differs primarily based on disease severity, ANCA status, and organ involvement, with EGPA requiring specific attention to asthma and eosinophilia.

Diagnostic Differences

• ANCA status: GPA patients are typically PR3-ANCA positive (80-90%), while only 30-40% of EGPA patients are ANCA positive (mostly MPO-ANCA) 1
• Eosinophilia: Hallmark of EGPA (not typically seen in GPA)
• Asthma: Present in nearly all EGPA patients, uncommon in GPA
• Organ involvement patterns:
  • EGPA: More cardiac involvement, asthma, eosinophilic infiltrates
  • GPA: More destructive upper airway disease, nodular lung lesions, renal involvement

Treatment Algorithm

1. Initial Assessment

• For both conditions: Obtain ANCA testing, complete blood count with differential, renal function, urinalysis, and chest imaging
• For EGPA: Calculate Five-Factor Score (FFS) to guide therapy 1
  • FFS factors: renal insufficiency, proteinuria >1g/day, cardiomyopathy, GI involvement, CNS involvement
  • Obtain echocardiogram at diagnosis for all EGPA patients 1

2. Remission Induction

For GPA:

• Severe/organ-threatening disease: Combination of glucocorticoids with either:
  • Cyclophosphamide OR
  • Rituximab (especially for PR3-ANCA positive patients) 1
• Non-severe disease: Glucocorticoids plus methotrexate 1

For EGPA:

• Severe disease (with unfavorable prognostic factors):
  • Glucocorticoids plus cyclophosphamide or rituximab 1
• Non-severe disease:
  • Glucocorticoids alone may be sufficient 1
  • For steroid-dependent asthma/ENT disease: Consider mepolizumab (300mg SC every 4 weeks) 2

3. Remission Maintenance

For GPA:

• Rituximab, azathioprine, or methotrexate after cyclophosphamide induction
• Continue for at least 18-24 months

For EGPA:

• Methotrexate, azathioprine, or mycophenolate mofetil 1
• Mepolizumab for steroid-dependent asthma/ENT manifestations 2
• Consider asthma control as part of remission definition 1

4. Monitoring and Follow-up

For GPA:

• Monitor ANCA titers, as rising titers may predict relapse
• Regular urinalysis and renal function tests

For EGPA:

• Monitor eosinophil counts, though they don't always correlate with disease activity 2
• Regular pulmonary function tests and cardiac monitoring 1
• ANCA monitoring in initially positive patients 1

Special Considerations

Overlap Syndromes

Rare cases of GPA-EGPA overlap have been reported 3, 4. These patients typically present with:

• Features of both conditions
• Often c-ANCA positive
• Eosinophilia
• May require more aggressive immunosuppression

Relapse Management

For GPA:

• Major relapse: Treat as new disease with cyclophosphamide or rituximab 1

For EGPA:

• Severe relapse: Consider rituximab (even after prior cyclophosphamide) 1
• Non-severe relapse (asthma/sinonasal): Add mepolizumab 1

Prophylaxis

For both conditions when using cyclophosphamide or rituximab:

• Pneumocystis jirovecii pneumonia prophylaxis with trimethoprim-sulfamethoxazole 1

Prognostic Differences

• EGPA: Better overall survival (90% at 7 years) when treatment is stratified by FFS 5
• GPA: Generally more aggressive renal disease with higher relapse rates
• ANCA status in EGPA: ANCA-negative patients have worse survival (more cardiac involvement), while ANCA-positive patients have more frequent relapses 1

Common Pitfalls

1. Misdiagnosis: Overlap syndromes exist but are rare; careful attention to clinical features is essential
2. Undertreatment: EGPA cardiac involvement may be subclinical but carries poor prognosis
3. Overreliance on biomarkers: Eosinophil count alone is not a reliable marker of EGPA disease activity
4. Neglecting asthma control: In EGPA, asthma control should be considered part of remission definition
5. Inappropriate steroid tapering: Many EGPA relapses occur when prednisone is tapered below 10mg/day 5

Remember that while these conditions share features of ANCA-associated vasculitis, their distinct pathophysiology requires tailored treatment approaches focusing on the predominant disease manifestations.