Clinical Manifestations: GPA vs EGPA
The key distinguishing features are that EGPA presents with asthma, peripheral eosinophilia, and peripheral neuropathy as dominant features, while GPA characteristically shows destructive sinonasal lesions, pulmonary nodules, and more severe renal involvement with pauci-immune glomerulonephritis 1.
a) General Patient Symptomatology
GPA patients present with:
- Destructive sinonasal lesions (necrotizing granulomatous inflammation)
- Pulmonary nodules and cavitary lesions
- Constitutional symptoms (fever, weight loss)
- PR3-ANCA positivity (cytoplasmic pattern) in most cases
- No history of atopy or asthma 1
EGPA patients present with:
- Asthma as a cardinal feature (present in virtually all cases)
- Rhinosinusitis (allergic-type, non-destructive)
- Marked peripheral blood eosinophilia (often >1,500/mm³)
- History of allergic diseases in 86.7% of cases
- Only 30-40% are ANCA-positive (predominantly MPO-ANCA/P-ANCA) 2, 1, 3
- Elevated IgE levels (median 445 KU/L vs 153 KU/L in other eosinophilic conditions) 3
The prodromic phase of EGPA includes asthma and rhinosinusitis, followed by an eosinophilic phase with peripheral eosinophilia, then a vasculitic phase 4.
b) Gastrointestinal Symptoms
GPA: Gastrointestinal involvement is uncommon and not a prominent feature 1.
EGPA:
- Gastrointestinal involvement occurs but is less common than other manifestations
- When present, manifests as abdominal pain, diarrhea, and gastrointestinal bleeding
- GI involvement in EGPA carries worse prognosis with higher risk of perforation, organ failure, and death 3, 5
- Presents with fever (50% vs 6.5% in isolated eosinophilic gastroenteritis), higher ESR (25 mm/h) and CRP (48.9 mg/L) 3
- Lower prevalence of distension and intestinal obstruction compared to isolated eosinophilic gastroenteritis 3
c) Peripheral Nervous System Involvement
GPA: Peripheral neuropathy is uncommon and not a defining feature 1.
EGPA:
- Peripheral neuropathy is a prominent and common manifestation
- Presents as mononeuritis multiplex or severe axonal sensorimotor polyneuropathy
- Can be severe enough to cause wheelchair dependence 6, 7
- MPO-ANCA positivity is specifically associated with peripheral neuropathy (along with renal involvement and purpura) 2
- Neurological involvement can be progressive and aggressive, requiring early immunosuppressive intervention 6, 7
d) Renal Involvement (Proteinuria - Hematuria)
GPA:
- Pauci-immune glomerulonephritis is a hallmark feature
- Rapidly progressive glomerulonephritis common
- Severe renal involvement requiring cyclophosphamide therapy 1, 8
- Necrotizing crescentic glomerulonephritis on biopsy 9
EGPA:
- Renal involvement occurs but is less frequent and less severe than in GPA
- When present, associated with MPO-ANCA positivity 2
- ANCA-negative EGPA patients have lower frequency of renal involvement 2
- Glomerulonephritis can occur but is not the dominant feature 4
Critical distinction: Severe renal disease with rapidly progressive glomerulonephritis strongly suggests GPA over EGPA.
e) Cardiac Involvement
GPA: Cardiac involvement is uncommon 1.
EGPA:
- Cardiac manifestations are more frequent and clinically significant
- ANCA-negative EGPA patients have higher frequency of cardiac involvement 2
- Cardiac involvement contributes to worse overall survival in ANCA-negative patients 2
- Manifestations include myocarditis, pericarditis, and cardiac dysfunction 7
- MPO-ANCA positivity confers lower risk of cardiac manifestations 2
Important caveat: The presence of PR3-ANCA in rare EGPA cases creates a phenotype closer to GPA, with more lung nodules and skin manifestations but less asthma, peripheral neuropathy, and hypereosinophilia 2. Overlap syndromes can occur, presenting diagnostic challenges 9.
Clinical algorithm for differentiation:
- Asthma present → strongly favors EGPA
- Peripheral eosinophilia >1,500/mm³ → strongly favors EGPA
- Severe renal disease → favors GPA
- Peripheral neuropathy → favors EGPA
- Destructive sinonasal lesions → favors GPA
- Cardiac involvement → favors EGPA (especially if ANCA-negative)
- PR3-ANCA/C-ANCA positive → favors GPA
- MPO-ANCA/P-ANCA positive with asthma → favors EGPA