What are the clinical features of Eosinophilic Granulomatosis with Polyangiitis (EGPA)?

Clinical Features of Eosinophilic Granulomatosis with Polyangiitis (EGPA)

EGPA is characterized by asthma, eosinophilia, and multi-organ vasculitis, typically presenting in a three-phase clinical course with distinct manifestations at each stage. 1

Key Clinical Features

Prodromal "Allergic" Phase

• Asthma: Present in >90% of patients
  • Usually adult-onset
  • Rarely shows seasonal exacerbations
  • Tends to worsen over time
  • Often refractory to conventional treatment 1
• ENT manifestations (60-80% of patients):
  • Chronic rhinosinusitis with nasal polyps (polyps commonly recur after surgical excision)
  • Otitis media 1

Eosinophilic Phase

• Blood eosinophilia: >10% or >1,500 cells per μl in almost all patients
  • May be masked by systemic glucocorticoid use 1
• Pulmonary infiltrates (40-50% of patients):
  • Often multiple and migratory
  • Respond to glucocorticoid treatment
  • Ground-glass opacities (79.1% of patients) 2
  • Bronchial wall thickening and/or bronchial dilatation (51.2% of patients) 2

Vasculitic Phase

• Peripheral neuropathy (50-70% of patients):
  • Mononeuritis multiplex pattern
  • Usually sensory but may cause motor deficits
  • Axonal damage pattern on nerve conduction studies 1
• Skin manifestations:
  • Palpable purpura (most vasculitis-specific lesion)
  • Various other heterogeneous skin lesions 1
• Cardiac involvement:
  • Myocarditis
  • Pericarditis 1
• Gastrointestinal involvement:
  • Gastroenteritis 1
• Renal involvement:
  • Proteinuria
  • Hematuria
  • Varying degrees of kidney failure 1
• Systemic manifestations:
  • Fatigue
  • Weight loss
  • Myalgia
  • Arthralgia
  • Fever (more common in ANCA-positive patients) 1, 2

ANCA Status and Clinical Phenotypes

EGPA has two distinct phenotypes based on ANCA status:

ANCA-Positive (30-40% of patients)

• Predominantly MPO-ANCA positive
• More frequent manifestations:
  • Glomerulonephritis
  • Peripheral neuropathy
  • Purpura
  • Fever
  • Renal disease
  • Honeycombing pattern on HRCT
  • More significant decrease in pulmonary diffusion function 1, 2

ANCA-Negative (60-70% of patients)

• More frequent manifestations:
  • Cardiac involvement
  • Gastroenteritis
  • More significant obstructive ventilatory defect 1, 2

Diagnostic Considerations

While there are no validated diagnostic criteria for EGPA, diagnosis should be based on:

1. Highly suggestive clinical features
2. Objective evidence of vasculitis (e.g., from histology)
3. ANCA testing 1

The clinical suspicion of EGPA should be raised in patients with asthma, chronic rhinosinusitis, and eosinophilia who develop end-organ involvement, particularly peripheral neuropathy, lung infiltrates, cardiomyopathy, or other complications 1.

Disease Course and Prognosis

• The three phases (allergic, eosinophilic, vasculitic) often overlap and may not develop in sequence
• Some patients may not manifest vasculitic complications
• After vasculitis resolution, asthma remains severe in up to 50% of patients 3
• Incidence of isolated asthma and rhinosinus exacerbations remains high during follow-up 3

Clinical Pitfalls and Caveats

1. Masked eosinophilia: Blood eosinophilia may be masked by prior glucocorticoid use, potentially leading to missed diagnosis 1

2. Overlapping phases: The three phases of EGPA often overlap and may not develop in the classic sequence, making diagnosis challenging 1

3. Refractory sinusitis: Refractory sinusitis in the presence of constitutional symptoms and peripheral eosinophilia should raise suspicion for EGPA, particularly in patients with late-onset asthma 4

4. Pulmonary function: Obstructive ventilatory defects are common, but patterns may differ based on ANCA status 2

5. Histopathology: Tissue biopsy may show eosinophil infiltration without granulomas in many cases 2