Is a nasal biopsy required for diagnosing Eosinophilic Granulomatosis with Polyangiitis (EGPA)?

Nasal Biopsy is Not Required for Diagnosing EGPA

A nasal biopsy is recommended when feasible but is not essential for making a diagnosis of Eosinophilic Granulomatosis with Polyangiitis (EGPA). 1

Diagnostic Approach for EGPA

Evidence-Based Diagnostic Criteria

• The diagnosis of EGPA should be based on a combination of:
  • Highly suggestive clinical features (asthma, chronic rhinosinusitis with polyps, eosinophilia)
  • Objective evidence of vasculitis (from histology when available)
  • ANCA status 1
• There are no formal diagnostic criteria for EGPA, only classification criteria such as:
  • 1990 ACR criteria
  • 2022 ACR-EULAR criteria (sensitivity 85%, specificity 99%)
  • MIRRA trial criteria 1

Role of Biopsy in Diagnosis

• While biopsy of affected organs is encouraged to contribute to diagnostic evaluation, it is not mandatory 1
• Biopsies can help:
  • Confirm vasculitis
  • Exclude differential diagnoses
  • Reflect disease activity/chronicity 1
• When sinonasal tissue is examined in EGPA:
  • Eosinophilic infiltration is seen in 35-100% of cases
  • Necrotizing vasculitis and eosinophilic granulomas are often not seen 1
  • This means nasal biopsies frequently lack the classic histopathological triad required for definitive diagnosis

Limitations of Nasal Biopsy

• Nasal mucosa biopsy is less reliable than kidney, lung, or sinus tissue biopsies 2
• Nasal biopsies rarely demonstrate all three required histopathological features (granulomatous inflammation, necrosis, and vasculitis) 2
• Results from nasal biopsies are often reported as "consistent with" rather than definitively diagnostic of EGPA 2

Alternative Diagnostic Approaches

Clinical and Laboratory Features

• Active EGPA is characterized by:
  • Marked peripheral eosinophilia (usually >1500 cells/μl or >10%) 1
  • Non-specific increase in IgE (if not on systemic steroids) 1
  • ANCA positivity in 30-40% of cases (mostly MPO-ANCA) 1

Multidisciplinary Evaluation

• A multidisciplinary approach is essential for diagnosis 1, 3
• Baseline investigations should include:
  • Complete blood count with differential
  • ANCA testing (all patients with suspected EGPA should undergo this) 1, 3
  • Imaging of affected organs
  • Assessment of heart, respiratory, skin, renal, and nervous system involvement 1

Diagnostic Algorithm

1. Identify patients with the clinical triad:
   • Asthma
   • Chronic rhinosinusitis with nasal polyps
   • Peripheral blood eosinophilia 3
2. Look for evidence of end-organ involvement:
   • Peripheral neuropathy
   • Lung infiltrates
   • Cardiomyopathy
   • Other complications (skin, gastrointestinal, kidney) 1
3. Perform ANCA testing (especially MPO-ANCA)
4. Consider biopsy of the most affected and accessible organ when feasible
5. Rule out other eosinophilic and vasculitic disorders 1

Clinical Pearls and Pitfalls

Important Considerations

• EGPA should be considered in any patient with severe nasal polyposis not responding to conventional therapy 1
• ANCA-positive patients more frequently show features of vasculitis (glomerulonephritis, neuropathy, purpura)
• ANCA-negative patients more frequently manifest cardiomyopathy and lung involvement 1

Potential Biomarkers

• Emerging research suggests sputum GM-CSF and eosinophils might be useful biomarkers to support early diagnosis in patients with severe eosinophilic asthma suspected of having EGPA 4

Differential Diagnosis

• Other eosinophilic pneumonias
• Idiopathic hypereosinophilic syndrome
• c-ANCA positive granulomatosis
• Microscopic polyangiitis
• Sarcoidosis
• Allergic bronchopulmonary aspergillosis
• Parasitic infections 1

In conclusion, while histopathological confirmation through biopsy is valuable when available, the diagnosis of EGPA can be made without nasal biopsy based on characteristic clinical features, laboratory findings, and multidisciplinary assessment. Early diagnosis and treatment are crucial for improving outcomes and reducing mortality.