How do I diagnose eosinophilic granulomatosis with polyangiitis (Churg‑Strauss syndrome) in a 30‑60‑year‑old adult with asthma, allergic rhinitis, peripheral eosinophilia and possible systemic vasculitis manifestations?

Diagnosis of Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)

Diagnose EGPA when at least four of the six American College of Rheumatology criteria are present in a patient with vasculitis: asthma, eosinophilia >10%, mono- or polyneuropathy, non-fixed pulmonary infiltrates, paranasal sinus abnormalities, and biopsy showing extravascular eosinophils. 1

Primary Diagnostic Approach

The 2022 ACR-EULAR classification criteria provide the most current framework, requiring a cumulative score of ≥6 points in patients with small- or medium-sized vessel vasculitis (sensitivity 85%, specificity 99%) 1:

Positive scoring features:

• Maximum eosinophil count ≥1 × 10⁹/L (+5 points) 1
• Obstructive airway disease (+3 points) 1
• Nasal polyps (+3 points) 1
• Extravascular eosinophilic-predominant inflammation on biopsy (+2 points) 1
• Mononeuritis multiplex or motor neuropathy not due to radiculopathy (+1 point) 1

Negative scoring features:

• C-ANCA pattern or anti-PR3-ANCA positivity (−3 points) 1
• Hematuria (−1 point) 1

Essential Clinical Features to Identify

Asthma is present in >90% of EGPA cases and is the most consistent feature. 2, 3 Look specifically for adult-onset asthma that preceded other manifestations, often by years 4. The disease typically evolves through three sequential phases 4, 5:

1. Prodromic/allergic phase: Asthma, allergic rhinitis, chronic rhinosinusitis with nasal polyps 4, 5
2. Eosinophilic phase: Peripheral blood eosinophilia with tissue infiltration causing lung infiltrates (86% of patients), cardiac involvement, or gastrointestinal symptoms 3, 4
3. Vasculitic phase: Mononeuritis multiplex, glomerulonephritis, purpura, constitutional symptoms 4, 5

Required Laboratory and Imaging Workup

Baseline investigations mandatory for all suspected cases 1:

• Complete blood count with differential: Marked peripheral eosinophilia is a key diagnostic feature 2
• ANCA testing (both MPO and PR3): Only 30-40% of EGPA patients are ANCA-positive, so a negative result does not exclude the diagnosis 2, 3, 4
• Total IgE level 2
• Specific IgE and IgG for Aspergillus fumigatus: Essential to exclude allergic bronchopulmonary aspergillosis (ABPA), a critical differential diagnosis 2, 3
• High-resolution CT chest: Look for "fluffy" or nodular migratory infiltrates, ground glass opacities, peripheral nodules, bronchial wall thickening, and bronchiectasis 2
• CT sinuses: Paranasal sinus abnormalities are part of diagnostic criteria 1

Additional testing based on clinical suspicion 2:

• Serologic testing for toxocariasis
• HIV testing
• Tryptase and vitamin B12 levels
• Cardiac evaluation (ECG, troponin, echocardiogram) if any cardiac symptoms—cardiac involvement is more common in ANCA-negative patients and is a leading cause of death 4
• Nerve conduction studies if peripheral neuropathy suspected 3
• Urinalysis and renal function to assess for glomerulonephritis (more frequent in ANCA-positive phenotype) 3, 4

Role of Biopsy

Biopsy is recommended when feasible but is not essential to make the diagnosis of EGPA. 1 The classic histopathological triad includes tissue eosinophilia, necrotizing vasculitis, and eosinophil-rich granulomatous inflammation 1, 4. However, nasal biopsies often lack sufficient specific features to confirm the diagnosis 1. When biopsy is performed, target symptomatic organs (skin, nerve, kidney) rather than the sinonasal tract 1.

Understanding ANCA Status and Clinical Phenotypes

ANCA status defines two distinct clinical phenotypes with different organ involvement patterns 3, 4:

ANCA-positive (MPO-ANCA, 30-40% of cases):

• More frequent vasculitic features 4
• Higher rates of glomerulonephritis, peripheral neuropathy, and purpura 3, 4

ANCA-negative (60-70% of cases):

• More frequent eosinophilic features 4
• Higher rates of cardiac involvement and gastroenteritis 4
• Increased risk of cardiomyopathy requiring cardiac monitoring 2

Critical Differential Diagnoses to Exclude

The multidisciplinary evaluation must rule out 1, 3:

• Allergic bronchopulmonary aspergillosis (ABPA): Distinguished by presence of IgE/IgG specific for Aspergillus fumigatus and absence of systemic vasculitis 3
• Idiopathic hypereosinophilic syndrome: Lacks asthma and vasculitic features 3
• Other eosinophilic pneumonias: Lack systemic vasculitis 3
• Granulomatosis with polyangiitis (GPA): Distinguished by C-ANCA/PR3-ANCA positivity (scored negatively in EGPA criteria) and different clinical pattern 1

Common Diagnostic Pitfalls

Asthma may be the primary manifestation for years before other features develop, and chronic corticosteroid use for asthma may mask vasculitic manifestations. 6 Maintain high suspicion in any adult-onset asthmatic with marked eosinophilia, especially when developing rhinosinusitis with polyps, neuropathy, or unexplained systemic symptoms 7, 8. The diagnosis requires a multidisciplinary approach involving rheumatology, pulmonology, and other specialists based on organ involvement 1, 7.