What are the diagnostic and presentation criteria for eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg Strauss, in a patient with a history of asthma and suspected vasculitis?

Diagnostic and Presentation Criteria for Eosinophilic Granulomatosis with Polyangiitis (EGPA)

There are no validated diagnostic criteria for EGPA; diagnosis must be based on highly suggestive clinical features (asthma, eosinophilia, and end-organ involvement), objective evidence of vasculitis from histology when feasible, and ANCA testing. 1

Critical Diagnostic Principle

Classification criteria (1990 ACR, 2022 ACR-EULAR, MIRRA trial criteria) should never be used as diagnostic criteria—they were developed to distinguish between vasculitis types in research settings, not for clinical diagnosis. 1, 2

Clinical Presentation: The Diagnostic Triad

Core Features Present in Nearly All Patients

• Asthma: Present in almost all EGPA patients and typically precedes other manifestations 1, 3
• Eosinophilia: Observed in almost all patients, defined as >10% or >1,500 cells/μl, though can be masked by systemic glucocorticoids 1, 4
• Chronic rhinosinusitis: Often accompanied by nasal polyps, otitis media, and other ENT manifestations 1, 5

End-Organ Involvement That Triggers Diagnostic Suspicion

When patients with the above triad develop the following complications, EGPA diagnosis should be strongly considered: 1

• Peripheral neuropathy (50-70% of patients): Presents as mononeuritis multiplex pattern, usually sensory but may cause motor deficits, with axonal damage on nerve conduction studies 1
• Lung infiltrates (40-50%): Multiple, migratory infiltrates that respond to glucocorticoids 1
• Cardiac involvement: Myocarditis, pericarditis, or eosinophilic cardiomyopathy—the most common cause of death in EGPA 1, 3
• Skin lesions: Palpable purpura is the most vasculitis-specific lesion, though presentations are heterogeneous 1
• Renal disease: Proteinuria, hematuria, and varying degrees of kidney failure, though less common than in other ANCA-associated vasculitides 1
• Gastrointestinal involvement: Eosinophilic gastroenteritis 1

Systemic Manifestations

• Fatigue, weight loss, myalgia, and arthralgia are common 1

Laboratory and Diagnostic Evaluation

Baseline Investigations Required

• ANCA testing: Only 30-40% of EGPA patients are ANCA-positive (typically MPO-ANCA/p-ANCA); PR3-ANCA positivity argues against EGPA 1, 4
• Complete blood count with differential: To document eosinophilia 1
• Inflammatory markers: ESR and CRP 1
• Urinalysis: To detect hematuria and proteinuria 1
• Renal function tests: Creatinine and BUN 1

Tissue Biopsy (When Feasible)

Biopsy of affected organs is recommended when feasible but is not essential for diagnosis. 1 Potential biopsy sites include:

• Kidney: Shows crescentic necrotizing glomerulonephritis with eosinophilic infiltrates, granulomatous changes, and necrotizing vasculitis 1
• Skin: Reveals leukocytoclastic vasculitis in palpable purpura 1
• Nerve: Demonstrates vasculitic neuropathy 1
• Lung, ENT region, gastrointestinal tract: Can show eosinophilic infiltration and vasculitis 1

Organ-Specific Investigations

• Cardiac evaluation: ECG, echocardiography, cardiac MRI, and troponin levels (cardiac involvement is the leading cause of mortality) 3, 6
• Pulmonary assessment: Chest CT is more sensitive than plain radiographs for detecting infiltrates 1
• Neurological evaluation: Nerve conduction studies and EMG for peripheral neuropathy 1
• ENT evaluation: Sinus CT when upper respiratory tract involvement is suspected 1

Classification Criteria for Reference (Not Diagnosis)

2022 ACR-EULAR Classification Criteria (For Classification Only)

These criteria achieve 85% sensitivity and 99% specificity for classification but should not be used diagnostically: 1

Positive scoring parameters:

• 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 and/or motor neuropathy not due to radiculopathy: +1 point 1

Negative scoring parameters:

• C-ANCA pattern or PR3-ANCA positivity: -3 points 1
• Hematuria: -1 point 1

A score ≥6 classifies a patient with small- or medium-vessel vasculitis as having EGPA 1

1990 ACR Classification Criteria (Historical Reference)

Four or more of six criteria needed (85% sensitivity, 99.7% specificity for classification): 1

• Asthma 1
• Eosinophilia >10% 1
• Neuropathy 1
• Non-fixed lung infiltrates 1
• Paranasal sinus abnormalities 1
• Histological evidence of extravascular eosinophils 1

Multidisciplinary Diagnostic Approach

The diagnostic evaluation must always be multidisciplinary and should rule out other eosinophilic and vasculitic disorders while investigating major organ complications. 1 Key specialties to involve:

• Rheumatology (primary coordination) 1
• Pulmonology (asthma and lung infiltrates) 1
• Cardiology (cardiac involvement assessment) 1
• Neurology (peripheral neuropathy evaluation) 1
• Nephrology (renal involvement) 1
• ENT (upper respiratory tract disease) 1
• Dermatology (skin manifestations) 1

Critical Diagnostic Pitfalls

• Do not rely solely on ANCA status: Unlike other ANCA-associated vasculitides, most EGPA patients are ANCA-negative 4
• Glucocorticoids mask eosinophilia: Check eosinophil counts before initiating steroids when possible 1
• Cardiac involvement is often subclinical: Actively screen for cardiac disease even without symptoms, as it is the leading cause of death 3, 6
• Disease evolves over time: EGPA may not present with all features simultaneously; maintain high suspicion in patients with asthma and eosinophilia who develop new organ involvement 3
• ANCA-positive patients have different phenotype: MPO-ANCA positivity associates with more renal involvement and vasculitic features 1, 6