Eosinophilic Granulomatosis with Polyangiitis - EGPA

Indications for Testing

• Asthma with multiorgan systemic disease

Criteria for Diagnosis

• Definition and classification criteria for eosinophilic granulomatosis with polyangiitis

  Eosinophilic Granulomatosis with Polyangiitis (EGPA) Criteria
  	Chapel Hill Consensus Conference (2012)	American College of Rheumatology (1990)
  Definition/Classification	Eosinophil-rich and necrotizing granulomatous inflammation often involving the respiratory tract Necrotizing vasculitis predominantly affecting small to medium vessels Associated with asthma and eosinophilia	If ≥4 of the 6 findings below plus asthma are present – sensitivity of 85%; specificity of 99.7%
  Laboratory Testing	ANCA – more frequently present when glomerulonephritis is present	Eosinophilia >10% of differential white blood cell count Nonfixed pulmonary infiltrates on roentgenography
  Histology	Common – granulomatous and nongranulomatous extravascular inflammation	Extravascular eosinophils revealed at biopsy Biopsy containing a blood vessel with extravascular eosinophils
  Clinical Signs/Symptoms	Common – nasal polyps May occur –  EGPA confined to the upper and lower respiratory tract	Mononeuropathy (including multiplex) or polyneuropathy Paranasal sinus abnormality

Laboratory Testing

• No reliable biomarkers to distinguish disease from similar eosinophilic diseases or for use in monitoring of therapeutic response
• Nonspecific testing –  helpful in excluding other diagnoses or identifying organ dysfunction (most likely abnormal during acute disease)
  • CBC – may have eosinophilia; often marked
    • Eosinophilia heralds relapse in established disease
  • Urinalysis – may have hematuria
  • C-reactive protein (CRP)
    • Preferred test to detect inflammatory processes (Choosing Wisely: 5 Things Physicians and Patients Should Question, 2015; American Society for Clinical Pathology)
    • Usually elevated in vasculitic phase
    • If CRP not available, order erythrocyte sedimentation rate (ESR)
• Immunoglobulins
  • Serum IgG levels – may be elevated, but lacks specificity
  • IgA – recent data suggest elevations in up to 75% of patients with acute disease
• ANCA
  • pANCA with MPO+ – most common, but <50% are positive
  • cANCA with PR3 – uncommon

Histology

• Tissue biopsy of involved organ site – small-to-medium sized artery vasculitis, extravascular eosinophilic necrotic  granulomas, eosinophilic infiltration of arterial and venous walls

Imaging Studies

• Chest radiograph – infiltrates common (often migratory); pleural effusion may be present

Prognosis

• Relapses are common, especially if maintenance treatments are fully withdrawn
• Flare-ups may follow reductions of corticosteroid doses

Differential Diagnosis

• Vasculitis (small vessel)
  • Granulomatosis with polyangiitis (formerly Wegener granulomatosis)
  • Microscopic polyangiitis
  • Eosinophilic vasculitis
• Malignancy
  • Myeloid or lymphoid neoplasm associated with eosinophilia
  • Chronic eosinophilia leukemia
• Parasitic infection
  • Toxocara spp
  • Schistosoma spp
  • Trichinella spiralis
  • Strongyloides stercoralis
  • Wuchereria bancrofti
  • Paragonimus westermani
• Eosinophilic syndromes
  • Bronchopulmonary aspergillosis
  • Hypersensitivity pneumonitis
  • Hypereosinophilic syndrome
  • Eosinophilic pneumonia (acute or chronic)
  • Bronchocentric granulomatosis
• Drug reactions (numerous)
  • Antibiotics
  • Antiasthmatics
  • Anticonvulsants