Eosinophilic Granulomatosis with Polyangiitis - EGPA

Diagnosis

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 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
    • Asthma
    • 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
    • Erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) – elevated
  • Immunoglobulins
    • Serum IgG levels – may be elevated, but lack 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 

Clinical Background

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss, is distinguishable from other pulmonary eosinophilic syndromes by the presence of eosinophilic vasculitis in concert with asthma and multiorgan involvement (lungs, heart, gastrointestinal tract, skin, nervous system). It is categorized as small- to medium-vessel ANCA-associated vasculitis (Chapel Hill 2012).

Epidemiology

  • Incidence – 1-3/1,000,000 in U.S.; in asthma patients, may be as high as 67/1,000,000
  • Age – 40-50 years
  • Sex – M>F

Pathophysiology

  • Small and medium vessel necrotizing vasculitis/angiitis – involves arteries and veins
    • Dependent on site of tissue sampling and stage of disease
  • Extravascular necrotizing granulomas and eosinophilic infiltration
    • Observation of granulomas less common than in the past due to recognition of disease in earlier stage
    • Vasculitis may not always be necrotizing

Clinical Presentation

  • 3 phases of disease
    • Prodromal phase
      • Characterized by asthma and allergic rhinitis, +/- nasal polyposis
      • Typically occurs when individual is 20-30 years and persists for many years
    • Eosinophilic infiltrative phase
      • Peripheral eosinophilia, eosinophilic tissue infiltration of various organs, including lungs and GI tract
    • Vasculitic phase
      • Constitutional – fever, fatigue, malaise, weight loss
      • Pulmonary – asthma (~100%)
      • Cardiovascular – myocarditis, endocarditis, pericarditis, coronary vasculitis
        • Prominent cause of disease-related mortality
      • Neurologic – peripheral neuropathy (typically mononeuritis multiplex), polyneuropathy, confusion, seizures, cranial nerve palsies, coma
      • Dermatologic – nodules, papules, petechial rash
      • Gastrointestinal – abdominal pain, nausea, emesis, diarrhea
      • Renal – glomerulonephritis
      • Ophthalmologic – uveitis, retinopathy
      • Otorhinologic – paranasal sinus disease

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Assess for presence of eosinophilia

May help in ruling out infectious process

   
Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Screen for hematuria, proteinuria, RBC casts

   
Sedimentation Rate, Westergren (ESR) 0040325
Method: Visual Identification

Initial evaluation for suspected vasculitis

   
C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Initial evaluation for suspected vasculitis

   
Anti-Neutrophil Cytoplasmic Antibody with Reflex to Titer and MPO/PR-3 Antibodies 2002068
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Initial evaluation for suspected vasculitis

If screen is positive, titer and MPO/PR-3 antibodies testing will be added to aid in antibody determination