Eosinophilic Granulomatosis with Polyangiitis - EGPA

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss, is distinguishable from other pulmonary eosinophil-associated 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).

Quick Answers for Clinicians

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Diagnosis

Indications for Testing

Asthma with multiorgan systemic disease

Criteria for Diagnosis

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 sized 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

  • Anti-neutrophil cytoplasmic antibody (ANCA) – more frequently present when glomerulonephritis is present
  • Eosinophilia >10% of differential white blood cell count
  • Nonfixed pulmonary infiltrates on roentgenography

Histopathology

  • Common – granulomatous and nongranulomatous extravascular inflammation
  • ​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 eosinophil-associated 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 hypereosinophilia (>10% or 1500 cells/µL) (Valent, 2012)
      • Eosinophilia heralds relapse in established disease – may rapidly disappear with steroid initiation
    • Urinalysis – may have hematuria
    • C-reactive protein (CRP)
  • Immunoglobulins
    • Serum IgG levels – may be increased, but lack specificity
      • IgG4 often increased in active disease
      • EGPA is being considered as belonging to the list of IgG4-related diseases (Greco, 2014)
    • IgA – recent data suggest elevations in up to 75% of patients with acute disease
  • ANCA
    • Perinuclear ANCA (pANCA) with myeloperoxidase (MPO)+ – most common, but <50% are positive
      • Does not correlate with disease activity
    • Cytoplasmic ANCA (cANCA) with serine proteinase 3 (PR3) – uncommon
    • MPO and PR3 are enzymes to which ANCA antibodies are directed

Histopathology

  • Tissue biopsy of involved organ site – small-to-medium sized artery vasculitis, extravascular eosinophilic necrotic  granulomas, eosinophilic infiltration of arterial and venous walls
    • Skin, nerve, and muscle biopsies have highest yields (Mouthon, 2014)

Imaging Studies

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

Prognosis

  • Relapses are common, especially if maintenance treatments are fully withdrawn
    • May be heralded by increasing eosinophilia
  • Flare-ups may follow reductions of corticosteroid doses

Differential Diagnosis

Background

Epidemiology

  • Incidence – 1-3/1,000,000 in U.S.
    • In asthma patients, may be as high as 67/1,000,000 (Greco, 2014)
  • Age – 40-50 years
  • Sex – M>F (minimal)

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, cardiac, and GI tract
    • Vasculitic phase
      • Constitutional – fever, fatigue, malaise, weight loss
      • Pulmonary – asthma (~100%); migratory pulmonary infiltrates
      • Cardiovascular – myocarditis, endocarditis, pericarditis, coronary vasculitis, arrhythmias
        • Prominent cause of disease-related mortality
      • Neurologic – peripheral neuropathy (typically mononeuritis multiplex), polyneuropathy, confusion, seizures, cranial nerve palsies, coma
      • Dermatologic – nodules, papules, petechial rash, palpable purpura 
      • Gastrointestinal – abdominal pain, nausea, emesis, diarrhea
      • Renal – glomerulonephritis
      • Ophthalmologic – uveitis, retinopathy
      • Otorhinologic – paranasal sinus disease

ARUP Laboratory Tests

Assess for presence of eosinophilia

May help in ruling out infectious process

Screen for hematuria, proteinuria, RBC casts

Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)

Preferred reflex panel for the workup for suspected vasculitis

For patients with a history of vasculitis, refer to ANCA with reflex to titer and MPO/PR3 antibodies

MPO and PR3 tests may be ordered individually

Panel detects ANCA, MPO, and PR3

Preferred panel for managing patients with a known diagnosis of vasculitis; may be assistive in evaluating suspected vasculitis

Preferred reflex panel for the workup of suspected vasculitis is ANCA/MPO/PR3 with reflex to ANCA titer

Panel includes ANCA, IgG; MPO; and PR3

Related Tests

Nonspecific test used to detect inflammation associated with infections, cancers, and autoimmune diseases

When used in conjunction with other autoantibody tests (ANCA, MPO), may assist in differentiating suspected Wegener granulomatosis (WG) from other vasculitides

May be useful when monitoring patients with PR3 antibodies

Panel tests are available

For the workup of suspected vasculitis, refer to ANCA-associated vasculitis profile (ANCA/MPO/PR3) with reflex to ANCA titer

For patients with a history of vasculitis, refer to the ANCA reflex to titer and MPO/PR3 antibodies

When used in conjunction with other autoantibody tests (ANCA, PR3), may assist in evaluating suspected immune-mediated vasculitis, especially microscopic polyangiitis (MPA)

May be useful when monitoring MPA disease and/or treatment response

Panel tests are available

For the workup of suspected vasculitis, refer to ANCA-associated vasculitis profile (ANCA/MPO/PR3) with reflex to ANCA titer

For patients with a history of vasculitis, refer to the ANCA reflex to titer and MPO/PR3 antibodies

Medical Experts

Contributor

Genzen

Jonathan R. Genzen, MD, PhD
Associate Professor of Clinical Pathology, University of Utah
Chief Operations Officer: Medical Director, Automated Core Laboratory, ARUP Laboratories
Contributor

Gleich

 

Professor, Dermatology and Medicine; Emeritus Professor, Pediatrics, University of Utah
Consultant, Immunodermatology at ARUP Laboratories
Contributor

Leiferman

Picture of Kristin M. Leiferman, MD

 

Co-Director, Immunodermatology Laboratory, Professor of Dermatology, and Adjunct Professor of Pathology, University of Utah
Medical Director, Immunodermatology, ARUP Laboratories
Contributor

References

Additional Resources
  • 2202307

    Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990 Aug;33(8):1094-100. PubMed

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  • Resources from the ARUP Institute for Clinical and Experimental Pathology®