Eosinophilic Granulomatosis with Polyangiitis - EGPA

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Asthma with multiorgan systemic disease

Criteria for Diagnosis

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 protease 3 (PR-3) – uncommon
    • MPO and PR-3 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  • Relapses are common, especially if maintenance treatments are fully withdrawn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

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).

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
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.

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Recommended Use 

Assess for presence of eosinophilia

May help in ruling out infectious process

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Recommended Use 

Screen for hematuria, proteinuria, RBC casts

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Recommended Use 

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

ANCA-Associated Vasculitis Profile (ANCA/MPO/PR-3) with Reflex to ANCA Titer 2006480
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Recommended Use 

Preferred reflex panel for the workup for suspected vasculitis

Panel detects ANCA, MPO, and PR-3

For patients with a history of vasculitis, refer to ANCA with reflex to titer and MPO/PR-3 antibodies

MPO and PR-3 tests may be ordered individually

Reflex pattern – if the ANCA screen detects antibodies at a 1:20 dilution or greater, then a titer to end point will be added

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

Recommended Use 

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/PR-3 with reflex to ANCA titer

Panel includes ANCA, IgG; MPO; and PR-3

Reflex pattern – if screen is positive, then titer and MPO/PR-3 antibodies testing will be added to aid in antibody determination

Guidelines

Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Jan 2017]

Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013; 65(1): 1-11. PubMed

Masi AT, Hunder GG, Lie JT, Michel BA, Bloch DA, Arend WP, Calabrese LH, Edworthy SM, Fauci AS, Leavitt RY, 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

General References

Abril A. Churg-strauss syndrome: an update. Curr Rheumatol Rep. 2011; 13(6): 489-95. PubMed

Boyer D, Vargas SO, Slattery D, Rivera-Sanchez YM, Colin AA. Churg-Strauss syndrome in children: a clinical and pathologic review. Pediatrics. 2006; 118(3): e914-20. PubMed

Comarmond C, Cacoub P. Granulomatosis with polyangiitis (Wegener): clinical aspects and treatment. Autoimmun Rev. 2014; 13(11): 1121-5. PubMed

Greco A, Rizzo MI, De Virgilio A, Gallo A, Fusconi M, Ruoppolo G, Altissimi G, De Vincentiis M. Churg-Strauss syndrome. Autoimmun Rev. 2015; 14(4): 341-8. PubMed

Haubitz M. ANCA-associated vasculitis: diagnosis, clinical characteristics and treatment. Vasa. 2007; 36(2): 81-9. PubMed

Mahr A, Moosig F, Neumann T, Szczeklik W, Taillé C, Vaglio A, Zwerina J. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): evolutions in classification, etiopathogenesis, assessment and management. Curr Opin Rheumatol. 2014; 26(1): 16-23. PubMed

Monach PA. Biomarkers in vasculitis. Curr Opin Rheumatol. 2014; 26(1): 24-30. PubMed

Mouthon L, Dunogue B, Guillevin L. Diagnosis and classification of eosinophilic granulomatosis with polyangiitis (formerly named Churg-Strauss syndrome). J Autoimmun. 2014; 48-49: 99-103. PubMed

Ozaki S. ANCA-associated vasculitis: diagnostic and therapeutic strategy. Allergol Int. 2007; 56(2): 87-96. PubMed

Seo P, Stone JH. Small-vessel and medium-vessel vasculitis. Arthritis Rheum. 2007; 57(8): 1552-9. PubMed

Vaglio A, Buzio C, Zwerina J. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): state of the art. Allergy. 2013; 68(3): 261-73. PubMed

Valent P, Klion AD, Horny H, Roufosse F, Gotlib J, Weller PF, Hellmann A, Metzgeroth G, Leiferman KM, Arock M, Butterfield JH, Sperr WR, Sotlar K, Vandenberghe P, Haferlach T, Simon H, Reiter A, Gleich GJ. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol. 2012; 130(3): 607-612.e9. PubMed

Medical Reviewers

Genzen, Jonathan R., MD, PhD, Co-Medical Director, Automated Core Laboratory at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Gleich, Gerald J., MD, Consultant, Immunodermatology at ARUP Laboratories; Professor, Dermatology and Medicine; Emeritus Professor, Pediatrics, University of Utah

Leiferman, Kristin M., MD, Consultant, Immunodermatology at ARUP Laboratories; Co-Director, Immunodermatology Laboratory, Professor of Dermatology, University of Utah

Tebo, Anne E., PhD, D(ABMLI), Medical Director, Immunology at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Last Update: November 2016