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 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)
  • 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  • Relapses are common, especially if maintenance treatments are fully withdrawn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

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

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

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

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

Related Tests

Guidelines

American Society for Clinical Pathology. Choosing Wisely - Five Things Physicians and Patients Should Question. An initiative of the ABIM Foundation. [Last revision Feb 2015; Accessed: Jan 2016]

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 M, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG I, 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

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

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

Medical Reviewers

Last Update: December 2015