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).

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Clinical Overview

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 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)
  - Preferred test to detect inflammatory processes (Choosing Wisely: 20 Things Physicians and Patients Should Question, 2017; American Society for Clinical Pathology)
  - Usually increases in vasculitic phase
  - If CRP not available, order erythrocyte sedimentation rate (ESR)
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

Vasculitis
- Granulomatosis with polyangiitis (formerly Wegener granulomatosis)
- Microscopic polyangiitis
- Polyarteritis nodosa
- 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
Eosinophil-associasted syndromes
- Bronchopulmonary aspergillosis
- Hypersensitivity pneumonitis
- Hypereosinophilic syndrome
- Eosinophil-associasted pneumonia (acute or chronic)
- Bronchocentric granulomatosis
Drug reactions – most common
- Antibiotics
- Antiasthmatics
- Anticonvulsants

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 Lab Tests

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

Medical Experts

Genzen, Jonathan R., MD, PhD, Laboratory Section Chief, Clinical Chemistry, and Medical Director, Automated Core Laboratory, at ARUP Laboratories; Associate 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

References

Guidelines

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
Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Mar 2019]
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

Resources from the ARUP Institute for Clinical and Experimental Pathology®

Filkins LM, Gaston DC, Mathison B, Smith T, Couturier MR, Murphy RD, Ciarkowski C, Hanson KE, Cariello PF. Biliary With Cholecystitis and Extensive Portal Vein Thrombosis. Open Forum Infect Dis. 2017; 4(4): ofx217. PubMed

Testing Algorithms

Vasculitis in Adults Testing Algorithm

Read more about Vasculitis in Adults Testing Algorithm

Last Update: December 2018

Eosinophilic Granulomatosis with Polyangiitis - EGPA

Diagnosis

Indications for Testing

Criteria for Diagnosis

Laboratory Testing

Histopathology

Imaging Studies

Prognosis

Differential Diagnosis

Background

Epidemiology

Pathophysiology

Clinical Presentation

ARUP Lab Tests

Medical Experts

References

Guidelines

General References

Resources from the ARUP Institute for Clinical and Experimental Pathology®

Vasculitis in Adults Testing Algorithm

ARUP Laboratories

ARUP Websites

ARUP Consult


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	Eosinophilic Granulomatosis with Polyangiitis - EGPA. ARUP Consult^©. Retrieved April 17, 2019, from: https://arupconsult.com/content/eosinophilic-granulomatosis-polyangiitis

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Eosinophilic Granulomatosis with Polyangiitis - EGPA

Diagnosis

Indications for Testing

Criteria for Diagnosis

Laboratory Testing

Histopathology

Imaging Studies

Prognosis

Differential Diagnosis

Background

Epidemiology

Pathophysiology

Clinical Presentation

ARUP Lab Tests

Medical Experts

References

Guidelines

General References

Resources from the ARUP Institute for Clinical and Experimental Pathology®

Vasculitis in Adults Testing Algorithm

ARUP Laboratories

ARUP Websites

ARUP Consult