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
Diagnosis
Indications for Testing
Asthma with multiorgan systemic disease
Criteria for Diagnosis
Chapel Hill Consensus Conference (2012) | American College of Rheumatology (1990) | |
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Definition/Classification |
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Laboratory Testing |
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Histopathology |
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Clinical Signs/Symptoms |
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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: Thirty 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)
- CBC – may have hypereosinophilia (>10% or 1500 cells/µL) (Valent, 2012)
- 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
- Serum IgG levels – may be increased, but lack specificity
- 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
- Perinuclear ANCA (pANCA) with myeloperoxidase (MPO)+ – most common, but <50% are positive
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
- Prodromal phase
ARUP Laboratory Tests
Assess for presence of eosinophilia
May help in ruling out infectious process
Automated Cell Count/Differential
Screen for hematuria, proteinuria, RBC casts
Reflectance Spectrophotometry/Microscopy
Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)
Quantitative Immunoturbidimetry
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
Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay
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
Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay
Panel includes ANCA, IgG; MPO; and PR3
Nonspecific test used to detect inflammation associated with infections, cancers, and autoimmune diseases
Visual Identification
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
Semi-Quantitative Multiplex Bead Assay
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
Semi-Quantitative Multiplex Bead Assay
Medical Experts
Genzen

Gleich
Leiferman

Tebo

References
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Choosing Wisely
Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Dec 2020]
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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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Valent P, Klion AD, Horny HP, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol. 2012;130(3):607-612.e9.
Panel detects ANCA, MPO, and PR3