Kidney nontumor / medical renal
Vascular disease
Vasculitis
Eosinophilic granulomatosis with polyangiitis (EGPA)
Authors: Aubre Gilbert, M.D., Nicole K. Andeen, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 6 June 2022
Last staff update: 24 September 2024
Copyright: 2019-2024, PathologyOutlines.com, Inc.
PubMed Search: Churg-Strauss syndrome kidney
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Prognostic factors | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Immunofluorescence description | Immunofluorescence images | Positive stains | Electron microscopy description | Electron microscopy images | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2 | Board review style question #3 | Board review style answer #3Cite this page: Gilbert A, Andeen NK. Eosinophilic granulomatosis with polyangiitis (EGPA). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneychurgstrauss.html. Accessed December 3rd, 2024.
Definition / general
- Systemic, small to medium vessel, eosinophil rich granulomatous vasculitis
Essential features
- Rare, systemic, small to medium vessel granulomatous vasculitis (Allergy 2013;68:261)
- Diagnosed clinically by the presence of
- Asthma
- Blood eosinophilia exceeding 1,500/mm3
- Evidence of vasculitis involving 2 or more organs
- Renal manifestations occur in 45% of those with the diagnosis and include
- Pauci-immune crescentic glomerulonephritis
- Renal arteritis, arteriolitis and medullary angiitis
- Microscopic features include
- Glomerular crescents
- Fibrinoid necrosis
- Necrotizing vasculitis
- Extravascular eosinophil rich granulomatous inflammation
- Associated with HLA-DRB4 and antineutrophil cytoplasmic antibodies (ANCA)
Terminology
- Eosinophilic granulomatosis with polyangiitis (EGPA), Churg-Strauss syndrome
ICD coding
- ICD-10: M30.1 - polyarteritis with lung involvement (Churg-Strauss)
Epidemiology
- Annual incidence of 0.5 - 4.2 cases per 1 million people (Best Pract Res Clin Rheumatol 2005;19:191)
- Prevalence of 11 - 14 cases per 1 million adults (Arthritis Rheum 2004;51:92)
- Age 40 - 60 years, mean age at diagnosis is ~49 years (Ann Rheum Dis 2013;72:1011)
- Pediatric cases have been described (Semin Arthritis Rheum 2009;39:108)
- No identified gender predominance, ethnic predisposition or familial pattern
- Renal manifestations occur in 45% of patients with the diagnosis (N Engl J Med 1997;337:1512)
Sites
- Upper airway tract and lungs
- Kidneys
- Peripheral nervous system
- Gastrointestinal tract
- Heart
- Skin
Pathophysiology
- Immune dysregulation
- Eosinophil infiltration (Ann N Y Acad Sci 2005;1051:121, Rheumatology (Oxford) 2008;47:804)
- Activated Th2 cells release cytokines IL4, IL13 and IL5
- IL4, IL13 and IL5 promote eotaxin3 release from endothelial and epithelial cells
- Eotaxin3 brings eosinophils from the blood stream into tissue
- Activated eosinophils secrete granules containing eosinophil basic protein and eosinophil derived neurotoxin, damaging tissue
- Activated eosinophils secrete IL25, which activates Th2
- Dysregulation of the following immune cells are also implicated: Th1, Th17, IL17A, B cells
- ANCA induced endothelial damage: ANCA leads to neutrophil degranulation and tissue damage (Ann N Y Acad Sci 2005;1051:121, Rheumatology (Oxford) 2008;47:804)
Etiology
- Considered an idiopathic condition (Ann N Y Acad Sci 2005;1051:121, Rheumatology (Oxford) 2008;47:804)
- Exposure to allergens or drugs (Autoimmun Rev 2012;12:235)
- Propylthiouracil, hydralazine, minocycline, penicillamine (Int J Rheumatol 2009;2009:504105)
Clinical features
- Strongly associated with asthma
- Associated with HLA-DRB4
- 40 - 70% of patients have antimyeloperoxidase ANCA positivity (Arthritis Rheum 2005;52:2926, N Engl J Med 1997;337:1512)
- ANCA positivity is associated with renal and peripheral nervous system disease (Arthritis Care Res (Hoboken) 2016;68:374)
- ANCA positivity is less common in eosinophilic granulomatosis with polyangiitis than in granulomatosis with polyangiitis (Arthritis Rheum 2005;52:2926)
-
- Symptomatology
- Prodromal phase (months to years) (Allergy 2013;68:261)
- Asthma, rhinitis arthralgia, fever, malaise, weight loss, nasal polyps, chronic sinusitis
- Eosinophilic phase (Allergy 2013;68:261)
- Peripheral eosinophilia and eosinophilic infiltrative disease involving lung, heart or gastrointestinal tract
- Vasculitic phase (Allergy 2013;68:261)
- Vasculitis with peripheral neuropathy, renal and skin involvement
- Usually within 3 years of onset of asthma, though may be delayed for decades (N Engl J Med 1997;337:1512)
- Prodromal phase (months to years) (Allergy 2013;68:261)
Diagnosis
- Clinical diagnosis
- Biopsy of an affected organ with microscopic confirmation: characteristic pathological changes are helpful but not essential to make the diagnosis
- In 1984, new clinical diagnostic criteria were proposed (Medicine (Baltimore) 1984;63:65)
- 3 diagnostic criteria, all must be present
- Asthma
- Blood eosinophilia exceeding 1,500/mm3 or > 10%
- Evidence of vasculitis involving 2 or more organs
- 3 diagnostic criteria, all must be present
Laboratory
- Peripheral eosinophilia (usually > 1,500 cells/μl or > 10%) is present in active disease
- Perinuclear / antimyeloperoxidase ANCA
- Renal involvement: hematuria, proteinuria, elevated serum creatinine
- Emerging biomarkers: eotaxin3 (at cutoff level of 80 pg/ml, the sensitivity and specificity of eotaxin3 for the diagnosis was 87.5% and 98.6%, respectively) (Rheumatology (Oxford) 2011;50:1737)
Prognostic factors
- Overall 5 year survival rate is 97% (Medicine (Baltimore) 2011;90:19)
- The following criteria are associated with a higher 5 year mortality (Medicine (Baltimore) 2011;90:19)
- Age > 65
- Cardiac symptoms
- Gastrointestinal involvement
- Renal insufficiency (serum creatinine > 150 μmol/l)
- Lack of ear, nose and throat manifestations
Case reports
- 51 year old man presented with a stomach perforation (Case of the month #541)
- 54 year old man with pauci-immune necrotizing and crescentic glomerulonephritis, accompanied by acute coronary syndrome due to vasospasm (Am J Kidney Dis 2010;56:e5)
- 58 year old man with polyneuropathy, peripheral eosinophilia, pauci-immune necrotizing and crescentic glomerulonephritis, small bowel eosinophilic vasculitis, without asthma (Saudi J Kidney Dis Transpl 2014;25:402)
- 59 year old woman with Churg-Strauss syndrome and eosinophilic tubulointerstitial nephritis (Intern Med 2012;51:1555)
- 67 year old woman with pauci-immune necrotizing and crescentic glomerulonephritis, tubulointerstitial nephritis with eosinophils and peripheral blood eosinophilia without asthma (Am J Kidney Dis 1998;31:1032)
Treatment
- Immunosuppressants (e.g. cyclophosphamide, glucocorticoids, azathioprine) (Postepy Hig Med Dosw (Online) 2016;70:654, Eur J Rheumatol 2016;3:122)
- B cell depleting agent rituximab (several case series) (Ann Rheum Dis 2016;75:396)
- Anti-IL5 antibody mepolizumab (efficacy has been described in small clinical trials) (J Allergy Clin Immunol 2010;125:1336)
Microscopic (histologic) description
- Systemic (Jennette: Heptinstall's Pathology of the Kidney, 7th Edition, 2015):
- Necrotizing vasculitis and extravascular eosinophil rich granulomatous inflammation
- Kidney (Jennette: Heptinstall's Pathology of the Kidney, 7th Edition, 2015):
- Necrotizing and crescentic glomerulonephritis, without significant immune complex deposition
- Fibrinoid necrosis of arteries
- Medullary angiitis
- Tubulointerstitial nephritis with eosinophils
Microscopic (histologic) images
Contributed by Nicole K. Andeen, M.D., Patrick A. Maher, M.D., Juhi D. Mahadik, M.B.B.S., M.D. and Naziheh Assarzadegan, M.D. (Case #541)
Crescent
Arteritis
Medullary angiitis
Immunofluorescence description
- Variable staining for immunoglobulin (< 2+ on a scale from 0 - 4+) (Jennette: Heptinstall's Pathology of the Kidney, 7th Edition, 2015)
- Variable staining for complement components
- Immunoglobulin or complement staining often focally and segmentally present in areas of necrosis / crescents (nonspecific)
Immunofluorescence images
Contributed by Nicole K. Andeen, M.D.
Fibrin / fibrinogen
Positive stains
- Fibrinoid necrosis is fuchsinophilic with trichrome staining (Jennette: Heptinstall's Pathology of the Kidney, 7th Edition, 2015)
- Disruption of the glomerular basement membrane in areas of fibrinoid necrosis highlighted with Jones methenamine silver (JMS) stain
Electron microscopy description
- Scant or absent immune complex deposits (Jennette: Heptinstall's Pathology of the Kidney, 7th Edition, 2015)
- Elongated aggregations of fibrin (fibrin tactoids)
- May have breaks in glomerular basement membrane
- May have capillaries with endothelial swelling, necrosis, marginating neutrophils
Electron microscopy images
Contributed by Nicole K. Andeen, M.D.
Fibrin tactoids
Sample pathology report
- Kidney, biopsy:
- Focally necrotizing and crescentic glomerulonephritis, pauci-immune complex type (see comment)
- Comment: Consistent with this patient's positive ANCA, the acute renal insufficiency and hematuria are due to a focally necrotizing and crescentic glomerulonephritis, pauci-immune complex (vasculitic) type. Active injury is manifest as segmental necrosis or cellular crescents in 36% of glomeruli. Chronic injury is manifest as segmental glomerulosclerosis / scarring in 9% of glomeruli, global glomerulosclerosis in 9% and approximately 10% tubular atrophy and interstitial fibrosis. Extraglomerular vasculitis is not identified.
Differential diagnosis
- Etiologies of necrotizing and crescentic glomerulonephritis, pauci-immune complex (vasculitic) type are generally best distinguished clinically, not histologically (J Autoimmun 2014;48:99)
- Granulomatosis with polyangiitis:
- No asthma, eosinophilia or nondestructive sinus involvement
- Has anti-PR3 (versus antimyeloperoxidase antineutrophil cytoplasmic antibodies for eosinophilic granulomatosis with polyangiitis)
- Polyarteritis nodosa:
- No asthma, eosinophilia or lung infiltrates
- Hypereosinophilic syndrome:
- No vasculitis, no antineutrophil cytoplasmic antibodies, lower eosinophil count
- Helminth infection:
- No systemic vasculitis
Additional references
Board review style question #1
A 56 year old man presents with acute kidney injury and positive antineutrophil cytoplasmic antibodies (ANCA). Kidney biopsy demonstrates the above finding in 30% of glomeruli, with trace granular mesangial staining for IgA by immunofluorescence microscopy and no deposits by electron microscopy. What is the best diagnosis?
- ANCA associated glomerulonephritis superimposed on IgA nephropathy
- Antiglomerular basement membrane antibody (anti-GBM) disease
- Crescentic IgA nephropathy
- Focally necrotizing and crescentic glomerulonephritis, pauci-immune complex type, consistent with ANCA associated disease
Board review style answer #1
D. Focally necrotizing and crescentic glomerulonephritis, pauci-immune complex type, consistent with ANCA associated disease
Comment Here
Reference: Churg-Strauss syndrome
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Reference: Churg-Strauss syndrome
Board review style question #2
Criteria for the diagnosis of eosinophilic granulomatosis with polyangiitis / Churg-Strauss syndrome include
- Asthma, peripheral eosinophilia, vasculitis
- Elevated eotaxin levels
- Kidney biopsy demonstrating pauci-immune complex mediated necrotizing and crescentic glomerulonephritis
- Positive antimyeloperoxidase antineutrophil cytoplasmic antibodies (MPO ANCA)
Board review style answer #2
Board review style question #3
Which antibody is most commonly associated with eosinophilic granulomatosis with polyangiitis?
- Antimitochondrial antibody (AMA)
- Antinuclear antibody (ANA)
- MPO-Anti neutrophil cytoplasmic antibody (P-ANCA)
- PR3-Anti neutrophil cytoplasmic antibody (C-ANCA)
Board review style answer #3
C. MPO-Anti neutrophil cytoplasmic antibody (P-ANCA) is the most common antibody associated with eosinophilic granulomatosis with polyangiitis.
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Reference: Churg-Strauss syndrome
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Reference: Churg-Strauss syndrome
