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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: 19 December 2023

Copyright: 2019-2024, PathologyOutlines.com, Inc.

PubMed Search: Churg-Strauss syndrome kidney

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Table of Contents

Cite this page: Gilbert A, Andeen NK. Eosinophilic granulomatosis with polyangiitis (EGPA). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneychurgstrauss.html. Accessed April 25th, 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)
- 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)

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

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

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.

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

Autoimmun Rev 2015;14:341

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

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

A. Asthma, peripheral eosinophilia, vasculitis

Comment Here

Reference: Churg-Strauss syndrome

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