Welcome to AstraZeneca
Medical Information

The information provided on this site is intended for use by healthcare professionals practicing in the US. The dissemination of this information may be subject to different medical and regulatory requirements in other countries.

This web site is intended to help healthcare professionals practicing in the US and AstraZeneca authorized persons find scientifically balanced, evidence-based information about AstraZeneca drugs, submit a question, ask for field medical follow-up, and explore links to professional and patient support resources.

Are you a healthcare professional practicing in the United States?

I am an AstraZeneca authorized person

I am a payer or formulary decision-maker

I am neither (take me to AstraZeneca.com)

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

AstraZeneca Medical's ambition is to address unmet needs for people living with inflammatory diseases driven by eosinophilic inflammation.

Watch Eosinophils in Action in EGPA

What is EGPA?

EGPA is a complex, rare, multisystem disease characterized by necrotizing vasculitis and eosinophilic inflammation, which is associated with adult-onset asthma and nasal polyps.^1-3 The US incidence rate is estimated at 1 to 3 cases per 100,000 adults per year.⁴

EGPA is the rarest subgroup among the AAVs, although the majority of patients with EGPA are ANCA negative.^1,2

Characteristics of the 3 Diseases of AAV

AAV Diseases	Key clinical manifestations^1-3,5,6	ANCA positivity^2,7^,^a
EGPA	Asthma, eosinophilia, and nasal polyps are common^b Necrotizing vasculitis of small to medium-sized blood vessels and eosinophilic granulomatous inflammation	30-47%
MPA	Necrotizing arteritis involving small and medium arteries may be present Necrotizing glomerulonephritis is very common Inflammation that is not centered on vessels, including granulomatous inflammation, is absent Skin involvement is common	70-90%
GPA	Necrotizing glomerulonephritis and granulomatous and non-granulomatous extravascular inflammation are very common Nasal crusting, stuffiness and bleeding, and eye involvement are common	70-90%

^aANCA are autoantibodies directed against antigens found in the cytoplasmic granules of neutrophils and monocytes; ^bThese characteristics are rare in MPA and GPA.

What are Eosinophils?

Eosinophils are terminally differentiated granulocytes that have a role in inflammation and tissue injury in multiple diseases and across many organ systems.^8-10

Eosinophils can have reciprocal interactions with other immune cells to perpetuate chronic inflammation.^8,10 They exert inflammatory effects by releasing cytotoxic granules (eg, EDN, ECP, EPO, MBP), extracellular traps, and lipid body inflammatory mediators.¹⁰

Eosinophils contribute to inflammation both directly and indirectly³

Direct Mechanisms of Inflammation

An eosinophil producing eosinophil cationic protein and major basic protein. ECP is associated with cardiotoxicity and fibrogenesis. MBP is associated with airway remodeling.

Cytotoxicity and Microenvironment Manipulation

Eosinophils can produce diverse cytotoxic proteins that cause organ damage through direct cytotoxic effects.¹¹

Eosinophils produce thrombin and can induce a prothrombotic environment.

Indirect Mechanisms of Inflammation

An eosinophil cell interacting with dendritic cell, ILC2, neutrophil, basophil and T cell.

Chronic Inflammation

Eosinophils can drive cytotoxicity by interacting with other inflammatory cell types to perpetuate chronic inflammation.¹¹

Ischemic Damage

Eosinophils may contribute to ischemic damage via inflammation and thrombosis, irrespective of ANCA status.^3,8,12

Eosinophils Are Involved in All Phases of EGPA

These phases may not appear in every patient, may not appear in a defined order, or may partially overlap.^7,13

Characteristics

Severe adult-onset asthma^7,13
Upper respiratory symptoms^a
Non-specific symptoms^b

Role of Eosinophils

Increased numbers of eosinophils contribute to respiratory and ENT manifestations³

Characteristics

Peripheral blood eosinophilia^13,14^,c
Tissue eosinophilia, particularly in the lungs, heart, and GI system

Role of Eosinophils

Eosinophilic infiltration contributes to organ damage³

Characteristics

Systemic blood vessel vasculitis with granulomatous inflammation^13,14

Role of Eosinophils

Eosinophilic vasculitis of small arteries and veins³
Extravascular eosinophilic granulomas contribute to organ damage

^aSuch as allergic rhinitis and nasal polyps.

^bIncluding malaise, fever, migrating polyarthralgia, and weight loss.

^cTypically defined as 5.0-9.0 x 10⁹/L.

Spectrum of Clinical Manifestations of EGPA

Although EGPA has historically been segregated into 2 distinct phenotypes based on the underlying pathophysiological mechanisms, it may present as a spectrum of disease phenotypes with overlapping pathological mechanisms that cannot be defined by a single serological or clinical parameter.^7,11

The spectral distribution of clinical features in predominantly eosinophilic (left side) and vasculitic mechanisms (right side) of organ damage seen in EGPA. The left side is predominantly clinical manifestations associated with eosinophilic inflammation and moving to the right, it shifts to predominantly vasculitis associated clinical manifestations. From left to right, there is a lung indicating asthma and pulmonary infiltration, a heart indicating myocarditis and pericardial effusion, in the middle is the GI tract with stomach indicating GI involvement, following is a neuron indicating mononeuritis multiplex and the last is a kidney indicating rapidly progressive glomerulonephritis.

Note: Mononeuritis multiplex is a form of peripheral neuropathy, involving damage to at least 2 different areas of the peripheral nervous system.

Abbreviations

AAV = antineutrophil cytoplasmic antibody-associated vasculitis

;

ANCA = antineutrophil cytoplasmic antibody

;

ECP = eosinophilic cationic protein

;

EDN = eosinophil-derived neurotoxin

;

EGPA = eosinophilic granulomatosis with polyangiitis

;

ENT = ear, nose, and throat

;

EPO = eosinophil peroxidase

;

GI = gastrointestinal

;

GPA = granulomatosis with polyangiitis

;

ILC2 = type 2 innate lymphoid cell(s)

;

MBP = major basic protein

;

MPA = microscopic polyangiitis

;

US = United States

References

1. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Arthritis Rheum. 2013;65(1):1-11. doi:10.1002/art.37715

2. Furuta S, Iwamoto T, Nakajima H. Update on eosinophilic granulomatosis with polyangiitis. Allergol Int. 2019;68(4):430-436. doi:10.1016/j.alit.2019.06.004

3. Khoury P, Grayson PC, Klion AD. Eosinophils in vasculitis: characteristics and roles in pathogenesis. Nat Rev Rheumatol. 2014;10(8):474-483. doi:10.1038/nrrheum.2014.98

4. Vasculitis Foundation. Pediatric vasculitis. Who gets EGPA? Vasculitis Foundation website. https://www.vasculitisfoundation.org/pediatrics-vasculitis/pediatric-types/pediatric-eosinophilic-granulomatosis-with-polyangiitis/

5. Yates M, Watts R. ANCA-associated vasculitis. Clin Med (Lond). 2017;17(1):60-64. doi:10.7861/clinmedicine.17-1-60

6. Chung SA, Seo P. Microscopic polyangiitis. Rheum Dis Clin North Am. 2010;36(3):545-558. doi:10.1016/j.rdc.2010.04.003

7. Trivioli G, Terrier B, Vaglio A. Eosinophilic granulomatosis with polyangiitis: understanding the disease and its management. Rheumatology (Oxford). 2020;59(suppl 3):iii84-iii94. doi:10.1093/rheumatology/kez570

8. Ramirez GA, Yacoub MR, Ripa M, et al. Eosinophils from physiology to disease: a comprehensive review. BioMed Res Int. 2018;2018:9095275. doi:10.1155/2018/9095275

9. Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol. 2013;13(1):9-22. doi:10.1038/nri3341

10. Jacobsen EA, Jackson DJ, Heffler E, et al. Eosinophilic knockout humans: uncovering the role of eosinophils through eosinophil-directed biologic therapies. Annu Rev Immunol. 2021;39:719-757. doi:10.1146/annurev-immunol-093019-125918

11. Fagni F, Bello F, Emmi G. Eosinophilic granulomatosis with polyangiitis: dissecting the pathophysiology. Front Med (Lausanne). 2021;8:627776. doi:10.3389/fmed.2021.627776

12. Koike H, Nishi R, Furukawa S, et al. In vivo visualization of eosinophil secretion in eosinophilic granulomatosis with polyangiitis: an ultrastructural study. Allergol Int. 2022;71(3):373-382. doi:10.1016/j.alit.2022.02.009

13. Chakraborty RK, Aeddula NR. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). In: StatPearls [Internet]. StatPearls Publishing; March 23, 2023.

14. Gioffredi A, Maritati F, Oliva E, et al. Eosinophilic granulomatosis with polyangiitis: an overview. Front Immunol. 2014;5:549. doi:10.3389/fimmu.2014.00549

US-88106, US-91275 Last Updated 7/24

Welcome to AstraZeneca Medical Information

Direct Mechanisms of Inflammation

Indirect Mechanisms of Inflammation

Abbreviations

References

Welcome to AstraZeneca
Medical Information