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PubMed This is a summary of 16 peer-reviewed journal articles Updated
Rheumatology

The Biology of EGPA: Eosinophils, ANCA, and Look-Alikes

At a Glance

EGPA is driven by two main biological forces: hyperactive eosinophils that damage tissues, and ANCA antibodies that inflame blood vessels. Knowing whether you are ANCA-positive or ANCA-negative helps your doctors predict which organs are most at risk and choose the most effective treatment.

EGPA is a unique disease because it essentially behaves like two different conditions rolled into one. While all patients with EGPA share a history of asthma and high levels of white blood cells called eosinophils, the underlying biology can differ significantly depending on whether a patient is “ANCA-positive” or “ANCA-negative” [1][2].

The Two Driving Forces of EGPA

The damage in EGPA is caused by two main biological “engines” that can run independently or at the same time:

  1. Eosinophil-Mediated Damage: Eosinophils are white blood cells meant to fight parasites. In EGPA, they become hyperactive and flood into tissues like the lungs, heart, and digestive tract [3]. They release toxic proteins that cause direct damage and can even clog small blood vessels [1][2].
  2. ANCA-Mediated Vasculitis: Roughly 30% to 40% of patients produce ANCA (anti-neutrophil cytoplasmic antibodies) [4][5]. These are “autoantibodies” that mistakenly tell the immune system to attack the walls of the blood vessels, causing necrotizing vasculitis—a severe type of inflammation that can cut off blood flow to vital organs [1][3].

ANCA-Positive vs. ANCA-Negative

Your ANCA status (most often MPO-ANCA) provides your medical team with a roadmap of which symptoms to watch for most closely [1][6].

  • ANCA-Positive (MPO+): Associated with true blood vessel inflammation, a higher risk of kidney inflammation, very common nerve damage, lower heart risk, and higher risk of vasculitic flares [1][7][8][9].
  • ANCA-Negative: Associated more with tissue infiltration by eosinophils, a lower kidney risk, lower nerve damage risk, but a higher risk of heart muscle inflammation, with flares often driven by asthma and eosinophils [2][7][10][11].

Look-Alike Conditions

Because EGPA involves asthma and high eosinophils, it can be confused with other rare diseases. Doctors rule these out using specific antibody blood tests, imaging, and tissue biopsies to ensure you get the right treatment [12][13].

  • GPA (Granulomatosis with Polyangiitis): Formerly Wegener’s, this is also a vasculitis but rarely involves asthma. Doctors rule this out if you test positive for PR3-ANCA instead of MPO-ANCA, and if you have severe nose/ear cartilage damage without high eosinophils [12].
  • HES (Hypereosinophilic Syndrome): This condition involves high eosinophils and organ damage, but without the blood vessel inflammation or the characteristic asthma seen in EGPA. Doctors may use genetic testing or bone marrow biopsies to rule this out [14][13].
  • IgG4-Related Disease: This is an inflammatory condition that can cause swelling in organs. It lacks the ANCA markers and has completely different cellular findings on a biopsy [15][16].

Common questions in this guide

What is the difference between ANCA-positive and ANCA-negative EGPA?
ANCA-positive EGPA involves autoantibodies that cause severe blood vessel inflammation, leading to a higher risk of kidney issues and nerve damage. ANCA-negative EGPA is primarily driven by high eosinophil levels and carries a higher risk of heart muscle inflammation.
Why is it important for my doctor to know my ANCA status?
Your ANCA status acts as a roadmap for your medical team. It helps them predict which organs need the closest monitoring, such as your heart versus your kidneys, and influences which medications will work best for your specific disease type.
How do doctors tell the difference between EGPA and GPA?
While both are types of blood vessel inflammation, EGPA typically involves severe asthma and high levels of eosinophils. Doctors use blood tests to look for different markers, as GPA usually tests positive for PR3-ANCA rather than the MPO-ANCA typically seen in EGPA.
Can my EGPA be driven entirely by eosinophils?
Yes, in ANCA-negative cases, the disease is primarily driven by hyperactive eosinophils. These white blood cells flood into tissues like the lungs and heart, releasing toxic proteins that cause inflammation and damage without the traditional blood vessel-attacking antibodies.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Am I ANCA-positive or ANCA-negative, and specifically which type of ANCA (MPO or PR3) was detected?
  2. 2.Based on my ANCA status, should we be more focused on monitoring my heart health or my kidney and nerve function?
  3. 3.How did you rule out other conditions like GPA or Hypereosinophilic Syndrome in my case?
  4. 4.Does my ANCA status change the type of medication you recommend, such as choosing between rituximab or mepolizumab?
  5. 5.If my ANCA status is negative, does that mean my disease is driven entirely by eosinophils?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (16)
  1. 1

    Differential clinicopathologic features of EGPA-associated neuropathy with and without ANCA.

    Nishi R, Koike H, Ohyama K, et al.

    Neurology 2020; (94(16)):e1726-e1737 doi:10.1212/WNL.0000000000009309.

    PMID: 32217776
  2. 2

    Eosinophilic Granulomatosis With Polyangiitis: Dissecting the Pathophysiology.

    Fagni F, Bello F, Emmi G

    Frontiers in medicine 2021; (8()):627776 doi:10.3389/fmed.2021.627776.

    PMID: 33718405
  3. 3

    In vivo visualization of eosinophil secretion in eosinophilic granulomatosis with polyangiitis: An ultrastructural study.

    Koike H, Nishi R, Furukawa S, et al.

    Allergology international : official journal of the Japanese Society of Allergology 2022; (71(3)):373-382 doi:10.1016/j.alit.2022.02.009.

    PMID: 35428588
  4. 4

    Eosinophilic granulomatosis with polyangiitis: case report and literature review.

    Alam V, Nanzer AM

    Breathe (Sheffield, England) 2022; (18(4)):220170 doi:10.1183/20734735.0170-2022.

    PMID: 36865937
  5. 5

    Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status.

    Lyons PA, Peters JE, Alberici F, et al.

    Nature communications 2019; (10(1)):5120 doi:10.1038/s41467-019-12515-9.

    PMID: 31719529
  6. 6

    [ANCA-associated small-vessel vasculitides].

    Bayrashevskaya AV, Degtyareva ND, Radenska-Lopovok SG

    Arkhiv patologii 2022; (84(1)):50-58 doi:10.17116/patol20228401150.

    PMID: 35166479
  7. 7

    Renal involvement in eosinophilic granulomatosis with polyangiitis (EGPA): a multicentric retrospective study of 63 biopsy-proven cases.

    Durel CA, Sinico RA, Teixeira V, et al.

    Rheumatology (Oxford, England) 2021; (60(1)):359-365 doi:10.1093/rheumatology/keaa416.

    PMID: 32856066
  8. 8

    Severe mononeuritis multiplex in a patient with eosinophilic granulomatosis with polyangiitis.

    Kalinova D, Kukushev G, Kolarov Z, Rashkov R

    Reumatologia 2019; (57(5)):288-291 doi:10.5114/reum.2019.89522.

    PMID: 31844342
  9. 9

    ANCA-negative EGPA: only eosinophils without vasculitis? Insights from anti-T2 biologics.

    Piga MA, Fraticelli P, Antonicelli L, et al.

    Frontiers in immunology 2023; (14()):1325299 doi:10.3389/fimmu.2023.1325299.

    PMID: 38090592
  10. 10

    Antineutrophil Cytoplasmic Antibodies and Organ-Specific Manifestations in Eosinophilic Granulomatosis with Polyangiitis: A Systematic Review and Meta-Analysis.

    Chang HC, Chou PC, Lai CY, Tsai HH

    The journal of allergy and clinical immunology. In practice 2021; (9(1)):445-452.e6 doi:10.1016/j.jaip.2020.07.038.

    PMID: 32771687
  11. 11

    Clinical Characteristics of EGPA Patients in Comparison to GPA Subgroup with Increased Blood Eosinophilia from POLVAS Registry.

    Drynda A, Padjas A, Wójcik K, et al.

    Journal of immunology research 2024; (2024()):4283928 doi:10.1155/2024/4283928.

    PMID: 38699219
  12. 12

    Significance of PR3-ANCA positivity in eosinophilic granulomatosis with polyangiitis (Churg-Strauss).

    Papo M, Sinico RA, Teixeira V, et al.

    Rheumatology (Oxford, England) 2021; (60(9)):4355-4360 doi:10.1093/rheumatology/keaa805.

    PMID: 33347592
  13. 13

    A new index for distinguishing hypereosinophilic syndrome and antineutrophil cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis.

    Ahn SS, Yoo J, Park YB, et al.

    Asian Pacific journal of allergy and immunology 2023; (41(3)):244-252 doi:10.12932/AP-080420-0805.

    PMID: 33068368
  14. 14

    When inflammation is not just inflammation-A review of systemic diseases of the nose and sinuses part 2: Granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis.

    Cler SJ, Ogden MA, Farrell NF, et al.

    American journal of otolaryngology 2024; (45(3)):104207 doi:10.1016/j.amjoto.2023.104207.

    PMID: 38176206
  15. 15

    ANCA-associated vasculitis and IgG4-related disease overlap syndrome: a case report and literature review.

    Faz-Muñoz D, Hinojosa-Azaola A, Mejía-Vilet JM, et al.

    Immunologic research 2022; (70(4)):550-559 doi:10.1007/s12026-022-09279-8.

    PMID: 35449491
  16. 16

    Definite IgG4-related disease had no overlap with eosinophilic granulomatosis with polyangiitis in Korean patients: a pilot study in one centre.

    Yoo J, Song JJ, Park YB, Lee SW

    Clinical rheumatology 2020; (39(10)):3009-3015 doi:10.1007/s10067-020-05104-5.

    PMID: 32367405

This page explains the biology and ANCA testing of EGPA for educational purposes only. Always consult your healthcare provider to interpret your specific lab results and diagnosis.

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