EGPA (eosinophilic granulomatosis with polyangiitis) is a rare, chronic inflammatory disease characterized by eosinophil-rich granulomatous inflammation and small‑ to medium‑sized vessel vasculitis, associated with adult-onset asthma, eosinophilia and multi-organ involvement.1–6 Learn more about the role of eosinophils in EGPA, their contribution to disease pathology, and the clinical impact of current treatment approaches in this educational module.
EGPA is a systemic inflammatory disorder characterized by late-onset asthma, peripheral eosinophilia, and small- to medium-vessel vasculitis.1–4 While traditionally classified as a form of ANCA-associated vasculitis, EGPA is distinguished from other forms in this group by its association with peripheral eosinophilia, asthma, and chronic rhinosinusitis with nasal polyps.3,8 Although classified as an ANCA-associated vasculitis, the majority of patients (60–70%) are ANCA negative.3
EGPA is now understood as a complex, multi-phase disease.2,4,12 Disease evolution typically follows a step-wise pattern, beginning with a prodromal phase characterized by asthma and sinusitis.12 After a variable period of time, patients may progress to an eosinophilic phase, categorized by marked eosinophilia with lung tissue infiltration, gastrointestinal involvement, and eosinophilic cardiomyopathy.12 Some patients then progress to a vasculitic phase, with manifestations including glomerulonephritis, palpable purpura, and neuropathy.2,12 Importantly, disease progression may not occur, with some patients not experiencing any eosinophilic or vasculitic manifestations. When progression does occur, it can be at varying speeds, with disease phases sometimes overlapping.12 This heterogeneity in disease presentation and progression can contribute to diagnostic delays.2,12
Asthma is a defining feature of EGPA, affecting more than 95% of patients and often preceding systemic disease by several years.2,3 This asthma is frequently severe, adult-onset, and difficult to control.2,3 Chronic rhinosinusitis and nasal polyposis were also highly prevalent, reflecting eosinophilic inflammation throughout the upper and lower airways.3,8
Beyond the airways, EGPA is a multisystem disease with manifestations driven by eosinophilic tissue infiltration, immune-mediated vascular inflammation, or a combination of both.2,4,6,7,12
Clinical manifestations of EGPA are therefore diverse and frequently severe:2
The breadth of organ involvement highlights the systemic nature of EGPA and the cumulative burden imposed by eosinophilic inflammation and other disease mechanisms.10,12 Even when life-threatening manifestations are avoided, ongoing symptoms such as asthma, sinonasal disease, peripheral neuropathy, and fatigue represent a high disease burden.10
Importantly, EGPA is a chronic and relapsing condition.10,12 While survival has improved with modern treatment approaches, many patients experience recurrent disease flares, progressive organ damage, or persistent symptoms over time.1 Disease activity may fluctuate independently across organ systems, with airway disease often remaining active even when vasculitic features are controlled.12,13 This relapsing-remitting course contributes to long-term morbidity and underpins the need for sustained disease control strategies.10
Eosinophils are recognized as key effector cells in EGPA, where they accumulate in multiple organs, contributing directly and indirectly to tissue injury and the amplification of local inflammatory responses.14
Eosinophils induce direct tissue damage through the release of diverse cytotoxic proteins, including MBP, ECP, and EPX.14 These proteins exert direct cytotoxic effects on various cell types, including epithelial cells, endothelial cells, cardiomyocytes, and neural tissue, explaining the diverse organ involvement observed in EGPA.14,15
Eosinophils also interact dynamically with their local micro-environment, engaging with endothelial cells, fibroblasts, smooth muscle cells, and immune cells.9,14,16,17 Through these interactions, eosinophils can promote tissue remodeling and fibrosis, and sustain inflammatory signaling, particularly within the airways and myocardium.14 Eosinophils can also induce a prothrombotic environment through several mechanisms, including increased expression of adhesion molecules, tissue factor, and vasoactive substances, leading to increased coagulation.14
Beyond their capacity to cause direct tissue damage, eosinophils contribute to organ-specific damage through the indirect mechanisms of chronic inflammation and ischemic damage.7,18
Eosinophils contribute to chronic inflammation by interacting locally with numerous inflammatory and resident cell types, including T cells, mast cells, neutrophils, dendritic cells, and type 2 innate lymphoid cells.5,9,14 These interactions create a self-sustaining inflammatory microenvironment in which eosinophils both respond to, and propagate, inflammatory signals.12,19 In the airways, this process contributes to persistent asthma symptoms, airway hyperresponsiveness, and structural remodeling, even when systemic inflammatory markers appear controlled.18 Eosinophils also participate in the inflammation of vessel walls and may thereby play a role in the vasculitis-related ischemia of downstream tissues such as nerves.7
Chronic eosinophil-driven inflammation and vascular injury can persist over time, contributing to cumulative organ damage and relapse.3
Clinical practice continues to rely on peripheral blood eosinophil counts as a biomarker in EGPA, with consistently elevated eosinophil levels (typically absolute count ≥1000 cells/µL) in patients presenting with adult-onset asthma, chronic rhinosinusitis, or neuropathy as a strong diagnostic clue.20 High eosinophil counts are associated with systemic manifestations in EGPA, including increased likelihood of extrapulmonary disease and peripheral nerve involvement.20 Eosinophil counts are generally lower in patients treated with SCS or biologic therapies, in whom a lower absolute eosinophil count of ≥500 cells/µL may be used as a threshold to suspect EGPA.21,22
Beyond traditional measures such as BEC, there is growing interest in the potential role of eosinophil-derived proteins as clinical biomarkers.9 Galectin-10, also known as CLC, and eosinophil-derived granule proteins, such as ECP and EDN, are elevated in the serum of patients with active EGPA compared with those in remission.9 Upon normalization of serum concentrations by BEC, Galectin-10 demonstrated the strongest relationship with disease activity, positively correlating with BVAS score (p<0.0001), therefore underscoring its potential as a biomarker of active disease.9
Systemic corticosteroids, particularly OCS, have historically formed the backbone of EGPA disease management due to their rapid and broad anti-inflammatory effects.10 In some patients, additional immunosuppressive agents, such as cyclophosphamide, azathioprine, and methotrexate, are prescribed with the aim of inducing remission, managing relapses, and maintaining disease control.10,13,23 However, the use of these immunosuppressants in EGPA is off label and largely based on evidence and clinical experience in other vasculitic diseases.10,13,23–26
In a large, retrospective, non-interventional, longitudinal European chart review, 98.8% of patients with EGPA had received OCS, with a median (IQR) maximum daily dose of 30 (10–50) mg and a median (IQR) treatment duration of 22.2 (11.5–34.8) months. Over half of patients were treated with additional immunosuppressive therapies.10 Importantly, treatment exposure did not equate to disease quiescence.10 Despite OCS use, many patients with EGPA continue to experience a high burden of disease activity and multisystem involvement.4,10
The reliance on prolonged OCS therapy comes with associated risks.4,10 Most patients with EGPA receive high-dose systemic corticosteroids for extended periods, and many require repeated courses due to relapses.4,10 Evidence from broader inflammatory disease populations demonstrates that long-term or frequent OCS use, even at relatively low doses (~5 mg/day for >1 year), is associated with a high risk of side effects.27,28 Over time, these adverse effects contribute to impaired quality of life, reduced work productivity, and long-term comorbidity.3,4,10,29
Similarly, long-term use of other non-specific immunosuppressants (eg cyclophosphamide, azathioprine, and methotrexate) is associated with considerable adverse events, including increased susceptibility to infections, malignancy risk, cytopenias, hepatotoxicity, and cumulative organ damage.11,24–26 This further limits their suitability for sustained disease management and underscores the need for alternative approaches.
Collectively, these data illustrate a key aim in EGPA management: the ability to achieve sustained disease control while reducing long-term exposure to systemic corticosteroids and non-specific immunosuppressants.4,10,11,30 Despite intensive treatment, many patients continue to experience ongoing symptoms, relapses, and treatment-related side effects.10
ANCA, antineutrophil cytoplasmic antibody; BEC, blood eosinophil count; BVAS, Birmingham Vasculitis Activity Score; CLC, Charcot-Leyden crystals; CRSwNP, chronic rhinosinusitis with nasal polyps; ECP, eosinophil cationic protein; EDN, eosinophil-derived neurotoxin; EPX, eosinophil peroxidase; EGPA, eosinophilic granulomatosis with polyangiitis; IQR, interquartile range; MBP, major basic protein; OCS, oral corticosteroid(s); SCS, systemic corticosteroid(s).
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Date of preparation: May 2026
