Eosinophils in the immunologic spectrum of Eosinophilic Granulomatosis with Polyangiitis: From Fundamental Pathobiology to Emerging Therapeutic Strategies and Future Perspectives

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis characterized by asthma, chronic rhinosinusitis with nasal polyps, eosinophil-driven tissue inflammation, and necrotizing small- to medium-sized vessel vasculitis. Myeloperoxidase - Anti-Neutrophil Cytoplasmic Antibody (MPO-ANCA) is detectable in approximately 30%-40% of patients, and ANCA-positive and ANCA-negative diseases exhibit distinct yet overlapping clinical patterns. Type 2 immune responses are predominant, with interleukin-5 (IL-5) driving eosinophil differentiation and survival, and IL-4 and IL-13 promoting eosinophil recruitment and IgE-associated pathways. Activated eosinophils contribute to tissue injury through degranulation and eosinophil extracellular trap formation (EETosis). Glucocorticoids remain the foundation of therapy, but they are often insufficient to achieve a sustained remission as monotherapy. Conventional immunosuppressants are used for severe disease, and B-cell-targeted therapy may be considered for selected vasculitic presentations. Biological agents targeting the IL-5/IL-5 receptor axis have been shown to prolong remission, reduced relapse risk, and enabled glucocorticoid sparing. However, some patients remain symptomatic, and reliable biomarkers to guide individualized therapy are lacking. Ongoing research focuses on biomarker panels and cell-free DNA to clarify the role of EETosis and define molecular endotypes to support precision-medicine approaches.