Eosinophilic granulomatosis with polyangiitis across the eosinophilic spectrum: from molecular mechanisms to practical differential diagnosis and targeted therapy

Introduction Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis defined by asthma, hypereosinophilia, and multiorgan involvement. Differentiating EGPA from other eosinophilic disorders is crucial because management differs substantially. The aim of the study is to summarize the pathogenesis, epidemiology, genetics, clinical manifestation, and treatment of EGPA and to provide a comparative differential diagnosis of eosinophilic disorders. Material and Methods Narrative review using the 2022 American College of Rheumatology (ACR)/Euro­pean Alliance of Associations for Rheumatology (EULAR) classification criteria, 2024 EULAR re­com­mendations, pivotal randomized trials, and major consensus statements; search strategy and selection criteria are detailed in the Introduction. Results Eosinophilic granulomatosis with polyangiitis comprises 2 immunologic endotypes – anti- neutrophil cytoplasmic antibody (ANCA)-positive and ANCA-negative – with distinct organ tropism and therapeutic implications. The interleukin-5 (IL-5)–eosinophil axis is central, supporting anti-IL-5/IL-5R biologics in relapsing or refractory disease. A structured differential first excludes secondary hypereosinophilia (parasites, drugs, malignancies) and then addresses pulmonary “mimics”. Conclusions An algorithm combining exclusion of secondary causes with organ and endotype profiling enables targeted therapy and reduced glucocorticoid exposure.