Hypereosinophilia: clinical and therapeutic approach in 2025

Abstract

Purpose of review: This review addresses the clinical and biological complexities of hypereosinophilia (HE) and hypereosinophilic syndrome (HES), highlighting the need for improved diagnostic frameworks and therapeutic strategies. Due to the increasing recognition of HE and its potential for severe multiorgan involvement, a structured, multidisciplinary approach to diagnosis and management is essential for optimizing patient outcomes.

Recent findings: Recent literature categorizes HE into hereditary, reactive, and neoplastic forms, with significant advancements in defining associated conditions and their pathophysiological mechanisms. Clinical manifestations range from asymptomatic eosinophilia to life-threatening complications involving the skin, lungs, gastrointestinal tract, heart, and nervous system. Corticosteroids remain the first-line treatment across most subtypes. Imatinib has shown high efficacy, particularly in patients with FIP1L1::PDGFRA fusion. However, therapeutic resistance and relapse still occur. Biologic therapies targeting interleukin (IL)-5 or its receptor, such as mepolizumab and benralizumab, have demonstrated promise in reducing eosinophils counts and preventing flare-ups. Additional agents under investigation include dupilumab and lirentelimab.

Summary: The findings highlight the importance of accurate classification and tailored management of HE and HES, which are crucial for preventing organ damage and improving quality of life. Ongoing clinical trials and research will expand therapeutic options, clarify underlying mechanisms, and address current unmet needs.

Keywords: classification; eosinophils; hypereosinophilia; hypereosinophilic syndrome; treatment.

Box 1

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FIGURE 1

Clinical manifestations of HES. Imagine created by Biorender.

FIGURE 2

Diagnostic algorithm for HES. Imagine created by Biorender. BALF, bronchoalveolar lavage fluid; CBC, complete blood count; CRP, C-reactive protein; ECG, electrocardiogram; EGPA, eosinophilic granulomatosis with polyangiitis; EMG, electromyography; FISH, fluorescence in situ hybridization; HRCT, high-resolution computed tomography; IBD, inflammatory bowel disease; Ig, immunoglobulins; LFTs, liver function tests; MRI, magnetic resonance imaging; NGS, next-generation sequencing; RT-PCR, reverse transcription polymerase chain reaction; sCr, serum creatinine; SPE, serum protein electrophoresis.