Eosinophilic Disorders: Best Practices for HES and EGPA at ATS 2026

Eosinophilic disorders, including hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA), are characterised by persistent eosinophilia and diverse organ involvement. The clinical dilemma lies in differentiating these conditions and initiating appropriate, often immunosuppressive, therapy before irreversible organ damage occurs. HES is defined by peripheral blood eosinophil counts exceeding 1.5 x 10⁹/L for at least six months, or for less than six months in the presence of signs or symptoms of eosinophil-related organ damage, after exclusion of secondary causes.¹ EGPA, conversely, is a systemic vasculitis characterised by asthma, eosinophilia, and extravascular granulomas.² Both conditions necessitate a nuanced diagnostic approach and a treatment strategy that balances efficacy with minimisation of adverse effects.

Gaining Control of Eosinophilic Disorders: Best Practices

ATS 2026 sessions on eosinophilic disorders focused on refining diagnostic pathways and optimising therapeutic interventions. For HES, the diagnostic workup typically involves excluding secondary causes such as parasitic infections, allergic reactions, and malignancies. Genetic testing for FIP1L1-PDGFRA fusion gene is critical, as its presence identifies a specific HES subtype (myeloproliferative HES) that responds dramatically to imatinib.³ In patients without this fusion gene, further subtyping into lymphocytic HES, idiopathic HES, or other variants guides treatment selection. For EGPA, diagnosis relies on the American College of Rheumatology (ACR) criteria, which include asthma, eosinophilia (>10% on differential white blood cell count), mononeuropathy or polyneuropathy, non-fixed pulmonary infiltrates, paranasal sinus abnormality, and extravascular eosinophils on biopsy.⁴ Anti-neutrophil cytoplasmic antibodies (ANCA), particularly anti-myeloperoxidase (MPO-ANCA), are detected in approximately 30-40% of EGPA patients and may correlate with specific clinical phenotypes.⁵

Treatment strategies for both HES and EGPA typically begin with corticosteroids. For HES, prednisone at 1 mg/kg/day is a common initial approach.¹ However, long-term corticosteroid use is associated with significant adverse effects, prompting the exploration of corticosteroid-sparing agents. Mepolizumab, an anti-IL-5 monoclonal antibody, has demonstrated efficacy in reducing eosinophil counts and corticosteroid dependence in patients with HES.⁶ Reslizumab and benralizumab, also targeting IL-5 or its receptor, represent additional options. For EGPA, induction therapy often involves high-dose corticosteroids, sometimes combined with cyclophosphamide for severe organ-threatening disease.⁷ Maintenance therapy frequently includes azathioprine or methotrexate. Mepolizumab is approved for the treatment of EGPA and has shown significant reductions in relapse rates and corticosteroid dose.⁸ A randomised, placebo-controlled trial (N=136) demonstrated that mepolizumab, added to standard therapy, increased the accrued time in remission by 32 weeks (95% CI, 16 to 48 weeks; p<0.001) over 52 weeks compared to placebo.⁸

The integration of biologics into earlier lines of therapy for both HES and EGPA was a key theme. The data suggest that early initiation of targeted therapies, particularly anti-IL-5 agents, can lead to better disease control, reduced corticosteroid exposure, and improved quality of life.^6,8 This approach moves beyond simply managing symptoms to addressing the underlying eosinophilic inflammation more directly. Limitations in current practice include the heterogeneity of these disorders, which can make a one-size-fits-all approach challenging. Further research is needed to identify biomarkers that can predict response to specific therapies and to explore novel targets beyond the IL-5 pathway. The long-term safety and efficacy of newer biologics also require continued surveillance.