Definition and epidemiology
Hypereosinophilic syndrome (HES) describes a heterogeneous group of disorders unified by persistent marked blood eosinophilia with eosinophil-mediated end-organ damage, after exclusion of a defined secondary cause. The classic threshold, originating with Chusid in 1975, is a peripheral eosinophil count ≥1500/μL on at least two occasions (or tissue hypereosinophilia) plus organ damage attributable to eosinophils, with no identifiable secondary cause. The historic requirement for 6 months’ persistence is no longer mandatory: treatment should not be withheld when end-organ damage is already present. HES is rare in children but potentially life-threatening, particularly through cardiac involvement.
Clinical features
Presentation reflects the organs infiltrated. Cardiac disease (eosinophilic endomyocarditis progressing to fibrosis, mural thrombus and restrictive cardiomyopathy) is the leading cause of morbidity and mortality and may be clinically silent early. Other manifestations include dermatological (urticaria, angioedema, eczema), respiratory (cough, wheeze, infiltrates), gastrointestinal (eosinophilic gastroenteritis, diarrhoea), neurological (thromboembolic stroke, peripheral neuropathy, encephalopathy) and constitutional symptoms (fever, weight loss). The myeloid (M-HES) variant — often FIP1L1-PDGFRA-driven — carries a higher risk of cardiac fibrosis, while the lymphocytic (L-HES) variant is driven by an aberrant T-cell clone producing IL-5.
Diagnosis
Confirm true, persistent eosinophilia and quantify it, then systematically exclude secondary causes — parasitic infection (especially Strongyloides before any immunosuppression), drug reactions, atopy, malignancy and adrenal insufficiency. Work-up for organ damage includes cardiac evaluation (troponin, ECG, echocardiography, and MRI where indicated), and assessment of lung, gut, skin and nervous-system involvement. Distinguish clinical subtypes — myeloproliferative/M-HES (screen for FIP1L1-PDGFRA and related fusions), lymphocytic/L-HES (T-cell immunophenotyping and clonality), familial, overlap and idiopathic — because the subtype dictates therapy. The diagnostic algorithm walks through count thresholds, exclusions and subtype assignment.
See the full criteria: Hypereosinophilic Syndromes
Red flags
- Any cardiac involvement — rising troponin, new murmur, heart failure or mural thrombus (emergency)
- Thromboembolic events: stroke, limb or visceral ischaemia
- Eosinophil count escalating rapidly or marked leucocytosis suggesting leukaemic transformation
- Neurological deficits or encephalopathy
- Strongyloides exposure risk before starting corticosteroids (hyperinfection risk)
Management overview
Treatment is subtype-directed and urgency-driven. Life-threatening (especially cardiac or thromboembolic) disease warrants prompt high-dose systemic corticosteroids as first-line for most non-myeloid HES, after empiric anti-helminthic cover where Strongyloides cannot be excluded. The myeloid/PDGFRA-positive subtype responds dramatically to a tyrosine kinase inhibitor (imatinib class), which is first-line for that group. Anti-IL-5 biologic agents are increasingly used as steroid-sparing therapy, particularly in the lymphocytic and idiopathic subtypes, and other steroid-sparing immunosuppressants (e.g. hydroxyurea, interferon class) remain options in refractory disease. Anticoagulation is indicated for thrombosis. Manage in conjunction with haematology/immunology, monitor eosinophil counts and serial cardiac assessment, and re-evaluate the diagnosis if response is poor.
References
- Valent P, et al. Consensus criteria and classification of eosinophilic disorders. J Allergy Clin Immunol, 2012.
- Shomali W, Gotlib J. WHO/ICC eosinophilic disorders 2024 update. Am J Hematol, 2024.
- Klion AD. Approach to hypereosinophilia and HES. Hematology ASH Education Program.
- Nelson Textbook of Pediatrics, 21st ed.
Decision support for qualified clinicians only — verify against current primary guidelines and your clinical judgement.