Journal List > Allergy Asthma Respir Dis > v.3(6) > 1059136

Park and Lee: Recent advances in the classification and management of hypereosinophilia


Numerous disorders and etiologies may underlie increased eosinophil counts. Hypereosinophilia (HE) is defined as a peripheral blood eosinophil count greater than 1,500/mm3 and may be potentially harmful because of tissue damage. Hypereosinophilic syndrome (HES) also represents a heterogeneous disorder characterized by persistent HE with the evidence of organ dysfunction, clinical symptoms, or both caused by eosinophilia. The refining criteria and subclassification of HE and HES are currently being revised on cellular and molecular based diagnostic methods. Initial approaches focus on evaluating various underlying causes, including helminthic infections, adverse drug reactions, allergic diseases, and neoplastic diseases. When secondary causes of HE are excluded, the workup should proceed to the evaluation of primary/clonal bone marrow disease, including fip 1-like 1-platelet driven growth factor receptor alpha (FIP1L1-PDGFRA) mutation. Concurrently, if the patient has symptoms and signs, organ damage or dysfunction must be evaluated. Although, corticosteroids are the mainstay of therapy in confirmed HES, imatinib is considered a definitive treatment for FIP1L1-PDGFRA, platelet driven growth factor receptor beta rearranged HE and HES. In this article, we discuss recent advances in the classification of and practical approaches to HE and HES. In addition, we introduce several promising therapies for HE and HES.

Figures and Tables

Fig. 1

Algorithm for diagnosis and treatment of hypereosinophilia. Adapted from Roufosse F, et al. J Allergy Clin Immunol 2010;126:39-44,18 with permission of Elsevier Ltd. CBC, complete blood count; PFT, pulmonary function test; CT, computed tomography; EKG, electrocardiogram; FISH, fluorescent in situ hybridization; HES, hypereosinophilic syndrome; RT-PCR, reverse transcription polymerase chain reaction; TCR, T-cell receptor; BM, bone marrow; CS, corticosteroids.

Table 1

Definition and classification of HE and HES

Proposed term Proposed abbreviation Definition and criteria
Hypereosinophilia HE > 1.5 Eosinophils × 109/L blood on 2 examinations (interval ≥ 1 month) and/or tissue HE
Hereditary (familial) HE HEFA Familial clustering, no signs or symptoms of hereditary immunodeficiency, and no evidence of a reactive or neoplastic condition
Primary (clonal/neoplastic) HE HEN Underlying stem cell, myeloid, or eosinophil neoplasm, as classified by WHO criteria; eosinophils considered neoplastic cells
Secondary (reactive) HE HER Underlying condition/disease in which eosinophils are considered nonclonal cells
HE of undetermined significance HEUS No underlying causes HE, no evidence of familial, reactive or neoplastic condition/disorders and no end-organ damage attributable to HE
Hypereosinophilic syndrome HES (1) Criteria for peripheral blood HE fulfilled and; (2) organ damage and/or dysfunction attributable to tissue HE and; (3) exclusion of other disorders or conditions as major reason for organ damage
Primary (neoplastic) HES HESN (1) Criteria for HEN fulfilled and; (2) end-organ damage attributable to HE, and (3) eosinophils are considered (or shown) neoplastic (clonal) cells
Secondary (reactive) HES HESR (1) Criteria for HER fulfilled and; (2) end-organ damage attributable to HE*
Idiopathic HES HESi (1) Criteria for HE fulfilled and; (2) end-organ damage attributable to HE
Eosinophil-associated single organ disease (1) Criteria of HE fulfilled and; (2) single-organ disease
Specific syndromes accompanied by HE Specific syndromes in which the effect of eosinophilia remains unclear but the clinical presentation is distinct and accompanied by HE

Adapted from Valent P, et al. J Allergy Clin Immunol 2012;130:607-12.e9,7 with permission of Elsevier Ltd.

HE, hypereosinophilia; HES, hypereosinophilic syndrome; WHO, World Health Organization.

*Sub variant: lymphoid variant HES (clonal T cells identified as the only potential causes).

Table 2

Medications commonly associated with eosinophilia and drug induced hypersensitivity syndrome

Class Drug
Antibiotics Penicillins, cephalosporins, fluoroquinolones, tetracyclines, minocycline, vancomycin, doxycycline, linezolid, nitrofurantoin, metronidazole
Antiepileptics Phenytoin, carbamazepine, phenobarbital, lamotrigine, valproate, oxacarbazepine
Antidepressants Desipramine, amitriptyline, fluoxetine
Antiinflammatories Piroxicam, naproxen, diclofenac, ibuprofen
Antihypertensives Hydrochlorothiazide, β-blockers, angiotensin-converting enzyme inhibitors
Sulfonamides/sulfones Dapsone, sulfasalazine, trimethoprim-sulfamethoxazole
Others Abacavir, nevirapine, allopurinol, ranitidine, cyclosporine, hydroxichloroquine


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