International consensus group definitions for HE and HES
| Proposed term . | Proposed abbreviation . | Pathogenesis/definition . |
|---|---|---|
| Hypereosinophilia | HE | >1.5 × 109/L eosinophils in the blood on 2 examinations (interval >1 mo*) and/or tissue HE defined by the following:† Percentage of eosinophils in bone marrow (BM) section exceeds 20% of all nucleated cells; and/or Pathologist is of the opinion that tissue infiltration by eosinophils is extensive; and/or Marked deposition of eosinophil granule proteins is found (in the absence or presence of major tissue infiltration by eosinophils). |
| Subtypes of HE | ||
| Hereditary (familial) HE | HEFA | Pathogenesis unknown; familial clustering, no signs or symptoms of hereditary immunodeficiency, and no evidence of a reactive or neoplastic condition/disorder underlying HE |
| HE of undetermined significance | HEUS | No underlying cause of HE, no family history, no evidence of a reactive or neoplastic condition/disorder underlying HE, and no end-organ damage attributable to HE |
| Primary (clonal/neoplastic) HE¶ | HEN | Underlying stem cell, myeloid, or eosinophilic 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 considered cytokine-driven in most cases§ |
| Hypereosinophilic syndrome | HES | Criteria for peripheral blood HE fulfilled*; and Organ damage and/or dysfunction attributable to tissue HE#; and Exclusion of other disorders or conditions as major reason for organ damage |
| Proposed term . | Proposed abbreviation . | Pathogenesis/definition . |
|---|---|---|
| Hypereosinophilia | HE | >1.5 × 109/L eosinophils in the blood on 2 examinations (interval >1 mo*) and/or tissue HE defined by the following:† Percentage of eosinophils in bone marrow (BM) section exceeds 20% of all nucleated cells; and/or Pathologist is of the opinion that tissue infiltration by eosinophils is extensive; and/or Marked deposition of eosinophil granule proteins is found (in the absence or presence of major tissue infiltration by eosinophils). |
| Subtypes of HE | ||
| Hereditary (familial) HE | HEFA | Pathogenesis unknown; familial clustering, no signs or symptoms of hereditary immunodeficiency, and no evidence of a reactive or neoplastic condition/disorder underlying HE |
| HE of undetermined significance | HEUS | No underlying cause of HE, no family history, no evidence of a reactive or neoplastic condition/disorder underlying HE, and no end-organ damage attributable to HE |
| Primary (clonal/neoplastic) HE¶ | HEN | Underlying stem cell, myeloid, or eosinophilic 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 considered cytokine-driven in most cases§ |
| Hypereosinophilic syndrome | HES | Criteria for peripheral blood HE fulfilled*; and Organ damage and/or dysfunction attributable to tissue HE#; and Exclusion of other disorders or conditions as major reason for organ damage |
In the case of evolving life-threatening end-organ damage, the diagnosis can be made immediately to avoid delay in therapy.
Validated quantitative criteria for tissue HE do not exist for most tissues at the present time. As a consequence, tissue HES is defined by a combination of qualitative and semiquantitative findings that will require revision as new information becomes available.
Clonality of eosinophils is often difficult to demonstrate or is not examined. However, if a myeloid or stem cell neoplasm known to present typically with clonal HE is present or atypical molecular defect is demonstrable (eg, PDGFR or FGFR mutations or BCR/ABL1), eosinophilia should be considered clonal.
HEN and HER are prediagnostic checkpoints that should guide further diagnostic evaluations but cannot serve as final diagnoses.
In a group of patients, HER might be caused/triggered by other as-yet-unknown processes because no increase in eosinophilopoietic cytokine levels can be documented.
HE-related organ damage (damage attributable to HE): organ dysfunction with marked tissue eosinophil infiltrates and/or extensive deposition of eosinophil-derived proteins (in the presence or absence of marked tissue eosinophils) and 1 or more of the following: fibrosis (lung, heart, digestive tract, skin, and others); thrombosis with or without thromboembolism; cutaneous (including mucosal) erythema, edema/angioedema, ulceration, pruritus, and eczema; and peripheral or central neuropathy with chronic or recurrent neurologic deficit. Less commonly, other organ system involvement (liver, pancreas, kidney, and other organs) and the resulting organ damage can be judged as HE-related pathology, so the clinician concludes the clinical situation resembles HES. Note that HES can manifest in 1 or more organ systems.