Table 6.
Classification of hypereosinophilic syndromes (HES) and related disorders
| Variant | Typical features |
|---|---|
| Idiopathic HES | No underlying cause of HE, no evidence of a reactive or neoplastic condition/disorder underlying HE, and end organ damage attributable to HE |
| Primary (neoplastic ) HES (HESN) | Underlying stem cell, myeloid, or eosinophil neoplasm classified according to WHO and end organ damage attributable to HE. Eosinophils are considered (or shown) to be neoplastic (clonal) cells*; HESN |
| Secondary (reactive) HES(HESR) | Underlying condition/disease where eosinophils are considered non-clonal cells, and HE is considered to be cytokine-driven (HESR), and end organ damage attributable to HE |
| Special variants/syndromes | |
| Lymphoid variant of HES (HES-L)** | Abnormal clonal T cells often detected, HES-related organ damage found, but angioedema and elevated IgM usually absent |
| Episodic angioedema and eosinophilia (Gleich’s syndrome) | Abnormal clonal T cells usually detected, angioedema, and elevated polyclonal IgM |
| Eosinophilic granulomatosis with polyangiitis = (EGPA) = Churg-Strauss syndrome | Polyangiitis, necrotizing angiitis, asthma, lung infiltrates; in a subset of patients, ANCA can sometimes be detected (ANCA+ form of EGPA) |
| Eosinophilia myalgia syndrome (EMS) | Myalgia, muscle weakness, cramping, skin rash, dyspnea, fatigue |
| Omenn syndrome | Autosomal recessive disease with hypomorphic missense mutations in immunologically relevant genes, like RAG1 or RAG2, severe combined immunodeficiency with recurrent infections, auto-reactive T cells, skin rash, erythroderma, splenomegaly, lymphadenopathy, GvHD-like symptomatology |
| Hyper-IgE syndrome | Hereditary immunodeficiency syndrome, elevated serum IgE, recurrent bacterial infections, often with eczema and facial anomalies. Autosomal dominant variant: STAT3 mutations. Autosomal recessive variant: DOCK8 mutations |
*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 a typical molecular defect is demonstrable (e.g., PDGFR or FGFR mutations or BCR-ABL1), eosinophilia should be considered clonal
**The lymphoid variant of HES is regarded a special form of secondary HES, although its exact nature and pathogenesis remain controversial
HE hypereosinophilia, HES hypereosinophilic syndrome, ANCA anti-neutrophil cytoplasmic antibodies