The 3 diagnostic criteria are:
- Peripheral hypereosinophilia (HE) (> 1.5 x 109/L) on 2 occasions separated in time by 4 weeks with or without marked tissue eosinophilia
- HE-related organ damage or dysfunction:
- Greater than 20% eosinophils as compared to all nucleated cells on bone marrow section
- Extensive tissue infiltration by eosinophils as determined by pathologist
- Significant deposition of eosinophil granule proteins in tissue in absence of major tissue infiltration with eosinophils
- Primary HES – Monoclonal HE due to an underlying stem cell, myeloid, or eosinophilic neoplasm.
- Secondary HES – Polyclonal HE due to an overproduction of eosinophilopoietic cytokines. Potential causes include allergic disorders, malignancy, parasitic infection, and drug reactions.
- Idiopathic HES – The underlying cause of the HE is unknown.
- T-cell lymphocytic HES is associated with abnormal clones of T-cells producing Th-2 cytokines, specifically interleukin-5, which results in increased eosinophil production. These patients are at increased risk of developing lymphoma.
- Myeloproliferative HES is most commonly associated with the FIP1L1-PDGFRA fusion gene (encoding an activated tyrosine kinase), as well other chromosomal aberrations. This genetic mutation is found in various forms of myeloproliferative HES including eosinophilic leukemia.
- Familial HES is associated with autosomal dominant inheritance and linkage to chromosome 5q31-33. Although most affected individuals are asymptomatic, fatal progression of the disease has occurred.
- Other eosinophilic disorders: eosinophilic vasculitis; eosinophilic gastritis; episodic angioedema with eosinophilia (also known as Gleich syndrome); nodules, eosinophilia, rheumatism, dermatitis, and swelling (NERDS) syndrome; etc.
- Myeloproliferative variant (3 types):
- PDGFRA-associated HES (FIP1L1-PDGFRA: interstitial deletion of chromosome 4q12).
- Unknown etiology (FIP1L1-PDGFRA negative) associated HES.
- Chronic eosinophilic leukemia (CEL) characterized by cytogenetic abnormalities and/or peripheral blasts.
- Findings associated with the myeloproliferative variant are hepatosplenomegaly, anemia, thrombopenia, bone marrow dysplasia or fibrosis, and elevated cobalamin levels.
Morbidity and mortality from HES is variable. This condition may be quiescent or rapidly fatal from heart failure secondary to progressive restrictive cardiomyopathy. Poorer prognoses are associated with malignant transformation to eosinophilic leukemia, higher eosinophil counts, and cardiac or neurologic involvement.