Hypereosinophilic Syndrome Diagnosis and Classification

Diagnostic Criteria

Hypereosinophilic syndrome (HES) is defined as persistent blood eosinophilia ≥1.5 × 10⁹/L on two examinations at least one month apart (or tissue hypereosinophilia) with end-organ damage attributable to eosinophil infiltration, after excluding secondary causes such as parasitic infections, allergic disorders, and malignancies, as recommended by the National Comprehensive Cancer Network 1, 2
The diagnosis requires three essential elements: peripheral blood hypereosinophilia, end-organ damage attributable to eosinophilia, and exclusion of other disorders, according to the National Comprehensive Cancer Network 2

Initial clinical assessment must address travel history, new medications, recurrent infections, and family history of eosinophilia or autoimmune disease, as suggested by the National Comprehensive Cancer Network 1, 4, 5, 6
Mandatory laboratory testing includes CBC with differential, comprehensive metabolic panel, liver function tests, serum tryptase levels, and vitamin B12 levels, as recommended by the National Comprehensive Cancer Network 4, 5, 6
Bone marrow evaluation with immunohistochemistry, reticulin/collagen stains, conventional cytogenetics, FISH for CHIC2 deletion, and RT-PCR for tyrosine kinase fusion genes is necessary for diagnosis, according to the National Comprehensive Cancer Network 4, 7, 8

Once HES is confirmed, classify into subtypes: primary (neoplastic) HES, secondary (reactive) HES, idiopathic HES, and hereditary HES, as recommended by the National Comprehensive Cancer Network 1, 2, 3
Primary HES is characterized by an underlying myeloid or stem cell neoplasm with clonal eosinophils, including cases with PDGFRA/PDGFRB/FGFR1/JAK2 rearrangements or chronic eosinophilic leukemia-NOS, according to the National Comprehensive Cancer Network 1, 2, 5

Failing to test for PDGFRA rearrangements with FISH can lead to missed diagnosis and treatment opportunities, as highlighted by the National Comprehensive Cancer Network 3
Overlooking parasitic infections, especially Strongyloides, in travelers can lead to delayed diagnosis and treatment, as noted by Praxis Medical Insights 6
Not assessing cardiac involvement early can result in irreversible heart failure and poor prognosis, as emphasized by Praxis Medical Insights 6