Clinical Presentation and Diagnosis of Hypereosinophilic Syndrome

Diagnostic Criteria and Clinical Manifestations

The American College of Cardiology and other guideline societies recommend that Hypereosinophilic syndrome (HES) be diagnosed based on persistent peripheral blood eosinophilia (>1500 cells/μL) and organ damage from eosinophilic tissue infiltration, most commonly affecting the skin, gastrointestinal tract, heart, lungs, and nervous system 1, 2.
HES requires three essential components: peripheral blood eosinophil count >1.5 × 10⁹/L on two examinations at least one month apart, organ damage and/or dysfunction attributable to tissue eosinophilic infiltration, and exclusion of secondary causes 3, 1.
The National Comprehensive Cancer Network recommends that the diagnostic workup for HES include a CBC with differential, serum chemistries, vitamin B12 and serum tryptase, and serum immunoglobulins 1, 5.

Up to 38% of HES patients develop gastrointestinal symptoms, including esophageal involvement that mimics eosinophilic esophagitis with dysphagia and food impaction 2, 6.
The American Gastroenterological Association recommends that patients with esophageal symptoms and hypereosinophilia require screening of upper and lower GI tract plus monitoring for other organ involvement 2, 6.
Endomyocardial thrombosis and fibrosis are frequently documented in HES patients, particularly in primary (neoplastic) HES variants, and cardiac involvement represents the most critical prognostic factor 1.

Primary (neoplastic) HES is characterized by an underlying myeloid or stem cell neoplasm where eosinophils are clonal cells, and is often associated with elevated serum tryptase and vitamin B12 levels 3, 1.
Secondary (reactive) HES is characterized by cytokine-driven eosinophilia with non-clonal eosinophils, and may be associated with lymphocyte-variant HES (L-HES) or other conditions 3, 1.

Before diagnosing HES, it is essential to systematically exclude secondary causes, including allergic disorders, parasitic infections, and other conditions 1, 7.
The National Institute of Allergy and Infectious Diseases recommends that stool examination for ova and parasites, Strongyloides serology, and comprehensive medication review be performed to exclude secondary causes 1, 5, 7.

The diagnostic workup for HES should include initial laboratory evaluation, exclusion of secondary causes, molecular and cytogenetic testing, and organ-specific evaluation 1, 5.
The American Society of Hematology recommends that bone marrow aspirate and biopsy with immunohistochemistry, conventional cytogenetics and FISH for tyrosine kinase fusion genes, and flow cytometry with T-cell immunophenotyping be performed to establish a diagnosis of HES 5, 1.