Definition of Eosinophilia

Eosinophilia is defined as a peripheral blood eosinophil count greater than 0.45 × 10^9/L (450 cells/μL). 1, 2

Classification of Eosinophilia

Eosinophilia can be classified based on severity:

Hypereosinophilia (HE) is defined as:

Persistent elevated eosinophil count >1.5 × 10^9/L in blood on two examinations at least one month apart and/or tissue hypereosinophilia 1, 4
Tissue hypereosinophilia can be defined by one of the following:
- Percentage of eosinophils in bone marrow exceeds 20% of all nucleated cells 4
- Pathologist assessment that tissue infiltration by eosinophils is extensive 4
- Marked deposition of eosinophil granule proteins 4

Hypereosinophilia is divided into four variant types:

Hereditary (familial) HE (HE-FA): Characterized by familial clustering and no signs of hereditary immunodeficiency 1, 4
Primary (clonal/neoplastic) HE (HE-N): Characterized by neoplastic proliferation of eosinophils and associated with WHO-defined myeloid and/or lymphoid neoplasms 1, 4
Secondary (reactive) HE (HE-R): Characterized by an underlying condition/disease where eosinophils are non-clonal and usually cytokine-driven (particularly IL-5) 4
HE of undetermined significance (HE-US): No underlying cause identified and no family history 4

HES refers to any hypereosinophilia variant with evidence of eosinophil-induced tissue/organ damage 1, 4
Idiopathic HES is diagnosed when hypereosinophilia with associated organ damage is detected with no apparent underlying disease or syndrome 1, 4

Helminth infections are the most common identifiable cause of eosinophilia in returning travelers (diagnosis rates 19-80%) 1, 5
Strongyloides stercoralis infection can persist lifelong and later present as hyperinfection syndrome with high mortality in immunocompromised patients 5

Defined as ≥15 eosinophils/high power field (or ≥15 eosinophils/0.3 mm² or >60 eosinophils/mm²) in esophageal biopsies 1
Characterized by symptoms of dysphagia and/or food impaction in adults, and feeding problems, abdominal pain and/or vomiting in children 1
Peripheral eosinophilia occurs in 10-50% of adults and 20-100% of children with EoE, though usually only modestly elevated (2-fold) 2

Even mild persistent eosinophilia can cause end-organ damage if left untreated 5
In cases of evolving life-threatening end-organ damage, immediate diagnosis and treatment are necessary 4
Patients with eosinophilia ≥1.5 × 10^9/L for more than 3 months without evidence of end-organ damage should be referred to a hematologist after exclusion of infectious causes 4

Obtain detailed travel history, as helminth infections are a common cause of eosinophilia in returning travelers 5
Review medications, as drugs are among the most common non-infectious causes of eosinophilia in countries with low rates of endemic helminth infections 5
Consider stool examination for ova and parasites (three samples on different days) as a first-line test for patients with eosinophilia 5
Serological tests for common helminth infections should be based on travel history 5
For suspected myeloid/lymphoid neoplasms with eosinophilia, diagnostic evaluation relies on morphologic review of blood and marrow, standard cytogenetics, fluorescent in situ-hybridization, flow immunocytometry, and T-cell clonality assessment 7, 8, 6

For mild eosinophilia with travel history to endemic areas and no other obvious cause, empirical treatment with albendazole plus ivermectin may be considered 5
For specific helminth infections identified, targeted therapy should be used 5
Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib 7, 8, 6
Corticosteroids are first-line therapy for patients with lymphocyte-variant hypereosinophilia and HES 7, 8, 6