What is eosinophilia?

What is Eosinophilia?

Eosinophilia is defined as a peripheral blood eosinophil count greater than 0.45 × 10^9/L (450 cells/μL), representing an elevated absolute number of eosinophilic leukocytes in the blood. 1

Classification by Severity

Eosinophilia is stratified into three categories based on absolute eosinophil count:

• Mild eosinophilia: 500-1,500 cells/μL 2
• Moderate eosinophilia: 1,500-5,000 cells/μL 2
• Severe eosinophilia: >5,000 cells/μL 2

Hypereosinophilia: A Distinct Entity

Hypereosinophilia (HE) is defined as a persistent elevated eosinophil count >1.5 × 10^9/L in blood on two examinations at least one month apart and/or tissue hypereosinophilia. 1, 3

Classification of Hypereosinophilia

The National Comprehensive Cancer Network classifies HE into four variant types 1, 3:

• Hereditary (familial) HE: Characterized by familial clustering without signs of hereditary immunodeficiency 3
• Primary (clonal/neoplastic) HE: Neoplastic proliferation of eosinophils associated with WHO-defined myeloid and/or lymphoid neoplasms 3
• Secondary (reactive) HE: Non-clonal eosinophils driven by underlying conditions, typically cytokine-mediated (particularly IL-5) 3
• HE of undetermined significance (HE-US): No underlying cause identified and no family history 3

Common Causes

The causes can be summarized by the acronym "APLV" 2:

• Allergic disorders: Including asthma, eczema, and hay fever; typically associated with mild eosinophilia 1, 2
• Parasitic infections: Helminth infections are the most common identifiable cause in returning travelers (diagnosis rates 19-80%) 1, 4
• Leukemia/Lymphomas: Values >20,000 cells/μL are highly suggestive for myeloproliferative disorders 2
• Vasculitis-Immunodeficiency diseases: Including eosinophilic granulomatosis with polyangiitis 5

Important Non-Infectious Causes

Medications are among the most common non-infectious causes, including NSAIDs, beta-lactam antibiotics, and nitrofurantoin. 1, 4

Clinical Significance and Organ Damage

Even mild persistent eosinophilia can cause end-organ damage if left untreated. 1, 4 Eosinophils may directly damage organs through release of granule products, lipid mediators, and cytokines 2:

• Cardiac involvement: Endomyocardial fibrosis 6
• Pulmonary involvement: Lung infiltration 2
• Cutaneous involvement: Skin manifestations 2
• Gastrointestinal involvement: Eosinophilic gastroenteritis 7
• Neurologic involvement: Central and peripheral nervous system damage 7

Hypereosinophilic Syndrome (HES)

HES refers to any hypereosinophilia variant with evidence of eosinophil-induced tissue/organ damage. 3 Idiopathic HES is diagnosed when hypereosinophilia with associated organ damage is detected with no apparent underlying disease 3.

Critical Pitfalls

• Strongyloides stercoralis infection can persist lifelong and later present as hyperinfection syndrome with high mortality in immunocompromised patients. 1 This requires specific attention in patients with travel history to endemic areas.
• Testing for eosinophilia alone is not an adequate screening strategy for helminth infection, as many people with helminth infections do not have eosinophilia. 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. 1, 3