What are the causes of hypereosinophilia?

Causes of Hypereosinophilia

Allergic and atopic disorders are the most common cause of hypereosinophilia, accounting for approximately 80% of secondary reactive cases, followed by parasitic infections as the second most frequent etiology. 1, 2

Primary Categories of Hypereosinophilia

Secondary (Reactive) Causes - Most Common

Allergic/Atopic Disorders (80% of cases):

• Allergic asthma 3, 1
• Food allergies 1, 2
• Atopic dermatitis 3, 1, 2
• Drug reactions 3, 1
• Urticaria and eczema 3

Parasitic Infections (Second Most Common):

• Strongyloides stercoralis is the most common parasitic cause, particularly important because it can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients 3, 2
• Hookworm (Ancylostoma duodenale, Necator americanus) 1, 2
• Ascaris lumbricoides 1, 2
• Schistosomiasis (especially with freshwater exposure in Africa) 1, 2
• Filariasis (particularly in West Africa) 1, 2
• Onchocerca volvulus 2
• Toxocara canis/catis (visceral larva migrans) 2

Drug Reactions:

• Non-steroidal anti-inflammatory drugs 1, 2
• Beta-lactam antibiotics 1, 2
• Nitrofurantoin 1, 2

Autoimmune and Inflammatory Disorders:

• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) 3
• Allergic bronchopulmonary aspergillosis 3

Primary (Neoplastic) Causes

Myeloid Neoplasms:

• FIP1L1-PDGFRA fusion-positive chronic eosinophilic leukemia - this is critical to identify as it responds dramatically to imatinib 3, 4
• Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes 3, 1
• Chronic myeloid leukemia (CML) 3
• Acute myeloid leukemia (AML) 3
• Advanced systemic mastocytosis 3

Lymphoid Neoplasms:

• Hodgkin lymphoma 3
• T-cell lymphomas (more frequent than B-cell) 3
• B-cell lymphomas 3

Lymphocytic Variant Hypereosinophilic Syndrome (L-HES):

• Characterized by clonal T-cells with aberrant immunophenotype (CD3-, CD4+, CD8- or CD3+, CD4-, CD7-) 3
• Secondary reactive eosinophilia due to IL-4, IL-5, and IL-13 production from abnormal T-cells 3
• 10-20% risk of evolution to T-cell lymphoma or Sézary syndrome 3
• Elevated serum TARC and IgE levels 3

Solid Tumors:

• Generally limited to advanced stage disease 3, 1
• Eosinophilia results from increased production of eosinophilopoietic cytokines 3

Immunodeficiency Syndromes

• Hyperimmunoglobulin E syndrome (formerly Job syndrome) 3
• Omenn syndrome 3
• Wiskott-Aldrich syndrome 3

Critical Diagnostic Considerations

Geographic and Exposure History:

• Helminth infections are the most common identifiable cause in returning travelers and migrants (19-80% diagnosis rate) 2
• Geographic area visited helps narrow differential diagnosis 2
• Timing matters: eosinophilia may be transient during tissue migration phase when stool microscopy is negative 1, 2

Temporal Patterns:

• Serological tests for helminths may not become positive until 4-12 weeks after infection 1, 2
• Hypereosinophilic syndrome requires persistent eosinophilia >1.5 × 10⁹/L for more than 6 months with organ damage after excluding secondary causes 4

Common Pitfalls to Avoid

Many people with helminth infection do not have eosinophilia, so testing for eosinophilia alone is not an adequate screening strategy. 2

• Serological tests may exhibit cross-reactivity between different helminth species 2
• Stool microscopy may be negative during tissue migration phase when eosinophilia is present 2
• Protozoa generally do not cause hypereosinophilia (except occasional low-grade eosinophilia in toxoplasmosis) 5

Organ Damage Risk

Persistent high-grade eosinophilia (>1.5 × 10⁹/L) can cause significant organ damage even without an identifiable cause, affecting: 1, 2

• Heart (endomyocardial thrombosis and fibrosis, myocarditis) 3, 2
• Lungs (pulmonary infiltrates) 3, 2
• Gastrointestinal tract 3, 1
• Nervous system (meningitis, encephalitis) 3, 2
• Skin 3, 2

Patients with eosinophilia and evidence of end-organ damage need urgent medical assessment. 2