Causes of Eosinophilia
Primary Classification
Eosinophilia has two fundamental pathogenic mechanisms: allergic/atopic disorders account for approximately 80% of cases, while helminth infections represent the most common identifiable infectious cause, particularly in travelers and migrants from tropical regions. 1, 2
Infectious Causes
Helminth Infections (Most Common Infectious Etiology)
- Helminths are the leading identifiable infectious cause, with diagnosis rates ranging from 19-80% in returning travelers and migrants 1
- Common tissue-invasive helminths causing eosinophilia include:
- Strongyloides stercoralis - can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients 1
- Schistosomiasis - particularly with freshwater exposure in Africa; can lead to bladder carcinoma and portal hypertension 1
- Hookworm (Ancylostoma duodenale, Necator americanus) - often causes eosinophilia >3,000 cells/mm³ 1
- Ascaris lumbricoides - worldwide distribution 3
- Filariasis - especially with West Africa exposure 1
- Onchocerciasis (Onchocerca volvulus) - associated with river exposure in Africa 1
- Toxocariasis (T. canis, T. catis) - causes visceral larva migrans 1
Fungal Infections
- Coccidioidomycosis and paracoccidioidomycosis can cause eosinophilia, especially in immunocompromised patients 1
- Cryptococcosis, endemic systemic mycoses, and invasive mold infections (Aspergillus fumigatus, Mucor spp.) are non-parasitic causes 4
Non-Infectious Causes
Allergic/Atopic Disorders (80% of Cases)
- Allergic and atopic conditions constitute the overwhelming majority of secondary reactive eosinophilia 1, 2
- Common allergic causes include:
Drug Reactions
Hematologic Malignancies
- Myeloid and lymphoid neoplasias with eosinophilia and tyrosine kinase fusion genes (e.g., FIP1L1-PDGFRA) 2, 5
- Severe eosinophilia (>5,000/µl) is mostly caused by myeloproliferative disorders 6
Other Causes
- Solid tumors, especially in advanced disease 2
- Autoimmune diseases and vasculitides 2, 6
- Eosinophilic granulomatosis with polyangiitis 6
- Hypereosinophilic syndrome (eosinophilia >1,500/µl for >6 months with end-organ damage after exclusion of other causes) 6
Geographic and Temporal Considerations
Geographic Distribution
- Detailed travel history is essential, as helminth distribution varies by region 1
- Schistosomiasis requires freshwater exposure in endemic areas (primarily Africa) 1
- Filariasis is concentrated in West Africa 1
- Onchocerciasis occurs near fast-flowing rivers in Africa, Central/South America, and Arabian peninsula 3
Timing of Eosinophilia
- Eosinophilia may be transient during the tissue migration phase of helminth infection (pre-patent period) 3, 2
- Serological tests for helminths may not become positive until 4-12 weeks after infection 1, 2
- Stool microscopy may be negative during tissue migration when eosinophilia is present 1
Clinical Significance and End-Organ Damage
Organ Involvement
- Persistent eosinophilia, especially >1.5 × 10⁹/L, can cause significant end-organ damage 1
- Target organs include:
Specific Complications
- Schistosomiasis can cause spinal cord compression, bladder carcinoma, and portal hypertension 3, 1
- S. stercoralis hyperinfection syndrome has high mortality in immunocompromised patients 1
- Onchocerciasis causes dermatitis, keratitis, anterior uveitis, and choroidoretinitis 1
Critical Diagnostic Pitfalls
- Many people with helminth infection do not have eosinophilia, so eosinophilia testing alone is inadequate for screening 1
- Serological tests may exhibit cross-reactivity between different helminth species 1
- Stool microscopy may be negative during tissue migration phase when eosinophilia is present 1
- Patients with eosinophilia and evidence of end-organ damage need urgent medical assessment 1
- For persistent eosinophilia ≥1.5 × 10⁹/L for >3 months with no identified cause, referral to hematology is mandatory 1