What causes elevated eosinophils (eosinophilia)?

Causes of Elevated Eosinophils (Eosinophilia)

Eosinophilia (>0.5 × 10^9/L in peripheral blood) is most commonly caused by parasitic infections, allergic disorders, drug reactions, and autoimmune conditions, with rarer causes including hypereosinophilic syndromes and hematologic malignancies. 1

Common Causes of Eosinophilia

Infectious Causes

• Parasitic infections - Most common infectious cause 2
  • Helminths (particularly during tissue migration phase)
    • Strongyloidiasis
    • Schistosomiasis
    • Filariasis
    • Hookworm infections
    • Toxocariasis (visceral larva migrans)
    • Ascaris lumbricoides
    • Trichuris trichiura
  • Geographic exposure is important - certain parasites have defined geographical limits 2

Allergic/Atopic Causes

• Asthma
• Allergic rhinitis
• Atopic dermatitis/eczema
• Food allergies
• Eosinophilic esophagitis (EoE) 1
• Drug hypersensitivity reactions

Medication-Related Causes

• Common culprits include:
  • Non-steroidal anti-inflammatory drugs (NSAIDs)
  • Beta-lactam antibiotics
  • Nitrofurantoin
  • Antiepileptics
  • Allopurinol 2

Autoimmune/Inflammatory Disorders

• Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) 2
• Other vasculitides
• Connective tissue disorders
• Inflammatory bowel disease (including Crohn's disease) 2

Primary Hematologic Disorders

• Hypereosinophilic syndromes (HES) - Characterized by:
  • Persistent eosinophilia >1.5 x 10^9/L
  • Evidence of eosinophil-mediated organ damage
  • Exclusion of secondary causes 1
• Hematologic malignancies:
  • Chronic eosinophilic leukemia
  • Acute myeloid leukemia with eosinophilia
  • Lymphomas (especially T-cell lymphomas)
  • Mastocytosis 3

Other Causes

• Adrenal insufficiency
• Solid tumors (paraneoplastic)
• Pulmonary disorders (eosinophilic pneumonia)
• Lymphocytic esophagitis (LyE) 2
• HIV infection (although helminth co-infection is more likely) 2

Diagnostic Approach to Eosinophilia

Initial Evaluation

1. Complete blood count with differential to confirm eosinophilia (>0.5 × 10^9/L) 1
2. Detailed clinical history focusing on:
   • Travel history (especially to tropical/subtropical regions)
   • Exposure to freshwater
   • Consumption of raw foods
   • Walking barefoot
   • Current and recent medications
   • Allergy history 1
3. Physical examination looking for:
   • Skin manifestations (rashes, urticaria)
   • Respiratory symptoms
   • Gastrointestinal symptoms
   • Lymphadenopathy
   • Organomegaly

Further Investigations

• Stool examination for ova and parasites (may need multiple samples)
• Serological tests for parasitic infections (may be negative in early infection) 2
• Peripheral blood smear to evaluate blood cell morphology
• Comprehensive metabolic panel with liver function tests
• Urinalysis with protein-to-creatinine ratio
• C-reactive protein to assess inflammation
• Serum tryptase to evaluate mast cell activation 1
• Tissue biopsy of affected organs if indicated

Important Clinical Considerations

Severity Assessment

• Mild eosinophilia (0.5-1.5 × 10^9/L) is often reactive
• Moderate to severe eosinophilia (>1.5 × 10^9/L) warrants more urgent evaluation 1
• Long-standing moderate/high-grade eosinophilia can result in significant end-organ damage 2

Population Differences

• Migrants tend to have higher burden of infection and may have multiple helminth species
• Travelers are often newly infected with more pronounced immune response and eosinophilia
• Chronic complications like bladder carcinoma from schistosomiasis are more common in migrants 2

Timing Considerations

• Eosinophilia may be transient during tissue migration phase of parasitic infections
• Stool samples may be negative during pre-patent period
• Serological tests often don't become positive until 4-12 weeks after infection 2

Common Pitfalls

• Not considering geographic exposure - Travel history is crucial for diagnosing parasitic causes
• Premature discontinuation of evaluation after initial negative tests
• Overlooking drug causes - Always review medication history thoroughly
• Failure to recognize hypereosinophilic syndrome which requires persistent eosinophilia >1.5 x 10^9/L and evidence of organ damage 1
• Missing underlying malignancy - Consider bone marrow examination in unexplained persistent eosinophilia

Remember that while many causes of eosinophilia are benign and self-limiting, some can lead to significant morbidity and mortality if not properly diagnosed and treated.