Do elevated eosinophils (eosinophilia) always indicate a parasitic infection?

Elevated Eosinophils Do Not Always Indicate Parasitic Infection

Elevated eosinophils (eosinophilia) can be caused by many conditions beyond parasitic infections, including allergies, medications, autoimmune disorders, and certain malignancies. While parasitic infections are an important cause to consider, they represent just one category among many potential etiologies.

Definition and Classification

Eosinophilia is defined as a peripheral blood eosinophil count >0.5 × 10⁹/L, with severity classified as:

• Mild: >0.5 × 10⁹/L
• Moderate: >1.5 × 10⁹/L
• Severe: >5.0 × 10⁹/L 1

Common Causes of Eosinophilia

Infectious Causes

• Parasitic infections: Most commonly helminth infections (worms)
  • Only tissue-invasive helminths cause eosinophilia 2
  • Common parasites: Strongyloides, schistosomiasis, hookworm, filariasis 3
  • Parasitic infections represent the second most common cause of reactive eosinophilia 3

Non-infectious Causes

• Allergic disorders: Most common cause of reactive eosinophilia (approximately 80% of cases) 3
  • Allergic asthma
  • Food allergies
  • Atopic dermatitis
  • Drug reactions
• Medications: NSAIDs, beta-lactam antibiotics, nitrofurantoin 3
• Hematologic malignancies:
  • Lymphomas (especially T-cell lymphomas)
  • Myeloid neoplasms with eosinophilia and tyrosine kinase fusion genes 3
• Autoimmune/inflammatory disorders:
  • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
  • Allergic bronchopulmonary aspergillosis 3
• Solid tumors: Particularly in advanced stage disease 3
• Immunodeficiency syndromes: Hyperimmunoglobulin E syndrome, Omenn syndrome, Wiskott-Aldrich syndrome 3
• Idiopathic hypereosinophilia: When no cause is identified despite thorough investigation 3

Diagnostic Approach

Initial Evaluation

1. Detailed history:

   • Travel history (especially to tropical/subtropical areas)
   • Medication review
   • Allergy history
   • Exposure to freshwater, raw foods, walking barefoot 1

2. Laboratory testing:

   • CBC with differential
   • Peripheral blood smear
   • Comprehensive metabolic panel with liver function tests
   • Serum tryptase and vitamin B12 levels (elevated in myeloproliferative variants) 3, 1

Additional Testing Based on Clinical Suspicion

1. For suspected parasitic infection:

   • Stool examination for ova and parasites (multiple samples)
   • Serological tests for specific parasites based on geographic exposure
   • Strongyloides serology (particularly important as infection can persist for decades) 3

2. For suspected allergic/atopic causes:

   • IgE levels
   • Specific allergen testing

3. For persistent unexplained eosinophilia:

   • Bone marrow aspirate and biopsy with cytogenetics
   • FISH and/or RT-PCR to detect tyrosine kinase fusion gene rearrangements 3

Management Considerations

Management depends on the underlying cause:

1. Parasitic infections: Targeted antiparasitic therapy

   • Strongyloidiasis: Ivermectin 200 μg/kg/day for 1-2 days
   • Schistosomiasis: Praziquantel 40 mg/kg twice daily for 5 days
   • Hookworm: Albendazole 400 mg daily for 3 days 1

2. Drug-induced eosinophilia: Discontinuation of the causative medication 1

3. Allergic disorders: Allergen avoidance, antihistamines, corticosteroids

4. Persistent eosinophilia without identified cause:

   • Consider empirical treatment with albendazole 400 mg plus ivermectin 200 μg/kg for asymptomatic eosinophilia in travelers/migrants with negative initial testing 1
   • Referral to hematology if eosinophilia ≥1.5 × 10⁹/L persists for more than 3 months 3

Important Clinical Pearls

1. Timing matters: Eosinophilia may be transient during the tissue migration phase of parasitic infection, and stool samples may be negative during this pre-patent period 3

2. Geographic considerations: The likelihood of specific parasitic infections varies by geographic region visited 3

3. End-organ damage: Persistent eosinophilia (especially >1.5 × 10⁹/L for >3 months) can cause significant damage to organs, particularly cardiac, pulmonary, and neurological complications 1

4. Strongyloides risk: Don't miss strongyloidiasis, as it can persist lifelong and later present as hyperinfection syndrome with high mortality in immunocompromised patients 3, 1

5. Negative initial testing: Serological tests for parasites may not become positive until 4-12 weeks after infection 3

In conclusion, while parasitic infections are an important consideration in patients with eosinophilia, particularly in returning travelers and migrants, they are far from the only cause. A systematic approach to diagnosis considering the broad differential is essential for appropriate management.