What is the initial workup for a patient with elevated eosinophils (eosinophilia)?

Workup for Elevated Eosinophils

The initial workup for elevated eosinophils should include a detailed travel and medication history, comprehensive laboratory testing with CBC and differential, stool studies for parasites, and serology tests based on suspected etiology, with subsequent investigations guided by clinical presentation and eosinophil count severity.

Initial Assessment

Defining Eosinophilia

• Eosinophilia: >0.45-0.5 × 10⁹/L (450-500 cells/μL)
• Mild: 500-1500 cells/μL
• Moderate: 1500-5000 cells/μL
• Severe: >5000 cells/μL
• Hypereosinophilia: ≥1500 cells/μL on at least two occasions, 4 weeks apart 1

Critical First Steps

1. Calculate absolute eosinophil count (percentage of eosinophils × total WBC count)
2. Assess for end-organ damage - persistent eosinophilia >1.5 × 10⁹/L can cause damage to heart, lungs, and CNS 1
3. Determine severity - hypereosinophilia (≥1500 cells/μL) rarely caused by allergy alone and requires thorough investigation 2

Diagnostic Algorithm

Step 1: Detailed History

• Travel history: Specific regions visited, timing, and activities (swimming in freshwater, walking barefoot) 1
• Medication review: NSAIDs, beta-lactams, nitrofurantoin (common causes) 1
• Allergy/atopy history: Asthma, eczema, hay fever 1
• Symptom assessment: Respiratory, gastrointestinal, cutaneous, neurological symptoms 1
• Timing: Recent onset vs. persistent eosinophilia 1

Step 2: Laboratory Testing

First-line Tests for All Patients:

• CBC with differential
• Comprehensive metabolic panel with liver function tests
• Serum tryptase levels
• Vitamin B12 levels
• Peripheral blood smear review 1

Stool Studies:

• Concentrated stool microscopy for ova and parasites (3 samples) 1
• Gastrointestinal PCR for parasites if available 1

Serological Testing Based on Geography:

• For all returning travelers/migrants: Strongyloides serology 1
• For Africa travel history: Schistosomiasis serology 1
• For West Africa travel history: Filarial serology 1
• For suspected parasitic infection: Specific parasite serology based on exposure 1

Step 3: Additional Testing Based on Clinical Suspicion

For Suspected Allergic Disease:

• IgE levels
• Allergen-specific IgE 1

For Suspected Autoimmune Disease:

• Antineutrophil cytoplasmic antibodies (ANCA)
• Antinuclear antibodies (ANA) 1

For Suspected Hematologic Malignancy (especially if AEC ≥1500 cells/μL):

• Bone marrow aspirate and biopsy with:
  • Immunohistochemistry (CD117, CD25, tryptase)
  • Cytogenetics
  • FISH and/or RT-PCR for TK fusion gene rearrangements 1
• Next-generation sequencing (NGS) via myeloid mutation panels 1

For Suspected Pulmonary Involvement:

• Chest imaging
• Pulmonary function tests
• Bronchoalveolar lavage if indicated 1

Special Considerations

Severity-Based Approach

• Mild eosinophilia (500-1500 cells/μL): Often due to allergic disorders, parasitic infections
• Moderate to severe (>1500 cells/μL): Consider hematologic malignancies, hypereosinophilic syndromes, vasculitis 3
• Very severe (>20,000 cells/μL): Highly suggestive of myeloproliferative disorders 3

Geographic Considerations

• Returning travelers/migrants: Focus on parasitic infections (strongyloidiasis, schistosomiasis, filariasis) 1
• No travel history: Focus on allergic, medication-related, autoimmune, and hematologic causes 1

Common Pitfalls and Caveats

1. Don't assume allergy alone: Hypereosinophilia (≥1500 cells/μL) is rarely explained by allergy alone 2

2. Beware of timing issues: Eosinophilia may be transient during tissue migration phase of parasitic infections, and stool studies may be negative during this period 1

3. Cross-reactivity in serological tests: Many helminth serological tests cross-react (e.g., filarial serology may be positive in strongyloidiasis) 1

4. Don't miss Strongyloides: Strongyloidiasis can persist for decades and lead to hyperinfection syndrome in immunocompromised patients 1

5. Consider persistent monitoring: If no cause is found but eosinophilia persists at ≥1.5 × 10⁹/L for more than 3 months, refer to a hematologist 1

6. End-organ damage assessment: Evaluate for cardiac, pulmonary, neurological, and cutaneous involvement in cases of persistent hypereosinophilia 3