Workup of Eosinophilia
Begin with a detailed travel history (including specific freshwater exposure, barefoot walking, and raw food consumption), medication review, and assessment for atopic conditions, followed by CBC with differential to calculate absolute eosinophil count (AEC), then proceed with stool microscopy and targeted serology based on geographic exposure. 1, 2
Initial Clinical Assessment
History Taking - Key Elements
- Travel history: Document exact countries visited, duration, and specific exposures (freshwater swimming in Africa suggests schistosomiasis; barefoot walking suggests hookworm; raw fish consumption suggests anisakiasis) 1
- Medication review: Focus on recent additions, particularly NSAIDs, beta-lactam antibiotics, and nitrofurantoin 3
- Timing: Note when eosinophilia first appeared relative to travel or medication changes, as eosinophilia may be transient during tissue migration phases (4-12 weeks post-exposure) 1
- Symptoms of end-organ damage: Assess for cardiac symptoms (chest pain, dyspnea), neurological symptoms (headache, focal deficits), respiratory symptoms (cough, wheeze), and skin manifestations 2, 3
- Atopic history: Document asthma, allergic rhinitis, atopic dermatitis, and food allergies 3, 4
Physical Examination Focus
- Skin evaluation for urticarial rash, serpiginous lesions (cutaneous larva migrans), or nodules 1
- Hepatosplenomegaly palpation 1
- Conjunctival suffusion (suggests leptospirosis) 1
- Signs of immunodeficiency 1
Laboratory Workup Algorithm
First-Line Testing (All Patients)
- CBC with differential: Calculate AEC (percentage × total WBC count); eosinophilia defined as >500/μL, hypereosinophilia as ≥1500/μL 5, 6
- Comprehensive metabolic panel with uric acid, LDH, and liver function tests 1
- Peripheral blood smear: Review for dysplasia, monocytosis, circulating blasts 1
- Concentrated stool microscopy (3 samples on separate days): Essential for all patients regardless of symptoms 1, 3
- Serum tryptase and vitamin B12 levels: Elevated in myeloproliferative variants, particularly PDGFRA fusion genes 1
Second-Line Testing Based on Exposure/Symptoms
For travelers/migrants from endemic areas:
- Strongyloides serology: High yield across all tropical regions 1, 3
- Schistosomiasis serology: If freshwater exposure in Africa, South America, or Southeast Asia (note: may be negative in first 4-12 weeks) 1
- Filariasis serology: If travel to West Africa or other endemic areas 3
- Stool ova and parasites with GI PCR 1
For specific clinical presentations:
- Aspergillus-specific IgE and total IgE: If respiratory symptoms suggest ABPA 1
- HIV testing: Recommended as HIV associated with eosinophilia, though helminth co-infection more likely 3
- ANCA and ANA: If vasculitis suspected 1
- ESR and CRP: For inflammatory conditions 1
Third-Line Testing (Persistent Hypereosinophilia ≥1500/μL)
When secondary causes excluded and eosinophilia persists >3 months:
- Bone marrow aspirate and biopsy with:
- NGS via myeloid mutation panels: To establish clonality when no TK fusion genes detected 1
Diagnostic Classification Framework
Mild Eosinophilia (<1500/μL)
- Most commonly secondary to allergic conditions (80% of cases) or parasitic infections 3, 7
- Watch-and-wait approach acceptable if asymptomatic and no organ involvement 7, 5, 8
- Close follow-up with repeat AEC 7
Hypereosinophilia (≥1500/μL)
- Never explained by allergy alone - always requires further workup 6
- Exclude secondary causes first (parasites, drugs, allergic conditions) 7, 5
- If persistent >3 months with no identified cause: refer to hematology 2, 4
Critical Pitfalls to Avoid
- Serology timing: Most helminth serologies negative until 4-12 weeks post-infection; repeat if initial testing negative but clinical suspicion high 1
- Cross-reactivity: Filarial serology may be positive in strongyloidiasis; interpret with expert consultation 1
- Stool microscopy limitations: May be negative during tissue migration phase when eosinophilia is highest 1
- Screening misconception: Many helminth infections occur without eosinophilia; eosinophil testing alone inadequate for helminth screening 2, 3
- Urgent assessment needed: Any evidence of end-organ damage (cardiac, neurological, pulmonary) requires immediate evaluation regardless of AEC level 2, 3
Special Considerations
Katayama Syndrome (Acute Schistosomiasis)
- Suspect with: freshwater exposure 4-8 weeks prior + fever + urticarial rash + eosinophilia 1
- Serology and stool/urine may be negative initially 1
- Empiric treatment justified based on clinical presentation 1
Gastrointestinal Symptoms
- Consider endoscopy with multiple biopsies (≥6 from ≥2 sites) to evaluate for eosinophilic esophagitis if dysphagia or food impaction present 2, 4
- Histological diagnosis requires >15 eosinophils per 0.3 mm² 2, 4