What is the initial step in the workup and treatment of a patient with hypereosinophilia?

Hypereosinophilia Workup

The initial step in evaluating hypereosinophilia is to confirm the eosinophil count with a complete blood count with differential, then immediately assess for end-organ damage (cardiac, pulmonary, neurologic, gastrointestinal) and exclude secondary causes—particularly parasitic infections, allergies, and drug reactions—before considering primary hematologic disorders. 1, 2

Immediate Assessment for End-Organ Damage

Any patient with hypereosinophilia presenting with symptoms of organ involvement requires urgent medical evaluation and consideration of emergency treatment 1:

• Cardiac: Perform echocardiography and/or cardiac MRI to detect endomyocardial thrombosis and fibrosis, which are particularly common in primary neoplastic variants 1, 2
• Pulmonary: Order pulmonary function tests and chest imaging for respiratory symptoms 2
• Neurologic: Conduct neurological evaluation with imaging if central nervous system involvement is suspected 1, 2
• Gastrointestinal: Perform endoscopy with biopsies for suspected GI involvement 2

Classification by Eosinophil Count

The degree of eosinophilia guides the urgency and depth of workup 2, 3:

• Mild eosinophilia (500-1500 cells/μL): Evaluate for common causes including allergies, atopy (asthma, eczema, hay fever), drug reactions, and autoimmune disorders 1, 2
• Hypereosinophilia (≥1500 cells/μL): Requires more extensive investigation, particularly if persistent for more than 3 months, with referral to hematology once infectious causes are excluded or treated 1, 2

Initial Laboratory Workup

Basic Testing

• Complete blood count with differential: Assess for dysplasia, monocytosis, and circulating blasts that suggest myeloproliferative disorders 2
• Routine serum chemistries: Include liver function tests, lactate dehydrogenase, and uric acid 2
• Vitamin B12 levels: May be elevated in myeloproliferative variants 2
• Serum immunoglobulins: Measure IgG, IgA, IgM, and IgE (note the inverse relationship between IgE and eosinophil counts in certain conditions) 2
• Inflammatory markers: C-reactive protein and erythrocyte sedimentation rate 2
• Urinalysis: Assess for proteinuria using 24-hour collection or protein-to-creatinine ratio 2

Exclude Secondary (Reactive) Causes

Parasitic Infections

In returning travelers and migrants, helminths are the most common identifiable cause (19-80% of cases) 1:

• Serology testing: For Strongyloides (the most common parasitic infection causing eosinophilia), Schistosoma, Toxocara, and filarial infections 1, 2, 4
• Stool examination: Three concentrated stool samples for ova and parasites if gastrointestinal symptoms present 1, 2
• Geographic considerations: Filarial investigations now recommended only for those with history of travel to/residence in West Africa 1
• Timing caveat: Eosinophilia may be transient during tissue migration phase when microscopic studies are negative; serology may not become positive until 4-12 weeks post-infection 4

Non-Infectious Causes

Allergic disorders account for approximately 80% of secondary eosinophilia cases 1, 4:

• Medications: Review all drugs, particularly NSAIDs, beta-lactam antibiotics, and nitrofurantoin 4
• Allergic/atopic conditions: Asthma, food allergies, atopic dermatitis, drug reactions 1, 4
• Autoimmune/vasculitis: ANCA testing for eosinophilic granulomatosis with polyangiitis (EGPA), which typically presents with marked eosinophilia (>1500 cells/μL or >10%), asthma, and recurrent nasal polyps 1

Advanced Testing for Primary (Neoplastic) Causes

If secondary causes are excluded and eosinophilia persists ≥1500 cells/μL for >3 months, proceed with hematology referral for 1, 2, 5:

Bone Marrow Evaluation

• Bone marrow aspirate and biopsy with immunohistochemistry 2
• Conventional cytogenetics and fluorescence in situ hybridization (FISH) 2
• Molecular testing: Nested RT-PCR to detect tyrosine kinase fusion gene rearrangements (PDGFRA, PDGFRB, FGFR1, JAK2) 1, 2, 5

Flow Cytometry

• T-cell immunophenotyping: To detect lymphocyte-variant HES, characterized by aberrant T-cells (CD3-, CD4+, CD8- or CD3+, CD4-, CD7-) that produce IL-5 and drive reactive eosinophilia 1
• T-cell clonality assessment: 10-20% of lymphocyte-variant HES can evolve to T-cell lymphoma 1

Critical Pitfalls to Avoid

• Missing life-threatening Strongyloides: This parasite can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients; always test for Strongyloides in at-risk populations 1
• Overlooking cardiac involvement: Endomyocardial damage is an independent risk factor for mortality and requires early detection 1
• Not testing for PDGFRA/PDGFRB rearrangements: These mutations predict exquisite responsiveness to imatinib, making their identification critical for treatment selection 5
• Assuming eosinophilia equals helminth infection: Many helminth-infected individuals do not have eosinophilia, and eosinophilia screening alone is inadequate for helminth detection 1

Special Population Considerations

Returning Travelers and Migrants

• Empirical treatment with albendazole 400 mg single dose plus ivermectin 200 μg/kg single dose is now recommended for asymptomatic eosinophilia in those >24 months after first-line testing 1
• Consider geographic exposure history when selecting parasitic testing 1, 4

Idiopathic Hypereosinophilia

If no cause is identified after comprehensive workup, the condition is termed idiopathic hypereosinophilia (or idiopathic hypereosinophilic syndrome if end-organ damage is present) 1