What is the initial step in the workup for a patient presenting with eosinophilia?

Eosinophilia Workup

The initial step in evaluating eosinophilia is to calculate the absolute eosinophil count (AEC) from the CBC with differential, followed immediately by a detailed travel history (focusing on geographic exposures and timing), medication review, and assessment for atopic conditions, then proceed with concentrated stool microscopy (three separate specimens) and targeted serology based on geographic exposure patterns. 1, 2

Calculate Absolute Eosinophil Count First

• Multiply the percentage of eosinophils by the total white blood cell count to determine AEC - this is the critical first calculation that guides all subsequent workup 3
• Eosinophilia is defined as AEC >500 cells/μL, while hypereosinophilia is AEC ≥1,500 cells/μL - this distinction fundamentally changes your diagnostic approach 3, 4
• Mild eosinophilia (500-1,500 cells/μL) is most commonly caused by allergic disorders or medications in non-endemic areas, but helminth infections account for 19-80% of cases in returning travelers 1, 5
• Hypereosinophilia (≥1,500 cells/μL) is never explained by allergy alone and always requires further workup to exclude parasites, drugs, or clonal disorders 2, 3

Obtain Critical History Elements

• Document exact countries visited, duration of stay, and specific exposures: freshwater swimming in Africa suggests schistosomiasis; barefoot walking suggests hookworm; raw/undercooked meat consumption suggests various helminths 2, 6
• Record timing of eosinophilia onset relative to travel - eosinophilia typically appears 4-12 weeks post-exposure during tissue migration phases, which is when serologic tests may still be negative 2, 5
• Review all medications started within the past 3-6 months, particularly NSAIDs, beta-lactam antibiotics, and nitrofurantoin, as these are common culprits 2, 5
• Assess for symptoms of end-organ damage: chest pain, dyspnea, heart failure symptoms (cardiac); persistent cough, wheezing, infiltrates (pulmonary); altered mental status, focal deficits, peripheral neuropathy (neurological); dysphagia or food impaction (gastrointestinal) 1, 2

Perform Initial Laboratory Testing

• Order concentrated stool microscopy on three separate specimens collected on different days - this is mandatory for all patients with eosinophilia regardless of symptoms, as it has high diagnostic yield for intestinal helminths 6, 2
• Obtain Strongyloides serology immediately - this has high diagnostic yield across all geographic regions and is critical because Strongyloides can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients 2, 1, 5
• Order schistosomiasis serology if any freshwater exposure occurred in endemic areas (Africa, parts of Southeast Asia, South America, Arabian peninsula) 2, 6
• Obtain HIV testing, as HIV is associated with eosinophilia, though helminth co-infection is more likely the cause 2

Additional Initial Workup for Moderate-to-Severe Eosinophilia

• Order comprehensive metabolic panel with uric acid, LDH, and liver function tests to assess for organ involvement 2
• Review peripheral blood smear for dysplasia, monocytosis, and circulating blasts to evaluate for myeloproliferative disorders 2
• Measure serum tryptase and vitamin B12 levels - elevated levels are characteristic of myeloproliferative variants, particularly PDGFRA/PDGFRB fusion genes, which respond exquisitely to imatinib 2, 4

Geographic-Based Serologic Testing Algorithm

• Africa exposure with freshwater contact: Schistosoma serology is essential, as Katayama syndrome (acute schistosomiasis) presents 2-9 weeks post-exposure with high-grade eosinophilia, fever, dry cough, and urticarial rash 6
• West Africa exposure: Add filariasis serology (Loa loa, Onchocerca volvulus) 5
• Southeast Asia, South America, or Arabian peninsula: Consider schistosomiasis and filariasis based on specific exposures 6, 5
• Any tropical region: Strongyloides serology is universally indicated 2, 1

Critical Red Flags Requiring Urgent Assessment

• Any eosinophilia with symptoms suggesting end-organ damage requires urgent evaluation and consideration of emergency treatment 1
• Cardiac involvement (chest pain, dyspnea, heart failure, arrhythmias) demands immediate attention, as eosinophil-mediated myocarditis and endomyocardial fibrosis carry high mortality 1, 5
• AEC >5,000 cells/μL at any time or AEC ≥1,500 cells/μL persisting >3 months carries significant risk of morbidity and mortality from end-organ damage 1
• Immunocompromised patients with eosinophilia and potential helminth exposure require urgent evaluation for Strongyloides due to high mortality risk of hyperinfection syndrome 1, 5

Common Pitfalls to Avoid

• Do not assume eosinophilia alone is adequate screening for helminth infection - many infected patients have normal eosinophil counts, so absence of eosinophilia does not exclude parasitic infection 1, 5
• Do not rely solely on stool microscopy during early infection - stool tests may be negative during the tissue migration phase when eosinophilia is present, and serologic tests may not become positive until 4-12 weeks after infection 2, 5
• Do not wait for symptoms to develop before investigating persistent moderate-to-severe eosinophilia - end-organ damage can be subclinical initially 1
• Be aware that serological tests for helminths cross-react (e.g., filarial serology may be positive in strongyloidiasis) - expert consultation is recommended for interpretation 6

When to Refer to Hematology

• Refer if eosinophilia ≥1,500 cells/μL persists for more than 3 months after infectious causes have been excluded or adequately treated 1, 5
• Refer immediately if peripheral blood smear shows dysplasia, monocytosis, or circulating blasts 2
• Refer if serum tryptase or vitamin B12 are elevated, as this suggests myeloproliferative disease requiring molecular testing for PDGFRA/PDGFRB rearrangements 2, 4