What is the appropriate work‑up and management for an adult with an elevated peripheral eosinophil count?

Workup and Management of Elevated Peripheral Eosinophil Count in Adults

For adults with elevated eosinophils, the first priority is to determine the absolute eosinophil count (AEC) and immediately assess for end-organ damage, because hypereosinophilia (≥1.5 × 10⁹/L) with cardiac, pulmonary, or neurologic involvement requires urgent evaluation and can cause irreversible injury even before symptoms appear. 1

Immediate Risk Stratification

Red Flags Requiring Emergency Assessment

Any patient presenting with eosinophilia plus the following symptoms needs urgent evaluation: 1

• Cardiac: chest pain, dyspnea, heart failure symptoms, arrhythmias
• Pulmonary: persistent cough, wheezing, infiltrates on imaging
• Neurologic: altered mental status, focal deficits, peripheral neuropathy

Obtain ECG, cardiac troponin, and NT-proBNP immediately in all patients with hypereosinophilia to screen for myocardial injury. 1 Echocardiography and cardiac MRI are indicated when troponin is elevated or cardiac symptoms are present. 1

Severity Classification

The AEC determines your diagnostic and management pathway: 1, 2, 3

• Mild eosinophilia (0.5–1.5 × 10⁹/L): Most commonly allergic disorders or medications in non-endemic areas; helminth infections in 19–80% of travelers/migrants
• Moderate-to-severe eosinophilia (≥1.5 × 10⁹/L): Allergy alone rarely causes this level; requires comprehensive infectious workup and hematology referral if persistent >3 months after excluding/treating infections
• Severe eosinophilia (≥5.0 × 10⁹/L): Carries significant risk of morbidity/mortality at any time point

Diagnostic Algorithm

Step 1: Focused History

Travel and exposure history (critical for helminth screening): 1

• Fresh water exposure in Africa/tropical regions (schistosomiasis risk)
• Raw/undercooked meat consumption
• Timing of travel relative to eosinophilia onset
• Geographic regions visited (helminth-endemic areas)

Medication review: 1

• Nitrofurantoin is specifically implicated
• Any new medications coinciding with eosinophilia onset

Symptom assessment for organ involvement: 1

• GI: dysphagia, food impaction (eosinophilic esophagitis)
• Respiratory: chronic cough (40% of cases with cough alone have eosinophilia), wheezing
• Cardiac: as above
• Skin: urticaria, pruritic rash, dermatitis
• Constitutional: fever, weight loss, night sweats (malignancy/vasculitis concern)

Atopic disease history: 1

• 50–80% of adults with mild eosinophilia have concurrent allergic rhinitis, asthma, or atopic dermatitis
• Seasonal variation and pollen exposure can modulate eosinophil counts

Step 2: Initial Laboratory Workup

For all patients with eosinophilia >0.5 × 10⁹/L and travel history: 1

• Three separate concentrated stool specimens for ova and parasites
• Strongyloides serology and culture (critical—can persist lifelong and cause fatal hyperinfection in immunocompromised patients)
• Schistosomiasis serology if fresh water exposure in endemic areas (risk of bladder carcinoma and spinal cord compression)

For hypereosinophilia (≥1.5 × 10⁹/L): 1, 3

• Peripheral blood smear
• Bone marrow biopsy
• Conventional cytogenetics, FISH, and molecular testing for tyrosine-kinase fusions (PDGFRA, PDGFRB, FGFR1)—identification is critical because these respond dramatically to imatinib
• Serum tryptase and vitamin B12 (elevated in myeloid neoplasms with eosinophilia)

Organ-specific screening when indicated: 1

• Chest X-ray and pulmonary function tests for respiratory symptoms
• High-resolution chest CT if infiltrates present
• Bronchoscopy with BAL if parenchymal disease suspected (BAL eosinophils >1% support eosinophilic pattern)

Step 3: Gastrointestinal Evaluation

If dysphagia or food impaction present, perform upper endoscopy with ≥6 biopsies (2–3 proximal, 2–3 distal esophagus). 1

Critical pitfall: Peripheral eosinophilia occurs in only 10–50% of adults with eosinophilic esophagitis—normal blood counts do not exclude the disease; tissue biopsy is the gold standard. 1 Diagnosis requires ≥15 eosinophils per 0.3 mm² (high-power field). 1

Step 4: Empiric Treatment Considerations

For suspected helminthic infection with moderate-to-severe eosinophilia while awaiting results: 1

• Single-dose empirical regimen: albendazole 400 mg plus ivermectin 200 µg/kg

Critical warning for Loa loa: Do not use diethylcarbamazine if microfilariae are seen on blood film—it can cause fatal encephalopathy. Use corticosteroids with albendazole first to reduce microfilarial load to <1,000/mL before definitive treatment. 1

For tropical pulmonary eosinophilia (typically AEC >3 × 10⁹/L): 1

• Diethylcarbamazine (DEC) promptly to prevent irreversible pulmonary fibrosis
• First exclude Loa loa and Onchocerca volvulus co-infection
• Adjunctive prednisolone 20 mg/day for 5 days for ongoing alveolitis
• 20% relapse and require second DEC course

For schistosomiasis: 1

• Praziquantel 40 mg/kg single dose, repeated at 6–8 weeks
• Add prednisolone 20 mg/day for 5 days in acute Katayama syndrome

Management by Etiology

Eosinophilic Esophagitis

First-line treatment: Topical swallowed corticosteroids (fluticasone or budesonide)—achieve blood eosinophil reduction in ~88% of patients. 1

Maintenance therapy is mandatory after achieving remission because relapse rates are high after steroid withdrawal. 1

For fibrostenotic disease: Endoscopic dilation is safe but must be combined with anti-inflammatory therapy. 1

Monitoring: Repeat endoscopy with biopsies if symptoms recur during treatment. 1

Hypereosinophilic Syndrome (HES)

Corticosteroids are first-line therapy for lymphocyte-variant hypereosinophilia and idiopathic HES. 3

Second-line options: 3

• Hydroxyurea
• Interferon-alfa (demonstrated efficacy in steroid-refractory cases)
• Mepolizumab (anti-IL-5 antibody)

Myeloid Neoplasms with PDGFRA/PDGFRB Rearrangements

Imatinib is the treatment of choice—these diseases show exquisite responsiveness. 1, 3

Mild Eosinophilia from Allergic Disorders

For AEC <1.5 × 10⁹/L without organ involvement: 1

• Watch-and-wait approach with eosinophil monitoring every 3–6 months is appropriate after addressing secondary causes
• Optimize control of co-existing atopic diseases (asthma, allergic rhinitis, eczema)
• Consider aeroallergen sensitivity testing (skin-prick or specific IgE)

Referral Criteria

Refer to hematology if: 1

• Eosinophilia ≥1.5 × 10⁹/L persists >3 months after infectious causes excluded or treated
• Any evidence of clonal disorder on initial workup
• PDGFRA/PDGFRB rearrangements identified

Refer to gastroenterology if: 1

• Dysphagia or food impaction present
• Suspected eosinophilic esophagitis

Refer to infectious disease if: 1

• Immunocompromised patient with potential helminth exposure (urgent—high mortality risk from Strongyloides hyperinfection)
• Complex parasitic infection requiring specialized treatment

Common Pitfalls to Avoid

1. Do not assume eosinophilia alone screens for helminth infection—many infected patients have normal eosinophil counts. 1

2. Do not wait for symptoms before investigating persistent moderate-to-severe eosinophilia—end-organ damage can be subclinical initially. 1

3. Do not rely solely on peripheral eosinophil counts to diagnose eosinophilic esophagitis—histologic confirmation is required. 1

4. Do not use diethylcarbamazine in Loa loa microfilaremia—risk of fatal encephalopathy. 1

5. Do not attribute hypereosinophilia (≥1.5 × 10⁹/L) to allergy alone—this level always warrants further workup. 2

6. Do not forget to factor in seasonal pollen exposure, patient age, and control of comorbid allergic disease when interpreting eosinophil trends. 4, 1

Follow-Up and Monitoring

Regular clinic visits every 3–6 months to assess: 1

• Development of symptoms or end-organ damage
• Medication adherence and adverse effects (corticosteroid side effects, imatinib hepatotoxicity)
• Treatment response

For treated eosinophilic esophagitis: Consider surveillance endoscopy every 2–3 years in asymptomatic patients with persistent esophageal eosinophilia, balancing procedural risk against uncertain benefit. 1