What investigations are recommended for a patient with persistent eosinophilia?

Investigations for High Eosinophil Count

Immediate Risk Stratification and Urgent Evaluation

Any patient with eosinophilia presenting with cardiac symptoms (chest pain, dyspnea, heart failure), pulmonary symptoms (persistent cough, wheezing, infiltrates), or neurological symptoms (altered mental status, focal deficits, neuropathy) requires urgent evaluation for end-organ damage and consideration of emergency treatment. 1, 2, 3

• An absolute eosinophil count ≥5.0 × 10⁹/L at any time or ≥1.5 × 10⁹/L persisting for more than 3 months carries significant risk of morbidity and mortality from irreversible cardiac, pulmonary, and neurological injury. 2, 3, 4, 5

Essential History Components

Obtain a detailed travel history focusing on exact timing and locations, particularly fresh water exposure in Africa or tropical regions, consumption of raw or undercooked meat, and walking barefoot, as helminth infections account for 19-80% of eosinophilia cases in returning travelers. 1, 2, 3

• Document all medications, especially NSAIDs, beta-lactam antibiotics, nitrofurantoin, olmesartan, mycophenolate mofetil, and azathioprine, as these commonly cause drug-induced eosinophilia. 2, 3, 6
• Ask specifically about dysphagia or food impaction, which suggest eosinophilic esophagitis requiring endoscopic evaluation. 2, 3
• Assess for atopic conditions (asthma, allergic rhinitis, atopic dermatitis), which account for 50-80% of mild eosinophilia cases in non-travelers. 2

First-Line Laboratory Investigations

All patients with eosinophilia require complete blood count with differential, comprehensive metabolic panel including LDH and liver function tests, and three separate concentrated stool microscopy samples for ova and parasites. 1, 2, 3

Parasitic Evaluation (Mandatory in All Cases)

• Strongyloides serology is critical because this parasite persists lifelong and causes fatal hyperinfection syndrome in immunocompromised patients, even decades after initial exposure. 1, 2, 3
• Schistosomiasis serology if any fresh water exposure in endemic areas (Africa, Southeast Asia, South America, Arabian peninsula), as chronic infection causes squamous cell bladder carcinoma and portal hypertension. 1, 2
• Filarial serology if travel to endemic areas, noting that cross-reactivity with Strongyloides is common. 1

Critical timing consideration: Stool microscopy may be negative during the tissue migration phase (prepatent period) when eosinophilia is highest, and serological tests may not become positive until 4-12 weeks after infection. 1, 3

Additional Initial Laboratory Studies

• Peripheral blood smear to evaluate for dysplasia, monocytosis, or circulating blasts. 3, 4, 5
• Serum tryptase (elevated in myeloproliferative neoplasms with PDGFRA fusion and systemic mastocytosis). 3
• Vitamin B12 (elevated in myeloproliferative variants). 3
• IgE level and specific allergen testing if atopic disease suspected. 2

Organ-Specific Investigations Based on Symptoms

Cardiac Evaluation (If Any Cardiac Symptoms or AEC ≥1.5 × 10⁹/L)

• Electrocardiogram, cardiac troponin, and NT-proBNP measurement in all patients with hypereosinophilia. 2, 3
• Echocardiography when troponin elevated or clinical features suggest cardiac injury. 2, 3
• Cardiac MRI when elevated troponin or clinical cardiac features present to distinguish eosinophilic cardiac disease from other etiologies. 2, 3

Pulmonary Evaluation (If Respiratory Symptoms)

• Chest radiograph to identify pulmonary infiltrates (migratory infiltrates suggest Loeffler's syndrome; interstitial/reticulonodular patterns suggest tropical pulmonary eosinophilia). 2
• Pulmonary function tests in all patients with respiratory symptoms. 2, 3
• High-resolution chest CT to delineate distribution and nature of infiltrates. 2
• Bronchoscopy with bronchoalveolar lavage when imaging suggests parenchymal disease (BAL eosinophil proportion >1% supports eosinophilic lung disease). 2

Gastrointestinal Evaluation (If Dysphagia, Food Impaction, or GI Symptoms)

Upper endoscopy with at least 6 biopsies (2-3 from proximal and 2-3 from distal esophagus) is mandatory for suspected eosinophilic esophagitis, as peripheral eosinophilia occurs in only 10-50% of adult cases. 1, 2, 3

• Diagnosis requires ≥15 eosinophils per 0.3 mm² (high-power field) on esophageal biopsy. 2, 3
• Look for endoscopic features: linear furrowing, white exudates, circular rings, "crêpe paper" mucosa, strictures. 1

Neurological Evaluation (If Neurological Symptoms)

• Electromyography to confirm eosinophil-induced peripheral neuropathy. 2, 3
• Nerve biopsy if EMG findings consistent with neuropathy. 2, 3

Hematology Referral and Advanced Testing

If eosinophilia ≥1.5 × 10⁹/L persists for more than 3 months after excluding or treating infectious causes, refer to hematology for bone marrow evaluation. 2, 3, 4, 5, 7

Bone Marrow Evaluation Includes:

• Bone marrow aspiration and biopsy with immunohistochemistry for CD117, CD25, tryptase, and reticulin/collagen stains for fibrosis. 3
• Standard cytogenetics and fluorescence in situ hybridization (FISH). 3, 4, 5, 7
• Nested RT-PCR or next-generation sequencing for tyrosine kinase fusion gene rearrangements (PDGFRA, PDGFRB, FGFR1, PCM1-JAK2) is critical, as these respond exquisitely to imatinib. 3, 4, 5, 7, 8
• Flow immunophenotyping to detect clonal hematolymphoid neoplasm. 4, 5, 7, 8
• T-cell clonality assessment to evaluate for lymphocyte-variant hypereosinophilia. 4, 5, 7, 8

Empirical Treatment Considerations While Awaiting Results

For asymptomatic patients with moderate-to-severe eosinophilia (≥1.5 × 10⁹/L) and travel history to endemic areas, empirical treatment with albendazole 400 mg single dose plus ivermectin 200 μg/kg single dose is recommended while awaiting parasitic test results. 2, 6

Critical warning for Loa loa: Do not use diethylcarbamazine if microfilariae are seen on blood film, as it may cause fatal encephalopathy; use corticosteroids with albendazole first to reduce microfilarial load to <1000/mL before definitive treatment. 2

Common Pitfalls to Avoid

• Do not assume eosinophilia alone is adequate screening for helminth infection—many infected patients have normal eosinophil counts, so screening based on exposure history is essential even without eosinophilia. 1, 2, 3
• Do not wait for symptoms before investigating persistent moderate-to-severe eosinophilia—end-organ damage can be subclinical initially and may become irreversible. 2, 3
• Do not rely solely on peripheral eosinophil counts to diagnose eosinophilic esophagitis—tissue biopsy is the gold standard, as 50-90% of adult cases have normal peripheral counts. 1, 2, 3
• Do not send stool samples only once—three separate concentrated specimens are required for adequate sensitivity. 1, 2, 3
• Do not overlook medication-induced eosinophilia, particularly olmesartan, which can mimic refractory celiac disease. 6