What is the appropriate evaluation and management of a patient with elevated eosinophils (eosinophilia)?

Evaluation and Management of Elevated Eosinophils

For patients with elevated eosinophils, immediately assess for end-organ damage (cardiac, pulmonary, neurologic) and obtain a detailed travel history focusing on helminth exposure, as these two factors determine urgency and initial diagnostic direction. 1

Immediate Red Flags Requiring Urgent Assessment

Any patient presenting with the following requires emergency evaluation:

• Cardiac symptoms (chest pain, dyspnea, heart failure, arrhythmias) - obtain ECG, cardiac troponin, NT-proBNP, and echocardiography immediately 1
• Pulmonary involvement (persistent cough, wheezing, infiltrates on imaging) - perform chest X-ray and pulmonary function tests urgently 1
• Neurological symptoms (altered mental status, focal deficits, peripheral neuropathy) - obtain electromyography and consider nerve biopsy 1
• Absolute eosinophil count >5.0 × 10⁹/L at any time - this carries significant mortality risk and requires immediate hematology consultation 1

Severity-Based Diagnostic Approach

Mild Eosinophilia (0.5-1.5 × 10⁹/L)

In non-travelers, allergic disorders and medications are the primary causes; in travelers or migrants, helminth infections account for 19-80% of cases. 1

• Obtain detailed medication history and assess for allergic conditions (asthma, allergic rhinitis, atopic dermatitis) 2, 3
• For any travel history to endemic regions, perform stool microscopy for ova and parasites (3 separate concentrated specimens) 1, 2
• Order Strongyloides serology and culture, as this parasite can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients 1
• Order Schistosomiasis serology if fresh water exposure in Africa or tropical regions occurred 1
• Critical warning: If Loa loa microfilariae are seen on blood film, do NOT use diethylcarbamazine as it may cause fatal encephalopathy; use corticosteroids with albendazole first to reduce microfilarial load to <1000/ml 1

Moderate to Severe Eosinophilia (≥1.5 × 10⁹/L)

If eosinophilia persists >3 months after infectious causes have been excluded or treated, refer to hematology for evaluation of primary eosinophilic disorders. 1

• Perform bone marrow biopsy with morphologic review, standard cytogenetics, fluorescent in situ hybridization, flow immunocytometry, and T-cell clonality assessment 4, 5
• Test for PDGFRA, PDGFRB, and FGFR1 rearrangements - these are critical as they predict exquisite responsiveness to imatinib 4, 5
• Measure serum tryptase and vitamin B12 levels, which are commonly elevated in myeloproliferative variants 1
• Assess for lymphocyte-variant hypereosinophilia through T-cell clonality studies 4, 5

Organ-Specific Evaluation

Gastrointestinal Symptoms (Dysphagia, Food Impaction)

Perform endoscopy with multiple biopsies (six biopsies from at least two different sites in the esophagus) to evaluate for eosinophilic esophagitis. 6, 2

• Peripheral eosinophilia occurs in only 10-50% of adults with eosinophilic esophagitis, so tissue diagnosis is essential 1, 3
• Histological remission is defined as <15 eosinophils per 0.3 mm² 6, 2
• Deep/complete remission is defined as <5 eosinophils per 0.3 mm² 6, 2
• For patients with persistent dysphagia despite histological remission and absence of fibrostenotic disease, perform high-resolution manometry to evaluate for motility disorders 6, 2

Treatment Approach Based on Etiology

Helminth Infections

• Albendazole 400 mg single dose for most helminth infections 2
• Ivermectin 200 μg/kg single dose for strongyloidiasis 2
• For returning travelers with asymptomatic eosinophilia, consider empiric treatment with albendazole 400 mg plus ivermectin 200 μg/kg as single doses 2

Eosinophilic Esophagitis

• Topical corticosteroids (fluticasone or budesonide) decrease blood eosinophil counts in 88% of patients 2, 3
• Two-food elimination diet for 8-12 weeks with support from an experienced dietitian 2
• Allergy testing to foods is NOT recommended for choosing dietary restriction therapy 2

Primary Eosinophilic Disorders

• Imatinib for patients with PDGFRA or PDGFRB rearrangements - these show exquisite responsiveness 4, 5
• Corticosteroids as first-line therapy for lymphocyte-variant hypereosinophilia and idiopathic hypereosinophilic syndrome 4, 5
• Hydroxyurea and interferon-alpha for steroid-refractory cases 4, 5

Critical Pitfalls to Avoid

• Do not assume normal eosinophil counts exclude helminth infection - many infected patients have normal counts 1
• Do not rely solely on peripheral eosinophil counts to assess tissue eosinophilia - tissue biopsy is the gold standard for eosinophilic esophagitis and other organ-specific diseases 6, 1
• Do not wait for symptoms before investigating persistent moderate-to-severe eosinophilia - end-organ damage can be subclinical initially 1
• Do not overlook Strongyloides in immunocompromised patients - this requires urgent evaluation due to high mortality risk of hyperinfection syndrome 1

Monitoring Response to Treatment

• Obtain follow-up eosinophil counts after treatment to assess response 2
• For eosinophilic esophagitis, repeat endoscopy with biopsies if symptoms recur while on treatment 2
• For patients with hypereosinophilia <1,500/mm³ without symptoms or organ involvement, a watch-and-wait approach with close follow-up is appropriate 4, 5