What is the management approach for a patient presenting with hypereosinophilia?

Management of Hypereosinophilia

All patients with hypereosinophilia (≥1.5 × 10⁹/L) require immediate evaluation for end-organ damage—particularly cardiac, pulmonary, and neurological involvement—as these complications can progress to irreversible damage and death if not treated emergently. 1

Immediate Assessment for Life-Threatening Complications

The first priority is identifying patients who need emergency intervention:

• Cardiac evaluation is mandatory in all patients with hypereosinophilia, including electrocardiogram, cardiac troponin, and NT-proBNP measurement to detect myocardial injury 1, 2
• Echocardiography and cardiac MRI are indicated when troponin is elevated or clinical features suggest cardiac injury (chest pain, dyspnea, heart failure symptoms, arrhythmias) to distinguish eosinophilic cardiac disease from other etiologies 1, 2
• Any absolute eosinophil count >5.0 × 10⁹/L at any time carries significant risk of morbidity and mortality and demands urgent comprehensive evaluation 1, 2
• Pulmonary compromise (persistent cough, wheezing, infiltrates on imaging) requires pulmonary function tests, chest radiography, and bronchoscopy with bronchoalveolar lavage when imaging suggests parenchymal disease 1, 2
• Neurological compromise (altered mental status, focal deficits, peripheral neuropathy) necessitates electromyography to confirm eosinophil-induced peripheral neuropathy, with nerve biopsy if EMG findings are consistent 1, 2

Critical History and Initial Workup

After stabilizing any acute organ damage, obtain specific historical details:

• Travel history focusing on fresh water exposure in Africa/tropical regions (schistosomiasis), consumption of raw or undercooked meat, and timing of travel relative to eosinophilia onset, as helminth infections account for 19-80% of cases in returning travelers 1, 3
• Medication review for NSAIDs, beta-lactam antibiotics, and nitrofurantoin, which are common causes of drug-induced eosinophilia 1
• Gastrointestinal symptoms such as dysphagia or food impaction suggest eosinophilic esophagitis and require endoscopy with at least 6 biopsies from different anatomical sites in the esophagus 4
• Constitutional symptoms including fever, weight loss, or night sweats raise concern for malignancy or systemic vasculitis 1

Mandatory Initial Laboratory Studies

• Complete blood count with differential, comprehensive metabolic panel with uric acid, LDH, and liver function tests 1
• Serum tryptase levels (elevated in myeloproliferative neoplasms with PDGFRA fusion and systemic mastocytosis) 1
• Vitamin B12 levels (elevated in myeloproliferative variants) 1
• Peripheral blood smear to evaluate for dysplasia, monocytosis, or circulating blasts 1

Parasite Evaluation (Essential in All Patients with Travel History)

• Three separate concentrated stool microscopy samples for eggs and parasites 1, 3
• Strongyloides serology is critical because this parasite can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients 1, 2, 3
• Schistosomiasis serology if there was exposure to fresh water in endemic areas 1, 3

Empirical Antiparasitic Treatment

• For patients >24 months with asymptomatic eosinophilia and suspected helminthic infection: empirical treatment with albendazole 400 mg plus ivermectin 200 μg/kg in a single dose 1
• For confirmed hookworm infection: albendazole 400 mg in a single dose 1, 3
• Critical warning for Loa loa: Do not use diethylcarbamazine if microfilariae are observed in blood, as it can cause fatal encephalopathy; use corticosteroids with albendazole first to reduce microfilarial load to <1000/ml before definitive treatment 1, 2

Hematology Referral Criteria

If eosinophilia ≥1.5 × 10⁹/L persists for more than 3 months after excluding or treating infectious causes, referral to hematology is required for bone marrow evaluation 1, 2

The hematology workup includes:

• Bone marrow aspiration and biopsy with immunohistochemistry for CD117, CD25, tryptase, and reticulin/collagen stains for fibrosis 1
• Conventional cytogenetics 1
• FISH and/or nested RT-PCR for tyrosine kinase fusion gene rearrangements (especially PDGFRA, PDGFRB, FGFR1), as these respond exquisitely to imatinib 1, 5, 6
• Next-generation sequencing using myeloid mutation panels to establish clonality when no tyrosine kinase fusion gene rearrangements are detected 1

Treatment Based on Etiology

Myeloproliferative Neoplasms with Tyrosine Kinase Fusions

Identification of rearranged PDGFRA or PDGFRB is critical because these diseases respond exquisitely to imatinib 1, 5, 6

• Special precaution for hypereosinophilic syndrome with cardiac involvement: Consider performing echocardiogram and serum troponin in patients with HES/CEL; if either is abnormal, consider prophylactic systemic steroids (1-2 mg/kg) for 1-2 weeks concomitantly with imatinib at initiation of therapy to prevent cardiogenic shock from HES cell degranulation 7, 8
• Pemigatinib was recently approved for patients with relapsed or refractory FGFR1-rearranged neoplasms 5

Lymphocytic Variant Hypereosinophilia and Idiopathic HES

Corticosteroids are first-line therapy for patients with lymphocytic variant hypereosinophilia (aberrant T-cell clone-driven reactive eosinophilia) and idiopathic hypereosinophilic syndrome 1, 5, 6

• Hydroxyurea and interferon-α have demonstrated efficacy as initial treatment and in steroid-refractory cases of HES 5, 6
• Mepolizumab (IL-5 antagonist monoclonal antibody) is FDA-approved for patients with idiopathic HES 5
• Cytotoxic chemotherapy agents and hematopoietic stem cell transplantation have been used for aggressive forms of HES and chronic eosinophilic leukemia 5, 6

Eosinophilic Esophagitis

• Topical corticosteroids (budesonide oral suspension is FDA-approved) or dupilumab (IL-4 receptor alpha antibody, FDA-approved) are effective therapies 4
• Dietary therapy (specific antigen removal or elemental formula) should be considered as effective therapy in all children diagnosed with eosinophilic esophagitis; consultation with a registered dietitian is strongly encouraged 4
• Esophageal dilations are therapeutic options for strictures 4

Watch and Wait Approach

For patients with milder forms of eosinophilia (<1.5 × 10⁹/L) without symptoms or signs of organ involvement, a watch and wait approach with close follow-up may be undertaken 5, 6

Common Pitfalls to Avoid

• Do not assume eosinophilia alone is adequate screening for helminth infection, as many infected patients have normal eosinophil counts 2, 3
• Do not wait for symptoms to develop before investigating persistent moderate-to-severe eosinophilia, as end-organ damage can be subclinical initially 2
• Do not rely solely on peripheral eosinophil counts to assess tissue eosinophilia in conditions like eosinophilic esophagitis, as tissue biopsy is the gold standard 2
• Serological tests for helminths may not become positive until 4-12 weeks after infection 3
• Stool microscopy may be negative during the tissue migration phase of infection when eosinophilia is present 3