What is the appropriate management for a patient presenting with significant eosinophilia?

Management of Significant Eosinophilia

For patients presenting with significant eosinophilia, immediately assess for end-organ damage (cardiac, pulmonary, neurologic) and exclude helminth infections before initiating any immunosuppressive therapy, as these two factors determine both urgency and treatment approach. 1, 2

Immediate Risk Stratification

Define the Severity

• Mild eosinophilia (0.5-1.5 × 10⁹/L): Most commonly caused by allergic disorders or medications in non-endemic areas 1
• Moderate-to-severe eosinophilia (≥1.5 × 10⁹/L): Requires hematology referral if persisting >3 months after infectious causes excluded 1, 2
• Critical threshold (>5.0 × 10⁹/L): Carries significant risk of morbidity and mortality at any time, demands urgent comprehensive evaluation 2

Assess for Life-Threatening Complications Immediately

Cardiac evaluation is mandatory for all patients with hypereosinophilia: 2

• Obtain electrocardiogram, cardiac troponin, and NT-proBNP immediately 1, 2
• If troponin elevated or symptoms present (chest pain, dyspnea, heart failure, arrhythmias): perform echocardiography and cardiac MRI to distinguish eosinophilic cardiac disease from other etiologies 1, 2

Pulmonary assessment if respiratory symptoms present: 1

• Obtain chest X-ray to identify infiltrates 1
• Perform pulmonary function tests for persistent cough, wheezing, or dyspnea 1
• Consider bronchoscopy with bronchoalveolar lavage if imaging suggests parenchymal disease 1, 2

Neurologic evaluation if deficits present: 1

• Perform electromyography to confirm eosinophil-induced peripheral neuropathy 1, 2
• Consider nerve biopsy if EMG findings consistent with neuropathy 1

Critical History Elements

Travel and exposure history (helminth infections account for 19-80% of cases in travelers): 1, 3, 2

• Fresh water exposure in Africa/tropical regions (schistosomiasis risk) 1, 3
• River exposure in Africa, Central/South America, Arabian peninsula (onchocerciasis) 3
• Raw or undercooked meat consumption 1
• Timing of travel relative to eosinophilia onset 1, 3

Medication review for common culprits: 3

• NSAIDs, beta-lactam antibiotics, nitrofurantoin 3, 2

Gastrointestinal symptoms: 1

• Dysphagia or food impaction suggests eosinophilic esophagitis, requires endoscopy with minimum 6 biopsies (2-3 proximal, 2-3 distal esophagus) 1, 2

Mandatory Initial Workup

Parasitic Evaluation (Must Complete Before Corticosteroids)

Critical warning: Never initiate corticosteroids before excluding Strongyloides, as this can trigger fatal hyperinfection syndrome in infected patients. 1, 3, 2

Required tests for all patients with eosinophilia >0.5 × 10⁹/L and travel history: 1

• Three separate concentrated stool specimens for ova and parasites 1, 3, 2
• Strongyloides serology and culture (can persist lifelong and cause fatal hyperinfection in immunocompromised patients) 1, 3, 2
• Schistosomiasis serology if freshwater exposure in endemic areas 1, 3, 2

Important caveat: Many helminth-infected patients do not have eosinophilia, so normal counts do not exclude infection. 1, 3, 2

Additional pitfalls to avoid: 3, 2

• Serological tests may not become positive until 4-12 weeks after infection 3, 2
• Stool microscopy may be negative during tissue migration phase when eosinophilia is present 3, 2

Hematologic Evaluation

Complete blood count with differential, comprehensive metabolic panel, LDH, liver function tests 2

Peripheral blood smear to evaluate for: 2

• Dysplasia, monocytosis, or circulating blasts 2

Additional markers if primary eosinophilia suspected: 2

• Serum tryptase (elevated in myeloproliferative neoplasms with PDGFRA fusion) 2
• Vitamin B12 (elevated in myeloproliferative variants) 2

Treatment Based on Etiology

Helminth Infections

For hookworm/Ascaris (Loeffler's syndrome): 1

• Albendazole 400 mg twice daily for 3 days 1

For Strongyloidiasis: 1

• Ivermectin 200 μg/kg daily for 2 days 1

For Schistosomiasis: 1

• Praziquantel 40 mg/kg single dose, repeat at 6-8 weeks 1
• Add prednisolone 20 mg/day for 5 days in acute Katayama syndrome 1

For tropical pulmonary eosinophilia: 1

• Diethylcarbamazine (DEC) promptly to prevent irreversible pulmonary fibrosis 1
• Critical warning for Loa loa: Do not use DEC if microfilariae seen on blood film—can cause fatal encephalopathy. Use corticosteroids with albendazole first to reduce microfilarial load to <1000/ml before definitive treatment. 1
• Adjunctive prednisolone 20 mg/day for 5 days for ongoing alveolitis 1
• 20% of patients relapse and require second DEC course 1

Empiric treatment for asymptomatic patients >24 months with suspected helminth infection: 3

• Albendazole 400 mg plus ivermectin 200 μg/kg as single doses 3

Eosinophilic Esophagitis

First-line treatment: 1

• Topical swallowed corticosteroids (fluticasone or budesonide) decrease blood eosinophil counts in 88% of patients 1

Maintenance therapy is mandatory after achieving remission due to high relapse rates after steroid withdrawal 1

For fibrostenotic disease: 1

• Endoscopic dilation is safe and effective but must be combined with anti-inflammatory therapy 1

Primary Eosinophilia/Hypereosinophilic Syndrome

Hematology referral criteria: 1, 2

• Eosinophilia ≥1.5 × 10⁹/L persisting >3 months after excluding/treating infectious causes 1, 2

Bone marrow evaluation required: 2

• Aspiration and biopsy with immunohistochemistry for CD117, CD25, tryptase, reticulin/collagen stains 2
• FISH and/or nested RT-PCR for tyrosine kinase fusion gene rearrangements (PDGFRA, PDGFRB, FGFR1) 2, 4

Treatment based on molecular findings: 5, 4, 6

• PDGFRA or PDGFRB rearrangements: Imatinib (exquisite responsiveness) 2, 5, 4, 6
• FGFR1-rearranged neoplasms: Pemigatinib (recently approved for relapsed/refractory cases) 4

For idiopathic hypereosinophilic syndrome or lymphocyte-variant HE: 5, 4, 6

• Corticosteroids are first-line therapy 5, 4, 6
• Hydroxyurea and interferon-α for initial treatment or steroid-refractory cases 4, 6
• Mepolizumab (IL-5 antagonist) is FDA-approved for idiopathic HES 4

For aggressive forms of HES or chronic eosinophilic leukemia: 4, 6

• Cytotoxic chemotherapy agents 4, 6
• Hematopoietic stem cell transplantation 4, 6

Monitoring Strategy

For mild eosinophilia (<1.5 × 10⁹/L) without symptoms or organ involvement: 4, 6

• Watch and wait approach with close follow-up 4, 6

For treated patients: 1

• Monitor eosinophil counts after treatment to confirm resolution 3
• Monitor for treatment-related complications (corticosteroid side effects, imatinib hepatotoxicity) 1
• Repeat endoscopy with biopsies if symptoms recur during treatment for eosinophilic esophagitis 1