What is the approach for evaluating and treating eosinophilia?

Evaluation and Treatment of Eosinophilia

Initial Diagnostic Approach

Begin by determining the absolute eosinophil count and assessing for secondary causes, particularly parasitic infections in patients with travel history to endemic regions, as these represent the most common and treatable etiologies. 1, 2

Key Historical Elements to Obtain

• Travel history to tropical or subtropical regions, with specific attention to exposure risk for helminthic infections 1
• Medication history, as drug reactions are a common cause of eosinophilia 3
• Gastrointestinal symptoms (dysphagia, food impaction, abdominal pain, diarrhea) suggesting eosinophilic esophagitis or other GI eosinophilic disorders 1
• Respiratory symptoms (cough, wheeze, dyspnea) indicating possible Loeffler's syndrome, tropical pulmonary eosinophilia, or Churg-Strauss syndrome 1, 3
• Cardiac symptoms or risk factors, as eosinophil-mediated cardiac damage can be life-threatening 4, 5

Initial Laboratory and Diagnostic Testing

• Stool microscopy (concentrated specimens) for parasitic ova and larvae 1, 2
• Serology for helminth infections based on geographic exposure (schistosomiasis, strongyloidiasis, filariasis, toxocariasis) 1, 2
• Complete blood count to quantify absolute eosinophil count 5, 6, 7
• Peripheral blood smear and bone marrow morphology if primary hematologic disorder suspected 5, 6, 7

Risk Stratification Based on Eosinophil Count

Mild Eosinophilia (<1,500/mm³)

For patients with eosinophil counts below 1,500/mm³ without symptoms or signs of organ involvement, adopt a watch-and-wait approach with close follow-up monitoring. 5, 6, 7, 8

• Monitor eosinophil counts at regular intervals 2
• Reassess if symptoms develop or counts increase 5

Hypereosinophilia (≥1,500/mm³)

Hypereosinophilia warrants urgent evaluation for end-organ damage and underlying etiology, as this degree of eosinophilia carries significant risk for irreversible tissue damage affecting the heart, lungs, and central nervous system. 3, 5, 6

• Perform echocardiogram and serum troponin to assess for cardiac involvement, particularly in patients with hypereosinophilic syndrome, chronic eosinophilic leukemia, or conditions with high eosinophil levels 4
• Chest imaging if respiratory symptoms present 1
• Liver and renal function tests to assess for organ involvement 4

Treatment Algorithm by Etiology

Parasitic Infections (Most Common Secondary Cause)

For asymptomatic eosinophilia in patients >24 months with travel history, empiric treatment with albendazole 400 mg single dose plus ivermectin 200 μg/kg single dose is recommended. 2

Specific Helminth Infections:

• Strongyloidiasis: Ivermectin 200 μg/kg daily for 2 days 2
• Schistosomiasis: Praziquantel 40 mg/kg in two divided doses for 1 day 2
• Katayama syndrome (acute schistosomiasis): Praziquantel plus corticosteroids 1
• Hookworm, roundworm, whipworm: Albendazole 400 mg single dose 1
• Pinworm: Albendazole 400 mg or mebendazole 100 mg single dose 1
• Trichinellosis: Albendazole 400 mg daily for 3 days (mild) or longer courses for severe disease 1
• Toxocariasis: Albendazole with corticosteroids if neurological involvement 1, 2
• Tropical pulmonary eosinophilia: Diethylcarbamazine (seek specialist advice due to potential severe adverse reactions) 1, 2

Critical Pitfall: Many helminth-infected patients do not have eosinophilia, so absence of eosinophilia does not exclude parasitic infection. 2

Eosinophilic Esophagitis

Treatment should aim primarily at relieving symptoms while achieving histologic remission (<15 eosinophils per high-power field), as persistent esophageal eosinophilia can lead to irreversible fibrotic changes and strictures. 9

First-Line Treatment Options:

• Proton pump inhibitor therapy twice daily for 8-12 weeks 2
• Topical corticosteroids (swallowed fluticasone or budesonide) can induce histological and clinical remission 9, 2
• Dietary elimination: Two-food elimination diet (milk +/- wheat or egg) for 8-12 weeks with dietitian support 2

Monitoring Strategy:

• Regular clinic visits to assess symptoms, compliance, and adverse effects 1
• Repeat endoscopy with biopsy no sooner than 4 weeks after therapeutic intervention to assess histologic response 1
• For asymptomatic patients with persistent eosinophilia: Consider repeat endoscopy every 2-3 years, though risks must be weighed against unknown benefits 1

Critical Pitfall: Patients may modify their diet to compensate for dysphagia, masking inflammatory activity. Symptomatic improvement alone without endoscopic/histologic assessment is inadequate, as substantial eosinophilia can persist in minimally symptomatic patients. 9

Primary Hematologic Eosinophilic Disorders

After excluding secondary causes, pursue molecular and cytogenetic testing to identify specific subtypes, as this determines prognosis and guides targeted therapy. 5, 6, 7, 8

Diagnostic Workup for Primary Eosinophilia:

• Cytogenetics and FISH for PDGFRA, PDGFRB, FGFR1, or PCM1-JAK2 rearrangements 5, 6, 7, 8
• Flow cytometry to detect aberrant immunophenotypes 5, 6, 7
• T-cell clonality assessment to identify lymphocyte-variant hypereosinophilia 5, 6, 7, 8
• Bone marrow biopsy with morphologic review 5, 6, 7

Treatment by Subtype:

Myeloid/Lymphoid Neoplasms with PDGFRA or PDGFRB Rearrangements:

• Imatinib is the treatment of choice due to exquisite responsiveness of these diseases 4, 5, 6, 7, 8
• Dosing for hypereosinophilic syndrome/chronic eosinophilic leukemia: 100 mg/day or 400 mg/day depending on FIP1L1-PDGFRα fusion kinase status 4
• Critical precaution: In patients with high eosinophil levels and cardiac involvement, consider prophylactic systemic steroids (1-2 mg/kg) for 1-2 weeks when initiating imatinib to prevent cardiogenic shock from eosinophil degranulation 4

Lymphocyte-Variant Hypereosinophilia and Idiopathic Hypereosinophilic Syndrome:

• Corticosteroids are first-line therapy 5, 6, 7, 8
• Steroid-refractory cases: Hydroxyurea or interferon-alpha have demonstrated efficacy 5, 6, 7, 8
• Second-line options: Cytotoxic chemotherapy agents, hematopoietic cell transplant for aggressive forms 5, 6, 7, 8
• Investigational therapies: Anti-IL-5 antibodies (mepolizumab, benralizumab) and anti-CD52 (alemtuzumab) remain under investigation 5

Chronic Eosinophilic Leukemia, NOS:

• Hydroxyurea for initial management 5, 6, 7, 8
• Aggressive disease: Consider cytotoxic chemotherapy or hematopoietic cell transplant 5, 6, 7, 8

Complications Requiring Emergency Management

Any patient with evidence of end-organ damage needs urgent medical assessment and consideration of emergency treatment. 2

• Eosinophilic meningitis: Corticosteroids plus albendazole 2
• Neuroschistosomiasis: Praziquantel 40 mg/kg twice daily for 5 days plus dexamethasone 4 mg four times daily 2
• Cardiogenic shock: Systemic steroids, circulatory support, temporarily withhold causative agents 4
• Tumor lysis syndrome: Correct dehydration, treat hyperuricemia prior to initiating therapy in high-burden disease 4

Referral Criteria

Refer to hematology for persistent eosinophilia ≥1.5 × 10⁹/L for more than 3 months without evidence of organ damage or identifiable secondary cause. 2

• Immediate hematology referral if clonal disorder suspected based on morphology or cytogenetics 5, 6, 7
• Consider joint management with appropriate specialists for refractory eosinophilia with significant atopic disease 2

Post-Treatment Monitoring

• Follow-up eosinophil counts after treatment to assess response 2
• Repeat stool studies 4-6 weeks post-treatment for parasitic infections 1
• Serial echocardiograms if cardiac involvement present 4
• Endoscopic surveillance for eosinophilic esophagitis based on symptom control and histologic response 1