What is the treatment approach for a patient presenting with eosinophilia?

Treatment of Eosinophilia

For patients with eosinophilia, empirical treatment with albendazole 400 mg plus ivermectin 200 μg/kg (both as single doses) should be initiated for suspected helminth infection in those with travel history to endemic regions, while patients with confirmed hypereosinophilic syndrome require corticosteroids as first-line therapy, and those with PDGFRA/PDGFRB rearrangements require imatinib. 1, 2, 3

Initial Risk Stratification and Urgent Assessment

Before initiating treatment, assess for life-threatening complications:

• Any patient with eosinophilia plus evidence of end-organ damage requires urgent evaluation and emergency treatment consideration 4
• Cardiac involvement (chest pain, dyspnea, heart failure, arrhythmias) demands immediate attention with ECG, troponin, NT-proBNP, and echocardiography 4
• Pulmonary involvement (persistent cough, wheezing, infiltrates) necessitates urgent evaluation with chest X-ray and pulmonary function tests 4
• Neurological involvement (altered mental status, focal deficits, peripheral neuropathy) requires prompt assessment with EMG and potential nerve biopsy 4
• Absolute eosinophil count ≥5.0 × 10⁹/L at any time or ≥1.5 × 10⁹/L persisting >3 months carries significant morbidity and mortality risk 4

Treatment Algorithm Based on Underlying Etiology

For Helminth Infections (Most Common in Travelers/Migrants)

Empirical therapy for asymptomatic eosinophilia with negative stool microscopy:

• Albendazole 400 mg single dose PLUS ivermectin 200 μg/kg single dose for patients >24 months 1, 2
• CRITICAL WARNING: Exclude Loa loa infection BEFORE administering ivermectin by checking for microfilariae on blood film in patients who traveled to endemic regions (Central/West Africa), as ivermectin can cause fatal encephalopathy if Loa loa is present 1, 4
• Repeat treatment at 8 weeks to treat residual worms that have matured into adults, as eggs and immature schistosomulae are relatively resistant 1

Specific helminth treatments based on identified pathogen:

• Strongyloides: Ivermectin 200 μg/kg daily for 2 days 5, 2
• Hookworm/Ascaris (Loeffler's syndrome): Albendazole 400 mg twice daily for 3 days 5
• Schistosomiasis: Praziquantel 40 mg/kg as single dose, repeated at 6-8 weeks 5, 2
• Acute Katayama syndrome: Praziquantel 25 mg/kg three times daily for 2-3 consecutive days PLUS prednisolone 20 mg/day for 5 days 1, 5
• Tropical pulmonary eosinophilia: Diethylcarbamazine (DEC) promptly initiated (after excluding Loa loa) PLUS prednisolone 20 mg/day for 5 days to prevent irreversible pulmonary fibrosis; 20% relapse and require second DEC course 5

For Hypereosinophilic Syndrome (HES)

First-line therapy:

• Corticosteroids are the first-line treatment for idiopathic HES and lymphocyte-variant hypereosinophilia 3, 6, 7
• Goal is to mitigate eosinophil-mediated organ damage 3, 7

Second-line options for steroid-refractory cases:

• Hydroxyurea has demonstrated efficacy as initial treatment and in steroid-refractory HES 3, 6, 7
• Interferon-α has demonstrated efficacy in steroid-refractory cases 3, 6, 7
• Mepolizumab (IL-5 antagonist monoclonal antibody) is FDA-approved for idiopathic HES 3, 7
• Benralizumab (IL-5 receptor antibody) is under active investigation 3, 7

Aggressive disease:

• Cytotoxic chemotherapy agents and hematopoietic stem cell transplantation for aggressive HES and chronic eosinophilic leukemia (CEL) 3, 7

For Myeloid/Lymphoid Neoplasms with Tyrosine Kinase Gene Fusions

Critical to identify PDGFRA/PDGFRB rearrangements:

• Imatinib is the treatment of choice due to exquisite responsiveness of PDGFRA/PDGFRB-rearranged diseases 3, 6, 7
• Pemigatinib was recently approved for relapsed/refractory FGFR1-rearranged neoplasms 3
• Identification requires molecular testing including standard cytogenetics, FISH, and next-generation sequencing 3, 7

For Eosinophilic Esophagitis

First-line therapy:

• Topical swallowed corticosteroids (fluticasone or budesonide) decrease blood eosinophil counts in 88% of patients 4
• Maintenance therapy is mandatory after achieving remission due to high clinical relapse rates after steroid withdrawal 4
• Endoscopic dilation is safe and effective for fibrostenotic disease but must be combined with anti-inflammatory therapy 4

Monitoring:

• Repeat endoscopy with biopsies if symptoms recur during treatment 4
• Histological remission defined as <15 eosinophils per 0.3 mm²; deep remission as <5 eosinophils per 0.3 mm² 4

Watch-and-Wait Approach

For mild eosinophilia without organ involvement:

• Patients with eosinophilia <1.5 × 10⁹/L without symptoms or signs of organ involvement may be observed with close follow-up 3, 6, 7
• Mild eosinophilia (0.5-1.5 × 10⁹/L) is most commonly caused by allergic disorders or medications in non-endemic areas 4, 2

Referral Criteria

Hematology referral indicated when:

• Eosinophilia ≥1.5 × 10⁹/L persists for >3 months after infectious causes have been excluded or treated 4, 2
• Evidence of clonal disease or myeloid/lymphoid neoplasm suspected 3, 7

Common Pitfalls to Avoid

• Do not administer ivermectin without first excluding Loa loa in patients from endemic regions (Central/West Africa), as this can cause fatal encephalopathy 1, 4
• Do not assume normal eosinophil counts exclude helminth infection, as many infected patients have normal counts 4
• Do not wait for symptoms before investigating persistent moderate-to-severe eosinophilia, as end-organ damage can be subclinical initially 4
• Do not rely solely on peripheral eosinophil counts for eosinophilic esophagitis, as peripheral eosinophilia occurs in only 10-50% of adults; tissue biopsy is the gold standard 4, 2
• Do not use montelukast for managing eosinophilia, as it has no proven efficacy (OR 0.48,95% CI 0.10-2.16, p=0.33) 2
• Do not use anti-IgE therapy (omalizumab) for eosinophilia management, as it showed no effect on eosinophil counts 2

Diagnostic Testing Before Treatment

Essential first-line tests:

• Three separate concentrated stool specimens for ova and parasites 5, 2
• Strongyloides serology and culture (has higher sensitivity than stool microscopy for Strongyloides) 1, 2
• Schistosomiasis serology if freshwater exposure in endemic areas 5, 2
• Detailed geographic and exposure history including exact times of exposures, freshwater swimming, barefoot walking, raw/undercooked meat consumption 5, 2

For suspected primary eosinophilia:

• Morphologic review of blood and marrow, standard cytogenetics, FISH, molecular testing, and flow immunophenotyping to detect clonal evidence 3, 7