What are the treatment approaches for primary vs secondary hypereosinophilia?

Treatment Approaches for Primary vs Secondary Hypereosinophilia

The fundamental treatment principle is to treat the underlying cause in secondary hypereosinophilia, while primary hypereosinophilia requires targeted therapy based on molecular/genetic findings—with imatinib for PDGFRA/PDGFRB rearrangements and corticosteroids for idiopathic hypereosinophilic syndrome. 1, 2

Initial Critical Assessment

Any patient with end-organ damage requires urgent medical assessment and emergency treatment regardless of eosinophil count. 3 The most life-threatening complication is cardiac involvement (Löeffler endocarditis), which presents with myocardial fibrosis, systemic thromboembolism, and acute heart failure—the primary cause of mortality in hypereosinophilic syndromes. 1, 3

Immediate Cardiac Evaluation for High-Risk Patients

• Perform echocardiogram and serum troponin in patients with hypereosinophilic syndrome/chronic eosinophilic leukemia, and in those with myelodysplastic/myeloproliferative disease or systemic mastocytosis associated with high eosinophil levels. 4
• If cardiac abnormalities are detected, consider prophylactic systemic steroids (1-2 mg/kg) for 1-2 weeks concomitantly with targeted therapy at initiation. 4
• Myocardial biopsy remains the gold standard for diagnosis of eosinophilic myocarditis, though echocardiography and cardiac MRI are helpful. 1

Treatment Algorithm for Secondary (Reactive) Hypereosinophilia

Secondary eosinophilia accounts for approximately 80% of cases, with allergic disorders being most common, followed by parasitic infections. 1

Parasitic Infections (Most Common Identifiable Cause in Travelers)

• For asymptomatic eosinophilia in patients aged >24 months: Albendazole 400 mg single dose plus ivermectin 200 μg/kg single dose. 5, 3
• For strongyloidiasis (critical to identify due to hyperinfection risk): Ivermectin 200 μg/kg daily for 2 days. 5
• For schistosomiasis: Praziquantel 40 mg/kg in two divided doses for 1 day. 5
• For neuroschistosomiasis: Praziquantel 40 mg/kg twice daily for 5 days plus dexamethasone 4 mg four times daily. 5

Allergic/Inflammatory Disorders

• Identify and remove offending allergen or medication. 1
• For eosinophilic esophagitis: Proton pump inhibitor therapy twice daily for 8-12 weeks, or topical steroids, or two-food elimination diet (milk +/- wheat or egg) for 8-12 weeks with dietitian support. 5

Malignancy-Associated Eosinophilia

• Treat the underlying malignancy (solid tumors, Hodgkin lymphoma, T-cell lymphomas). 1
• Eosinophilia in these cases results from increased production of growth factors and eosinophilopoietic cytokines from neoplastic cells. 1

Treatment Algorithm for Primary (Clonal) Hypereosinophilia

Accurate molecular/genetic diagnosis is essential as it dictates therapy. 1, 2

Myeloid/Lymphoid Neoplasms with Tyrosine Kinase Gene Fusions

Identification of PDGFRA or PDGFRB rearrangements is critical because these diseases show exquisite responsiveness to imatinib. 2, 6

• For PDGFRA/PDGFRB-rearranged disease: Imatinib is the treatment of choice with dramatic responses. 2, 6
• For FGFR1-rearranged neoplasms: Pemigatinib was recently approved for relapsed or refractory cases. 6
• Mandatory testing includes: FISH for CHIC2 deletion and RT-PCR for tyrosine kinase fusion genes. 7

Chronic Eosinophilic Leukemia (CEL, NOS)

• Hydroxyurea as initial treatment. 2, 6
• Interferon-alpha for steroid-refractory cases. 2, 6
• Cytotoxic chemotherapy agents for aggressive forms. 2, 6
• Hematopoietic stem cell transplantation for eligible patients with aggressive disease. 2, 6

Lymphocyte-Variant Hypereosinophilia (L-HES)

This represents an aberrant T-cell clone-driven reactive eosinophilia with 10-20% risk of evolution to T-cell lymphoma. 1, 2

• First-line therapy: Corticosteroids. 2, 6
• Characterized by clonal T-cells with aberrant immunophenotype (CD3-, CD4+, CD8- or CD3+, CD4-, CD7-). 1
• Requires flow cytometry with T-cell immunophenotyping and molecular analysis. 1

Idiopathic Hypereosinophilic Syndrome (Diagnosis of Exclusion)

Corticosteroids are first-line therapy for idiopathic HES. 2, 6

• Initial treatment: Prednisone (dose not specified in guidelines, but typically 1 mg/kg/day). 8
• Steroid-refractory cases: Hydroxyurea or interferon-alpha. 2, 6
• FDA-approved option: Mepolizumab (IL-5 antagonist monoclonal antibody) for patients with idiopathic HES. 6
• Under investigation: Benralizumab (IL-5 receptor antibody) and depemokimab (IL-5 monoclonal antibody). 6

Monitoring and Follow-Up Strategy

• For mild eosinophilia (<1.5 × 10⁹/L) without organ involvement: Watch and wait approach with close follow-up. 2, 6
• For persistent eosinophilia ≥1.5 × 10⁹/L for >3 months after treating infectious causes: Refer to hematology. 5, 3
• Obtain follow-up eosinophil counts after treatment to assess response. 5
• Serial cardiac imaging if cardiac involvement was present. 3

Critical Pitfalls to Avoid

• Do not delay treatment in patients with end-organ damage—this is a medical emergency requiring prompt aggressive therapy. 3
• Failing to test for PDGFRA rearrangements can lead to missed treatment opportunities with highly effective imatinib therapy. 7
• Do not overlook Strongyloides in travelers—it can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients. 3
• Testing for eosinophilia alone is inadequate screening for helminth infection—many infected patients do not have eosinophilia. 5, 3
• Monitor for cardiac complications early—irreversible heart failure is the leading cause of mortality and can develop rapidly. 1, 3
• Growth retardation has been reported in children receiving imatinib; monitor growth closely. 4