What is the approach to treating hypereosinophilia (excessive eosinophils)?

Approach to Hypereosinophilia

The approach to hypereosinophilia requires urgent assessment for end-organ damage, systematic exclusion of secondary causes (particularly helminth infections in travelers/migrants), followed by targeted therapy based on the underlying etiology—with imatinib for tyrosine kinase fusion disorders, corticosteroids for idiopathic cases, and empirical antiparasitic treatment when indicated. 1, 2

Initial Assessment and Risk Stratification

Define the Severity

• Hypereosinophilia is defined as peripheral blood eosinophil count >0.5 × 10⁹/L, with significant hypereosinophilia at ≥1.5 × 10⁹/L. 1, 2
• Any patient with evidence of end-organ damage (cardiac, pulmonary, or neurological involvement) requires urgent medical assessment and consideration of emergency treatment regardless of eosinophil count. 1
• Persistent eosinophilia ≥1.5 × 10⁹/L for more than 3 months without end-organ damage warrants hematology referral after infectious causes are excluded or treated. 1

Assess for Life-Threatening Complications

• Cardiac involvement (Löeffler endocarditis) presents with myocardial fibrosis, systemic thromboembolism, and acute heart failure—the primary cause of mortality in hypereosinophilic syndromes. 1
• Eosinophilic myocarditis progresses through three stages: necrotic (often subclinical but can present as fulminant myocarditis), thrombotic (high thromboembolism risk), and fibrotic (restrictive cardiomyopathy). 1
• Echocardiography and cardiac MRI are helpful, but myocardial biopsy remains the gold standard for diagnosis. 1

Systematic Evaluation for Secondary Causes

Helminth Infections (Most Common in Travelers/Migrants)

• Helminths are the most common identifiable cause of eosinophilia in returning travelers or migrants, with diagnosis rates of 19-80%. 1
• First-line investigation for asymptomatic eosinophilia now includes serology as the sole test; filarial investigations are only recommended for those with travel/residence history in West Africa. 1
• Critical helminth to identify: Strongyloides stercoralis can persist lifelong and present as hyperinfection syndrome with high mortality in immunocompromised patients. 1
• Schistosoma haematobium is associated with squamous cell bladder carcinoma. 1

Other Secondary Causes to Exclude

• In non-endemic areas, the most common non-infectious causes are allergy/atopy (asthma, eczema, hay fever) and drug reactions. 1
• Rarer but serious causes include systemic vasculitis and malignancy (lymphomas, myeloid neoplasms). 1
• Eosinophilic esophagitis should be considered in patients with dysphagia or food impaction. 1

Diagnostic Workup for Primary Eosinophilias

Molecular and Cytogenetic Testing

• After excluding secondary causes, perform morphologic review of blood and marrow, standard cytogenetics, FISH, molecular testing, and flow immunophenotyping to detect clonal evidence of hematolymphoid neoplasm. 2
• Identification of PDGFRA or PDGFRB rearrangements is critical—these patients show exquisite responsiveness to imatinib. 2, 3
• Test for FGFR1 rearrangements, as pemigatinib was recently approved for relapsed/refractory FGFR1-rearranged neoplasms. 2
• Assess for PCM1-JAK2 fusion and other tyrosine kinase gene fusions. 2, 3

Classification of Primary Eosinophilias

• Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-eo-TK) 2
• Chronic eosinophilic leukemia (CEL) as a myeloproliferative neoplasm subtype 2
• Lymphocyte-variant hypereosinophilia: aberrant T-cell clone-driven reactive eosinophilia (requires T-cell clonality assessment) 2, 3
• Idiopathic hypereosinophilic syndrome (HES): diagnosis of exclusion 2, 3

Treatment Approach Based on Etiology

For Travelers/Migrants with Suspected Helminth Infection

• Empirical treatment for asymptomatic eosinophilia in those aged >24 months: albendazole 400 mg single dose plus ivermectin 200 μg/kg single dose. 1
• This updated recommendation reflects changes in global prevalence of filarial infections. 1

For MLN-eo-TK (PDGFRA/PDGFRB Rearrangements)

• Imatinib is the treatment of choice with excellent response rates. 2, 4, 3
• These patients demonstrate exquisite responsiveness to tyrosine kinase inhibition. 2, 3

For Lymphocyte-Variant HE and Idiopathic HES

• Corticosteroids are first-line therapy. 2, 3
• Hydroxyurea and interferon-α have demonstrated efficacy as initial treatment and in steroid-refractory cases. 2, 3
• Mepolizumab (anti-IL-5 monoclonal antibody) is FDA-approved for idiopathic HES. 2
• Benralizumab (IL-5 receptor antibody) and depemokimab are under active investigation. 2

For Hypereosinophilic Syndrome with Cardiac Involvement

• Corticosteroid therapy is generally considered primary therapy for eosinophilic myocarditis, though efficacy is not well supported. 1
• Hematology consultation is warranted for specific analysis to guide treatment. 1

For Aggressive Forms (CEL, Refractory HES)

• Cytotoxic chemotherapy agents have been used with outcomes reported for limited numbers of patients. 2, 3
• Hematopoietic stem cell transplantation has been employed for aggressive forms. 2, 3

Monitoring Strategy

Watch and Wait Approach

• For patients with milder eosinophilia (<1.5 × 10⁹/L) without symptoms or signs of organ involvement, close follow-up with a watch-and-wait approach may be undertaken. 2, 3

For Treated Patients

• Monitor for resolution of eosinophilia and organ damage. 2
• Serial cardiac imaging if cardiac involvement was present. 1
• Refer to hematology if eosinophilia ≥1.5 × 10⁹/L persists for >3 months after treating infectious causes. 1

Critical Pitfalls to Avoid

• Do not delay treatment in patients with end-organ damage—this is a medical emergency requiring prompt aggressive therapy to reduce morbidity and mortality. 1, 4
• Do not miss Strongyloides stercoralis—it can cause fatal hyperinfection syndrome decades later in immunocompromised patients. 1
• Do not fail to test for PDGFRA/PDGFRB rearrangements—these patients have dramatically different prognosis and treatment with imatinib. 2, 3
• Testing for eosinophilia alone is not adequate screening for helminth infection—many infected patients do not have eosinophilia. 1
• Idiopathic HES is a diagnosis of exclusion—ensure thorough evaluation for secondary causes and clonal disorders before labeling as idiopathic. 2, 3