Management of Eosinophilia with Increased CD4/CD8 T-cells Without Overt Aberrancy
This patient requires immediate evaluation for lymphocytic variant hypereosinophilic syndrome (L-HES), with urgent assessment for end-organ damage and consideration of corticosteroid therapy while awaiting confirmatory testing. 1, 2
Immediate Diagnostic Priorities
Confirm L-HES Diagnosis
Flow cytometry with comprehensive T-cell immunophenotyping is essential to identify the aberrant T-cell population, specifically looking for CD3-CD4+ cells with loss of other T-cell markers (CD3-, CD4+, CD8- or CD3+, CD4+, CD7dim/-, CD8-). 1, 3, 4
The absence of "overt T cell aberrancy" on initial flow cytometry does not exclude L-HES, as the aberrant T-cell subset may represent only 2% or less of total lymphocytes in nearly half of cases. 3
Serum CCL17/TARC level above 1,500 pg/ml strongly supports L-HES diagnosis, particularly when the aberrant T-cell population is small and TCR gene rearrangement appears polyclonal on whole blood. 1, 3
T-cell receptor (TCR) gene rearrangement analysis should be performed, though a polyclonal result does not exclude L-HES when other features are present. 1, 3
Rule Out Secondary Causes
Obtain detailed travel and exposure history focusing on helminth-endemic regions, as parasitic infections account for 19-80% of eosinophilia in travelers/migrants. 2, 5
Perform three separate concentrated stool specimens for ova and parasites, Strongyloides serology, and Schistosomiasis serology if freshwater exposure occurred. 2, 5, 6
Review all medications for potential drug-induced eosinophilia, as this represents a common cause in non-travelers. 5, 6
Screen for Myeloid Neoplasms
Screen for tyrosine kinase (TK) fusion genes (PDGFRA, PDGFRB, FGFR1, JAK2, ABL1, FLT3) to exclude myeloid/lymphoid neoplasms with eosinophilia, as these require different management. 1
Bone marrow evaluation with cytogenetics and molecular testing is indicated if TK fusion screening is negative but clinical suspicion for clonal disease remains. 1
Urgent End-Organ Damage Assessment
Cardiac Evaluation (Highest Priority)
Obtain electrocardiogram, cardiac troponin, and NT-proBNP immediately, as cardiac involvement is the most life-threatening complication. 2
Perform echocardiography urgently if troponin is elevated or any cardiac symptoms present (chest pain, dyspnea, heart failure symptoms, arrhythmias). 2
Cardiac MRI is indicated when troponin elevation or clinical cardiac features exist to distinguish eosinophilic cardiac disease from other etiologies. 2
Other Organ Systems
Pulmonary function tests and chest X-ray if respiratory symptoms (cough, wheezing, dyspnea) are present. 2
Neurologic examination with electromyography if peripheral neuropathy symptoms exist. 2
Skin examination for dermatologic manifestations, as all symptomatic L-HES patients in the largest cohort had cutaneous lesions and/or angioedema. 3
Treatment Algorithm
Initial Management
Start oral corticosteroids (typically prednisone 1 mg/kg/day) immediately if end-organ damage is present or eosinophil count ≥5.0 × 10⁹/L, as this represents high risk for morbidity and mortality. 2, 3
For patients without immediate organ damage but confirmed L-HES, corticosteroids remain first-line therapy, with response expected in all cases initially. 3
Second-Line Options for Steroid-Dependent or Refractory Disease
Interferon-alpha is the most effective second-line agent, achieving response in 8/8 patients in the largest L-HES cohort, though tolerance issues and secondary resistance commonly develop. 3
Anti-IL-5 antibodies (mepolizumab, reslizumab, benralizumab) effectively reduce blood eosinophilia but clinical responses are often disappointing in L-HES, unlike other eosinophilic conditions. 3
Approximately one-third of L-HES patients have mild disease not requiring maintenance therapy, while two-thirds require long-term corticosteroids and/or second-line agents. 3
Critical Monitoring and Follow-Up
Serial Assessment
Monitor CD3-CD4+ T-cell counts serially, as progression to T-cell lymphoma occurs in approximately 10-20% of L-HES cases. 1, 3
Three of five patients with severe treatment-refractory L-HES in the largest cohort progressed to T-cell lymphoma, highlighting the importance of close surveillance. 3
Repeat flow cytometry and TCR analysis if clinical deterioration occurs or lymphadenopathy develops. 1, 3
Hematology Referral
Refer to hematology immediately for confirmed or suspected L-HES, as this is a rare disorder requiring specialized management. 2, 5
Referral is mandatory if eosinophilia ≥1.5 × 10⁹/L persists for more than 3 months after excluding infectious causes. 2, 5
Common Pitfalls to Avoid
Do not dismiss the diagnosis based on "absence of overt T-cell aberrancy" on initial flow cytometry, as aberrant populations may be small and require specific markers (CD3-CD4+ phenotype) to detect. 1, 3
Do not assume normal eosinophil counts exclude helminth infection, as many infected patients lack eosinophilia, and parasitic workup should be guided by exposure history rather than eosinophil level alone. 2, 5
Do not delay cardiac evaluation, as eosinophil-mediated cardiac damage can progress rapidly to irreversible fibrosis. 2
Do not use montelukast, cromolyn, or anti-IgE therapy for eosinophilia management, as these have no proven efficacy in reducing eosinophil counts or treating eosinophilic conditions. 5
Recognize that L-HES represents a spectrum from mild disease to severe treatment-refractory cases with significant morbidity, mortality, and risk of lymphoma progression, requiring individualized treatment intensity and surveillance. 3