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Severe Persistent Hypereosinophilia of Undetermined Significance: Diagnostic Challenges in Clinical Practice and Two-Year Follow-Up Cover

Severe Persistent Hypereosinophilia of Undetermined Significance: Diagnostic Challenges in Clinical Practice and Two-Year Follow-Up

Open Access
|Jun 2026

Figures & Tables

Figure 1.

Clinical aspect of cutaneous lesions on admission

Figure 2.

Blood eosinophilia and therapeutic response between 2023–2025

Diagnostic workup

Diagnostic domainSpecific tests performedClinical interpretation
Infectious DiseaseToxocara canis IgG: positive; Trichinella, Ascaris, and Toxoplasma IgG serology: Negative; Strongyloides stercoralis by agar plate culture and repeated stool microscopy: NegativeToxocara exposure noted, however lack of response to a 6-week course of albendazole argues against active infection. Strongyloides infection was strictly ruled out prior to corticosteroid initiation to eliminate the risk of hyperinfection.
AllergyALEX Multiplex Test: Class 3 sensitization to ragweed pollen (r Amb a4); Elevated total serum IgE: 3,603 IU/mLHypersensitisation to Ragweed pollen confirmed, without clinical allergy symptoms.
Autoimmune and inflammationANA, ANCA, C3, C4, anti-dsDNA, Rheumatoid Factor: Negative; ESR, CRP, fibrinogen – normal, Anti-TPO, Anti-tireoglobulin antibodies: NegativeNo evidence of systemic autoimmune disease, active vasculitis (such as EGPA), or autoimmune thyroiditis.
Hematological and molecularLDH, B12 vitamin, Beta-2 microglobulin, immunoelectrophoresis. Serum Tryptase: Normal (Repeated); FISH: Negative for FIP1L1-PDGFRA, PDGFRB, JAK2, c-KIT mutations. ECP: Persistently elevated (>200 ng/mL)Excludes primary clonal myeloid neoplasms. High ECP confirms systemic eosinophil activation.
Peripheral blood pheno-typing (flow cytometry):The expression of the following antigens: CD3, CD4, CD5, CD8, CD10, CD19, CD20, CD23, CD33, CD38, CD45, CD56, CD57, kappa and lambda light chains, and T cell gamma/delta receptor Number of lymphocytes with mildly increased B cells, no evidence of clonal B cell population, normal CD4/CD8 ratio, expression of the T cell antigens CD3 and CD5, kappa/lambda light chain ratioNo aberrant T-cell phenotype or clonal B-cell population detected; findings argue against lymphocytic-variant HES, although this cannot be definitively excluded without lymph-node biopsy and/or molecular clonality assessment.
Bone marrow examinationHypercellular bone marrow (85%) with granulocytic hyperplasia; marked granulocytic hyperplasia G/E ratio 7:1, mild left shift, maturation preserved, mild eosinophilia (<10%); normoblastic maturation; normal size megakaryocytes. Gomori sylver impregnation: MF-1 (>30%). Immunohistochemistry: CD20 positive in isolated reactive B cells, CD14 positive in rare monocytes (10%), CD 34 ~ 3%.No morphology of evident leukemia or lymphoma. Mild reticulin fibrosis requires close monitoring as a potential indicator of early clonal hematopoiesis
ImagingWhole-body CT: Multiple small lymph nodes ≤11 mm (cervical, thoracic, abdominal, pelvic); Echocardiography: Normal EF (60%), no fibrosis/thrombi; Spirometry: Normal (FEV1 90%, FVC 95%);Generalized small reactive lymphadenopathy documented. Absence of definitive eosinophil-mediated end-organ damage
DOI: https://doi.org/10.2478/rjim-2026-0014 | Journal eISSN: 2501-062X | Journal ISSN: 1220-4749
Language: English
Submitted on: May 18, 2026
Published on: Jun 23, 2026
In partnership with: Paradigm Publishing Services

© 2026 Polliana Mihaela Leru, Vlad Florin Anton, Daniela Georgeta Georgescu, published by N.G. Lupu Internal Medicine Foundation
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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