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Severe persistent hypereosinophilia of undetermined significance: diagnostic challenges in clinical practice and
Polliana Mihaela Leru1,2, Vlad Florin Anton2, Daniela Georgeta Georgescu3,4
1Carol Davila University of Medicine and Pharmacy, Department 5, 050474 Bucharest, Romania.
Background:
Hypereosinophilia of undetermined significance (HE-US) represents a rare subtype of hypereosinophilia (HE) defined by a persistent absolute eosinophil count (AEC) ≥ 1500/uL without an identifiable reactive or clonal cause, and importantly, without evidence of eosinophil-mediated end-organ damage. Long-term structured follow-up is essential due to its unpredictable outcome and the risk of transition into overt hypereosinophilic syndrome (HES) or occult malignancies.
Case Presentation:
We report the case of a 47-year-old woman with severe, persistent blood hypereosinophilia (up to 13600/uL) accompanied by chronic inconstant fixed erythematous-violaceous skin lesions. Extensive diagnostic evaluation for secondary, autoimmune, and clonal etiologies was negative, including fluorescence in situ hybridization (FISH) for FIP1L1-PDGFRA mutation. Bone marrow biopsy showed granulocytic hyperplasia with eosinophils <10% and mild reticulin fibrosis (MF-1). Whole-body computed tomography (CT) revealed small generalized lymphadenopathy (≤ 11 mm) without parenchymal infiltration. The patient declined lymph-node biopsy. Although skin biopsy revealed eosinophilic infiltration, it was characterized as a non-specific reactive pattern without objective evidence of eosinophil-mediated cytotoxicity. The case was provisionally diagnosed as HE-US, acknowledging that lymphoproliferative disease could not be definitively excluded in the absence of the lymph-node biopsy. Intermittent systemic corticosteroids provide rapid hematologic response, but prompted immediate recurrence when tapered.
Conclusion:
The reported case underscores the diagnostic complexity and difficulties in managing hypereosinophilia of undetermined significance in clinical practice. While current evidence suggests a generally benign course, rare progression to hypereosinophilic syndrome or other malignancies requires structured long-term monitoring and individualized therapeutic decision-making.
