Pediatric Severe Eosinophilia: Etiological Spectrum, Diagnostic Algorithm, and Case-Based Insights From a Tertiary Care Center.

[PURPOSE] Pediatric hypereosinophilia (HE) is rare, and its evaluation is challenging due to diverse etiologies and limited access to advanced laboratory testing in low- and middle-income countries (LMICs).

[METHODS] We retrospectively analyzed five children with HE (absolute eosinophil count > 5.0 × 10/L) evaluated at a tertiary center. Clinical, hematologic, and molecular findings were reviewed, and diagnostic timelines were compared between clonal and non-clonal cases. Based on these observations, a tiered, laboratory-driven diagnostic pathway adapted for LMICs was developed.

[RESULTS] Five patients (median age: 6 years; range: 1.5-10 years) were included. The median absolute eosinophil count (AEC) at presentation was 12.8 × 10/L (range: 6.5-21.5 × 10/L). Three cases (60%) were clonal eosinophilia-one PDGFRB-rearranged myeloid/lymphoid neoplasm and two acute myeloid leukemia subtypes [AML with CBFB::MYH11, AML with RUNX1::RUNX1T1]-and two cases (40%) were non-clonal [one Hyper-IgE syndrome with secondary hemophagocytic lymphohistiocytosis (HLH), one secondary eosinophilia (drug-induced, phenytoin/phenobarbitone)]. Clonal cases demonstrated higher leukocyte counts, earlier bone marrow and molecular testing, and shorter median time to diagnosis (6 vs. 14 days), enabling prompt initiation of imatinib or AML-directed therapy with remission in all. In contrast, non-clonal HE required sequential exclusion of clonal disease, delaying immunosuppressive or drug-withdrawal strategies.

[CONCLUSION] A structured, laboratory-driven algorithm beginning with blood counts, smear, and parasitic testing, and escalating to early bone marrow with cytogenetic/molecular studies for high-risk phenotypes, enabled timely identification of clonal HE while conserving resources in reactive cases. This LMIC-adapted pathway highlights laboratory turnaround time as a critical determinant of outcomes and provides a practical framework for pediatric HE evaluation.