Hyper-Eosinophilic Syndrome and Partial Duplication of Chromosome 21

Abstract

RATIONALE: Hypereosinophilia is defined as a peripheral blood absolute eosinophil count (AEC) of >0.5 x10 9 /L, while severe hypereosinophilia is defined as an AEC of >1.5x10 9 /L. Much has been published on hypereosinphilia in the adult literature; however, there is limited literature on pediatric patients with hypereosinophilia (especially severe eosinophila) or hypereosinophilic syndrome (HES). The goal of this study was to characterize children with severe hypereosinophilia hospitalized in a tertiary care center. METHODS: We reviewed the charts of allergy/immunology consults performed from January 2013-April 2016 at Saint Louis Children's Hospital. Children were included in this study if their AEC was >1.5x10 9 at the time of the allergy/immunology consult. Data was collected on demographics, comorbidities, treatment, laboratory data, and clinical outcomes. Patients were sorted into diagnostic groups that included: overlap hypereosinophilic syndrome, allergic/atopy, hypereosinophilic syndrome myeloproliferative subtype, immunodeficiency, and unknown. RESULTS:We reviewed that chart of 289 inpatient consults and 13 met our inclusion criteria. Mean age at presentation was 19.5 months (range 1-49 months). Mean peak peripheral blood AEC was 5.5x10 9 /L (range 1800-12,524x10 9 /L). Four patients were found to have atopic driven eosinophilia, three with an underlying primary immunodeficiency, two with HES myeloproliferative variant, one with overlap HES. Four patients had an unknown etiology. Mortality in our cohort was 23%. CONCLUSIONS: Severe hypereosinophilia was the reason for 4.5% of inpatient Allergy/Immunology consults. A variety of reasons caused underlying eosinophilia. As many life threatening conditions were identified, prompt recognition of the underlying pathology is critical for proper treatment. RATIONALE: Monitoring of EoE would benefit from biomarkers to replace invasive endoscopy and pathology. We hypothesized that beta1integrin activation, which enables arrest of eosinophils in inflamed vessels and predicts disease activity in non-severe asthma, correlates with eosinophilic inflammation and disease activity in EoE. METHODS: Ten EoE patients were recruited following two-month proton-pump-inhibitor therapy and diagnostic endoscopy, with visit 1 (V1) within one week of endoscopy. Patients received standard of care EoE treatment (swallowed steroid or food elimination) followed by visit 2 and repeat endoscopy (V2) two months later. Beta1-integrin activation (mAb N29 intensity) and 15 other eosinophil-surface markers were assayed by whole blood flow cytometry. The EoE Histological Scoring System (EoEHSS), including an eosinophilic inflammation subscore of 0 to 3, was used. RESULTS: N29 correlated with eosinophilic inflammation subscore (r s/ Spearman coefficient50.91, p50.001) or EoEHSS total score (r s 50.70, p 5 0.03) at V2 but not V1. Further, the change in N29 from V1 to V2 correlated with inflammation subscore change (r s 50.81, p50.007). The five patients for whom N29 was increased the most at V2 ...