Pediatric Hypereosinophilia: Characteristics, Clinical Manifestations, and Diagnoses

Abstract

Background: Eosinophilia is associated with various conditions, including allergic, infectious, and neoplastic disorders. The diagnostic differential is broad, and data on hypereosinophilia in pediatric patients are limited.

Objective: The objectives of this study were to identify cases of hypereosinophilia in a tertiary pediatric medical center, determine clinical characteristics and disease associations, and estimate the incidence of hypereosinophilia in the hospital and geographic populations.

Methods: A retrospective chart review included patients younger than 18 years presenting to a tertiary pediatric medical center (January 1, 2008, to May 31, 2017) with absolute eosinophil counts (AECs) greater than or equal to 1.50 thousand eosinophils/microliter (K/μL) recorded on at least 2 occasions at least 4 weeks apart (N = 176). Clinical characteristics, laboratory values, treatment course, and associated diagnoses were evaluated.

Results: The most common cause of hypereosinophilia in this cohort was secondary hypereosinophilia. Atopic dermatitis, graft-versus-host disease, sickle cell disease, and parasitic infections were the most common conditions associated with hypereosinophilia. Median age at diagnosis was 4.6 (interquartile range, 1.5-10.5) years. Median peak AEC was 3.16 (2.46-4.78) K/μL. Hypereosinophilia occurred most frequently in patients aged between 6 and 11 years (24.4%) and younger than 1 year (18.2%). Patients with neoplasms and immune deficiencies had significantly higher peak AECs than did patients with overlap hypereosinophilic syndrome and atopic diseases (P < .0001).

Conclusions: Pediatric hypereosinophilia has an incidence of 54.4 per 100,000 persons per year, with children younger than 1 year and aged 6 to 11 years accounting for most affected patients. Pediatric hypereosinophilia is not uncommon and remains underrecognized, highlighting a need for clinicians to identify patients who meet criteria for hypereosinophilia and to pursue a thorough evaluation.

Keywords: Eosinophil; Eosinophilia; Hypereosinophilic syndrome.

Figure 1.. Absolute Eosinophil Counts by Gender and Age.

(A) Peak absolute eosinophil counts and (B) Absolute eosinophil counts at time of diagnosis. Box and whisker plots demonstrate the distribution of the absolute eosinophil counts (peak, time of diagnosis) by gender (males: N = 97, females: N = 79) and age categories (under 1 year: N = 32, 1-2 years: N = 34, 3-5 years: N = 34, 6-11 years: N = 43, 12-17 years: N = 33) with outliers plotted as individual dots. *Significant difference in peak absolute eosinophil counts between age groups (P < 0.05).

Figure 2.. Disease Categories associated with Hypereosinophilia.

(A) Diagnosis frequency (N = 176). There were no individuals diagnosed with myeloproliferative or lymphocytic hypereosinophilic syndrome (HES). (B) Absolute eosinophil count at time of diagnosis for each disease category associated with hypereosinophilia. Box and whisker plots demonstrate the distribution of the absolute eosinophil count at the time of diagnosis for each disease category. Individual dots represent outliers. For disease categories with less than five individuals, dots are used to represent unique absolute eosinophil count levels. DRESS, drug reaction with eosinophilia and systemic symptoms; GVHD, graft-versus-host disease; HES, hypereosinophilic syndrome; HEUS, hypereosinophilia of unknown significance; IBD, inflammatory bowel disease; probable secondary, probable secondary hypereosinophilia; unknown, insufficient information to determine a diagnosis related to the hypereosinophilia.

Figure 3.. Outcome of Hypereosinophilia by Diagnosis Category.

Resolution of hypereosinophilia was defined as a decrease to an absolute eosinophil count < 1.50 K/mcL at the time of last recorded absolute eosinophil count. Hypereosinophilia that did not resolve was defined as absolute eosinophil count values persistently ≥ 1.50 K/mcL at the time of last recorded absolute eosinophil count; this included cases in which no further absolute eosinophil count levels were obtained after diagnosis date. DRESS, drug reaction with eosinophilia and systemic symptoms; GVHD, graft-versus-host disease; HES, hypereosinophilic syndrome; HEUS, hypereosinophilia of unknown significance; IBD, inflammatory bowel disease; probable secondary, probable secondary hypereosinophilia; unknown, insufficient information to determine a diagnosis related to the hypereosinophilia.