An Approach to the Evaluation of Persistent Hypereosinophilia in Pediatric Patients

Abstract

Hypereosinophilia (HE) is currently defined by a peripheral blood absolute eosinophil count (AEC) of ≥1,500 cells/microL. Although mild blood eosinophilia (AEC 500-1,500 cells/microL) is observed relatively frequently within the pediatric population, persistent HE is uncommon and should prompt additional clinical evaluation. While the clinical manifestations and underlying etiologies of HE in adults have been well-characterized, there is a paucity of data on HE in children. Limited evidence suggests that many similarities between adult and pediatric HE likely exist, but some important differences remain between these populations. The evaluation of HE in children can be challenging given the broad differential diagnosis, which includes primary hematologic disorders and secondary eosinophilia in which the increased eosinophil levels are propagated by disease states that promote eosinophil production and survival. On the basis of the underlying etiology, clinical manifestations can range from benign, self-resolving elevations in the AEC to life-threatening disorders with the potential for significant end-organ damage. Given the broad differential diagnosis of HE, it remains essential to systematically approach the evaluation of unexplained HE in children. This review will discuss the differential diagnosis for pediatric HE, highlighting etiologies that are more prevalent within the pediatric population. Additionally, a summary of the epidemiology of pediatric HE will be presented, with focus on some of the differences that exist between pediatric and adult HE. Finally, a directed approach to the diagnostic evaluation of children with HE will be discussed.

Keywords: children; diagnostic testing; differential diagnosis; eosinophil; epidemiology; hypereosinophilia.

Figure 1

Differential diagnosis for hypereosinophilia (HE) in children. Pediatric HE can be separated into two main categories (primary and secondary HE) on the basis of the underlying mechanisms driving the eosinophil expansion. Primary HE results from myeloid and stem cell abnormalities that propagate the expansion of an eosinophil clone. Secondary HE results from a diverse group of disease states that drive the expansion of the eosinophil population through increased eosinophilopoietic cytokine (IL-3, IL-5, and GM-CSF) production. ABPA, allergic bronchopulmonary aspergillosis; HIV, human immunodeficiency virus; NSAIDs, nonsteroidal anti-inflammatory drugs; DRESS, drug reaction with eosinophilia and systemic symptoms; EoE, eosinophilic esophagitis; EGID, eosinophilic gastrointestinal disease; IBD, inflammatory bowel disease; STAT3, signal transducer and activator of transcription 3, DOCK8, dedicator of cytokinesis 8; LRBA, lipopolysaccharide-responsive-beige-like-anchor; WAS, Wiskott-Aldrich syndrome; IPEX, immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome; ALPS, autoimmune lymphoproliferative syndrome; EGPA, eosinophilic granulomatosis with polyangiitis; SLE, systemic lupus erythematosus, GVHD, graft-vs.-host disease.

Figure 2

Diagnostic approach for the child who presents with unexplained hypereosinophilia (HE) and/or moderate-to-severe eosinophilia with clinical manifestations. Concerning symptoms/laboratory findings that should prompt medical providers to pursue more intensive evaluation are noted in the red flag. ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; LDH, lactate dehydrogenase.