Hypereosinophilia in Children and Adults: A Retrospective Comparison

Abstract

Background: The differential diagnosis of hypereosinophilia is broad and includes asthma, atopic disease, drug hypersensitivity, parasitic infection, connective tissue disorders, malignancy, and rare hypereosinophilic disorders. Hypereosinophilia in children has not been well characterized to date.

Objective: The objective of this study was to identify the common causes of marked eosinophilia in children and to characterize and compare the clinical symptoms at presentation, laboratory findings, final diagnosis, and therapeutic responses between children and adults with hypereosinophilic syndromes.

Methods: A retrospective analysis of consecutive subjects evaluated for unexplained eosinophilia ≥ 1.5 × 10(9)/L was conducted. All subjects underwent standardized clinical and laboratory evaluations with yearly follow-up. Clinical and laboratory parameters, final diagnoses, treatment responses, and outcomes were assessed. Medians and proportions were compared using Mann-Whitney U and Fisher Exact tests, respectively.

Results: Of the 291 subjects evaluated, 37 (13%) were children and 254 were adults (87%). Whereas the frequencies of clinical hypereosinophilic syndrome (HES) variants were similar between children and adults, primary immunodeficiency was a more common secondary cause of HES in children (5% vs 0.4% in adults). Excluding subjects with treatable secondary causes, the median peak absolute eosinophil count was increased in pediatric subjects (9376 vs 5543/μL; P = .002), and children had more gastrointestinal complaints (62% vs 34%; P = .003) and less pulmonary involvement (34% vs 59%; P = .01) than adults. Despite these differences, corticosteroid responsiveness and overall prognosis were similar between the 2 groups.

Conclusions: Although children with HES often present with higher peak eosinophil counts than adults, the differential diagnosis, clinical characteristics, and prognosis of HES are similar in the 2 groups.

Keywords: Children; Eosinophil; Hypereosinophilic syndrome; Pediatric.

Figure 1

Clinical manifestations and organ involvement in subjects with HES. Bars represent the % of adults (black) or children (grey) with signs or symptoms consistent with involvement in each category. Patients with associated HES have been excluded from this analysis. Gastrointestinal manifestations included abdominal pain, nausea/vomiting, diarrhea; dermatologic manifestations included rash, urticaria, angioedema; allergic manifestations included outside physician diagnostic history of asthma, allergic rhinitis, or sinusitis; hematologic manifestations included thrombus, splenomegaly, lymphadenopathy, neoplasm; constitutional manifestations included fever and fatigue; pulmonary manifestations included infiltrates identified with imaging and pleural effusion(s); rheumatologic manifestations included myalgia/arthralgia and eosinophilic fasciitis; neurologic manifestations included clinical history of stroke or neuropathy; cardiac manifestations included valvular disease, endomyocardial fibrosis, pericarditis, elevated troponin. *p<0.05, **p<0.01, Mann-Whitney test

Figure 2

Frequency of clinical variants among patients presenting with HE/HES. Bars represent the % of adults (black) or children (grey) meeting the diagnostic criteria for each HE/HES variant. IHES refers to idiopathic hypereosinophilic syndrome; overlap disorder includes those subjects with evidence of single organ disease and peripheral eosinophilia ≥ 1.5 × 10⁹/L or evidence of a clinical overlap between Eosinophilic Granulomatosis with Polyangiitis and HES; myeloproliferative disorders with eosinophilia includes those subjects with myeloproliferative variant HES, those with myeloproliferative disease and a known mutation, and those with chronic eosinophilic leukemia-not otherwise specified; LHES refers to lymphocytic variant HES; and FE refers to familial eosinophilia.

Figure 3

Prescribed treatments in patients with HES. Bars represent the % of adults (black) or children (grey) who received the specified therapy prior to or during the course of the study. Patients with associated HES have been excluded from this analysis. Corticosteroids included prednisone, prednisolone, and methylprednisolone.