The Aetiology of Elevated Total Serum Immunoglobulin E in Children

The paucity of real-world data on the aetiology of elevated total serum immunoglobulin E (TS-IgE) in children afflicts families and health care systems with diagnostic uncertainty. We explored a cohort of children with TS-IgE levels over 1000 kU/L, focusing on the prevalence of atopic and non-atopic conditions, the aetiology of extremely elevated TS-IgE and the relevance of TS-IgE levels for the diagnosis of non-atopic diseases.

Data from paediatric patients managed at HUS Group hospitals in Finland between 1998 and 2024 were queried for TS-IgE levels and International Classification of Diseases (ICD)-10 diagnostic codes. A chart review was performed for patients with non-atopic conditions.

Our cohort included 2431 children with TS-IgE levels over 1000 kU/L; for 2061 of them, ICD-10 codes were available. Non-atopic conditions rarely caused TS-IgE elevation (45/2061 patients, 2%), even in children with extremely high (> 15 000 kU/L, N = 76) TS-IgE levels. Graft-versus-host disease and inborn errors of immunity were the most common non-atopic aetiologies of TS-IgE elevation. All children with non-atopic conditions manifested distinct clinical symptoms, and TS-IgE level was irrelevant for reaching the diagnosis.

Non-atopic conditions were uncommon and clinically obvious in children with elevated TS-IgE; therefore, we question the diagnostic relevance of TS-IgE measurement.