Long-Term Outcomes of Paediatric Patients With Unexplained Elevated Total Immunoglobulin E

To clarify the aetiology and clinical relevance of markedly elevated total serum immunoglobulin E (IgE) levels (≥ 1000 IU/mL) in children and to characterise the longitudinal outcomes of patients with persistently elevated IgE levels in whom no underlying cause can be identified.

This retrospective cohort study included children aged 1-18 years evaluated between September 2019 and June 2025 with total serum IgE levels ≥ 1000 IU/mL. Patients with at least three outpatient visits and a minimum follow-up of 12 months were eligible for final analysis. Comprehensive clinical, allergic, immunologic and laboratory assessments were performed to identify aetiologies. Children without an identifiable cause were followed longitudinally and classified according to IgE trajectories and clinical evolution.

Among 1840 children with markedly elevated IgE levels, 1508 were eligible for final analysis. An aetiologic diagnosis was established in 1449 patients (96.1%), predominantly allergic diseases (97.4%). Only 59 children (3.9%) had unexplained IgE elevation despite extensive evaluation. Over a median follow-up of 27 months, most of these children remained asymptomatic or demonstrated spontaneous declines in IgE levels. However, 13.6% developed new allergic diseases during follow-up. Persistently elevated IgE levels were associated with transient differences in eosinophil counts but not with consistent immunologic abnormalities or severe clinical outcomes.

In childhood, markedly elevated total IgE levels almost always reflect an identifiable underlying condition, most commonly atopic disease. Truly unexplained IgE elevation is rare and typically follows a benign course. In the absence of clinical warning signs, careful longitudinal monitoring, rather than aggressive or invasive diagnostic testing, appears to be the most appropriate management strategy, since a minority of these children, particularly those with persistently elevated IgE, go on to develop atopic disease.