Non-syndromic hyper-IgE in children: A practical approach.
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Hyper-IgE, generally defined as serum IgE levels exceeding 2000 IU/mL, presents a common yet complex diagnostic challenge in pediatric practice. While elevated serum IgE are frequently observed in atopic conditions such as food allergy or atopic eczema, or parasitic infections, they may also signal underlying monogenic immunological diseases, specifically inborn errors of immunity (IEI) categorized under hyper-IgE syndrome (HIES). Distinguishing between common atopic diseases and HIES is essential, especially in children with early-onset, severe, or treatment-resistant presentations. This review focuses on non-syndromic causes of hyper-IgE in children, aiming to provide a practical, structured framework for clinicians. A broad array of conditions, including allergic diseases, infections, inflammatory disorders, malignancies, drug reactions, and environmental exposures, can result in elevated IgE levels. Given this wide differential, a systematic approach that incorporates detailed clinical history, physical examination, and targeted investigations is critical to guide diagnostic reasoning. To aid clinical decision-making, the authors propose a stepwise diagnostic algorithm that prioritizes common causes while also alerting clinicians to red flags suggestive of IEI or other rare conditions. This approach facilitates timely referral for immunologic or genetic evaluation when appropriate and minimizes unnecessary testing. Increased awareness of the diverse etiologies of hyper-IgE can improve diagnostic accuracy, enhance early intervention, and reduce morbidity. Future research should aim to refine diagnostic strategies, validate clinical algorithms, and develop standardized guidelines. Moreover, long-term data regarding characterization and subsequent follow-up of children with an isolated increase in serum IgE levels is fundamental to understanding the clinical and immunological trajectories of these patients.