Beyond atopy: etiological evaluation of markedly elevated serum total IgE (>1000 IU/ml)

Aims: Marked elevation of serum total immunoglobulin E (IgE) levels (>1000 IU/ml) is most commonly associated with atopic diseases; however, its underlying etiology is highly heterogeneous. This study aimed to systematically evaluate the etiological factors associated with markedly elevated serum total IgE levels in patients attending an allergy and immunology outpatient clinic. Methods: Medical records of 1103 patients with serum total IgE levels >1000 IU/ml who presented to the allergy and immunology outpatient clinic between January 1 and September 1, 2023, were retrospectively reviewed. Patients with only a single outpatient visit and those who did not undergo adequate diagnostic evaluation to determine the cause of IgE elevation were excluded. A total of 643 patients who completed comprehensive clinical, laboratory, and diagnostic assessments were included in the final analysis. Etiological causes of IgE elevation were classified based on clinical and laboratory findings. Results: The mean age of the 643 patients was 47.55±17.00 years, and 52.9% were female. The median serum total IgE level was 1520 (1001–62,753) IU/ml. Atopic diseases were identified as the most common etiological factor (n:530, 82.4%). Other causes included infectious diseases (5.3%), inflammatory diseases (1.2%), neoplasms (0.5%), primary immunodeficiency disorders (0.2%), drug-related causes (0.2%), and other conditions (0.2%). Despite comprehensive evaluation, no underlying cause could be identified in 65 patients (10.1%), who were classified as having idiopathic total IgE elevation. Conclusion: Although markedly elevated serum total IgE levels are predominantly associated with atopic diseases, a substantial proportion of patients have alternative or unidentified etiologies. A systematic and multidisciplinary diagnostic approach is essential to accurately identify the underlying cause of IgE elevation and to guide appropriate clinical management.