Clinical significance of very high IgE levels (≥1000 IU/mL): Population-based study of 118,211 adults

Background: Very high serum IgE (≥1000 IU/mL) is reported in atopic disorders. However, data on its significance in nonallergic disorders are limited. Objective: We aimed to analyze the diagnostic value of very high IgE in adults. Methods: A retrospective nationwide study was conducted using the electronic database of Clalit Health Services, covering adults (≥18 years) treated between 2002 and 2022. Subjects with IgE ≥ 1000 IU/mL were compared to the controls with IgE < 100 IU/mL across 3 age groups (18-30, 31-64, and ≥65 years). Outcomes included eosinophilic, autoimmune, autoinflammatory, and cardiovascular disorders (CVD), cancer, and inborn errors of immunity (IEI). A multivariable Cox regression model determined statistical significance (P < .05). Results: The study included 118,211 subjects: 110,116 controls and 8635 with very high IgE levels. Excluding insect sting and drug allergies, very high IgE was more common across all tested allergic disorders, with asthma showing the highest rate (64.49%). Univariable analysis showed higher prevalence of CVD (3.88% vs 2.72%, P < .001), eosinophilic disorders (0.42% vs 0.06%, P < .001), and IEI (0.35% vs 0.20%, P = .004) in the very high IgE group. Multivariable analysis revealed age-dependent significant results: higher CVD risk in ages 31-64 (hazard ratio = 1.249; 95% confidence interval, 1.054-1.481; P = .010) and borderline IEI association in ages 18-30 (hazard ratio = 1.802; 95% confidence interval, 0.978-3.321; P = .059). Risk of eosinophilic disorders was increased across all age groups (P < .001). Conclusions: Very high IgE level of ≥1000 IU/mL is associated with increased risks of CVD, IEI, and eosinophilic disorders. Physicians should consider further assessment for these conditions in nonallergic patients with very high IgE levels.