Severe eosinophilia and risk of major disease and mortality: A nationwide cohort study of children and adults

Background: Severe eosinophilia (SE), defined as greater than 5000 cells/μL, is uncommon but may indicate serious underlying disease. Its long-term prognostic implications across age groups remain unclear. Objectives: We sought to investigate the long-term risk of morbidity and all-cause mortality in children and adults with SE. Methods: We conducted a nationwide, population-based, matched cohort study using data from Clalit Health Services, Israel (2000-2023). Individuals with SE (n = 3822) were matched 1:10 to subjects without SE with normal eosinophil counts (<500/μL; n = 39,005). Five-year risks of cancer, autoimmune disease, thromboembolic events, allergic disorders, and all-cause mortality were assessed using multivariable Cox proportional hazards models. Results: The study included 42,827 participants, both with and without SE. Among the 29,289 adults, 2,497 had SE and 26,792 did not. Among the 13,538 children, 1,325 had SE and 12,213 did not. Among adults, SE was associated with increased risk of hematologic malignancy (hazard ratio [HR], 2.86; 95% CI, 1.88-4.36), autoimmune disease (HR, 1.64; 95% CI, 1.38-1.95), thromboembolic events (HR, 1.91; 95% CI, 1.45-2.53), and mortality (HR, 2.20; 95% CI, 1.84-2.62). In children, SE predicted solid tumors (HR, 14.24; 95% CI, 2.39-85.00), autoimmune disease (HR, 2.48; 95% CI, 1.97-3.12), allergic disorders (HR, 1.45; 95% CI, 1.26-1.67), and markedly increased mortality (HR, 7.95; 95% CI, 3.23-19.56). Conclusions: Severe eosinophilia is a strong prognostic marker in both children and adults, associated with malignancy, autoimmune and thromboembolic disease, and premature death. Recognition of SE should prompt comprehensive evaluation and close follow-up in general and specialty caregivers.