Comorbidity burden in patients with anaphylaxis: A 25-year nationwide population-based matched case-control study

Background: Anaphylaxis is a severe systemic hypersensitivity reaction that occurs in diverse clinical contexts. Its broader comorbidity profile in population-based settings has not been well characterized. Objective: The objective was to evaluate the prevalence and spectrum of comorbid diseases in patients with anaphylaxis compared with matched controls in a nationwide population. Methods: We conducted a retrospective population-based matched case-control study by using electronic health record data from a nationwide health maintenance organization in Israel between 2001 and 2024. Anaphylaxis cases were confirmed by manual chart review according to World Allergy Organization criteria with documented epinephrine treatment. The controls were matched on age, sex, and calendar time, and had no history of anaphylaxis. Baseline comorbidities documented at least 3 months before the index date were analyzed by using conditional logistic regression. Multiple comparisons were addressed by using false discovery rate adjustment. Results: The study included 778 patients with anaphylaxis and 3112 matched controls. The patients with anaphylaxis had a significantly higher prevalence of atopic and allergic diseases, including asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, contact dermatitis, and chronic idiopathic urticaria. The composite atopic disease burden was markedly higher in the anaphylaxis group. Selected immune-mediated and cardiovascular conditions were also more prevalent, although the effect sizes were generally modest and several associations did not remain statistically significant after a multiple-comparison correction. An eliciting allergen was identified in 82.4% of the patients, with drugs as the most frequent triggers, followed by food and insect venom. Idiopathic anaphylaxis accounted for 17.6% of the patients. Baseline medication utilization was higher among the patients with anaphylaxis, particularly for allergic, respiratory, and gastrointestinal therapies. Conclusion: In this nationwide adult cohort, individuals with anaphylaxis demonstrated a higher prevalence of atopic disease and modest differences in selected systemic comorbidities compared with matched controls. These findings describe epidemiologic associations and do not imply causality. Further prospective studies are warranted.