Association Between Kounis Syndrome and Allergy-Associated Coronary Events: A Disproportionality Analysis Using the Japanese Adverse Drug Event Report Database.

Background Kounis syndrome (KS) is an allergy-induced acute coronary syndrome (ACS); however, the lack of established diagnostic criteria raises concerns regarding underdiagnosis. Misclassification of allergy-associated coronary events as non-KS conditions may hinder appropriate treatment and risk stratification. This study aimed to elucidate the clinical differences between KS and allergy-associated coronary events not diagnosed as KS (non-KS) to improve diagnostic recognition and clinical awareness.  Methods Using the Japanese Adverse Drug Event Report database (2012Q3-2024Q2), we compared patient backgrounds, suspected drugs, and clinical features between the KS (n = 130) and non-KS (n = 115) groups. Multivariate analysis identified predictors of non-KS events.  Results The KS group was associated with anesthetics and contrast media (e.g., iodinated agents such as iopamidol and iohexol), whereas the non-KS group was associated with heparin and the coronavirus disease 2019 vaccine. The non-KS group showed higher mortality and prevalence of specific underlying diseases than the KS group. Multivariate analysis identified heparin-induced thrombocytopenia (odds ratio (OR), 198.38; 95% confidence interval (CI), 39.45-3621.42), antineoplastic drug use (OR, 20.30; 95% CI, 6.68-76.87), fatal outcomes (OR, 11.98; 95% CI, 4.63-34.28), shock (OR, 10.02; 95% CI, 2.13-73.12), and ACS (OR, 5.66; 95% CI, 1.59-21.53) as independent predictors of non-KS events (all P < 0.05; area under the curve, 0.891).  Conclusions Patients without KS often have severe underlying conditions and worse outcomes, suggesting a potential oversight of KS in clinical practice. These findings underscore the importance of improving the diagnostic clarity for KS and may contribute to future efforts to refine diagnostic criteria and pharmacovigilance practices.