Kounis Syndrome in the Modern Era: A Comprehensive Review of Allergic Acute Coronary Syndromes

Kounis syndrome (KS) is a largely underdiagnosed cause of acute coronary syndromes
triggered by allergic or hypersensitivity reactions. The syndrome results from complex
immune cell activation with the release of vasoactive and prothrombotic mediators leading
to coronary vasospasm (type I KS) or thrombosis of plaque (type II KS), stent (type III KS)
or coronary artery bypass graft (type IV KS). Despite increasing recognition over the past
few decades, its pathophysiological mechanisms, diagnostic boundaries, and therapeutic
implications remain incompletely understood. A comprehensive diagnostic approach,
including signs, symptoms, biochemical findings, electrocardiography, echocardiography,
coronary angiography, and multimodality imaging, as well as invasive assessment in se-
lected cases, can be recommended, although its implementation in routine practice remains
limited. Available data indicate that angiographically documented epicardial coronary
spasm is observed in only a minority of patients, while normal or non-obstructive coronary
arteries are frequently encountered. Emerging data from provocative testing, invasive
coronary functional assessment, cardiac magnetic resonance and nuclear imaging sug-
gests that coronary microvascular dysfunction may contribute substantially to the clinical
phenotype, expanding the traditional concept of allergic epicardial vasospasm. Current ev-
idence supports the recognition of type I KS as a distinct allergic vasomotor acute coronary
syndrome within the myocardial infarction non-obstructive coronary artery (MINOCA)
spectrum, deserving greater recognition in future diagnostic classifications and clinical
practice guidelines. This narrative review critically appraises current evidence, integrating
historical perspectives with contemporary insights into classification, pathophysiology,
triggers, diagnostic strategies and therapeutic approaches, focusing on the most frequent
manifestation represented by the vasospastic variant.