{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:13:09Z","timestamp":1791724389688,"version":"4.3.4"},"reference-count":217,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>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 selected 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 suggests that coronary microvascular dysfunction may contribute substantially to the clinical phenotype, expanding the traditional concept of allergic epicardial vasospasm. Current evidence 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.<\/jats:p>","DOI":"10.3390\/jcm15166417","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T13:14:01Z","timestamp":1787145241000},"page":"6417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Kounis Syndrome in the Modern Era: A Comprehensive Review of Allergic Acute Coronary Syndromes"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7191-9595","authenticated-orcid":false,"given":"Lucio Giuseppe","family":"Granata","sequence":"first","affiliation":[{"name":"Cardiology Division, Garibaldi-Nesima Hospital, Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione (ARNAS) Garibaldi, 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5552-6382","authenticated-orcid":false,"given":"Giuseppe","family":"And\u00f2","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Azienda Ospedaliera Papardo, 98158 Messina, Italy"},{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1243-0600","authenticated-orcid":false,"given":"Marcello","family":"Marchetta","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Policlinico Tor Vergata, Viale Oxford, 81, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1915-585X","authenticated-orcid":false,"given":"Simona","family":"Giubilato","sequence":"additional","affiliation":[{"name":"Cardiology Division, Cannizzaro Hospital, 95126 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9751-6710","authenticated-orcid":false,"given":"Nicholas G.","family":"Kounis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Faculty of Medicine, University of Patras, 26500 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3022-266X","authenticated-orcid":false,"given":"Cesare","family":"de Gregorio","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Clinical and Experimental Medicine, Heart Failure and Cardiomyopathy Outpatient Office, G. Martino Hospital Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1515\/cclm-2016-0010","article-title":"Kounis syndrome: An update on epidemiology, pathogenesis, diagnosis and therapeutic management","volume":"54","author":"Kounis","year":"2016","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_2","unstructured":"(1938). Queries and Minor Notes: Tetanus Antitoxin or Coronary Thrombosis as a Cause of Death. 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