Review ArticleKounis syndrome: A concise review with focus on management☆
Introduction
Kounis syndrome (KS) is defined as the co-incidental occurrence of an acute coronary syndrome (ACS) with hypersensitivity reactions following an allergenic event. It was first described by Kounis and Zavras in 1991 as an allergic angina syndrome [1].
Multiple causes for KS have been described so far, including drugs, insect stings, foods, environmental exposures, medical conditions and following the performance of skin prick test to amoxicillin [2], [3], [4].
Most of the data in the literature are derived from the description of isolated clinical cases (almost 300) corresponding principally to adults, so the exact pathophysiological mechanisms remain elusive.
An interesting case series of children presenting with KS has also been published [5]. Two of them developed an allergic reaction to amoxicillin/clavulanic acid, and the other two after a hymenoptera sting. All four children developed chest pain associated with ST segment elevation and positive cardiac enzymes, while serum tryptase level was elevated only in one of them.
Hitherto, three different variants of KS have been defined [6], [7], [8]:
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Type I (without coronary disease): chest pain during an acute allergic reaction in patients without risk factors or coronary lesions in which the allergic event induces coronary spasm that electrocardiographic changes secondary to ischemia. The cardiac enzymes and troponins may be either normal or reflect progression toward acute myocardial infarction. The explanation for this type would be endothelial dysfunction and/or microvascular angina have been posit as probable pathophysiological mechanisms.
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Type II (with coronary disease): includes patients with pre-existing atheromatous disease, either previously quiescent or symptomatic, in which acute hypersensitive reactions cause plaque erosion or rupture, culminating in acute myocardial infarction.
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More recently a type-III variant of KS has been defined in patients with pre-existing coronary disease and drug eluting coronary stent thrombosis [9]. In these patients, Giemsa and hematoxylin–eosin staining reveals the presence of mast cells and eosinophils, respectively [10]. Virmani [11] first described in 2004 a case of hypersensitivity vasculitis in a patient with very late drug-eluting stent thrombosis. More recently, the hallmarks of hypersensitivity reactions have been demonstrated in autopsy specimens of patients with very late drug-eluting stent thrombosis, while using intravascular ultrasound in the same patients a high incidence of incomplete stent apposition and vessel remodeling has been demonstrated [12]. Very late stent thrombosis could be another manifestation to be recognized as part of the Kounis syndrome.
This review article is based on scientific publications on Kounis syndrome and the selection of articles has been made searching on PubMed these terms: Kounis syndrome; allergic angina; and acute allergic coronary syndrome. The search was not limited for a time period. As the great majority of literature data come from single case-reports or small case-series, all the published data have been taken into consideration and summarized into this review article.
Section snippets
Pathogenesis
Mast cells play a central role in hypersensitivity reactions, and they are necessary for the development of allergic reactions [13]. Mast cells are activated either by IgE-bound antigen cross-linking, anaphylotoxins (C3a and C5a) or a variety of stimuli [14]. Their activation leads to degranulation of preformed inflammatory mediators (e.g. histamine, tryptase, chymase, heparin), increased production of arachidonic acid-derived mediators (e.g. prostaglandin D2, leukotrienes B4 and C4, platelet
Treatment
Kounis syndrome is a complex acute coronary manifestation which requires rapid treatment decisions aimed not only at myocardium revascularization, but aimed also at treating the concomitant allergic reaction.
Until now, guidelines for the treatment of Kounis syndrome are lacking and most of the evidence on the efficacy of the treatment is based on individual case reports or case series. A recent review by Kounis grants suitable recommendations for each variant [29]. In this context, it has to be
Learning points
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Kounis syndrome is the co-incidental occurrence of an acute coronary syndrome with hypersensitivity reactions following an allergenic event.
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Mast cells and their products are crucial for the pathogenesis of Kounis syndrome.
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Three types of Kounis syndromes: type 1, in patients without pre-existing coronary disease; type 2, in patients with coronary disease; and type 3, in patients with coronary disease and drug eluting coronary stent thrombosis.
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Treatment consists of myocardium revascularization
Conflict of interests
The authors state that they have no conflicts of interest.
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Cited by (76)
Case series: Kounis syndrome, an underdiagnosed entity
2023, REC: CardioClinicsAllergic Acute Coronary Syndrome—Kounis Syndrome
2023, Immunology and Allergy Clinics of North AmericaPerioperative Presentations of Kounis Syndrome: A Systematic Literature Review
2022, Journal of Cardiothoracic and Vascular AnesthesiaCitation Excerpt :Opioids, such as morphine, commonly are given during acute coronary syndrome; however, they can induce mast cell degranulation, and, therefore, fentanyl and its derivatives are preferred.1,60 With the type-III variant, acute coronary management, along with the immediate aspiration of stent thrombus and the examination of aspirated material for mast cell and eosinophils, are recommended, with patients possibly benefitting from dual-antiplatelet therapy, heparin, removal of stent, and myocardial revascularization.60 The use of mast-cell stabilizers, antihistamines, and steroids, along with allergy testing, followed by desensitization measures, also are recommended measures to prevent its recurrence.1,37
Analysis of clinical characteristics of Kounis syndrome induced by contrast media
2022, American Journal of Emergency MedicineAllergic Acute Coronary Syndrome—Kounis Syndrome
2022, Emergency Medicine Clinics of North AmericaCitation Excerpt :Mast cells can infiltrate areas of plaque erosion or rupture and act on the underlying smooth muscle cells. The cardiac mast cell load of patients with coronary plaques is up to 200-fold higher than in coronary arteries of healthy people.11 Mast cell–induced release of mediators has many effects on the coronary arteries including vasospasm, plaque rupture, and thrombosis.
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This study was conducted without any external financial support.