Kounis Syndrome—not a Single-organ Arterial Disorder but a Multisystem and Multidisciplinary Disease

Abstract

Coronary symptoms associated with conditions related to mast cell activation and inflammatory cell interactions, such as those involving T-lymphocytes and macrophages, further inducing allergic, hypersensitivity, anaphylactic, or anaphylactic insults, are currently referred to as the Kounis syndrome. Kounis syndrome is caused by inflammatory mediators released during allergic insults, postinflammatory cell activation, and interactions via multidirectional stimuli. A platelet subset of 20% with high-and low-affinity IgE surface receptors is also involved in this process. Kounis syndrome is not just a single-organ but also a complex multisystem and multiorgan arterial clinical condition; it affects the coronary, mesenteric, and cerebral arteries and is accompanied by allergy-hypersensitivityanaphylaxis involving the skin, respiratory, and vascular systems in the context of anesthesia, surgery, radiology, oncology, or even dental and psychiatric medicine; further, it has significantly influences both morbidity and mortality. Kounis syndrome might be caused by numerous and continuously increasing causes, with broad clinical symptoms and signs, via multi-organ arterial system involvement, in patients of any age, thereby demonstrating predominant anaphylactic features in terms of a wide spectrum of mast cell-association disorders. Cardiac symptoms, such as chest pain, coronary vasospasm, angina pectoris, myocardial infarction, stent thrombosis, acute cardiac failure, and sudden cardiac death associated with subclinical, clinical, acute, or chronic allergic reactions, constitute the clinical manifestations of this syndrome. Since its first description, a common pathway between allergic and non-allergic coronary events has been demonstrated. The hypothesis is based on the existence of a much higher degree of mast cell degranulation at plaque erosion or rupture sites compared with at the adjacent areas or even more distant segments in post-acute myocardial infarction of non-allergic etiology. Although mast cell activation, differentiation, and mediator release takes days or weeks, the mast cell degranulation may occur just before any acute coronary event, further resulting in coronary artery vasoconstriction and atheromatous plaque rupture. It seems that medications and natural molecules stabilizing the mast cell membrane as well as monoclonal antibodies protecting the mast cell surface can emerge as novel therapeutic modalities for acute coronary and cerebrovascular event prevention.

Kounis syndrome uncovers severe coronary disease: an unusual case of acute coronary syndrome secondary to allergic coronary vasospasm

“…This mechanism links a hypersensitivity reaction with raised IgE and eosinophilia with vasospasm and/or atheromatous plaque erosion or rupture. In patients with pre-existing coronary atheromatous disease, that is, type II variant, an acute release of inflammatory mediators results in either coronary vasospasm with normal cardiac biomarker levels or coronary vasospasm with plaque rupture or erosion resulting in an acute myocardial infarction 6. The latter was the case in our patient, as troponin levels increased and imaging was suggestive of an acute myocardial infarction.…”

“…Multiple causes of Kounis syndrome have been described in the literature, including environmental exposure (insect stings, venom poisoning, latex exposure, plants such as stinging nettle), drug exposure (antibiotics, analgesics, non-steroidal anti-inflammatory drugs, contrast media and corticosteroids) and various diseases (angioedema, asthma, exercise-related anaphylaxis, food allergy, Churg-Strauss syndrome) 1 2 6…”

Type I Kounis Syndrome after Protracted Anaphylaxis and Myocardial Bridge—Brief Literature Review and Case Report

“…This conduct is necessary until the diagnostic angiogram proves normal coronary arteries, especially since the paraclinical diagnostic of Kounis syndrome can be challenging, as histamine has a short half-life and circulation time of only 8 min (which renders it unpractical to use as a biomarker for acute allergic reactions). Tryptase should be measured 30 min after the onset of symptoms and later every 30 min during the following 2 h [12]. Nevertheless, raised tryptase levels could indicate atheromatous plaque instability [30]; thus, it is advisable to be measured whenever accessible.…”

“…Both the local and systemic effects can play a role in the generation Kounis syndrome. Arachidonic acid products (AAP), atherosclerotic (ATS), cytokines (CK), growth factors (GFs), hypersensitivity reaction (HSR) [12], platelet-activating factor (PAF).…”

Contrast Media Induced Kounis Syndrome: A Case Report

“…Local inflammatory cell interactions induce hypersensitivity and anaphylactic results by releasing inflammatory mediators after activation. In the Nicholas G. Kounis et al [8] summary, Kounis syndrome is a complex multisystem disease accompanied by allergy-hypersensitivity-anaphylaxis. During hypersensitivity, the mast cells and lymphocytes release inflammatory mediators, promoting an allergic reaction via a high serum level of histamine, proteases, arachidonic acid products, and chemokines.…”