Abstract and Introduction
Abstract
Kounis syndrome is the concurrence of acute coronary syndromes with conditions associated with mast cell activation, such as allergies or hypersensitivity and anaphylactic or anaphylactoid insults that can involve other interrelated and interacting inflammatory cells behaving as a 'ball of thread'. It is caused by inflammatory mediators such as neutral proteases including tryptase and chymase, arachidonic acid products, histamine, platelet activating factor and a variety of cytokines and chemokines released during the activation process. Platelets with FCεRI and FCεRII receptors also participate in the above cascade. Vasospastic allergic angina, allergic myocardial infarction and stent thrombosis with occluding thrombus infiltrated by eosinophils and/or mast cells constitute the three reported variants of this syndrome. Kounis syndrome is a ubiquitus disease that represents a magnificent natural paradigm and nature's own experiment, in a final trigger pathway implicated in cases of coronary artery spasm and plaque rupture. Kounis syndrome can complicate anesthesia, vaccination, medical therapy and stent implantation and it seems to be associated with coronary allograft vasculopathy and takotsubo syndrome, it can often be confused with hypersensitivity myocarditis and can be the cause of unexplained sudden death. Kounis syndrome has revealed that the same mediators released from the same inflammatory cells are present in acute coronary events of nonallergic etiology. These cells are not only present in the culprit region before plaque erosion or rupture but they release their contents just before an actual coronary event. Therefore, does Kounis syndrome represent a magnificent natural paradigm and nature's own experiment in a final trigger pathway implicated in cases of coronary artery spasm and plaque rupture showing a novel way towards our effort to prevent acute coronary syndromes? Drugs, substances targeting the stem cell factor that is essential for mast cell development, proliferation, survival, adhesion and homing as well as monoclonal antibodies and natural molecules that protect mast cell surface and stabilize mast cell membrane could emerge as novel therapeutic ways capable to prevent acute coronary and acute cerebrovascular events.
Introduction
Three words, taken from the Hellenic vocabulary, constitute the main cornerstones of today's immunology:
squo;Anaphylaxis' (from Hellenic aphylaxis = no phylaxis, meaning without protection, whereas prophylaxis means protection) was introduced by the French physiologists Paul Portier and Michael Richet in 1902, when they described a dog that developed cardiorespiratory arrest and died after injection of a jellyfish toxin called actinotoxin, although 14 days earlier the dog had well tolerated the same injection.[1] Both scientists were awarded the Nobel Prize in Medicine and Physiology in 1913;
'Allergy' (from Hellenic allergia = allo ergo, meaning altered capacity to react) was coined in 1906 by the Viennese pediatrician and immunologist Clements von Piquet, who recognized that in both protective immunity and hypersensitivity reactions, antigens had induced changes in reactivity;[2]
'Atopy' (from the Hellenic atopos = no topos, meaning out of place) which is often used to describe IgE-mediated diseases (Box 1).
An important contributor in allergy, atopy and anaphylaxis is a unique cell named by Paul Erlich in 1887 as a 'mast cell' because of its numerous metachromatic granules, which reminded him of a 'well-fed cell' (mastzellen in German).[3] Mast cells are ubiquitous in the human body, including the brain, which does not suffer from allergic reactions because IgE antibody complexes do not cross the blood–brain barrier. Mast cells preform and store approximately 500 secretory granules and many others which are made de novo and are released locally and in systemic circulation when specific antigens react with IgE antibodies attached to mast cells and induce mast cell degranulation. This degranulation resembles a bag of popcorn 'popping' until the contents overflow[4] and occurs only in approximately 10% of atopic individuals. Mast cells have been linked to many human organs and systems and, as has been stated by Theoharides, their role is versatile and compels a more appropriate name to indicate its polydimensional potential,[5] perhaps 'pleiotropocyte' (multifaceted cell in Hellenic).
Despite cardiovascular symptoms and signs being the main clinical manifestations associated with allergic or hypersensitivity and anaphylactic or anaphylactoid attacks, it was not until six decades ago, when Pfister reported a 49-year-old man who developed anteroseptal myocardial infarction and urticaria after 4 days of treatment with 300,000 units/day penicillin in oil. The patient was treated with dicumarol, papaverine, morphine and diphenhydramine hydrochloride.[6]
In 1991, Kounis and Zavras described the syndrome of allergic angina as the concurrence of chest pain and allergic reactions, accompanied by clinical and laboratory findings of classical angina pectoris caused by inflammatory mediators released during the allergic insult.[7] Allergic angina could progress to acute myocardial infarction which was named allergic myocardial infarction.[8–10]
In 1995, Kovanen et al. examined specimens of coronary arteries from 20 patients who had died of acute myocardial infarction and found that the degree of mast cell degranulation was much higher (200:1) at the sites of plaque erosion or rupture than in adjacent areas or in the more distant unaffected areas.[11] He concluded that collagen-degrading proteases, from mast cells, could induce plaque erosion and/or rupture. Following this clinical description, in 1995 Constantinides raised the possibility that "even ordinary allergic reactions could promote plaque disruption".[12] This was based on Constantinides's observation that circulating mast cell precursors could penetrate the open junctions between endothelial cells that line human atheromatous plaques in contrast to closed junctions over the normal arterial intima.[13] In 1998, Braunwald categorized allergic angina in a subgroup of dynamic coronary occlusion lesions by stating that "allergic reactions with mediators such as histamine or leukotrienes acting on coronary vascular smooth muscle" can induce vasospastic angina.[14]
Today, allergic angina and allergic myocardial infarction is a ubiquitous disease covering a wide spectrum of mast cell activation disorders that are referred to as 'Kounis syndrome'[15–17] and are described in major cardiovascular textbooks,[18] as a new clinical entity.
Kounis syndrome is regarded as a magnificent natural paradigm and nature's own experiment which might have profound clinical and therapeutic implications and may shed light on potential therapeutic strategies that may apply to the area of interference with plaque erosion or rupture and primary as well as secondary prevention of acute coronary and cerebrovascular events.
Future Cardiol. 2011;7(6):805-824. © 2011 Future Medicine Ltd.
Cite this: Kounis Syndrome - Medscape - Nov 01, 2011.
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