Kounis syndrome (aka allergic acute coronary syndrome) is defined as acute coronary syndrome (symptoms such as chest pain relating to reduced blood flow to the heart) caused by an allergic reaction or a strong immune reaction to a drug or other substance. It is a rare syndrome with authentic cases reported in 130 males and 45 females, as reviewed in 2017; however, the disorder is suspected of being commonly overlooked and therefore much more prevalent. Mast cell activation and release of inflammatory cytokines as well as other inflammatory agents from the reaction leads to spasm of the artery leading to the heart muscle or a plaque breaking free and blocking that artery.
The Kounis syndrome is distinguished from two other causes of coronary artery spasms and symptoms viz., the far more common, non-allergic syndrome, Prinzmetal's angina and eosinophilic coronary periarteritis, an extremely rare disorder caused by extensive eosinophilic infiltration of the adventitia and periadventitia, i.e. the soft tissues, surrounding the coronary arteries.
Signs and symptoms
Acute coronary syndrome (ACS) is usually associated with a constrictive pain in the chest, characteristically with radiation to the neck or the left arm and often associated with pallor, sweatiness, nausea and breathlessness. In allergic ACS there may also be specific symptoms relating to the underlying allergic reaction, such as swelling of the face and tongue, wheeze, hives and potentially very low blood pressure (anaphylactic shock).
In allergy, mast cells release inflammatory substances such as histamine, neutral proteases, arachidonic acid derivatives, platelet activating factor and a variety of cytokines and chemokines. These mediators can precipitate coronary artery spasm and accelerate the rupture of atheromatous plaques of the coronary arteries. This interferes with the blood flow to the heart muscle and causes symptoms otherwise indistinguishable from unstable angina.
It is possible that even in people without direct evidence of allergy, the allergic response may be playing a role in acute coronary syndrome: markers of mast cell activation are found in people with ACS.
Three variants of Kounis syndrome are recognised:
- Type I occurs in people without underlying coronary artery disease who have allergic ACS secondary to coronary artery spasm. This may lead to myocardial infarction.
- Type II occurs in people with underlying asymptomatic coronary artery disease where an allergic reaction leads to either coronary artery spasm or plaque erosion.
- Type III occurs in the setting of coronary thrombosis (including stent thrombosis) where aspirated thrombus stained with hematoxylin-eosin and Giemsa demonstrate the presence of eosinophils and mast cells respectively. It also includes those with people who have died suddenly after previous coronary stent insertion, where evidence of an allergic reaction to the stent is found on post-mortem examination
The management of these patients may be challenging for clinicians. Although beta blockers can be beneficial in ACS, they are contraindicated in Kounis syndrome. In allergic ACS, blocking beta receptors while giving epinephrine (which is the basis of treatment of anaphylaxis) can lead to an unopposed activity of α-adrenergic receptors which would aggravate the coronary spasm. Also opioids, indicated to relieve chest pain, may induce massive mast cell degranulation which in turn will worsen the anaphylaxis. They should hence be given carefully in such patients
Type I variant
Treatment of the allergic event alone can abolish type I variant. Giving vasodilators such as nitroglycerin or calcium channel blockers is recommended. Antihistamine and mast cell stabilizers e.g. cromoglicate or nedocromil can be also considered.
Type II variant
acute coronary event protocol is applied. Corticosteroids, antihistamine, vasodilators such as nitroglycerin and calcium channel blockers are given when appropriate.
Type III variant
The use of mast cell stabilizers in association with steroids and antihistamines are recommended. Harvesting of intrastent thrombus together with histological examination of aspirated material and staining for eosinophils and mast cells should be undertaken. When allergic symptoms are present following stent implantation, desensitization measures should be applied.
While there are several older reports of possible allergy-mediated acute coronary syndrome, the first full description is attributed to the Greek cardiologist Nicholas Kounis, who in 1991 reported on the possible role of allergy in cases of coronary artery spasm.
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