Kounis syndrome is defined as acute coronary syndrome 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 arteries leading to the heart muscle or a plaque breaking free and blocking one or more of those arteries. 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 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.
Patients with systemic allergic reactions associated with clinical, electrocardiographic, angiographic, echocardiographic and laboratory findings of acute myocardial ischemia should be diagnosed as having Kounis syndrome. Serum tryptase, histamine, immunoglobulins , cardiac enzymes, cardiac troponins are helpful to confirm the diagnosis. In Kounis syndrome, the newer techniques such as thallium-201 single-photon emission computer tomography and 125I-15--3- methylpentadecanoic acid SPECT have revealed severe myocardial ischemia while coronary angiography showed normal coronary arteries. Furthermore, with cardiac magnetic resonance imaging, the delayed contrast-enhanced images show normal washout in the subendocardial lesion area in patients with Kounis syndrome type I variant.
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 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. Type III is subdivided now to stent thrombosis and stent restenosis.
Management
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 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
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.
History
While there are several older reports associating, clinically, allergy and the heart with names such as morphologic cardiac reactions, acute carditis or lesions with basic characteristics of rheumatic carditis, the first full description of allergy-mediated acute coronary syndrome is attributed to the Greek cardiologist Nicholas Kounis, who in 1991 reported on the possible role of allergy in cases of coronary artery spasm.
