Kounis syndrome

Kounis syndrome is defined as acute coronary syndrome,  caused by an allergic reaction or a strong immune reaction to a drug or other substance.

Kounis syndrome, also known as allergic angina or allergic myocardial infarction, is a rare medical condition in which an allergic or hypersensitivity reaction triggers acute coronary events. 

It occurs when an allergen, such as certain medications, insect bites or stings, or food, stimulates the release of inflammatory substances, such as histamine, that can cause narrowing or spasm of the coronary arteries. 

This can lead to reduced blood flow to the heart and potentially result in angina or even a heart attack.

Symptoms of Kounis syndrome can vary and may include chest pain, shortness of breath, palpitations, sweating, dizziness, or loss of consciousness. 

These symptoms can resemble a heart attack, so it’s important to seek immediate medical attention if experiencing any of these symptoms.

The treatment for Kounis syndrome primarily focuses on managing the allergic reaction itself and providing supportive care for the cardiovascular symptoms. 

This may involve the use of antihistamines, corticosteroids, and medications to open up the coronary arteries. In severe cases, emergency interventions like coronary angioplasty or stenting may be necessary.

It is a rare syndrome.

It 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 by the far more common, non-allergic syndrome.

Is it an allergic reaction that triggers mast cell degranulation that leads to the release of numerous inflammatory mediators that have clinically relevant effects on coronary arteries: histamine, proteases, and platelet activating factor, which can induce coronary vasospasm or plaque disruption, or can promote stent thrombosis, ultimately leading to one of three variants of the Kounis syndrome.

No specific test exists for the diagnosis of the Kounis syndrome.

Kounis syndrome diagnosed this, based on the clinical signs and symptoms of an allergic reaction with signs and symptoms of acute coronary syndrome. 

Most patients have cutaneous symptoms, bronchospasm, or anaphylaxis.

87% of patients have chest pain and more than 95% have abnormal ECG findings most commonly ST elevations.T4

Most cases have been found in southern Europe including Turkey, Greece, Italy, and Spain. 

A wide age range is observed from from 2 to 90 years.

Commonly seen comorbidities include hyperlipidemia, diabetes, smoking, hypertension, and prior allergic reactions to a precipitating factor.

A possible gene-environment interactions with evaluation showing a heterozygous E148Q mutation.

Causes that precipitate this syndrome include:  drugs, various health conditions, food, and environmental exposures,  precipitating IgE antibody production can contribute to this syndrome. 

Drugs include: analgesics such as aspirin and dipyrone, anesthetics, multiple antibiotics, anticoagulants such as heparin and Lepirudin, thrombolytics such as TPA, anti-platelet therapy including Clopidogrel, anti-neoplastics, glucocorticoids, nonsteroidal anti-inflammatory drugs, proton pump inhibitors, skin disinfectants, sympathomimetics, volume expanders, antifungals, antivirals, and oral contraceptives,  allopurinol, enalapril, losartan, insulin, and others can also trigger this syndrome.

Conditions that incriminate Kounis syndrome include bronchial asthma, Churg–Strauss syndrome, serum sickness, scombroid syndrome, angioedema, hay fever, anaphylaxis,anisakiasis, and corronary stenting.

Environmental exposure to poison ivy, grass, latex, and nicotine have been found to be contributory. 

Bites can precipitate Kounis syndrome: spiders, snakes, scorpions, fire ants and jellyfish. 

Miscellaneous triggers include contrast media. 

Reactions to various foods that cause an allergic and inflammatory response can lead to acute coronary syndrome.

Allergic acute coronary syndrome is a syndrome has two components: an immune mediated resulting in hypersensitivity, allergy, and an anaphylactic or anaphylactoid reaction: and a second component involving  cardiac signs and symptoms seen with acute coronary syndrome.

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 anaphylactic shock, stridor, drowsiness, syncope, abdominal pain, diarrhea, vomiting, and acute pulmonary edema.

Myocardial infarction, acute cardiac failure, and sudden cardiac death may also be seen with Kounis syndrome.

As high as 13% of adult onset  sudden cardiac deaths are coupled with mast cell degranulation: Kounis syndrome can involve a silent allergic reaction.

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. 

Such mediators can precipitate coronary artery spasm and accelerate the rupture of atheromatous plaques of the coronary arteries, causing  symptoms otherwise indistinguishable from unstable angina.

It is possible a allergic response may be playing a role in acute coronary syndrome: markers of mast cell activation are found in people with ACS.


Kounis syndrome is often missed or underdiagnosed.

The majority of the cases had a duration of under one hour while some had a duration of 6 hours. 

EKG, chest x-ray, echocardiography, and angiography and cardiac enzyme are needed if suspicion for myocardial ischemia

 or infarction is present.

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. 

EKG changes can be consistent with infarction most commonly in the inferior leads, ischemia, sinus bradycardia or tachycardia, heart block, atrial fibrillation, ventricular fibrillation, ventricular ectopic beats, QRS and QT prolongation, and findings similar to digoxin toxicity.

Serum tryptase, histamine, immunoglobulins (IgE), cardiac enzymes, cardiac troponins are helpful to confirm the diagnosis. 

In Kounis syndrome, thallium-201 single-photon emission computer tomography (SPECT) may  reveal severe myocardial ischemia while coronary angiography shows normal coronary arteries. 

Three variants of Kounis syndrome are recognized:

Type I is also known as allergic vasospastic angina due to endothelial dysfunction. 

KS occurs in people without underlying coronary artery disease or predisposing factors who have allergic ACS secondary to coronary artery spasm. 

Inflammatory mediators during an allergic reaction can cause arterial spasms with normal troponins. 

However, this PROCESS may lead to myocardial infarction which will elevate troponins. 

MINOCA, myocardial infarction with non-obstructive coronary arteries, that includes endothelial dysfunction and can be caused by this 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. 

Type III includes patients 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 (subtype a) and stent restenosis (subtype b).

The management of these patients is complicated: beta blockers can be beneficial in ACS, they are contraindicated in Kounis syndrome, as giving epinephrine the basis of treatment of anaphylaxis can lead to an unopposed activity of α-adrenergic receptors which would aggravate the coronary spasm: opioids, indicated to relieve chest pain, may induce massive mast cell degranulation which in turn will worsen the anaphylaxis. 

Type I variant is treated based on its clinical presentation and how severe the allergic reaction is. 

With a mild reaction: antihistamines and corticosteroids can help control the symptoms. 

If the patient’s presentation involves anaphylaxis, intramuscular adrenaline should be given.

Treatment of the allergic event alone can abolish type I variant. 

Giving vasodilators such as nitroglycerin or calcium channel blockers is recommended. 

Type I consequences include hypotension and worsening of anaphylaxis.

Antihistamine and mast cell stabilizers e.g. cromoglicate or nedocromil can be also considered.

Type II variant

Acute coronary event protocol is the treatment and type II can be treated similarly to type I for cardiac symptom control. 

Glucagon may be a better option than adrenaline for acute anaphylaxis in patients with prior use of chronic beta-blockers. 

In addition, beta-blockers can increase coronary vasospasm and ischemia. 

Opiates should be used with caution.

Type III variant

An acute coronary syndrome protocol is instituted, thrombus aspiration, and placing a new stent is needed.

The use of mast cell stabilizers in association with steroids and antihistamines are recommended. 

Histological examination of aspirated thrombus material and staining for eosinophils and mast cells should be undertaken. 

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