Kounis Syndrome

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Kounis syndrome (also known as allergic angina) is a series of coronary symptoms (like concurrent chest pain) caused by the activation of mast cells due to an allergic reaction or severe immune reaction to a drug or other substances. Read More

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Kounis Syndrome

What is Kounis Syndrome?

Kounis syndrome (also referred to as allergic angina) is a series of coronary symptoms (like concurrent chest pain) caused by activation of mast cells as a result of a sensitivity or strong immune response to a drug or other substances. Kounis syndrome is rare. It has been kept aside by medical research, making the probability of the incidence and prevalence of Kounis syndrome seemingly high.  As of 2021, the administering of the COVID-19 vaccines has led to allergic reactions in the immune systems of some individuals, giving way to the development of Kounis syndrome. The most known triggers are antibiotics (28%) and insects (23%). Meanwhile, the exact underlying mechanism is not fully understood. Other Names for Kounis Syndrome
  • Allergic myocardial infarction.
  • Allergic acute coronary syndrome.
  • Coronary hypersensitivity disorder.

Variants of Kounis Syndrome

There are three types of counts syndrome. They are:
  • KS Type-1 Variant (Vasospatic allergic angina).
  • The KS Type-2 Variant (Allergic myocardial infarction).
  • KS Type-3 Variant (Stent thrombosis), with occluding thrombus infiltrated by eosinophils and/or mast cells.

Risks and Complications of Kounis Syndrome

Kounis syndrome has brought severe risks and complications to people due to diagnostic difficulties. If left untreated or its diagnosis is delayed, it can lead to severe complications. These risks and complications may range from moderate to severe and, in some cases, are life-threatening. They include:
  • Allergy.
  • Hypersensitivity.
  • Low blood pressure.
  • Slow heartbeat.
  • Wheezing.
  • Breathlessness.
  • Sweating.
  • Myocardial infarction.
  • Swellings in the face and tongue.
  • Drowsiness.
  • Loss of consciousness.
  • Pulmonary oedema.
  • Seizures.
  • Cardiac arrest.
  • Anaphylactic shock.
  • Recurrent hospitalisation.
  • Sudden death.


Kounis syndrome is often underdiagnosed. Therefore, a thorough diagnosis is essential in treating this syndrome. The doctor will likely run some tests for Kounis syndrome diagnosis, and the symptoms can serve to make a benchmark. The doctor may also want to know your medical details and family history.  Tests may include:
  • Blood tests.
  • Chest x-ray.
  • ECG, EKG, and MRI.
  • Angiography.
NOTE: Tests for serum tryptase, histamine, immunoglobulins (IgE), cardiac enzymes, cardia troponins, etc., help confirm the diagnosis. Newer diagnostic techniques include:
  • SPECT (thallium-201 single-proton emission computer tomography).
  • BMIPP (1251-15-(p-iodophenyl)-3-(R, S) methylpenta-decanoic acid SPECT).


Management of Kounis syndrome involves removing the causative allergen, managing the acute coronary vasospasm, and treating the allergic response. Careful choice and using medicines are needed while managing the acute condition to avoid further histamine release or coronary vasospasm aggravation. Up to date, Kounis syndrome has been associated with a variety of medicines, which include:
  • Beta-lactam antibiotics.
  • Non-steroidal anti-inflammatory drugs (NSAIDs).
  • Opiates such as codeine, morphine, and meperidine are used with extreme caution to relieve acute chest pain in myocardial infection.
  • Intravenous iron preparations.
  • Rocuronium.
Currently, good medicines for Kounis syndrome include:
  • Diclofenac.
  • Carboplatin.
  • Clopidogrel.
  • Mersyndol (paracetamol + codeine + doxylamine).
  • In KS type-1 variant.
Antihistamines (H1 and H2 antihistamines such as diphenhydramine and ranitidine) and corticosteroids (hydrocortisone) can help control mild reactions. If it involves anaphylaxis, intramuscular adrenaline should be given. Given vasodilators, such as nitroglycerin or calcium channel blockers is recommended. Also, antihistamines and mast cell stabilisers (for example, cromoglicate or nedocromil) can be considered.
  • In KS type-2 variant.
It can be treated similarly to type-1 for cardiac symptom control. For acute anaphylaxis in patients with prior use of chronic beta-blockers, glucagon may be a better option than adrenaline.
  • In KS type-3 variant.
Applying the acute coronary syndrome protocol, thrombus aspiration, and placing a new stent is needed. Using mast cell stabilisers in association with steroids and antihistamines is recommended. Apply the desensitisation measure for patients who develop allergic symptoms after stent implantation [1].


Kounis syndrome prognosis depends on the patient’s sensitivity, the concentration of the allergen, number of allergens the patient is exposed to, the magnitude of the initial allergic response, the environment as well as the syndrome’s variance, with type-1 KS having a better prognosis than type-2 and type-3.  Besides coronary arteries, Kounis syndrome affects the cerebral and mesenteric arteries. The syndrome’s manifestations are broadening, and its aetiology is continuously increasing. It is a ubiquitous disease that represents an exceptional natural paradigm. Hence, awareness of aetiology, epidemiology, pathogenesis, and clinical manifestations, is essential for diagnosis, treatment, prevention, and prognosis.  Kounis syndrome remains a specific project for researchers, health providers, governments, and non-governmental organisations (NGOs).



Signs and symptoms of Kounis syndrome include:

  • Nausea.
  • Sweatiness.
  • Cold extremities.
  • Breathlessness.
  • Pain in the neck, chest, and left arm.
  • Hypersensitivity.
  • Allergy.
  • Hypotension (low blood pressure).
  • Slow heartbeat.
  • Rapid resting heart rate.
  • Anaphylactic reaction, including shock.
  • Cardiac arrest.
  • Swelling of the face and tongue.
  • Wheezes.
  • Hives.
  • Drowsiness.
  • Abdominal pain.
  • Diarrhea.
  • Vomiting.
  • Acute pulmonary edema.
  • Loss of consciousness.
  • Stridor (resulting from airway obstruction), a high-pitched sound.



The causes of Kounis syndrome are primarily allergic reactions and reactions to immunization drugs or vaccines by the immune system, although the real cause of the syndrome is not yet known. 

The causes which precipitate this allergic syndrome include:

  1. Drugs.
  • Analgesics like aspirin and dipyrone.
  • Anesthetics.
  • Multiple antibiotics.
  • Anticoagulants, such as heparin and lepirudin.
  • Thrombolytics such as TPA.
  • Anti-platelet therapy, including Clopidogrel.
  • Antineoplastics.
  • Glucocorticoids.
  • Non-steroidal anti-inflammatory drugs (NSAIDs).
  • Proton pump inhibitors.
  • Skin disinfectants.
  • Antifungals.
  • Antivirals.
  • Oral contraceptives.
  • Other specific medications like: Allopurinol, Enalapril, Losartan, Insulin.
  1. Foods.

Various foods can cause an allergic and inflammatory response that can lead to Kounis syndrome.

  1. Environmental exposures to:
  • Poison ivy, grass, latex, and nicotine.
  • Bites from creatures like:
    • Spiders.
    • Snakes.
    • Scorpions.
    • Fire ants.
    • Jellyfish.
  1. Health conditions.

These include:

  • Bronchial asthma.
  • Anaphylaxis (exercise-induced or idiopathic).
  • Hay fever.
  • Angioedema.
  • Serum sickness.
  • Churg-Strauss syndrome.
  • Scombroid syndrome.
  • Intracoronary stenting.

This is a common procedure used in coronary artery disease (CAD)patients.

  • Contrast media.

It is thought that with the allergies of kounis syndrome, mast cells present in the connective tissues are activated. 

The mast cells release inflammatory substances, such as histamine, neutral proteases, and a variety of cytokines and chemokines, causing coronary artery spasm, and accelerate the rupture of atheromatous plaques of the coronary arteries. The plaques block or reduce the blood flow to the heart muscle and cause symptoms similar to angina.


  • Is Kounis syndrome rare?

The prevalence of Kounis syndrome is rare, seemingly because it does not have good statistical data due to the overlook approach to the disease. Only a few authentic cases were reported in 130 males and 45 females (as reviewed in 2017).

  • Can diclofenac cause Kounis syndrome?

Diclofenac sodium, generally a non-steroidal anti-inflammatory drug (NSAID), may lead to allergic reactions apart from hepatic, hematologic, gastrointestinal, and renal adverse effects. In addition, various drugs may trigger allergic angina (Kounis syndrome) and MI (myocardial infarction).

  • How is Kounis syndrome treated?

The treatment of Kounis syndrome consists primarily of aborting the allergic or anaphylactic reaction followed by stabilisation of the coronary vasculature with known medical or interventional techniques. Abortive therapies include the use of corticosteroids, epinephrine, and antihistamines until a therapeutic effect is achieved.

  • What is allergic angina?

Allergic angina (also known as Kounis syndrome) is the occurrence of acute myocardial ischemia in the presence of allergic reactions. Drugs or conditions which cause mast cell degranulation with the release of vasoactive inflammatory mediators (leukotrienes, histamine, and serotonin) can potentially lead to coronary vasoconstriction.

  • Does histamine cause chest tightness?

If any histamine release occurs somewhere in your lungs, you might have wheezing, chest tightness, shortness of breath, as well as cough.