Kounis Syndrome - Causes, Symptoms, Diagnosis, and Treatment

What Is Kounis Syndrome?

Kounis Syndrome, also known as allergic acute coronary syndrome, is uncommon but can be life-threatening. Kounis syndrome (KS) is defined as the coincidental occurrence of acute coronary syndromes (ACS) that occur secondary to allergic or hypersensitivity reactions. Heart attacks and unstable angina are examples of acute coronary syndrome, which happens when the blood supply to the heart muscle is suddenly blocked. Three distinct variants of Kounis syndrome (KS) have been identified:

• Type I (Without Coronary Disease): This variant involves individuals experiencing chest pain during an acute allergic reaction with no pre-existing risk factors or coronary lesions. The allergic event induces coronary spasm, resulting in electrocardiographic changes indicative of ischemia. Cardiac enzymes and troponins may either remain within the normal range or reflect progression toward acute myocardial infarction. Proposed pathophysiological mechanisms for this type include endothelial dysfunction and/or microvascular angina.

• Type II (With Coronary Disease): This variant encompasses patients with pre-existing atheromatous disease, whether previously asymptomatic or symptomatic. Acute hypersensitivity reactions in these individuals lead to plaque erosion or rupture, ultimately culminating in acute myocardial infarction.

• Type III (With Pre-existing Coronary Disease and Drug-Eluting Coronary Stent Thrombosis): A more recent addition to the classification, type III is observed in patients with pre-existing coronary disease and the occurrence of drug-eluting coronary stent thrombosis. Histological examinations using Giemsa and hematoxylin-eosin staining revealed the presence of mast cells and eosinophils.

What Are the Causes of Kounis Syndrome?

Kounis Syndrome primarily arises from an allergic or hypersensitivity reaction, where the release of inflammatory mediators, such as histamine, activates platelets and induces coronary vasospasm. Some allergens that induce allergic reactions can give rise to Kounis syndrome, such as insect stings and bites (bees and wasps), certain drugs (Dipyrone, Ampicillin, Diclofenac, Naproxen, Ibuprofen), foreign bodies can also cause Kounis Syndrome, including conventional or drug-eluting stents.

What Are the Symptoms of Kounis Syndrome?

Kounis Syndrome may present with the following symptoms:

• Dyspnea (shortness of breath).

• Chest pain.

• Weakness.

• Malaise (feeling of discomfort).

• Nausea.

• Abnormal heart rate.

• Vomiting.

• Sudden loss of consciousness.

• Pruritus (itchy skin).

• Urticaria (skin rashes).

How Is Kounis Syndrome Diagnosed?

Diagnosis of Kounis syndrome involves:

1. Clinical Assessment: The diagnosis of Kounis syndrome is primarily based on clinical examinations. Doctors may look for the symptoms associated with Kounis syndrome. The patient presents chest pain similar to angina and simultaneously also shows symptoms of allergic reaction (rashes, pruritus, dyspnea, wheezing

2. Medical History: A thorough medical history is crucial. Explore known allergies, recent exposures to potential triggers (food, medications, insect stings), and past episodes of chest pain or allergic reactions.

3. Other Tests: The diagnostic test for Kounis syndrome does not exist. The following actions must be taken when the syndrome is suspected:

• Electrocardiogram (ECG): ECG findings may show ST-segment elevation in the four anterior and inferior leads.

• Cardiac Enzymes (Troponin, Creatine Kinase-Myocardial Band) Test: Elevated levels suggest heart damage but can be normal in type I Kounis.

• Allergy Markers Test: Tryptase (most useful), histamine, eosinophils, IgE (immunoglobulin E). Normal levels do not rule out Kounis, but serial measurements (three to four within 24 hours) can be helpful.

• Echocardiogram: This diagnostic tool can differentiate the Kounis syndrome from other causes of chest pain.

• Arteriography: This diagnostic tool evaluates the coronary anatomy, treats vasospasm with intracoronary drugs, or performs angioplasty where needed; it is performed to identify occult coronary disease in those patients in which type II Kounis syndrome is suspected.

What Is the Treatment of Kounis Syndrome?

Once diagnosed, the management of Kounis Syndrome involves addressing both the allergic reaction and the ACS.

Management of Anaphylaxis:

• Adrenaline: The treatment of choice for anaphylaxis. Administered intramuscularly, it prevents and reverses bronchospasm and cardiovascular collapse. However, caution is advised in Kounis syndrome, as it may worsen ischemia, prolong QT intervals, induce coronary vasospasm, and trigger arrhythmias.

• H1 Blockers: Considered second-line after adrenaline. They improve symptoms like pruritus, rash, urticaria, and angioedema. Administered cautiously to avoid hypotension, they are recommended in Kounis syndrome.

• H2 Blockers: when combined with H1 blockers, they may offer better results than H1 blockers alone.

• Corticosteroids: Potent anti-inflammatory drugs with a role in preventing biphasic and prolonged anaphylaxis. Their use in Kounis syndrome, while possibly safe, requires further investigation.

• Intravascular Volume Replacement: Intravenous fluids are often employed to counteract potential hypovolemia resulting from the allergic response.

• Mast Cell Stabilizers (Nedocromil, Sodium Cromoglycate, Ketotifen): Addressing the primary mechanism behind Kounis syndrome, these stabilizers may alleviate allergic reactions and reduce thrombotic phenomena. Their efficacy is debatable, but they can be considered in patients developing ACS following drug reactions.

Management of ACS:

• Aspirin (Acetylsalicylic Acid): Aspirin is a standard treatment for acute coronary syndrome (ACS). Its use in Kounis syndrome requires careful evaluation due to the potential risk of exacerbating anaphylaxis.

• Nitroglycerin: Useful in ACS for myocardial oxygen release. Caution is needed due to the potential for hypotension and tachycardia, complicating anaphylactic reactions.

• Beta-Blockers: While beneficial in coronary syndrome, their use may diminish the effects of adrenaline, the primary treatment for anaphylaxis. In such cases, glucagon can be considered.

• Calcium Channel Antagonists: Preferred when chest pain results from vasospasm, common in unstable angina. Considering their potential efficacy in treating hypersensitivity-induced bronchospasm, they may be a suitable option for Kounis syndrome.

• Morphine: Offers potent analgesia but must be used cautiously due to possible nonspecific mast cell granulation and potentially worsening allergic reactions. Fentanyl and its derivatives may be safer alternatives.

• Oxygen: Recommended for ACS with saturation values below 90 percent or a risk of hypoxemia. Indicated in anaphylactic shock without debate.

Conclusion:

Kounis syndrome is a coincidental occurrence of acute coronary syndromes (ACS) that occur secondary to hypersensitivity reactions. Healthcare professionals need to recognize and understand it so they can give the right care at the right time. Ongoing research might find better ways to diagnose and treat this unusual syndrome, improving the outlook for people affected by it.