ALLERGY-INDUCED HEART ATTACK (Kounis Syndrome)

Kounis syndrome is defined as the simultaneous occurrence of an acute coronary syndrome (ACS) together with allergy, hypersensitivity, anaphylaxis, or anaphylactoid reactions. It was first described in 1991 by Dr. Nicholas Kounis as allergic angina. Although the exact mechanisms are not fully understood, the syndrome is mediated by inflammatory mediators released by cardiac or thrombus-associated mast cells that are systemically activated during anaphylaxis. Its incidence is estimated to range from 0.002% to 3.4%.

A wide variety of triggers may cause Kounis syndrome, including medications (analgesics, antibiotics, anticoagulants, anesthetics, antineoplastic agents, contrast media, glucocorticoids, losartan, nonsteroidal anti-inflammatory drugs, proton pump inhibitors), environmental exposures, Anisakis simplex, histamine fish poisoning known as scombroid syndrome, gelofusin, latex, systemic mastocytosis, and mast cell activation syndromes.

Clinical Manifestations

Clinical presentation varies widely, ranging from subclinical reactions to coronary vasospasm, acute thrombotic myocardial infarction, and stent thrombosis involving cerebral, mesenteric, or coronary arteries. Various electrocardiographic changes such as ST-segment elevation or depression, heart blocks, and cardiac arrhythmias often accompany these cardiac symptoms.

Common clinical symptoms include acute chest pain, chest tightness, dysphagia, dyspnea, syncope, headache, fatigue, nausea, vomiting, and pruritus. Physical findings may include cold extremities, hypotension, pallor, tachycardia, flushing, bradycardia, cardiorespiratory arrest, and sudden death.

Variants of Kounis Syndrome

Three variants of the syndrome have been described:

• Type I Variant: Occurs in patients without underlying atherosclerotic coronary artery disease. Acute release of inflammatory mediators leads to coronary artery spasm. Cardiac biomarkers may be normal or elevated, but electrocardiographic abnormalities—especially ST-segment elevation—are common.
  
• Type II Variant: Occurs in patients with pre-existing atheromatous coronary disease.
  
• Type III Variant: Occurs in patients who have previously undergone percutaneous coronary intervention and present with stent thrombosis or stent restenosis following a severe allergic reaction.
  

Coronary stents are made of stainless steel containing chromium, titanium, nickel, molybdenum, and manganese. Drug-eluting stents consist of a metal platform coated with a polymer layer impregnated with antiproliferative drugs. All these components form an antigenic complex. In patients with stents, allergic reactions may lead to intrastent thrombosis and fatal anaphylactic shock. Additionally, allergic reactions to clopidogrel, commonly used to prevent stent thrombosis, have also been reported to precipitate stent thrombosis. Such possibilities should be kept in mind in patients suspected of having Kounis syndrome, and metal allergies should always be questioned.

Management

Treatment of Kounis syndrome involves management of ACS and suppression of the allergic reaction.

• In young and otherwise healthy patients without risk factors for coronary artery disease—suspected to have Type I Kounis syndrome—the primary mechanism is coronary vasospasm; therefore, first-line therapy includes nitrates and calcium channel blockers. Suppression of the allergic reaction with steroids and antihistamines alone may relieve coronary vasospasm. β-blockers should be avoided, as they may worsen vasospasm.
  
• In patients with the Type II variant, the standard ACS protocol should be followed along with consideration of antihistamines and corticosteroids. The cornerstone of ACS management includes coronary angiography to define coronary anatomy, direct intracoronary agents to relieve vasospasm when necessary, and angioplasty when indicated.

Recommendations for At-Risk Individuals

Individuals with allergic tendencies should avoid using unfamiliar medications, refrain from unnecessary analgesics and antibiotics, and be cautious after exposure to potential allergens such as bee or insect stings. If unexpected symptoms such as shortness of breath or chest pain occur, they should consider the possibility of an allergic heart attack and seek immediate care at the nearest emergency department or cardiology clinic.