Kounis syndrome is defined as acute coronary syndrome (symptoms such as chest pain relating to reduced blood flow to the heart) 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.
Epidemiology
Through various case observations, Kounis syndrome was noted in many different races and geographical areas. However, most cases have been found in southern Europe including Turkey, Greece, Italy, and Spain. A wide age range is observed from pediatric patients to the elderly including the ages from 2 to 90. Commonly seen comorbidities include hyperlipidemia, diabetes, smoking, hypertension, and prior allergic reactions to a precipitating factor. The exact prevalence is difficult to determine given that this diagnosis is missed or under-diagnosed. There is a possibility for gene-environment interactions as a study reported all patients admitted following emergency department evaluation had a heterozygous E148Q mutation.
Etiology
Many causes have been discovered to precipitate this syndrome including drugs, various health conditions, food, and environmental exposures. Any of these precipitating factors that cause IgE antibody production can contribute to this syndrome. Drugs that have been found previously 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, and skin disinfectants. Additionally, sympathomimetics, volume expanders, antifungals, antivirals, and oral contraceptives can also trigger this syndrome. Other specific common medications include Allopurinol, Enalapril, Losartan, insulin, and many more. Conditions that incriminate Kounis syndrome include bronchial asthma, Churg–Strauss syndrome, serum sickness, scombroid syndrome, angioedema, hay fever, anaphylaxis (exercise induced or idiopathic), and anisakiasis. Coronary stenting, a common procedure used in coronary artery disease patients has also been found to be a cause. Environmental exposure to poison ivy, grass, latex, and nicotine have been found to be contributory. Bites from creatures that can precipitate Kounis syndrome include 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.
Signs and symptoms
Allergic ACS is a syndrome involving two components. One component is immune mediated resulting in hypersensitivity, allergy, and an anaphylactic or anaphylactoid reaction. The second component involves cardiac signs and symptoms seen with acute coronary syndrome (ACS). Cardiac symptoms vary depending on the type of variant the patient presents with. 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. Cardiac signs on exam also include cold extremities, bradycardia, tachycardia, hypotension, possible cardiorespiratory arrest, or sudden death. Just as in an allergic reaction can vary from a mild and localized reaction to something that is widespread and life-threatening, the allergic component of allergic ACS presents the same way. 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 (anaphylactic shock). Additional findings can include stridor, drowsiness, syncope, abdominal pain, diarrhea, vomiting, and acute pulmonary edema if severe.