Introduction
Kounis syndrome is an acute coronary syndrome mediated by allergic reactions and can be triggered by food, medications, or environmental factors. During an allergic reaction, mast cells release a variety of inflammatory mediators, which can induce coronary artery smooth muscle spasm and promote the rupture of atherosclerotic plaques, leading to thrombosis and myocardial ischaemia.
Clinical manifestations of allergic reactions and myocardial ischaemia overlap, such as chest discomfort, breathing difficulty, and shock. The treatment of both conditions can contradict each other, leading to misdiagnosis and mistreatment with severe consequences. This report discusses a successful case of type II Kounis syndrome at our hospital, where the patient experienced an allergic reaction after consuming oyster accompanied by ST-elevation myocardial infarction. This case aims to provide experience for peers in treating similar patients.
Case presentation
A 35-year-old male courier presented to our emergency department with chest discomfort lasting for 2 hours. He was generally healthy and had no habits of smoking or drinking. The patient had no family history of early-onset coronary artery disease and no known allergies to food or drugs. About 2 hours after consuming oyster, he developed itchy skin and scattered urticaria on his face and trunk. He visited a community clinic where he was diagnosed with acute urticaria and treated with 5 mg of intravenous dexamethasone and 10 mg of oral levocetirizine. Shortly after the treatment, his rash and itching subsided, but he then experienced progressive chest discomfort with sweating. Seeking further treatment, he came to our emergency department. Upon examination, the patient appeared slightly anxious but cooperative. His vital signs were stable: blood pressure 126/91 mmHg, heart rate 90 beats/min, respiratory rate 20 breaths/min, and oxygen saturation at 98% on room air. There were no significant traces of urticaria on his face and trunk, and lung auscultation revealed clear breath sounds without any rales or wheezing.
The electrocardiogram showed sinus rhythm with a heart rate of 83 beats/min, ST-segment elevation in leads I, aVL, V1-V3, and ST-segment depression in leads II, III, aVF, and V4-V6, indicating ST-elevation myocardial infarction (Figure 1). Cardiac troponin levels were not yet elevated. Echocardiography revealed normal chamber dimensions, reduced motion of the anterior septum and anterior wall of the left ventricle, and a left ventricular ejection fraction of 43%. An emergency coronary angiography was planned, and he was administered oral loading doses of dual antiplatelet therapy (300 mg of aspirin and 300 mg of clopidogrel). During the procedure, the patient suddenly lost consciousness, and ventricular fibrillation was detected on the electrocardiogram monitor. After a single 200 J biphasic shock from the defibrillator, his sinus rhythm and spontaneous circulation were restored. Coronary angiography revealed a right-dominant coronary system, with the left main and circumflex arteries (LCx) appearing normal, without any significant narrowing, maintaining a Thrombolysis in Myocardial Infarction (TIMI) flow grade III. The proximal segment of the left anterior descending artery (LAD) was completely occluded, with a TIMI flow grade of 0 (Figure 2B). Following the administration of 200 ug of intracoronary nitroglycerin, there was no appreciable change in the caliber of the left coronary artery system or in the obstructive lesion of the LAD (Figure 2C). Additionally, the right coronary artery showed no significant narrowing (Figure 2A). Successful recanalization of the left anterior descending artery was achieved with the implantation of a 2.75*14 mm rapamycin stent in the proximal segment.
Figure 1. The electrocardiogram shows ST-segment elevation in leads I, aVL, V1-V3, and ST-segment depression in leads II, III, aVF, and V4-V6, indicative of ST-elevation myocardial infarction.
Figure 2. A. No significant narrowing observed in the right coronary artery. B. No significant narrowing in the left main and circumflex arteries (LCx), with complete occlusion of the proximal segment of the left anterior descending artery (LAD). C. Post-procedure image showing the LAD is patent with a stent implanted.
Postoperatively, the patient was admitted to the cardiac care unit. Laboratory tests, including a complete blood count, liver and kidney function tests, and a coagulation profile, revealed no significant abnormalities. The low-density lipoprotein cholesterol level was measured at 2.73 mmol/L, and triglycerides were at 8.99 mmol/L. The peak level of cardiac troponin I, reached 10 hours post the onset of chest discomfort, was 17.83ng/ml (within the normal range of 0-0.1 ng/ml), and then it started to decline. A follow-up echocardiogram post-surgery showed an improvement in the ejection fraction to 60%. After five days of ongoing treatment and given the patient’s relatively stable condition, he was discharged from the hospital. During a one-month follow-up period, the patient did not experience any further episodes of chest discomfort or pain.
Discussion
Kounis syndrome is defined as an acute coronary syndrome accompanied by an allergic reaction, manifesting as coronary spasm, acute myocardial infarction, or thrombosis within a stent. This syndrome can occur in people of different races, genders, and ages,Reference Abdelghany, Subedi and Shah1 including children and teenagers.Reference Ishikura, Endo and Sakamoto2 The first case of an acute cardiac event related to an allergic reaction was reported in 1950, involving a 49-year-old male who developed acute myocardial infarction and urticaria following treatment with penicillin oil.Reference Pfister and Plice3 Subsequent similar cases were reported, but it was not until 1991 that Kounis officially proposed the term “allergic angina syndrome,” also known as Kounis syndrome.Reference Kounis and Zavras4 The concept was later expanded to include all allergy-mediated acute coronary syndrome.Reference Kounis, Hahalis and Theoharides5
Currently, Kounis syndrome is well-recognized in the scientific community, with a growing body of clinical reports from around the world substantiating its existence.Reference Leibee, Leibee and Ehmann6,Reference Tambe, Tambe and Goodman7 A comprehensive review in 2017, which examined all available literature in the MEDLINE database, identified only 130 male and 45 female cases of Kounis syndrome.Reference Abdelghany, Subedi and Shah1 Typically, patients with Kounis syndrome are older males. While the syndrome can potentially affect individuals of any age, it is most commonly observed in the age group between 40 and 70 years, accounting for 68% of cases. Cases like the one we reported, involving young males, are relatively rare.
Triggers for Kounis syndrome include various drugs such as nonsteroidal anti-inflammatory drugs, antibiotics, antineoplastic agents, contrast agents, environmental exposures, insect stings, and foods.Reference Poggiali, Benedetti and Vertemati8 New triggers are continually being identified, such as recent reports of Type I cases caused by SARS-CoV-2 vaccinations.Reference Özdemir İbrahim, Bülent, Özen, Gündüz and Özgür9 Additionally, only 25.1% of patients had a history of allergies, Reference Abdelghany, Subedi and Shah1 and the patient in this case also had no clear history of allergies.
The pathogenesis of Kounis syndrome is not fully understood, but mast cells are generally considered the main inflammatory cells involved.Reference Poggiali, Benedetti and Vertemati8 Allergens trigger the production of specific immunoglobulin E, which binds to high-affinity immunoglobulin E receptors on the surface of mast cells. When allergens diffuse near mast cells, they interact with immunoglobulin E, leading to cell activation and release of inflammatory mediators such as histamine, proteases, leukotrienes, and cytokines.Reference Sinkiewicz, Sobański and Bartuzi10 These mediators play a crucial role in cardiovascular regulation, including inducing vasoconstriction,Reference Genovese and Spadaro11 degrading fibrous caps of plaques,Reference Johnson, Jackson and Angelini12 and activating platelets and the coagulation system,Reference Kounis, Tsigkas and Almpanis13 leading to coronary artery spasm, in-stent thrombosis, and acute myocardial injury.Reference Clemen, Nwosu and Chukwuka14
Kounis syndrome is classified into three types: vasospastic angina (Type I), acute coronary artery thrombosis (Type II), and thrombosis within a stent (Type III).Reference Biteker15 In Type I, the patient has normal coronary arteries, and the allergic reaction induces increased reactivity of vascular smooth muscle and endothelial dysfunction, leading to coronary spasm. In Type II, the patient already has atherosclerosis, and the allergic reaction can induce plaque erosion or rupture, leading to acute myocardial infarction. Type III occurs in patients with drug-eluting stents who develop hypersensitivity and thrombosis within the stent, with infiltration of mast cells and eosinophils in the thrombus.Reference Kogias, Papadakis and Tsatiris16 Additionally, Type III Kounis syndrome can be further subdivided into two subtypes: subtype IIIa is characterised by stent thrombosis, while subtype IIIb involves stent restenosis. These complications are thought to be induced by various factors, including stent polymers, stent metals, eluted drugs, dual antiplatelet therapy, and environmental exposures.Reference Kounis, Koniari and Tsigkas17
Patients with Kounis syndrome may present with acute cardiac symptoms like ischaemia chest pain, chest tightness, and difficulty breathing, along with acute or chronic allergic reactions, including skin itching and rashes. Acute allergic skin manifestations like urticaria and angioedema are common, while chronic urticaria can also trigger the syndrome.Reference Erxun, Wei and Shuying18 It’s important to note that the absence of skin manifestations does not rule out Kounis syndrome; instead, it might indicate severe shock Reference Adachi, Ihara and Nojima19—as reduced cardiac output and hypotension-induced vasoconstriction may prevent allergic mediators from reaching the skin.Reference Kounis, Cervellin and Koniari20 Symptoms may also include dizziness, headache, nausea, vomiting, diarrhoea, pallor, palpitations, and hypotension, which can lead to sudden death if untreated.
In patients with simultaneous allergic reactions and cardiac symptoms, Kounis syndrome should be considered. In our case, the acute allergic reaction and acute myocardial infarction occurred in close succession, confirming a diagnosis of Type II Kounis syndrome. A study by Lippi et al.Reference Lippi, Buonocore and Schirosa21 found higher levels of cardiac troponin I in patients with anaphylactic shock, angioedema, and urticaria compared to a healthy control group, suggesting the coronary artery as a primary target organ in severe allergic reactions. Therefore, all patients visiting the emergency department for allergic reactions should undergo electrocardiogram and cardiac troponin testing to detect and treat potential myocardial injury. Cha et al.Reference Cha, Kim and Bang22 reported that 7.3% of 300 patients with anaphylactic shock had myocardial injury, caused by Kounis syndrome and stress cardiomyopathy. Stress cardiomyopathy, also known as Takotsubo syndrome, primarily affects postmenopausal women but can also occur in systemic allergic reactions.Reference Y-Hassan and Tornvall23 It presents as transient segmental left ventricular dysfunction without significant coronary artery disease, with symptoms like chest pain and electrocardiogram changes including ST segment and the T-wave (ST-T) alterations, often accompanied by elevated cardiac troponin levels, requiring further evaluation through coronary angiography, echocardiography, or left ventriculography. In this case, coronary angiography revealed occlusion of the proximal left anterior descending artery, and echocardiography showed no segmental wall motion abnormalities beyond the coronary artery supply area, ruling out stress cardiomyopathy.
Kounis syndrome is a life-threatening emergency that often requires rapid intervention, yet there are no current guidelines for its management.Reference Fassio, Losappio and Antolin-Amerigo24 For Type I Kounis syndrome, anti-allergy treatment, including corticosteroids and H1 and H2 receptor antagonists, is often effective and considered the first line of therapy. Vasodilators such as calcium channel blockers or nitrates can alleviate vascular spasms. For Type II patients, acute coronary syndrome must be promptly addressed with treatments including antithrombotic therapy and revascularization.Reference Alblaihed and Huis in ‘t Veld25 It’s important to note that the treatment of allergic reactions and acute coronary syndrome can be contradictory. For example, adrenaline is the first-line treatment for systemic allergic reactions, but its use is controversial as it can increase myocardial oxygen consumption. Beta-blockers and morphine can relieve angina but may exacerbate allergic reactions and coronary artery spasms, so their use should be cautious.Reference Fassio, Losappio and Antolin-Amerigo24 Type III patients require urgent aspiration of in-stent thrombosis, with staining for eosinophils and mast cells. Liu et al. Reference Liu, Lu and Guo26 reported a 48-year-old patient with Type III Kounis syndrome who, despite aggressive antihistamine, antithrombotic, and reperfusion therapies, continued to have elevated immunoglobulin E levels and chronic urticaria. The chronic urticaria improved and the immunoglobulin E levels decreased after treatment with omalizumab (Xolair®), also alleviating cardiac symptoms.
Conclusion
Despite Kounis syndrome mostly being reported in isolated cases, its actual incidence is not low. Its triggers are varied and increasing, including foods, medications, and insect bites. The clinical presentations of allergic reactions and myocardial ischaemia overlap, making them hard to distinguish, and the treatment requires consideration of both, making misdiagnosis and mistreatment likely. Emergency physicians should be aware of allergic reactions in patients with acute coronary syndrome; for patients with allergies, particularly those suspected of systemic allergic reactions, attention to cardiac symptoms is crucial. Early recognition and appropriate treatment can significantly improve the prognosis of patients with Kounis syndrome.
Competing interests
None to declare.
