Kounis Syndrome Type II after Diclofenac Exposure: Unmasking a Link Between Drug Allergy and Acute Coronary Syndrome

Introduction

Kounis syndrome (KS), first identified in 1991 as “allergic angina,” marks a significant intersection between cardiology and allergology. It involves episodes of acute coronary syndrome (ACS), such as vasospasm, myocardial infarction, or stent thrombosis, occurring during allergic, anaphylactic, or hypersensitivity reactions. This syndrome demonstrates the direct impact of systemic inflammation on coronary vessels, primarily through mast cell activation and degranulation. Although it was first described more than 30 years ago, KS remains highly underdiagnosed and frequently overlooked, leading to delays in proper treatment. Its pathophysiology includes the release of various inflammatory mediators like histamine, leukotrienes, tryptase, chymase, and platelet-activating factor. These substances can cause coronary artery vasospasm, trigger plaque erosion or rupture in existing atheromatous plaques, and promote a prothrombotic environment, resulting in ACS.^, Systematic reviews of existing literature, mainly case reports and series, are beginning to clarify KS’s epidemiological and clinical features. A recent comprehensive review by Cahuapaza-Gutierrez et al. of 214 patients showed a male predominance (69.6%), with an average age of 54.4 years, and hypertension was the most common comorbidity (33.6%). The most frequent triggers are medications (38.3%), especially antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs), followed by insect stings (26.2%). KS is classified into three main types: type I (coronary spasm without pre-existing disease), type II (myocardial infarction with underlying coronary artery disease), and type III (stent thrombosis). A proposed “type IV” involves thrombosis of coronary artery bypass grafts. Recognizing this classification is crucial for clinicians, as treatment must address both the acute cardiac ischemia and the allergic reaction. This case report of typical type II KS triggered by diclofenac sodium aims to contribute to the growing body of evidence and underscore the importance of heightened clinical awareness.

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