Kounis Syndrome: An Updated Narrative Review of Pathophysiology, Clinical Manifestations, and Management

Kounis syndrome is an increasingly recognized clinical entity characterized by the coexistence of acute coronary syndrome and allergic or hypersensitivity reactions. The syndrome represents the interaction between inflammatory pathways activated during allergic responses and the coronary circulation, leading to coronary vasospasm, plaque rupture, or coronary thrombosis. Various mediators released during mast cell activation, including histamine, leukotrienes, tryptase, and platelet-activating factor, play a central role in the pathophysiology by promoting vasoconstriction, endothelial dysfunction, platelet activation, and plaque destabilization. Although the condition has been reported in a wide range of clinical settings, its true incidence remains uncertain because it is frequently underdiagnosed or misinterpreted as either isolated anaphylaxis or conventional acute coronary syndrome. Kounis syndrome may be triggered by numerous allergens, most commonly drugs, insect stings, foods, and contrast media. Three clinical variants have been described depending on the underlying coronary anatomy and mechanism of injury: type I involving coronary vasospasm in patients with normal coronary arteries, type II occurring in individuals with preexisting atherosclerotic disease, and type III associated with coronary stent thrombosis. Clinical presentation is heterogeneous and may include chest pain, electrocardiographic changes, elevated cardiac biomarkers, and signs of systemic allergic reactions. Diagnosis relies on the integration of clinical history, laboratory findings, electrocardiography, and coronary imaging. Management requires simultaneous treatment of the allergic reaction and the acute coronary event, which can create therapeutic challenges. Identification and avoidance of triggering allergens are important for preventing recurrence. Increased awareness among clinicians is essential for early recognition and appropriate management. This review summarizes current knowledge regarding the epidemiology, pathophysiology, clinical manifestations, diagnostic strategies, and treatment approaches of Kounis syndrome.