429 KOUNIS-ZAVRAS SYNDROME: UNDERREPRESENTED OR UNDERDIAGNOSED?
Authors: Scala Antonella , Trichilo Michele , Boccadoro Alberto , Biscaglia Simone , Campo Gianluca 
Published: December 2022

A 64-year-old man was admitted to the emergency department for a major allergic reaction to an insect bite. On physical examination, he presented with tachycardia, hypotension and diffuse pomphoid erythema requiring treatment with intravenous cortisone and antihistamines, with partial benefit. From his past medical history hypertension and previous percutaneous coronary intervention (PCI) with drug eluting stents (DES) on left anterior descendant (LAD) and circumflex coronary artery (Cx) for stable angina emerged.

Almost 15 minutes after his admission he developed oppressive chest pain and dyspnea, so an electrocardiogram (EKG) was performed showing an ST segment elevation in inferior-posterior-lateral leads. Therefore, the patient was transferred to the Cath Lab to perform a coronary angiography study with finding of intrastent thrombosis (IST) of Cx and LAD and sub-occlusion of the posterior interventricular branch of the right coronary artery (RCA), not responsive to nitrates. PCI was performed with manual thrombus aspiration and high pressure non-compliant balloons of the IST and PCI with a single DES of the RCA lesion. The patient was then transferred to coronary intensive care unit. Echocardiography revealed a normal left ventricle ejection fraction without any wall motion abnormalities and the EKG showed a complete ST resolution. Laboratory exams showed increased troponin, typical of myocardial infarction, and an increase in IgE and serum tryptase, typical for an allergic reaction. Based on clinical, angiographic and biochemical data, diagnosis of type III Kounis-Zavras (KS) syndrome was made. KS is an acute coronary event in the setting of a hypersensitivity reaction which trigger the release of inflammatory mediators by activated mast cell leading to coronary artery spasm, atheromatous plaque rupture or stent thrombosis. Optimal medical therapy for both ischemic heart disease and allergic reaction was set, with ace inhibitor, high dose statin, non-dihydropyridine calcium channel blocker, dual antiplatelet therapy, antihistamines and cortisone with a decalage scheme. There is no consensus for KS management and the difficulty lies in the fact that treating one of the two concomitant conditions could worsen the other.

Three variants of this syndrome have been described in the literature. Type I KS is characterized by coronary spasm in patients typically lacking cardiovascular risk factors and coronary arteries free from atheromatous lesions. Type II KS is characterized by instability of an already present coronary plaque. Type III KS is characterized by intrastent thrombosis in patients with previous coronary angioplasty. Several factors incriminated in KS syndrome have been described, including medications (such as antibiotics, analgesics and anti-inflammatories) and environmental factors (such as, bee sting, viper venom, wasp sting). The underlying pathophysiological process involves a series of mediators, such as histamine and tryptase, released by activated mast cells locally during an immunological reaction. KS syndrome is a real challenge since there is no definitive guidelines for diagnosis, management and treatment and the plethora of clinical presentation range from angina pectoris with mild atopic dermatitis to acute coronary syndrome with cardiogenic shock and anaphylaxis. This broad spectrum of clinical manifestations associated with the increasing new triggers (drugs, contrast dye, insects) often leads to a misdiagnosis with a delay of the proper administration of the effective therapy, sometimes resulting fatal.