Kounis syndrome: an underestimated emergency.

Summary: Background. Kounis syndrome (KS) is defined as a rare cause of an acute coronary syndrome associated with systemic allergic reactions. To establish the prevalence of KS among the patients with diagnosis of anaphylaxis, we described clinical features, cardiological and allergological outcomes of patients evaluated in our allergy outpatient clinic. Methods. A retrospective study was carried out in the Allergy Unit of Novara hospital, from January 2008 to March 2020. Skin tests and in vitro tests were performed with suspected etiological agents. Results. We found 9 adults with KS (2%) out of 444 subjects who had experienced anaphylactic reactions (4/9 to Hymenoptera stings, 5/9 to drugs). Conclusions. The present study highlights the importance of suspicion of KS that appears not so uncommon in patients with anaphylaxis. KS seems to be a rare disease because unrecognized in diagnosis of anaphylaxis.

Kounis Syndrome­not a Single-organ Arterial Disorder but a Multisystem and Multidisciplinary Disease

Coronary symptoms associated with conditions related to mast cell activation and inflammatory cell interactions, such as those involving T-lymphocytes and macrophages, further inducing allergic, hypersensitivity, anaphylactic, or anaphylactic insults, are currently referred to as the Kounis syndrome. Kounis syndrome is caused by inflammatory mediators released during allergic insults, post-inflammatory cell activation, and interactions via multidirectional stimuli. A platelet subset of 20% with high- and low-affinity IgE surface receptors is also involved in this process. Kounis syndrome is not just a single-organ but also a complex multisystem and multi-organ arterial clinical condition; it affects the coronary, mesenteric, and cerebral arteries and is accompanied by allergy­hypersensitivity­anaphylaxis involving the skin, respiratory, and vascular systems in the context of anesthesia, surgery, radiology, oncology, or even dental and psychiatric medicine; further, it has significantly influences both morbidity and mortality. Kounis syndrome might be caused by numerous and continuously increasing causes, with broad clinical symptoms and signs, via multi-organ arterial system involvement, in patients of any age, thereby demonstrating predominant anaphylactic features in terms of a wide spectrum of mast cell-association disorders. Cardiac symptoms, such as chest pain, coronary vasospasm, angina pectoris, myocardial infarction, stent thrombosis, acute cardiac failure, and sudden cardiac death associated with subclinical, clinical, acute, or chronic allergic reactions, constitute the clinical manifestations of this syndrome. Since its first description, a common pathway between allergic and non-allergic coronary events has been demonstrated. The hypothesis is based on the existence of a much higher degree of mast cell degranulation at plaque erosion or rupture sites compared with at the adjacent areas or even more distant segments in post-acute myocardial infarction of non-allergic etiology. Although mast cell activation, differentiation, and mediator release takes days or weeks, the mast cell degranulation may occur just before any acute coronary event, further resulting in coronary artery vasoconstriction and atheromatous plaque rupture. It seems that medications and natural molecules stabilizing the mast cell membrane as well as monoclonal antibodies protecting the mast cell surface can emerge as novel therapeutic modalities for acute coronary and cerebrovascular event prevention.

Epidemiology of acute coronary syndrome co-existent with allergic/hypersensitivity/anaphylactic reactions (Kounis syndrome) in the United States: A nationwide inpatient analysis.

BACKGROUND: The nationwide epidemiological data on Kounis Syndrome (KS), still remains indistinct in the United States (US) after it was first reported in 1991. METHODS: We assessed the prevalence of KS among patients primarily hospitalized for allergic/hypersensitivity/anaphylactic reactions. We then compared baseline demographics, comorbidities, and outcomes of KS with patients with only allergic/hypersensitivity/anaphylactic reactions using the National Inpatient Sample, 2007-2014. RESULTS: The cohort comprised of 235,420 patients primarily hospitalized with allergy/hypersensitivity/anaphylactic reactions. Of these, 2616 [1.1%; 0.2% unstable angina, 0.2% ST-elevation myocardial infarction & 0.7% non-ST-elevation myocardial infarction] patients experienced ACS and were identified as having KS. Patients with KS were older (mean 65.9 ±â€¯14.1 vs. 57.2 ±â€¯17.8 yrs), more often White (71.1% vs. 58.6%), male (46.4% vs. 39.9%) and Medicare enrollees (58.9% vs. 41.5%) admitted non-electively (96.8% vs. 95.3%) as compared to non-KS group (p < 0.001). The hospitalizations with KS demonstrated higher all-cause in-hospital mortality (7.0% vs. 0.4%, p < 0.001), prolonged hospitalization stay (mean 5.8 ±â€¯6.0 vs. 3.0 ±â€¯3.9 days, p < 0.001), higher hospitalization charges ($52,656 vs. $20,487, p < 0.001) and more frequent transfers to other facilities. The rates of stroke (1.0% vs. 0.2%), arrhythmias (30.4% vs. 12.4%), venous thromboembolism (1.6% vs. 1.0%), and diagnostic and therapeutic coronary interventions were also found to be significantly higher in patients with KS (p < 0.05). Patients with KS had increased odds of in-hospital mortality [unadjusted OR: 18.52; 95% CI: 15.74-21.80, p < 0.001 & adjusted OR: 9.74, 95% CI: 8.08-11.76, p < 0.001] compared to non-KS group. CONCLUSIONS: Overall US prevalence of KS among patients hospitalized for allergic/hypersensitivity/anaphylactic reactions is 1.1% with a subsequent all-cause inpatient mortality rate of 7.0%.

Kounis syndrome: A retrospective analysis of individual case safety reports from the international WHO database in pharmacovigilance
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OBJECTIVE: Kounis syndrome (KS) is an acute coronary syndrome with coronary spasm, acute myocardial infarction and stent thrombosis that can be associated with a variety of drugs as an adverse drug reaction (ADR). To characterize this rare phenomenon, we analyzed all cases of KS in the WHO database for pharmacovigilance. MATERIALS AND METHODS: All cases of KS worldwide until December 31, 2017, were included and analyzed in terms of age, sex, country, year of ADR, seriousness, clinical outcome, suspected drugs, administration, reported reaction, and -MedDRA terms. Time to onset of the ADR was calculated, and a subgroup analysis of KS associated with analgesics was performed. IC025 values were calculated for the most frequently reported pain medication to indicate the strength of relation between ADR and the suspected analgesics. RESULTS: A total of 403 cases of KS reported from 17 countries were included, of which 121 cases were associated with analgesics (subgroup). Males were more frequently affected overall (267 (66%) males vs. 123 (31%) females), whereas in the subgroup, males and females were equally affected (58 (48%) males vs. 56 (46%) females). Median reported patient age was 57 years (range 2 - 99) overall vs. 48 years (range 20 - 85) in the subgroup. Nearly all cases were classified as serious (370 (92%) overall vs. 119 (98%) subgroup). The most frequently suspected substance was amoxicillin/clavulanic acid (n = 50, 9.3%) overall and ibuprofen (n = 33, 6.2%) in the subgroup, respectively. Most drugs were administered orally (21% overall vs. 21% subgroup) and intravenously (18.7% overall vs. 8% subgroup) in either group. A high proportion of patients with "life threatening" reactions received intravenous administration (37%) of the suspected drug. CONCLUSION: Antibiotics and analgesics are the drug classes most often associated with KS. The way of administration might have an influence on the seriousness of the reaction.
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Kounis syndrome: A review article on epidemiology, diagnostic findings, management and complications of allergic acute coronary syndrome.

Kounis syndrome (KS) is a hypersensitivity coronary disorder induced by exposure to drugs, food, environmental and other triggers. Vasospastic allergic angina, allergic myocardial infarction (MI) and stent thrombosis with occluding thrombus infiltrated by eosinophils and/or mast cells constitute the three main variants of this syndrome. We reviewed 175 patients who fulfilled the definition of one of the three types of KS. The epidemiology, diagnostic findings, management and complications were reviewed in this article.