Allergies are not infrequently encountered in clinical medicine especially in the setting of adverse drug reactions where they can be identified after signs and symptoms such as hives, itching, and rash occur. Seldom do we think of an allergic reaction as the cause of an acute coronary syndrome but there is a specific medical term that describes such an entity. Kounis syndrome is defined as acute coronary syndrome (ACS) due to an allergic reaction to a drug or other substance [ ]. The main triggers of Kounis syndrome are antibiotics (27%) and insect bites (23%) [ ]. Kounis syndrome are categorized in 3 variants; Type I represents ACS due to spasm of coronary artery without underlying atherosclerosis (most common, 73%); Type II occurs in patients with pre-existing but asymptomatic coronary artery disease in which ACS is due to plaque rupture or erosion of an atherosclerotic plaque or can be secondary to coronary artery spasm (22%); Type III represents stent thrombosis due to an allergic reaction (5%). Symptoms occur within the first hour of exposure to the trigger in most cases (80%). Risk factors for Kounis syndrome include history of previous allergy, smoking, hypertension, hyperlipidemia, and diabetes mellitus [ ].
In the current issue of Cardiovascular Revascularization Medicine, Ferreira et al. [ ] report a case of a 57 year-old man with history of hyperlipidemia and hypertension presented with ST elevated myocardial infarction (STEMI). Aspirin and clopidogrel were initiated, and primary PCI was performed. After an aspiration thrombectomy, a total of 3 synergy drug-eluting stents (DES) were implanted in the proximal and distal segment of the RCA. Nineteen hours after the primary PCI, the patient suffered from STEMI due to acute stent thrombosis, along with skin rash. After an aspiration thrombectomy followed by implantation of another Synergy DES, clopidogrel was replaced by prasugrel. However, recurrence of STEMI occurred 18 h after the second intervention, and two additional Synergy DES were implanted. Platelet inhibition was within the therapeutic range according to the aspirin platelet reactivity test, therefore anti-platelet resistance was ruled out as a cause of stent thrombosis. Patient had no history of prior allergy. Subsequently, type III Kounis syndrome was suspected and an oral steroid as well as an anti-histamine agent were initiated after the last intervention. Total IgE level was elevated that supported the diagnosis of Kounis syndrome. The skin rash improved after the initiation of steroid and anti-histamine agent, and no thrombotic events occurred thereafter. The authors presumed that clopidogrel might have been responsible for the allergic manifestations.
Stent implantation in the coronary arteries has also been known as a trigger for Kounis syndrome. We have previously reported pathologically verified hypersensitivity reactions following stent implantation in bare metal stents (BMS) [ ], 1st generation Cypher sirolimus-eluting stents (SES) [ ] ( Fig. 1 ), as well as in 2nd generation Xience everolimus-eluting stents and Resolute Integrity zotarolimus-eluting stents [ ]. The main trigger for hypersensitivity reaction in 1st generation SES was thought to be its polymer [poly-ethylene- co -vinyl acetate (PEVA) and poly-n-butyl methacrylate (PBMA)]. Hypersensitivity reaction in 2nd generation DES have only been rarely reported, probably not because of their biocompatible polymers but likely related to the drug, i.e., sirolimus and its analogs. Sirolimus, everolimus and zotarolimus, coated in the latest generation DES, have been reported to cause hypersensitivity pneumonitis. These usually appear as granulomatous reactions consisting of lymphocytic infiltrate accompanied by eosinophils and giant cells. On the other hand, metals such as cobalt, chromium, nickel, and stainless steel, used in the currently available coronary stents are also known to be a trigger of hypersensitivity reaction due to metal allergy [ ]. However, contrary to the acute hypersensitivity reaction to polymers, metal allergy is generally categorized as a delayed type hypersensitivity reaction, and associated with restenosis, but not thrombosis [ ]. In the current case, a total of 6 Synergy DESs (Boston Scientific) were implanted. Synergy, known as a 3rd generation DES, consists of platinum chromium stent platform that delivers everolimus from a biodegradable polymer [poly- dl -lactide- co -glycolide (PLGA)] applied to the abluminal stent surface only [ ]. An abluminally coated biodegradable polymer might have caused hypersensitivity reaction in the current case, although hypersensitivity reactions to the biodegradable polymer have not been reported previously.
