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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In the very interesting paper by Jo&#227;o Almeida et al&#46; published in the <span class="elsevierStyleItalic">Journal</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">1</span></a> an 85-year-old hypertensive man&#44; a former smoker&#44; allergic to quinolones&#44; with bladder cancer and chronic kidney disease and taking hydroxyzine and alprazolam&#44; developed a type I variant Kounis syndrome in the operating theater immediately after administration of ciprofloxacin&#46; Following suspension of ciprofloxacin and treatment with morphine&#44; aspirin and ticagrelor the patient recovered&#46; Coronary arteriography was normal&#44; troponin was slightly elevated and the patient had leukocytosis with neutrophilia&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">This report raises important questions concerning the role of the drugs the patient had taken before the operation&#44; quinolone treatment&#44; the presence of neutrophilia and morphine administration&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0015" class="elsevierStylePara elsevierViewall">The described patient was allergic to quinolones and was taking the antihistaminic agent hydroxyzine and the benzodiazepine-class anxiolytic alprazolam&#44; followed by administration of ciprofloxacin in the operating theater&#46; He developed constricting chest discomfort associated with dyspnea&#44; sweating and hypotension&#46; Hydroxyzine and alprazolam can rarely and unexpectedly induce allergic reactions such as cutaneous drug eruption<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">2</span></a> and cold-induced urticaria&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a> respectively&#46; It seems likely that these three agents could have acted as a dangerous antigenic triplet able to induce allergic mediator release and Kounis syndrome&#46; Indeed&#44; clinical studies have shown that atopic patients allergic to and simultaneously exposed to several antigens have more symptoms than monosensitized individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">4</span></a> At the same time&#44; IgE antibodies with different specificities can have an additive effect&#44; and even sub-threshold numbers of these antibodies can join forces and trigger allergic mediator release when the patient is simultaneously exposed to the corresponding antigens&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0020" class="elsevierStylePara elsevierViewall">Fluoroquinolones are generally considered well-tolerated antibiotics&#44; but their consumption is steadily increasing&#46; Kounis syndrome has been induced not only by ciprofloxacin&#44; but also by levofloxacin<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">6</span></a> and the original quinolone cinoxacin&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">7</span></a> Indeed&#44; ciprofloxacin-induced Kounis syndrome&#44; apart from the case currently under discussion&#44; has been reported in one additional case&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">It is anticipated that more cases will appear in the future&#46; Therefore&#44; a high index of suspicion seems to be important&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0030" class="elsevierStylePara elsevierViewall">Morphine and other opiates and opioids can induce anaphylactic reactions via mast cell degranulation that continue to cause concern&#46; IgE antibodies to morphine and codeine have been detected in the serum of at least one subject who experienced a life-threatening anaphylactic reaction following the administration of a combination of papaveretum and hyoscine&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">9</span></a> Indeed&#44; Kounis syndrome has been also induced by morphine administration in two patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">10&#44;11</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The described patient was fortunate when he received treatment with morphine&#44; aspirin and ticagrelor for his constricting chest discomfort associated with dyspnea&#44; sweating and hypotension and had an uneventful recovery&#46; Fentanyl and its derivatives show little mast cell activation and are preferable&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0040" class="elsevierStylePara elsevierViewall">The described patient had coronary angiography&#44; performed two hours after symptom onset&#44; that excluded coronary disease&#46; However&#44; he had slightly raised high-sensitivity troponin levels with leukocytosis and neutrophilia during the anaphylactic event that denote type I variant Kounis syndrome attributed to coronary spasm&#46; Indeed&#44; leukocytes and polymorphonuclear neutrophils as well as other inflammatory markers have been found to be significantly associated with coronary artery spasm&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">12</span></a></p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5&#46;</span><p id="par0045" class="elsevierStylePara elsevierViewall">We entirely agree with the authors of this report<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">1</span></a> that there is no consensus on treatment for Kounis syndrome&#44; and most of the data on it are from case reports&#46; However&#44; a large group of eminent cardiologists&#44; immunologists&#44; allergists&#44; anesthetists and surgeons have agreed to convene in order to establish diagnostic and treatment criteria&#44; and we urge any scientist with interest and experience in this syndrome to participate&#46;</p></li></ul></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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