Letter to the Editor Cardiac troponin I is increased in patients admitted to the emergency department with severe allergic reactions. A case–control study Giuseppe Lippi a, ⁎, Ruggero Buonocore a , Fabio Schirosa b , Gianfranco Cervellin b a Laboratory of Clinical Chemistry and Hematology, Academic Hospital of Parma, Parma, Italy b Emergency Department, Academic Hospital of Parma, Parma, Italy article info Article history: Received 26 April 2015 Accepted 17 May 2015 Available online 19 May 2015 Keywords: Allergy Anaphylaxis Emergency medicine Cardiac injury Troponin Although the values of immunoglobulin E are frequently increased in patients with ischemic heart disease [1], an acute coronary syndrome caused by allergic reactions is an extremely rare clinical entity, which is conventionally known as “Kounis syndrome” [2]. This paradigmatic condition, characterized by the onset of an allergic reaction followed by chest pain and clinical and laboratory features of angina, is mainly attributable to the release of inflammatory mediators during an allergic event [3]. The pathophysiology and treatment of the Kounis syndrome are now clearly defined [4,5], but the occurrence of cardiac involvement in patients with different forms of acute allergic reaction requiring emergency department (ED) visit or hospital admission remains uncertain. Since cardiac troponins are now regarded as the biochemical gold standards for diagnosing cardiac injury [6], we performed a retro- spective study to investigate the values of cardiac troponin I (cTnI) in patients admitted to the ED with acute allergic reactions. The study population consisted in all consecutive adult patients (i.e., aged 17 years or older) admitted to the ED of the University Hospital of Parma (Italy) for acute allergic reactions, during the entire year 2013, and for whom laboratory testing was available. Information about ED admission was identified from the electronic hospital database using a double extraction key, i.e., ICD-9 codes 999, 995, 716, 708, 477 and 287 (including all the 4th and 5th digits), as well as verbal “strings”, i.e., “allergy”, “anaphylaxis”, “urticaria”, “angioedema”, and “shock”. The control population consisted in 125 healthy blood donors (60 women and 65 men, mean age 42 ± 10 years). The concentration of cTnI was measured in EDTA plasma using Beckman Coulter AccuTnI on Unicel DxI (Beckman Coulter, Brea, CA, USA). The lower limit of detection of this test is 10 ng/L, whereas the upper limit of the reference range (i.e., the 99th percentile of an ostensibly healthy population) is 30 ng/L [7]. The significance of difference of cTnI values between cases and controls was analyzed with the Wilcoxon–Mann–Whitney test (for continues variables) and Pearson's χ 2 statistics with Yates' correction (for categorical variables). Results of measurements were expressed as median and interquartile range (IQR). The statistical analysis was performed using Analyse-it (Analyse-it Software Ltd, Leeds, UK) and MedCalc Version 12.3.0 (MedCalc Software, Mariakerke, Belgium). The study was carried out in accord with the Declaration of Helsinki, under the terms of relevant local legislation. A total number of 3237 records were identified and analyzed by two separate physicians. Patients with unavailable laboratory data or those admitted to the ED for allergic rhinitis, asthma and chronic urticaria were excluded, thus limiting the analysis to cases of acute urticaria, acute angioedema, urticaria-angioedema and anaphylaxis. Overall, the final study population consisted in 31 patients and 125 controls (Table 1). Ten patients met the diagnostic criteria for anaphylaxis, 2 for angioedema, 15 for urticaria and 4 for urticaria– angioedema. The concentration of cTnI was found to be significantly higher in patients with acute allergic reactions requiring ED admission than in controls (Table 1). The percentage of measurable cTnI values (i.e., ≥10 ng/L) and of values exceeding the upper limit of the reference range (i.e., ≥ 30 ng/L) was also significantly higher in cases than in controls (Table 1). The relative risk (RR) and 95% confidence interval (95% CI) for cTnI values ≥ 10 ng/L and ≥ 30 ng/L in patients admitted to the ED with acute allergic reactions was 3.02 (95% CI, 95% CI, 1.60– 5.72) and 5.38 (95% CI, 1.27–22.80). Interestingly, the cTnI values of patients admitted to the ED with anaphylaxis (15 ng/L, IQR b 10 to 20 ng/mL) were significantly higher than those of the control popula- tion (b 10 ng/L, IQR, b 10 to 10 ng/L; p b 0.001), but also higher than those of patients with milder allergic reactions (b 10 ng/L, IQR, b 10 to 10 ng/L; p = 0.019) (Fig. 1). Acute allergic reactions are important causes of ED admission, whose frequency exhibited a remarkable increase in the past decades International Journal of Cardiology 194 (2015) 68–69 ⁎ Corresponding author at: U.O. Diagnostica Ematochimica, Dipartimento di Patologia e Medicina di Laboratorio, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci, 14, 43126 Parma, Italy. E-mail addresses: glippi@ao.pr.it, ulippi@tin.it (G. Lippi). http://dx.doi.org/10.1016/j.ijcard.2015.05.093 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved. 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