Confirmed penicillin allergy among patients receiving benzathine penicillin prophylaxis for acute rheumatic fever

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Ciółkowski, H. Mazurek, B. Stasiowska" "autores" => array:3 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Ciółkowski" ] 1 => array:2 [ "nombre" => "H." "apellidos" => "Mazurek" ] 2 => array:2 [ "nombre" => "B." "apellidos" => "Stasiowska" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054613000530?idApp=UINPBA00004N" "url" => "/03010546/0000004200000004/v1_201407030035/S0301054613000530/v1_201407030035/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "cabecera" => "Original Article" "titulo" => "Confirmed penicillin allergy among patients receiving benzathine penicillin prophylaxis for acute rheumatic fever" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "289" "paginaFinal" => "292" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. Kaya, M. Erkoçoğlu, O.G. Şenkon, F.K. Ekici, M. Toyran, İ.İ. Çetin, C.N. Kocabaş" "autores" => array:7 [ 0 => array:3 [ "nombre" => "A." "apellidos" => "Kaya" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Erkoçoğlu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "O.G." "apellidos" => "Şenkon" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "F.K." "apellidos" => "Ekici" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "M." "apellidos" => "Toyran" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "İ.İ." "apellidos" => "Çetin" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 6 => array:4 [ "nombre" => "C.N." "apellidos" => "Kocabaş" "email" => array:1 [ 0 => "cankocabas@yahoo.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Ankara Children's Hematology Oncology Education and Research Hospital, Department of Pediatric Allergy and Immunology, Ankara, Turkey" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Ankara Children's Hematology Oncology Education and Research Hospital, Department of Pediatrics, Ankara, Turkey" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Ankara Children's Hematology Oncology Education and Research Hospital, Department of Pediatric Cardiology, Ankara, Turkey" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "IntroductionBeta-lactam antibiotics are the most frequent drugs prescribed in children worldwide.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Suspected allergic reactions to beta-lactams are reported by 10 to 20% of patients.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Although a large majority of these children are labelled “penicillin-allergic” with a fear of severe reactions,<a class="elsevierStyleCrossRef" href="#bib0015">3</a> only 5–10% are proven to have allergy when appropriate clinical investigation is performed.<a class="elsevierStyleCrossRefs" href="#bib0020">4–7</a>Acute rheumatic fever (ARF) is the major cause of acquired heart disease among children and adolescents,<a class="elsevierStyleCrossRefs" href="#bib0040">8,9</a> and a repository form of penicillin, benzathine penicillin G, remains the treatment of choice for secondary prevention of the disease.<a class="elsevierStyleCrossRefs" href="#bib0045">9,10</a>Recurrences due to inadequate penicillin prophylaxis are responsible for chronic valvular lesions requiring surgery.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> The fear of a severe allergic reaction is the leading cause of discontinuing prophylaxis.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> Most children reporting allergy-like reactions to beta-lactams are not allergic to beta-lactams and it has been shown that after further diagnostic work up the true frequency of beta-lactam allergy was 3.3% among children with suspected drug allergy.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> There are not enough data on the real frequency of proven penicillin allergy among children on penicillin prophylaxis for ARF.In this study we aimed to reveal the frequency of adverse events and real allergic reactions to benzathine Penicillin among children who are followed in our paediatric cardiology clinic with a diagnosis of ARF.Materials and methodsThe patient files of children followed with a diagnosis of ARF between January 2005 and December 2011 were reviewed for an immediate or non-immediate allergic reaction to prophylactic penicillin treatment. Patients with a recorded reaction to penicillin were invited for participation in the study and were evaluated retrospectively. All patients enrolled in the study fulfilled the Jones criteria for diagnosis of rheumatic fever: Major criteria include: (1) carditis; (2) polyarthritis; (3) chorea; (4) erythema marginatum; and (5) subcutaneous nodules. Minor criteria include: (1) fever; (2) arthralgia; (3) previous rheumatic fever or rheumatic heart disease; (4) leucocytosis; elevated eritrocyte sedimentation rate and C-reactive protein; and (5) prolonged P–R interval on electrocardiogram. A firm diagnosis requires that two major or one major and two minor criteria are satisfied, in addition to evidence of recent streptococcal infection.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> Benzathine Penicillin G had been given intramuscularly once every three weeks, 0.6 million unit for children under 27kg and 1.2 million unit for children over 27kg until they had a reaction to the drug. Penicillin treatment had been terminated after the reaction. The number of injections was calculated according to the follow up period until the reaction. Median follow up period was 24 months and ranged between 12 and 36 months. Detailed history of the drug reaction was recorded both from the patient files and from the patients and their parents. Skin tests (prick and intradermal) and provocation test was performed to patients who had suspected allergic reactions.<a class="elsevierStyleCrossRefs" href="#bib0070">14,15</a>Skin testsTests were performed using penicillin G (10,000U/ml), benzylpenicilloyl polylysine(PPL®) (5×10−5mmol/L), and minor determinant mixture (MDM®)(2×10−2mmol/L) (Kit DAP from Diater Laboratorios S.A., Madrid, Spain).<a class="elsevierStyleCrossRef" href="#bib0080">16</a> Histamine (1%) was used as positive and 0.9% NaCl was used as negative control. Epidermal prick test was undertaken first and intradermal test followed when the former was negative. In the skin prick tests 15minutes after testing, a wheal larger than 3mm accompanied by erythema with a negative response to the control saline was considered positive (26). In the intradermal tests the wheal area was marked initially and 20minutes after testing, and an increase in diameter greater than 3mm was considered positive.<a class="elsevierStyleCrossRef" href="#bib0085">17</a>Provocation testFinally, both for immediate and non-immediate reactions, a provocation test was performed if all the other investigations were inconclusive and if the provocation test was not contra-indicated. ENDA guidelines on skin and drug provocation tests were carefully respected.<a class="elsevierStyleCrossRefs" href="#bib0085">17,18</a> Oral provocation was performed with 50,000U, 100,000U and 250,000U penicillin V suspensions at 20min intervals. If there was no reaction during oral provocation, benzathine penicillin was administered intramuscularly (0.6 million unit for children under 27kg and 1.2 million unit for children over 27kg).The study was approved by the local ethics committee (Approval number: 2012-018). Informed consent was taken from parents of patients for participation in the study.ResultsIn total 535 children with a diagnosis of ARF were analysed for the study. Mean age of patients was 10.8±2.3 years (5–16) and 46% of them were boys. Median follow up period was 24 months (12–36) [median (%25–75)]. Three hundred and sixteen patients were diagnosed as suffering ARF while in acute period, according to Jones criteria. Two hundred and nineteen patients were attended in our clinic with late complications of ARF.Within the 316 patients with acute symptoms, recurrence rates were 4.1% and 65.2% respectively (p<0.001) for patients who were compatible and incompatible with penicillin prophylaxis respectively. Valvular lesions were recorded in 44.6% and 68.9% of patients who were compatible and incompatible with penicillin prophylaxis respectively (p=0.003).For all patients, 21,169.2 million units benzathine penicillin by 17,641 injections was administered. The median number of injections per patient was 32 (4–96). Eleven patients (2%) were reported to have suspected allergic reaction after penicillin injection; a suspected allergic reaction was recorded after 0.06% of all injections.Among these 11 patients, eight had only cutaneous symptoms, one had nausea and vomiting, one had dizziness (vertigo), and one had syncope with dyspnoea. There were no fatal reactions. Nine of these patients consented to have further clinical evaluation. Two patients who had maculopapular rash after penicillin injection refused to have further evaluation for drug allergy. Among nine patients who accepted diagnostic evaluation, both skin prick tests and intradermal tests were all negative and provocation was positive in only one patient. This patient had had urticaria after her third injection and she had urticaria again after intramuscular injection during the provocation test. She was diagnosed to have immediate type hypersensitivity reaction to penicillin (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). According to these results, 0.18% (1/535) of the patients had immediate type hypersensitivity reaction to penicillin and allergic reaction was positive in 0.0056% (1/17,641) of all injections.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Eight of 11 patients continued to have prophylaxis with benzathine penicillin without any allergic reaction during subsequent penicillin injections.DiscussionEleven of our 535 ARF patients were suspected to have allergic reactions after 17,641 penicillin injections but only one (0.18%) was diagnosed with immediate type hypersensitivity reaction to penicillin after detailed evaluation. All patients with negative results during allergy testing continued their benzathine penicillin prophylaxis without adverse events. Even the patient with a history suggesting anaphylaxis tested negative with skin test and oral provocation and did not have any allergic reaction during subsequent penicillin injections.In an international study undertaken in 11 countries including 1790 adults and children having rheumatic fever, allergic reactions to penicillin were reported as 3.2% (57/1790) in a 3.4 year period. Anaphylaxis was present in 0.2% of patients and there was not any anaphylactic reaction among patients less than 12 years of age. The risk of fatal anaphylaxis was reported as 1/32,000 injections in that study.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> In a smaller study from Taiwan, 10 of 171 rheumatic fever patients (5.8%) were reported to have allergic reactions after benzathine penicillin injection.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> In accordance with these data, 2% of our patients had had suspected allergic reactions.Although commonly reported, most patients who have a history of a prior reaction to penicillin are not found to be allergic to penicillin upon skin testing.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> In our study only one of 11 patients with suspected allergic reaction was determined to have proven immediate type hypersensitivity reaction to penicillin. Overall, penicillin allergy was established in 0.18% of our ARF patients who were on prophylaxis with benzathine penicillin. Allergic evaluation with skin tests and oral provocation was not performed in the aforementioned studies about penicillin allergy among ARF patients. To our knowledge, this is the first study giving data on proven penicillin allergy among children with ARF. Our data suggest that the frequency of penicillin allergy is very much lower than suspected among children on penicillin prophylaxis for ARF.One of the reasons for ceasing prophylaxis with penicillin is the suspicion that longer duration of penicillin treatment can increase the risk of allergy. The frequency of allergic reactions to beta-lactam antibiotics are reported to be 1–10%<a class="elsevierStyleCrossRef" href="#bib0105">21</a> Weiss et al. reported a frequency of 2.24% in patients who received short term treatment with benzathine penicillin.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> Thus, according to our results and the data mentioned above, the frequency of allergic reactions among patients having long-term or short-term penicillin treatment seems to be similar. In an early study of benzathine penicillin prophylaxis for rheumatic fever, allergic reaction rates of patients receiving long term benzathine penicillin prophylaxis for ARF were similar to patients without rheumatic fever who receive short-term treatment with parenteral penicillin.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> Penicillin prophylaxis is important in the prevention of recurrences in ARF: The recurrence rate was 4% for our patients on regular penicillin prophylaxis, compared to 65.2 among patients who were incompatible with treatment. In another study, rheumatic fever recurred in eight (0.45%) of 1790 patients while on regular prophylaxis compared with 11 (11.5%) of 96 who were not.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> The remarkable increase of the recurrence rate among patients without regular penicillin prophylaxis emphasizes the importance of proper evaluation of penicillin allergy.Avoidance of penicillin, based on self-reported allergic history alone often leads to the use of an alternate antibiotic with greater cost or side effect profile or treatment failure.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> Macrolide group antibiotics are commonly preferred for the treatment and prophylaxis for group A streptococcus with a fear of severe allergic reactions but macrolide resistance in group A Streptococcus has been well documented in several countries.<a class="elsevierStyleCrossRef" href="#bib0120">24</a>In conclusion, allergic reactions to penicillin in patients with a history of rheumatic fever and under prophylaxis with benzathine penicillin are rare, and are no more frequent than in patients without rheumatic fever who receive short courses of parenteral penicillin for other indications. Penicillin prophylaxis is of utmost importance to decrease recurrences of ARF and only a minority of the patients with suspected reactions after injection have real penicillin allergy. Consequently, penicillin prophylaxis should not be given up without proper evaluation of drug allergy.Ethical disclosuresProtection of human subjects and animals in researchWe declare that the procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration.Patients’ data protectionWe declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study.Right to privacy and informed consentThe authors have obtained the informed consent of the patients mentioned in the article. The author for correspondence is in possession of this document.Conflict of interestAll of the authors have no conflicts of interest in the manuscript." 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Acute rheumatic fever (ARF) is the major cause of acquired heart disease among children and adolescents. Recurrences due to inadequate penicillin prophylaxis are responsible for chronic valvular lesions requiring surgery. The fear of a severe allergic reaction is the leading cause of discontinuing prophylaxis. ObjectiveIn this study, we aimed to reveal the frequency of adverse events and real allergic reactions to benzathine penicillin among children who are followed in our paediatric cardiology clinic with a diagnosis of ARF. Materials methodsThe children who were followed with a diagnosis of ARF between January 2005 and December 2011 were searched for a history of penicillin allergy. Patients with a positive history were evaluated in our paediatric allergy clinic. Skin tests and provocation tests were performed with parental consent. ResultsIn total 535 children with a diagnosis of ARF were analysed for the study. Median follow up period was 24 months (12–36) [median (%25–75)]. Eleven of our 535 (11/17.641 injection) ARF patients were suspected to have allergic reactions after 17.641 penicillin injections but only one (0.18%) was diagnosed to have penicillin allergy after detailed evaluation. ConclusionOur data suggest that the frequency of penicillin allergy is much lower than suspected among children on penicillin prophylaxis for ARF. Consequently, penicillin prophylaxis should not be given up without proper evaluation of drug allergy." ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Gender \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Age at diagnosis (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Symptoms after injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Dose when the reaction occurred \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Prick test \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">ID test \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Provocation test \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Maculopapular rash \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refused \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refused \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refused \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Maculopapular rash \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Urticaria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Maculopapular rash with pruritus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Urticaria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dizziness \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nausea, vomiting \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Syncope, dyspnoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Maculopapular rash with pruritus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Maculopapular rash \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refused \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refused \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refused \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hyperaemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab522895.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of patients with a history of suspected allergic reaction after penicillin injection." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:24 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Variation in antibiotic use in the European Union" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "O. 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Original Article

A. Kayaa, M. Erkoçoğlua, O.G. Şenkonb, F.K. Ekicic, M. Toyrana, İ.İ. Çetinc, C.N. Kocabaşa,

Corresponding author

cankocabas@yahoo.com

Corresponding author.

a Ankara Children's Hematology Oncology Education and Research Hospital, Department of Pediatric Allergy and Immunology, Ankara, Turkey

b Ankara Children's Hematology Oncology Education and Research Hospital, Department of Pediatrics, Ankara, Turkey

c Ankara Children's Hematology Oncology Education and Research Hospital, Department of Pediatric Cardiology, Ankara, Turkey

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is the major cause of acquired heart disease among children and adolescents&#44;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a> and a repository form of penicillin&#44; benzathine penicillin G&#44; remains the treatment of choice for secondary prevention of the disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Recurrences due to inadequate penicillin prophylaxis are responsible for chronic valvular lesions requiring surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The fear of a severe allergic reaction is the leading cause of discontinuing prophylaxis&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Most children reporting allergy-like reactions to beta-lactams are not allergic to beta-lactams and it has been shown that after further diagnostic work up the true frequency of beta-lactam allergy was 3&#46;3&#37; among children with suspected drug allergy&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> There are not enough data on the real frequency of proven penicillin allergy among children on penicillin prophylaxis for ARF&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In this study we aimed to reveal the frequency of adverse events and real allergic reactions to benzathine Penicillin among children who are followed in our paediatric cardiology clinic with a diagnosis of ARF&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Materials and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">The patient files of children followed with a diagnosis of ARF between January 2005 and December 2011 were reviewed for an immediate or non-immediate allergic reaction to prophylactic penicillin treatment&#46; Patients with a recorded reaction to penicillin were invited for participation in the study and were evaluated retrospectively&#46; All patients enrolled in the study fulfilled the Jones criteria for diagnosis of rheumatic fever&#58; Major criteria include&#58; &#40;1&#41; carditis&#59; &#40;2&#41; polyarthritis&#59; &#40;3&#41; chorea&#59; &#40;4&#41; erythema marginatum&#59; and &#40;5&#41; subcutaneous nodules&#46; Minor criteria include&#58; &#40;1&#41; fever&#59; &#40;2&#41; arthralgia&#59; &#40;3&#41; previous rheumatic fever or rheumatic heart disease&#59; &#40;4&#41; leucocytosis&#59; elevated eritrocyte sedimentation rate and C-reactive protein&#59; and &#40;5&#41; prolonged P&#8211;R interval on electrocardiogram&#46; A firm diagnosis requires that two major or one major and two minor criteria are satisfied&#44; in addition to evidence of recent streptococcal infection&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Benzathine Penicillin G had been given intramuscularly once every three weeks&#44; 0&#46;6 million unit for children under 27<span class="elsevierStyleHsp" style=""></span>kg and 1&#46;2 million unit for children over 27<span class="elsevierStyleHsp" style=""></span>kg until they had a reaction to the drug&#46; Penicillin treatment had been terminated after the reaction&#46; The number of injections was calculated according to the follow up period until the reaction&#46; Median follow up period was 24 months and ranged between 12 and 36 months&#46; Detailed history of the drug reaction was recorded both from the patient files and from the patients and their parents&#46; Skin tests &#40;prick and intradermal&#41; and provocation test was performed to patients who had suspected allergic reactions&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Skin tests</span><p id="par0030" class="elsevierStylePara elsevierViewall">Tests were performed using penicillin G &#40;10&#44;000<span class="elsevierStyleHsp" style=""></span>U&#47;ml&#41;&#44; benzylpenicilloyl polylysine&#40;PPL<span class="elsevierStyleSup">&#174;</span>&#41; &#40;5<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;5</span><span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41;&#44; 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and an increase in diameter greater than 3<span class="elsevierStyleHsp" style=""></span>mm was considered positive&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Provocation test</span><p id="par0035" class="elsevierStylePara elsevierViewall">Finally&#44; both for immediate and non-immediate reactions&#44; a provocation test was performed if all the other investigations were inconclusive and if the provocation test was not contra-indicated&#46; ENDA guidelines on skin and drug provocation tests were carefully respected&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> Oral provocation was performed with 50&#44;000<span class="elsevierStyleHsp" style=""></span>U&#44; 100&#44;000<span class="elsevierStyleHsp" style=""></span>U and 250&#44;000<span class="elsevierStyleHsp" style=""></span>U penicillin V suspensions at 20<span class="elsevierStyleHsp" style=""></span>min intervals&#46; If there was no reaction during oral provocation&#44; benzathine penicillin was administered intramuscularly &#40;0&#46;6 million unit for children under 27<span class="elsevierStyleHsp" style=""></span>kg and 1&#46;2 million unit for children over 27<span class="elsevierStyleHsp" style=""></span>kg&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The study was approved by the local ethics committee &#40;Approval number&#58; 2012-018&#41;&#46; Informed consent was taken from parents of patients for participation in the study&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">In total 535 children with a diagnosis of ARF were analysed for the study&#46; Mean age of patients was 10&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;3 years &#40;5&#8211;16&#41; and 46&#37; of them were boys&#46; Median follow up period was 24 months &#40;12&#8211;36&#41; &#91;median &#40;&#37;25&#8211;75&#41;&#93;&#46; Three hundred and sixteen patients were diagnosed as suffering ARF while in acute period&#44; according to Jones criteria&#46; Two hundred and nineteen patients were attended in our clinic with late complications of ARF&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Within the 316 patients with acute symptoms&#44; recurrence rates were 4&#46;1&#37; and 65&#46;2&#37; respectively &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; for patients who were compatible and incompatible with penicillin prophylaxis respectively&#46; Valvular lesions were recorded in 44&#46;6&#37; and 68&#46;9&#37; of patients who were compatible and incompatible with penicillin prophylaxis respectively &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">For all patients&#44; 21&#44;169&#46;2 million units benzathine penicillin by 17&#44;641 injections was administered&#46; The median number of injections per patient was 32 &#40;4&#8211;96&#41;&#46; Eleven patients &#40;2&#37;&#41; were reported to have suspected allergic reaction after penicillin injection&#59; a suspected allergic reaction was recorded after 0&#46;06&#37; of all injections&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Among these 11 patients&#44; eight had only cutaneous symptoms&#44; one had nausea and vomiting&#44; one had dizziness &#40;vertigo&#41;&#44; and one had syncope with dyspnoea&#46; There were no fatal reactions&#46; Nine of these patients consented to have further clinical evaluation&#46; Two patients who had maculopapular rash after penicillin injection refused to have further evaluation for drug allergy&#46; Among nine patients who accepted diagnostic evaluation&#44; both skin prick tests and intradermal tests were all negative and provocation was positive in only one patient&#46; This patient had had urticaria after her third injection and she had urticaria again after intramuscular injection during the provocation test&#46; She was diagnosed to have immediate type hypersensitivity reaction to penicillin &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; According to these results&#44; 0&#46;18&#37; &#40;1&#47;535&#41; of the patients had immediate type hypersensitivity reaction to penicillin and allergic reaction was positive in 0&#46;0056&#37; &#40;1&#47;17&#44;641&#41; of all injections&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Eight of 11 patients continued to have prophylaxis with benzathine penicillin without any allergic reaction during subsequent penicillin injections&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">Eleven of our 535 ARF patients were suspected to have allergic reactions after 17&#44;641 penicillin injections but only one &#40;0&#46;18&#37;&#41; was diagnosed with immediate type hypersensitivity reaction to penicillin after detailed evaluation&#46; All patients with negative results during allergy testing continued their benzathine penicillin prophylaxis without adverse events&#46; Even the patient with a history suggesting anaphylaxis tested negative with skin test and oral provocation and did not have any allergic reaction during subsequent penicillin injections&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In an international study undertaken in 11 countries including 1790 adults and children having rheumatic fever&#44; allergic reactions to penicillin were reported as 3&#46;2&#37; &#40;57&#47;1790&#41; in a 3&#46;4 year period&#46; Anaphylaxis was present in 0&#46;2&#37; of patients and there was not any anaphylactic reaction among patients less than 12 years of age&#46; The risk of fatal anaphylaxis was reported as 1&#47;32&#44;000 injections in that study&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> In a smaller study from Taiwan&#44; 10 of 171 rheumatic fever patients &#40;5&#46;8&#37;&#41; were reported to have allergic reactions after benzathine penicillin injection&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> In accordance with these data&#44; 2&#37; of our patients had had suspected allergic reactions&#46;Although commonly reported&#44; most patients who have a history of a prior reaction to penicillin are not found to be allergic to penicillin upon skin testing&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In our study only one of 11 patients with suspected allergic reaction was determined to have proven immediate type hypersensitivity reaction to penicillin&#46; Overall&#44; penicillin allergy was established in 0&#46;18&#37; of our ARF patients who were on prophylaxis with benzathine penicillin&#46; Allergic evaluation with skin tests and oral provocation was not performed in the aforementioned studies about penicillin allergy among ARF patients&#46; To our knowledge&#44; this is the first study giving data on proven penicillin allergy among children with ARF&#46; Our data suggest that the frequency of penicillin allergy is very much lower than suspected among children on penicillin prophylaxis for ARF&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">One of the reasons for ceasing prophylaxis with penicillin is the suspicion that longer duration of penicillin treatment can increase the risk of allergy&#46; The frequency of allergic reactions to beta-lactam antibiotics are reported to be 1&#8211;10&#37;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Weiss et al&#46; reported a frequency of 2&#46;24&#37; in patients who received short term treatment with benzathine penicillin&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Thus&#44; according to our results and the data mentioned above&#44; the frequency of allergic reactions among patients having long-term or short-term penicillin treatment seems to be similar&#46; In an early study of benzathine penicillin prophylaxis for rheumatic fever&#44; allergic reaction rates of patients receiving long term benzathine penicillin prophylaxis for ARF were similar to patients without rheumatic fever who receive short-term treatment with parenteral penicillin&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Penicillin prophylaxis is important in the prevention of recurrences in ARF&#58; The recurrence rate was 4&#37; for our patients on regular penicillin prophylaxis&#44; compared to 65&#46;2 among patients who were incompatible with treatment&#46; In another study&#44; rheumatic fever recurred in eight &#40;0&#46;45&#37;&#41; of 1790 patients while on regular prophylaxis compared with 11 &#40;11&#46;5&#37;&#41; of 96 who were not&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> The remarkable increase of the recurrence rate among patients without regular penicillin prophylaxis emphasizes the importance of proper evaluation of penicillin allergy&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Avoidance of penicillin&#44; based on self-reported allergic history alone often leads to the use of an alternate antibiotic with greater cost or side effect profile or treatment failure&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Macrolide group antibiotics are commonly preferred for the treatment and prophylaxis for group A streptococcus with a fear of severe allergic reactions but macrolide resistance in group A Streptococcus has been well documented in several countries&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">In conclusion&#44; allergic reactions to penicillin in patients with a history of rheumatic fever and under prophylaxis with benzathine penicillin are rare&#44; and are no more frequent than in patients without rheumatic fever who receive short courses of parenteral penicillin for other indications&#46; Penicillin prophylaxis is of utmost importance to decrease recurrences of ARF and only a minority of the patients with suspected reactions after injection have real penicillin allergy&#46; Consequently&#44; penicillin prophylaxis should not be given up without proper evaluation of drug allergy&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical disclosures</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Protection of human subjects and animals in research</span><p id="par0100" class="elsevierStylePara elsevierViewall">We declare that the procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patients&#8217; data protection</span><p id="par0105" class="elsevierStylePara elsevierViewall">We declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Right to privacy and informed consent</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors have obtained the informed consent of the patients mentioned in the article&#46; The author for correspondence is in possession of this document&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">All of the authors have no conflicts of interest in the manuscript&#46;</p></span></span>"
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        0 => array:2 [
          "identificador" => "xres349806"
          "titulo" => array:6 [
            0 => "Abstract"
            1 => "Background"
            2 => "Objective"
            3 => "Materials methods"
            4 => "Results"
            5 => "Conclusion"
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec331469"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        3 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Materials and methods"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Skin tests"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Provocation test"
            ]
          ]
        ]
        4 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Results"
        ]
        5 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Discussion"
        ]
        6 => array:3 [
          "identificador" => "sec0035"
          "titulo" => "Ethical disclosures"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Protection of human subjects and animals in research"
            ]
            1 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Patients&#8217; data protection"
            ]
            2 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Right to privacy and informed consent"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Conflict of interest"
        ]
        8 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2012-10-11"
    "fechaAceptado" => "2012-12-20"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec331469"
          "palabras" => array:3 [
            0 => "Acute rheumatic fever"
            1 => "Penicillin allergy"
            2 => "Benzathine penicillin prophylaxis"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Beta-lactam antibiotics are the most frequent drugs prescribed in children worldwide&#46; Acute rheumatic fever &#40;ARF&#41; is the major cause of acquired heart disease among children and adolescents&#46; Recurrences due to inadequate penicillin prophylaxis are responsible for chronic valvular lesions requiring surgery&#46; The fear of a severe allergic reaction is the leading cause of discontinuing prophylaxis&#46;</p> <span class="elsevierStyleSectionTitle">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">In this study&#44; we aimed to reveal the frequency of adverse events and real allergic reactions to benzathine penicillin among children who are followed in our paediatric cardiology clinic with a diagnosis of ARF&#46;</p> <span class="elsevierStyleSectionTitle">Materials methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The children who were followed with a diagnosis of ARF between January 2005 and December 2011 were searched for a history of penicillin allergy&#46; Patients with a positive history were evaluated in our paediatric allergy clinic&#46; Skin tests and provocation tests were performed with parental consent&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In total 535 children with a diagnosis of ARF were analysed for the study&#46; Median follow up period was 24 months &#40;12&#8211;36&#41; &#91;median &#40;&#37;25&#8211;75&#41;&#93;&#46; Eleven of our 535 &#40;11&#47;17&#46;641 injection&#41; ARF patients were suspected to have allergic reactions after 17&#46;641 penicillin injections but only one &#40;0&#46;18&#37;&#41; was diagnosed to have penicillin allergy after detailed evaluation&#46;</p> <span class="elsevierStyleSectionTitle">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Our data suggest that the frequency of penicillin allergy is much lower than suspected among children on penicillin prophylaxis for ARF&#46; Consequently&#44; penicillin prophylaxis should not be given up without proper evaluation of drug allergy&#46;</p>"
      ]
    ]
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        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "tabla" => array:1 [
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Gender&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Age at diagnosis &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Symptoms after injection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Dose when the reaction occurred&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Prick test&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">ID test&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Provocation test&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maculopapular rash&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refused&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refused&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refused&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maculopapular rash&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Urticaria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maculopapular rash with pruritus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Urticaria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dizziness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nausea&#44; vomiting&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Syncope&#44; dyspnoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maculopapular rash with pruritus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maculopapular rash&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refused&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refused&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refused&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hyperaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab522895.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Characteristics of patients with a history of suspected allergic reaction after penicillin injection&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:24 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Variation in antibiotic use in the European Union"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "O&#46; Cars"
                            1 => "S&#46; Molstad"
                            2 => "A&#46; Melander"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(00)04972-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2001"
                        "volumen" => "357"
                        "paginaInicial" => "1851"
                        "paginaFinal" => "1853"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11410197"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Accuracy in diagnosis of allergy to beta-lactams"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46; Iglesias-Souto"
                            1 => "R&#46; Gonzalez"
                            2 => "P&#46; Poza-Guedes"
                            3 => "I&#46; Sanchez-Machin"
                            4 => "V&#46; Matheu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/cc11193"
                      "Revista" => array:5 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2012"
                        "volumen" => "16"
                        "paginaInicial" => "414"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22405259"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
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Article information

ISSN: 03010546
Original language: English

DOI:10.1016/j.aller.2012.12.007

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	5	3	8
2024 October	99	18	117
2024 September	98	13	111
2024 August	87	16	103
2024 July	88	14	102
2024 June	86	22	108
2024 May	78	23	101
2024 April	86	17	103
2024 March	80	25	105
2024 February	98	23	121
2024 January	124	12	136
2023 December	98	16	114
2023 November	130	13	143
2023 October	176	22	198
2023 September	97	9	106
2023 August	94	8	102
2023 July	102	14	116
2023 June	92	16	108
2023 May	114	13	127
2023 April	109	7	116
2023 March	111	7	118
2023 February	64	8	72
2023 January	41	16	57
2022 December	39	28	67
2022 November	28	25	53
2022 October	23	25	48
2022 September	13	33	46
2022 August	21	24	45
2022 July	14	19	33
2022 June	8	15	23
2022 May	14	20	34
2022 April	18	24	42
2022 March	11	46	57
2022 February	5	32	37
2022 January	15	50	65
2021 December	11	34	45
2021 November	9	33	42
2021 October	12	37	49
2021 September	13	35	48
2021 August	6	31	37
2021 July	11	39	50
2021 June	11	26	37
2021 May	14	45	59
2021 April	19	109	128
2021 March	9	51	60
2021 February	9	26	35
2021 January	8	29	37
2020 December	2	24	26
2020 November	0	29	29
2020 October	0	17	17
2020 September	0	17	17
2020 August	0	14	14
2020 July	0	9	9
2020 June	0	15	15
2020 May	0	17	17
2020 April	0	21	21
2020 March	0	18	18
2020 February	0	6	6
2020 January	0	6	6
2019 December	0	3	3
2019 November	0	3	3
2019 October	0	2	2
2019 September	0	5	5
2019 August	0	4	4
2019 July	0	3	3
2019 June	0	7	7
2019 May	0	9	9
2019 April	0	14	14
2019 February	0	2	2
2018 December	0	5	5
2018 April	0	2	2
2018 February	9	3	12
2018 January	6	4	10
2017 December	8	0	8
2017 November	16	5	21
2017 October	7	4	11
2017 September	9	5	14
2017 August	12	5	17
2017 July	9	5	14
2017 June	20	9	29
2017 May	29	8	37
2017 April	21	24	45
2017 March	15	11	26
2017 February	20	9	29
2017 January	7	6	13
2016 December	25	12	37
2016 November	15	11	26
2016 October	33	12	45
2016 September	7	2	9
2016 August	17	12	29
2016 July	7	2	9
2016 June	19	5	24
2016 May	10	16	26
2016 April	16	7	23
2016 March	19	8	27
2016 February	17	10	27
2016 January	15	10	25
2015 December	13	8	21
2015 November	7	6	13
2015 October	22	7	29
2015 September	11	6	17
2015 August	16	4	20
2015 July	6	6	12
2015 May	0	1	1
2015 April	0	3	3
2015 March	0	6	6
2015 February	2	0	2
2015 January	1	3	4
2014 December	1	0	1
2014 October	1	2	3
2014 September	1	2	3
2014 August	1	6	7
2014 July	3	12	15

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Allergologia et Immunopathologia is no longer published on Elsevier since the 2021 year.Transferred to Codon Publications

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Allergologia et Immunopathologia is no longer published on Elsevier since the 2021 year.Transferred to Codon Publications

Indexed in:

Follow us:

Statistics

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