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Short protocol for the study of paediatric patients with suspected betalactam antibiotic hypersensitivity and low risk criteria
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Ortega" "apellidos" => "Martell" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054610002855?idApp=UINPBA00004N" "url" => "/03010546/0000003900000006/v1_201304101057/S0301054610002855/v1_201304101057/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Short protocol for the study of paediatric patients with suspected betalactam antibiotic hypersensitivity and low risk criteria" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "337" "paginaFinal" => "341" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "L. Moral, J. Garde, T. Toral, M.J. Fuentes, N. Marco" "autores" => array:5 [ 0 => array:4 [ "nombre" => "L." "apellidos" => "Moral" "email" => array:1 [ 0 => "lmoralg@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J." "apellidos" => "Garde" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "T." "apellidos" => "Toral" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "M.J." "apellidos" => "Fuentes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "N." "apellidos" => "Marco" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Pediatric Allergology Unit, Hospital General Universitario de Alicante, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Pediatric Allergology Unit, Hospital General Universitario de Elche, Spain" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Pediatric Allergology Unit, Hospital General de Elda, Spain" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Pediatric Allergology Unit, Hospital Vega Baja, Orihuela, Spain" "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 861 "Ancho" => 1451 "Tamanyo" => 80157 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Distribution of the betalactam antibiotics implicated in the suspect reactions.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The suspicion of hypersensitivity (HS) to drugs is a very frequent cause of medical consultation. In Spain, such situations account for about 7.5% of all patients seen in paediatric allergology clinics.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Betalactam antibiotics (BLAs) are the drugs most often implicated in cases of suspected HS, due to their widespread use in the empirical treatment of infections in childhood. However, evaluation of these patients rarely confirms such suspicion.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2-4</span></a> In our prior series of 503 children under 15 years of age seen for suspected HS to BLAs over a period of seven years, tolerance was confirmed in 68% of the cases, while 25% failed to complete the study (generally due to lack of consent or dropout), and only 6% (32) were diagnosed with allergy to BLA.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> This diagnosis proved significantly more probable in patients with a history of repeated or serious reactions, and in those administered BLAs via the parenteral route.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Based only on the clinical history, it is often difficult to establish whether the suspect reaction was of an immediate type or not. Although skin and laboratory tests are of little help in studying non-immediate reactions<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> – which seem to be the reactions most commonly seen in children – they are often performed in order to add supposed safety and reliability to the study of the patients. The study protocols developed by different scientific societies require several patient visits and are targeted at adults.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Only oral provocation allows the establishment of a definitive diagnosis.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Based on these considerations, our group developed a protocol for the clinical study of children referred to our clinics with suspected HS to BLAs. The main characteristic of the protocol is its simplicity, justified by the very low frequency of HS to BLAs in childhood, and the mild nature of the symptoms involved. The present study describes the results obtained in the first year of application of the protocol, with a view to establishing its clinical applicability, and proposes a study algorithm inspired by the experience gained.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Material and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">After evaluating our own experience and reviewing the recent literature, a protocol was developed for the study of paediatric patients (under 15 years of age) referred for the evaluation of suspected HS to some BLA. The data compiled on the first visit allowed us to evaluate the plausibility of the suspicion and assign the patients to one of the following two groups:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Group A</span>, corresponding to risk subjects, defined by the presence of at least one of the following circumstances:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">*</span><p id="par0030" class="elsevierStylePara elsevierViewall">Typical urticaria within the first hour after administration of a BLA.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">*</span><p id="par0035" class="elsevierStylePara elsevierViewall">Multiple reactions (two or more) with the same or with different BLAs.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">*</span><p id="par0040" class="elsevierStylePara elsevierViewall">Serious reactions: all types of systemic reactions and non-mild skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, etc).</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">*</span><p id="par0045" class="elsevierStylePara elsevierViewall">Reactions related to BLA administration via the parenteral route.</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">•</span><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Group B</span>, corresponding to low risk subjects, defined by the absence of all of the above-mentioned circumstances. These are patients with a single non-serious episode and non-immediate skin manifestations (exanthema, urticaria, angio-oedema, etc.) associated with the oral administration of a BLA.</p></li></ul></p><p id="par0055" class="elsevierStylePara elsevierViewall">In group A, a study was recommended based on the short algorithm proposed by the European Network for Drug Allergy (ENDA) / European Academy of Allergy and Clinical Immunology (EAACI), except when contraindicated due to the seriousness of the reaction.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The study sequentially comprised the determination of specific IgE (at least for penicillin G and amoxicillin), skin tests (prick and intradermal with PPL, MDM, penicillin and the implicated antibiotic at the maximum concentrations suggested by ENDA/EAACI) and, if the results proved negative (according to ENDA/EAACI criteria), an open oral provocation test (sequential study). In group B, the recommended study was limited to an open oral provocation test (short study). This test was made in the hospital with the culprit drug at doses of approximately 1/50 the usual single dose, 1/5 the usual single dose, and the usual single dose – administered with a one-hour interval between each dose. In all cases written authorisation was required from at least one of the parents, after having informed them of the available options and of the risks and benefits of each option. In abidance with the legal requirements of the Valencian Community, at least one day was required to elapse between parent authorisation and conduction of the study.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">In the first year of application of the described protocol, we attended 78 children referred due to suspected HS to BLA. There were 37 males and 41 females, with a mean age of 3.4 years at the time of the suspect episode and of 6.7 years at the time of consultation. The implicated drugs are reported in <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>. Twenty-two patients were assigned to group A (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) and 56 (72%) to group B. Compilation of the case history in turn showed that five patients had tolerated the suspect BLA at some point in time following the episode (three in group A and two in B) (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>). One patient of one year of age suffered a suspect reaction with cefotaxime via the intravenous route, and a sequential study was made with oral provocation with amoxicillin and cefixime, but testing with cefotaxime was not considered advisable. The short study was proposed to 55 patients, including five patients in group A. Of these, 50 accepted, one preferred the sequential study, and four rejected or failed to report for the study. The sequential study was proposed in 17 patients (13 in group A and 4 in group B). Of these, 16 accepted and one rejected the study. The skin and specific IgE tests were negative in the 17 patients subjected to the sequential study. Of the 67 patients who completed the study, oral provocation proved negative in 66. The only diagnosis of hypersensitivity to amoxicillin corresponded to a two-year-old girl with a history of two episodes of rash during two treatments (with amoxicillin and with amoxicillin - clavulanate). In the oral provocation test she developed a late reaction consisting of mild generalised erythema after eight hours, without itching. As a result, the patient was re-evaluated with a sequential study. Although the specific IgE and skin tests were negative (including the late reading after 48<span class="elsevierStyleHsp" style=""></span>hours), the repeat oral provocation test elicited a reaction similar to the previous one – the patient therefore being diagnosed as hypersensitive. The final results of the study of the 78 patients are reported in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">As in many other aspects of medical and allergological practice, children are not small adults. The study protocols proposed by the main expert groups and warranted by the scientific societies are based on experiences and studies from adult populations.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Studies in children are fewer, and have not allowed the development of specific protocols for securing a correct diagnosis.</p><p id="par0070" class="elsevierStylePara elsevierViewall">However, paediatric allergology clinics receive an important number of patients requiring evaluation for suspected hypersensitivity (HS) to drugs – very particularly including betalactam antibiotics (BLAs). Our own experience and that of other authors published in the medical literature indicate that most suspected reactions are not confirmed. However, drawing this conclusion is costly for both the families of the patients and for the healthcare system, particularly because of the time consumed and the visits required. Our protocol aims to reduce this cost without compromising patient safety.</p><p id="par0075" class="elsevierStylePara elsevierViewall">The protocols recommended by the expert groups of the different allergological societies imply several stages with the aim of detecting sensitised patients in which oral provocation is not considered indicated. These protocols are designed to reduce the risks for the patient, but also hide deleterious effects that are more patent in the case of children. In effect, given the extremely low true incidence of the problem in childhood, exhaustive patient study poses two significant inconveniences: the excessive cost of the study, which affect the families and the healthcare system, and the risk of false-positive results.</p><p id="par0080" class="elsevierStylePara elsevierViewall">The excess cost of a study based on the official recommendations has not been quantified, but it is easy to understand on analysing the number of visits, the healthcare professionals involved, and the material resources required. Our protocol has allowed 49 patients (73% of all those who completed the study) to avoid blood and skin tests. Apart from the direct cost savings and patient discomfort avoided, the families have had to visit the hospital less than half as often, and the associated time saved has been made available for the care of other patients. All this has afforded non-quantified satisfaction for both the families of the children, and the professionals implicated.</p><p id="par0085" class="elsevierStylePara elsevierViewall">On the other hand, all the patient studies culminated in oral provocation testing, which proved negative in 66 of the 67 patients. In the event the sequential study had been made and some patients were sensitised to BLAs, an erroneous diagnosis of allergy would have been established. We do not know the sensitivity and specificity of the skin tests and of the determination of specific IgE in children, and thus of the corresponding positive and negative predictive values – these parameters moreover being conditioned by the true prevalence of BLA allergy, which is undoubtedly very low. In one study, up to 10% of the children were sensitised to BLAs without a prior history of allergy.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> In fact, most subjects diagnosed with allergy to BLA are diagnosed on the basis of the results of the mentioned tests, rather than on provocation testing.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,14</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Our previous and current experiences suggest that patient safety is not compromised by this short protocol. Even the patients in group A were seen to tolerate provocation with the drug, thus indicating the low specificity of the criteria considered to define risk (immediate or multiple reactions) in detecting subjects with HS to BLAs.</p><p id="par0095" class="elsevierStylePara elsevierViewall">The main limitation of our study is the small number of patients studied. However, our pilot experience offers support for continuing this line of work, and adds to similar experience gained in predominantly adult populations.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Although it is not possible to quantify the risk associated with this study procedure, our data suggest that the risk is reasonable and no greater than that involved in other more laborious protocols.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Our prior experience and the studies made in children show positive oral provocation reactions to be mild in all cases,<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,16</span></a> with a risk possibly lower than that assumed in provocation testing with foods. The contradictory fact that some patients in group A were subjected to the short protocol may be due to specific factors in their clinical histories that led the clinician and family to choose this option. Our study does not allow the detection of patients with late-type HS to BLAs, which is both infrequent and mild.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,16</span></a> On the other hand, the procedure which allows us to guarantee the absence of late-type HS, particularly as regards the duration of exposure, has not been established. Thus, considering the above, we do not feel it justified to prolong exposure of the child to the suspect BLA in order to complete the study. By discarding immediate or serious HS to the BLA, the patient is allowed to use the medication under real life conditions (with medical indication), with sufficient safety. If exposure of this kind does not cause symptoms, use of the medication is completely safe. In contrast, if new suspect symptoms develop, the patient should be seen again in the specialised clinic to evaluate their importance and programme whatever study is considered opportune.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Based on our prior experience, enriched by the present study and backed by the articles published by other authors, we propose an algorithm for the study of paediatric patients with suspected HS to BLA, as shown in <a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>. This algorithm allows application of a short protocol to a large proportion of patients, with a reasonable level of safety, sparing families and the healthcare system from excessive dedication to a problem which in any case is generally shown to be non-existent.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Financial support</span><p id="par0110" class="elsevierStylePara elsevierViewall">This study has received no external funding, but has been awarded the second prize for the best oral communication at the XXXIV Congress of the Spanish Society of Pediatric Allergy and Clinical Immunology.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">No specific conflict of interest can be detected.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:2 [ "identificador" => "xres86021" "titulo" => array:5 [ 0 => "Abstract" 1 => "Background" 2 => "Methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec74199" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and methods" ] 4 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 5 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Financial support" ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2010-08-02" "fechaAceptado" => "2010-10-06" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec74199" "palabras" => array:5 [ 0 => "Drug hypersensitivity" 1 => "Betalactam antibiotic allergy" 2 => "Children" 3 => "Oral provocation test" 4 => "Efficiency" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Suspected hypersensitivity to betalactam antibiotics in children is a frequent cause of consultation that proves costly in terms of resource utilization – particularly time. Such hypersensitivity is, however, rarely confirmed.</p> <span class="elsevierStyleSectionTitle">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A short protocol was introduced in which patients at low risk (single episode with mild, non-immediate skin symptoms after the administration of a betalactam antibiotic via the oral route) were subjected to oral provocation (following the obtaining of informed consent) without any other prior evaluations. Patients failing to meet these requirements were studied according to the protocol of the EAACI (specific IgE and skin testing prior to oral provocation).</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 78 patients (56 at low risk) were studied. Five patients had tolerated the medication after the episode, while another six patients failed to complete the study. The study with oral provocation was completed in the remaining 67 patients: according to the protocol of the EAACI in 17 patients, and using the short protocol in 50 patients. Only one patient showed a positive provocation test, of a delayed and mild nature.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Direct oral provocation in low risk patients has been shown to be effective and safe in discarding hypersensitivity to betalactam antibiotics in the majority of the patients studied.</p>" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 861 "Ancho" => 1451 "Tamanyo" => 80157 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Distribution of the betalactam antibiotics implicated in the suspect reactions.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1965 "Ancho" => 2792 "Tamanyo" => 405769 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Flowchart of the patients attended during the study.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2674 "Ancho" => 2285 "Tamanyo" => 278914 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Diagnostic algorithm for suspected hypersensitivity to betalactam antibiotics in children.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Two patients presented two risk factors: multiple reactions and immediate-type reaction in one case, and immediate-type reaction and parenteral administration in the other.</p>" "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=""><tbody title="tbody"><tr title="table-row"><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">• Multiple (more than one) episodes: 12 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>∘ With the same BLA: 7 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>∘ With different BLAs: 5 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Immediate-type reaction: 9 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Parenteral administration: 3 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Severe reaction: 0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab165271.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Reasons for the assignment of 22 patients to group A (risk subjects) for true HS to BLA.</p>" ] ] 4 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "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=""><tbody title="tbody"><tr title="table-row"><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">1. Demonstrated tolerance: 71 (91%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1.1. Clinical history: 5 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1.2. Oral provocation test: 66 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. Hypersensitivity: 1 (1%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3. Not evaluated: 6 (8%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3.1. Rejection of study: 5 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3.2. Evaluation not indicated: 1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab165270.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Results obtained in the 78 patients studied for suspected hypersensitivity to betalactam antibiotics.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:16 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Allergy in patients under fourteen years of age in Alergológica 2005" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.D. Ibáñez" 1 => "J.M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 0 | 3 |
| 2024 October | 6 | 7 | 13 |
| 2024 September | 11 | 5 | 16 |
| 2024 August | 12 | 9 | 21 |
| 2024 July | 9 | 7 | 16 |
| 2024 June | 9 | 11 | 20 |
| 2024 May | 17 | 5 | 22 |
| 2024 April | 34 | 5 | 39 |
| 2024 March | 21 | 9 | 30 |
| 2024 February | 11 | 6 | 17 |
| 2024 January | 36 | 5 | 41 |
| 2023 December | 39 | 7 | 46 |
| 2023 November | 23 | 3 | 26 |
| 2023 October | 22 | 10 | 32 |
| 2023 September | 11 | 1 | 12 |
| 2023 August | 15 | 4 | 19 |
| 2023 July | 14 | 5 | 19 |
| 2023 June | 14 | 10 | 24 |
| 2023 May | 44 | 6 | 50 |
| 2023 April | 41 | 5 | 46 |
| 2023 March | 24 | 7 | 31 |
| 2023 February | 15 | 3 | 18 |
| 2023 January | 12 | 5 | 17 |
| 2022 December | 12 | 6 | 18 |
| 2022 November | 9 | 5 | 14 |
| 2022 October | 14 | 6 | 20 |
| 2022 September | 12 | 20 | 32 |
| 2022 August | 17 | 16 | 33 |
| 2022 July | 26 | 11 | 37 |
| 2022 June | 16 | 8 | 24 |
| 2022 May | 17 | 5 | 22 |
| 2022 April | 16 | 8 | 24 |
| 2022 March | 20 | 9 | 29 |
| 2022 February | 12 | 13 | 25 |
| 2022 January | 19 | 9 | 28 |
| 2021 December | 21 | 8 | 29 |
| 2021 November | 16 | 14 | 30 |
| 2021 October | 42 | 47 | 89 |
| 2021 September | 40 | 10 | 50 |
| 2021 August | 26 | 4 | 30 |
| 2021 July | 9 | 8 | 17 |
| 2021 June | 13 | 5 | 18 |
| 2021 May | 27 | 7 | 34 |
| 2021 April | 23 | 22 | 45 |
| 2021 March | 10 | 8 | 18 |
| 2021 February | 15 | 9 | 24 |
| 2021 January | 11 | 11 | 22 |
| 2020 December | 3 | 0 | 3 |
| 2020 August | 0 | 1 | 1 |
| 2020 July | 0 | 1 | 1 |
| 2020 April | 0 | 1 | 1 |
| 2020 January | 0 | 1 | 1 |
| 2019 May | 0 | 11 | 11 |
| 2018 March | 0 | 1 | 1 |
| 2018 February | 9 | 1 | 10 |
| 2018 January | 10 | 1 | 11 |
| 2017 December | 5 | 3 | 8 |
| 2017 November | 9 | 2 | 11 |
| 2017 October | 12 | 3 | 15 |
| 2017 September | 10 | 4 | 14 |
| 2017 August | 14 | 1 | 15 |
| 2017 July | 14 | 3 | 17 |
| 2017 June | 29 | 13 | 42 |
| 2017 May | 28 | 17 | 45 |
| 2017 April | 20 | 40 | 60 |
| 2017 March | 10 | 5 | 15 |
| 2017 February | 26 | 6 | 32 |
| 2017 January | 22 | 2 | 24 |
| 2016 December | 14 | 5 | 19 |
| 2016 November | 21 | 5 | 26 |
| 2016 October | 29 | 4 | 33 |
| 2016 September | 18 | 9 | 27 |
| 2016 August | 25 | 2 | 27 |
| 2016 July | 14 | 6 | 20 |
| 2016 June | 14 | 6 | 20 |
| 2016 May | 11 | 9 | 20 |
| 2016 April | 14 | 32 | 46 |
| 2016 March | 17 | 17 | 34 |
| 2016 February | 18 | 20 | 38 |
| 2016 January | 17 | 20 | 37 |
| 2015 December | 14 | 13 | 27 |
| 2015 November | 18 | 11 | 29 |
| 2015 October | 21 | 14 | 35 |
| 2015 September | 18 | 7 | 25 |
| 2015 August | 38 | 4 | 42 |
| 2015 July | 29 | 5 | 34 |
| 2015 June | 19 | 1 | 20 |
| 2015 May | 28 | 3 | 31 |
| 2015 April | 13 | 8 | 21 |
| 2015 March | 13 | 6 | 19 |
| 2015 February | 11 | 3 | 14 |
| 2015 January | 16 | 3 | 19 |
| 2014 December | 26 | 10 | 36 |
| 2014 November | 22 | 6 | 28 |
| 2014 October | 16 | 6 | 22 |
| 2014 September | 17 | 8 | 25 |
| 2014 August | 11 | 6 | 17 |
| 2014 July | 17 | 2 | 19 |
| 2014 June | 10 | 1 | 11 |
| 2014 May | 21 | 2 | 23 |
| 2014 April | 10 | 3 | 13 |
| 2014 March | 32 | 19 | 51 |
| 2014 February | 34 | 7 | 41 |
| 2014 January | 21 | 13 | 34 |
| 2013 December | 31 | 7 | 38 |
| 2013 November | 31 | 8 | 39 |
| 2013 October | 45 | 12 | 57 |
| 2013 September | 41 | 7 | 48 |
| 2013 August | 32 | 11 | 43 |
| 2013 July | 30 | 8 | 38 |
| 2013 June | 20 | 7 | 27 |
| 2013 May | 21 | 4 | 25 |
| 2013 April | 23 | 9 | 32 |
| 2013 March | 26 | 8 | 34 |
| 2013 February | 9 | 5 | 14 |
| 2013 January | 3 | 1 | 4 |
| 2012 December | 2 | 1 | 3 |
| 2012 November | 0 | 3 | 3 |
| 2012 October | 2 | 2 | 4 |
| 2011 November | 396 | 0 | 396 |
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