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array:23 [ "pii" => "S0301054609711127" "issn" => "03010546" "doi" => "10.1016/S0301-0546(09)71112-7" "estado" => "S300" "fechaPublicacion" => "2009-04-01" "aid" => "71112" "copyright" => "Sociedad Española de Inmunología Clínica y Alergología Pediátrica y Elsevier España, S.L." "copyrightAnyo" => "2009" "documento" => "article" "crossmark" => 0 "subdocumento" => "rev" "cita" => "Allergol Immunopathol (Madr). 2009;37:98-104" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 4569 "formatos" => array:3 [ "EPUB" => 9 "HTML" => 4210 "PDF" => 350 ] ] "itemSiguiente" => array:18 [ "pii" => "S0301054609711139" "issn" => "03010546" "doi" => "10.1016/S0301-0546(09)71113-9" "estado" => "S300" "fechaPublicacion" => "2009-04-01" "aid" => "71113" "copyright" => "Sociedad Española de Inmunología Clínica y Alergología Pediátrica y Elsevier España, S.L." "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "cor" "cita" => "Allergol Immunopathol (Madr). 2009;37:105-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 3905 "formatos" => array:3 [ "EPUB" => 10 "HTML" => 3536 "PDF" => 359 ] ] "es" => array:9 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">RESEARCH LETTERS</span>" "titulo" => "Successful desensitisation to ceftriaxone in a patient with doxycicline resistant Lyme disease" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "105" "paginaFinal" => "106" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Linda Graça Cruz, Josefina Rodrigues, Carmen Botelho, Edite Rio, Maria Graça Castel-Branco" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Linda" "apellidos" => "Graça Cruz" ] 1 => array:2 [ "nombre" => "Josefina" "apellidos" => "Rodrigues" ] 2 => array:2 [ "nombre" => "Carmen" "apellidos" => "Botelho" ] 3 => array:2 [ "nombre" => "Edite" "apellidos" => "Rio" ] 4 => array:2 [ "nombre" => "Maria" "apellidos" => "Graça Castel-Branco" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054609711139?idApp=UINPBA00004N" "url" => "/03010546/0000003700000002/v1_201304101125/S0301054609711139/v1_201304101125/es/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0301054609711115" "issn" => "03010546" "doi" => "10.1016/S0301-0546(09)71111-5" "estado" => "S300" "fechaPublicacion" => "2009-04-01" "aid" => "71111" "copyright" => "Sociedad Española de Inmunología Clínica y Alergología Pediátrica y Elsevier España, S.L." "documento" => "article" "crossmark" => 0 "subdocumento" => "sco" "cita" => "Allergol Immunopathol (Madr). 2009;37:93-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1794 "formatos" => array:3 [ "EPUB" => 6 "HTML" => 1448 "PDF" => 340 ] ] "es" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">SERIES: BASIC STATISTICS FOR BUSY CLINICIANS (II)</span>" "titulo" => "Design and debugging databases for statistical analysis" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "93" "paginaFinal" => "97" ] ] "contieneResumen" => array:1 [ "es" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 808 "Ancho" => 999 "Tamanyo" => 50539 ] ] "descripcion" => array:1 [ "es" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Boxplot of FEV<span class="elsevierStyleInf">25–75</span> in a group of adults asthmatic patients.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.M. Rodríguez del Águila, P. Garrido-Fernández" "autores" => array:2 [ 0 => array:2 [ "nombre" => "M.M." "apellidos" => "Rodríguez del Águila" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Garrido-Fernández" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054609711115?idApp=UINPBA00004N" "url" => "/03010546/0000003700000002/v1_201304101125/S0301054609711115/v1_201304101125/es/main.assets" ] "es" => array:17 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">REVIEW</span>" "titulo" => "Diagnosing immune-mediated reactions to drugs" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "98" "paginaFinal" => "104" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A.T. Nagao-Dias, F.M. Teixeira, H.L.L. Coelho" "autores" => array:3 [ 0 => array:4 [ "nombre" => "A.T." "apellidos" => "Nagao-Dias" "email" => array:1 [ 0 => "tiemindi@yahoo.com.br" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">†</span>" "identificador" => "cor1" ] ] ] 1 => array:3 [ "nombre" => "F.M." "apellidos" => "Teixeira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] ] ] 2 => array:3 [ "nombre" => "H.L.L." "apellidos" => "Coelho" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Dept. Clinical Analysis and Toxicology, Faculty of Pharmacy, Universidade Federal do Ceará, Brazil" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Dept of Pharmacy, Faculty of Pharmacy, Universidade Federal do Ceará, Brazil" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "†" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1398 "Ancho" => 2074 "Tamanyo" => 134948 ] ] "descripcion" => array:1 [ "es" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Representation of a clinical practice algorithm. Adapted from Forrest et al, 2001; Gruchalla and Pirmohamed, 2006.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0005">Introduction</span><p id="p0105" class="elsevierStylePara elsevierViewall">The percentage of the population who reports a history of penicillin allergy is estimated to be 0.7-10 %; however, only 20–30 % of the patients have IgE-mediated allergy <a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a>. Adverse drug reactions (ADR) are considered to be an important public health problem and can be life-threatening. ADR is classified into two main types: type A reactions, which are dose dependent and predictable. These kinds of reactions constitute 70–80 % of adverse drug reactions; and type B, which are unpredictable adverse drug reactions, include idiosyncrasy, drug intolerance, or drug allergy, and may comprise approximately 10–15 % of all ADR <a class="elsevierStyleCrossRefs" href="#bb0010"><span class="elsevierStyleSup">2,3</span></a>. Clinical manifestations of drug allergy include anaphylaxis, bronchospasm, dermatitis, fever, granulocytopenia, haemolytic anaemia, hepatitis, lupus erythematosus-like syndrome, nephritis, thrombocytopenia, and vasculitis <a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a>. Symptoms and signs without demonstration of being an immunological process are classified as non-immune hypersensitivity drug reactions, and they are generally related to nonspecific histamine release, to nonspecific complement activation, to bradykinin accumulation or to induction of leukotriene synthesis in type I hypersensitivity reactions <a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a>. Non-steroidal anti-inflammatory drugs and antibiotics are most often implicated in drug allergies, besides anaesthetic drugs, latex, insulin, and immunomodulators <a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRefs" href="#bb0030"><span class="elsevierStyleSup">6,7</span></a> (<a class="elsevierStyleCrossRef" href="#t0005">Table I</a>).</p><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0110" class="elsevierStylePara elsevierViewall">Drug allergy reactions are generally classified according to Coomb's classification <a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a>. Type I include IgE-mediated reactions, such as urticaria, anaphylaxis, and asthma; type II comprises IgM and IgG-cytotoxic mechanisms (e.g. blood cell dyscrasias); type III are related to soluble IgG and IgM immune complexes (e.g. vasculitis, nephritis). Type IV reactions include distinct manifestations (e.g. maculopapular exanthema, bullous exanthema, acute, generalized exanthemous pustulosis) according to the kind of cytokines secreted by T cells. In this type of reaction, a subclassification has been suggested according to the distinct effector cells responsible for the lesions <a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a>. The type I hypersensitivity reactions are called immediate reactions when they occur within one hour after the drug intake and the common manifestations are systemic anaphylaxis, urticaria, angioedema; they are called accelerated when they occur between 1 to 72 hours after receiving the drug, and the most frequent manifestations are urticaria and maculopapular rashes. Types II to IV hypersensitivity reactions occur in general after 72 hours of the drug intake <a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a>. The most frequent clinical manifestations caused by betalactamic drugs, which are the commonest implicating agents of drug hypersensitivity, are anaphylaxis (immediate reaction); maculopapular exanthema (late reaction) and isolated urticaria (occurs at any time) <a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a>. In a follow-up study done in two hospitals in Fortaleza, Brazil, it has been verified that from 130 paediatric patients exposed to oxacillin, a drug included in the list of essential medicines, 20.8 % presented drug adverse reactions, in a mean time of 14<span class="elsevierStyleHsp" style=""></span>days after the drug exposure <a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a>. Half of the patients had fever and 35.7 % showed cutaneous rashes.</p><p id="p0115" class="elsevierStylePara elsevierViewall">A pharmacovigilance evaluation can be done for monitoring a drug adverse reaction. A case report in pharmacovigilance can be defined as “a notification relating to a patient with an adverse medical event (or laboratory test abnormality) suspected to be induced by a medicine” <a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a>. In general, case reports describe suspected adverse drug reactions <a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a>. Various approaches have been developed for determining the likelihood of a causal relationship between drug exposure and adverse events, based on four main considerations, which are: the association in time (or place) between drug administration and event, pharmacology (including current knowledge of nature and frequency of adverse reactions), medical or pharmacological plausibility (signs and symptoms, laboratory tests, pathological findings, mechanism) (<a class="elsevierStyleCrossRef" href="#t0010">Table II</a>).</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><p id="p0120" class="elsevierStylePara elsevierViewall">The Uppsala Monitoring Centre (the UMC)/WHO Collaborating Centre for International Drug Monitoring <a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a> has proposed a way for assessing causality categories, which have the advantages of being internationally agreed and easy to use (<a class="elsevierStyleCrossRef" href="#t0015">Table III</a>).</p><elsevierMultimedia ident="t0015"></elsevierMultimedia></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Diagnosis</span><p id="p0125" class="elsevierStylePara elsevierViewall">In the evaluation of a possible adverse drug reaction, a careful investigation of the medical history as well as the laboratorial parameters is extremely important <a class="elsevierStyleCrossRefs" href="#bb0065"><span class="elsevierStyleSup">13,14</span></a>.</p><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Clinical history investigation</span><p id="p0130" class="elsevierStylePara elsevierViewall">A well-kept history is essential to help in the investigation of adverse drug reaction and should include: (1) timing of the onset, course and duration of symptoms; (2) description of clinical and evolutive features; (3) temporal relationship of symptoms with medication use; (4) a detailed list of all drugs taken during the onset of the reactions; (5) personal and familiar history of adverse drug reactions; and (6) co-associated diseases. Some laboratory parameters, such as full blood count; platelet count; blood sedimentation rate; serum creatinine; bilirubin; alkaline phosphatise; transaminases; biopsy, among others, and specific confirmatory tests (skin and patch tests, in vitro assays for specific IgE, also serology to check for some infectious diseases, such as cytomegalovirosis, infectious mononucleosis, parvovirosis, hepatitis B and C <a class="elsevierStyleCrossRefs" href="#bb0065"><span class="elsevierStyleSup">13,14</span></a>.</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Diagnostic tests</span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Skin testing</span><p id="p0135" class="elsevierStylePara elsevierViewall">The diagnostic value of skin tests varies depending on the drug involved in the reaction. They should be done 4 to 6<span class="elsevierStyleHsp" style=""></span>weeks after the reaction is resolved <a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a>. Their sensitivity and predictive value are considered to be very good for penicillin, myorelaxant, heterologous sera, enzymes; satisfactory for vaccines, hormones, opiates; and poor or unknown for local anaesthetics, sulphonamides, iodine radiocontrast media, non-steroidal anti-infl ammatory drugs, cephalosporin <a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a>. Skin testing for penicillin is the only test regularly used for diagnosis of drug allergy <a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a>. The majority of patients with negative results for major and minor determinants of penicillin will tolerate the drug without risk of a severe immediate reaction <a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a>.</p><p id="p0140" class="elsevierStylePara elsevierViewall">Penicillin is one of the most useful antimicrobial drugs <a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a>. A percentage of 20 % of patients admitted to a hospital refer to have allergy to the drug; however, most of these reports are unreliable <a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> and make the physicians prescribe alternative antibiotics, which in general are more expensive, can be associated with toxic effects, and can lead to antibiotic resistance <a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a>. Allergic reactions to penicillin are estimated to occur in 2 % of the patients treated with the drug and most of them are maculopapular or urticarial rashes <a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a>.</p><p id="p0145" class="elsevierStylePara elsevierViewall">Penicillin test should be performed in every patient with a background history of penicillin allergy who needs a therapy with antibiotics <a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a>. The risk of systemic reactions to penicillin skin tests is considered to be very low and may be related to incorrect dose of the drug and the lack of performing the prick test before the intradermal test <a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a>. It is important to remember that skin testing may give false-negative results for 1 to 2<span class="elsevierStyleHsp" style=""></span>weeks or even longer after an episode of anaphylaxis <a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a> (<a class="elsevierStyleCrossRef" href="#f0005">Fig. 1</a>).</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><p id="p0150" class="elsevierStylePara elsevierViewall">A clinical practice guideline for penicillin skin testing in patients who have a history of penicillin allergy does not increase the costs nor improve financial savings, instead, it increases the percentage of eligible patients for skin testing and, on the other hand, it reduces the necessity of alternative antibiotics <a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a>. It is necessary to take into account that the skin testing for penicillin is useful only for the diagnosis of IgE-mediated reactions to penicillins, not for delayed reactions such as Stevens-Johnson syndrome, or other reactions which are not IgE-mediated <a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a>. The penicillin skin test has a negative predictive value of 99 % and a positive predictive value of 50 % <a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a>, when it includes major and minor determinants of the drugs. Because minor determinants are not commercially available, some authors have suggested a dilution of penicillin G, to a concentration of 10,000 units/ml with 0.9 % sodium chloride <a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a>. However, the diluted solution should be freshly prepared <a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a>. Using benzyl penicilloyl as the major determinant, commercially named Pre-Pen, and diluted penicillin G, the negative predictive value of the test is 97 % <a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a>. Nonetheless, the Pre-Pen solution is nowadays unavailable commercially <a class="elsevierStyleCrossRefs" href="#bb0075"><span class="elsevierStyleSup">15,16</span></a>, which makes penicillin allergy diagnosis very difficult.</p><p id="p0155" class="elsevierStylePara elsevierViewall">Penicillin skin testing has been proposed to be performed by using lab made reagents. Sarti <a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a> has performed penicillin skin tests in 6,764 patients in an outpatient clinic, by employing fresh diluted penicillin G (PG) and hydrolysate penicillin as minor determinant mixtures (MDM). His data showed that only 96 patients presented positive results. None of the 6,668 patients with negative skin tests re-exposed to penicillin showed any immediate systemic reaction. According to the author, MDM correlates well with diluted penicillin G and can be employed for diagnosing patients susceptible to immediate severe reactions, such as oedema of the larynx and anaphylactic shock; although it could miss some accelerated reactions which are mainly caused by the major determinants. In our country, the Ministry of Health has adopted the mentioned schedule for penicillin drug allergy diagnosis <a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a>.</p><p id="p0160" class="elsevierStylePara elsevierViewall">The Center for Diseases Control <a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a> states that as no proven alternatives to penicillin are available for treating neurosyphilis, congenital syphilis or syphilis in pregnant women, it is recommended that if the major determinants are not available, patients with a history of immediate IgE-mediated reactions should be desensitised in a hospital service.</p><p id="p0165" class="elsevierStylePara elsevierViewall">In general, penicillin skin testing is useful for detecting any beta-lactam antibiotics <a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a>; however, it is important to note that penicillins share the beta-lactamic ring structure and the thiazolidine rings, but not necessarily the R side chains <a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a>. It is possible that the patient has non cross-reactive responses to various beta lactam antibiotics <a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a>.</p><p id="p0170" class="elsevierStylePara elsevierViewall">It is estimated that 50 % of patients who experienced immediate reactions to penicillin will have a negative skin test after 5<span class="elsevierStyleHsp" style=""></span>years, and 75–80 % will be negative at 10<span class="elsevierStyleHsp" style=""></span>years <a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a>. Nonetheless, penicillin is no longer considered the most commonly prescribed p-lactam <a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a>, therefore it is recommended to include other determinants in skin tests such as amoxicillin and cephalosporin <a class="elsevierStyleCrossRefs" href="#bb0120"><span class="elsevierStyleSup">24,25</span></a>. According to the data from Blanca et al. <a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a> in patients who suffered penicillin allergy adverse reactions after treatment, the drugs most involved in the reactions were amoxicillin (87.8 %), followed by benzopenicillin (8.1 %), ampicillin (2.7 %), and cloxacillin (1.3 %).</p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">In vitro IgE-RAST/CAP and ELISA testing</span><p id="p0175" class="elsevierStylePara elsevierViewall">The radioallergosorbent test (RAST), cellulose fluorescent assay-IgE (CAP-IgE) or enzyme-linked immunosorbent assay for detecting anti-drug IgE has variable specificity and sensitivity. For instance, a negative result does not exclude allergy to penicillin, as the assays detect only IgE to the major determinant; however, a positive result can indicate an increased risk for allergic reactions <a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a>. The specificity and sensitivity of the CAP-IgE for p-lactam are 85.7-100 % and 12.5-25.0 %, respectively, depending on the initial clinical manifestations <a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a>. The positive predictive values are considered to be high in severe clinical conditions, such as anaphylactic shock <a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a>. Therefore it could be useful in these situations if the skin test is negative, in order to avoid the necessity of drug provocation <a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a>. However, the sensitivity and specificity of the in vitro IgE antibodies test decrease more than one year after the allergy episode <a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a>.</p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Drug provocation test</span><p id="p0180" class="elsevierStylePara elsevierViewall">The drug provocation test is recommended to confirm drug hypersensitivity reactions by the European Network for Drug Allergy from the European Academy of Allergology and Clinical Immunology <a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a>. The test is cumbersome but can be considered as a reference test when skin tests are not available or not validated <a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0140"><span class="elsevierStyleSup">28</span></a>. It should be performed in cases of inconclusive or negative skin and/or CAP-IgE tests in patients with history of immediate drug allergy <a class="elsevierStyleCrossRef" href="#bb0145"><span class="elsevierStyleSup">29</span></a>. In most cases, the same route of administration in the clinical history is used, unless the oral form of the culprit drug is available <a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a>.</p><p id="p0185" class="elsevierStylePara elsevierViewall">Increasing doses of a suspected drug are given at 0.5 to 1-h intervals until the full age/weight-adjusted dose is achieved, and depending on the protocol, this procedure may take 1, 2 or more days <a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0140"><span class="elsevierStyleSup">28</span></a>. H1-antihistamines and p-blockers should be denied for 2 and 5<span class="elsevierStyleHsp" style=""></span>days, respectively, before the drug provocation test <a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a>. Placebo challenges may be necessary to avoid false positive reactions <a class="elsevierStyleCrossRef" href="#bb0145"><span class="elsevierStyleSup">29</span></a>. False negative results can occur and could be explained by cofactors such as exercise, sunlight, and tolerance induction <a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a>. Contraindications for the test are patients with severe comorbidities such as cardiac, hepatic, renal or other diseases and patients who had experienced severe life-threatening reactions as with Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis, drug reaction with eosinophilia and systemic symptoms (DRESS) <a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0150"><span class="elsevierStyleSup">30</span></a>.</p><p id="p0190" class="elsevierStylePara elsevierViewall">Drug provocation tests can reproduce the hypersensitivity reactions of the clinical episode, but they are in general milder and have a shorter duration <a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a>. Although they are dangerous procedures and potentially life-threatening, these tests are important to confirm drug hypersensitivity, and therefore non-hypersensitive patients would not need to avoid the related drugs in the future if the test were negative <a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a>.</p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Intradermal and patch tests for non-immediate allergy</span><p id="p0195" class="elsevierStylePara elsevierViewall">Intradermal and patch tests are recommended for the routine screening of patients with suspected non-immediate allergy <a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a>. The drug skin tests should be performed 6<span class="elsevierStyleHsp" style=""></span>weeks to 6<span class="elsevierStyleHsp" style=""></span>months after resolution of the drug reaction. Barbaud et al. <a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a> proposed a guideline for performing skin tests in order to standardise these procedures in cutaneous adverse drug reactions. According to the authors, skin testing should be performed with the commercialised drug whenever possible, and also with the pure active products and excipients. Systemic corticosteroid or immunosuppressive therapy must be interrupted for at least one month. For patients who have experienced severe reactions such as Stevens-Johnson syndrome, the drugs must be diluted first at 0.1 %; if negative then at 1.0 %; and if negative up to 10 % in patch tests <a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a>. The intradermal tests are contraindicated in these patients. Healthy volunteers with or without previous exposure to the drug can be used as negative controls. The highest frequency of positive drug patches are related to p lactam antibiotics, especially amoxicillin; cotrimoxazole; corticosteroids; heparin derivatives; carbamazepine; diazepam; and pseudoephedrine <a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a>. Delayed positive results in intradermal tests can be obtained in maculopapular rash, eczema, erythroderma or fixed drug reactions. The threshold of specificity has been determined for various drugs, such as p lactam antibiotics, erythromycin and spyramicin, and needs to be determined for other drugs, because of the risk of false positives in intradermal tests <a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a>.</p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Basophil activation test</span><p id="p0200" class="elsevierStylePara elsevierViewall">The CD63 molecule was discovered in the 1990s and since then it has been used as a basophil activation marker in flow cytometry. The technique, which is named basophil activation test (BAT), relies upon anti-IgE to characterize basophiles and anti-CD63 to assess activation of these cells <a class="elsevierStyleCrossRefs" href="#bb0155"><span class="elsevierStyleSup">31,32</span></a>. The molecule is expressed by different types of cells, e.g. basophiles, mast cells, macrophages and platelets. In the resting cells, CD63 is anchored in the basophilic granule and weakly expressed on the surface membrane; upon activation, its expression is upregulated, besides other molecules, such as CD45, CD203c <a class="elsevierStyleCrossRef" href="#bb0155"><span class="elsevierStyleSup">31</span></a>.The BAT test allows the diagnosis of immediate drug allergy and pseudoallergy mainly for drugs that are not always detectable by CAP-IgE <a class="elsevierStyleCrossRef" href="#bb0165"><span class="elsevierStyleSup">33</span></a>. The BAT test is more sensitive and specific than other in vitro diagnostic techniques in drug allergy <a class="elsevierStyleCrossRef" href="#bb0165"><span class="elsevierStyleSup">33</span></a>, and is essentially complementary to skin tests and allergen-specific IgE determinations <a class="elsevierStyleCrossRef" href="#bb0170"><span class="elsevierStyleSup">34</span></a>.</p><p id="p0205" class="elsevierStylePara elsevierViewall">This technique has been proven to be a useful tool for assessment of the diagnosis of IgE-mediated allergies, including drug allergy <a class="elsevierStyleCrossRef" href="#bb0165"><span class="elsevierStyleSup">33</span></a>. The upregulation of CD63 and CD203c has been observed in tests for pollen, food, drugs, natural rubber latex, and recombinant pollen allergens <a class="elsevierStyleCrossRef" href="#bb0155"><span class="elsevierStyleSup">31</span></a>. Nevertheless, it suffers from some drawbacks. It depends on various factors, such as temperature, incubation time, a diluting buffer, type of allergen, and a positive control as anti-IgE <a class="elsevierStyleCrossRef" href="#bb0155"><span class="elsevierStyleSup">31</span></a>. The density of IgE and IgE receptors may vary considerably among individuals and also among basophiles from the same individual. This may play a negative role, particularly in nonatopic individuals and when the number of activated basophiles is low <a class="elsevierStyleCrossRef" href="#bb0170"><span class="elsevierStyleSup">34</span></a>. The necessity of anti-IgE as a positive control in CD63 testing is considered to be an important drawback, once some patients are non-responders; also, the results might be influenced by the intake of drugs, such as glucocorticosteroids, immunossuppressives, and immunomodulators <a class="elsevierStyleCrossRef" href="#bb0155"><span class="elsevierStyleSup">31</span></a>. Moreover, IL-3 may be necessary for the priming of basophiles without up-regulating the activation markers, since in drug allergy it can occur that the drugs <span class="elsevierStyleItalic">per se</span> induce a low rate of basophil activation in the test <a class="elsevierStyleCrossRef" href="#bb0175"><span class="elsevierStyleSup">35</span></a>.</p><p id="p0210" class="elsevierStylePara elsevierViewall">Other alternative means of detecting basophiles have recently been identified, such as the CD203c marker, a neural cell surface differentiation antigen E-NPP3 (ectonucleotide pyrophosphatase/phosphodiesterase), which is exclusively present on basophiles among blood cells, mast cells and progenitors. The CD 203c marker is upregulated in response to allergen-specific and anti-IgE-induced IgE cross-linking similar to CD63 <a class="elsevierStyleCrossRef" href="#bb0160"><span class="elsevierStyleSup">32</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0170"><span class="elsevierStyleSup">34</span></a> and can be applied in flow-assisted allergy diagnosis to improve the sensitivity of the BAT technique, but multi-centre studies are necessary in order to make the technique useful for clinical routine <a class="elsevierStyleCrossRef" href="#bb0175"><span class="elsevierStyleSup">35</span></a>.</p><p id="p0215" class="elsevierStylePara elsevierViewall">In a study evaluating immediate reactions to p-lactam, the sensitivity of the BAT test was 50 % and its specificity 94 % <a class="elsevierStyleCrossRef" href="#bb0180"><span class="elsevierStyleSup">36</span></a>. Torres et al. <a class="elsevierStyleCrossRef" href="#bb0185"><span class="elsevierStyleSup">37</span></a> also assessing reactions to these antibiotics, found similar results to BAT with a sensitivity of 48.6 % and specificity of 93 %; moreover, the BAT for cephalosporin was positive in 77 % of the patients, indicating that this test seems to be very promising for cephalosporin allergy. Nonetheless, studies in larger samples are required in order to validate the technique <a class="elsevierStyleCrossRef" href="#bb0190"><span class="elsevierStyleSup">38</span></a>.</p><p id="p0220" class="elsevierStylePara elsevierViewall">Gamboa et al. <a class="elsevierStyleCrossRef" href="#bb0195"><span class="elsevierStyleSup">39</span></a> found a specificity of 90 % and sensitivity of 60 % to 70 % in BAT for non-steroidal anti-inflammatory drugs (NSAIDs). The results with BAT are suggestive that when it is positive there would be no need to perform the provocation test. However, Malbran et al. <a class="elsevierStyleCrossRef" href="#bb0200"><span class="elsevierStyleSup">40</span></a> showed that diclofenac activates basophiles in sensitive individuals in a way that does not induce CD63 expression, suggesting that the BAT test may not be reliable for NSAID hypersensitivity.</p></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Lymphocyte transformation test</span><p id="p0225" class="elsevierStylePara elsevierViewall">The lymphocyte transformation test (LTT) is a test that assesses drug-specific T cells activation after in vitro stimulation with various concentrations of the culprit drug <a class="elsevierStyleCrossRef" href="#bb0205"><span class="elsevierStyleSup">41</span></a>. It has several advantages as it is not harmful for the patient; it can be positive in drug reactions caused by different immunopathogenic mechanisms <a class="elsevierStyleCrossRef" href="#bb0210"><span class="elsevierStyleSup">42</span></a>. Although it is thought to be a reliable test <a class="elsevierStyleCrossRef" href="#bb0205"><span class="elsevierStyleSup">41</span></a>, it has been considered more as a research tool than for diagnostic purposes <a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a>. There are several variables which can influence its performance: time of testing; influence of therapy as corticosteroids; stimulation index; reproducibility; sensitivity; and specificity <a class="elsevierStyleCrossRefs" href="#bb0205"><span class="elsevierStyleSup">41,42</span></a>. According to Kano et al. <a class="elsevierStyleCrossRef" href="#bb0205"><span class="elsevierStyleSup">41</span></a>, the right time to perform the test depends on the type of reactions, within one week from the onset of the skin rashes in patients with maculopapular exanthema or Stevens-Johnson syndrome/toxic epidermal necrolysis, and 5 to 8<span class="elsevierStyleHsp" style=""></span>weeks after the onset of skin rashes in patients with drug-induced hypersensitivity syndrome/drug rash and eosinophilia with systemic symptoms.</p></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">Detection of cytokines as IL-5</span><p id="p0230" class="elsevierStylePara elsevierViewall">The IL-5 secretion cells can be analysed in vitro in culture supernatants from LTT after activation with specific drugs, and improve LTT sensitivity <a class="elsevierStyleCrossRef" href="#bb0215"><span class="elsevierStyleSup">43</span></a>. According to Sachs et al. <a class="elsevierStyleCrossRef" href="#bb0220"><span class="elsevierStyleSup">44</span></a> the determination of drug-specific IL-5 secretion was more sensitive (92 %) than the LTT (75 %) and patch test (55 %) in patients with drug-induced maculopapular exanthemas. As Th1 and Th2 patterns occur together or not in drug allergy, and as IL-5 is a representative of the Th2 profile, the tests should include the determination of a cytokine representative of the Th1 pattern, as IFNγ.</p></span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">Markers of T cell activation such as CD69</span><p id="p0235" class="elsevierStylePara elsevierViewall">Considering the several disadvantages of LTT, as mentioned above, the detection of surface markers, such as CD69 and CD25, which upregulate upon T cell activation after contact with a specific antigen, peptide or drug, can also be a promising alternative for diagnostic purposes <a class="elsevierStyleCrossRef" href="#bb0150"><span class="elsevierStyleSup">30</span></a>. The test consists in culturing peripheral mononuclear cells with nontoxic concentrations of the culprit drug for 36 to 72<span class="elsevierStyleHsp" style=""></span>h and submitting them to flow cytometry after the addition of fluorochrome-labelled anti-human CD69 monoclonal antibodies <a class="elsevierStyleCrossRef" href="#bb0150"><span class="elsevierStyleSup">30</span></a>.</p><p id="p0240" class="elsevierStylePara elsevierViewall">Beeler et al. <a class="elsevierStyleCrossRef" href="#bb0150"><span class="elsevierStyleSup">30</span></a> evaluating 15 drug-allergic, LTT positive patients, found a CD69 upregulation in both TCD4 cells and TCD8 cells after drug stimulation, except when the cells were cultivated with clavulanic acid, which induced an increase of CD4 T cells only. The test has shown a high specificity since non-allergic individuals showed no increase of CD69 detection of T cells cultivated with drugs. However, the authors demonstrated that clavulanic acid could induce CD69 upregulation without proliferation of non-allergic cells and that vancomycin promoted the proliferation of non-allergic cells without CD69 upregulation. Therefore, the authors <a class="elsevierStyleCrossRef" href="#bb0150"><span class="elsevierStyleSup">30</span></a> strongly suggest the necessity of an assay evaluation for every drug to be tested in non-allergic individuals.</p></span></span></span><span id="s0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Conclusion</span><p id="p0245" class="elsevierStylePara elsevierViewall">The development of new tests and the validation of already developed techniques have been contributing enormously in the diagnosis of drug allergy. The diagnostic tests, together with a carefully detailed clinical history of the patient, physical examination and routine laboratorial parameters, are critical to identify the culprit drug, for the hypersensitivity drug reaction classification, and finally for taking a decision upon the treatment of patients.</p><span id="s0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Conflict of interest</span><p id="p0250" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare.</p></span></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:2 [ "identificador" => "xres86273" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec74400" "titulo" => "KEYWORDS" ] 2 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "s0010" "titulo" => "Diagnosis" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "s0015" "titulo" => "Clinical history investigation" ] 1 => array:3 [ "identificador" => "s0020" "titulo" => "Diagnostic tests" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "s0025" "titulo" => "Skin testing" ] 1 => array:2 [ "identificador" => "s0030" "titulo" => "In vitro IgE-RAST/CAP and ELISA testing" ] 2 => array:2 [ "identificador" => "s0035" "titulo" => "Drug provocation test" ] 3 => array:2 [ "identificador" => "s0040" "titulo" => "Intradermal and patch tests for non-immediate allergy" ] 4 => array:2 [ "identificador" => "s0045" "titulo" => "Basophil activation test" ] 5 => array:2 [ "identificador" => "s0050" "titulo" => "Lymphocyte transformation test" ] 6 => array:2 [ "identificador" => "s0055" "titulo" => "Detection of cytokines as IL-5" ] 7 => array:2 [ "identificador" => "s0060" "titulo" => "Markers of T cell activation such as CD69" ] ] ] ] ] 4 => array:3 [ "identificador" => "s0065" "titulo" => "Conclusion" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "s0070" "titulo" => "Conflict of interest" ] ] ] 5 => array:2 [ "identificador" => "xack31955" "titulo" => "Acknowledgement" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "KEYWORDS" "identificador" => "xpalclavsec74400" "palabras" => array:7 [ 0 => "Adverse drug reactions" 1 => "Diagnosis" 2 => "Drug allergy" 3 => "Hypersensitivity drug reactions" 4 => "Basophil activation test" 5 => "Lymphoproliferative tests" 6 => "Skin test" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "es" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">Drug allergy is a type B adverse drug reaction, which is unpredictable and difficult to prevent or manage. In patients who have a previous history of drug allergy it must be confirmed by laboratorial diagnosis. However, the diagnostic test remains a major problem in clinical practice. Skin testing is validated for some drugs, such as penicillin, but not for others. Provocation test is a confirmatory test but bears the risk of severe reactions. Lymphocyte transformation test is a reliable test but is considered as a research tool. This review addresses the most recent published literature regarding the techniques which have already been developed as well as the new tests that can be promising alternatives for diagnosis of drug allergy.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1398 "Ancho" => 2074 "Tamanyo" => 134948 ] ] "descripcion" => array:1 [ "es" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Representation of a clinical practice algorithm. Adapted from Forrest et al, 2001; Gruchalla and Pirmohamed, 2006.</p>" ] ] 1 => array:7 [ "identificador" => "t0005" "etiqueta" => "Table I" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Data adapted from 3,6-7. Vervloet and Durham, 1998; Hepner et al., 2003; Greenberg, 2006.</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=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Agents</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical manifestations \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Aspirin, non-steroidal anti-inflammatory drugs \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"><span class="elsevierStyleInlineFigure"><elsevierMultimedia class="elsevierStyleLink" ident="gr2"></elsevierMultimedia></span> \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">Asthma \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">Penicillin \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"><span class="elsevierStyleInlineFigure"><elsevierMultimedia class="elsevierStyleLink" ident="gr2"></elsevierMultimedia></span> \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, asthma, neutropenia, haemolytic anaemia \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">Antibiotics, muscle relaxants, natural rubber latex, hynotics \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"><span class="elsevierStyleInlineFigure"><elsevierMultimedia class="elsevierStyleLink" ident="gr2"></elsevierMultimedia></span> \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">Perioperative anaphylaxis \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">Anticonvulsivants, antibiotics, hydralazine, procainamide \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"><span class="elsevierStyleInlineFigure"><elsevierMultimedia class="elsevierStyleLink" ident="gr2"></elsevierMultimedia></span> \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">Serum sickness, drug fever, vasculitis, lymphadenopathy \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">Thalidomide \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"><span class="elsevierStyleInlineFigure"><elsevierMultimedia class="elsevierStyleLink" ident="gr2"></elsevierMultimedia></span> \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 rashes, Steven Johnson syndrome, toxic epidermal necrolysis \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">Infliximab, etanercept \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"><span class="elsevierStyleInlineFigure"><elsevierMultimedia class="elsevierStyleLink" ident="gr2"></elsevierMultimedia></span> \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">Anti-dsDNA antibodies, reversible systemic erythematosus lupus \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">Interferon alfa \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"><span class="elsevierStyleInlineFigure"><elsevierMultimedia class="elsevierStyleLink" ident="gr2"></elsevierMultimedia></span> \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, angioedema, anti-thyroid antibodies \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">Rituximab, alemtuzumab \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"><span class="elsevierStyleInlineFigure"><elsevierMultimedia class="elsevierStyleLink" ident="gr2"></elsevierMultimedia></span> \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">Dyspnoea, hypotension, urticaria \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">Sulphonamides, phenytoin \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"><span class="elsevierStyleInlineFigure"><elsevierMultimedia class="elsevierStyleLink" ident="gr2"></elsevierMultimedia></span> \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">Stevens Johnson syndrome \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">Vancomycin \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"><span class="elsevierStyleInlineFigure"><elsevierMultimedia class="elsevierStyleLink" ident="gr2"></elsevierMultimedia></span> \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">Bullous skin disease \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab165829.png" ] ] ] ] "descripcion" => array:1 [ "es" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Clinical manifestations of drug allergy</p>" ] ] 2 => array:7 [ "identificador" => "t0010" "etiqueta" => "Table II" "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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Topic \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Information \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="left" 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">The patient \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">Age, gender and brief medical history \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 \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">Adverse event \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">Description (nature, localisation, severity, characteristics), laboratorial parameters, start date, course and outcome \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 \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">Suspected drug(s) \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">Name (brand or ingredient name + manufacturer), dose, route, start/stop dates, indication for use (with particular drugs, e.g. vaccines, a batch number is important) \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">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">All other drugs used (including self-medication): \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">Names, doses, routes, start/stop dates \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">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">Risk factors \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">(e.g. impaired renal function, previous exposure to suspected drug, previous allergies, social drug use) \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">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">Name and address of reporter \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">(to be considered confidential and to be used only for data verification, completion and case follow-up) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab165828.png" ] ] ] ] "descripcion" => array:1 [ "es" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Reporting information for associating causal relationship between drug exposure and adverse events (UMC-WHO, 2000)</p>" ] ] 3 => array:7 [ "identificador" => "t0015" "etiqueta" => "Table III" "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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Causality term \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Assessment criteria* \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Certain \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"><ul class="elsevierStyleList" id="l0005"><li class="elsevierStyleListItem" id="u0005"><span class="elsevierStyleLabel">•</span><p id="p0005" class="elsevierStylePara elsevierViewall">Event of laboratory test abnormality, with plausible time relationship to drug intake</p></li><li class="elsevierStyleListItem" id="u0010"><span class="elsevierStyleLabel">•</span><p id="p0010" class="elsevierStylePara elsevierViewall">Cannot be explained by disease or other drugs</p></li><li class="elsevierStyleListItem" id="u0015"><span class="elsevierStyleLabel">•</span><p id="p0015" class="elsevierStylePara elsevierViewall">Response to withdrawal plausible (pharmacologically, pathologically)</p></li><li class="elsevierStyleListItem" id="u0020"><span class="elsevierStyleLabel">•</span><p id="p0020" class="elsevierStylePara elsevierViewall">Event definitive pharmacollogically or phenomenologically (i.e. an objective and specific medical idsorder or a recognised pharmacological phenomenon)</p></li><li class="elsevierStyleListItem" id="u0025"><span class="elsevierStyleLabel">•</span><p id="p0025" class="elsevierStylePara elsevierViewall">Rechallenge satisfactory, if necessary</p></li></ul> \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">Probable/likely \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"><ul class="elsevierStyleList" id="l0010"><li class="elsevierStyleListItem" id="u0030"><span class="elsevierStyleLabel">•</span><p id="p0030" class="elsevierStylePara elsevierViewall">Event of laboratory test abnormality, with reasonable time relationship to drug intake</p></li><li class="elsevierStyleListItem" id="u0035"><span class="elsevierStyleLabel">•</span><p id="p0035" class="elsevierStylePara elsevierViewall">Unlikely to be attributed to disease or ohter drugs</p></li><li class="elsevierStyleListItem" id="u0040"><span class="elsevierStyleLabel">•</span><p id="p0040" class="elsevierStylePara elsevierViewall">Response to withdrawal clinically reasonable</p></li><li class="elsevierStyleListItem" id="u0045"><span class="elsevierStyleLabel">•</span><p id="p0045" class="elsevierStylePara elsevierViewall">Rechallenge not required</p></li></ul> \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">Possible \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"><ul class="elsevierStyleList" id="l0015"><li class="elsevierStyleListItem" id="u0050"><span class="elsevierStyleLabel">•</span><p id="p0050" class="elsevierStylePara elsevierViewall">Event of laboratory test abnormality, with reasonable time relationship to drug intake</p></li><li class="elsevierStyleListItem" id="u0055"><span class="elsevierStyleLabel">•</span><p id="p0055" class="elsevierStylePara elsevierViewall">Could also be explained by disease or other drugs</p></li><li class="elsevierStyleListItem" id="u0060"><span class="elsevierStyleLabel">•</span><p id="p0060" class="elsevierStylePara elsevierViewall">Information on drug withdrawal may be lacking or unclear</p></li></ul> \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">Unlikey \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"><ul class="elsevierStyleList" id="l0020"><li class="elsevierStyleListItem" id="u0065"><span class="elsevierStyleLabel">•</span><p id="p0065" class="elsevierStylePara elsevierViewall">Event of laboratory test abnormality, with a time to drug intake that makes a relationship improbable (but not impossible)</p></li><li class="elsevierStyleListItem" id="u0070"><span class="elsevierStyleLabel">•</span><p id="p0070" class="elsevierStylePara elsevierViewall">Disease or ohter drugs provide plausible explanations</p></li></ul> \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">Conditional/unclassified \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"><ul class="elsevierStyleList" id="l0025"><li class="elsevierStyleListItem" id="u0075"><span class="elsevierStyleLabel">•</span><p id="p0075" class="elsevierStylePara elsevierViewall">Event of laboratory test abnormality</p></li><li class="elsevierStyleListItem" id="u0080"><span class="elsevierStyleLabel">•</span><p id="p0080" class="elsevierStylePara elsevierViewall">More data for proper assessment neeeded, or</p></li><li class="elsevierStyleListItem" id="u0085"><span class="elsevierStyleLabel">•</span><p id="p0085" class="elsevierStylePara elsevierViewall">Additional data under examination</p></li></ul> \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">Unassessable/unclassifiable \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"><ul class="elsevierStyleList" id="l0030"><li class="elsevierStyleListItem" id="u0090"><span class="elsevierStyleLabel">•</span><p id="p0090" class="elsevierStylePara elsevierViewall">Report suggesting an adverse reaction</p></li><li class="elsevierStyleListItem" id="u0095"><span class="elsevierStyleLabel">•</span><p id="p0095" class="elsevierStylePara elsevierViewall">Cannot be judged because information is insufficient or contradictory</p></li><li class="elsevierStyleListItem" id="u0100"><span class="elsevierStyleLabel">•</span><p id="p0100" class="elsevierStylePara elsevierViewall">Data cannot be supplemented or verified</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab165830.png" ] ] ] ] "descripcion" => array:1 [ "es" => "<p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">Assessment criteria for determining causality categories for drug adverse reactions<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a> (The UMC/Who, 2000)</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:44 [ 0 => array:3 [ "identificador" => "bb0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Introduction of a practice guideline for penicillin skin testing improves the appropriateness of antibiotic therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D.M. Forrest" 1 => "R.R. Schellenberg" 2 => "V.V.S. Thien" 3 => "S. King" 4 => "A.H. Anis" 5 => "P.M. Dodek" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "CID" "fecha" => "2001" "volumen" => "32" "paginaInicial" => "1685" "paginaFinal" => "1690" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bb0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of hypersensitivity drug reactions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E.R. Gomes" 1 => "P. Demoly" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Curr Opin Allergy Clin Immunol" "fecha" => "2005" "volumen" => "5" "paginaInicial" => "309" "paginaFinal" => "316" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15985812" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bb0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drug allergy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P.A. Greenberg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaci.2005.11.002" "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2006" "volumen" => "117" "paginaInicial" => "S464" "paginaFinal" => "S470" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16455348" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bb0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adverse drug reactions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.W. Bates" 1 => "L. Leape" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:5 [ "titulo" => "Clinical pharmacology: Basic principles in therapeutics" "paginaInicial" => "1223" "paginaFinal" => "1254" "edicion" => "4th ed." "serieFecha" => "2000" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bb0025" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anaphylactic reactions – value of skin and provocation tests" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P. Demoly" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.tox.2004.12.027" "Revista" => array:6 [ "tituloSerie" => "Toxicology" "fecha" => "2005" "volumen" => "209" "paginaInicial" => "221" "paginaFinal" => "223" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15767040" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bb0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ABC of allergies: adverse reactions to drugs" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D. Vervloet" 1 => "S. Durham" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "BMJ" "fecha" => "1998" "volumen" => "316" "paginaInicial" => "1511" "paginaFinal" => "1514" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9582146" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bb0035" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anaphylaxis during the perioperative period" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.L. Hepner" 1 => "M.C. Castells" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Anesth Analg" "fecha" => "2003" "volumen" => "97" "paginaInicial" => "1381" "paginaFinal" => "1395" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14570656" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bb0040" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pathogenesis of drug-induced exanthems" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "W. Pichler" 1 => "N. Yawalkar" 2 => "S. Schmid" 3 => "A. Helbling" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Allergy" "fecha" => "2002" "volumen" => "57" "paginaInicial" => "884" "paginaFinal" => "893" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12269933" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bb0045" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Penicillin allergy: considering trying penicillin again" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.E. Arroliga" 1 => "L. Pien" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Cleveland Clin J Med" "fecha" => "2003" "volumen" => "70" "paginaInicial" => "313" "paginaFinal" => "326" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bb0050" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical presentation and time course in hypersensitivity reactions to β-lactams" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.J. Bousquet" 1 => "V. Kvedariene" 2 => "H.B. Co-Minh" 3 => "P. Martins" 4 => "M. Rongier" 5 => "B. Arnoux" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1398-9995.2007.01463.x" "Revista" => array:6 [ "tituloSerie" => "Allergy" "fecha" => "2007" "volumen" => "62" "paginaInicial" => "872" "paginaFinal" => "876" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17620063" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bb0055" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adverse reactions to oxacillin in hospitalized children: a prospective study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.O.B. Souza" 1 => "M.C.C. Araujo" 2 => "R.A. Santiago" 3 => "H.L.L. Coelho" 4 => "M.M.F. Fonteles" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Bras Saúde Matern. Infant" "fecha" => "2007" "volumen" => "7" "paginaInicial" => "55" "paginaFinal" => "61" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bb0060" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "The Uppsala Monitoring Centre (the UMC)/WHO Collaborating Centre for International Drug Monitoring. Safety monitoring of medicinal products: Guidelines for setting up and running a Pharmacovigilance Centre, Uppsala, Sweden, 2005, 25 pp." ] ] ] 12 => array:3 [ "identificador" => "bb0065" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guidelines for performing skin tests with drugs in the investigation of cutaneous adverse drug reactions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Barbaud" 1 => "M. Goncalo" 2 => "D. Bruynzeel" 3 => "A. Bircher" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Contact Dermatitis" "fecha" => "2001" "volumen" => "45" "paginaInicial" => "321" "paginaFinal" => "328" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11846746" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bb0070" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Annotations of the algorithm for disease management of drug hypersensitivity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "ACAAI" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Ann Allergy Asthma Immunol" "fecha" => "1999" "volumen" => "83" "paginaInicial" => "667" "paginaFinal" => "671" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bb0075" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antibiotic allergy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.S. Gruchalla" 1 => "M. Pirmohamed" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMcp043986" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2006" "volumen" => "354" "paginaInicial" => "601" "paginaFinal" => "609" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16467547" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bb0080" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis and management of penicillin allergy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.A. Park" 1 => "J.T.C. Li" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4065/80.3.405" "Revista" => array:6 [ "tituloSerie" => "Mayo Clin Proc" "fecha" => "2005" "volumen" => "80" "paginaInicial" => "405" "paginaFinal" => "410" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15757022" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bb0085" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacist-managed service providing penicillin allergy skin tests" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "G.C. Wall" 1 => "L. Peters" 2 => "C.B. Leaders" 3 => "J.A. Wille" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Health-Syst Pharm" "fecha" => "2004" "volumen" => "61" "paginaInicial" => "1271" "paginaFinal" => "1275" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15259758" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bb0090" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypersensitivity reactions to drugs: evaluation and management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G.M. Shepherd" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "The Mount Sinai J Med" "fecha" => "2003" "volumen" => "70" "paginaInicial" => "113" "paginaFinal" => "125" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bb0095" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Routine use of skin testing for immediate penicillin allergy to 6,764 patients in an outpatient clinic" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "W. Sarti" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Allergy" "fecha" => "1985" "volumen" => "55" "paginaInicial" => "157" "paginaFinal" => "161" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4025959" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bb0100" "etiqueta" => "20." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Brasil. Ministério da Saúde. Secretaria de Políticas de Saúde. Coordenação nacional de DST e Aids – Manual de teste de sensibilidade à penicilina. Brasília, 1999. <a class="elsevierStyleInterRef" href="http://www.aids.gov.br/testes_penicilina.pdf">http://www.aids.gov.br/testes_penicilina.pdf</a>." ] ] ] 20 => array:3 [ "identificador" => "bb0105" "etiqueta" => "21." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Center for Diseases Control. Management of patients who have a history of penicillin allergy. Sexually transmitted diseases treatment guideline. 2006. <a class="elsevierStyleInterRef" href="http://www.cdc.gov/std/treatment/2006/penicillin-allergy.htm">http://www.cdc.gov/std/treatment/2006/penicillin-allergy.htm</a>. access in 12/3/2007." ] ] ] 21 => array:3 [ "identificador" => "bb0110" "etiqueta" => "22." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drug allergy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R.S. Gruchalla" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2003" "volumen" => "111" "paginaInicial" => "S548" "paginaFinal" => "S559" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12592301" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bb0115" "etiqueta" => "23." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Non-immediate reactions to b-lactams: diagnostic value of skin testing and drug provocation test" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Padial" 1 => "C. Antunez" 2 => "N. Blanca-Lopez" 3 => "T.D. Fernandez" 4 => "J.A. Cornejo-Garcia" 5 => "C. Mayorga" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2222.2008.02961.x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Allergy" "fecha" => "2008" "volumen" => "38" "paginaInicial" => "822" "paginaFinal" => "828" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18331363" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bb0120" "etiqueta" => "24." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical evaluation of Pharmacia CAP system RAST FEIA amoxicilloyl and benzylpenicilloyl in patients with penicillin allergy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Blanca" 1 => "C. Mayorga" 2 => "M.J. Torres" 3 => "M. Roche" 4 => "M.C. Moya" 5 => "J.L. Rodriguez" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Allergy" "fecha" => "2001" "volumen" => "56" "paginaInicial" => "862" "paginaFinal" => "870" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11551251" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bb0125" "etiqueta" => "25." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.J. Torres" 1 => "A. Romano" 2 => "C. Mayorga" 3 => "M.C. Moya" 4 => "A.E. Guzman" 5 => "M. Reche" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Allergy" "fecha" => "2001" "volumen" => "56" "paginaInicial" => "850" "paginaFinal" => "856" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11551249" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0015028200017088" "estado" => "S300" "issn" => "00150282" ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bb0130" "etiqueta" => "26." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "evance of the determination of serum specific IgE antibodies in the diagnosis of immediate β-lactam allergy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Fontaine" 1 => "C. Mayorga" 2 => "P.J. Bousquet" 3 => "B. Arnoux" 4 => "M.J. Torres" 5 => "M. Blanca" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Allergy" "fecha" => "2007" "volumen" => "62" "paginaInicial" => "47" "paginaFinal" => "52" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23470425" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bb0135" "etiqueta" => "27." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drug provocation tests in patients with a history suggesting an immediate drug hypersensitivity reaction" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D. Messaad" 1 => "H. Sahia" 2 => "S. Benahmed" 3 => "P. Godard" 4 => "J. Bousquet" 5 => "P. Demoly" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2004" "volumen" => "140" "paginaInicial" => "1001" "paginaFinal" => "1006" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15197017" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bb0140" "etiqueta" => "28." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drug allergy claims in children: from self-reporting to confirmed diagnosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "E.R. Gomes" 1 => "J. Fonseca" 2 => "L. Araujo" 3 => "P. Demoly" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2222.2007.02870.x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Allergy" "fecha" => "2007" "volumen" => "38" "paginaInicial" => "191" "paginaFinal" => "198" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18028465" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bb0145" "etiqueta" => "29." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Patients with drug reactions – is it worth testing?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. Wöhrl" 1 => "K. Vigl" 2 => "G. Sting" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1398-9995.2006.01148.x" "Revista" => array:6 [ "tituloSerie" => "Allergy" "fecha" => "2006" "volumen" => "61" "paginaInicial" => "928" "paginaFinal" => "934" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16867044" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bb0150" "etiqueta" => "30." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CD69 upregulation on T cells as an in vitro marker for delayed-type drug hypersensitivity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Beeler" 1 => "L. Zaccaria" 2 => "T. Kawabata" 3 => "B.O. Gerber" 4 => "W.J. Pichler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1398-9995.2007.01516.x" "Revista" => array:6 [ "tituloSerie" => "Allergy" "fecha" => "2008" "volumen" => "63" "paginaInicial" => "181" "paginaFinal" => "188" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18005225" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bb0155" "etiqueta" => "31." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "In vitro allergy diagnosis: should we follow the flow?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D.G. Ebo" 1 => "M.M. Hagendorens" 2 => "C.H. Bridts" 3 => "A.J. Schuerwegh" 4 => "L.S. de Clerk" 5 => "W.J. Stevens" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Exp Allergy" "fecha" => "2004" "volumen" => "34" "paginaInicial" => "332" "paginaFinal" => "339" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15005724" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bb0160" "etiqueta" => "32." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Flow-assisted allergy diagnosis: current applications and future perspectives" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.G. Ebo" 1 => "J. Sainte-Laudy" 2 => "C.H. Bridts" 3 => "C.H. Mertens" 4 => "M.M. Hagendorens" 5 => "A.J. Schuerwegh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1398-9995.2006.01039.x" "Revista" => array:6 [ "tituloSerie" => "Allergy" "fecha" => "2006" "volumen" => "61" "paginaInicial" => "1028" "paginaFinal" => "1039" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16918504" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bb0165" "etiqueta" => "33." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cellular tests in the diagnosis of drug hypersensitivity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.L. Sanz" 1 => "P.M. Gamboa" 2 => "A.L. de Weck" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Curr Pharm Design" "fecha" => "2008" "volumen" => "14" "paginaInicial" => "2803" "paginaFinal" => "2808" ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bb0170" "etiqueta" => "34." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnostic tests based on human basophils: more potencials and perspectives than pitfalls. II. Technical issues" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.L. De Weck" 1 => "M.L. Sanz" 2 => "P.M. Gamboa" 3 => "W. Aberer" 4 => "J. Bienvenu" 5 => "M. Blanca" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Investig Allergol Clin Immunol" "fecha" => "2008" "volumen" => "18" "paginaInicial" => "143" "paginaFinal" => "155" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18564624" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bb0175" "etiqueta" => "35." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "In vitro allergy diagnosis: should we follow the flow?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:11 [ 0 => "S.M. Erdmann" 1 => "B. Sachs" 2 => "K. Hoffmann-Sommergruber" 3 => "O. Scheiner" 4 => "H. Merk" 5 => "D.G. Regarding Ebo" 6 => "M.M. Hagendorens" 7 => "C.H. Bridts" 8 => "A.J. Schuerwegh" 9 => "L.S. De Clerck" 10 => "W.J. Stevens" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Exp Allergy" "fecha" => "2004" "volumen" => "34" "paginaInicial" => "332" "paginaFinal" => "339" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15005724" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bb0180" "etiqueta" => "36." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Flow cytometric basophil activation test by detection of CD63 expression in patients with immediate-type reactions to betalactam antibiotics" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.L. Sanz" 1 => "P.M. Gamboa" 2 => "I. Antépara" 3 => "C. Uasuf" 4 => "L. Vila" 5 => "C. Garcia-Avilés" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Exp Allergy" "fecha" => "2002" "volumen" => "32" "paginaInicial" => "277" "paginaFinal" => "286" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11929494" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bb0185" "etiqueta" => "37." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The diagnostic interpretation of basophil activation test in immediate allergic reactions to betalactams" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.J. Torres" 1 => "A. Padial" 2 => "C. Mayorga" 3 => "T. Fernández" 4 => "E. Sanchez-Sabate" 5 => "J.A. Cornejo-Garcia" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2222.2004.02110.x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Allergy" "fecha" => "2004" "volumen" => "34" "paginaInicial" => "1768" "paginaFinal" => "1775" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15544603" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bb0190" "etiqueta" => "38." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recent advances in the diagnosis of drug allergy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Romano" 1 => "P. Demoly" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/ACI.0b013e328216f4d4" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Allergy Clin Immunol" "fecha" => "2007" "volumen" => "7" "paginaInicial" => "299" "paginaFinal" => "303" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17620820" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bb0195" "etiqueta" => "39." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The flow-cytometric determination of basophil activation induced by aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) is useful for in vitro diagnosis of the NSAID hypersensitivity syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Gamboa" 1 => "M.L. Sanz" 2 => "M.R. Caballero" 3 => "I. Urrutia" 4 => "I. Antépara" 5 => "R. Esparza" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2222.2004.02050.x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Allergy" "fecha" => "2004" "volumen" => "34" "paginaInicial" => "1448" "paginaFinal" => "1457" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15347380" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bb0200" "etiqueta" => "40." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diclofenac induces basophil degranulation without increasing CD63 expression in sensitive patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Malbran" 1 => "E. Yeyati" 2 => "G.L. Rey" 3 => "N. Galassi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Exp Allergy" "fecha" => "2006" "volumen" => "147" "paginaInicial" => "99" "paginaFinal" => "105" ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bb0205" "etiqueta" => "41." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Utility of the lymphocyte transformation test in the diagnosis of drug sensitivity: dependence on its timing and the type of drug eruption" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Y. Kano" 1 => "K. Hirahara" 2 => "Y. Mitsuyama" 3 => "R. Takahashi" 4 => "T. Shiohara" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1398-9995.2007.01553.x" "Revista" => array:6 [ "tituloSerie" => "Allergy" "fecha" => "2007" "volumen" => "62" "paginaInicial" => "1439" "paginaFinal" => "1444" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17983378" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bb0210" "etiqueta" => "42." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The lymphocyte transformation test in the diagnosis of drug hypersensitivity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "W.J. Pichler" 1 => "J. Tilch" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1398-9995.2004.00547.x" "Revista" => array:6 [ "tituloSerie" => "Allergy" "fecha" => "2004" "volumen" => "59" "paginaInicial" => "809" "paginaFinal" => "820" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15230812" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bb0215" "etiqueta" => "43." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis of drug hypersensitivity: lymphocyte transformation test and cytokines" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "H.F. Merck" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.tox.2004.12.026" "Revista" => array:6 [ "tituloSerie" => "Toxicology" "fecha" => "2005" "volumen" => "209" "paginaInicial" => "217" "paginaFinal" => "220" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15767039" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bb0220" "etiqueta" => "44." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Determination of interleukin-5 secretion from drug-specific activated ex vivo peripheral blood mononuclear cells as a test system for the in vitro detection of drug sensitization" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "B. Sachs" 1 => "S. Erdmann" 2 => "J. Malte Baron" 3 => "M. Neis" 4 => "T. al MasaoudI" 5 => "H.F. Merk" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Exp Allergy" "fecha" => "2002" "volumen" => "32" "paginaInicial" => "736" "paginaFinal" => "744" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11994099" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:3 [ "identificador" => "xack31955" "titulo" => "Acknowledgement" "texto" => "<p id="p0255" class="elsevierStylePara elsevierViewall">This article is part of a project entitled “Incidence evaluation of allergy hypersensitivity reactions to beta-lactamics through laboratorial investigation of patients exposed to the drug”, sponsored by MCT/CNPq/MS-SCTIEDECIT-DAF 54/2005, process 402509/2005-6.</p>" ] ] ] "idiomaDefecto" => "es" "url" => "/03010546/0000003700000002/v1_201304101125/S0301054609711127/v1_201304101125/es/main.assets" "Apartado" => array:4 [ "identificador" => "5555" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Review" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03010546/0000003700000002/v1_201304101125/S0301054609711127/v1_201304101125/es/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054609711127?idApp=UINPBA00004N" ]
