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array:23 [ "pii" => "S0301054613000037" "issn" => "03010546" "doi" => "10.1016/j.aller.2012.11.001" "estado" => "S300" "fechaPublicacion" => "2014-01-01" "aid" => "475" "copyright" => "SEICAP" "copyrightAnyo" => "2012" "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "cor" "cita" => "Allergol Immunopathol (Madr). 2014;42:78-80" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1354 "formatos" => array:3 [ "EPUB" => 10 "HTML" => 844 "PDF" => 500 ] ] "itemSiguiente" => array:18 [ "pii" => "S030105461200300X" "issn" => "03010546" "doi" => "10.1016/j.aller.2012.07.017" "estado" => "S300" "fechaPublicacion" => "2014-01-01" "aid" => "469" "copyright" => "SEICAP" "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "cor" "cita" => "Allergol Immunopathol (Madr). 2014;42:80-2" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1400 "formatos" => array:3 [ "EPUB" => 15 "HTML" => 914 "PDF" => 471 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Research letter</span>" "titulo" => "Occupational airborne contact dermatitis caused by usnic acid in a domestic worker" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "80" "paginaFinal" => "82" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 669 "Ancho" => 900 "Tamanyo" => 83769 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Positivity to usnic acid, after UVA irradiation with 5<span class="elsevierStyleHsp" style=""></span>J/cm<span class="elsevierStyleSup">2</span>.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "D. Pacheco, A.R. Travassos, J. Antunes, L. Soares de Almeida, P. Filipe, T. Correia" "autores" => array:6 [ 0 => array:2 [ "nombre" => "D." "apellidos" => "Pacheco" ] 1 => array:2 [ "nombre" => "A.R." "apellidos" => "Travassos" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Antunes" ] 3 => array:2 [ "nombre" => "L." "apellidos" => "Soares de Almeida" ] 4 => array:2 [ "nombre" => "P." "apellidos" => "Filipe" ] 5 => array:2 [ "nombre" => "T." "apellidos" => "Correia" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S030105461200300X?idApp=UINPBA00004N" "url" => "/03010546/0000004200000001/v1_201402140100/S030105461200300X/v1_201402140100/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0301054613001560" "issn" => "03010546" "doi" => "10.1016/j.aller.2013.03.010" "estado" => "S300" "fechaPublicacion" => "2014-01-01" "aid" => "530" "copyright" => "SEICAP" "documento" => "article" "crossmark" => 0 "subdocumento" => "rev" "cita" => "Allergol Immunopathol (Madr). 2014;42:69-77" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 5188 "formatos" => array:3 [ "EPUB" => 10 "HTML" => 4199 "PDF" => 979 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Modulation of gut microbiota downregulates the development of food allergy in infancy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "69" "paginaFinal" => "77" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1289 "Ancho" => 2151 "Tamanyo" => 113813 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Succession of gut microbiota.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "S. Tsabouri, K.N. Priftis, N. Chaliasos, A. Siamopoulou" "autores" => array:4 [ 0 => array:2 [ "nombre" => "S." "apellidos" => "Tsabouri" ] 1 => array:2 [ "nombre" => "K.N." "apellidos" => "Priftis" ] 2 => array:2 [ "nombre" => "N." "apellidos" => "Chaliasos" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Siamopoulou" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054613001560?idApp=UINPBA00004N" "url" => "/03010546/0000004200000001/v1_201402140100/S0301054613001560/v1_201402140100/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Research letter</span>" "titulo" => "Successful treatment of severe delayed pressure angio-oedema with omalizumab" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">To the Editor</span>," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "78" "paginaFinal" => "80" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M. Rodríguez-Rodríguez, D. Antolin-Amerigo, J. Barbarroja-Escudero, M.J. Sánchez-González, M. Alvarez-Mon" "autores" => array:5 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Rodríguez-Rodríguez" "email" => array:1 [ 0 => "mercedesrr@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "D." "apellidos" => "Antolin-Amerigo" "email" => array:1 [ 0 => "dario.antolin@gmail.com" ] ] 2 => array:3 [ "nombre" => "J." "apellidos" => "Barbarroja-Escudero" "email" => array:1 [ 0 => "jose.barbarroja@uah.es" ] ] 3 => array:3 [ "nombre" => "M.J." "apellidos" => "Sánchez-González" "email" => array:1 [ 0 => "medicimj@yahoo.es" ] ] 4 => array:3 [ "nombre" => "M." "apellidos" => "Alvarez-Mon" "email" => array:1 [ 0 => "mademons@gmail.com" ] ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Servicio de Enfermedades del Sistema Inmune-Alergia, Hospital Principe de Asturias, Departamento de Medicina, Universidad de Alcalá, Hospital Universitario Príncipe de Asturias, Madrid, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 672 "Ancho" => 900 "Tamanyo" => 51536 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Pressure test was performed using a forearm sling with a 4<span class="elsevierStyleHsp" style=""></span>kg weight attached for 10<span class="elsevierStyleHsp" style=""></span>min and local forearm angio-oedema was observed 6<span class="elsevierStyleHsp" style=""></span>h after pressure had been applied.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Delayed pressure angio-oedema (DPA) is a very rare form of physical cutaneous disorder.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The symptoms typically occur 4 to 6<span class="elsevierStyleHsp" style=""></span>h after applying any type of pressure such as wearing tight clothing, hammering, walking or sitting down. Therapeutic management is complex and frustrating and the impairment of quality of life is very relevant. Omalizumab is a recombinant, humanised, monoclonal antibody directed towards Immunoglobulin E (IgE), approved as an option for the treatment of severe allergic asthma.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It has also been used in the treatment of other cutaneous diseases like atopic dermatitis, mastocytosis and chronic urticaria. We present a unique case of complete symptom relief from DPA 48<span class="elsevierStyleHsp" style=""></span>h after the first dose of omalizumab.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 45-year-old woman suffering from isolated delayed pressure angio-oedema without urticaria during the previous 11 years. At first, symptoms occasionally occurred after intensive and prolonged pressure on different body regions, afterwards those episodes appeared while performing daily activities, to such an extent as to alter and void the patient daily work activities as a highway cashier, as they appeared almost daily. She did not have hives in any of the episodes. Not immediate but delayed dermographism appeared; pressure test was positive. Pressure test was performed using a forearm sling with a 4<span class="elsevierStyleHsp" style=""></span>kg weight attached for 10<span class="elsevierStyleHsp" style=""></span>min, local forearm angio-oedema was observed 6<span class="elsevierStyleHsp" style=""></span>h after the pressure had been applied (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). This test was later reproduced in the same patient and was negative in two controls. The carried out study revealed an increased of total IgE of 600<span class="elsevierStyleHsp" style=""></span>UI/mL (<100<span class="elsevierStyleHsp" style=""></span>UI/mL). Skin-prick-testing was negative both against a common battery of aeroallergens and of foods. Moreover, the assessment included thorax X-rays, blood count and biochemistry, renal, hepatic and thyroid function analyses, stool parasite exam, hepatitis B and C serologies, Antinuclear-Antibody-Test, cryoagglutinins, complement (C3, C4, C1-inh, C1q), Immunoglobulins G, A, M. All the results were within the normal range or negative. Initially, symptoms became occasionally evident during moderate exercise and were controlled with antihistamines H1-blockers, but subsequently they increased their frequency until they disrupted her daily work activities, not achieving enough therapeutic response, although the patient was taking maximum daily doses of H1-blockers. Therefore, she required oral corticosteroids, firstly on a tapered basis and later on a daily basis (prednisone 5–25<span class="elsevierStyleHsp" style=""></span>mg/day). After three years of daily intake of corticosteroids, methotrexate (7.5<span class="elsevierStyleHsp" style=""></span>mg/week) was added to the former medication and attained total control of the symptoms just after 24<span class="elsevierStyleHsp" style=""></span>h of the first dose, the patient was able to discontinue the corticosteroids treatment. After five months of treatment, methotrexate had to be suspended due to hepatotoxicity and four months later we had to reintroduce oral corticosteroids. Two years later, despite taking daily corticosteroids treatment the patient showed an intense decrease of her Quality of Life, measured by Dermatology-Life-Questionnaire: 20 (0–30). Finally, omalizumab 300<span class="elsevierStyleHsp" style=""></span>mg fortnightly was initiated as an off-label therapy.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Patient's symptomatology disappeared 48<span class="elsevierStyleHsp" style=""></span>h after the first dose, letting us taper off oral corticosteroids until complete discontinuation. Our patient remained symptom-free for five months, while using omalizumab, the anti-IgE treatment was stopped after these five months. However, two months after the anti-IgE last dose extremely intense symptoms reappeared, eliciting delayed pressure angio-oedema, the patient required an increase on the dosage of prednisone up to 1<span class="elsevierStyleHsp" style=""></span>mg/kg/day without symptomatic control. Omalizumab was then reinstated at the same dose as had been used previously (300<span class="elsevierStyleHsp" style=""></span>mg fortnightly), due to the total IgE level maintenance. The patient's symptoms disappeared after six days of the reinstatement of omalizumab attaining total control of the symptoms which continues at present, so as to avoid corticosteroids intake. Nine months later she remained asymptomatic receiving monotherapy with omalizumab and we could prescribe it monthly, at a dose of 300<span class="elsevierStyleHsp" style=""></span>mg/month. We tried to increase the dose interval to five weeks, inducing symptoms relapse at the end of the fourth week, probably due to the 26-day half-life previously described for omalizumab<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>. Therefore we prescribed omalizumab at a fixed four-week interval showing effectiveness, as to maintain total symptomatic control.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Recently, the utility of omalizumab as a treatment for chronic urticaria has been described.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> There is a general consensus that, in chronic urticaria the underlying cause is never an allergy, despite the fact that high levels of total IgE and several autoallergic mechanisms have been identified and reported as autoimmune chronic urticaria.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Omalizumab has been used to treat both severe and antihistamine-resistant chronic urticaria. A total amount of 63 patients with chronic urticaria treated with omalizumab have been reported in the literature. Although several clinical trials have been developed demonstrating a satisfactory response to omalizumab, no studies have been performed with this drug to treat DPA.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> The former results have demonstrated that the use of omalizumab as a treatment for chronic urticaria, which seemed a promising therapeutic option, has become a recommended therapeutic option for those patients who do not achieve total control of their symptoms after using conventional treatments, as stated by the recent EAACI/GA<span class="elsevierStyleSup">2</span>LEN/WAO/EDF guidelines as fourth-line therapy.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">However, this has not happened to the same extent to angio-oedema, presumably due to the small number of patients reported in the literature.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> When conventional treatment included in current guidelines for angio-oedema management such as corticosteroids and antihistamines are not effective, some therapies, namely immunosuppressive agents (i.e. cyclosporine and methotrexate) are used.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Nevertheless, potential severe side effects shall arise due to the high doses of this drugs required and their long-term use. Cyclosporine has been used, showing no response. Non-responsive patients may require alternative therapies such as methotrexate, which elicited hepatotoxicity in our patient. Therefore, omalizumab constitutes a safer option and, on a long-term basis, and demonstrates cost-effectiveness for delayed pressure angio-oedema.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The unusual nature of this case of severe long standing delayed pressure angio-oedema, together with the exclusivity of its rapid and spectacular preliminary response to omalizumab, similar to that achieved with methotrexate, and the fast response after its reinstatement, following a cessation and severity relapse, reinforces the theory of immunomodulation beyond the presumed free-IgE blockage mechanism. Additional mechanisms of action which have been suggested for omalizumab are the reduction of expression of <span class="elsevierStyleItalic">Fc¿RI</span> on the surface of basophils and the prevention of the release of mast cell mediators<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,8</span></a> induction of eosinophil apoptosis and the downregulation of the inflammatory cytokines IL-2 and IL-13.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Moreover, a reduction in B-cell activation and homing and in TNF-α and IL-4 production has been proven as well as an increase in INF-γ synthesis and an enhancement of the activity in peripheral blood CD4+ by measurement of ATP release.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The aetiopathogenesis of DPA is still unclear and different mediators could play a significant role. The demonstrated and sustained efficacy of omalizumab in the treatment of DPA in our case suggests an immunomodulator mechanism that needs further observations. Omalizumab could be a valid, safe and an effective therapeutic option for patients suffering from DPA who do not respond to conventional treatment.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical disclosures</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patients’ data protection</span><p id="par0040" class="elsevierStylePara elsevierViewall">Confidentiality of Data. The authors declare that no patient data appears in this article.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Right to privacy and informed consent</span><p id="par0045" class="elsevierStylePara elsevierViewall">Right to privacy and informed consent. The authors declare that no patient data appears in this article.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Protection of human subjects and animals in research</span><p id="par0050" class="elsevierStylePara elsevierViewall">Protection of human and animal subjects. The authors declare that no experiments were performed on humans or animals for this investigation.</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Author's contribution</span><p id="par0055" class="elsevierStylePara elsevierViewall">MRR, JBE and DAA were involved in patient follow-up, pharmacologic advisory and data analysis.</p><p id="par0060" class="elsevierStylePara elsevierViewall">MRR, DAA, JBE, MJSG and MAMS were involved in patient follow-up and writing manuscript.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">There are no known conflicts of interest for the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:3 [ "identificador" => "sec0005" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Patients’ data protection" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Right to privacy and informed consent" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Protection of human subjects and animals in research" ] ] ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Author's contribution" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 672 "Ancho" => 900 "Tamanyo" => 51536 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Pressure test was performed using a forearm sling with a 4<span class="elsevierStyleHsp" style=""></span>kg weight attached for 10<span class="elsevierStyleHsp" style=""></span>min and local forearm angio-oedema was observed 6<span class="elsevierStyleHsp" style=""></span>h after pressure had been applied.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Urticaria and angioedema" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:1 [ 0 => "A.P. Kaplan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:5 [ "titulo" => "Middleton's allergy principles & practice" "paginaInicial" => "1071" "paginaFinal" => "1072" "edicion" => "7th ed." "serieFecha" => "2009" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Spotlight on omalizumab in allergic asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "L.M. Bang" 1 => "G.L. 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Vena" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1529-8019.2009.01268.x" "Revista" => array:7 [ "tituloSerie" => "Dermatol Ther" "fecha" => "2009" "volumen" => "22" "numero" => "Suppl. 1" "paginaInicial" => "S22" "paginaFinal" => "S26" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19891688" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatmen of chronic autoimmune urticaria with omalizumab" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.P. Kaplan" 1 => "K. Joseph" 2 => "R.J. Maykut" 3 => "G.P. Geba" 4 => "R.K. Zeldin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaci.2008.07.006" "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2008" "volumen" => "122" "paginaInicial" => "569" "paginaFinal" => "573" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18774392" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EAACI/GA<span class="elsevierStyleSup">2</span>LEN/EDF/WAO guideline: management of urticaria" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Zuberbier" 1 => "R. Asero" 2 => "C. Bindslev-Jensen" 3 => "G. Walter Canonica" 4 => "M.K. 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