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array:24 [ "pii" => "S1578219013001479" "issn" => "15782190" "doi" => "10.1016/j.adengl.2013.01.001" "estado" => "S300" "fechaPublicacion" => "2013-09-01" "aid" => "803" "copyright" => "Elsevier España, S.L. and AEDV" "copyrightAnyo" => "2012" "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Actas Dermosifiliogr. 2013;104:598-616" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 17368 "formatos" => array:3 [ "EPUB" => 81 "HTML" => 12718 "PDF" => 4569 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0001731013000380" "issn" => "00017310" "doi" => "10.1016/j.ad.2013.01.003" "estado" => "S300" "fechaPublicacion" => "2013-09-01" "aid" => "803" "copyright" => "Elsevier España, S.L. y AEDV" "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Actas Dermosifiliogr. 2013;104:598-616" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 19748 "formatos" => array:3 [ "EPUB" => 4 "HTML" => 14980 "PDF" => 4764 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Documento de consenso</span>" "titulo" => "Acitretina: guía de uso en psoriasis" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "598" "paginaFinal" => "616" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Guidelines for the Use of Acitretin in Psoriasis" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1466 "Ancho" => 3266 "Tamanyo" => 405255 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Mecanismo de acción de los retinoides.</p> <p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">ADH: alcohol deshidrogenasa; COUP-TFII: <span class="elsevierStyleItalic">chicken ovalbumin upstream promoter-transcription factor <span class="elsevierStyleSmallCaps">ii</span></span>; CRBP: <span class="elsevierStyleItalic">cellular retinol binding proteins</span>; CYP: citocromo P 450 familia 26; FOG2: <span class="elsevierStyleItalic">friend of</span> GATA; GATA4: guanina, adenina, timina, adenina; LRAT: <span class="elsevierStyleItalic">lecitin retinol acetil transferasa</span>; RAR: <span class="elsevierStyleItalic">retinoic acid receptors</span>; RARE: <span class="elsevierStyleItalic">retinoic acid response elements</span>; RBP: <span class="elsevierStyleItalic">retinol binding proteins</span>; RDH: <span class="elsevierStyleItalic">retinal dehidrogenasa</span>; RXR: retinoid <span class="elsevierStyleSmallCaps">X</span> receptors; STRAT6: <span class="elsevierStyleItalic">stimulated by retinoic acid 6</span>.</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Fuente: Saurat<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a>; Siegenthaler et al.<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">145</span></a>; y Napoli<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">146</span></a>.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "G. Carretero, M. Ribera, I. Belinchón, J.M. Carrascosa, Ll. Puig, C. Ferrandiz, L. Dehesa, D. Vidal, F. Peral, E. Jorquera, A. Gonzalez-Quesada, C. Muñoz, J. Notario, F. Vanaclocha, J.C. Moreno" "autores" => array:16 [ 0 => array:2 [ "nombre" => "G." "apellidos" => "Carretero" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Ribera" ] 2 => array:2 [ "nombre" => "I." "apellidos" => "Belinchón" ] 3 => array:2 [ "nombre" => "J.M." "apellidos" => "Carrascosa" ] 4 => array:2 [ "nombre" => "Ll." "apellidos" => "Puig" ] 5 => array:2 [ "nombre" => "C." "apellidos" => "Ferrandiz" ] 6 => array:2 [ "nombre" => "L." "apellidos" => "Dehesa" ] 7 => array:2 [ "nombre" => "D." "apellidos" => "Vidal" ] 8 => array:2 [ "nombre" => "F." "apellidos" => "Peral" ] 9 => array:2 [ "nombre" => "E." "apellidos" => "Jorquera" ] 10 => array:2 [ "nombre" => "A." "apellidos" => "Gonzalez-Quesada" ] 11 => array:2 [ "nombre" => "C." "apellidos" => "Muñoz" ] 12 => array:2 [ "nombre" => "J." "apellidos" => "Notario" ] 13 => array:2 [ "nombre" => "F." "apellidos" => "Vanaclocha" ] 14 => array:2 [ "nombre" => "J.C." "apellidos" => "Moreno" ] 15 => array:1 [ "colaborador" => "Grupo de Psoriasis de la AEDV" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1578219013001479" "doi" => "10.1016/j.adengl.2013.01.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219013001479?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731013000380?idApp=UINPBA000044" "url" => "/00017310/0000010400000007/v1_201308270831/S0001731013000380/v1_201308270831/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S1578219013001480" "issn" => "15782190" "doi" => "10.1016/j.adengl.2012.11.020" "estado" => "S300" "fechaPublicacion" => "2013-09-01" "aid" => "770" "copyright" => "Elsevier España, S.L. and AEDV" "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Actas Dermosifiliogr. 2013;104:617-22" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2694 "formatos" => array:3 [ "EPUB" => 43 "HTML" => 2023 "PDF" => 628 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Novelties in dermatology</span>" "titulo" => "Advances in the Diagnosis and Treatment of Tumor Necrosis Factor Receptor–Associated Periodic Syndrome" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "617" "paginaFinal" => "622" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Novedades en el diagnóstico y tratamiento del síndrome periódico asociado al receptor del factor de necrosis tumoral" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Aguado-Gil, I. Irarrazaval-Armendáriz, M. Pretel-Irazabal" "autores" => array:3 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Aguado-Gil" ] 1 => array:2 [ "nombre" => "I." "apellidos" => "Irarrazaval-Armendáriz" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Pretel-Irazabal" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731012005455" "doi" => "10.1016/j.ad.2012.11.008" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731012005455?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219013001480?idApp=UINPBA000044" "url" => "/15782190/0000010400000007/v1_201308270818/S1578219013001480/v1_201308270818/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1578219013001467" "issn" => "15782190" "doi" => "10.1016/j.adengl.2012.12.006" "estado" => "S300" "fechaPublicacion" => "2013-09-01" "aid" => "795" "copyright" => "Elsevier España, S.L. and AEDV" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Actas Dermosifiliogr. 2013;104:593-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2550 "formatos" => array:3 [ "EPUB" => 54 "HTML" => 1988 "PDF" => 508 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Patterns of Visceral Metastasis in Cutaneous Melanoma: A Descriptive Study" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "593" "paginaFinal" => "597" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estudio descriptivo del patrón de diseminación visceral del melanoma cutáneo" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Marcoval, J.R. Ferreres, C. Martín, S. Gómez, R.M. Penín, M. Ochoa de Olza, À. Fabra" "autores" => array:7 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Marcoval" ] 1 => array:2 [ "nombre" => "J.R." "apellidos" => "Ferreres" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Martín" ] 3 => array:2 [ "nombre" => "S." "apellidos" => "Gómez" ] 4 => array:2 [ "nombre" => "R.M." "apellidos" => "Penín" ] 5 => array:2 [ "nombre" => "M." "apellidos" => "Ochoa de Olza" ] 6 => array:2 [ "nombre" => "À." "apellidos" => "Fabra" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731013000173" "doi" => "10.1016/j.ad.2012.12.012" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731013000173?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219013001467?idApp=UINPBA000044" "url" => "/15782190/0000010400000007/v1_201308270818/S1578219013001467/v1_201308270818/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Consensus Document</span>" "titulo" => "Guidelines for the Use of Acitretin in Psoriasis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "598" "paginaFinal" => "616" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "G. Carretero, M. Ribera, I. Belinchón, J.M. Carrascosa, Ll. Puig, C. Ferrandiz, L. Dehesa, D. Vidal, F. Peral, E. Jorquera, A. Gonzalez-Quesada, C. Muñoz, J. Notario, F. Vanaclocha, J.C. Moreno" "autores" => array:16 [ 0 => array:4 [ "nombre" => "G." "apellidos" => "Carretero" "email" => array:1 [ 0 => "gcarrete@aedv.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Ribera" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "I." "apellidos" => "Belinchón" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 3 => array:3 [ "nombre" => "J.M." "apellidos" => "Carrascosa" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 4 => array:3 [ "nombre" => "Ll." "apellidos" => "Puig" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] 5 => array:3 [ "nombre" => "C." "apellidos" => "Ferrandiz" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] ] 6 => array:3 [ "nombre" => "L." "apellidos" => "Dehesa" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">h</span>" "identificador" => "aff0040" ] ] ] 7 => array:3 [ "nombre" => "D." "apellidos" => "Vidal" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">i</span>" "identificador" => "aff0045" ] ] ] 8 => array:3 [ "nombre" => "F." "apellidos" => "Peral" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">j</span>" "identificador" => "aff0050" ] ] ] 9 => array:3 [ "nombre" => "E." "apellidos" => "Jorquera" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">k</span>" "identificador" => "aff0055" ] ] ] 10 => array:3 [ "nombre" => "A." "apellidos" => "Gonzalez-Quesada" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">l</span>" "identificador" => "aff0060" ] ] ] 11 => array:3 [ "nombre" => "C." "apellidos" => "Muñoz" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">m</span>" "identificador" => "aff0065" ] ] ] 12 => array:3 [ "nombre" => "J." "apellidos" => "Notario" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">n</span>" "identificador" => "aff0070" ] ] ] 13 => array:3 [ "nombre" => "F." "apellidos" => "Vanaclocha" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">o</span>" "identificador" => "aff0075" ] ] ] 14 => array:3 [ "nombre" => "J.C." "apellidos" => "Moreno" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">p</span>" "identificador" => "aff0080" ] ] ] 15 => array:1 [ "colaborador" => "of the Psoriasis Group of the AEDV" ] ] "afiliaciones" => array:16 [ 0 => array:3 [ "entidad" => "Grupo de Psoriasis de la Academia Española de Dermatología y Venereología, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Hospital Universitario de Gran Canaria Dr. Negrín, Gran Canaria, Spain" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Hospital Universitario de Sabadell - Corporació Parc Taulí, Sabadell, Spain" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Hospital General de Alicante, Alicante, Spain" "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Hospital Universitario Germans Tiras i Pujol, Badalona, Spain" "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Hospital de la Santa Creu i Sant Pau, Barcelona, Spain" "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Hospital Universitario Germans Tiras i Pujol, Badalona, Spain" "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Mount Sinai Medical Center, Miami Beach, United States" "etiqueta" => "<span class="elsevierStyleSup">h</span>" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Hospital Sant Joan Despí Moisès Broggi, San Joan Despí, Spain" "etiqueta" => "<span class="elsevierStyleSup">i</span>" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Hospital Universitario Virgen Macarena, Sevilla, Spain" "etiqueta" => "<span class="elsevierStyleSup">j</span>" "identificador" => "aff0050" ] 10 => array:3 [ "entidad" => "Hospital Juan Ramón Jiménez, Huelva, Spain" "etiqueta" => "<span class="elsevierStyleSup">k</span>" "identificador" => "aff0055" ] 11 => array:3 [ "entidad" => "Hospital Universitario de Gran Canaria Dr. Negrín, Gran Canaria, Spain" "etiqueta" => "<span class="elsevierStyleSup">l</span>" "identificador" => "aff0060" ] 12 => array:3 [ "entidad" => "Hospital Clinic, Barcelona, Spain" "etiqueta" => "<span class="elsevierStyleSup">m</span>" "identificador" => "aff0065" ] 13 => array:3 [ "entidad" => "Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Spain" "etiqueta" => "<span class="elsevierStyleSup">n</span>" "identificador" => "aff0070" ] 14 => array:3 [ "entidad" => "Hospital Universitario 12 de Octubre, Madrid, Spain" "etiqueta" => "<span class="elsevierStyleSup">o</span>" "identificador" => "aff0075" ] 15 => array:3 [ "entidad" => "Hospital Universitario Reina Sofía, Córdoba, Spain" "etiqueta" => "<span class="elsevierStyleSup">p</span>" "identificador" => "aff0080" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding Author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Acitretina: guía de uso en psoriasis" ] ] "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" => 2642 "Ancho" => 3372 "Tamanyo" => 698584 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Treatment monitoring form for acitretin.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The treatment of psoriasis has changed considerably in the last 10 years with the advent of biologic therapy—a development that has increased the arsenal of drugs available for the systemic treatment of this condition. Acitretin fulfills a unique role in the strategies used to treat psoriasis because its mechanism of action is different from that of other systemic drugs. This distinction is the main reason for the continued usefulness of acitretin in the treatment of psoriasis despite the more than 35 years that have elapsed since it was first synthesized and the 25 years since it was first introduced in Spain. Acitretin continues to be useful as monotherapy and in combination with other systemic treatments or phototherapy, and its role as a rescue drug or in combination with biologic agents is particularly interesting, as has been shown by recent reviews on this topic.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The retinoids are a group of nonsteroid hormone compounds related to retinol. These intracrine and paracrine mediators intervene in a wide range of essential biologic processes in vertebrates, including embryogenesis, morphogenesis, and organogenesis, the regulation of cell growth, differentiation, and apoptosis, as well as immune regulation.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6–8</span></a> Retinoids exert their effects by binding to cytoplasmic proteins, which determine their intracellular distribution, and by binding to and/or activating nuclear receptors belonging to the superfamily of the ligand-inducible transcription factors, including steroid, vitamin D<span class="elsevierStyleInf">3</span>, and thyroid hormone receptors. There are 2 known families of retinoid nuclear receptors, the retinoic acid receptor (RAR) and the retinoid <span class="elsevierStyleSmallCaps">X</span> receptor (RXR), each one comprising 3 types and various isoforms. In normal skin, the concentration of RXR is 5 times that of RAR. Before binding to the nuclear response elements, which determine the transcription of the various retinoid-dependent genes, the activated retinoid receptors bind to form homodimers (RAR/RAR, RXR/RXR) or heterodimers (RAR/RXR, RAR/VDR or RXR/VDR); the target genes sensitive to therapeutic retinoids respond predominantly to the RXR/RAR heterodimers.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The development of the retinoids currently on the market has mirrored the discovery of the specificity of action of different intranuclear receptors in an effort to reduce the toxicity and increase the specificity of action of these drugs.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,10–12</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The retinoids were first synthesized in the 1970s to assess their usefulness in skin cancer,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> and their use in dermatology was soon extended to the treatment of other proliferative diseases.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> In psoriasis, their usefulness arises from their effects on keratinization, cell proliferation and inflammation,<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,15–18</span></a> and immune regulation.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19,20</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">When first developed in 1972, the monoaromatic retinoid etretinate had a considerable impact on the systemic treatment of psoriasis and other disorders of keratinization because of its antiproliferative activity and effect on cell differentiation, especially in epithelial tissues.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,21,22</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The introduction of etretinate, the first retinoid used to treat psoriasis, revolutionized psoriasis therapy, adding an interesting new option to the limited therapeutic arsenal available at that time for severe cases—essentially methotrexate and psoralen-UV-A (PUVA) therapy. The introduction of etretinate was also accompanied by a methodological revolution because the Psoriasis Area and Severity Index (PASI) was first used to assess the efficacy of the new retinoid in clinical trials.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Like all the synthetic retinoids, etretinate is highly teratogenic, and this risk—further increased by the drug's long elimination half-life—greatly restricted its use in women of reproductive potential. As a result, etretinate was replaced in 1997 by its active metabolite, acitretin, a drug with similar efficacy but a shorter half-life. It was hoped that this shorter half-life would reduce the duration of the drug's teratogenic effects; however, it did not.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Even though acitretin is used to treat many skin conditions, the present review will focus only on its usefulness in psoriasis. We felt it would be of interest to develop guidelines by consensus among the members of the Psoriasis Group of the Spanish Academy of Dermatology and Venereology.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Pharmacology</span><p id="par0040" class="elsevierStylePara elsevierViewall">Acitretin (C<span class="elsevierStyleInf">21</span>H<span class="elsevierStyleInf">26</span>O<span class="elsevierStyleInf">3</span>, PM 326.42934 [g/mol]) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) is a second-generation monoaromatic retinoid and a free acid form and active metabolite of its precursor etretinate. It has the advantage over its precursor of having a much shorter half-life.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Despite their structural similarity, the 2 drugs have very different physical and chemical properties. Owing to its better pharmacokinetic profile, efficacy, and safety acitretin has now completely replaced etretinate.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Mechanism of Action</span><p id="par0050" class="elsevierStylePara elsevierViewall">Acitretin acts by modulating the proliferation of epidermal keratinocytes. In hyperproliferative tissue, such as psoriasis plaques, acitretin has an antiproliferative effect, whereas in healthy tissues it induces proliferation.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> In psoriasis, this antiproliferative action reduces desquamation, erythema, and the overall thickness of the lesion. Some authors have also attributed retinoids a role in the modulation of the T-cell response,<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> the inhibition of chemotaxis, and the activation of polymorphonuclear leukocytes.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Unlike other systemic antipsoriatic therapies, acitretin is not considered to be cytotoxic or immunosuppressive.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Acitretin binds to RAR and RXR nuclear receptors, activating all 3 subtypes (α, β, and γ) and modulating the transcription of the genes that code for various proteins involved in the pathogenesis of psoriasis.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Although retinoids act primarily by binding to nuclear receptors, they also act indirectly by antagonizing a number of transcription factors, competing with coactivator proteins which are essential for the activation of genes on which retinoids have no direct effect (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,28,29</span></a> In addition to its direct mechanism of positive transcription, acitretin also exerts an indirect effect by inhibiting certain genes that regulate proliferation, angiogenesis, and inflammation in psoriasis.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,30</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Although the specific action that derives from this acitretin-induced transcription and inhibition is not fully understood, various hypotheses have focused on 2 areas of action: the modification of the metabolism and action of endogenous retinoids,<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29,31</span></a> and the overall immune regulation of the inflammatory molecules and cells involved in psoriasis,<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19,31,32</span></a> particularly helper T (T<span class="elsevierStyleInf">h</span>) 1 and T<span class="elsevierStyleInf">h</span>17 cells.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,20,33</span></a> These theories would explain the mechanisms of action that make acitretin capable of reversing the pathological and clinical manifestations of plaque psoriasis.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,34–37</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Absorption and Distribution</span><p id="par0065" class="elsevierStylePara elsevierViewall">The mean absolute bioavailability of acitretin is 59% (range, 36% to 95%). Absorption is linear up to 50<span class="elsevierStyleHsp" style=""></span>mg/d and nonlinear at higher doses. The rate and extent of absorption can be 2 to 5 times higher when acitretin is taken with food.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">38,39</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Absorbed acitretin is transported bound to plasma proteins (95%)—mostly albumin—with the remainder binding to high-density lipoprotein, low-density lipoprotein, and very low-density lipoprotein.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">38,40</span></a> The drug is distributed rapidly throughout the body and does not accumulate in any particular tissue. It is about 50 times less lipophilic than etretinate, and does not therefore tend to accumulate in adipose tissue.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Metabolism</span><p id="par0075" class="elsevierStylePara elsevierViewall">Acitretin is metabolized primarily by the liver, giving rise to 2 metabolites: 13-cis-acitretin and etretinate. The amount of 13-cis-acitretin formed is independent of dose, formulation, and administration with food. Steady state concentrations of acitretin and 13-cis-acitretin are reached after approximately 3 weeks of daily administration of acitretin.</p><p id="par0080" class="elsevierStylePara elsevierViewall">It has been found that etretinate is naturally produced from acitretin through a re-esterification process that varies in each individual.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> The amount of etretinate produced is very small, but this process is potentiated by the presence of ethanol through the action of a liver enzyme that catalyzes the ethyl esterification of acitretin to etretinate.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,43</span></a> Since the accumulation of etretinate in fatty tissue, and in the liver, kidney, brain, and testes, is 50 times greater than that of acitretin, retinoid activity can persist for a long time even after the patient has stopped taking acitretin.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Once it has exerted its action on the target cell, the unused acitretin and etretinate are converted to polar metabolites by the enzymatic action of the cytochrome P450 complex.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,44</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Half-life</span><p id="par0090" class="elsevierStylePara elsevierViewall">Chemically, acitretin and etretinate are very similar, with the only difference being that etretinate is the ethylester form of acitretin. This small chemical difference, however, results in major differences in the pharmacokinetic profiles of the 2 drugs. Etretinate, unlike acitretin, is an uncharged molecule and therefore highly lipophilic, a characteristic that leads to considerable accumulation of the drug in body fat. Acitretin, on the other hand, has a negative ionic charge and therefore accumulates less in adipose tissue. Its higher rate of clearance and lower volume of distribution means that it has a much shorter elimination half-life than etretinate (50<span class="elsevierStyleHsp" style=""></span>hours vs 120 days).<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">45–47</span></a> In fact, this was the main reason why acitretin replaced etretinate in clinical practice.</p><p id="par0095" class="elsevierStylePara elsevierViewall">However, the hydrolysis that occurs naturally in the human body to convert etretinate to acitretin can be reversed in the presence of heavy alcohol consumption.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> Etretinate has been detected in the plasma of patients on monotherapy with acitretin, and since etretinate accumulates in adipose tissue and has a long half-life, its presence prolongs the teratogenic potential of acitretin.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Larsen et al<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> reported that maximum plasma concentrations of acitretin were reached between 0.9 and 4.6<span class="elsevierStyleHsp" style=""></span>hours after oral administration, with an absorption half-life ranging from 0.2 to 1.7<span class="elsevierStyleHsp" style=""></span>hours and a distribution half-life of between 1.2 and 3.5<span class="elsevierStyleHsp" style=""></span>hours.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> In the same study, the elimination half-life of the drug after cessation of treatment varied between 16.5 and 111.1<span class="elsevierStyleHsp" style=""></span>hours (mean [SD], 47.1<span class="elsevierStyleHsp" style=""></span>hours [29.8]), while that of its metabolite (13-cis-acitretin) varied between 36.5 and 249.4<span class="elsevierStyleHsp" style=""></span>hours (mean [SD], 119.4 [7.4]).</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Excretion</span><p id="par0105" class="elsevierStylePara elsevierViewall">The conjugates produced by the metabolism of acitretin and its metabolite 13-cis-acitretin are eliminated by the kidney (16% to 53%) or excreted into bile and ultimately eliminated in feces (34% to 54%). Acitretin is eliminated within approximately 49<span class="elsevierStyleHsp" style=""></span>hours (range, 33 to 96<span