Case and Research Letter
JAK Inhibitors in Atopic Dermatitis Associated With Risk of Viral Infections: A Critical Appraisal
Inhibidores de JAK en dermatitis atópica asociados al riesgo de infecciones virales: evaluación crítica
Y.S. Pathania
Department of Dermatology, Venereology and Leprology, All India Institute of Medical Sciences, Rajkot, Gujarat, India
Leído
3457
Vecesse ha leído el artículo
1394
Total PDF
2063
Total HTML
Compartir estadísticas
array:24 [ "pii" => "S0001731022009486" "issn" => "00017310" "doi" => "10.1016/j.ad.2022.03.025" "estado" => "S300" "fechaPublicacion" => "2023-03-01" "aid" => "3302" "copyrightAnyo" => "2022" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2023;114:277-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:18 [ "pii" => "S0001731023000431" "issn" => "00017310" "doi" => "10.1016/j.ad.2022.03.035" "estado" => "S300" "fechaPublicacion" => "2023-03-01" "aid" => "3354" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2023;114:T277-T278" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta científico-clínica</span>" "titulo" => " Inhibidores de JAK en dermatitis atópica asociados al riesgo de infecciones virales: evaluación crítica" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "T277" "paginaFinal" => "T278" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "JAK Inhibitors in Atopic Dermatitis Associated With Risk of Viral Infections: A Critical Appraisal" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Y.S. Pathania" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Y.S." "apellidos" => "Pathania" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731023000431?idApp=UINPBA000044" "url" => "/00017310/0000011400000003/v1_202303051528/S0001731023000431/v1_202303051528/es/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S0001731023000443" "issn" => "00017310" "doi" => "10.1016/j.ad.2022.07.032" "estado" => "S300" "fechaPublicacion" => "2023-03-01" "aid" => "3355" "copyright" => "AEDV" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2023;114:T274-T276" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">CARTA CIENTÍFICO-CLÍNICA</span>" "titulo" => " Síndrome de Gianotti-Crosti de localización atípica en un adulto después de la vacunación contra el SARS-CoV-2" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "T274" "paginaFinal" => "T276" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Gianotti-Crosti Syndrome of Atypical Location in an Adult Following SARS-CoV-2 Vaccination" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 404 "Ancho" => 1256 "Tamanyo" => 70714 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Características clínicas en el momento de la presentación: pápulas eritematosas de 2-4 mm, algunas de ellas costrosas, localizadas principalmente en el pecho (a), la superficie flexora del brazo derecho (b) y ligeramente en las nalgas (c).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Pestana, R. Araújo Carvalho, M.M. Valejo Coelho, G. Esteves" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Pestana" ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Araújo Carvalho" ] 2 => array:2 [ "nombre" => "M.M." "apellidos" => "Valejo Coelho" ] 3 => array:2 [ "nombre" => "G." "apellidos" => "Esteves" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731023000443?idApp=UINPBA000044" "url" => "/00017310/0000011400000003/v1_202303051528/S0001731023000443/v1_202303051528/es/main.assets" ] "asociados" => array:1 [ 0 => array:18 [ "pii" => "S0001731023000431" "issn" => "00017310" "doi" => "10.1016/j.ad.2022.03.035" "estado" => "S300" "fechaPublicacion" => "2023-03-01" "aid" => "3354" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2023;114:T277-T278" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta científico-clínica</span>" "titulo" => " Inhibidores de JAK en dermatitis atópica asociados al riesgo de infecciones virales: evaluación crítica" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "T277" "paginaFinal" => "T278" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "JAK Inhibitors in Atopic Dermatitis Associated With Risk of Viral Infections: A Critical Appraisal" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Y.S. Pathania" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Y.S." "apellidos" => "Pathania" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731023000431?idApp=UINPBA000044" "url" => "/00017310/0000011400000003/v1_202303051528/S0001731023000431/v1_202303051528/es/main.assets" ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letter</span>" "titulo" => "JAK Inhibitors in Atopic Dermatitis Associated With Risk of Viral Infections: A Critical Appraisal" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">To the Editor</span>," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "277" "paginaFinal" => "278" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Y.S. Pathania" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Y.S." "apellidos" => "Pathania" "email" => array:1 [ 0 => "yashdeepsinghpathania@gmail.com" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Department of Dermatology, Venereology and Leprology, All India Institute of Medical Sciences, Rajkot, Gujarat, India" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Inhibidores de JAK en dermatitis atópica asociados al riesgo de infecciones virales: evaluación crítica" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Atopic dermatitis (AD) is one of the commonest inflammatory dermatoses. AD related cytokines such as IFN-γ, IL-4, IL-13, IL-31, IL-33, IL-23, IL-22, and IL-17 have downstream signalling through Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway. JAK inhibitors have shown to decrease the symptoms and severity of AD. Albeit, JAK inhibitors are not approved by the United States Food and Drug Administration (U.S. FDA) for the treatment of AD. JAK inhibitors such as abrocitinib, upadacitinib, baricitinib (oral) and ruxolitinib, delgocitinib (topical) are currently in clinical trials for the treatment of AD.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Headache, nausea, nasopharyngitis are the common systemic adverse events seen with these agents. Viral infections and reactivation of herpes simplex virus (HSV), eczema herpeticum (EH), herpes zoster (HZ) are the dermatological adverse effects reported with JAK inhibitors. Shah et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> described the vulnerability of AD patients on JAK inhibitors treatment to HSV infection, reactivation, EH and HZ.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Most of the data for HSV infection has been derived from tofacitinib which is FDA approved in rheumatoid arthritis, psoriatic arthritis and inflammatory bowel disease (IBD). However, there has been much less incidence of HSV infection, HZ and EH from the clinical trials of specified JAK inhibitors in AD.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> It may be due to exclusion of patients with history of EH, HSV infection in the studies. Moreover, baricitinib has been approved in the European Union for AD in November 2020, but history of EH is not included as a contraindication.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The host adaptive response to viruses is directed mainly by Th1 cells. The main cytokines responsible for Th1 polarisation are interferon (IFN)-γ and interleukin (IL)-12 and the intracellular pathways of these are mediated by JAK 1-2/STAT1 and JAK 2-TYK2/STAT4 respectively.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> The inhibition of JAK-3 and JAK-1 significantly inhibit the effective production of antibodies.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Both innate and acquired immunity are essential to generate response against viral infections. Therefore, JAK inhibitors in AD have every possible theoretical chance of virus infection, reactivation and dissemination. There is further increased chances of EH, HSV infection, reactivation and dissemination with the concomitant use of immunosuppressive agents such as oral corticosteroids, cyclosporine, azathioprine.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Prophylactic use of anti-viral agents (acyclovir, valacyclovir) in those patients who have an established history of HSV infection with severe and recurrent outbreaks have been suggested by authors and recommended valacyclovir 500<span class="elsevierStyleHsp" style=""></span>mg twice daily for the prevention of HSV reactivation.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Furthermore, a prophylaxis with acyclovir 200<span class="elsevierStyleHsp" style=""></span>mg twice daily or valacyclovir 500<span class="elsevierStyleHsp" style=""></span>mg per day is also recommended in AD patients with a history of EH and recurrent episodes. In addition, the concomitant use of topical tacrolimus should be avoided in AD patients on JAK inhibitors to prevent induction of EH.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">It is prudent to discuss regarding the prevention of HZ, HSV reactivation and EH in AD patients on JAK inhibitors. The American College of Rheumatology (ACR) recommends vaccination for patients ≥50 years before treatment of biologics and tofacitinib.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> The American College of Gastroenterology recently recommended vaccination against HZ in IBD patients ≥50 years of age, including immunosuppressed patients.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Therefore, it is suggested to start JAK inhibitor treatment at least 2–4 weeks after live attenuated zoster vaccine.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Early detection either clinically or serologically and prophylaxis with valacyclovir or acyclovir can prevent severe episodes of EH, HSV reactivation and dissemination. In a study by Fleming et al.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> which included 8 randomized controlled trials with 2706 participants found a risk reduction of nearly 70% for EH in dupilumab treated AD patients.</p><p id="par0030" class="elsevierStylePara elsevierViewall">JAK inhibitors have a wider pleiotropic biological effect than biologics as they are able to simultaneously suppress the action of different cytokines. This intrinsic characteristic of JAK inhibitors can explain the higher risk of HZ, induction of EH and HSV reactivation. During the literature search, JAK 2 and 3 are found to be associated with increased risk of zoster infection and selectively JAK1 inhibition with a lower risk. Therefore, it may be speculated that selective JAK 1 inhibitor in AD might pose a relatively lesser risk of HSV, HZ, and EH. Moreover, anti-viral prophylaxis and vaccination may also be considered for alleviating the risk of viral infections. However, further long-term clinical studies are required to validate the findings.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interests</span><p id="par0035" class="elsevierStylePara elsevierViewall">The author declares they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interests" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety of Janus kinase (JAK) inhibitors in the short-term treatment of atopic dermatitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "H. Wood" 1 => "A. Chandler" 2 => "N. Nezamololama" 3 => "K. Papp" 4 => "M.J. Gooderham" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/ijd.15853" "Revista" => array:2 [ "tituloSerie" => "Int J Dermatol" "fecha" => "2021" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0060" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Should atopic dermatitis patients starting JAK inhibitors take prophylactic acyclovir?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.A. Shah" 1 => "K.G. Beuerlein" 2 => "J.L. Jorizzo" 3 => "S.R. Feldman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/09546634.2021.1978665" "Revista" => array:5 [ "tituloSerie" => "J Dermatol Treat" "fecha" => "2021" "volumen" => "32" "paginaInicial" => "669" "paginaFinal" => "672" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0065" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.L. Simpson" 1 => "R. Sinclair" 2 => "S. Forman" 3 => "A. Wollenberg" 4 => "R. Aschoff" 5 => "M. Cork" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(20)30732-7" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2020" "volumen" => "396" "paginaInicial" => "255" "paginaFinal" => "266" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32711801" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0070" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interferon-gamma: an overview of signals, mechanisms and functions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K. Schroder" 1 => "P.J. Hertzog" 2 => "T. Ravasi" 3 => "D.A. Hume" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1189/jlb.0603252" "Revista" => array:6 [ "tituloSerie" => "J Leukoc Biol" "fecha" => "2004" "volumen" => "75" "paginaInicial" => "163" "paginaFinal" => "189" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14525967" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0075" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tofacitinib suppresses antibody responses to protein therapeutics in murine hosts" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Onda" 1 => "K. Ghoreschi" 2 => "S. Steward-Tharp" 3 => "C. Thomas" 4 => "J.J. O'Shea" 5 => "I.H. Pastan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4049/jimmunol.1400063" "Revista" => array:6 [ "tituloSerie" => "J Immunol" "fecha" => "2014" "volumen" => "193" "paginaInicial" => "48" "paginaFinal" => "55" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24890727" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0080" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adults with atopic dermatitis and herpes simplex and topical therapy with tacrolimus: what kind of prevention?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. Lübbe" 1 => "S. Sanchez-Politta" 2 => "C. Tschanz" 3 => "J.H. Saurat" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archderm.139.5.670" "Revista" => array:6 [ "tituloSerie" => "Arch Dermatol" "fecha" => "2003" "volumen" => "139" "paginaInicial" => "670" "paginaFinal" => "671" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12756112" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0085" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.A. Singh" 1 => "K.G. Saag" 2 => "S.L. Bridges Jr." 3 => "E.A. Akl" 4 => "R.R. Bannuru" 5 => "M.C. Sullivan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.39977" "Revista" => array:7 [ "tituloSerie" => "Arthritis Rheumatol" "fecha" => "2016" "volumen" => "68" "paginaInicial" => "1" "paginaFinal" => "26" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27870508" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1470204520304459" "estado" => "S300" "issn" => "14702045" ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0090" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ACG clinical guideline: preventive care in inflammatory bowel disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "F.A. Farraye" 1 => "G.Y. Melmed" 2 => "G.R. Lichtenstein" 3 => "S.V. Kane" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ajg.2016.537" "Revista" => array:6 [ "tituloSerie" => "Am J Gastroenterol" "fecha" => "2017" "volumen" => "112" "paginaInicial" => "241" "paginaFinal" => "258" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28071656" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0095" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2013 IDSA clinical practice guideline for vaccination of the immunocompromised host" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.G. Rubin" 1 => "M.J. Levin" 2 => "P. Ljungman" 3 => "E.G. Davies" 4 => "R. Avery" 5 => "M. Tomblyn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/cid/cit816" "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2014" "volumen" => "58" "paginaInicial" => "309" "paginaFinal" => "318" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24421306" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0100" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk of infection in patients with atopic dermatitis treated with dupilumab: a meta- analysis of randomized controlled trials" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P. Fleming" 1 => "A.M. Drucker" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2018" "volumen" => "78" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/00017310/0000011400000003/v1_202303051528/S0001731022009486/v1_202303051528/en/main.assets" "Apartado" => array:4 [ "identificador" => "6160" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Cartas científico-clínicas" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/00017310/0000011400000003/v1_202303051528/S0001731022009486/v1_202303051528/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731022009486?idApp=UINPBA000044" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 36 | 16 | 52 |
| 2024 Octubre | 105 | 85 | 190 |
| 2024 Septiembre | 85 | 61 | 146 |
| 2024 Agosto | 102 | 87 | 189 |
| 2024 Julio | 81 | 62 | 143 |
| 2024 Junio | 97 | 67 | 164 |
| 2024 Mayo | 104 | 66 | 170 |
| 2024 Abril | 64 | 50 | 114 |
| 2024 Marzo | 80 | 61 | 141 |
| 2024 Febrero | 63 | 53 | 116 |
| 2024 Enero | 72 | 46 | 118 |
| 2023 Diciembre | 60 | 43 | 103 |
| 2023 Noviembre | 53 | 50 | 103 |
| 2023 Octubre | 74 | 53 | 127 |
| 2023 Septiembre | 62 | 54 | 116 |
| 2023 Agosto | 80 | 57 | 137 |
| 2023 Julio | 100 | 72 | 172 |
| 2023 Junio | 65 | 30 | 95 |
| 2023 Mayo | 85 | 41 | 126 |
| 2023 Abril | 101 | 37 | 138 |
| 2023 Marzo | 231 | 72 | 303 |
| 2023 Febrero | 66 | 44 | 110 |
| 2023 Enero | 76 | 54 | 130 |
| 2022 Diciembre | 106 | 75 | 181 |
| 2022 Noviembre | 15 | 58 | 73 |
Mostrar todo
