Van der Woude Syndrome and Alopecia Areata: More Than a Fortuitous Association?

array:24 ["pii" => "S0001731023000741" "issn" => "00017310" "doi" => "10.1016/j.ad.2022.07.034" "estado" => "S300" "fechaPublicacion" => "2023-11-01" "aid" => "3383" "copyright" => "AEDV" "copyrightAnyo" => "2023" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2023;114:921-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:18 [ "pii" => "S0001731023007470" "issn" => "00017310" "doi" => "10.1016/j.ad.2023.09.018" "estado" => "S300" "fechaPublicacion" => "2023-11-01" "aid" => "3665" "copyright" => "AEDV" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2023;114:T921-T922" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "CARTA CIENTÍFICO-CLÍNICA" "titulo" => " Síndrome de Van der Woude y alopecia areata: más que una asociación fortuita?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "T921" "paginaFinal" => "T922" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Van der Woude Syndrome and Alopecia Areata: More Than a Fortuitous Association?" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "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" => 2303 "Ancho" => 752 "Tamanyo" => 265285 ] ] "descripcion" => array:1 [ "en" => "(a) Multilocular alopecia areata; (b) and (c) Fingernail pitting and trachyonychia." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A.L. João, N. Cunha, A.I. Cordeiro, M.J.Paiva Lopes" "autores" => array:4 [ 0 => array:2 [ "nombre" => "A.L." "apellidos" => "João" ] 1 => array:2 [ "nombre" => "N." "apellidos" => "Cunha" ] 2 => array:2 [ "nombre" => "A.I." "apellidos" => "Cordeiro" ] 3 => array:2 [ "nombre" => "M.J.Paiva" "apellidos" => "Lopes" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731023007470?idApp=UINPBA000044" "url" => "/00017310/0000011400000010/v1_202311020433/S0001731023007470/v1_202311020433/en/main.assets" ] "itemAnterior" => array:17 [ "pii" => "S0001731023007366" "issn" => "00017310" "doi" => "10.1016/j.ad.2023.09.007" "estado" => "S300" "fechaPublicacion" => "2023-11-01" "aid" => "3654" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2023;114:T918-T920" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "CARTA CIENTÍFICO-CLÍNICA" "titulo" => "[Articulo traducido] Efectos clínicos diferentes de las displasias ectodérmicas en cuatro generaciones" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "T918" "paginaFinal" => "T920" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Different Clinical Effects of Ectodermal Dysplasias in Four Generations" ] ] "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" => 631 "Ancho" => 1257 "Tamanyo" => 93741 ] ] "descripcion" => array:1 [ "es" => "Paciente de 14 años con hipoplasia mamaria (pequeña mama derecha) (B, C), pequeño pezón izquierdo (B, C), parálisis facial (A), manos pequeñas (D), ausencia de dientes (E) y dientes de la madre (F)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "O. Demirhan, B. Yüksel, S. Yilmaz, N. Cetinel" "autores" => array:4 [ 0 => array:2 [ "nombre" => "O." "apellidos" => "Demirhan" ] 1 => array:2 [ "nombre" => "B." "apellidos" => "Yüksel" ] 2 => array:2 [ "nombre" => "S." "apellidos" => "Yilmaz" ] 3 => array:2 [ "nombre" => "N." "apellidos" => "Cetinel" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731023007366?idApp=UINPBA000044" "url" => "/00017310/0000011400000010/v1_202311020433/S0001731023007366/v1_202311020433/es/main.assets" ] "asociados" => array:1 [ 0 => array:18 [ "pii" => "S0001731023007470" "issn" => "00017310" "doi" => "10.1016/j.ad.2023.09.018" "estado" => "S300" "fechaPublicacion" => "2023-11-01" "aid" => "3665" "copyright" => "AEDV" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2023;114:T921-T922" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "CARTA CIENTÍFICO-CLÍNICA" "titulo" => " Síndrome de Van der Woude y alopecia areata: más que una asociación fortuita?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "T921" "paginaFinal" => "T922" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Van der Woude Syndrome and Alopecia Areata: More Than a Fortuitous Association?" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "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" => 2303 "Ancho" => 752 "Tamanyo" => 265285 ] ] "descripcion" => array:1 [ "en" => "(a) Multilocular alopecia areata; (b) and (c) Fingernail pitting and trachyonychia." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A.L. João, N. Cunha, A.I. Cordeiro, M.J.Paiva Lopes" "autores" => array:4 [ 0 => array:2 [ "nombre" => "A.L." "apellidos" => "João" ] 1 => array:2 [ "nombre" => "N." "apellidos" => "Cunha" ] 2 => array:2 [ "nombre" => "A.I." "apellidos" => "Cordeiro" ] 3 => array:2 [ "nombre" => "M.J.Paiva" "apellidos" => "Lopes" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731023007470?idApp=UINPBA000044" "url" => "/00017310/0000011400000010/v1_202311020433/S0001731023007470/v1_202311020433/en/main.assets" ] ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "Case and Research Letter" "titulo" => "Van der Woude Syndrome and Alopecia Areata: More Than a Fortuitous Association?" "tieneTextoCompleto" => true "saludo" => "To the Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "921" "paginaFinal" => "922" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A.L. João, N. Cunha, A.I. Cordeiro, M.J. Paiva Lopes" "autores" => array:4 [ 0 => array:4 [ "nombre" => "A.L." "apellidos" => "João" "email" => array:1 [ 0 => "luisajoao92@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "N." "apellidos" => "Cunha" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "A.I." "apellidos" => "Cordeiro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "M.J." "apellidos" => "Paiva Lopes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Dermatology Department, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Pediatrics Department, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome de Van der Woude y alopecia areata: ¿más que una asociación fortuita?" ] ] "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" => 558 "Ancho" => 755 "Tamanyo" => 76945 ] ] "descripcion" => array:1 [ "en" => "Median lower lip pit (circle) and scar from the previous surgical correction of cleft of the primary palate (square)." ] ] ] "textoCompleto" => "A 9-year-old Caucasian boy was referred to the outpatient Dermatology Department for alopecia and fingernail fragility, which had been notorious for the past nine months. On examination, there was multilocular alopecia with extensive confluent areas involving 70% of the scalp (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>(a)), with black dots and scattered exclamation mark hairs on trichoscopy, consistent with the diagnosis of alopecia areata. Eyebrows were also affected, especially the outer portion. Fingernail pitting and trachyonychia were evident on all digits (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>(b), (c)), with normal toe nails. In addition, a median lower lip pit was noted, and the patient had been previously submitted to the surgical correction of a cleft palate in early infancy (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), which together define the diagnosis of Van der Woude Syndrome (VWS). Past medical history and physical examination were otherwise unremarkable. Namely, skin and limb abnormalities (such as popliteal pterygium, syndactyly, toe changes) or genitourinary malformations that could point toward Popliteal Pterygium Syndrome (PPS), an allelic variant of VWS, were absent. The existence of cleft lift/palate in the family members was denied by the parents. The patient was started on clobetasol 0.5mg/g lotion and minoxidil 5% solution, with a favorable response after one year (partial regrowth, with alopecia in 40% of the scalp). Genetic testing was positive for a heterozygous mutation in the interferon regulatory factor 6 (IRF6) gene, specifically the replacement of a T by A at position 178, resulting in the replacement of a tryptophan by an arginine at position 60 (c.178T>A (p.(Trp60Arg)), a previously undescribed variant.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>VWS is a rare congenital genetic disorder which represents the most common form of syndromic orofacial cleft, and 2% of all cleft cases. It has an autosomal dominant inheritance of several different mutations in a single gene, namely the IRF6 gene, with high penetrance but variable phenotypic expression. Besides its varied expressivity, VWS has an allelic variant, the PPS Syndrome, which also results from mutations in the IRF6 gene, but presents with additional features besides congenital lip pits and orofacial abnormalities,<a class="elsevierStyleCrossRef" href="#bib0035">1</a> which were not found in our patient.The child was considered to be the index case in the family. In fact, 30–50% of VWS cases arise as de novo mutations.<a class="elsevierStyleCrossRef" href="#bib0035">1</a> However, the presence of a mutation with reduced penetration could not be completely excluded, as genetic testing was not performed in the parents. There are approximately 170 different disease-causing mutations described in the IRF6 gene. Clinical phenotypes result from missense mutations, terminations, deletions, insertions, splicing site mutations, beyond others, but over 90% of IRF6 mutations are missense changes.<a class="elsevierStyleCrossRef" href="#bib0035">1</a> Moreover, the same missense mutation has already been described to be responsible for both VWS and PPS.<a class="elsevierStyleCrossRef" href="#bib0035">1</a> Nevertheless, as aforementioned, our patient phenotype was not compatible with PPS, and the identified mutation corresponds to a novel variant that so far has not been described.IRF6 protein is related to the formation of connective tissue, namely of the head and the face. The role of IRF6 in epidermal proliferation was also demonstrated in humans in histopathological studies, which were performed in children with VWS who underwent surgical cleft palate correction. However, in opposition to PPS that presents with popliteal pterygium, there are no clinical skin or appendage changes so far described in association with VWS in humans (except for squamous cell carcinoma associated with chronic inflammation of the lip pits).<a class="elsevierStyleCrossRef" href="#bib0040">2</a> Studies in mice have also shown that IRF6 is involved in keratinocyte proliferation and differentiation, and the mutant phenotype was highly similar to what was observed in repeated epilation (Er) mice, which show irregular hairloss.<a class="elsevierStyleCrossRef" href="#bib0045">3</a> On the other hand, interferon (IFN) molecules (α,β,γ) are well-established players in alopecia areata physiopathology<a class="elsevierStyleCrossRef" href="#bib0050">4</a> and interferon regulatory factors (IRF) are known to play a role in IFN-driven disease.<a class="elsevierStyleCrossRef" href="#bib0055">5</a> Although other IRF besides IRF6 are frequently implicated, the pleiotropic effects of these pathways raise awareness for a possible non-coincidental co-occurrence of VWS and AA, and it should be matter of future investigation. Furthermore, studies have suggested a cooperative role of p63 and IRF6 in orofacial development in mice and humans,<a class="elsevierStyleCrossRef" href="#bib0060">6</a> and mutations in TP63 gene cause a range of ectodermal dysplasias that include hair and nail abnormalities. Although these differ from alopecia areata, the link between IRF6 ant TP63 should merit further interest.The present case describes a new IRF6 mutation, although the experimental design lacks a direct functional test. It also raises awareness for a potential undescribed association between a common hair disorder and a rare genetic syndrome. Thus, it specifically sparks further interest in understanding the complex pathophysiological interplay on the involved pathways. Furthermore, it highlights the importance of Dermatologists in addressing the need for multidisciplinary endeavor of these syndromes.Conflicts of interestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2303 "Ancho" => 755 "Tamanyo" => 256603 ] ] "descripcion" => array:1 [ "en" => "(a) Multilocular alopecia areata; (b) and (c) Fingernail pitting and trachyonychia." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 558 "Ancho" => 755 "Tamanyo" => 76945 ] ] "descripcion" => array:1 [ "en" => "Median lower lip pit (circle) and scar from the previous surgical correction of cleft of the primary palate (square)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence and nonrandom distribution of exonic mutations in interferon regulatory factor 6 in 307 families with Van der Woude syndrome and 37 families with popliteal pterygium syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.L.L. Ferreira de Lima" 1 => "S.A. Hoper" 2 => "M. Ghassibe" 3 => "M.E. Cooper" 4 => "N.K. Rorick" 5 => "S. Kondo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/GIM.0b013e318197a49a" "Revista" => array:6 [ "tituloSerie" => "Genet Med" "fecha" => "2009" "volumen" => "11" "paginaInicial" => "241" "paginaFinal" => "247" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19282774" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0040" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interferon regulatory factor 6 controls proliferation of keratinocytes from children with Van der Woude Syndrome Ms" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "K. Hixon" 1 => "L. Rhea" 2 => "J. Standley" 3 => "F.J. Canady" 4 => "J.W. Canady" 5 => "M. Dunnwald" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1597/15-275" "Revista" => array:6 [ "tituloSerie" => "Cleft Palate Craniofac J" "fecha" => "2017" "volumen" => "54" "paginaInicial" => "281" "paginaFinal" => "286" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27115562" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0045" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Richardson" 1 => "J. Dixon" 2 => "S. Malhotra" 3 => "M. Hardman" 4 => "L. Knowles" 5 => "R. Boot-Handford" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng1894" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2006" "volumen" => "38" "paginaInicial" => "1329" "paginaFinal" => "1334" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17041603" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0050" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alopecia areata: a review of disease pathogenesis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "F. Rajabi" 1 => "L. Drake" 2 => "M. Senna" 3 => "N. Rezaei" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bjd.16808" "Revista" => array:5 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2018" "volumen" => "179" "paginaInicial" => "1033" "paginaFinal" => "1048" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0055" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Regulating IRFs in IFN driven disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "C.A. Jefferies" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fimmu.2019.00325" "Revista" => array:3 [ "tituloSerie" => "Front Immunol" "fecha" => "2019" "volumen" => "10" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0060" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cooperation between the transcription factors p63 and IRF6 is essential to prevent cleft palate in mice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.A. Thomason" 1 => "H. Zhou" 2 => "E.N. Kouwenhoven" 3 => "G.P. Dotto" 4 => "G. Restivo" 5 => "B.C. Nguyen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI40266" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "2010" "volumen" => "120" "paginaInicial" => "1561" "paginaFinal" => "1569" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20424327" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/00017310/0000011400000010/v1_202311020433/S0001731023000741/v1_202311020433/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/00017310/0000011400000010/v1_202311020433/S0001731023000741/v1_202311020433/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731023000741?idApp=UINPBA000044"]