Case and Research Letter
Relapse of morphea during Nivolumab therapy for lung adenocarcinoma
Recaída de morfea durante tratamiento con Nivolumab en adenocarcinoma de pulmón
A. Alegre-Sánchez
, P. Fonda-Pascual, D. Saceda-Corralo, E. de las Heras-Alonso
Autor para correspondencia
Dermatology Service, Ramon y Cajal Hospital, Madrid, Spain
Leído
4598
Vecesse ha leído el artículo
1881
Total PDF
2717
Total HTML
Compartir estadísticas
array:24 [ "pii" => "S1578219016303341" "issn" => "15782190" "doi" => "10.1016/j.adengl.2016.07.017" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "1481" "copyright" => "Elsevier España, S.L.U. and AEDV" "copyrightAnyo" => "2016" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2017;108:69-70" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 608 "formatos" => array:3 [ "EPUB" => 38 "HTML" => 382 "PDF" => 188 ] ] "Traduccion" => array:1 [ "en" => array:19 [ "pii" => "S0001731016302794" "issn" => "00017310" "doi" => "10.1016/j.ad.2016.07.013" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "1481" "copyright" => "AEDV" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2017;108:69-70" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 778 "formatos" => array:3 [ "EPUB" => 47 "HTML" => 334 "PDF" => 397 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letter</span>" "titulo" => "Relapse of morphea during Nivolumab therapy for lung adenocarcinoma" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "69" "paginaFinal" => "70" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Recaída de morfea durante tratamiento con Nivolumab en adenocarcinoma de pulmón" ] ] "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" => 622 "Ancho" => 950 "Tamanyo" => 74742 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patches in both breasts and left inframammary fold, showing a shinny white color, liliaceous ring and atrophic surface.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Alegre-Sánchez, P. Fonda-Pascual, D. Saceda-Corralo, E. de las Heras-Alonso" "autores" => array:4 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Alegre-Sánchez" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Fonda-Pascual" ] 2 => array:2 [ "nombre" => "D." "apellidos" => "Saceda-Corralo" ] 3 => array:2 [ "nombre" => "E." "apellidos" => "de las Heras-Alonso" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1578219016303341" "doi" => "10.1016/j.adengl.2016.07.017" "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/S1578219016303341?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731016302794?idApp=UINPBA000044" "url" => "/00017310/0000010800000001/v1_201612270122/S0001731016302794/v1_201612270122/en/main.assets" ] ] "itemSiguiente" => array:18 [ "pii" => "S1578219016303353" "issn" => "15782190" "doi" => "10.1016/j.adengl.2016.07.018" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "1471" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2017;108:70-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 674 "formatos" => array:3 [ "EPUB" => 41 "HTML" => 439 "PDF" => 194 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letter</span>" "titulo" => "Sweet's syndrome-like eruption in association with the exacerbation of Behçet's disease after the Great East Japan Earthquake" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "70" "paginaFinal" => "72" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Erupción tipo síndrome de Sweet asociada al empeoramiento de la enfermdad de Behçet después del Gran terremoto de Japón oriental" ] ] "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" => 1524 "Ancho" => 1661 "Tamanyo" => 681410 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histopathology showing dense inflammatory cell infiltrates through the dermis, mainly composed of neutrophils (hematoxylin and eosin stain, original magnification ×40).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "T. Miura, M. Ohtsuka, T. Yamamoto" "autores" => array:3 [ 0 => array:2 [ "nombre" => "T." "apellidos" => "Miura" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Ohtsuka" ] 2 => array:2 [ "nombre" => "T." "apellidos" => "Yamamoto" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0001731016302629" "doi" => "10.1016/j.ad.2016.07.006" "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/S0001731016302629?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219016303353?idApp=UINPBA000044" "url" => "/15782190/0000010800000001/v1_201612300037/S1578219016303353/v1_201612300037/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S157821901630289X" "issn" => "15782190" "doi" => "10.1016/j.adengl.2016.11.006" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "1373" "copyright" => "Elsevier España, S.L.U. and AEDV" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Actas Dermosifiliogr. 2017;108:68" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1131 "formatos" => array:3 [ "EPUB" => 54 "HTML" => 821 "PDF" => 256 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Images in Dermatology</span>" "titulo" => "Kaposi Varicelliform Eruption: A Dermatologic Complication" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:1 [ "paginaInicial" => "68" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Una complicación en dermatología, erupción variceliforme de Kaposi" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:6 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 622 "Ancho" => 600 "Tamanyo" => 99406 ] ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "I. Pérez-López, G. Blasco-Morente, A. Martínez-López, J. Tercedor-Sánchez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "I." "apellidos" => "Pérez-López" ] 1 => array:2 [ "nombre" => "G." "apellidos" => "Blasco-Morente" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Martínez-López" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Tercedor-Sánchez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731016000934" "doi" => "10.1016/j.ad.2015.09.024" "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/S0001731016000934?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S157821901630289X?idApp=UINPBA000044" "url" => "/15782190/0000010800000001/v1_201612300037/S157821901630289X/v1_201612300037/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letter</span>" "titulo" => "Relapse of morphea during Nivolumab therapy for lung adenocarcinoma" "tieneTextoCompleto" => true "saludo" => "Dear Editor" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "69" "paginaFinal" => "70" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. Alegre-Sánchez, P. Fonda-Pascual, D. Saceda-Corralo, E. de las Heras-Alonso" "autores" => array:4 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Alegre-Sánchez" "email" => array:1 [ 0 => "adrian.alegresanchez@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Fonda-Pascual" ] 2 => array:2 [ "nombre" => "D." "apellidos" => "Saceda-Corralo" ] 3 => array:2 [ "nombre" => "E." "apellidos" => "de las Heras-Alonso" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Dermatology Service, Ramon y Cajal Hospital, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Recaída de morfea durante tratamiento con Nivolumab en adenocarcinoma de pulmón" ] ] "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" => 1036 "Ancho" => 1583 "Tamanyo" => 152134 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patches in both breasts and left inframammary fold, showing a shinny white color, liliaceous ring and atrophic surface.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Nivolumab is a Programmed Death-1 (PD1) receptor (PD-1) inhibitor, first approved as cancer immune-checkpoint inhibitor therapy for stage IV malignant melanoma, with recent indications in different tumors such as non-small cell lung cancer, prostate cancer, renal-cell cancer or ovarian cancer. A wide variety of skin reactions have been described associated to cancer immunotherapy.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–7</span></a> We present a case of morphea relapsing during Nivolumab treatment.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 65 year-old woman came to our clinic referred by the Oncology department of our hospital. She was being followed due to a stage IV lung adenocarcinoma for which she had received different therapies. Just 2 months after initiating treatment with Nivolumab (3<span class="elsevierStyleHsp" style=""></span>mg/kg every 2 weeks), she developed cutaneous lesions on the trunk. On the physical examination she presented three patches: one on each breast, and one on the left inframammary fold (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). These lesions had a shiny white color with a discrete lilaceous ring. To the touch, they presented as clearly atrophic. She reported occasional itching but no other symptoms. The patient had a past medical history of morphea 8 years before (histologically diagnosed), having been treated with topical corticosteroids and oral methotrexate, with remission of the disease for more than 6 years. Postinflammatory hyperpigmentation was not detected.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">A skin biopsy of one of the patches was performed. Histological examination demonstrated findings of lichen sclerosus with underlying morphea (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Nivolumab was stopped after 6 months of treatment because of the lack of efficacy in oncological terms. In subsequent visits to our clinics, the patient showed improvement of her cutaneous lesions, without any topical or systemic treatment.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Relapse of morphea has been described in 50% of patients in the first 2 years after diagnosis.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> In the presented case, more than 6 years had passed since the last exacerbation of morphea, and this episode of relapsing happened only 2 weeks after initiating Nivolumab. Although natural evolution of the disease may have played a role, we considered Nivolumab as a possible trigger.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Many other medications have been associated with the development of morphea. The formation of autoantibodies and subsequent microvasculature injury has been proposed in the pathogenesis of these cases of drug-induced morphea.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In different clinical trials, anti-PD1 therapies such as Pembrolizumab or Nivolumab showed a relatively safe profile, with a low incidence of major adverse effects (drug-related grade 3 or 4 toxic effects only in 14% of the patients), being those related with pneumonitis the most severe of them.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> These adverse reactions related with immune-checkpoints inhibitors have been named as immune-related adverse events (irAEs). When focusing on the skin irAEs, non-specficic macular papular rash and pruritus have been described as the most common ones. Interestingly, vitiligo has also been reported, but only in patients with melanoma. Urticaria, alopecia and mucosal involvement are other frequently described skin irAEs.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The exacerbation of preexisting autoimune disorders related to immunotherapies has also been reported. These disorders include psoriasis, sarcoidosis, bullous pemphigoid and subacute lupus erythematosus.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5–7</span></a> To the best of our knowledge, this would be the first case of morphea relapsing due to any cancer immunotherapy treatment.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion, attending to the nature of this kind of immunotherapies, totally different from traditional chemotherapy, dermatologists should be aware not only of their typical irAEs, but also of the possibility of exacerbation or relapse of previously controlled skin diseases, especially immune-related ones. This will probably represent a new challenge for dermatologists in the future, as these treatments are being used more and more often. More experience is needed in order to conclude the exact relation of cancer immunotherapy and the relapse of these diseases.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interests</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interests" ] 1 => array:2 [ "identificador" => "xack262392" "titulo" => "Acknowledgement" ] 2 => 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" => 1036 "Ancho" => 1583 "Tamanyo" => 152134 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patches in both breasts and left inframammary fold, showing a shinny white color, liliaceous ring and atrophic surface.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1452 "Ancho" => 1583 "Tamanyo" => 386054 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histopathology (HE ×10): thickened collagen bundles in dermis, closely packed. Epidermal atrophy. Discrete perivascular limphocytic infiltrate.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety, activity, and immune correlates of anti-PD-1 antibody in cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.L. Topalian" 1 => "F.S. Hodi" 2 => "J.R. Brahmer" 3 => "S.N. Gettinger" 4 => "D.C. Smith" 5 => "D.F. McDermott" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1200690" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2012" "volumen" => "366" "paginaInicial" => "2443" "paginaFinal" => "2454" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22658127" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0060" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "quiz 237–8" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cutaneous adverse effects of targeted therapies: Part II: inhibitors of intracellular molecular signaling pathways" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.B. Macdonald" 1 => "B. Macdonald" 2 => "L.E. Golitz" 3 => "P. LoRusso" 4 => "A. Sekulic" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2014.07.033" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2015" "volumen" => "72" "paginaInicial" => "221" "paginaFinal" => "236" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25592339" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0065" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dermatologic complications of anti-PD-1/PD-L1 immune checkpoint antibodies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "V. Sibaud" 1 => "N. Meyer" 2 => "L. Lamant" 3 => "E. Vigarios" 4 => "J. Mazieres" 5 => "J.P. Delord" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CCO.0000000000000290" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Oncol" "fecha" => "2016" "volumen" => "28" "paginaInicial" => "254" "paginaFinal" => "263" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27136138" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0070" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V.R. Belum" 1 => "B. Benhuri" 2 => "M.A. Postow" 3 => "M.D. Hellmann" 4 => "A.M. Lesokhin" 5 => "N.H. Segal" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ejca.2016.02.010" "Revista" => array:6 [ "tituloSerie" => "Eur J Cancer" "fecha" => "2016" "volumen" => "60" "paginaInicial" => "12" "paginaFinal" => "25" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27043866" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0075" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ipilimumab therapy in patients with &advanced melanoma and preexisting autoimmune disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.B. Johnson" 1 => "R.J. Sullivan" 2 => "P.A. Ott" 3 => "M.S. Carlino" 4 => "N.I. Khushalani" 5 => "F. Ye" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jamaoncol.2015.4368" "Revista" => array:6 [ "tituloSerie" => "JAMA Oncol" "fecha" => "2016" "volumen" => "2" "paginaInicial" => "234" "paginaFinal" => "240" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26633184" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0080" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Exacerbation of psoriasis vulgaris during Nivolumab for oral mucosal melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Y. Kato" 1 => "A. Otsuka" 2 => "Y. Miyachi" 3 => "K. Kabashima" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "J Eur Acad Dermatol Venereol" "fecha" => "2015" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0085" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Exacerbation of psoriasis during Nivolumab therapy for metastatic melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "N. Matsumura" 1 => "M. Ohtsuka" 2 => "N. Kikuchi" 3 => "T. Yamamoto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2340/00015555-2212" "Revista" => array:6 [ "tituloSerie" => "Acta Derm Venereol" "fecha" => "2016" "volumen" => "96" "paginaInicial" => "259" "paginaFinal" => "260" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26270860" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0090" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "quiz 229–30" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Update on morphea: part I. Epidemiology, clinical presentation, and pathogenesis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "N. Fett" 1 => "V.P. Werth" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2010.05.045" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2011" "volumen" => "64" "paginaInicial" => "217" "paginaFinal" => "228" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21238823" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0095" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drug-induced morphea: report of a case induced by balicatib and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Peroni" 1 => "A. Zini" 2 => "V. Braga" 3 => "C. Colato" 4 => "S. Adami" 5 => "G. Girolomoni" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2008.03.009" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2008" "volumen" => "59" "paginaInicial" => "125" "paginaFinal" => "129" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18410981" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0100" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anti-PD-1-related pneumonitis during cancer immunotherapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Nishino" 1 => "L.M. Sholl" 2 => "F.S. Hodi" 3 => "H. Hatabu" 4 => "N.H. Ramaiya" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMc1505197" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2015" "volumen" => "373" "paginaInicial" => "288" "paginaFinal" => "290" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26176400" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack262392" "titulo" => "Acknowledgement" "texto" => "<p id="par0050" class="elsevierStylePara elsevierViewall">A C. M. García del Real for his collaboration.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010800000001/v1_201612300037/S1578219016303341/v1_201612300037/en/main.assets" "Apartado" => array:4 [ "identificador" => "6157" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case and Research Letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010800000001/v1_201612300037/S1578219016303341/v1_201612300037/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219016303341?idApp=UINPBA000044" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 8 | 3 | 11 |
| 2024 Octubre | 69 | 40 | 109 |
| 2024 Septiembre | 67 | 20 | 87 |
| 2024 Agosto | 73 | 49 | 122 |
| 2024 Julio | 67 | 27 | 94 |
| 2024 Junio | 69 | 29 | 98 |
| 2024 Mayo | 58 | 30 | 88 |
| 2024 Abril | 68 | 25 | 93 |
| 2024 Marzo | 69 | 26 | 95 |
| 2024 Febrero | 56 | 28 | 84 |
| 2024 Enero | 51 | 33 | 84 |
| 2023 Diciembre | 54 | 16 | 70 |
| 2023 Noviembre | 72 | 17 | 89 |
| 2023 Octubre | 65 | 22 | 87 |
| 2023 Septiembre | 44 | 33 | 77 |
| 2023 Agosto | 34 | 14 | 48 |
| 2023 Julio | 30 | 31 | 61 |
| 2023 Junio | 34 | 22 | 56 |
| 2023 Mayo | 40 | 30 | 70 |
| 2023 Abril | 35 | 15 | 50 |
| 2023 Marzo | 40 | 22 | 62 |
| 2023 Febrero | 39 | 22 | 61 |
| 2023 Enero | 42 | 38 | 80 |
| 2022 Diciembre | 52 | 40 | 92 |
| 2022 Noviembre | 22 | 29 | 51 |
| 2022 Octubre | 22 | 18 | 40 |
| 2022 Septiembre | 22 | 32 | 54 |
| 2022 Agosto | 51 | 23 | 74 |
| 2022 Julio | 38 | 34 | 72 |
| 2022 Junio | 32 | 29 | 61 |
| 2022 Mayo | 26 | 24 | 50 |
| 2022 Abril | 26 | 36 | 62 |
| 2022 Marzo | 43 | 42 | 85 |
| 2022 Febrero | 30 | 20 | 50 |
| 2022 Enero | 49 | 35 | 84 |
| 2021 Diciembre | 31 | 30 | 61 |
| 2021 Noviembre | 25 | 46 | 71 |
| 2021 Octubre | 45 | 48 | 93 |
| 2021 Septiembre | 27 | 49 | 76 |
| 2021 Agosto | 31 | 30 | 61 |
| 2021 Julio | 30 | 29 | 59 |
| 2021 Junio | 27 | 30 | 57 |
| 2021 Mayo | 40 | 51 | 91 |
| 2021 Abril | 56 | 79 | 135 |
| 2021 Marzo | 69 | 41 | 110 |
| 2021 Febrero | 40 | 37 | 77 |
| 2021 Enero | 32 | 32 | 64 |
| 2020 Diciembre | 40 | 34 | 74 |
| 2020 Noviembre | 25 | 23 | 48 |
| 2020 Octubre | 28 | 24 | 52 |
| 2020 Septiembre | 32 | 18 | 50 |
| 2020 Agosto | 28 | 36 | 64 |
| 2020 Julio | 29 | 24 | 53 |
| 2020 Junio | 30 | 32 | 62 |
| 2020 Mayo | 19 | 12 | 31 |
| 2020 Abril | 26 | 18 | 44 |
| 2020 Marzo | 25 | 16 | 41 |
| 2020 Febrero | 8 | 0 | 8 |
| 2020 Enero | 4 | 0 | 4 |
| 2019 Diciembre | 8 | 0 | 8 |
| 2019 Noviembre | 2 | 0 | 2 |
| 2019 Septiembre | 11 | 0 | 11 |
| 2019 Agosto | 7 | 0 | 7 |
| 2019 Julio | 4 | 0 | 4 |
| 2019 Junio | 4 | 0 | 4 |
| 2019 Mayo | 4 | 1 | 5 |
| 2019 Abril | 2 | 3 | 5 |
| 2019 Marzo | 1 | 2 | 3 |
| 2019 Febrero | 6 | 0 | 6 |
| 2018 Diciembre | 5 | 2 | 7 |
| 2018 Noviembre | 4 | 0 | 4 |
| 2018 Octubre | 5 | 0 | 5 |
| 2018 Septiembre | 2 | 0 | 2 |
| 2018 Febrero | 14 | 6 | 20 |
| 2018 Enero | 20 | 8 | 28 |
| 2017 Diciembre | 28 | 13 | 41 |
| 2017 Noviembre | 14 | 8 | 22 |
| 2017 Octubre | 10 | 7 | 17 |
| 2017 Septiembre | 18 | 7 | 25 |
| 2017 Agosto | 19 | 11 | 30 |
| 2017 Julio | 14 | 6 | 20 |
| 2017 Junio | 22 | 15 | 37 |
| 2017 Mayo | 17 | 11 | 28 |
| 2017 Abril | 25 | 13 | 38 |
| 2017 Marzo | 22 | 14 | 36 |
| 2017 Febrero | 33 | 23 | 56 |
| 2017 Enero | 47 | 35 | 82 |
| 2016 Diciembre | 5 | 3 | 8 |
Mostrar todo
