array:23 [
  "pii" => "S1699258X0673100X"
  "issn" => "1699258X"
  "doi" => "10.1016/S1699-258X(06)73100-X"
  "estado" => "S300"
  "fechaPublicacion" => "2006-11-01"
  "aid" => "73100"
  "copyright" => "Elsevier España S.L. Barcelona"
  "copyrightAnyo" => "2006"
  "documento" => "article"
  "crossmark" => 0
  "subdocumento" => "fla"
  "cita" => "Reumatol Clin. 2006;2 Supl 3:S6-9"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 5131
    "formatos" => array:3 [
      "EPUB" => 94
      "HTML" => 3868
      "PDF" => 1169
    ]
  ]
  "itemSiguiente" => array:18 [
    "pii" => "S1699258X06731011"
    "issn" => "1699258X"
    "doi" => "10.1016/S1699-258X(06)73101-1"
    "estado" => "S300"
    "fechaPublicacion" => "2006-11-01"
    "aid" => "73101"
    "copyright" => "Elsevier España S.L. Barcelona"
    "documento" => "article"
    "crossmark" => 0
    "subdocumento" => "fla"
    "cita" => "Reumatol Clin. 2006;2 Supl 3:S10-5"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 22630
      "formatos" => array:3 [
        "EPUB" => 131
        "HTML" => 6167
        "PDF" => 16332
      ]
    ]
    "es" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Esclerosis sist&#233;mica</span>"
      "titulo" => "Fen&#243;meno de Raynaud"
      "tienePdf" => "es"
      "tieneTextoCompleto" => 0
      "tieneResumen" => array:2 [
        0 => "es"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "S10"
          "paginaFinal" => "S15"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Raynaud&#8217;s phenomenon"
        ]
      ]
      "contieneResumen" => array:2 [
        "es" => true
        "en" => true
      ]
      "contienePdf" => array:1 [
        "es" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Miguel &#193;ngel Saavedra Salinas, Sandra Miriam Carrillo V&#225;zquez"
          "autores" => array:2 [
            0 => array:2 [
              "nombre" => "Miguel &#193;ngel"
              "apellidos" => "Saavedra Salinas"
            ]
            1 => array:2 [
              "nombre" => "Sandra Miriam"
              "apellidos" => "Carrillo V&#225;zquez"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X06731011?idApp=UINPBA00004M"
    "url" => "/1699258X/00000002000000S3/v1_201305061741/S1699258X06731011/v1_201305061741/es/main.assets"
  ]
  "itemAnterior" => array:18 [
    "pii" => "S1699258X06730996"
    "issn" => "1699258X"
    "doi" => "10.1016/S1699-258X(06)73099-6"
    "estado" => "S300"
    "fechaPublicacion" => "2006-11-01"
    "aid" => "73099"
    "copyright" => "Elsevier Espa&#241;a S&#46;L&#46; Barcelona"
    "documento" => "article"
    "crossmark" => 0
    "subdocumento" => "fla"
    "cita" => "Reumatol Clin. 2006;2 Supl 3:S2-5"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 5656
      "formatos" => array:3 [
        "EPUB" => 116
        "HTML" => 4402
        "PDF" => 1138
      ]
    ]
    "es" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Esclerosis sist&#233;mica</span>"
      "titulo" => "Epidemiolog&#237;a&#46; Diferencias &#233;tnicas en la esclerosis sist&#233;mica"
      "tienePdf" => "es"
      "tieneTextoCompleto" => 0
      "tieneResumen" => array:2 [
        0 => "es"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "S2"
          "paginaFinal" => "S5"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Epidemiology&#46; Ethnic differences in systemic sclerosis"
        ]
      ]
      "contieneResumen" => array:2 [
        "es" => true
        "en" => true
      ]
      "contienePdf" => array:1 [
        "es" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Jorge Rojas-Serrano"
          "autores" => array:1 [
            0 => array:2 [
              "nombre" => "Jorge"
              "apellidos" => "Rojas-Serrano"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X06730996?idApp=UINPBA00004M"
    "url" => "/1699258X/00000002000000S3/v1_201305061741/S1699258X06730996/v1_201305061741/es/main.assets"
  ]
  "es" => array:13 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Esclerosis sist&#233;mica</span>"
    "titulo" => "Etiopatogenia&#46; Nuevos conceptos"
    "tieneTextoCompleto" => 0
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "S6"
        "paginaFinal" => "S9"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Carmen Navarro, Martha L&#46; Bustos"
        "autores" => array:2 [
          0 => array:4 [
            "nombre" => "Carmen"
            "apellidos" => "Navarro"
            "email" => array:1 [
              0 => "mcnavigo&#64;yahoo&#46;com"
            ]
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">¿</span>"
                "identificador" => "cor1"
              ]
            ]
          ]
          1 => array:2 [
            "nombre" => "Martha L&#46;"
            "apellidos" => "Bustos"
          ]
        ]
        "afiliaciones" => array:1 [
          0 => array:1 [
            "entidad" => "Subdirecci&#243;n de Investigaci&#243;n Cl&#237;nica&#46; Instituto Nacional de Enfermedades Respiratorias&#46; Tlalpan&#46; M&#233;xico DF&#46; M&#233;xico"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor1"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Correspondencia&#58; Dra&#46; C&#46; Navarro&#46; Subdirecci&#243;n de Investigaci&#243;n Cl&#237;nica&#46; Instituto Nacional de Enfermedades Respiratorias&#46; Sistema Nacional de Investigadores-I&#46; Calzada de Tlalpan 4502&#44; Secci&#243;n XVI&#46; 14080 Tlalpan&#46; M&#233;xico DF&#46; M&#233;xico&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "en" => array:1 [
        "titulo" => "Etiopathogenesis&#46; New concepts"
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "PalabrasClave" => array:2 [
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec111997"
          "palabras" => array:4 [
            0 => "C&#233;lulas endoteliales"
            1 => "Matriz extracelular"
            2 => "Anticuerpos antitopoisomerasa I"
            3 => "Anticuerpos anticentr&#243;metro"
          ]
        ]
      ]
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Key words"
          "identificador" => "xpalclavsec111996"
          "palabras" => array:4 [
            0 => "Endotelial cells"
            1 => "Extracellular matrix"
            2 => "Antitopoisomerasa I antibodies"
            3 => "Anticentromeral antibodies"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<p class="elsevierStyleSimplePara elsevierViewall">La esclerosis sist&#233;mica progresiva es una enfermedad autoinmunitaria compleja&#44; de etiolog&#237;a desconocida&#44; que se caracteriza por anormalidades inmunol&#243;gicas&#44; da&#241;o endotelial y fibrosis tisular&#46; La interacci&#243;n entre la carga gen&#233;tica y el ambiente puede producir una respuesta inmunitaria alterada&#44; con expansi&#243;n de c&#233;lulas Th2&#44; exceso de producci&#243;n de citocinas antiinflamatorias profibr&#243;ticas y exceso de estimulaci&#243;n de c&#233;lulas B&#46; La producci&#243;n de autoanticuerpos espec&#237;ficos caracteriza subtipos cl&#237;nicos&#46; La activaci&#243;n y el da&#241;o vascular con alteraci&#243;n en la respuesta vasodilatadora y vasoconstrictora son eventos tempranos en la enfermedad&#46; La isquemia y el da&#241;o inmunitario persistente favorecen la proliferaci&#243;n de miofibroblastos&#44; con incremento en la producci&#243;n de prote&#237;nas de la matriz extracelular&#44; lo que finalmente lleva a la fibrosis y la p&#233;rdida de funci&#243;n&#46;</p>"
      ]
      "en" => array:1 [
        "resumen" => "<p class="elsevierStyleSimplePara elsevierViewall">Systemic sclerosis is a complex&#44; progressive autoimmune disease&#46; The origin is&#44; so far&#44; unknown and it is characterized by immunological and endothelial damage followed by fibrosis&#46; Interaction between the host genetic backgrounds with environmental factors is thought to turn out an abnormal immune response characterized by clonal expansion of Th2 repertoire&#44; upregulation of pro-fibrotic cytokines and dysregulated B cells&#46; Specific autoantibodies profiles are associated with clinical subtypes of the diseases&#46; Endothelial activation is an early feature with damage of the vasocontrictive and vasodilation response&#46; Finally&#44; persistent tissue ischemia and abnormal immune response produce myofibroblast proliferation andoverproduction of extracellular matrix proteins and fibrosis&#46;</p>"
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Bibliograf&#237;a"
      "seccion" => array:1 [
        0 => array:1 [
          "bibliografiaReferencia" => array:23 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association of polar amino acids at position 26 of the HLA-DQB1 first domain with the anticentromere autoantibody response in systemic sclerosis &#40;scleroderma&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46;D&#46; Reveille"
                            1 => "D&#46; Owerbach"
                            2 => "R&#46; Goldstein"
                            3 => "R&#46; Moreda"
                            4 => "R&#46;A&#46; Isern"
                            5 => "F&#46;C&#46; Arnett"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI115704"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "1992"
                        "volumen" => "89"
                        "paginaInicial" => "1208"
                        "paginaFinal" => "1213"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1556182"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib2"
              "etiqueta" => "2&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HLA and ethnic associations among systemic sclerosis patients with anticentromere antibodies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;A&#46; Morel"
                            1 => "H&#46;J&#46; Chang"
                            2 => "J&#46;W&#46; Wilson"
                            3 => "C&#46; Conte"
                            4 => "D&#46; Falkner"
                            5 => "D&#46;J&#46; Tweardy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Hum Immunol"
                        "fecha" => "1995"
                        "volumen" => "42"
                        "paginaInicial" => "35"
                        "paginaFinal" => "42"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7751158"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib3"
              "etiqueta" => "3&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Severe systemic sclerosis with anti-topoisomerase I antibodies is associated with an HLA-DRw11 allele"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;A&#46; Morel"
                            1 => "H&#46;J&#46; Chang"
                            2 => "J&#46;W&#46; Wilson"
                            3 => "C&#46; Conte"
                            4 => "S&#46;L&#46; Saidman"
                            5 => "J&#46;D&#46; Bray"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Hum Immunol"
                        "fecha" => "1994"
                        "volumen" => "40"
                        "paginaInicial" => "101"
                        "paginaFinal" => "110"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7928439"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib4"
              "etiqueta" => "4&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The HLA-DR and DQ genes control the autoimmune response to DNA topoisomerase I in systemic sclerosis &#40;scleroderma&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; Kuwana"
                            1 => "J&#46; Kaburaki"
                            2 => "Y&#46; Okano"
                            3 => "H&#46; Inoko"
                            4 => "K&#46; Tsuji"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI116703"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "1993"
                        "volumen" => "92"
                        "paginaInicial" => "1296"
                        "paginaFinal" => "1301"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7690776"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib5"
              "etiqueta" => "5&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autoantibodies to fibrillarin in systemic sclerosis &#40;scleroderma&#41;&#46; An immunogenetic&#44; serologic&#44; and clinical analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46;C&#46; Arnett"
                            1 => "J&#46;D&#46; Reveille"
                            2 => "R&#46; Goldstein"
                            3 => "K&#46;M&#46; Pollard"
                            4 => "K&#46; Leaird"
                            5 => "E&#46;A&#46; Smith"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "1996"
                        "volumen" => "39"
                        "paginaInicial" => "1151"
                        "paginaFinal" => "1160"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8670324"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib6"
              "etiqueta" => "6&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Maternal-fetal immunology and autoimmune disease&#46; Is some autoimmune disease auto-alloimmuneor allo-autoimmune&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46;L&#46; Nelson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "1996"
                        "volumen" => "39"
                        "paginaInicial" => "191"
                        "paginaFinal" => "194"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8849367"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib7"
              "etiqueta" => "7&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology of systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "T&#46; Medsger"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin&#46; Dermatol"
                        "fecha" => "1994"
                        "volumen" => "12"
                        "paginaInicial" => "207"
                        "paginaFinal" => "216"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8076257"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib8"
              "etiqueta" => "8&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Scleroderma-like changes due to chronic graft-versus-host disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46; Graham-Brown"
                            1 => "I&#46; Sarkany"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Dermatol"
                        "fecha" => "1983"
                        "volumen" => "8"
                        "paginaInicial" => "531"
                        "paginaFinal" => "538"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6357572"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib9"
              "etiqueta" => "9&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Detection of cellular microchimerism of male or female origin in systemic sclerosis patients by polymerase chain reaction analysis of HLA-Cw antigens"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "C&#46;M&#46; Artlett"
                            1 => "L&#46;A&#46; Cox"
                            2 => "S&#46;A&#46; Jimenez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/1529-0131(200005)43:5<1062::AID-ANR16>3.0.CO;2-P"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2000"
                        "volumen" => "43"
                        "paginaInicial" => "1062"
                        "paginaFinal" => "1067"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10817560"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib10"
              "etiqueta" => "10&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Microchimerism and HLA-compatible relationship of pregnancy in scleroderma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Nelson"
                            1 => "D&#46; Furst"
                            2 => "S&#46; Maloney"
                            3 => "T&#46; Gooley"
                            4 => "P&#46; Evans"
                            5 => "A&#46; Smith"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(97)08357-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "1998"
                        "volumen" => "351"
                        "paginaInicial" => "559"
                        "paginaFinal" => "562"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9492775"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Persistent fetal microchimerism in T lymphocytes is associated with HLA-DQA1&#42;0501&#58; Implications in autoimmunity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Lambert"
                            1 => "P&#46; Evans"
                            2 => "T&#46; Hashizumi"
                            3 => "S&#46; Maloney"
                            4 => "T&#46; Gooley"
                            5 => "D&#46; Furst"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Rheumatol Immunol"
                        "fecha" => "2000"
                        "volumen" => "164"
                        "paginaInicial" => "5545"
                        "paginaFinal" => "5548"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HLA-DQA1 is not an apparent risk factor for microchimerism in patients with various autoimmune diseases and in healthy individuals"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C&#46;M&#46; Artlett"
                            1 => "T&#46;P&#46; O&#8217;Hanlon"
                            2 => "A&#46;M&#46; Lopez"
                            3 => "Y&#46;W&#46; Song"
                            4 => "F&#46;W&#46; Miller"
                            5 => "L&#46;G&#46; Rider"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.11235"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2003"
                        "volumen" => "48"
                        "paginaInicial" => "2567"
                        "paginaFinal" => "2572"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/13130476"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Scleroderma&#58; from cell and molecular mechanisms to disease models"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46;J&#46; Abraham"
                            1 => "J&#46; Varga"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.it.2005.09.004"
                      "Revista" => array:7 [
                        "tituloSerie" => "Trends Immunol"
                        "fecha" => "2005"
                        "volumen" => "26"
                        "paginaInicial" => "587"
                        "paginaFinal" => "595"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16168711"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0002937804005538"
                          "estado" => "S300"
                          "issn" => "00029378"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cytokine profile and proteome analysis in bronchoalveolar lavage of patients with sarcoidosis&#44; pulmonary fibrosis associated with systemic sclerosis and idiopathic pulmonary fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Rottoli"
                            1 => "P&#46; Magi"
                            2 => "M&#46;G&#46; Perari"
                            3 => "S&#46; Liberatory"
                            4 => "N&#46; Nikiforakis"
                            5 => "E&#46; Bargagli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/pmic.200301007"
                      "Revista" => array:6 [
                        "tituloSerie" => "Proteomics"
                        "fecha" => "2005"
                        "volumen" => "5"
                        "paginaInicial" => "1423"
                        "paginaFinal" => "1430"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15761959"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "T cell and B cells in the pathogenesis of systemic sclerosis&#58; recent insights and therapeutic opportunities"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "F&#46; Del Galdo"
                            1 => "C&#46;M&#46; Artlett"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Rheumatol Rep"
                        "fecha" => "2006"
                        "volumen" => "8"
                        "paginaInicial" => "123"
                        "paginaFinal" => "130"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16569371"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib16"
              "etiqueta" => "16&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The pathogenic role of autoantibodies to nuclear autoantigens in systemic sclerosis &#40;scleroderma&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46;L&#46; Senecal"
                            1 => "J&#46; H&#233;nault"
                            2 => "Y&#46; Raymond"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Rheum"
                        "fecha" => "2005"
                        "volumen" => "32"
                        "paginaInicial" => "1643"
                        "paginaFinal" => "1648"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16142854"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0002937809007820"
                          "estado" => "S300"
                          "issn" => "00029378"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autoimmunity in scleroderma&#58; the origin&#44; pathogenetic role&#44; and clinical significance of autoantibodies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;L&#46; Harris"
                            1 => "A&#46; Rosen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Rheumatol"
                        "fecha" => "2003"
                        "volumen" => "15"
                        "paginaInicial" => "778"
                        "paginaFinal" => "784"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14569210"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;S&#46; Baroni"
                            1 => "M&#46; Santillo"
                            2 => "F&#46; Bevilacquia"
                            3 => "M&#46; Luchetti"
                            4 => "T&#46; Spadoni"
                            5 => "M&#46; Mancini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa052955"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2006"
                        "volumen" => "354"
                        "paginaInicial" => "2667"
                        "paginaFinal" => "2676"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16790699"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Capillary alterations in scleroderma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46; Fleischmajer"
                            1 => "J&#46;S&#46; Perlish"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "1980"
                        "volumen" => "2"
                        "paginaInicial" => "161"
                        "paginaFinal" => "170"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7364973"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib20"
              "etiqueta" => "20&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Scleroderma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46; Morro"
                            1 => "L&#46; Nelson"
                            2 => "R&#46; Watts"
                            3 => "D&#46; Isenberg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:5 [
                        "edicion" => "2&#46;&#170; ed&#46;"
                        "titulo" => "Autoimmune Rheumatic Disease"
                        "fecha" => "1999"
                        "editorial" => "Oxford University Press"
                        "editorialLocalizacion" => "New York"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib21"
              "etiqueta" => "21&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Microvascular damage in systemic sclerosis&#58; detection and monitoring with biomarkers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "L&#46;K&#46; Hummers"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Rheumatol Rep"
                        "fecha" => "2006"
                        "volumen" => "8"
                        "paginaInicial" => "131"
                        "paginaFinal" => "137"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16569372"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib22"
              "etiqueta" => "22&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Activation of key profibrotic mechanisms in transgenic fibroblasts expressing kinase-deficient type T II transforming growth factor- b receptor &#40;TbRIIdK&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;P&#46; Denton"
                            1 => "G&#46;E&#46; Lindahl"
                            2 => "K&#46; Khan"
                            3 => "X&#46; Shiwen"
                            4 => "V&#46;H&#46; Ong"
                            5 => "N&#46;J&#46; Gaspar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.M413134200"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "2005"
                        "volumen" => "280"
                        "paginaInicial" => "16053"
                        "paginaFinal" => "16065"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15708853"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib23"
              "etiqueta" => "23&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Targeted therapy comes of age in scleroderma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46;P&#46; Denton"
                            1 => "C&#46;M&#46; Black"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.it.2005.09.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Trends Immunol"
                        "fecha" => "2005"
                        "volumen" => "26"
                        "paginaInicial" => "596"
                        "paginaFinal" => "602"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16168710"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "es"
  "url" => "/1699258X/00000002000000S3/v1_201305061741/S1699258X0673100X/v1_201305061741/es/main.assets"
  "Apartado" => null
  "PDF" => "https://static.elsevier.es/multimedia/1699258X/00000002000000S3/v1_201305061741/S1699258X0673100X/v1_201305061741/es/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X0673100X?idApp=UINPBA00004M"
]
Compartir
Información de la revista
Vol. 2. Núm. S3.
Esclerosis sistémica
Páginas S6-S9 (noviembre 2006)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 2. Núm. S3.
Esclerosis sistémica
Páginas S6-S9 (noviembre 2006)
Esclerosis sistémica
Acceso a texto completo
Etiopatogenia. Nuevos conceptos
Etiopathogenesis. New concepts
Visitas
10543
Carmen Navarro
Autor para correspondencia
mcnavigo@yahoo.com

Correspondencia: Dra. C. Navarro. Subdirección de Investigación Clínica. Instituto Nacional de Enfermedades Respiratorias. Sistema Nacional de Investigadores-I. Calzada de Tlalpan 4502, Sección XVI. 14080 Tlalpan. México DF. México.
, Martha L. Bustos
Subdirección de Investigación Clínica. Instituto Nacional de Enfermedades Respiratorias. Tlalpan. México DF. México
Este artículo ha recibido
Información del artículo
Resumen
Bibliografía
Descargar PDF
Estadísticas
Resumen

La esclerosis sistémica progresiva es una enfermedad autoinmunitaria compleja, de etiología desconocida, que se caracteriza por anormalidades inmunológicas, daño endotelial y fibrosis tisular. La interacción entre la carga genética y el ambiente puede producir una respuesta inmunitaria alterada, con expansión de células Th2, exceso de producción de citocinas antiinflamatorias profibróticas y exceso de estimulación de células B. La producción de autoanticuerpos específicos caracteriza subtipos clínicos. La activación y el daño vascular con alteración en la respuesta vasodilatadora y vasoconstrictora son eventos tempranos en la enfermedad. La isquemia y el daño inmunitario persistente favorecen la proliferación de miofibroblastos, con incremento en la producción de proteínas de la matriz extracelular, lo que finalmente lleva a la fibrosis y la pérdida de función.

Palabras clave:
Células endoteliales
Matriz extracelular
Anticuerpos antitopoisomerasa I
Anticuerpos anticentrómetro

Systemic sclerosis is a complex, progressive autoimmune disease. The origin is, so far, unknown and it is characterized by immunological and endothelial damage followed by fibrosis. Interaction between the host genetic backgrounds with environmental factors is thought to turn out an abnormal immune response characterized by clonal expansion of Th2 repertoire, upregulation of pro-fibrotic cytokines and dysregulated B cells. Specific autoantibodies profiles are associated with clinical subtypes of the diseases. Endothelial activation is an early feature with damage of the vasocontrictive and vasodilation response. Finally, persistent tissue ischemia and abnormal immune response produce myofibroblast proliferation andoverproduction of extracellular matrix proteins and fibrosis.

Key words:
Endotelial cells
Extracellular matrix
Antitopoisomerasa I antibodies
Anticentromeral antibodies
El Texto completo está disponible en PDF
Bibliografía
[1.]
J.D. Reveille, D. Owerbach, R. Goldstein, R. Moreda, R.A. Isern, F.C. Arnett.
Association of polar amino acids at position 26 of the HLA-DQB1 first domain with the anticentromere autoantibody response in systemic sclerosis (scleroderma).
J Clin Invest, 89 (1992), pp. 1208-1213
[2.]
P.A. Morel, H.J. Chang, J.W. Wilson, C. Conte, D. Falkner, D.J. Tweardy, et al.
HLA and ethnic associations among systemic sclerosis patients with anticentromere antibodies.
Hum Immunol, 42 (1995), pp. 35-42
[3.]
P.A. Morel, H.J. Chang, J.W. Wilson, C. Conte, S.L. Saidman, J.D. Bray, et al.
Severe systemic sclerosis with anti-topoisomerase I antibodies is associated with an HLA-DRw11 allele.
Hum Immunol, 40 (1994), pp. 101-110
[4.]
M. Kuwana, J. Kaburaki, Y. Okano, H. Inoko, K. Tsuji.
The HLA-DR and DQ genes control the autoimmune response to DNA topoisomerase I in systemic sclerosis (scleroderma).
J Clin Invest, 92 (1993), pp. 1296-1301
[5.]
F.C. Arnett, J.D. Reveille, R. Goldstein, K.M. Pollard, K. Leaird, E.A. Smith, et al.
Autoantibodies to fibrillarin in systemic sclerosis (scleroderma). An immunogenetic, serologic, and clinical analysis.
Arthritis Rheum, 39 (1996), pp. 1151-1160
[6.]
J.L. Nelson.
Maternal-fetal immunology and autoimmune disease. Is some autoimmune disease auto-alloimmuneor allo-autoimmune?.
Arthritis Rheum, 39 (1996), pp. 191-194
[7.]
T. Medsger.
Epidemiology of systemic sclerosis.
Clin. Dermatol, 12 (1994), pp. 207-216
[8.]
R. Graham-Brown, I. Sarkany.
Scleroderma-like changes due to chronic graft-versus-host disease.
Clin Exp Dermatol, 8 (1983), pp. 531-538
[9.]
C.M. Artlett, L.A. Cox, S.A. Jimenez.
Detection of cellular microchimerism of male or female origin in systemic sclerosis patients by polymerase chain reaction analysis of HLA-Cw antigens.
[10.]
L. Nelson, D. Furst, S. Maloney, T. Gooley, P. Evans, A. Smith, et al.
Microchimerism and HLA-compatible relationship of pregnancy in scleroderma.
[11.]
N. Lambert, P. Evans, T. Hashizumi, S. Maloney, T. Gooley, D. Furst, et al.
Persistent fetal microchimerism in T lymphocytes is associated with HLA-DQA1*0501: Implications in autoimmunity.
J Rheumatol Immunol, 164 (2000), pp. 5545-5548
[12.]
C.M. Artlett, T.P. O’Hanlon, A.M. Lopez, Y.W. Song, F.W. Miller, L.G. Rider.
HLA-DQA1 is not an apparent risk factor for microchimerism in patients with various autoimmune diseases and in healthy individuals.
Arthritis Rheum, 48 (2003), pp. 2567-2572
[13.]
D.J. Abraham, J. Varga.
Scleroderma: from cell and molecular mechanisms to disease models.
Trends Immunol, 26 (2005), pp. 587-595
[14.]
P. Rottoli, P. Magi, M.G. Perari, S. Liberatory, N. Nikiforakis, E. Bargagli, et al.
Cytokine profile and proteome analysis in bronchoalveolar lavage of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis and idiopathic pulmonary fibrosis.
Proteomics, 5 (2005), pp. 1423-1430
[15.]
F. Del Galdo, C.M. Artlett.
T cell and B cells in the pathogenesis of systemic sclerosis: recent insights and therapeutic opportunities.
Curr Rheumatol Rep, 8 (2006), pp. 123-130
[16.]
J.L. Senecal, J. Hénault, Y. Raymond.
The pathogenic role of autoantibodies to nuclear autoantigens in systemic sclerosis (scleroderma).
J Rheum, 32 (2005), pp. 1643-1648
[17.]
M.L. Harris, A. Rosen.
Autoimmunity in scleroderma: the origin, pathogenetic role, and clinical significance of autoantibodies.
Curr Opin Rheumatol, 15 (2003), pp. 778-784
[18.]
S.S. Baroni, M. Santillo, F. Bevilacquia, M. Luchetti, T. Spadoni, M. Mancini, et al.
Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis.
N Engl J Med, 354 (2006), pp. 2667-2676
[19.]
R. Fleischmajer, J.S. Perlish.
Capillary alterations in scleroderma.
J Am Acad Dermatol, 2 (1980), pp. 161-170
[20.]
J. Morro, L. Nelson, R. Watts, D. Isenberg.
Scleroderma.
Autoimmune Rheumatic Disease, 2.ª ed., Oxford University Press, (1999),
[21.]
L.K. Hummers.
Microvascular damage in systemic sclerosis: detection and monitoring with biomarkers.
Curr Rheumatol Rep, 8 (2006), pp. 131-137
[22.]
C.P. Denton, G.E. Lindahl, K. Khan, X. Shiwen, V.H. Ong, N.J. Gaspar, et al.
Activation of key profibrotic mechanisms in transgenic fibroblasts expressing kinase-deficient type T II transforming growth factor- b receptor (TbRIIdK).
J Biol Chem, 280 (2005), pp. 16053-16065
[23.]
C.P. Denton, C.M. Black.
Targeted therapy comes of age in scleroderma.
Trends Immunol, 26 (2005), pp. 596-602
Copyright © 2006. Elsevier España S.L. Barcelona
Descargar PDF
Idiomas
Reumatología Clínica
Opciones de artículo
Herramientas
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?