metricas
covid
Buscar en
Clinics
Toda la web
Inicio Clinics The skin tissue is adversely affected by TNF-alpha blockers in patients with chr...
Journal Information

Statistics

Follow this link to access the full text of the article

CLINICAL SCIENCE
The skin tissue is adversely affected by TNF-alpha blockers in patients with chronic inflammatory arthritis: a 5-year prospective analysis
Natalia P. MachadoI, Edgard Torres dos Reis NetoI, Maria Roberta M.P. SoaresI, Daniele S. FreitasI, Adriana PorroII, Rozana M. CiconelliIII, Marcelo M. PinheiroI,
Corresponding author
mpinheiro@uol.com.br

Tel.: 55 11 5576-4239
I Universidade Federal de São Paulo, Escola Paulista de Medicina (Unifesp/EPM), Rheumatology Division, São Paulo/SP, Brazil
II Universidade Federal de São Paulo, Escola Paulista de Medicina (Unifesp/EPM), Dermatology Department, Psoriasis Clinic, São Paulo/SP, Brazil
III Universidade Federal de São Paulo, Escola Paulista de Medicina (Unifesp/EPM), Center for Health Economics, São Paulo/SP, Brazil
Read
747
Times
was read the article
331
Total PDF
416
Total HTML
Share statistics
 array:24 [
  "pii" => "S1807593222016209"
  "issn" => "18075932"
  "doi" => "10.6061/clinics/2013(09)03"
  "estado" => "S300"
  "fechaPublicacion" => "2013-09-01"
  "aid" => "1620"
  "copyright" => "CLINICS"
  "copyrightAnyo" => "2013"
  "documento" => "article"
  "crossmark" => 0
  "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/"
  "subdocumento" => "fla"
  "cita" => "Clinics. 2013;68:1189-96"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:1 [
    "total" => 0
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S1807593222016210"
    "issn" => "18075932"
    "doi" => "10.6061/clinics/2013(09)04"
    "estado" => "S300"
    "fechaPublicacion" => "2013-09-01"
    "aid" => "1621"
    "copyright" => "CLINICS"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/"
    "subdocumento" => "fla"
    "cita" => "Clinics. 2013;68:1197-205"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">CLINICAL SCIENCE</span>"
      "titulo" => "Magnetic resonance imaging and neuropsychological testing in the spectrum of normal aging"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "1197"
          "paginaFinal" => "1205"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig3"
          "etiqueta" => "Figure 3"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr3.jpeg"
              "Alto" => 579
              "Ancho" => 719
              "Tamanyo" => 19034
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">Relationship between Age and RMI&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Maria Paula Foss, Paula Rejane Beserra Diniz, Paulo Formigheri, Carlos Ernesto Garrido Salmon, Jos&#233; Geraldo Speciali, Ant&#244;nio Carlos Santos"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Maria Paula"
              "apellidos" => "Foss"
            ]
            1 => array:2 [
              "nombre" => "Paula Rejane Beserra"
              "apellidos" => "Diniz"
            ]
            2 => array:2 [
              "nombre" => "Paulo"
              "apellidos" => "Formigheri"
            ]
            3 => array:2 [
              "nombre" => "Carlos Ernesto Garrido"
              "apellidos" => "Salmon"
            ]
            4 => array:2 [
              "nombre" => "Jos&#233; Geraldo"
              "apellidos" => "Speciali"
            ]
            5 => array:2 [
              "nombre" => "Ant&#244;nio Carlos"
              "apellidos" => "Santos"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222016210?idApp=UINPBA00004N"
    "url" => "/18075932/0000006800000009/v1_202212010704/S1807593222016210/v1_202212010704/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S1807593222016192"
    "issn" => "18075932"
    "doi" => "10.6061/clinics/2013(09)02"
    "estado" => "S300"
    "fechaPublicacion" => "2013-09-01"
    "aid" => "1619"
    "copyright" => "CLINICS"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/"
    "subdocumento" => "fla"
    "cita" => "Clinics. 2013;68:1180-8"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">CLINICAL SCIENCE</span>"
      "titulo" => "Preliminary analysis of knee stress in Full Extension Landing"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "1180"
          "paginaFinal" => "1188"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig3"
          "etiqueta" => "Figure 3"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr3.jpeg"
              "Alto" => 1533
              "Ancho" => 792
              "Tamanyo" => 98898
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">I<span class="elsevierStyleBold">-</span>a Moving plate with specified velocity &#40;b&#41; applying instant load to &#40;II&#41; vertical impact force across different heights &#40;III&#41; Analytical and experimental comparison of impact force across different heights&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Majid Davoodi Makinejad, Noor Azuan Abu Osman, Wan Abu Bakar Wan Abas, Mehdi Bayat"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "Majid Davoodi"
              "apellidos" => "Makinejad"
            ]
            1 => array:2 [
              "nombre" => "Noor Azuan"
              "apellidos" => "Abu Osman"
            ]
            2 => array:2 [
              "nombre" => "Wan Abu Bakar"
              "apellidos" => "Wan Abas"
            ]
            3 => array:2 [
              "nombre" => "Mehdi"
              "apellidos" => "Bayat"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222016192?idApp=UINPBA00004N"
    "url" => "/18075932/0000006800000009/v1_202212010704/S1807593222016192/v1_202212010704/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">CLINICAL SCIENCE</span>"
    "titulo" => "The skin tissue is adversely affected by TNF-alpha blockers in patients with chronic inflammatory arthritis&#58; a 5-year prospective analysis"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "1189"
        "paginaFinal" => "1196"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Natalia P&#46; Machado, Edgard Torres dos Reis Neto, Maria Roberta M&#46;P&#46; Soares, Daniele S&#46; Freitas, Adriana Porro, Rozana M&#46; Ciconelli, Marcelo M&#46; Pinheiro"
        "autores" => array:7 [
          0 => array:3 [
            "nombre" => "Natalia P&#46;"
            "apellidos" => "Machado"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">I</span>"
                "identificador" => "aff1"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Edgard Torres"
            "apellidos" => "dos Reis Neto"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">I</span>"
                "identificador" => "aff1"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Maria Roberta M&#46;P&#46;"
            "apellidos" => "Soares"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">I</span>"
                "identificador" => "aff1"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Daniele S&#46;"
            "apellidos" => "Freitas"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">I</span>"
                "identificador" => "aff1"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Adriana"
            "apellidos" => "Porro"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">II</span>"
                "identificador" => "aff2"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "Rozana M&#46;"
            "apellidos" => "Ciconelli"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">III</span>"
                "identificador" => "aff3"
              ]
            ]
          ]
          6 => array:4 [
            "nombre" => "Marcelo M&#46;"
            "apellidos" => "Pinheiro"
            "email" => array:1 [
              0 => "mpinheiro@uol.com.br"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">I</span>"
                "identificador" => "aff1"
              ]
              1 => array:2 [
                "etiqueta" => "&#42;"
                "identificador" => "cor1"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:3 [
          0 => array:3 [
            "entidad" => "Universidade Federal de S&#227;o Paulo&#44; Escola Paulista de Medicina &#40;Unifesp&#47;EPM&#41;&#44; Rheumatology Division&#44; S&#227;o Paulo&#47;SP&#44; Brazil"
            "etiqueta" => "I"
            "identificador" => "aff1"
          ]
          1 => array:3 [
            "entidad" => "Universidade Federal de S&#227;o Paulo&#44; Escola Paulista de Medicina &#40;Unifesp&#47;EPM&#41;&#44; Dermatology Department&#44; Psoriasis Clinic&#44; S&#227;o Paulo&#47;SP&#44; Brazil"
            "etiqueta" => "II"
            "identificador" => "aff2"
          ]
          2 => array:3 [
            "entidad" => "Universidade Federal de S&#227;o Paulo&#44; Escola Paulista de Medicina &#40;Unifesp&#47;EPM&#41;&#44; Center for Health Economics&#44; S&#227;o Paulo&#47;SP&#44; Brazil"
            "etiqueta" => "III"
            "identificador" => "aff3"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor1"
            "etiqueta" => "&#42;"
            "correspondencia" => "Tel&#46;&#58; 55 11 5576-4239"
          ]
        ]
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig1"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 365
            "Ancho" => 745
            "Tamanyo" => 29498
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Grouping of CAEs according to mechanism involved &#40;immune-allergic vs&#46; infectious&#41;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle60">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">A number of studies have demonstrated that TNF-&#945; blockers&#44; including monoclonal antibodies &#40;infliximab &#91;IFX&#93;&#44; adalimumab &#91;ADA&#93; and golimumab &#91;GOL&#93;&#41; and soluble TNF receptors &#40;etanercept &#91;ETN&#93;&#41;&#44; are effective in the treatment of rheumatoid arthritis &#40;RA&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib1">1</a>&#41;&#44; ankylosing spondylitis &#40;AS&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib2">2</a>&#41;&#44; psoriatic arthritis &#40;PA&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib3">3</a>&#41;&#44; juvenile idiopathic arthritis &#40;JIA&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib4">4</a>&#41;&#44; psoriasis &#40;<a class="elsevierStyleCrossRef" href="#bib5">5</a>&#41; and inflammatory bowel disease &#40;<a class="elsevierStyleCrossRef" href="#bib6">6</a>&#41;&#46; However&#44; these medications are associated with the occurrence of skin manifestations &#40;dermatosis and dermatitis&#41;&#44; with a frequency ranging from 10&#37; to 60&#37; &#40;<a class="elsevierStyleCrossRefs" href="#bib7">7&#8211;9</a>&#41;&#46;</p><p id="para20" class="elsevierStylePara elsevierViewall">Undesirable events generally quickly resolved after the withdrawal of TNF-&#945; blockers or with the use of glucocorticoid steroids &#40;GCs&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib10">10</a>&#44;<a class="elsevierStyleCrossRef" href="#bib11">11</a>&#41; or antimicrobial agents&#46; In some cases&#44; it is possible to maintain treatment or to switch to another TNF-&#945; blocker or biologic agent&#44; such as rituximab &#40;RTX&#41;&#44; abatacept &#40;ABT&#41; or tocilizumab &#40;TCZ&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib1">1</a>&#41;&#46;</p><p id="para30" class="elsevierStylePara elsevierViewall">Among the types of acute lesions&#44; the main differential diagnoses include allergic&#44; urticariform and infectious manifestations caused by viruses &#40;especially herpes&#41;&#44; bacteria &#40;e&#46;g&#46;&#44; staphylococcus and streptococcus&#41;&#44; fungi &#40;candida&#41; and parasites &#40;especially scabies&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib7">7</a>&#44;<a class="elsevierStyleCrossRef" href="#bib8">8</a>&#44;<a class="elsevierStyleCrossRef" href="#bib12">12</a>&#44;<a class="elsevierStyleCrossRef" href="#bib13">13</a>&#41;&#46;</p><p id="para40" class="elsevierStylePara elsevierViewall">The majority of chronic lesions consist of psoriasis-like eczema &#40;<a class="elsevierStyleCrossRef" href="#bib13">13</a>&#44;<a class="elsevierStyleCrossRef" href="#bib14">14</a>&#41;&#44; although herpetiform dermatitis&#44; small vessel vasculitis&#44; alopecia areata&#44; palmoplantar pustulosis&#44; atopic dermatitis&#44; lichenoid rash&#44; purpura&#44; skin neoplasms&#44; polymorphic and multiform erythema have also been reported &#40;<a class="elsevierStyleCrossRef" href="#bib7">7</a>&#44;<a class="elsevierStyleCrossRef" href="#bib8">8</a>&#44;<a class="elsevierStyleCrossRef" href="#bib15">15</a>&#41;&#46;</p><p id="para50" class="elsevierStylePara elsevierViewall">The aim of the present study was to evaluate the incidence and the main risk factors associated with cutaneous adverse events &#40;CAEs&#41; in patients with chronic inflammatory arthropathies &#40;CIAs&#41; who receive TNF-&#945; blockers&#46;</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">PATIENTS AND METHODS</span><p id="para60" class="elsevierStylePara elsevierViewall">A total of 257 patients with active CIA and who were receiving TNF-&#945; blockers were evaluated&#44; including 158 &#40;61&#46;5&#37;&#41; patients with RA &#40;ACR&#44; 1987&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib16">16</a>&#41;&#44; 87 &#40;33&#46;8&#37;&#41; with AS &#40;modified New York criteria&#44; 1984&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib17">17</a>&#41; and 12 &#40;4&#46;7&#37;&#41; with PA &#40;CASPAR&#44; 2006&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib18">18</a>&#41;&#44; in a prospective analysis from January 2005 to December 2009&#46; All of the patients were regularly followed at the Immunobiological Clinic of the Rheumatology Division of the Universidade Federal de S&#227;o Paulo&#47;Escola Paulista de Medicina &#40;Brazil&#41;&#44; and all of the patients demonstrated moderate to severe disease activity and had received anti-TNF-&#945; therapy for the previous 6 months &#40;<a class="elsevierStyleCrossRef" href="#bib19">19</a>&#44;<a class="elsevierStyleCrossRef" href="#bib20">20</a>&#41;&#46; The patients were evaluated in the same manner every 3 months&#44; regardless of the type of TNF-blocker administration &#40;i&#46;e&#46;&#44; intravenous or subcutaneous&#41;&#46;</p><p id="para70" class="elsevierStylePara elsevierViewall">The following exclusion criteria were applied&#58; inability to answer the questions on the questionnaires&#59; active or chronic active infections&#44; including hepatitis B&#44; hepatitis C and human immunodeficiency virus&#59; overlapping of other autoimmune rheumatic diseases&#59; pulse with methylprednisolone&#59; recurrent infections involving the skin and&#47;or mucosal tissue&#44; such as erysipelas&#44; furunculosis&#44; human papillomavirus and herpes simplex&#59; and classic contraindications for TNF-&#945; inhibitors &#40;solid and hematological neoplasms&#44; demyelinating disease and heart failure&#41;&#46;</p><p id="para80" class="elsevierStylePara elsevierViewall">Anthropometric&#44; socioeconomic&#44; demographic and clinical data were evaluated&#44; including the Disease Activity Score-28 &#40;DAS28&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib21">21</a>&#41;&#44; Bath Ankylosing Spondylitis Disease Activity Index &#40;BASDAI&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib22">22</a>&#41;&#44; Psoriasis Area and Severity Index &#40;PASI&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib23">23</a>&#41; and Health Assessment Questionnaire &#40;HAQ&#41;&#46;</p><p id="para90" class="elsevierStylePara elsevierViewall">Comorbidities were grouped based on the International Classification of Diseases &#40;10th revision&#41; &#40;<a href="http://www.icd10data.com">http&#58;&#47;&#47;www&#46;icd10data&#46;com</a>&#41;&#44; and concomitant medications were classified according to the Dictionary of Pharmaceutical Specialties &#40;version 2009&#44; Brazil &#40;<a href="http://www.epuc.com.br/DEF/Home.htm">http&#58;&#47;&#47;www&#46;epuc&#46;com&#46;br&#47;DEF&#47;Home&#46;htm</a>&#41;&#46; Certain drugs have been associated with drug-induced skin conditions&#44; and others have been shown to increase the odds of infection&#46; For this reason&#44; these drugs were analyzed separately&#44; including analgesics&#44; non-steroidal anti-inflammatory drugs &#40;NSAIDs&#41;&#44; GCs&#44; disease-modifying anti-rheumatic drugs &#40;DMARDs&#59; including methotrexate&#44; leflunomide&#44; cyclosporine&#44; sulfasalazine&#44; and azathioprine&#41;&#44; hypertension medications &#40;methyldopa&#44; hydralazine&#44; angiotensin-converting-enzyme inhibitors&#41;&#44; anticonvulsants and treatment for latent tuberculosis infection &#40;isoniazid&#41;&#46;</p><p id="para100" class="elsevierStylePara elsevierViewall">Skin conditions were evaluated by two experienced dermatologists&#46; In cases of doubt or a lack of agreement between the examiners&#44; a biopsy of the skin lesion was performed following the standard routine procedures&#46; Staining with hematoxylin-eosin was used in all cases&#46; Special stains&#44; direct immunofluorescence and cultures of fragments were performed when necessary&#46; An adverse event was defined as any unexpected medical occurrence that arose following the onset of anti-TNF-&#945; therapy&#46; A serious adverse event was defined as any unexpected medical occurrence that resulted in death&#44; endangered the patient&#39;s life or required or prolonged hospitalization&#46; These events did not necessarily have a causal relationship with the factors evaluated in the study&#46;</p><p id="para110" class="elsevierStylePara elsevierViewall">Immunological reactions to the drugs were defined&#44; according to the classification proposed by Gell and Coombs &#40;1963&#41;&#44; as type I &#40;allergy or anaphylaxis&#44; such as urticariform reaction&#41;&#44; type II &#40;antibody-mediated cytotoxic reaction&#44; such as hemolytic anemia&#44; thrombocytopenia and nephritis&#41;&#44; type III &#40;immune complex-mediated reactions&#44; such as psoriasis-like lesions and drug-induced lupus&#41; or type IV &#40;cell-mediated reaction&#44; such as contact dermatitis&#41; hypersensitivity &#40;<a class="elsevierStyleCrossRef" href="#bib24">24</a>&#41;&#46; Infectious events were classified as viral&#44; parasitic&#44; fungal or bacterial&#44; depending on the clinical condition or on identification of the etiological agent through direct study&#44; culture or specific staining&#46;</p><p id="para120" class="elsevierStylePara elsevierViewall">The incidence was calculated based on the time interval between the first day of TNF-&#945; blocker use and the first CAE&#46; Recurring conditions were not included in this analysis&#46; The decision to maintain or discontinue &#40;temporarily or definitively&#41; the medication was made by the medical team based on the risks&#44; benefits&#44; severity&#44; duration&#44; likelihood and temporality between the CAEs and the TNF-&#945; inhibitors&#46;</p><p id="para130" class="elsevierStylePara elsevierViewall">Descriptive data are expressed as the means &#177; standard deviations&#44; and categorical variables are expressed as percentage values&#46; For the inferential analysis&#44; Student&#39;s t-test and the chi-square test were used for numerical data&#44; and the Mann-Whitney and Fisher&#39;s exact test were used for categorical variables&#46; Analysis of variance and Tukey&#39;s post-hoc test were used for the comparison of non-numerical data&#46; All of the data were initially evaluated for distribution normality&#46; Associations between CAEs and the clinical&#44; demographic and epidemiological variables were evaluated using the chi-square test and logistic regression models for the identification of associated risk factors&#46; The dependent variables were the CAEs&#46; The Statistical Package for Social Sciences &#40;SPSS&#44; version 15&#46;0&#41; was used for all of the analyses&#44; with the level of significance set at 5&#37; &#40;<span class="elsevierStyleItalic">p</span>&#60;0&#46;05&#41;&#46;</p><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">Ethics</span><p id="para140" class="elsevierStylePara elsevierViewall">All of the patients were informed about the study&#44; and those who agreed to participate signed a statement of informed consent&#46; This study received approval from the Human Research Ethics Committee of the Universidade Federal de S&#227;o Paulo&#47;Escola Paulista de Medicina &#40;no&#46; 1478&#47;09&#41;&#46;</p></span></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">RESULTS</span><p id="para150" class="elsevierStylePara elsevierViewall">After 60 months of follow-up&#44; 71 &#40;27&#46;6&#37;&#41; patients experienced some type of adverse event involving the skin &#40;<a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>&#41;&#46; The incidence of CAE was 73&#46;85&#47;1000 patient-years&#46; No patient presented evidence of a similar pre-existing clinical condition&#46; The first CAE appeared between 2 weeks and 45 months after the onset of anti-TNF-&#945; therapy &#40;mean&#58; 11&#46;2&#177;4&#46;7 months&#41;&#46; The diagnosis of skin lesions&#44; including lepromatous leprosy &#40;LL&#41;&#44; systemic lupus erythematosus &#40;SLE&#41;&#44; psoriasis-like lesions and vulvar lichen planus&#44; was confirmed through biopsy of the affected area&#46; Onychomycosis was proved according to the positivity of the direct mycological test&#46;</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia><p id="para160" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a> displays the clinical characteristics of the 257 patients according to the presence of CAEs&#46; Older individuals and those with a more elapsed time since their diagnoses&#44; those with greater disease activity and severity&#44; those of female sex&#44; those with a history of diabetes mellitus&#44; those with a diagnosis of RA and those with regular use of IFX demonstrated a greater likelihood of experiencing a CAE&#46;</p><elsevierMultimedia ident="tbl2"></elsevierMultimedia><p id="para170" class="elsevierStylePara elsevierViewall">Allergic and immune-mediated phenomena were the most frequent types of CAEs &#40;n &#61; 37&#59; 52&#46;1&#37;&#41;&#44; followed by infectious conditions &#40;n &#61; 34&#59; 47&#46;9&#37;&#41; involving bacterial &#40;47&#46;1&#37;&#41;&#44; parasitic &#40;23&#46;5&#37;&#41;&#44; fungal &#40;20&#46;6&#37;&#41; and viral &#40;8&#46;8&#37;&#41; agents &#40;<a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>&#41;&#59; <a class="elsevierStyleCrossRef" href="#tbl3">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><elsevierMultimedia ident="tbl3"></elsevierMultimedia><p id="para180" class="elsevierStylePara elsevierViewall">When the 71 patients with CAE were grouped according to the mechanism involved &#40;immune-allergic <span class="elsevierStyleItalic">vs&#46;</span> infectious&#41;&#44; the only significant variable associated with the greater frequency of the latter group was a diagnosis of diabetes mellitus&#46; In addition&#44; there was a tendency toward infectious CAEs occurring more frequently in patients under prolonged treatment with GCs&#44; regardless of the dose &#40;<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl4"></elsevierMultimedia><p id="para190" class="elsevierStylePara elsevierViewall">Although the severity of the events was considered moderate to severe in most patients&#44; the resolution of the CAEs was satisfactory in the vast majority of cases following withdrawal of the anti-TNF-&#945; agent and with the use of specific medications&#44; such as anti-histamines&#44; GCs&#44; antibiotics and antiviral&#44; antiparasitic and antimycotic agents&#44; depending on the event and needs of each case&#46; <a class="elsevierStyleCrossRef" href="#tbl5">Table 5</a> displays the strategies regarding the discontinuation &#40;temporary or definitive&#41; of TNF-&#945; blockers&#46; Among those patients for whom therapy was temporarily discontinued&#44; the same medication was reintroduced without recurrence of the CAE&#46; The replacement of anti-TNF-&#945; agents was the most frequent action undertaken following the definitive discontinuation of the first blocker&#44; with no recurrence of the CAE during the first 6 months following replacement&#46;</p><elsevierMultimedia ident="tbl5"></elsevierMultimedia><p id="para200" class="elsevierStylePara elsevierViewall">Among those who needed to switch medications to another TNF-&#945; inhibitor&#44; the majority switched from monoclonal antibody therapy to soluble receptor therapy &#40;53&#46;8&#37;&#41;&#44; followed by from treatment with one monoclonal antibody to another monoclonal antibody &#40;33&#46;1&#37;&#41; and from treatment with a soluble receptor to a monoclonal antibody &#40;13&#46;1&#37;&#41;&#46; Only four patients switched to a non-TNF-&#945; blocker&#44; including three who used RTX and one who used ABT&#46;</p><p id="para210" class="elsevierStylePara elsevierViewall">Three CAE &#40;4&#46;22&#37;&#41; cases required hospitalization and were therefore classified as serious&#46; In all of the cases&#44; the reason for hospitalization was an acute bacterial condition &#40;erysipelas&#44; recurring furunculosis and soft tissue abscess&#41;&#44; with toxemia and&#47;or evidence of septicemia and&#47;or an inadequate response to outpatient treatment&#46; In addition&#44; there was a close temporal and causal relationship between the study procedures or therapeutic agent employed and the patient&#39;s classification as moderately severe&#44; based on the investigator&#39;s opinion&#46; No cases resulted in death&#46; These serious adverse events exhibited satisfactory evolution following antibiotic therapy&#44; with complete resolution of the disease process&#46; In all three cases&#44; the anti-TNF-&#945; agent was switched &#40;to ETN in two of the cases and to RTX in the other case&#41;&#46; No statistically significant association was found between serious adverse events and age&#44; years since diagnosis&#44; functional capacity&#44; concomitant medications or associated diseases&#46;</p><p id="para220" class="elsevierStylePara elsevierViewall">In the logistic regression model&#44; the main risk factors significantly associated with CAE were advanced age&#44; female sex&#44; greater disease activity&#44; diagnosis of RA and the use of GCs and IFX&#46; HAQ&#44; DMARDs and other concomitant medications&#44; as well as the presence of diabetes mellitus&#44; did not achieve statistical significance as risk factors following multiple statistical adjustments&#46; The time since diagnosis exhibited multi-collinearity with age and was therefore removed from the final model&#46; No protection factors were identified&#46; The PASI did not remain in the model following the statistical adjustments&#44; whereas IFX remained in the model even after controlling for frequency&#44; duration of use and exposure&#46;</p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">DISCUSSION</span><p id="para230" class="elsevierStylePara elsevierViewall">TNF-&#945; blockers are associated with a variety of potentially serious adverse events&#44; especially allergic&#47;immune-mediated phenomena and opportunistic infections or infections caused by common germs involving the skin and internal squamous mucosae&#46;</p><p id="para240" class="elsevierStylePara elsevierViewall">Our findings demonstrate that CAEs are frequent in the clinical practice of rheumatology&#44; affecting approximately 25&#37; of patients with CIA who use TNF-&#945; blockers&#44; with a high incidence &#40;73&#46;85 in every 1&#44;000 patient-years&#41;&#46; Moreover&#44; advanced age&#44; female sex&#44; RA&#44; disease activity and current use of GCs and IFX were the main risk factors significantly associated with CAEs&#46; Thus&#44; patient-related aspects&#44; the diagnosis and the TNF-&#945; blocker itself play relevant roles in the clinical condition and management of affected individuals&#46;</p><p id="para250" class="elsevierStylePara elsevierViewall">The pharmacological and biochemical properties of three TNF-&#945; blockers could explain the variations in the risk of infection and other adverse reactions&#46; Chimeric &#40;IFX&#41; and human &#40;ADA&#47;GOL&#41; monoclonal antibodies neutralize soluble&#44; membrane-bound TNF-&#945; to a greater extent and for a longer time&#44; whereas ETN only binds to the soluble fraction in an irreversible manner over a shorter time span&#46; In addition&#44; IFX and ADA&#47;GOL more strongly promote apoptosis&#44; along with significant dose-dependent reductions in the level of interferon-gamma &#40;IFN-&#947;&#41;&#44; whereas ETN does not demonstrate these characteristics&#46; Furthermore&#44; this reduced level of IFN-&#947; could be associated with the failed inhibition of pathogen growth&#44; especially intracellular pathogens &#40;<a class="elsevierStyleCrossRef" href="#bib25">25</a>&#41;&#46;</p><p id="para260" class="elsevierStylePara elsevierViewall">Notably&#44; the spectrum of infectious conditions is quite variable&#44; depending on the country of registry and the type of TNF-&#945; blocker used&#46; The French registry &#40;RATIO&#41; found that 33&#37; of non-tuberculosis opportunistic infections among users of TNF-&#945; blockers were bacterial &#40;listeriosis&#44; nocardiosis&#44; atypical mycobacteria&#44; non-typhoid salmonellosis&#41;&#44; whereas 40&#37; were viral &#40;severe herpes zoster &#91;shingles&#93;&#44; chicken pox&#44; disseminated herpes simplex&#44; disseminated cytomegalovirus&#41;&#44; 22&#37; were fungal &#40;pneumocystosis&#44; invasive aspergillosis&#44; cryptococcosis&#41;&#44; and 4&#37; were parasitic &#40;leishmaniasis&#41;&#46; Furthermore&#44; nearly 25&#37; of patients required hospitalization in intensive care&#44; and the mortality rate was 10&#37;&#46; The main risk factors associated with these infections were treatment with IFX &#40;OR &#61; 17&#46;6&#59; 95&#37; CI&#58; 4&#46;3 to 72&#46;9&#59; <span class="elsevierStyleItalic">p</span>&#60;0&#46;0001&#41; or ADA &#40;OR &#61; 10&#59; 95&#37; CI&#58; 2&#46;3 to 44&#46;4&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;002&#41; <span class="elsevierStyleItalic">vs</span>&#46; ETN and previous use of GCs &#40;OR &#61; 6&#46;3&#59; 95&#37; CI&#58; 2 to 20&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;002&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib26">26</a>&#41;&#46; Lower hospitalization and mortality rates were observed in the present study&#44; which was undertaken at a tertiary university hospital and which involved patients with long-standing diagnoses and other factors associated with a poorer prognosis&#59; however&#44; no cases of non-tuberculosis opportunistic infection were observed over the 5 years of follow-up&#46;</p><p id="para270" class="elsevierStylePara elsevierViewall">According to a recent retrospective analysis &#40;1998 to 2005&#41; involving more than 20&#44;000 RA patients&#44; including nearly 4&#44;000 users of TNF-&#945; blockers&#44; the risk of hospitalization due to infection&#44; especially of the skin or airways&#44; was greater following the chronic use of GCs &#40;hazard ratio &#91;HR&#93; &#61; 2&#46;14&#59; 95&#37; CI&#58; 1&#46;88 to 2&#46;43&#41;&#44; even after controlling for demographic variables&#44; comorbidities and traditional DMARDs&#46; With some TNF-&#945; blockers&#44; the risk was 24&#37; greater &#40;HR &#61; 1&#46;24&#59; 95&#37; CI&#58; 1&#46;02 to 1&#46;5&#41;&#44; particularly when IFX was used &#40;HR &#61; 1&#46;51&#59; 95&#37; CI&#58; 1&#46;14 to 2&#46;0&#41;&#46; In addition&#44; the hospitalization rate was 7&#37;&#44; mainly in the first 6 to 12 months of treatment &#40;<a class="elsevierStyleCrossRef" href="#bib27">27</a>&#41;&#46;</p><p id="para280" class="elsevierStylePara elsevierViewall">In the present study&#44; the use of GCs was associated with a greater chance of experiencing a CAE&#46; Interestingly&#44; the greater risk of infection among RA patients has not achieved statistical significance in randomized clinical trials&#44; which might reflect the heterogeneity of the samples and the exclusion of patients with multiple comorbidities&#46; However&#44; the association has been significant in real-world reports&#44; as observed in the present investigation and in previous observational studies &#40;risk ratio &#91;RR&#93; &#61; 1&#46;67&#59; 95&#37; CI 1&#46;49 to 1&#46;87&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib28">28</a>&#41;&#46; It should also be emphasized that current use of GCs was not a protective factor against allergic or immune-mediated CAEs in the present study&#46;</p><p id="para290" class="elsevierStylePara elsevierViewall">Benucci et al&#46; found no significant differences among TNF-&#945; blockers in terms of the incidence of acute and late-onset hypersensitivity &#40;infused or local&#41; during the first year of treatment &#40;<a class="elsevierStyleCrossRef" href="#bib29">29</a>&#41;&#46; In the present study&#44; immune-mediated reactions&#44; especially types I and III hypersensitivity&#44; were more common than infectious CAEs&#44; and interestingly&#44; type II reactions were infrequent &#40;<a class="elsevierStyleCrossRef" href="#bib7">7</a>&#41;&#46;</p><p id="para300" class="elsevierStylePara elsevierViewall">Four CAEs were unexpected in the present cohort&#44; including two cases of immune-mediated reactions &#40;psoriasis-like lesions and SLE&#41; and two representative cases of latent infection &#40;lepromatous leprosy and herpes zoster&#41;&#46; Although TNF-&#945; blockers have been widely used for the treatment of psoriasis and PA in patients with inadequate responses to conventional DMARDs &#40;<a class="elsevierStyleCrossRef" href="#bib3">3</a>&#44;<a class="elsevierStyleCrossRef" href="#bib5">5</a>&#41;&#44; this treatment might paradoxically also induce psoriasis-like lesions&#44; even among individuals with no personal or family history of psoriasis&#44; as observed in three patients in our sample&#46; These lesions are generally new&#44; but some studies have reported a worsening of preexisting lesions &#40;psoriasis &#8220;de novo&#8221; or psoriasis-like rash&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib30">30</a>&#41;&#44; and such lesions are more common in women&#44; with a predilection for palm or plantar involvement or in uncommon regions of the body&#44; such as the groin and pubic region&#44; and they more commonly emerge between 12 weeks and 12 months after the onset of therapy &#40;<a class="elsevierStyleCrossRefs" href="#bib30">30&#8211;33</a>&#41;&#46; In the present study&#44; serology was negative for human immunodeficiency virus&#44; and no sex differences were found&#46; Moreover&#44; there was no evidence of palm or plantar involvement&#44; and all of the cases were associated with IFX&#46; Curiously&#44; patients with inflammatory bowel disease who received IFX did not appear to be at a greater risk for CAEs&#44; unlike those with CIA &#40;<a class="elsevierStyleCrossRef" href="#bib15">15</a>&#41;&#46; Patients with JIA were reported to experience greater difficulty in controlling these lesions&#44; even after the withdrawal of anti-TNF-&#945; therapy &#40;<a class="elsevierStyleCrossRef" href="#bib34">34</a>&#41;&#46;</p><p id="para310" class="elsevierStylePara elsevierViewall">According to the British Society for Rheumatology Biologics Registry &#40;2001 to 2007&#41;&#44; the incidence of psoriatic lesions in a group of 9&#44;826 RA patients taking TNF-&#945; inhibitors&#44; especially those using ADA&#44; was 1&#46;04 per 1&#44;000 patient-years &#40;95&#37; CI&#58; 0&#46;67 to 1&#46;54&#41;&#44; which is equivalent to 25 new cases of psoriasis&#46; In contrast&#44; no cases were found in the group of 2&#44;880 patients with RA treated with DMARDs only &#40;<a class="elsevierStyleCrossRef" href="#bib33">33</a>&#41;&#46;</p><p id="para320" class="elsevierStylePara elsevierViewall">The first hypothesis to explain this association would be initial diagnostic error&#44; as these lesions could actually be part of the spondyloarthritis spectrum&#44; and the association with psoriasis could be nothing more than the natural history of the disease &#40;<a class="elsevierStyleCrossRef" href="#bib33">33</a>&#41;&#46; Subsequently&#44; a modified Th1 response caused by TNF-&#945; blockers and the direct role of TNF-&#945; itself were indicated as the most likely mechanisms&#44; as the inflammatory response in plaque psoriasis is traditionally initiated by the activation of T cells &#40;<a class="elsevierStyleCrossRef" href="#bib30">30</a>&#44;<a class="elsevierStyleCrossRef" href="#bib35">35</a>&#41;&#46; Furthermore&#44; the inhibition of TNF-&#945; reduces the migration of lymphocytes from the skin to the lymph nodes&#44; and this imbalance can promote a relative increase in IFN-&#947; and intensive activation of T cells&#44; with a resulting increase in psoriatic lesions &#40;<a class="elsevierStyleCrossRef" href="#bib32">32</a>&#41;&#46; Other cytokine receptors have also been cited in this process&#44; such as CXCR3 &#40;<a class="elsevierStyleCrossRef" href="#bib36">36</a>&#41;&#46; In addition&#44; IFN-&#945;&#44; IL-17 and IL-23 have recently been reported to constitute another pathophysiological mechanism involved in psoriasis-like processes &#40;<a class="elsevierStyleCrossRef" href="#bib30">30</a>&#44;<a class="elsevierStyleCrossRef" href="#bib37">37</a>&#41;&#46; A number of authors also believe that greater exposure to infectious agents&#44; stemming from heightened susceptibility following anti-TNF-&#945; therapy&#44; represents another probable hypothesis &#40;<a class="elsevierStyleCrossRef" href="#bib31">31</a>&#44;<a class="elsevierStyleCrossRef" href="#bib38">38</a>&#41;&#59; the most commonly cited triggering microorganisms include Gram-positive cocci &#40;<a class="elsevierStyleCrossRef" href="#bib39">39</a>&#41; and&#44; more recently&#44; chlamydia &#40;<a class="elsevierStyleCrossRef" href="#bib31">31</a>&#41;&#46;</p><p id="para330" class="elsevierStylePara elsevierViewall">TNF-&#945; blockers are associated with the generation of autoantibodies&#44; including human anti-chimeric and anti-human antibodies&#44; as well as potentially clinically important autoimmune involvement &#40;<a class="elsevierStyleCrossRefs" href="#bib39">39&#8211;41</a>&#41;&#46; The most prevalent autoantibodies are generally directed against the nucleus &#40;AAN&#44; anti-histone and anti-DNA&#41;&#44; but antibodies are also formed against membrane phospholipids &#40;anticardiolipin&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib40">40</a>&#44;<a class="elsevierStyleCrossRef" href="#bib41">41</a>&#41;&#46; Clinically&#44; these autoantibodies can induce SLE&#44; preferentially affecting the skin&#44; joints and&#44; less frequently&#44; the blood and kidneys &#40;<a class="elsevierStyleCrossRefs" href="#bib42">42&#8211;46</a>&#41;&#46;</p><p id="para340" class="elsevierStylePara elsevierViewall">No risk factors &#40;previous positivity for autoantibodies&#44; age&#44; prolonged GC use or administration of other medications traditionally related to drug-induced lupus&#41; have yet been identified as being associated with a greater chance of stimulating lipopolysaccharide-induced TNF production&#46; Although a recent literature review indicated that IFX and ETN represented the drugs most associated with lipopolysaccharide-induced TNF production &#40;<a class="elsevierStyleCrossRef" href="#bib42">42</a>&#41;&#44; no recommendations have been reported for the study of autoantibodies in patients with an indication for anti-TNF-&#945; therapy&#46; In one patient in the present study&#44; lipopolysaccharide-induced TNF disappeared following the discontinuation of ETN and initiation of GCs&#44; and adequate clinical and laboratory control of the disease was achieved with RTX&#46;</p><p id="para350" class="elsevierStylePara elsevierViewall">Because TNF is important for the formation and maintenance of granulomas&#44; TNF-&#945; blockers can disorganize this process&#44; resulting in the reactivation of latent granulomatous infections&#44; such as tuberculosis and LL&#46; According to the Food and Drug Administration database&#44; the incidence of infection with <span class="elsevierStyleItalic">Mycobacterium leprae</span> is low &#40;0&#46;1&#37;&#41; and more closely related to IFX therapy &#40;<a class="elsevierStyleCrossRef" href="#bib47">47</a>&#41;&#46; In the present sample&#44; the Virchowian form of Hansen&#39;s disease emerged soon after the use of ADA&#44; requiring prolonged specific treatment and difficult management of the joint condition &#40;<a class="elsevierStyleCrossRef" href="#bib10">10</a>&#41;&#46;</p><p id="para360" class="elsevierStylePara elsevierViewall">Anti-TNF-&#945; therapy could also be associated with the reactivation of latent viral infections&#44; such as herpes zoster&#44; which has traditionally been reported in patients with some degree of immunosuppression&#46; The incidence of viral reactivation per 1&#44;000 patient-years was shown to be approximately two-fold greater &#40;11&#46;1&#59; 95&#37; CI&#58; 7&#46;9 to 15&#46;1&#41; for patients treated with monoclonal antibodies&#44; compared to those treated with traditional DMARDs &#40;5&#46;6&#59; 95&#37; CI&#58; 3&#46;6 to 8&#46;3&#41;&#44; especially among older patients and among those using concomitant GCs &#40;<a class="elsevierStyleCrossRef" href="#bib12">12</a>&#41;&#46; After assessing the German biologics registry database &#40;RABBIT&#41; and more than 5&#44;000 RA patients administered biologic agents between 2001 and 2006&#44; Strangefeld et al&#46; identified 86 cases &#40;16&#46;3&#37;&#41; of reactivation of shingles in 82 individuals&#59; of these&#44; 39 cases were temporarily related to treatment with ADA or IFX&#44; 23 were related to ETN&#44; and 24 were related to traditional DMARDs &#40;<a class="elsevierStyleCrossRef" href="#bib11">11</a>&#41;&#46; Similarly&#44; in a retrospective study&#44; McDonald et al&#46; assessed more than 20&#44;000 RA patients from the Veterans Affairs Healthcare System &#40;1998 to 2005&#41;&#44; and they found an incidence of 9&#46;96 episodes&#47;1&#44;000 patient-years&#46; The main risk factors in this previous study were age&#44; prolonged GCs&#44; cancer&#44; chronic liver and lung disease&#44; immunosuppressants and kidney failure&#59; ETN and ADA exhibited a smaller risk than IFX &#40;<a class="elsevierStyleCrossRef" href="#bib12">12</a>&#41;&#46;</p><p id="para370" class="elsevierStylePara elsevierViewall">Non-melanoma skin tumors constitute another commonly reported skin manifestation among patients taking TNF-&#945; blockers&#44; with a relative risk of 2&#46;02&#44; according to a recent meta-analysis involving three TNF-&#945; blockers &#40;<a class="elsevierStyleCrossRef" href="#bib15">15</a>&#41;&#46; These findings suggest that factors related to the immunopathology of the skin&#44; especially cells of the innate immune system&#44; such as dendritic cells&#44; could play a crucial role in the interrelationship of these events&#46; However&#44; further prospective studies are needed to better establish this association&#46;</p><p id="para380" class="elsevierStylePara elsevierViewall">The present study demonstrated certain strengths that should be highlighted&#44; such as the long-term follow-up of patients with CIA who were taking TNF-&#945; inhibitors&#46; Moreover&#44; the diagnostic accuracy of CAEs using gold-standard methods&#44; including dermatologic evaluation&#44; biopsies and cultures&#44; should be noted&#46; However&#44; the lack of a control group using DMARDs only was the main limitation of this longitudinal cohort study&#46;</p><p id="para390" class="elsevierStylePara elsevierViewall">Rheumatologists and dermatologists should be aware of the potential risks with TNF-&#945; blockers&#44; especially infectious and immune-mediated adverse skin events&#44; to establish an early diagnosis and to make proper treatment decisions&#46; Furthermore&#44; the adequate determination of epidemiological and personal historical data &#40;previous or recurrent infectious conditions&#44; subclinical fungal infections&#44; oral microbiota and oral health status&#41; is fundamental to the recognition and minimization of CAEs related to immunobiological therapy&#46;</p></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">AUTHOR CONTRIBUTIONS</span><p id="para400" class="elsevierStylePara elsevierViewall">Machado NP performed the clinical and rheumatologic examinations&#44; sample collection and processing&#44; data analysis and drafting of the manuscript&#46; Soares MR and Freitas DS recruited patients and helped with the data analysis&#46; Soares MR participated in the design of the study and helped with the data analysis&#46; Neto ET and Ciconelli RM participated in the design of the study and helped with the data analysis and drafting of the manuscript&#46; Machado NP and Porro A performed the skin biopsies&#46; Pinheiro MM participated in the design of the study&#44; performed the rheumatologic examinations and helped with the data analysis and drafting of the manuscript&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:8 [
        0 => array:2 [
          "identificador" => "xpalclavsec1581232"
          "titulo" => "KEYWORDS"
        ]
        1 => array:2 [
          "identificador" => "cesec10"
          "titulo" => "INTRODUCTION"
        ]
        2 => array:3 [
          "identificador" => "cesec20"
          "titulo" => "PATIENTS AND METHODS"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "cesec30"
              "titulo" => "Ethics"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "cesec40"
          "titulo" => "RESULTS"
        ]
        4 => array:2 [
          "identificador" => "cesec50"
          "titulo" => "DISCUSSION"
        ]
        5 => array:2 [
          "identificador" => "cesec60"
          "titulo" => "AUTHOR CONTRIBUTIONS"
        ]
        6 => array:2 [
          "identificador" => "xack638794"
          "titulo" => "ACKNOWLEDGMENTS"
        ]
        7 => array:1 [
          "titulo" => "REFERENCES"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2013-02-01"
    "fechaAceptado" => "2013-04-12"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "KEYWORDS"
          "identificador" => "xpalclavsec1581232"
          "palabras" => array:5 [
            0 => "TNF-alpha Blockers"
            1 => "Skin"
            2 => "Adverse Events"
            3 => "Rheumatoid Arthritis"
            4 => "Ankylosing Spondylitis"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:2 [
        "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">OBJECTIVE</span><p id="spara70" class="elsevierStyleSimplePara elsevierViewall">We evaluated the incidence of and the main risk factors associated with cutaneous adverse events in patients with chronic inflammatory arthritis following anti-TNF-&#945; therapy&#46;</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">METHODS</span><p id="spara80" class="elsevierStyleSimplePara elsevierViewall">A total of 257 patients with active arthritis who were taking TNF-&#945; blockers&#44; including 158 patients with rheumatoid arthritis&#44; 87 with ankylosing spondylitis and 12 with psoriatic arthritis&#44; were enrolled in a 5-year prospective analysis&#46; Patients with overlapping or other rheumatic diseases were excluded&#46; Anthropometric&#44; socioeconomic&#44; demographic and clinical data were evaluated&#44; including the Disease Activity Score-28&#44; Bath Ankylosing Spondylitis Disease Activity Index and Psoriasis Area Severity Index&#46; Skin conditions were evaluated by two dermatology experts&#44; and in doubtful cases&#44; skin lesion biopsies were performed&#46; Associations between adverse cutaneous events and clinical&#44; demographic and epidemiological variables were determined using the chi-square test&#44; and logistic regression analyses were performed to identify risk factors&#46; The significance level was set at <span class="elsevierStyleItalic">p</span>&#60;0&#46;05&#46;</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">RESULTS</span><p id="spara90" class="elsevierStyleSimplePara elsevierViewall">After 60 months of follow-up&#44; 71 adverse events &#40;73&#46;85&#47;1000 patient-years&#41; were observed&#44; of which allergic and immune-mediated phenomena were the most frequent events&#44; followed by infectious conditions involving bacterial &#40;47&#46;1&#37;&#41;&#44; parasitic &#40;23&#46;5&#37;&#41;&#44; fungal &#40;20&#46;6&#37;&#41; and viral &#40;8&#46;8&#37;&#41; agents&#46;</p></span> <span id="ceabs40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">CONCLUSION</span><p id="spara100" class="elsevierStyleSimplePara elsevierViewall">The skin is significantly affected by adverse reactions resulting from the use of TNF-&#945; blockers&#44; and the main risk factors for cutaneous events were advanced age&#44; female sex&#44; a diagnosis of rheumatoid arthritis&#44; disease activity and the use of infliximab&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "ceabs10"
            "titulo" => "OBJECTIVE"
          ]
          1 => array:2 [
            "identificador" => "ceabs20"
            "titulo" => "METHODS"
          ]
          2 => array:2 [
            "identificador" => "ceabs30"
            "titulo" => "RESULTS"
          ]
          3 => array:2 [
            "identificador" => "ceabs40"
            "titulo" => "CONCLUSION"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:1 [
        "nota" => "<p class="elsevierStyleNotepara" id="cenpara30">No potential conflict of interest was reported&#46;</p>"
      ]
    ]
    "multimedia" => array:6 [
      0 => array:7 [
        "identificador" => "fig1"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 365
            "Ancho" => 745
            "Tamanyo" => 29498
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Grouping of CAEs according to mechanism involved &#40;immune-allergic vs&#46; infectious&#41;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl1"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">Frequency&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Urticaria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">18 &#40;25&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Local erythema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12 &#40;16&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Scabies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8 &#40;11&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Impetigo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6 &#40;8&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Onychomycosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">4 &#40;5&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Psoriasis-like lesions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3 &#40;4&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Chronic eczema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3 &#40;4&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Tina corporis&#47;cruris&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3 &#40;4&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Boils&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2 &#40;2&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Recurrent furunculosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2 &#40;2&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Erysipelas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2 &#40;2&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Soft tissue abscess&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2 &#40;2&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Herpes simplex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1 &#40;1&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Genital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1 &#40;1&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Herpes zoster&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1 &#40;1&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Lichen planus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1 &#40;1&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Lepromatous leprosy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1 &#40;1&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Systemic lupus erythematosus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1 &#40;1&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">The frequency of 71 new CAEs in 257 patients with chronic inflammatory arthritis taking TNF-&#945; blockers after 60 months of follow-up&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl2"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="TFN01t02" class="elsevierStyleSimplePara elsevierViewall">CAEs&#58; cutaneous adverse events&#59; DAS28&#58; Disease Activity Score-28&#59; BASDAI&#58; Bath Ankylosing Spondylitis Disease Activity Index&#59; PASI&#58; Psoriasis Activity and Severity Index&#59; HAQ&#58; Health Assessment Questionnaire&#59; DM&#58; diabetes mellitus&#59; GCs&#58; glucocorticoid steroids&#59; DMARDs&#58; disease-modifying anti-rheumatic drugs&#59; RA&#58; rheumatoid arthritis&#59; AS&#58; ankylosing spondylitis&#59; PA&#58; psoriatic arthritis&#59; IFX&#58; infliximab&#59; ETN&#58; etanercept&#59; ADA&#58; adalimumab&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">Total &#40;n &#61; 257&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">No CAE &#40;n &#61; 186&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">With CAE &#40;n &#61; 71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">p-value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">47&#46;5&#177;12&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">46&#46;8&#177;11&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">50&#46;3<span class="elsevierStyleBold">&#177;</span>10&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Years since diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">13&#46;6&#177;7&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12&#46;5&#177;7&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&#46;8<span class="elsevierStyleBold">&#177;</span>8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Female sex&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">165&#40;64&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">107&#40;57&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">58&#40;81&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">DAS28 &#40;n &#61; 170&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;92&#177;1&#46;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;47&#177;1&#46;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;88<span class="elsevierStyleBold">&#177;</span>1&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">BASDAI &#40;n &#61; 91&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;2&#177;1&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">4&#46;9&#177;1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;3<span class="elsevierStyleBold">&#177;</span>2&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">PASI &#40;n &#61; 12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&#46;7&#177;4&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">7&#46;3&#177;3&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&#46;5<span class="elsevierStyleBold">&#177;</span>4&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">HAQ&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;72&#177;0&#46;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;63&#177;0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;79<span class="elsevierStyleBold">&#177;</span>0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Associated disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">DM&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">64 &#40;24&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">39 &#40;21&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">25 &#40;35&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Concomitant medication&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>GCs&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">151 &#40;58&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">98 &#40;52&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">53 &#40;74&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>DMARDs&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">238 &#40;92&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">173 &#40;93&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">65 &#40;91&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Antihypertensive&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">96 &#40;37&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">71 &#40;38&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">25 &#40;35&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Anticonvulsant&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6 &#40;2&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">4 &#40;2&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2 &#40;2&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Chronic inflammatory arthritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>RA&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">158 &#40;61&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">107 &#40;57&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">51 &#40;71&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>AS&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">87 &#40;33&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">72 &#40;38&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15 &#40;21&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PA&#46; N &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12 &#40;4&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">7 &#40;3&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5 &#40;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">TNF-&#945; blockers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>IFX&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">132 &#40;51&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">94 &#40;50&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">38 &#40;53&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ADA&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">75 &#40;29&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">56 &#40;30&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">19 &#40;28&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ETN&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">50 &#40;19&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">36 &#40;19&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">14 &#40;16&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics of the 257 patients with chronic inflammatory arthritis taking TNF-&#945; blockers according to the presence of CAEs&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl3"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="TFN01t03" class="elsevierStyleSimplePara elsevierViewall">DAS28&#58; Disease Activity Score-28&#59; BASDAI&#58; Bath Ankylosing Spondylitis Disease Activity Index&#59; HAQ&#58; Health Assessment Questionnaire&#59; RA&#58; rheumatoid arthritis&#59; AS&#58; ankylosing spondylitis&#59; PA&#58; psoriatic arthritis&#59; DM&#58; diabetes mellitus&#59; GCs&#58; glucocorticoid steroids&#59; DMARDs&#58; disease-modifying anti-rheumatic drugs&#59; IFX&#58; infliximab&#59; ETN&#58; etanercept&#59; ADA&#58; adalimumab&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">Total &#40;n &#61; 71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">Immune-allergic &#40;n &#61; 37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">Infectious &#40;n &#61; 34&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">50&#46;3<span class="elsevierStyleBold">&#177;</span>10&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">49&#46;2<span class="elsevierStyleBold">&#177;</span>10&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">50&#46;6<span class="elsevierStyleBold">&#177;</span>12&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Years since diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&#46;8<span class="elsevierStyleBold">&#177;</span>8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">14&#46;4<span class="elsevierStyleBold">&#177;</span>7&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&#46;8<span class="elsevierStyleBold">&#177;</span>8&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Female sex&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">58&#40;81&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">30&#40;81&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">28&#40;82&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">DAS28 &#40;n &#61; 170&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;88<span class="elsevierStyleBold">&#177;</span>1&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;81<span class="elsevierStyleBold">&#177;</span>1&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;97<span class="elsevierStyleBold">&#177;</span>1&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">BASDAI &#40;n &#61; 91&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;3<span class="elsevierStyleBold">&#177;</span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;0<span class="elsevierStyleBold">&#177;</span>1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;4<span class="elsevierStyleBold">&#177;</span>1&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">HAQ&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;79<span class="elsevierStyleBold">&#177;</span>0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;71<span class="elsevierStyleBold">&#177;</span>0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;82<span class="elsevierStyleBold">&#177;</span>0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Associated disease&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>DM&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">25 &#40;35&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8 &#40;21&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">17 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Concomitant medication&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>GCs&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">53 &#40;74&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">24 &#40;64&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">29 &#40;85&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>DMARDs&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">65 &#40;91&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">34 &#40;91&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">31 &#40;91&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Antihypertensive&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">25 &#40;35&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15 &#40;40&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">10 &#40;29&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Anticonvulsant&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2 &#40;2&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2 &#40;5&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0 &#40;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Chronic inflammatory arthritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>RA&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">51 &#40;71&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">24 &#40;64&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">27 &#40;79&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>AS&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15 &#40;21&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9 &#40;24&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6 &#40;17&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PA&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5 &#40;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2 &#40;5&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3 &#40;8&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">TNF&#945; blockers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>IFX&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">38 &#40;53&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">22 &#40;59&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">16 &#40;47&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ADA&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">19 &#40;28&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">13 &#40;35&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8 &#40;23&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ETN&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">14 &#40;16&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">10 &#40;27&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">4 &#40;11&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics of the 71 CAEs according to the mechanism involved &#40;immune-allergic <span class="elsevierStyleItalic">vs</span>&#46; infectious&#41;&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "tbl4"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="TFN01t04" class="elsevierStyleSimplePara elsevierViewall">Final logistic regression model&#58; RA&#58; rheumatoid arthritis&#59; DAS28&#58; Disease Activity Score-28&#59; BASDAI&#58; Bath Ankylosing Spondylitis Disease Activity Index&#59; GCs&#58; glucocorticoid steroids&#59; IFX&#58; infliximab&#59; CI&#58; confidence interval</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">OR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col"><span class="elsevierStyleItalic">p</span>-value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Age <a class="elsevierStyleCrossRef" href="#TFN02t04"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;09 &#40;1&#46;05-3&#46;72&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Female sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2&#46;84 &#40;1&#46;90-5&#46;63&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">RA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;89 &#40;1&#46;11-4&#46;62&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Disease activity index <a class="elsevierStyleCrossRef" href="#TFN03t04"><span class="elsevierStyleSup">&#8224;&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>DAS28 &#40;n &#61; 170&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;52 &#40;1&#46;2-4&#46;68&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>BASDAI &#40;n &#61; 91&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;13 &#40;1&#46;02-6&#46;37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;045&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">GCs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;21 &#40;1&#46;09-8&#46;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;037&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">IFX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;60 &#40;1&#46;06-4&#46;01&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "TFN02t04"
              "etiqueta" => "&#8224;"
              "nota" => "<p class="elsevierStyleNotepara" id="cenpara10">for each additional year</p>"
            ]
            1 => array:3 [
              "identificador" => "TFN03t04"
              "etiqueta" => "&#8224;&#8224;"
              "nota" => "<p class="elsevierStyleNotepara" id="cenpara20">for each additional unit&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara50" class="elsevierStyleSimplePara elsevierViewall">Final logistic regression model of the significant risk factors associated with CAEs in 257 patients with chronic inflammatory arthritis taking TNF-&#945; blockers&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "tbl5"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col">Strategy &#8211; Discontinuation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Temporary&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">34 &#40;47&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Definitive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">37 &#40;52&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Replace with other anti-TNF&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">33 &#40;46&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Replace with other non-TNF&#945; blocker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">4 &#40;5&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara60" class="elsevierStyleSimplePara elsevierViewall">Strategies used regarding immunobiological agents following adverse skin events&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "REFERENCES"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec10"
          "bibliografiaReferencia" => array:47 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              JS Smolen \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              R Landew&#233; \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              FC Breedveld \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              M Dougados \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              P Emery \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              C Gaujoux-Viala \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2009.126532"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2010"
                        "volumen" => "69"
                        "numero" => "6"
                        "paginaInicial" => "964"
                        "paginaFinal" => "975"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20444750"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib2"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2010 Update of the international ASAS recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              D van der Heijde \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              J Sieper \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              WP Maksymowych \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              M Dougados \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              R Burgos-Vargas \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              R Landew&#233; \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2011.151563"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2011"
                        "volumen" => "70"
                        "numero" => "6"
                        "paginaInicial" => "905"
                        "paginaFinal" => "911"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21540200"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib3"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment recommendations for psoriatic arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              CT Ritchlin \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              A Kavanaugh \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              DD Gladman \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              PJ Mease \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              P Helliwell \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              WH Boehncke \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2008.094946"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2009"
                        "volumen" => "68"
                        "numero" => "9"
                        "paginaInicial" => "1387"
                        "paginaFinal" => "1394"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18952643"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib4"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis&#58; Initiation and Safety Monitoring of Therapeutic Agents for the Treatment of Arthritis and Systemic Features"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              T Beukelman \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              NM Patkar \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              KG Saag \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              S Tolleson-Rinehart \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              RQ Cron \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              EM DeWitt \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/acr.20460"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arthritis Care Res &#40;Hoboken&#41;"
                        "fecha" => "2011"
                        "volumen" => "63"
                        "numero" => "4"
                        "paginaInicial" => "465"
                        "paginaFinal" => "482"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21452260"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib5"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Guidelines of care for the management of psoriasis and psoriatic arthritis&#58; section 6&#46; Guidelines of care for the treatment of psoriasis and psoriatic arthritis&#58; case-based presentations and evidence-based conclusions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              A Menter \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              NJ Korman \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              CA Elmets \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              SR Feldman \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              JM Gelfand \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              American Academy of Dermatology Work Group \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "2011"
                        "volumen" => "65"
                        "numero" => "1"
                        "paginaInicial" => "137"
                        "paginaFinal" => "174"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib6"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Guidelines for the management of inflammatory bowel disease in adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              C Mowat \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              A Cole \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              A Windsor \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              T Ahmad \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              I Arnott \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              R Driscoll \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Gut"
                        "fecha" => "2011"
                        "volumen" => "60"
                        "numero" => "5"
                        "paginaInicial" => "571"
                        "paginaFinal" => "607"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib7"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dermatological conditions during TNF-&#945;-blocking therapy in patients with rheumatoid arthritis&#58; a prospective study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              M Flendrie \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              WHPM Vissers \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              MCW Creemers \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              EMGJ Jong \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              PCM van de Kerkhof \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              PLCM van Riel \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Res Ther"
                        "fecha" => "2005"
                        "volumen" => "7"
                        "numero" => "3"
                        "paginaInicial" => "666"
                        "paginaFinal" => "676"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib8"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Frequency&#44; Phenotype&#44; Outcome&#44; and Therapeutic Impact of Skin Reactions Following Initiation of Adalimumab Therapy&#58; Experience from a Consecutive Cohort of Inflammatory Bowel Disease Patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              DC Baumgart \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              U Grittner \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              A Steingraber \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              M Azzaro \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              S Philipp \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ibd.21643"
                      "Revista" => array:7 [
                        "tituloSerie" => "Inflamm Bowel Dis"
                        "fecha" => "2011"
                        "volumen" => "17"
                        "numero" => "12"
                        "paginaInicial" => "2512"
                        "paginaFinal" => "2520"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21351201"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib9"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lepromatous leprosy associated with the use of anti-TNF &#945; therapy&#58; case report"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              DS Freitas \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              NP Machado \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              FV Andrigueti \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              ET Reis Neto \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              MM Pinheiro \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Bras J Rheumatol"
                        "fecha" => "2010"
                        "volumen" => "50"
                        "numero" => "3"
                        "paginaInicial" => "333"
                        "paginaFinal" => "339"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib10"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tuberculosis associated with infliximab&#44; a tumor necrosis factor-alfa neutralizing agent"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              J Keane \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              S Gershon \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              RP Wise \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              E Mirabile-Levens \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              J Kasznica \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              WD Schwieterman \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa011110"
                      "Revista" => array:7 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2001"
                        "volumen" => "345"
                        "numero" => "15"
                        "paginaInicial" => "1098"
                        "paginaFinal" => "1104"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11596589"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk of herpes zoster in patients with rheumatoid arthritis treated with anti-TNF-alpha agents"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              A Strangfeld \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              J Listing \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              P Herzer \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              A Liebhaber \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              K Rockwitz \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              C Richter \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.2009.146"
                      "Revista" => array:7 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2009"
                        "volumen" => "301"
                        "numero" => "7"
                        "paginaInicial" => "737"
                        "paginaFinal" => "744"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19224750"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Herpes zoster risk factors in a national cohort of veterans with rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              JR McDonald \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              AL Zeringue \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              L Caplan \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              P Ranganathan \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              H Xian \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              TE Burroughs \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1086/598331"
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Infect Dis"
                        "fecha" => "2009"
                        "volumen" => "48"
                        "numero" => "10"
                        "paginaInicial" => "1364"
                        "paginaFinal" => "1371"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19368499"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rates of new-onset psoriasis in patients with rheumatoid arthritis receiving anti-tumour necrosis factor alfa therapy&#58; results from the British Society for Rheumatology Biologics Register"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              MJ Harrison \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              WG Dixon \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              KD Watson \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              Y King \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              R Groves \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              KL Hyrich \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2007.087288"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2009"
                        "volumen" => "68"
                        "numero" => "2"
                        "paginaInicial" => "209"
                        "paginaFinal" => "215"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18385277"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anti TNF-alpha induced psoriasis in patients with inflammatory bowel disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              G Fiorino \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              M Allez \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              M Alberto \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              S Danese \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2036.2009.03955.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Aliment Pharmacol Ther"
                        "fecha" => "2009"
                        "volumen" => "29"
                        "numero" => "9"
                        "paginaInicial" => "921"
                        "paginaFinal" => "927"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19210297"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk of non-melanoma skin cancer in a national cohort of veterans with rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              W Amari \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              AL Zeringue \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JR McDonald \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              L Caplan \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              SA Eisen \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              P Ranganathan \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/rheumatology/ker113"
                      "Revista" => array:7 [
                        "tituloSerie" => "Rheumatology"
                        "fecha" => "2011"
                        "volumen" => "50"
                        "numero" => "8"
                        "paginaInicial" => "1431"
                        "paginaFinal" => "1439"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21415022"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib16"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The American Rheumatism Association 1987 revised criteria for classification of rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              FC Arnett \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              SM Edworthy \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              DA Bloch \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              DJ McShane \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              JF Fries \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              NS Cooper \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.1780310302"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "1988"
                        "volumen" => "31"
                        "numero" => "3"
                        "paginaInicial" => "315"
                        "paginaFinal" => "324"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3358796"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluation of diagnostic criteria for ankylosing spondylitis&#46; A proposal for modification of the New York criteria"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              S van der Linden \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              HA Valkenburg \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              A Cats \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.1780270401"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "1984"
                        "volumen" => "27"
                        "numero" => "4"
                        "paginaInicial" => "361"
                        "paginaFinal" => "368"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6231933"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Classification criteria for psoriatic arthritis&#58; development of new criteria from a large international study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              W Taylor \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              D Gladman \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              P Helliwell \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              A Marchesoni \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              P Mease \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              H Mielants \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.21972"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2006"
                        "volumen" => "54"
                        "numero" => "8"
                        "paginaInicial" => "2665"
                        "paginaFinal" => "2673"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16871531"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Atualiza&#231;&#227;o do consenso brasileiro no diagn&#243;stico e tratamento da artrite reumat&#243;ide"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              MB B&#233;rtolo \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              CV Brenol \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              CG Schainberg \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              F Neubarth \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              FAC de Lima \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              IM Laurindo \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Bras Reumatol"
                        "fecha" => "2007"
                        "volumen" => "47"
                        "numero" => "3"
                        "paginaInicial" => "151"
                        "paginaFinal" => "159"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib20"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Consenso Brasileiro de Espondiloartropatias&#58; Espondilite Anquilosante e Artrite Psori&#225;sica Diagn&#243;stico e Tratamento &#8211; Primeira Revis&#227;o"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              PD Sampaio-Barros \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              VF Azevedo \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              R Bonfiglioli \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              WR Campos \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              SCS Carneiro \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              MAP Carvalho \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Bras Reumatol"
                        "fecha" => "2007"
                        "volumen" => "47"
                        "numero" => "3"
                        "paginaInicial" => "233"
                        "paginaFinal" => "249"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib21"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Modified disease activity scores that include twenty-eight-joint counts&#46; Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              ML Prevoo \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              MA van &#8216;t Hof \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              HH Kuper \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              MA van Leeuwen \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              LB van de Putte \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              PL van Riel \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.1780380107"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "1995"
                        "volumen" => "38"
                        "numero" => "1"
                        "paginaInicial" => "44"
                        "paginaFinal" => "48"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7818570"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib22"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A new approach to defining disease status in ankylosing spondylitis&#58; the Bath Ankylosing Spondylitis Disease Activity Index"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              S Garrett \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              T Jenkinson \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              LG Kennedy \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              H Whitelock \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              P Gaisford \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              A Calin \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Rheumatol"
                        "fecha" => "1994"
                        "volumen" => "21"
                        "numero" => "12"
                        "paginaInicial" => "2286"
                        "paginaFinal" => "2291"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7699630"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib23"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Severe psoriasis-oral therapy with a new retinoid"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              T Fredriksson \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              U Pettersson \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000250839"
                      "Revista" => array:7 [
                        "tituloSerie" => "Dermatologica"
                        "fecha" => "1978"
                        "volumen" => "157"
                        "numero" => "4"
                        "paginaInicial" => "238"
                        "paginaFinal" => "244"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/357213"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib24"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              PGH Gell \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:3 [
                        "editores" => "R R ACoombs"
                        "titulo" => "Clinical Aspects of immunology"
                        "serieFecha" => "1963"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib25"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk and prevention of tuberculosis and other serious opportunistic infections associated with the inhibition of tumor necrosis factor"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              LK Winthrop \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ncprheum0336"
                      "Revista" => array:7 [
                        "tituloSerie" => "Nat Clin Pract Rheumatol"
                        "fecha" => "2006"
                        "volumen" => "2"
                        "numero" => "11"
                        "paginaInicial" => "602"
                        "paginaFinal" => "610"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17075599"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib26"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              D Salmon-Ceron \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              F Tubach \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              O Lortholary \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              O Chosidow \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              S Bretagne \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              N Nicolas \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2010.137422"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2011"
                        "volumen" => "70"
                        "numero" => "4"
                        "paginaInicial" => "616"
                        "paginaFinal" => "623"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21177290"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib27"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "TNF-&#945; Antagonist Use and Risk of Hospitalization for Infection in a National Cohort of Veterans With Rheumatoid Arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              MA Lane \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              JR McDonald \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              AL Zeringue \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              L Caplan \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              JR Curtis \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              P Ranganathan \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MD.0b013e318211106a"
                      "Revista" => array:7 [
                        "tituloSerie" => "Medicine &#40;Baltimore&#41;"
                        "fecha" => "2011"
                        "volumen" => "90"
                        "numero" => "2"
                        "paginaInicial" => "139"
                        "paginaFinal" => "145"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21358439"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib28"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The association between systemic glucocorticoid therapy and the risk of infection in patients with rheumatoid arthritis&#58; systematic review and meta-analyses"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              WG Dixon \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              S Suissa \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              M Hudson \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/ar3453"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Res Ther"
                        "fecha" => "2011"
                        "volumen" => "13"
                        "numero" => "4"
                        "paginaInicial" => "R139"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21884589"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib29"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Correlation between atopy and hypersensitivity reactions during therapy with three different TNF-alpha blocking agents in rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              M Benucci \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              M Manfredi \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              G Saviola \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              P Baiardi \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              P Campi \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Exp Rheumatol"
                        "fecha" => "2009"
                        "volumen" => "27"
                        "numero" => "2"
                        "paginaInicial" => "333"
                        "paginaFinal" => "336"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19473578"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib30"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy&#58; a literature review and potential mechanisms of action"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              AN Collamer \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              KT Guerrero \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JS Henning \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              DF Battafarano \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.23835"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2008"
                        "volumen" => "59"
                        "numero" => "7"
                        "paginaInicial" => "996"
                        "paginaFinal" => "1001"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18576309"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib31"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Psoriasiform lesions induced by tumour necrosis factor antagonists&#58; a skin-deep medical conundrum"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              JD Carter \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              HC Gerard \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              AP Hudson \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2007.082842"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2008"
                        "volumen" => "67"
                        "numero" => "8"
                        "paginaInicial" => "1181"
                        "paginaFinal" => "1183"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18299302"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib32"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A medical conundrum&#58; onset of psoriasis in patients receiving anti-tumor necrosis factor agents"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              C Ritchlin \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              F Tausk \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2006.059261"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2006"
                        "volumen" => "65"
                        "numero" => "12"
                        "paginaInicial" => "1541"
                        "paginaFinal" => "1544"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17105851"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib33"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rates of new-onset psoriasis in patients with rheumatoid arthritis receiving anti-tumour necrosis factor alfa therapy&#58; results from the British Society for Rheumatology Biologics Register"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              MJ Harrison \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              WG Dixon \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              KD Watson \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              Y King \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              R Groves \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              KL Hyrich \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2009"
                        "volumen" => "68"
                        "numero" => "2"
                        "paginaInicial" => "209"
                        "paginaFinal" => "215"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib34"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Skin manifestations induced by TNF-alpha inhibitors in juvenile idiopathic arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              I Pontikaki \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              E Shahi \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              LA Frasin \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              R Gianotti \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              C Gelmetti \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              V Gerloni \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12016-011-8262-2"
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Rev Allergy Immunol"
                        "fecha" => "2012"
                        "volumen" => "42"
                        "numero" => "2"
                        "paginaInicial" => "131"
                        "paginaFinal" => "134"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21403999"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib35"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Psoriasis pathophysiology&#58; current concepts of pathogenesis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              JG Krueger \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              A Bowcock \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2004.031120"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2005"
                        "volumen" => "64"
                        "numero" => "Suppl 2"
                        "paginaInicial" => "ii30"
                        "paginaFinal" => "ii36"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15708932"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib36"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increase of peripheral CXCR3 positive T lymphocytes upon treatment of RA patients with TNF-inhibitors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              D Aeberli \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              M Seitz \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              P Juni \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              PM Villiger \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rheumatology &#40;Oxford&#41;"
                        "fecha" => "2005"
                        "volumen" => "44"
                        "numero" => "2"
                        "paginaInicial" => "172"
                        "paginaFinal" => "175"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib37"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biologic therapy &#40;TNF-alpha antagonists&#41;-induced psoriasis&#58; a cytokine imbalance between TNF-alpha and IFN-alpha"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              R Cuchacovich \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              CG Espinoza \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              Z Virk \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              LR Espinoza \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Rheumatol"
                        "fecha" => "2008"
                        "volumen" => "14"
                        "numero" => "6"
                        "paginaInicial" => "353"
                        "paginaFinal" => "356"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib38"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "New onset or exacerbation of psoriatic skin lesions in patients with definite rheumatoid arthritis receiving tumour necrosis factor a antagonists"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              S Kary \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              M Worm \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              H Audring \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              D Huscher \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              M Renelt \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              H Sorensen \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2005.037424"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2006"
                        "volumen" => "65"
                        "numero" => "3"
                        "paginaInicial" => "405"
                        "paginaFinal" => "407"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16150791"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib39"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Staphylococcal toxins in patients with psoriasis&#44; atopic dermatitis&#44; and erythroderma&#44; and in healthy control subjects"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              NS Tomi \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              B Kranke \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              E Aberer \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaad.2005.02.034"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "2005"
                        "volumen" => "53"
                        "numero" => "1"
                        "paginaInicial" => "67"
                        "paginaFinal" => "72"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15965423"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib40"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Infliximab therapy in rheumatoid arthritis and ankylosing spondylitis-induced specific antinuclear and antiphospholipid autoantibodies without autoimmune clinical manifestations&#58; a two-year prospective study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              C Ferraro-Peyret \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              F Coury \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JG Tebib \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              J Bienvenu \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              N Fabien \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/ar1440"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arthritis Res Ther"
                        "fecha" => "2004"
                        "volumen" => "6"
                        "numero" => "6"
                        "paginaInicial" => "R535"
                        "paginaFinal" => "R543"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15535831"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib41"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autoantibody formation in patients with rheumatoid arthritis treated with anti-TNF&#945;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              C Eriksson \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              S Engstrand \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              KG Sundqvist \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              S Rantap&#228;&#228;-Dahlqvist \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2004.024182"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2005"
                        "volumen" => "64"
                        "numero" => "3"
                        "paginaInicial" => "403"
                        "paginaFinal" => "407"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15297281"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib42"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced lupus due to anti-tumor necrosis factor &#945; agents"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              MF Costa \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              NR Said \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              B Zimmermann \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.semarthrit.2007.08.003"
                      "Revista" => array:7 [
                        "tituloSerie" => "Semin Arthritis Rheum"
                        "fecha" => "2008"
                        "volumen" => "37"
                        "numero" => "6"
                        "paginaInicial" => "381"
                        "paginaFinal" => "387"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17977585"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib43"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced systemic lupus erythematosus associated with etanercept therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              N Shakoor \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              M Michalska \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              CA Harris \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              JA Block \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(02)07714-0"
                      "Revista" => array:7 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2002"
                        "volumen" => "359"
                        "numero" => "9306"
                        "paginaInicial" => "579"
                        "paginaFinal" => "580"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11867114"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib44"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced lupus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              RL Yung \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              BC Richardson \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Rheum Dis Clin North Am"
                        "fecha" => "1994"
                        "volumen" => "20"
                        "numero" => "1"
                        "paginaInicial" => "61"
                        "paginaFinal" => "86"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7512273"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib45"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced lupus erythematosus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              F Sarzi-Puttini \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              Atzeni \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              E Captano \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              F Soni \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              E Luibtano \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              A Doria \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Autoimmunity"
                        "fecha" => "2005"
                        "volumen" => "38"
                        "numero" => "7"
                        "paginaInicial" => "507"
                        "paginaFinal" => "518"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib46"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced lupus&#58; an update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              S Vasoo \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/0961203306070000"
                      "Revista" => array:7 [
                        "tituloSerie" => "Lupus"
                        "fecha" => "2006"
                        "volumen" => "15"
                        "numero" => "11"
                        "paginaInicial" => "757"
                        "paginaFinal" => "761"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17153847"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib47"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Beenhouwer DO&#46; Granulomatous Infectious Diseases Associated with Tumor Necrosis Factor Antagonists"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              RS Wallis \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              MS Broder \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JY Wong \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              ME Hanson \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1086/383317"
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Infect Dis"
                        "fecha" => "2004"
                        "volumen" => "38"
                        "numero" => "9"
                        "paginaInicial" => "1261"
                        "paginaFinal" => "1265"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15127338"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack638794"
        "titulo" => "ACKNOWLEDGMENTS"
        "texto" => "<p id="para410" class="elsevierStylePara elsevierViewall">The authors are grateful to the Universidade Federal de S&#227;o Paulo&#44; Rheumatology Division&#44; for the data collection and follow-up of these patients&#44; and we would also like to thank the Dermatology and Pathology departments for supporting this study&#46;</p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/18075932/0000006800000009/v1_202212010704/S1807593222016209/v1_202212010704/en/main.assets"
  "Apartado" => null
  "PDF" => "https://static.elsevier.es/multimedia/18075932/0000006800000009/v1_202212010704/S1807593222016209/v1_202212010704/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222016209?idApp=UINPBA00004N"
]
Article information
ISSN: 18075932
Original language: English
The statistics are updated each day
Year/Month Html Pdf Total
2024 November 5 0 5
2024 October 24 27 51
2024 September 20 25 45
2024 August 22 28 50
2024 July 18 21 39
2024 June 18 16 34
2024 May 10 17 27
2024 April 21 22 43
2024 March 12 12 24
2024 February 18 14 32
2024 January 12 15 27
2023 December 6 18 24
2023 November 10 17 27
2023 October 13 29 42
2023 September 15 25 40
2023 August 10 6 16
2023 July 14 23 37
2023 June 18 5 23
2023 May 35 0 35
2023 April 38 3 41
2023 March 52 2 54
2023 February 12 1 13
2023 January 4 4 8
2022 December 9 1 10
Show all

Follow this link to access the full text of the article

es en pt

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

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

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos