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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Beh&#231;et&#39;s disease &#40;BD&#41; is a multisystemic vasculitis&#46; Superficial or deep vein thrombosis is seen in approximately 30&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Herein we report a four-year-old boy who had BD complicated with superior sagittal sinus and transverse sinus thrombosis&#46; To the best of our knowledge&#44; this is the youngest case reported&#46; The patient showed a good response to infliximab administration for the treatment of refractory deep vein thrombosis&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Clinical observation</span><p id="par0010" class="elsevierStylePara elsevierViewall">A four-year-old boy was admitted to the hospital due to recurrent oral aphthae and erythema nodosum&#46; He had epididymitis in two occasions&#46; The patient has nonconsanguineous healthy parents&#46; Oral mucosa ulcerations and anal fissure were noticed in physical examination&#46; The patient did not have uveitis&#46; Pathergy test was positive&#46; Laboratory test results are presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; The patient was diagnosed with BD and treated with colchicine and prednisolone &#40;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The patient had normal blood pressure&#59; however&#44; bilateral papilledema was detected&#46; Magnetic resonance imaging &#40;MRI&#41; showed hyperintense thrombosis in the superior sagittal sinus and in both proximal segments of transverse sinuses &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>a&#41;&#46; Subcutaneous low-molecular-weight heparin &#40;LMWH&#41; was started&#46; The patient was investigated for a prothrombotic state and a methylenetetrahydrofolate reductase &#40;MTHFR&#41; heterozygous mutation was found&#46; Azathioprine was added&#46; One month later bilateral papilledema was detected again&#46; The brain MRI was repeated and a new thrombosis distal to the superior sagittal sinus was detected&#46; After permission from the ministry of health&#44; infliximab was used at a 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day dose and 3 doses were applied on the 0&#44; 2 and 6 weeks&#46; Before the infliximab&#44; azathioprine was stopped&#59; prednisolone was tapered and stopped at the 7th day of infliximab&#46; Ten days after first dose of infliximab&#44; C-reactive protein was decreased to normal range&#44; and both frequency and severity of the oral aphthous lesions were reduced&#46; Resolution of the thrombosis was seen after the second dose of infliximab in the brain MRI &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>b&#41;&#46; Ongoing therapies consist of colchicine and LMWH&#46; Infliximab was well tolerated by this patient&#59; no drug-induced side effects were recorded&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Discussion</span><p id="par0020" class="elsevierStylePara elsevierViewall">The mean age of onset in pediatric BD epidemiologic studies has been 7 years&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> The earliest age reported for thrombotic BD is 11-years&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> To the best of our knowledge&#44; this is the youngest Beh&#231;et&#39;s patient who had cerebral thrombosis&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Vascular lesions in BD can involve both arterial and venous vessels&#44; and cause refractory complications with poor prognosis&#46; In our patient&#44; cerebral thrombosis was refractory to treatment which corticosteroids&#44; immunosuppressants&#44; and anti-coagulants&#46; The administration of infliximab resulted in the improvement of clinical and laboratory findings&#46; In addition&#44; cerebral sinus thrombosis in MRI was reduced&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The vascular involvement of BD develops in the active stage&#46; Mononuclear cells infiltrate the vessel walls and damages them&#44; and this may cause thrombosis&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Infliximab may inhibit the activation of infiltrated mononuclear cells by blockade of TNF and TNF-producing cells&#44; resulting in the prevention of thrombosis&#46; Although long-term efficacy evaluations are still needed in this case&#44; infliximab therapy may be a good option in childhood BD with refractory sinus thrombosis&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Since the International Study Group criteria are accepted for adult BD but not for pediatric BD&#44; the delay in diagnosis of pediatric BD is unavoidable&#46; Especially in the Silk Road countries&#44; even in the absence of the cardinal findings of BD&#44; pediatric patients with recurrent oral aphthous ulcers should be followed up for early detection and treatment of BD complications&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Ethical disclosures</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Protection of human and animal subjects</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Confidentiality of data</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Right to privacy and informed consent</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors have obtained the informed consent of the patients and&#47;or subjects mentioned in the article&#46; The author for correspondence is in possession of this document&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflict of interest statement</span><p id="par0055" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:9 [
        0 => array:2 [
          "identificador" => "xres348911"
          "titulo" => "Abstract"
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec330604"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "xres348912"
          "titulo" => "Resumen"
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec330605"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Clinical observation"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Discussion"
        ]
        6 => array:3 [
          "identificador" => "sec0015"
          "titulo" => "Ethical disclosures"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Protection of human and animal subjects"
            ]
            1 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Confidentiality of data"
            ]
            2 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Right to privacy and informed consent"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Conflict of interest statement"
        ]
        8 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2012-11-03"
    "fechaAceptado" => "2013-05-08"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec330604"
          "palabras" => array:4 [
            0 => "Beh&#231;et&#39;s disease"
            1 => "Thrombosis"
            2 => "Children"
            3 => "Infliximab"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec330605"
          "palabras" => array:4 [
            0 => "Enfermedad de Beh&#231;et&#39;s"
            1 => "Trombosis"
            2 => "Ni&#241;os"
            3 => "Infliximab"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Beh&#231;et&#39;s disease &#40;BD&#41; is a multisystem disorder&#46; The main pathology in BD is vasculitis that involves arteries and veins of all calibers&#46; Central nervous system involvement occurs in 5&#8211;10&#37; of patients&#46; Increased morbidity and mortality is rarely observed in children&#46; The mean age at onset in pediatric BD is approximately 7 years&#46; Neurologic involvement in BD is usually observed after 3&#8211;6 years&#46; We report the case of a four-year-old Turkish boy with BD with sagittal sinus thrombosis treated with infliximab&#46; The patient presented papilledema without neurologic signs&#46; Although long-term efficacy evaluations are needed in this case&#44; infliximab therapy may be a good option in childhood BD with refractory sinus thrombosis&#46; This is the youngest case of BD with sagittal sinus thrombosis reported so far&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La enfermedad de Beh&#231;et&#39;s &#40;EB&#41; es una enfermedad multisist&#233;mica&#46; La principal patolog&#237;a es la vasculitis que involucra tanto las arterias como las venas&#44; de cualquier calibre&#46; La afecci&#243;n del sistema nervioso central ocurre en 5&#8211;10&#37; de los pacientes&#46; En ni&#241;os rara vez se ve un incremento en la morbilidad o mortalidad&#46; La edad media de inicio en ni&#241;os es aproximadamente 7 a&#241;os&#46; La afecci&#243;n neurol&#243;gica en EB se observa tras 3 a 6 a&#241;os de evoluci&#243;n&#46; Reportamos el caso de un ni&#241;o Turco de 4 a&#241;os de edad con EB y trombosis del seno sagital tratado con infliximab&#46; El paciente presenta papiledema sin datos neurol&#243;gicos&#46; Aunque la eficacia a largo plazo de su tratamiento no se evalu&#243; en este caso&#44; el infliximab pudiera ser una buena alternativa en ni&#241;os con EB y trombosis del seno refractaria&#46; Este es el caso m&#225;s joven de trombosis del seno sagital reportado hasta la fecha&#46;</p>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1112
            "Ancho" => 2232
            "Tamanyo" => 241268
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Magnetic resonance imaging of brain before the infliximab&#46; Hyperintense thrombosis filling the superior sagittal sinus and proximal segments of both transverse sinuses was showed and &#40;b&#41; after second dose of infliximab&#44; significant dissolution of the thrombosis was observed in the brain MRI&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "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"><td 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" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Patient&#39;s results at admission&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></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  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Complete blood count</span></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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hemoglobin&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;7<span class="elsevierStyleHsp" style=""></span>g&#47;dl&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>White blood cells &#40;WBC&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;300&#47;mm<span class="elsevierStyleSup">3</span>&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Neutrophils&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9150&#47;mm<span class="elsevierStyleSup">3</span>&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Thrombocytes&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">210&#44;000&#47;mm<span class="elsevierStyleSup">3</span>&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Erythrocyte sedimentation rate&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50<span class="elsevierStyleHsp" style=""></span>mm&#47;h&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>High sensitive C-reactive protein&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22<span class="elsevierStyleHsp" style=""></span>mg&#47;L&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  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Urinalysis</span></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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Specific gravity&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1020&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>pH&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Protein&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Glucose&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ketones&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Bilirubin&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Urobilinogen&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Normal&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Nitrite&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Microscopy&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 WBC&#47;hpf&#44; 2 RBCs&#47;hpf&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  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Immunological and microbiological analysis</span></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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HLA B5&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anti-streptolysin-O&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96<span class="elsevierStyleHsp" style=""></span>IU&#47;ml<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>300<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Antinuclear antibodies&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>C3&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;946<span class="elsevierStyleHsp" style=""></span>g&#47;l &#40;N&#58; 0&#46;9&#8211;1&#46;1<span class="elsevierStyleHsp" style=""></span>g&#47;l&#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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>C4&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;235<span class="elsevierStyleHsp" style=""></span>g&#47;l &#40;N&#58; 0&#46;1&#8211;0&#46;4<span class="elsevierStyleHsp" style=""></span>g&#47;l&#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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anticardiolipin antibodies IgG&#47;IgM&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&#47;negative&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>IgG&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">920<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>IgM&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>IgA&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Angiotensin converting enzyme&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22<span class="elsevierStyleHsp" style=""></span>mcg&#47;L&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pathergy test&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Papulopustular lesion on the left arm after 24<span class="elsevierStyleHsp" style=""></span>h and on both left and right arms after 48<span class="elsevierStyleHsp" style=""></span>h&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>PPD&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&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
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hepatitis B virus surface antigen&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hepatitis B virus Ig M antibody&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cold agglutinin test&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&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="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Epstein&#8211;Barr virus PCR&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="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Herpes simplex virus PCR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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Journal Information
Vol. 10. Issue 4.
Pages 254-256 (July - August 2014)
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Vol. 10. Issue 4.
Pages 254-256 (July - August 2014)
Case report
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Cerebral vein thrombosis in a four year old with Behçet's disease
Trombosis venosa cerebral en un paciente de cuatro años con enfermedad de Behçet
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Duygu Ovunc Hacihamdioglua,
Corresponding author
duyguovunc@yahoo.com.tr

Corresponding author.
, Murat Demirizb, Gungor Sobacic, Murat Kocaoglud, Erkan Demirkayaa, Faysal Goka
a Gulhane Military Medical Academy, Medicine School, Department of Pediatrics, Division of Pediatric Nephrology and Rheumatology, Turkey
b Gulhane Military Medical Academy, Medicine School, Department of Pathology, Turkey
c Gulhane Military Medical Academy, Medicine School, Department of Ophtalmology, Turkey
d Gulhane Military Medical Academy, Medicine School, Department of Radiology, Turkey
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Table 1. Patient's laboratory examinations.
Abstract

Behçet's disease (BD) is a multisystem disorder. The main pathology in BD is vasculitis that involves arteries and veins of all calibers. Central nervous system involvement occurs in 5–10% of patients. Increased morbidity and mortality is rarely observed in children. The mean age at onset in pediatric BD is approximately 7 years. Neurologic involvement in BD is usually observed after 3–6 years. We report the case of a four-year-old Turkish boy with BD with sagittal sinus thrombosis treated with infliximab. The patient presented papilledema without neurologic signs. Although long-term efficacy evaluations are needed in this case, infliximab therapy may be a good option in childhood BD with refractory sinus thrombosis. This is the youngest case of BD with sagittal sinus thrombosis reported so far.

Keywords:
Behçet's disease
Thrombosis
Children
Infliximab
Resumen

La enfermedad de Behçet's (EB) es una enfermedad multisistémica. La principal patología es la vasculitis que involucra tanto las arterias como las venas, de cualquier calibre. La afección del sistema nervioso central ocurre en 5–10% de los pacientes. En niños rara vez se ve un incremento en la morbilidad o mortalidad. La edad media de inicio en niños es aproximadamente 7 años. La afección neurológica en EB se observa tras 3 a 6 años de evolución. Reportamos el caso de un niño Turco de 4 años de edad con EB y trombosis del seno sagital tratado con infliximab. El paciente presenta papiledema sin datos neurológicos. Aunque la eficacia a largo plazo de su tratamiento no se evaluó en este caso, el infliximab pudiera ser una buena alternativa en niños con EB y trombosis del seno refractaria. Este es el caso más joven de trombosis del seno sagital reportado hasta la fecha.

Palabras clave:
Enfermedad de Behçet's
Trombosis
Niños
Infliximab
Full Text

Behçet's disease (BD) is a multisystemic vasculitis. Superficial or deep vein thrombosis is seen in approximately 30% of patients.1 Herein we report a four-year-old boy who had BD complicated with superior sagittal sinus and transverse sinus thrombosis. To the best of our knowledge, this is the youngest case reported. The patient showed a good response to infliximab administration for the treatment of refractory deep vein thrombosis.

Clinical observation

A four-year-old boy was admitted to the hospital due to recurrent oral aphthae and erythema nodosum. He had epididymitis in two occasions. The patient has nonconsanguineous healthy parents. Oral mucosa ulcerations and anal fissure were noticed in physical examination. The patient did not have uveitis. Pathergy test was positive. Laboratory test results are presented in Table 1. The patient was diagnosed with BD and treated with colchicine and prednisolone (1mg/kg/day).

Table 1.

Patient's laboratory examinations.

  Patient's results at admission 
Complete blood count
Hemoglobin  13.7g/dl 
White blood cells (WBC)  12,300/mm3 
Neutrophils  9150/mm3 
Thrombocytes  210,000/mm3 
Erythrocyte sedimentation rate  50mm/h 
High sensitive C-reactive protein  22mg/L 
Urinalysis
Specific gravity  1020 
pH 
Protein  Negative 
Glucose  Negative 
Ketones  Negative 
Bilirubin  Negative 
Urobilinogen  Normal 
Nitrite  Negative 
Microscopy  2 WBC/hpf, 2 RBCs/hpf 
Immunological and microbiological analysis
HLA B5  Positive 
Anti-streptolysin-O  96IU/ml<300IU/ml 
Antinuclear antibodies  Negative 
C3  0.946g/l (N: 0.9–1.1g/l) 
C4  0.235g/l (N: 0.1–0.4g/l) 
Anticardiolipin antibodies IgG/IgM  Negative/negative 
IgG  920mg/dl 
IgM  48mg/dl 
IgA  80mg/dl 
Angiotensin converting enzyme  22mcg/L 
Pathergy test  Papulopustular lesion on the left arm after 24h and on both left and right arms after 48
PPD  Negative 
Quanti-feron  Negative 
Hepatitis B virus surface antigen  Negative 
Hepatitis B virus Ig M antibody  Negative 
Cold agglutinin test  Negative 
Cytomegalovirus PCR  Negative 
Epstein–Barr virus PCR  Negative 
Herpes simplex virus PCR  Negative 
MEFV mutation  E148Q/– 

The patient had normal blood pressure; however, bilateral papilledema was detected. Magnetic resonance imaging (MRI) showed hyperintense thrombosis in the superior sagittal sinus and in both proximal segments of transverse sinuses (Fig. 1a). Subcutaneous low-molecular-weight heparin (LMWH) was started. The patient was investigated for a prothrombotic state and a methylenetetrahydrofolate reductase (MTHFR) heterozygous mutation was found. Azathioprine was added. One month later bilateral papilledema was detected again. The brain MRI was repeated and a new thrombosis distal to the superior sagittal sinus was detected. After permission from the ministry of health, infliximab was used at a 5mg/kg/day dose and 3 doses were applied on the 0, 2 and 6 weeks. Before the infliximab, azathioprine was stopped; prednisolone was tapered and stopped at the 7th day of infliximab. Ten days after first dose of infliximab, C-reactive protein was decreased to normal range, and both frequency and severity of the oral aphthous lesions were reduced. Resolution of the thrombosis was seen after the second dose of infliximab in the brain MRI (Fig. 1b). Ongoing therapies consist of colchicine and LMWH. Infliximab was well tolerated by this patient; no drug-induced side effects were recorded.

Fig. 1.

(a) Magnetic resonance imaging of brain before the infliximab. Hyperintense thrombosis filling the superior sagittal sinus and proximal segments of both transverse sinuses was showed and (b) after second dose of infliximab, significant dissolution of the thrombosis was observed in the brain MRI.

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Discussion

The mean age of onset in pediatric BD epidemiologic studies has been 7 years.2,3 The earliest age reported for thrombotic BD is 11-years.4 To the best of our knowledge, this is the youngest Behçet's patient who had cerebral thrombosis.

Vascular lesions in BD can involve both arterial and venous vessels, and cause refractory complications with poor prognosis. In our patient, cerebral thrombosis was refractory to treatment which corticosteroids, immunosuppressants, and anti-coagulants. The administration of infliximab resulted in the improvement of clinical and laboratory findings. In addition, cerebral sinus thrombosis in MRI was reduced.

The vascular involvement of BD develops in the active stage. Mononuclear cells infiltrate the vessel walls and damages them, and this may cause thrombosis.5 Infliximab may inhibit the activation of infiltrated mononuclear cells by blockade of TNF and TNF-producing cells, resulting in the prevention of thrombosis. Although long-term efficacy evaluations are still needed in this case, infliximab therapy may be a good option in childhood BD with refractory sinus thrombosis.

Since the International Study Group criteria are accepted for adult BD but not for pediatric BD, the delay in diagnosis of pediatric BD is unavoidable. Especially in the Silk Road countries, even in the absence of the cardinal findings of BD, pediatric patients with recurrent oral aphthous ulcers should be followed up for early detection and treatment of BD complications.

Ethical disclosuresProtection of human and animal subjects

The authors declare that no experiments were performed on humans or animals for this investigation.

Confidentiality of data

The authors declare that they have followed the protocols of their work center on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study.

Right to privacy and informed consent

The authors have obtained the informed consent of the patients and/or subjects mentioned in the article. The author for correspondence is in possession of this document.

Conflict of interest statement

None.

References
[1]
I. Koné-Paut, S. Yurdakul, S.A. Bahabri, N. Shafae, S. Ozen, H. Ozdogan, et al.
Clinical features of Behçet's disease in children: an international collaborative study of 86 cases.
J Pediatr, 132 (1998), pp. 721-725
[2]
M. Borlu, U. Ukşal, A. Ferahbaş, C. Evereklioglu.
Clinical features of Behçet's disease in children.
Int J Dermatol, 45 (2006), pp. 713-716
[3]
M. Laghmari, A. Karim, F. Allali, A. Elmadani, W. Ibrahımy, N. Hajjaj Hassouni, et al.
Childhood Behçet's disease: clinical and evolutive aspects. About 13 cases.
J Fr Ophtalmol, 25 (2002), pp. 904-908
[4]
J. Metreau-Vastel, Y. Mikaeloff, M. Tardieu, I. Koné-Paut, T.A. Tran.
Neurological involvement in paediatric Behçet's disease.
Neuropediatrics, 41 (2010), pp. 228-234
[5]
E. Seyahi, S. Yurdakul.
Behcet's syndrome and thrombosis.
Mediterr J Hematol Infect Dis, 3 (2011),
Copyright © 2012. Elsevier España, S.L.. All rights reserved
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