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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Dermatomyositis &#40;DM&#41; presents with various cutaneous manifestations&#44; some of which associate with internal malignancies&#46; To date&#44; single case reports of vesiculo-bullous DM have been reported in the English literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#8211;6</span></a> We describe herein 5 cases of vesiculo-bullous DM in patients with internal malignancy&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The present study included 5 patients with DM who developed vesicles and&#47;or bullae during the course&#46; The diagnosis of DM was based on the diagnostic criteria proposed by Bohan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> The diagnosis of clinically amyopathic DM was made based on the classification criteria proposed by Sontheimer&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> The patients consisted of 4 males and 1 female&#44; with an age range of 68 to 76 years &#40;mean age&#58; 71&#46;6 years&#41;&#46; The site of the bullous lesion was as follows&#58; elbow &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&#44; upper arm &#40;1&#41;&#44; knee &#40;1&#41;&#44; trunk &#40;1&#41; and shoulder &#40;1&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Biopsy was performed from the bullous lesion in 4 cases &#40;Cases 1&#8211;4&#41;&#44; which revealed marked subepidermal edema with mucin deposition in the upper dermis &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Direct immunofluorescence findings were negative at the basement membrane zone in all cases&#46; Other cutaneous signs observed were Gottron&#39;s papules &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&#44; poikiloderma &#40;3&#41;&#44; malignant erythema &#40;2&#41;&#44; seborrheic dermatitis-like facial erythema &#40;1&#41;&#44; and flagellate erythema &#40;1&#41;&#46; 3 cases &#40;Cases 1&#44; 3&#44; and 5&#41; were accompanied with myositis&#44; and 1 case &#40;Case 4&#41; was diagnosed with clinically amyopathic DM&#46; In only 1 case &#40;Case 1&#41;&#44; myositis-specific autoantibody was detected&#44; which was anti-TIF-1&#947; antibody&#46; Interstitial lung disease &#40;ILD&#41; was not observed in all cases&#46; Malignancies were observed in all cases&#58; lung cancer &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&#44; esophageal cancer &#40;1&#41; and ovarian cancer &#40;1&#41;&#46; 3 cases &#40;Cases 2&#44; 4&#44; and 5&#41; were treated with chemotherapy&#46; In Case 1&#44; esophageal cancer was diagnosed after discharge from our hospital&#44; and the patient&#39;s detailed medical condition was unclear&#46; In Case 3&#44; there were many metastatic lesions at the time of diagnosis of ovarian cancer&#44; and the patient could not be treated with chemotherapy due to poor general condition&#46; 3 cases &#40;Cases 1&#44; 3&#44; and 4&#41; were treated with oral prednisolone&#46; The patient in Case 1 had progressive and severe dysphagia&#44; and was treated with methylprednisolone &#40;1000<span class="elsevierStyleHsp" style=""></span>mg&#47;day for consecutive 3 days&#41;&#44; intravenous immunoglobulin therapy for 3 times&#44; prednisolone and methotrexate&#46; However&#44; swallowing function was not fully recovered&#44; and the patient repeatedly developed aspiration pneumonia&#46; 3 patients &#40;Cases 3&#8211;5&#41; died of malignancy 6 months&#44; 1 year and 2 years after the diagnosis of DM&#44; respectively&#46; Prognosis of the other 2 cases &#40;Cases 1 and 2&#41; was unknown&#46; In all cases&#44; the bullous lesions appeared in parallel with the onset of or increased disease activity of DM&#46; DM was diagnosed at around the same time as the discovery of cancer&#44; surgical operation of cancer or development of metastases &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Vesicular formation in DM is relatively rare&#44; but highly associated with internal malignancy&#46; All of our patients had solid cancers&#44; which were lung cancer &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&#44; esophageal cancer &#40;1&#41; and ovarian cancer &#40;1&#41;&#46; Drug-induced bullous eruption was excluded&#46; According to the report by Kubo et al&#46;&#44; 19 cases of vesiculo-bullous DM were reviewed&#44; of which 6 cases were males and 13 cases were females&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Internal malignancy was observed in 10 cases&#58; in the ovary &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&#44; cervix uteri &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&#44; stomach &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44; uterine tube &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44; mammary gland &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44; and lung &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#46; After their report&#44; we collected 17 cases of vesiculo-bulous DM&#44; including those having mammary cancer &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&#44; nasopharyngeal cancer &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&#44; ovarian cancer &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44; lung cancer &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44; malignant lymphoma &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44; colon cancer &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44; gastric cancer &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44; and thyroid cancer &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#46; However&#44; there was no malignancy in 6 cases&#44; while ILD was observed in 4 cases&#46; The incidence of internal malignancy was much higher in patients with vesiculo-bullous DM than in those without bullous lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Myositis-specific autoantibodies were examined in a few of our cases&#44; because examination of those autoantibodies became available only recently&#46; Anti-TIF-1&#947; antibody was examined in 1 case &#40;Case 1&#41;&#44; which showed positive titers&#46; The prevalence of cancer in anti-TIF-1&#947;-positive patients varies between 38&#37; and 80&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> A recent report suggests that abnormally changed tumor antigens can trigger autoimmune response by cross-reactive immunity&#44; leading to muscle damage<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a>&#59; however&#44; the mechanism of the induction of vesicular formation in association with tumor antigen is unknown&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In conclusion&#44; in DM&#44; a vesiculo-bullous lesion is a paraneoplastic cutaneous sign of internal malignancy&#44; rather than ILD&#46; Clinicians should be aware of the vesiculo-bullous DM&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest</p></span></span>"
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Vesiculo-bullous appearances &#40;a&#58; Case 4&#44; b&#58; Case 2&#44; c&#58; Case 5&#44; d&#58; Case 1&#41;&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 384
            "Ancho" => 1005
            "Tamanyo" => 102364
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histology showing subepidermal bulla &#40;a&#59; H&#8211;E stain&#41;&#46; Mucin deposition below the bulla &#40;b&#59; colloidal iron stain&#41;&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">mPSL&#44; methylprednisolone&#59; PSL&#44; prednisolone&#59; IVIG&#44; intravenous immunoglobulin&#59; MTX&#44; methotrexate&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Case&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sex&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Site of bullous lesion&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Other skin lesion&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Interstitial lung disease&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Malignancy&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Myositis&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CK &#40;U&#47;L&#41;45&#8211;163&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ANA&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">74&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">M&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">Elbow&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">Gottron&#39;s papules&#44; poikiloderma&#44; seborrheic dermatitis&#44; nail fold bleeding&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">&#8722;&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">Esophagus&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">&#43;&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">8028&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">320 &#40;homogeneous&#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">mPSL&#44; PSL&#44; IVIG&#44; MTX&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&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">M&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">Upper arm&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">Gottron&#39;s papules&#44; poikiloderma&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">&#8722;&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">Lung&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">No data&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">462&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">160 &#40;homogeneous &#38; speckled&#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">Chemotherapy&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76&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">F&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">Trunk&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">Gottron&#39;s papules&#44; malignant 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;&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">Ovarian&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">&#43;&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">264&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 &#40;homogeneous&#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">PSL&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&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">M&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">Elbow&#44; shoulder&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">Flagellate erythema&#44; malignant 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;&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">Lung&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">&#8722;&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">139&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">&#60;40&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">PSL&#44; chemotherapy&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&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">M&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">Knee&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">Gottron&#39;s papules&#44; poikiloderma&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">&#8722;&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">Lung&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">&#43;&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">2966&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">&#60;160&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">Chemotherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">5 patients presenting with vesiculo-bullous dermatomyositis&#46;</p>"
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Vol. 113. Issue 10.
Pages 1017-1019 (November - December 2022)
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Vol. 113. Issue 10.
Pages 1017-1019 (November - December 2022)
Case and Research Letter
Open Access
Vesiculo-bullous Dermatomyositis in Association with Internal Malignancy
Dermatomiositis vesículo-ampollosa asociada a neoplasia interna
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T. Mori
Corresponding author
mtatsu@fmu.ac.jp

Corresponding author.
, Y. Hanami, T. Yamamoto
Department of Dermatology, Fukushima Medical University, Fukushima, Japan
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Actas Dermosifiliogr. 2022;113:T1017-T101910.1016/j.ad.2022.10.006
T. Mori, Y. Hanami, T. Yamamoto
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Dear Editor:

Dermatomyositis (DM) presents with various cutaneous manifestations, some of which associate with internal malignancies. To date, single case reports of vesiculo-bullous DM have been reported in the English literature.1–6 We describe herein 5 cases of vesiculo-bullous DM in patients with internal malignancy.

The present study included 5 patients with DM who developed vesicles and/or bullae during the course. The diagnosis of DM was based on the diagnostic criteria proposed by Bohan et al.7 The diagnosis of clinically amyopathic DM was made based on the classification criteria proposed by Sontheimer.8 The patients consisted of 4 males and 1 female, with an age range of 68 to 76 years (mean age: 71.6 years). The site of the bullous lesion was as follows: elbow (n=2), upper arm (1), knee (1), trunk (1) and shoulder (1) (Fig. 1). Biopsy was performed from the bullous lesion in 4 cases (Cases 1–4), which revealed marked subepidermal edema with mucin deposition in the upper dermis (Fig. 2). Direct immunofluorescence findings were negative at the basement membrane zone in all cases. Other cutaneous signs observed were Gottron's papules (n=4), poikiloderma (3), malignant erythema (2), seborrheic dermatitis-like facial erythema (1), and flagellate erythema (1). 3 cases (Cases 1, 3, and 5) were accompanied with myositis, and 1 case (Case 4) was diagnosed with clinically amyopathic DM. In only 1 case (Case 1), myositis-specific autoantibody was detected, which was anti-TIF-1γ antibody. Interstitial lung disease (ILD) was not observed in all cases. Malignancies were observed in all cases: lung cancer (n=3), esophageal cancer (1) and ovarian cancer (1). 3 cases (Cases 2, 4, and 5) were treated with chemotherapy. In Case 1, esophageal cancer was diagnosed after discharge from our hospital, and the patient's detailed medical condition was unclear. In Case 3, there were many metastatic lesions at the time of diagnosis of ovarian cancer, and the patient could not be treated with chemotherapy due to poor general condition. 3 cases (Cases 1, 3, and 4) were treated with oral prednisolone. The patient in Case 1 had progressive and severe dysphagia, and was treated with methylprednisolone (1000mg/day for consecutive 3 days), intravenous immunoglobulin therapy for 3 times, prednisolone and methotrexate. However, swallowing function was not fully recovered, and the patient repeatedly developed aspiration pneumonia. 3 patients (Cases 3–5) died of malignancy 6 months, 1 year and 2 years after the diagnosis of DM, respectively. Prognosis of the other 2 cases (Cases 1 and 2) was unknown. In all cases, the bullous lesions appeared in parallel with the onset of or increased disease activity of DM. DM was diagnosed at around the same time as the discovery of cancer, surgical operation of cancer or development of metastases (Table 1).

Figure 1.

Vesiculo-bullous appearances (a: Case 4, b: Case 2, c: Case 5, d: Case 1).

(0.12MB).
Figure 2.

Histology showing subepidermal bulla (a; H–E stain). Mucin deposition below the bulla (b; colloidal iron stain).

(0.1MB).
Table 1.

5 patients presenting with vesiculo-bullous dermatomyositis.

Case  Age  Sex  Site of bullous lesion  Other skin lesion  Interstitial lung disease  Malignancy  Myositis  CK (U/L)45–163  ANA  Treatment 
74  Elbow  Gottron's papules, poikiloderma, seborrheic dermatitis, nail fold bleeding  −  Esophagus  8028  320 (homogeneous)  mPSL, PSL, IVIG, MTX 
68  Upper arm  Gottron's papules, poikiloderma  −  Lung  No data  462  160 (homogeneous & speckled)  Chemotherapy 
76  Trunk  Gottron's papules, malignant erythema  −  Ovarian  264  80 (homogeneous)  PSL 
72  Elbow, shoulder  Flagellate erythema, malignant erythema  −  Lung  −  139  <40  PSL, chemotherapy 
68  Knee  Gottron's papules, poikiloderma  −  Lung  2966  <160  Chemotherapy 

mPSL, methylprednisolone; PSL, prednisolone; IVIG, intravenous immunoglobulin; MTX, methotrexate.

Vesicular formation in DM is relatively rare, but highly associated with internal malignancy. All of our patients had solid cancers, which were lung cancer (n=3), esophageal cancer (1) and ovarian cancer (1). Drug-induced bullous eruption was excluded. According to the report by Kubo et al., 19 cases of vesiculo-bullous DM were reviewed, of which 6 cases were males and 13 cases were females.1 Internal malignancy was observed in 10 cases: in the ovary (n=4), cervix uteri (n=2), stomach (n=1), uterine tube (n=1), mammary gland (n=1), and lung (n=1). After their report, we collected 17 cases of vesiculo-bulous DM, including those having mammary cancer (n=3), nasopharyngeal cancer (n=2), ovarian cancer (n=1), lung cancer (n=1), malignant lymphoma (n=1), colon cancer (n=1), gastric cancer (n=1), and thyroid cancer (n=1). However, there was no malignancy in 6 cases, while ILD was observed in 4 cases. The incidence of internal malignancy was much higher in patients with vesiculo-bullous DM than in those without bullous lesions.1

Myositis-specific autoantibodies were examined in a few of our cases, because examination of those autoantibodies became available only recently. Anti-TIF-1γ antibody was examined in 1 case (Case 1), which showed positive titers. The prevalence of cancer in anti-TIF-1γ-positive patients varies between 38% and 80%.9 A recent report suggests that abnormally changed tumor antigens can trigger autoimmune response by cross-reactive immunity, leading to muscle damage10; however, the mechanism of the induction of vesicular formation in association with tumor antigen is unknown.

In conclusion, in DM, a vesiculo-bullous lesion is a paraneoplastic cutaneous sign of internal malignancy, rather than ILD. Clinicians should be aware of the vesiculo-bullous DM.

Conflict of interest

The authors declare that they have no conflict of interest

References
[1]
M. Kubo, S. Sato, H. Kitahara, T. Tsuchida, K. Tamaki.
Vesicle formation in dermatomyositis associated with gynecologic malignancies.
J Am Acad Dermatol, 34 (1996), pp. 391-394
[2]
T. Hiyami, K. Teramura, T. Tanaka, N. Fujimoto.
Anti-MDA5 antibody-positive bullous dermatomyositis with thyroid carcinoma.
Eur J Dermatol, 28 (2018), pp. 418-419
[3]
A. Mebazaa, H. Boussen, R. Nouira, A. Gamoudi, K. Rahal, M.R. Kamoun, et al.
Dermatomyositis and breast cancer: a multicenter Tunisian retrospective study of 13 cases.
Tunis Med, 89 (2011), pp. 18-22
[4]
Y.-P. Yang, Y. Zhou, H.-W. Guo, Y.-M. Fan.
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Eur J Dermatol, 21 (2011), pp. 778-779
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A case of vesiculobullous dermatomyositis: a marker of internal malignancy.
Int J Dermatol, 51 (2012), pp. 594-596
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E. Ayhan, S.N. Baykara, S. Ozekinci, S. Aytekin.
Vesiculobullous dermatomyositis with sensory motor neuropathy.
Skinmed, 11 (2013), pp. 185-187
[7]
A. Bohan, J.B. Peter, R.L. Bowman, C.M. Pearson.
Computer-assisted analysis of 153 patients with polymyositis and dermatomyositis.
[8]
R.D. Sontheimer.
Would a new name hasten the acceptance of amyopathic dermatomyositis (dermatomyositis siné myositis) as a distinctive subset within the idiopathic inflammatory dermatomyopathies spectrum of clinical illness?.
J Am Acad Dermatol, 46 (2002), pp. 626-636
[9]
E. Tiniakou, A.L. Mammen.
Idiopathic inflammatory myopathies and malignancy: a comprehensive review.
Clin Rev Allergy Immunol, 52 (2017), pp. 20-33
[10]
X. Lu, Q. Peng, G. Wang.
The role of cancer-associated autoantibodies as biomarkers in paraneoplastic myositis syndrome.
Curr Opin Rheumatol, 31 (2019), pp. 643-649
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