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The incidence of PF varies between different populations&#44; and the average age of onset is between 50 and 60 years&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The pathogenesis of PF is not completely understood&#44; but environmental exposure appears to be involved&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4&#44;5</span></a> We present an interesting case of a young woman with a difficult-to-treat&#44; localized form of PF that was unrelated to any known triggers&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical case</span><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was a 19-year-old Cuban-American woman who presented to our clinic with a 6-month history of eroded&#44; erythematous&#44; crusted lesions on the right side of her face&#46; The lesions had been treated unsuccessfully with topical antifungals&#44; antibiotics&#44; and oral antibiotics for a presumed diagnosis of tinea or impetigo&#46; The patient had no significant past medical history&#44; and her only medications included oral contraceptives and occasional ibuprofen&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">A physical examination revealed faint erythematous&#44; eroded impetiginized patches on the right cheek and temple &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; A culture from 1 lesion grew methicillin-sensitive staphylococcus aureus&#46; Further laboratory studies were undertaken to screen for antinuclear antibodies&#44; including anti-double-stranded DNA antibodies&#44; and antibodies against the extractable nuclear antigens Smith&#44; Ro&#44; and La&#44; and the histone proteins&#59; the results were negative in all cases&#46; A biopsy revealed superficial acantholysis and hyperchromatic nuclei in the granular layer&#44; consistent with PF&#46; Direct immunofluorescence studies demonstrated segmental intercellular staining with immunoglobulin &#40;Ig&#41; G and C3 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>a and b&#41;&#46; Enzyme-linked immunosorbent assay &#40;ELISA&#41; was negative for desmogleins 1 and 3&#46; Based on these results&#44; a diagnosis of PF was confirmed and the patient was started on clobetasol propionate 0&#46;05&#37; ointment with partial response&#46; A trial of dapsone 100<span class="elsevierStyleHsp" style=""></span>mg daily for 2 months resulted in no benefit&#46; Prednisone 60<span class="elsevierStyleHsp" style=""></span>mg daily with gradual taper induced clinical remission with no relapse during a follow-up of 18 months&#44; except for a recent development of a single erythematous patch on the right cheek with confirmation of PF by direct immunofluorescence testing&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Localized PF is rare&#44; and only 12 cases have been reported in the literature &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;6&#8211;12</span></a>&#59; moreover&#44; some of these cases later developed widespread lesions&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7&#44;12</span></a> Topical medications&#44; such as imiquimod and nonsteroidal anti-inflammatory drugs&#44; have been implicated in localized PF &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> In contrast&#44; to other cases reported&#44; our patient was younger&#44; she denied application of any topical medications&#44; and the lesions did not become disseminated&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Despite the clinical impression of impetigo&#44; the lack of response to appropriate antibiotic treatment and the persistence of the lesions prompted us to suspect an immunobullous disorder as the source of the secondarily impetiginized lesions&#46; The presence of subcorneal acantholysis and intercellular staining demonstrated by direct immunofluorescence confirmed the diagnosis of PF&#58; the histopathological features of bullous impetigo may be similar to those of PF&#44; but immunopathology would be negative in bullous impetigo&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In PF&#44; ELISA testing of anti-desmoglein-1 antibodies is usually positive&#44; with sensitivities as high as 97&#46;9&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> and this test has been found to have greater sensitivity and specificity than conventional indirect immunofluorescence &#40;IIF&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> A positive ELISA was reported in two of the published cases of localized PF&#44; and IIF results in these cases were variable &#40;see <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Interestingly&#44; our patient had a negative ELISA but IIF results were positive&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">With regard to management&#44; topical steroids may be used for more localized lesions &#40;see <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; but systemic steroids are currently the mainstay of treatment and were required in our patient to induce clinical remission&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Other treatments&#44; such as dapsone&#44; failed in our case&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion&#44; immunobullous disease should be suspected in presumed infectious disorders that are refractory to appropriate antimicrobial treatment&#46; This case exemplifies the need for proper pathological and immunopathological studies to establish a diagnosis of this very unusual variant of PF&#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 this study was carried out in accordance with the protocols of their institution concerning the publication of patient data&#44; and that all the patients included in the study were properly informed and gave their written informed consent to participation&#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 obtained the informed consent of the patients and&#47;or subjects referred to in this article&#46; The signed forms are in the possession of the corresponding author&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflicts of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
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          "identificador" => "xres335141"
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          "identificador" => "xpalclavsec316734"
          "titulo" => "Keywords"
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        2 => array:2 [
          "identificador" => "xres335140"
          "titulo" => "Resumen"
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          "identificador" => "xpalclavsec316733"
          "titulo" => "Palabras clave"
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        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
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        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Clinical case"
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        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" => "Conflicts of interest"
        ]
        8 => array:1 [
          "titulo" => "References"
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    "tienePdf" => true
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec316734"
          "palabras" => array:3 [
            0 => "Pemphigus foliaceus"
            1 => "Localized"
            2 => "Bullous disorders"
          ]
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      ]
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec316733"
          "palabras" => array:3 [
            0 => "P&#233;nfigo foli&#225;ceo"
            1 => "Localizado"
            2 => "Enfermedades ampollosas"
          ]
        ]
      ]
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    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Pemphigus foliaceus is a superficial vesiculobullous disease that typically presents with widespread lesions&#46; Localized presentations are less frequent&#44; and they typically occur in middle-aged patients&#44; following exposure to topical medications&#44; and later on&#44; become more disseminated&#46; We present a case of a 19-year-old female with a localized presentation of pemphigus foliaceus unrelated to previous topical medications&#44; that was a diagnostic and therapeutically challenging case&#46; We also discuss the literature on localized cases&#44; differences in presentations and responses to various treatment modalities&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El p&#233;nfigo foli&#225;ceo es una enfermedad ves&#237;culo-ampollosa superficial caracterizada por la aparici&#243;n de lesiones generalizadas&#46; Las presentaciones localizadas son menos frecuentes y suelen observarse en pacientes de mediana edad tras la exposici&#243;n a medicamentos t&#243;picos que posteriormente evolucionan a formas m&#225;s diseminadas&#46; Presentamos el caso de una mujer de 19 a&#241;os de edad con p&#233;nfigo foli&#225;ceo localizado no asociado a medicamentos t&#243;picos previos cuyo diagn&#243;stico y tratamiento han supuesto un reto&#46; Tambi&#233;n analizamos la literatura existente sobre los casos de p&#233;nfigo foli&#225;ceo localizado&#44; las diferencias en las presentaciones cl&#237;nicas y las respuestas a distintos tipos de tratamientos&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Maderal AD&#44; Miner A&#44; Nousari C&#44; Alonso-Llamazares J&#46; Localized emphigus Foliaceus with Unilateral Facial Involvement&#46; Actas Dermosifiliogr&#46; 2014&#59;105&#58;413&#8211;417&#46;</p>"
      ]
    ]
    "multimedia" => array:3 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 713
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            "Tamanyo" => 172778
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        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Faint erythematous and eroded impetiginized patches on the right cheek and temple&#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"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Superficial acantholysis and hyperchromatic nuclei in the granular layer &#40;hematoxylin&#8211;eosin&#44; original magnification &#215;20&#41; and &#40;b&#41; DIF at 40&#215; magnification displaying segmental intercellular staining for IgG and C3&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; DIF&#44; direct immunofluorescence&#59; ELISA&#44; enzyme-linked immunosorbent assay&#59; IgG&#44; immunoglobulin G&#59; IIF&#44; indirect immunofluorescence&#59; ND&#44; not determined&#59; N&#47;A&#44; not available information&#46;</p>"
          "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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Author&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">Age&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">Location of lesions&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">Presumed triggers&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">Pathology findings&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">DIF&#44; IIF&#44; and&#47;or ELISA&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">Therapy and response&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">Dissemination&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  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Newton et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></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">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Left side of nose&nbsp;\t\t\t\t\t\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">ND&nbsp;\t\t\t\t\t\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">Subcorneal bulla with considerable acantholysis&nbsp;\t\t\t\t\t\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">&#8226; <span class="elsevierStyleItalic">DIF</span>&#58; intercellular IgG and C3&#8226; <span class="elsevierStyleItalic">IIF</span>&#58; positive&nbsp;\t\t\t\t\t\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">Unresponsive to topical steroids&nbsp;\t\t\t\t\t\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&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">62&nbsp;\t\t\t\t\t\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">Nose&nbsp;\t\t\t\t\t\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">ND&nbsp;\t\t\t\t\t\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">Acantholysis in granular layer&nbsp;\t\t\t\t\t\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">&#8226; <span class="elsevierStyleItalic">DIF</span>&#58; intercellular C3&#8226; <span class="elsevierStyleItalic">IIF</span>&#58; positive at a titre of 1&#58;320&nbsp;\t\t\t\t\t\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">Unresponsive to topical steroids&#59; controlled with cyclophosphamide&nbsp;\t\t\t\t\t\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">Yes&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">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">Nose&nbsp;\t\t\t\t\t\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">ND&nbsp;\t\t\t\t\t\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">N&#47;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#47;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral prednisone 5&#8211;15<span class="elsevierStyleHsp" style=""></span>mg&#47;d prevented relapse&nbsp;\t\t\t\t\t\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">N&#47;A&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="8" 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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Paramsothy et al&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></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">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tip of nose&#44; external nares and nasolabial fold&nbsp;\t\t\t\t\t\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">ND&nbsp;\t\t\t\t\t\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">Subcorneal blister which was partially intra- and partially infra-granular with acantholytic cells&nbsp;\t\t\t\t\t\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">&#8226; <span class="elsevierStyleItalic">DIF</span>&#58; IgG between epidermal cells&#8226; <span class="elsevierStyleItalic">IIF</span>&#58; positive at a titre of 1&#58;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">Prednisolone 30<span class="elsevierStyleHsp" style=""></span>mg&#47;day cleared rash but discontinued due to side effects&nbsp;\t\t\t\t\t\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">Yes&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">65&nbsp;\t\t\t\t\t\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">Nose and behind left ear&nbsp;\t\t\t\t\t\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">ND&nbsp;\t\t\t\t\t\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">Intraepidermal bulla formation below the granular layer&#59; marked acantholysis&nbsp;\t\t\t\t\t\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">&#8226; <span class="elsevierStyleItalic">DIF</span>&#58; IgG between epidermal cells and granular IgM in basement membrane&#8226; <span class="elsevierStyleItalic">IIF</span>&#58; negative&nbsp;\t\t\t\t\t\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">Lesions improved after topical clobetasol propionate&nbsp;\t\t\t\t\t\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">N&#47;A&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="8" 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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yamamoto et al&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">81&nbsp;\t\t\t\t\t\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">Right cheek&nbsp;\t\t\t\t\t\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">ND&nbsp;\t\t\t\t\t\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">Intraepidermal cleft in granular layer and acantholytic cells within the cleft&nbsp;\t\t\t\t\t\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">&#8226; <span class="elsevierStyleItalic">DIF</span>&#58; IgG in intercellular spaces of upper cell layers&#8226; <span class="elsevierStyleItalic">IIF</span>&#58; negative&nbsp;\t\t\t\t\t\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">Received minocycline 100<span class="elsevierStyleHsp" style=""></span>mg daily&#44; nicotinamide 9&#46;0<span class="elsevierStyleHsp" style=""></span>g daily and betamethasone valerate 2&#46;0<span class="elsevierStyleHsp" style=""></span>g daily&#59; lesion cleared in 14 days&nbsp;\t\t\t\t\t\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&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="8" 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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Termeer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&nbsp;\t\t\t\t\t\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">Scalp&nbsp;\t\t\t\t\t\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">Appeared following small local injury&nbsp;\t\t\t\t\t\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">Split in upper granular layer of epidermis and superficial bulla filled with acantholytic keratinocytes and fibrin&nbsp;\t\t\t\t\t\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">&#8226; <span class="elsevierStyleItalic">DIF</span>&#58; IgG in upper epidermal layers&nbsp;\t\t\t\t\t\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">Treated with tacrolimus 0&#46;1&#37; twice daily and it significantly improved after 1 month&nbsp;\t\t\t\t\t\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&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="8" 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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&nbsp;\t\t\t\t\t\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">Left side of face&nbsp;\t\t\t\t\t\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">Topical 5&#37; imiquimod cream&nbsp;\t\t\t\t\t\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">Superficial acantholytic vesicular dermatitis&nbsp;\t\t\t\t\t\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">&#8226; <span class="elsevierStyleItalic">DIF</span>&#58; IgG at keratinocyte cell surface in granular layer&nbsp;\t\t\t\t\t\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">IM 0&#46;1&#37; TAC and topical clobetasol propionate resulted in improvement&#44; required oral prednisone to maintain clinical remission&nbsp;\t\t\t\t\t\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&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="8" 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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kishibe et al&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63&nbsp;\t\t\t\t\t\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">Tip of nose&nbsp;\t\t\t\t\t\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">ND&nbsp;\t\t\t\t\t\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">Subcorneal acantholysis&#44; especially of follicular infundibulum&nbsp;\t\t\t\t\t\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">&#8226; <span class="elsevierStyleItalic">DIF</span>&#58; IgG deposition&#8226; <span class="elsevierStyleItalic">IIF</span>&#58; negative<span class="elsevierStyleItalic">ELISA</span>&#58; negative for anti-desmogleins 1 and 3 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">Responded to oral prednisolone 40<span class="elsevierStyleHsp" style=""></span>mg daily&nbsp;\t\t\t\t\t\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&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="8" 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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zaraa et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></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">42&nbsp;\t\t\t\t\t\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">Scalp&nbsp;\t\t\t\t\t\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">ND&nbsp;\t\t\t\t\t\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">Acantholytic cells were present&nbsp;\t\t\t\t\t\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">&#8226; <span class="elsevierStyleItalic">DIF</span>&#58; positive&#8226; <span class="elsevierStyleItalic">IIF</span>&#58; positive<span class="elsevierStyleItalic">ELISA</span>&#58; positive for anti-desmoglein 1 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">Topical clobetasol propionate and infiltration of triamcinolone acetonide resulted in complete healing&nbsp;\t\t\t\t\t\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&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">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Right cheek&nbsp;\t\t\t\t\t\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">ND&nbsp;\t\t\t\t\t\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">Acantholytic cells were present&nbsp;\t\t\t\t\t\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">&#8226; <span class="elsevierStyleItalic">DIF</span>&#58; positive&#8226; <span class="elsevierStyleItalic">IIF</span>&#58; positive&nbsp;\t\t\t\t\t\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">Treated with oral prednisone and cyclophosphamide&nbsp;\t\t\t\t\t\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&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="8" 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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ohata et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</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="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">Right cheek&nbsp;\t\t\t\t\t\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">ND&nbsp;\t\t\t\t\t\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">Dyskeratotic acantholytic cells in infundibulum of hair follicle&nbsp;\t\t\t\t\t\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">&#8226; <span class="elsevierStyleItalic">ELISA</span>&#58; positive for anti-desmoglein 1 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">Did not receive immediate treatment and lesions spread&#59; later treated with prednisolone 30<span class="elsevierStyleHsp" style=""></span>mg&#47;d&nbsp;\t\t\t\t\t\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">Yes&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="8" 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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Our case&nbsp;\t\t\t\t\t\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">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">Right cheek and temple&nbsp;\t\t\t\t\t\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
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\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">Intercellular staining with IgG and 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
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                  \t\t\t\t">&#8226; <span class="elsevierStyleItalic">DIF</span>&#58; positive&#8226; <span class="elsevierStyleItalic">ELISA</span>&#58; negative for desmogleins 1 and 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Partial response to clobetasol 0&#46;05&#37; ointment&#59; failure of response to dapsone 100<span class="elsevierStyleHsp" style=""></span>mg daily&#59; prednisone 60<span class="elsevierStyleHsp" style=""></span>mg with gradual taper induced remission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
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Journal Information
Vol. 105. Issue 4.
Pages 413-417 (May 2014)
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Vol. 105. Issue 4.
Pages 413-417 (May 2014)
Case Report
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Localized Pemphigus Foliaceus with Unilateral Facial Involvement
Pénfigo foliáceo localizado con afectación facial unilateral
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A.D. Maderal, A. Miner, C. Nousari, J. Alonso-Llamazares
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Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
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Table 1. Previous reported cases of localized pemphigus foliaceus.
Abstract

Pemphigus foliaceus is a superficial vesiculobullous disease that typically presents with widespread lesions. Localized presentations are less frequent, and they typically occur in middle-aged patients, following exposure to topical medications, and later on, become more disseminated. We present a case of a 19-year-old female with a localized presentation of pemphigus foliaceus unrelated to previous topical medications, that was a diagnostic and therapeutically challenging case. We also discuss the literature on localized cases, differences in presentations and responses to various treatment modalities.

Keywords:
Pemphigus foliaceus
Localized
Bullous disorders
Resumen

El pénfigo foliáceo es una enfermedad vesículo-ampollosa superficial caracterizada por la aparición de lesiones generalizadas. Las presentaciones localizadas son menos frecuentes y suelen observarse en pacientes de mediana edad tras la exposición a medicamentos tópicos que posteriormente evolucionan a formas más diseminadas. Presentamos el caso de una mujer de 19 años de edad con pénfigo foliáceo localizado no asociado a medicamentos tópicos previos cuyo diagnóstico y tratamiento han supuesto un reto. También analizamos la literatura existente sobre los casos de pénfigo foliáceo localizado, las diferencias en las presentaciones clínicas y las respuestas a distintos tipos de tratamientos.

Palabras clave:
Pénfigo foliáceo
Localizado
Enfermedades ampollosas
Full Text
Introduction

Pemphigus foliaceus (PF) is a superficial vesiculobullous disease characterized by production of IgG4 antibodies targeting desmoglein 1, a protein important for epidermal cell–cell adhesion.1,2 Disruption of cell–cell adhesion causes acantholysis resulting in superficial, fragile blisters that are prone to rupture. Consequently, patients typically present with erosions rather than blisters.3 Typically, the lesions are well-demarcated and occur on the face or trunk. They tend to be disseminated, and localized presentations are rare. The incidence of PF varies between different populations, and the average age of onset is between 50 and 60 years.3 The pathogenesis of PF is not completely understood, but environmental exposure appears to be involved.2,4,5 We present an interesting case of a young woman with a difficult-to-treat, localized form of PF that was unrelated to any known triggers.

Clinical case

The patient was a 19-year-old Cuban-American woman who presented to our clinic with a 6-month history of eroded, erythematous, crusted lesions on the right side of her face. The lesions had been treated unsuccessfully with topical antifungals, antibiotics, and oral antibiotics for a presumed diagnosis of tinea or impetigo. The patient had no significant past medical history, and her only medications included oral contraceptives and occasional ibuprofen.

A physical examination revealed faint erythematous, eroded impetiginized patches on the right cheek and temple (Fig. 1). A culture from 1 lesion grew methicillin-sensitive staphylococcus aureus. Further laboratory studies were undertaken to screen for antinuclear antibodies, including anti-double-stranded DNA antibodies, and antibodies against the extractable nuclear antigens Smith, Ro, and La, and the histone proteins; the results were negative in all cases. A biopsy revealed superficial acantholysis and hyperchromatic nuclei in the granular layer, consistent with PF. Direct immunofluorescence studies demonstrated segmental intercellular staining with immunoglobulin (Ig) G and C3 (Fig. 2a and b). Enzyme-linked immunosorbent assay (ELISA) was negative for desmogleins 1 and 3. Based on these results, a diagnosis of PF was confirmed and the patient was started on clobetasol propionate 0.05% ointment with partial response. A trial of dapsone 100mg daily for 2 months resulted in no benefit. Prednisone 60mg daily with gradual taper induced clinical remission with no relapse during a follow-up of 18 months, except for a recent development of a single erythematous patch on the right cheek with confirmation of PF by direct immunofluorescence testing.

Figure 1.

Faint erythematous and eroded impetiginized patches on the right cheek and temple.

(0.16MB).
Figure 2.

(a) Superficial acantholysis and hyperchromatic nuclei in the granular layer (hematoxylin–eosin, original magnification ×20) and (b) DIF at 40× magnification displaying segmental intercellular staining for IgG and C3.

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Localized PF is rare, and only 12 cases have been reported in the literature (Table 1)4,6–12; moreover, some of these cases later developed widespread lesions.6,7,12 Topical medications, such as imiquimod and nonsteroidal anti-inflammatory drugs, have been implicated in localized PF (Table 1).4,5 In contrast, to other cases reported, our patient was younger, she denied application of any topical medications, and the lesions did not become disseminated.

Table 1.

Previous reported cases of localized pemphigus foliaceus.

Author  Age  Location of lesions  Presumed triggers  Pathology findings  DIF, IIF, and/or ELISA  Therapy and response  Dissemination 
Newton et al.627  Left side of nose  ND  Subcorneal bulla with considerable acantholysis  DIF: intercellular IgG and C3• IIF: positive  Unresponsive to topical steroids  No 
62  Nose  ND  Acantholysis in granular layer  DIF: intercellular C3• IIF: positive at a titre of 1:320  Unresponsive to topical steroids; controlled with cyclophosphamide  Yes 
43  Nose  ND  N/A  N/A  Oral prednisone 5–15mg/d prevented relapse  N/A 
Paramsothy et al.734  Tip of nose, external nares and nasolabial fold  ND  Subcorneal blister which was partially intra- and partially infra-granular with acantholytic cells  DIF: IgG between epidermal cells• IIF: positive at a titre of 1:40  Prednisolone 30mg/day cleared rash but discontinued due to side effects  Yes 
65  Nose and behind left ear  ND  Intraepidermal bulla formation below the granular layer; marked acantholysis  DIF: IgG between epidermal cells and granular IgM in basement membrane• IIF: negative  Lesions improved after topical clobetasol propionate  N/A 
Yamamoto et al.8  81  Right cheek  ND  Intraepidermal cleft in granular layer and acantholytic cells within the cleft  DIF: IgG in intercellular spaces of upper cell layers• IIF: negative  Received minocycline 100mg daily, nicotinamide 9.0g daily and betamethasone valerate 2.0g daily; lesion cleared in 14 days  No 
Termeer et al.9  83  Scalp  Appeared following small local injury  Split in upper granular layer of epidermis and superficial bulla filled with acantholytic keratinocytes and fibrin  DIF: IgG in upper epidermal layers  Treated with tacrolimus 0.1% twice daily and it significantly improved after 1 month  No 
Lin et al.4  53  Left side of face  Topical 5% imiquimod cream  Superficial acantholytic vesicular dermatitis  DIF: IgG at keratinocyte cell surface in granular layer  IM 0.1% TAC and topical clobetasol propionate resulted in improvement, required oral prednisone to maintain clinical remission  No 
Kishibe et al.10  63  Tip of nose  ND  Subcorneal acantholysis, especially of follicular infundibulum  DIF: IgG deposition• IIF: negativeELISA: negative for anti-desmogleins 1 and 3 antibodies  Responded to oral prednisolone 40mg daily  No 
Zaraa et al.1142  Scalp  ND  Acantholytic cells were present  DIF: positive• IIF: positiveELISA: positive for anti-desmoglein 1 antibodies  Topical clobetasol propionate and infiltration of triamcinolone acetonide resulted in complete healing  No 
34  Right cheek  ND  Acantholytic cells were present  DIF: positive• IIF: positive  Treated with oral prednisone and cyclophosphamide  No 
Ohata et al.12  68  Right cheek  ND  Dyskeratotic acantholytic cells in infundibulum of hair follicle  ELISA: positive for anti-desmoglein 1 antibody  Did not receive immediate treatment and lesions spread; later treated with prednisolone 30mg/d  Yes 
Our case  19  Right cheek and temple  ND  Intercellular staining with IgG and C3  DIF: positive• ELISA: negative for desmogleins 1 and 3  Partial response to clobetasol 0.05% ointment; failure of response to dapsone 100mg daily; prednisone 60mg with gradual taper induced remission  No 

Abbreviations: DIF, direct immunofluorescence; ELISA, enzyme-linked immunosorbent assay; IgG, immunoglobulin G; IIF, indirect immunofluorescence; ND, not determined; N/A, not available information.

Despite the clinical impression of impetigo, the lack of response to appropriate antibiotic treatment and the persistence of the lesions prompted us to suspect an immunobullous disorder as the source of the secondarily impetiginized lesions. The presence of subcorneal acantholysis and intercellular staining demonstrated by direct immunofluorescence confirmed the diagnosis of PF: the histopathological features of bullous impetigo may be similar to those of PF, but immunopathology would be negative in bullous impetigo.2 In PF, ELISA testing of anti-desmoglein-1 antibodies is usually positive, with sensitivities as high as 97.9%,13 and this test has been found to have greater sensitivity and specificity than conventional indirect immunofluorescence (IIF).14 A positive ELISA was reported in two of the published cases of localized PF, and IIF results in these cases were variable (see Table 1). Interestingly, our patient had a negative ELISA but IIF results were positive.

With regard to management, topical steroids may be used for more localized lesions (see Table 1) but systemic steroids are currently the mainstay of treatment and were required in our patient to induce clinical remission.15 Other treatments, such as dapsone, failed in our case.

In conclusion, immunobullous disease should be suspected in presumed infectious disorders that are refractory to appropriate antimicrobial treatment. This case exemplifies the need for proper pathological and immunopathological studies to establish a diagnosis of this very unusual variant of PF.

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 this study was carried out in accordance with the protocols of their institution concerning the publication of patient data, and that all the patients included in the study were properly informed and gave their written informed consent to participation.

Right to privacy and informed consent

The authors obtained the informed consent of the patients and/or subjects referred to in this article. The signed forms are in the possession of the corresponding author.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Maderal AD, Miner A, Nousari C, Alonso-Llamazares J. Localized emphigus Foliaceus with Unilateral Facial Involvement. Actas Dermosifiliogr. 2014;105:413–417.

Copyright © 2012. Elsevier España, S.L. and AEDV
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