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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Some of the subtypes of Darier disease&#46; A&#44; Acral hemorrhagic Darier disease&#58; dark red macules on the dorsum of the hand&#46; B&#44; Vesiculobullous type&#58; vesicles and blisters of various sizes are present along with erythematous-keratotic papules&#46; C&#44; Comedonal form&#58; comedones and cysts appear along with the typical lesions of Darier disease&#46; D&#44; Type 1 segmental Darier disease&#58; involvement limited to the lines of Blaschko on the left flank&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Darier disease is a rare autosomal dominant genetic disorder that presents with reddish-brown keratotic papules in seborrheic areas as well as with palmoplantar&#44; nail&#44; and mucosal tissue involvement&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Darier disease is due to a mutation in the sarcoplasmic&#47;endoplasmic reticulum calcium ATPase gene &#40;<span class="elsevierStyleItalic">ATP2A2</span>&#41;&#44; which codes for the endoplasmic reticulum ATPase calcium pump &#40;SERCA2b&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Few case series of patients with Darier disease have been published to date&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> We describe a series of Spanish patients with this disease in the interest of learning more about its characteristics&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">To that end we searched our hospital&#8217;s database to identify patients diagnosed with histologically confirmed Darier disease treated in our department between January 2008 and January 2019&#46; We extracted the following information for the 20 cases found&#58; age&#44; sex&#44; family history of Darier disease&#44; location of lesions&#44; and concurrent conditions &#40;whether cutaneous or extracutaneous&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The patients&#8217; median age of 46 &#40;range&#44; 15&#8211;76&#41; years was slightly higher than the ages reflected in the literature&#44; where symptoms debut in patients between 12 and 20 years old&#59; the distribution of sexes in our series was similar&#44; however&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> A family history of Darier disease was reported by 20&#37; of our patients&#44; a lower proportion than the 50&#37; to 60&#37; reported in the literature&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The most common clinical manifestation was the presence of brownish&#44; keratotic&#44; or erythematous papules that might or might not be grouped in verrucous plaques&#46; We observed the histologic features that are typical of the disease&#58; acantholysis&#44; dyskeratosis&#44; and negative direct immunofluorescence&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Some of the subtypes of Darier disease were represented in our study &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Patient 15 developed reddish-blackish macules on hands and feet&#44; a presentation consistent with the acral hemorrhagic type&#46; Such lesions are caused by bleeding within acantholytic vesicles and may be associated with the p&#46;N767S mutation in the <span class="elsevierStyleItalic">ATP2A2</span> gene&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The vesiculobullous variety was seen in patient 17&#44; who had vesicles and blisters mixed with keratotic papules as the primary lesions&#46; In such cases it is important to rule out infection&#44; especially by a virus&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Patient 11 had comedones and cysts along with keratotic papules&#44; consistent with comedonal Darier disease&#46; This subtype is difficult to diagnose because of its resemblance to acne vulgaris and familial dyskeratotic comedones&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Two patients had lesions following along the lines of Blaschko &#40;right breast and flank&#41;&#46; After biopsy&#44; these cases were confirmed as type 1 segmental Darier disease&#46; This type debuts later in life and must be distinguished from Grover disease and warty dyskeratoma&#44; which are clinically and histologically similar but whose lesions do not present in a blaschkoid distribution&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Although hypopigmented macules intermingled with keratotic papules&#44; a finding referred to as guttate leukoderma&#44; are sometimes present&#44; we saw no such eruptions in our series&#46; Other variants not represented were hypotrophic&#44; verrucous&#44; and erosive forms of Darier disease&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">However&#44; multiple associated disorders were present in our series &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Given that the calcium pump &#40;SERCA2b&#41; is present in all cells&#44; that a genetic mutation would cause symptoms in organs other than the skin seems logical&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Extracutaneous manifestations of Darier disease&#44; apparently due to the pleiotropic influence of <span class="elsevierStyleItalic">ATP2A2</span> mutations on other cells&#44; have been described&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Associated neuropsychiatric disorders were present in 30&#37; of the patients in our series in the form of epilepsy&#44; attention deficit hyperactivity disorder&#44; and anxiety-depressive disorder&#46; Another reported association is salivary gland obstruction caused by episodes of acantholysis and dyskeratosis in the epithelium of salivary ducts&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Another of our patients had &#8220;submaxillary&#8221; &#40;ie&#44; submandibular&#41; sialolithiasis that required submaxillectomy&#46; One of our patients had renal polycystic disease&#44; which is also a reported association<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#59; we underline the importance of bearing kidney disease in mind so that it can be diagnosed early&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Finally&#44; 3 patients in our series had melanomas&#46; This association has been described occasionally in the literature but is likely to be a chance finding&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&nbsp;\t\t\t\t\t\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">No&nbsp;\t\t\t\t\t\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">Skin folds &#40;between and under the breasts&#44; groin&#44; behind the ear&#41;&#44; external auditory canal&#44; over the shin&#44; hairline&#44; palmoplantar pitting&#44; dorsum of the hand&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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">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">Mother&#44; sister&nbsp;\t\t\t\t\t\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">Thorax&#44; behind the ear&#44; upper and lower limbs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\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">Mother&nbsp;\t\t\t\t\t\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">Side of the neck&#44; periumbilical region&#44; external auditory canal&#44; hairline&#44; palmoplantar pitting&#44; dorsum of the hands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\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">No&nbsp;\t\t\t\t\t\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">Side of the neck&#44; thorax&#44; periumbilical region&#44; palmoplantar pitting&#44; dorsum of the hands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\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">No&nbsp;\t\t\t\t\t\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">Side of the neck&#44; thorax &#40;between and under breasts&#41;&#44; abdomen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">73&nbsp;\t\t\t\t\t\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">No&nbsp;\t\t\t\t\t\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">Thorax &#40;between breasts&#41;&#44; groin&#44; hairline&#44;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" 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">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">No&nbsp;\t\t\t\t\t\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">Thorax &#40;between breasts&#41;&#44; periumbilical region&#44; upper and lower limbs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" 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">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">No&nbsp;\t\t\t\t\t\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">Thorax &#40;upper third&#41;&#44; thighs&#44; lumbar region&#44; external auditory canal&#44; hairline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" 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">No&nbsp;\t\t\t\t\t\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">Thorax&#44; periumbilical region&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\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">23&nbsp;\t\t\t\t\t\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">No&nbsp;\t\t\t\t\t\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">Side of the neck&#44; between shoulder blades&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\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">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">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">No&nbsp;\t\t\t\t\t\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">Thorax &#40;between breasts&#41;&#44; periumbilical region&#44; dorsum of the hands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\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">75&nbsp;\t\t\t\t\t\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">No&nbsp;\t\t\t\t\t\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">Thorax &#40;between breasts&#41;&#44; between the shoulder blades&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&nbsp;\t\t\t\t\t\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">No&nbsp;\t\t\t\t\t\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">Thorax &#40;under the breasts&#41;&#44; groin&#44; side of the abdomen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\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">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">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">No&nbsp;\t\t\t\t\t\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 breast &#40;segmental&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\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">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">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">Mother&#44; grandmother&nbsp;\t\t\t\t\t\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">Side of the neck&#44; thorax &#40;under the breasts&#41;&#44; antecubital&#44; popliteal&#44; lumbar region&#44; hairline&#44; palmoplantar pitting&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\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">66&nbsp;\t\t\t\t\t\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">No&nbsp;\t\t\t\t\t\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 the abdomen &#40;segmental&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\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">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">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">No&nbsp;\t\t\t\t\t\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">Side of the neck&#44; thorax &#40;under the breasts&#41;&#44; lumbar region&#44; behind the ear&#44; palmoplantar pitting&#44; dorsum of the hands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\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">58&nbsp;\t\t\t\t\t\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">Father&nbsp;\t\t\t\t\t\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">Side of the neck&#44; thorax &#40;between and under the breasts&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" 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
                  \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">51&nbsp;\t\t\t\t\t\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">No&nbsp;\t\t\t\t\t\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">Thorax &#40;between and under breasts&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\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">45&nbsp;\t\t\t\t\t\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">No&nbsp;\t\t\t\t\t\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">Thorax &#40;between and under breasts&#41;&#44; armpits&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Patient and Lesion Characteristics</p>"
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            "detalle" => "Table "
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              "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">Disease Type&nbsp;\t\t\t\t\t\t\n
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                  \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">Examples&nbsp;\t\t\t\t\t\t\n
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                  \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">No&#46; &#40;&#37;&#41; of Patients&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neuropsychiatric disorders&nbsp;\t\t\t\t\t\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">Epilepsy&#44; hyperactive attention deficit disorder&#44; anxiety-depressive disorder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#47;20 &#40;30&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dermatologic diseases&nbsp;\t\t\t\t\t\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">Melanoma&nbsp;\t\t\t\t\t\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">3&#47;20 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Salivary gland disorders&nbsp;\t\t\t\t\t\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">Submandibular sialolithiasis&nbsp;\t\t\t\t\t\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">1&#47;20 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kidney diseases&nbsp;\t\t\t\t\t\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">Renal polycystic disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#47;20 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Most Common Concomitant Conditions in Our Case Series</p>"
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      "titulo" => "References"
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        0 => array:2 [
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          "bibliografiaReferencia" => array:10 [
            0 => array:3 [
              "identificador" => "bib0005"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Darier disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Takagi"
                            1 => "M&#46; Kamijo"
                            2 => "S&#46; Ikeda"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/1346-8138.13230"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Dermatol"
                        "fecha" => "2016"
                        "volumen" => "43"
                        "paginaInicial" => "275"
                        "paginaFinal" => "279"
                      ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Five mutations of ATP2A2 gene in Chinese patients with Darier&#8217;s disease and a literature review of 86 cases reported in China"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46;-Q&#46; Ren"
                            1 => "M&#46; Gao"
                            2 => "Y&#46;-H&#46; Liang"
                            3 => "Y&#46;X&#46; Hou"
                            4 => "P&#46;G&#46; Wang"
                            5 => "L&#46;D&#46; Sun"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00403-006-0658-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Dermatol Res"
                        "fecha" => "2006"
                        "volumen" => "298"
                        "paginaInicial" => "58"
                        "paginaFinal" => "63"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16552539"
                            "web" => "Medline"
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                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Darier disease&#58; a review of the clinical features in 163 patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46;M&#46; Burge"
                            1 => "J&#46;D&#46; Wilkinson"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/0190-9622(92)70154-8"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "1992"
                        "volumen" => "27"
                        "paginaInicial" => "40"
                        "paginaFinal" => "50"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1619075"
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                          "pii" => "S0735109705003700"
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                          "issn" => "07351097"
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              "etiqueta" => "4"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recurrent p&#46;N767S mutation in the ATP2A2 gene in a Japanese family with haemorrhagic Darier Disease clinically mimicking epidermolysis bullosa simplex with mottled pigmentation"
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                        0 => array:2 [
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                          "autores" => array:3 [
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                            2 => "T&#46; Karashima"
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                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "B J Dermatol"
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                0 => array:2 [
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                      "titulo" => "Vesiculo-Bullous Darier&#8217;s Disease"
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                          "autores" => array:2 [
                            0 => "G&#46;B&#46; Colver"
                            1 => "D&#46;J&#46; Gawkrodger"
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                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2133.1992.tb00696.x"
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                        "fecha" => "1992"
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                        "paginaInicial" => "416"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comedonal Darier&#8217;s disease diagnosed incidentally in a patient undergoing a routine skin examination for sun cancer"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "L&#46; Buchanan"
                            1 => "G&#46; Strutton"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/ajd.12134"
                      "Revista" => array:7 [
                        "tituloSerie" => "Australas J Dermatol"
                        "fecha" => "2014"
                        "volumen" => "55"
                        "paginaInicial" => "237"
                        "paginaFinal" => "239"
                        "link" => array:1 [
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Journal Information
Vol. 112. Issue 7.
Pages 675-677 (July - August 2021)
Vol. 112. Issue 7.
Pages 675-677 (July - August 2021)
Case and Research Letters
Open Access
Darier Disease: A Case Series of 20 Patients and Review of the Literature
Enfermedad de Darier: serie de 20 casos y revisión de la literatura
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E.M. Sánchez Martínez
Corresponding author
eva.sanchez.m.92@gmail.com

Corresponding author.
, L.M. Moneva Léniz, H. Gegúndez Hernández, A. Mateu Puchades
Servicio de Dermatología, Hospital Universitario Doctor Peset de Valencia, Valencia, Spain
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Table 1. Patient and Lesion Characteristics
Table 2. Most Common Concomitant Conditions in Our Case Series
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To the Editor:

Darier disease is a rare autosomal dominant genetic disorder that presents with reddish-brown keratotic papules in seborrheic areas as well as with palmoplantar, nail, and mucosal tissue involvement.1 Darier disease is due to a mutation in the sarcoplasmic/endoplasmic reticulum calcium ATPase gene (ATP2A2), which codes for the endoplasmic reticulum ATPase calcium pump (SERCA2b).1,2 Few case series of patients with Darier disease have been published to date.2 We describe a series of Spanish patients with this disease in the interest of learning more about its characteristics.

To that end we searched our hospital’s database to identify patients diagnosed with histologically confirmed Darier disease treated in our department between January 2008 and January 2019. We extracted the following information for the 20 cases found: age, sex, family history of Darier disease, location of lesions, and concurrent conditions (whether cutaneous or extracutaneous) (Table 1).

Table 1.

Patient and Lesion Characteristics

Patient  Age, yr  Sex  Family History  Site of Skin Lesions 
46  No  Skin folds (between and under the breasts, groin, behind the ear), external auditory canal, over the shin, hairline, palmoplantar pitting, dorsum of the hand 
40  Mother, sister  Thorax, behind the ear, upper and lower limbs 
17  Mother  Side of the neck, periumbilical region, external auditory canal, hairline, palmoplantar pitting, dorsum of the hands 
25  No  Side of the neck, thorax, periumbilical region, palmoplantar pitting, dorsum of the hands 
15  No  Side of the neck, thorax (between and under breasts), abdomen 
73  No  Thorax (between breasts), groin, hairline, 
76  No  Thorax (between breasts), periumbilical region, upper and lower limbs 
63  No  Thorax (upper third), thighs, lumbar region, external auditory canal, hairline 
74  No  Thorax, periumbilical region 
10  23  No  Side of the neck, between shoulder blades 
11  34  No  Thorax (between breasts), periumbilical region, dorsum of the hands 
12  75  No  Thorax (between breasts), between the shoulder blades 
13  30  No  Thorax (under the breasts), groin, side of the abdomen 
14  53  No  Right breast (segmental) 
15  34  Mother, grandmother  Side of the neck, thorax (under the breasts), antecubital, popliteal, lumbar region, hairline, palmoplantar pitting 
16  66  No  Left side of the abdomen (segmental) 
17  40  No  Side of the neck, thorax (under the breasts), lumbar region, behind the ear, palmoplantar pitting, dorsum of the hands 
18  58  Father  Side of the neck, thorax (between and under the breasts) 
19  51  No  Thorax (between and under breasts) 
20  45  No  Thorax (between and under breasts), armpits 

The patients’ median age of 46 (range, 15–76) years was slightly higher than the ages reflected in the literature, where symptoms debut in patients between 12 and 20 years old; the distribution of sexes in our series was similar, however.3 A family history of Darier disease was reported by 20% of our patients, a lower proportion than the 50% to 60% reported in the literature.1

The most common clinical manifestation was the presence of brownish, keratotic, or erythematous papules that might or might not be grouped in verrucous plaques. We observed the histologic features that are typical of the disease: acantholysis, dyskeratosis, and negative direct immunofluorescence.1–3

Some of the subtypes of Darier disease were represented in our study (Fig. 1). Patient 15 developed reddish-blackish macules on hands and feet, a presentation consistent with the acral hemorrhagic type. Such lesions are caused by bleeding within acantholytic vesicles and may be associated with the p.N767S mutation in the ATP2A2 gene.4 The vesiculobullous variety was seen in patient 17, who had vesicles and blisters mixed with keratotic papules as the primary lesions. In such cases it is important to rule out infection, especially by a virus.5 Patient 11 had comedones and cysts along with keratotic papules, consistent with comedonal Darier disease. This subtype is difficult to diagnose because of its resemblance to acne vulgaris and familial dyskeratotic comedones.6 Two patients had lesions following along the lines of Blaschko (right breast and flank). After biopsy, these cases were confirmed as type 1 segmental Darier disease. This type debuts later in life and must be distinguished from Grover disease and warty dyskeratoma, which are clinically and histologically similar but whose lesions do not present in a blaschkoid distribution.7

Figure 1.

Some of the subtypes of Darier disease. A, Acral hemorrhagic Darier disease: dark red macules on the dorsum of the hand. B, Vesiculobullous type: vesicles and blisters of various sizes are present along with erythematous-keratotic papules. C, Comedonal form: comedones and cysts appear along with the typical lesions of Darier disease. D, Type 1 segmental Darier disease: involvement limited to the lines of Blaschko on the left flank.

(0.24MB).

Although hypopigmented macules intermingled with keratotic papules, a finding referred to as guttate leukoderma, are sometimes present, we saw no such eruptions in our series. Other variants not represented were hypotrophic, verrucous, and erosive forms of Darier disease.

However, multiple associated disorders were present in our series (Table 2). Given that the calcium pump (SERCA2b) is present in all cells, that a genetic mutation would cause symptoms in organs other than the skin seems logical.

Table 2.

Most Common Concomitant Conditions in Our Case Series

Disease Type  Examples  No. (%) of Patients 
Neuropsychiatric disorders  Epilepsy, hyperactive attention deficit disorder, anxiety-depressive disorder  6/20 (30%) 
Dermatologic diseases  Melanoma  3/20 (25%) 
Salivary gland disorders  Submandibular sialolithiasis  1/20 (5%) 
Kidney diseases  Renal polycystic disease  1/20 (5%) 

Extracutaneous manifestations of Darier disease, apparently due to the pleiotropic influence of ATP2A2 mutations on other cells, have been described.8 Associated neuropsychiatric disorders were present in 30% of the patients in our series in the form of epilepsy, attention deficit hyperactivity disorder, and anxiety-depressive disorder. Another reported association is salivary gland obstruction caused by episodes of acantholysis and dyskeratosis in the epithelium of salivary ducts.9 Another of our patients had “submaxillary” (ie, submandibular) sialolithiasis that required submaxillectomy. One of our patients had renal polycystic disease, which is also a reported association10; we underline the importance of bearing kidney disease in mind so that it can be diagnosed early.

Finally, 3 patients in our series had melanomas. This association has been described occasionally in the literature but is likely to be a chance finding.1

Conflicts of Interest

The authors declare that they have no conflicts of interest.

References
[1]
A. Takagi, M. Kamijo, S. Ikeda.
Darier disease.
J Dermatol, 43 (2016), pp. 275-279
[2]
Y.-Q. Ren, M. Gao, Y.-H. Liang, Y.X. Hou, P.G. Wang, L.D. Sun, et al.
Five mutations of ATP2A2 gene in Chinese patients with Darier’s disease and a literature review of 86 cases reported in China.
Arch Dermatol Res, 298 (2006), pp. 58-63
[3]
S.M. Burge, J.D. Wilkinson.
Darier disease: a review of the clinical features in 163 patients.
J Am Acad Dermatol, 27 (1992), pp. 40-50
[4]
T. Hamada, S. Yasumoto, T. Karashima.
Recurrent p.N767S mutation in the ATP2A2 gene in a Japanese family with haemorrhagic Darier Disease clinically mimicking epidermolysis bullosa simplex with mottled pigmentation.
B J Dermatol, 157 (2007), pp. 605-608
[5]
G.B. Colver, D.J. Gawkrodger.
Vesiculo-Bullous Darier’s Disease.
Br J Dermatol, 126 (1992), pp. 416-417
[6]
L. Buchanan, G. Strutton.
Comedonal Darier’s disease diagnosed incidentally in a patient undergoing a routine skin examination for sun cancer.
Australas J Dermatol, 55 (2014), pp. 237-239
[7]
J.C. Sartori-Valinotti, M.S. Peters, C.N. Wieland.
Segmental type 1 Darier disease: a case series highlighting late-onset disease.
Br J Dermatol, 173 (2015), pp. 587-589
[8]
T. Nakamura, A.-A. Kazuno, K. Nakajima, I. Kusumi, T. Tsuboi, T. Kato.
Loss of function mutations in ATP2A2 and psychoses: A case report and literature survey.
Psychiatry Clin Neurosci, 70 (2016), pp. 342-350
[9]
R.A. Graham-Brown, B.S. Mann, D. Downton, I. Sarkany.
Darier’s disease with salivary gland obstruction.
J R Soc Med, 76 (1983), pp. 609-611
[10]
L.Y. Matsuoka, J. Wortsman.
Renal involvement in Darier disease.
J Am Acad Dermatol, 75 (2016), pp. e235

Please cite this article as: Sánchez Martínez EM, Moneva Léniz LM, Gegúndez Hernández H, Mateu Puchades A. Enfermedad de Darier: serie de 20 casos y revisión de la literatura. Actas Dermosifiliogr. 2021;112:675–677.

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