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respectivamente&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Foram iniciadas ciclosporina A &#40;3&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;dia&#41; e prednisolona &#40;1&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;dia&#41;&#44; evolui com cicatriza&#231;&#227;o das les&#245;es&#44; ganho de peso e melhoria parcial da anemia&#44; por&#233;m a resposta terap&#234;utica piorou ap&#243;s regress&#227;o dos n&#237;veis de imunossupress&#227;o&#44; evoluiu com o agravamento de les&#245;es preexistentes e a forma&#231;&#227;o de les&#227;o ulcerada no ponto de feitura da bi&#243;psia hep&#225;tica transcut&#226;nea&#44; compat&#237;vel com patergia &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>D&#44;&#160;1E&#160;e&#160;1F&#41;&#46; Os n&#237;veis de imunossupress&#227;o foram restaurados e foi associado adalimumabe 40<span class="elsevierStyleHsp" style=""></span>mg quinzenalmente&#44; com melhoria significativa&#44; por&#233;m parcial&#44; das les&#245;es cut&#226;neas&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Em estudo gen&#233;tico da paciente encontrou&#8208;se a variante c&#46;748G<span class="elsevierStyleHsp" style=""></span>&#62;A&#160;p&#46; &#40;Glu250Lys&#41; no &#233;xon 1 do gene PSTPIP1&#44; em heterozigose&#46; Essa variante substitui um &#225;cido glut&#226;mico por uma lisina no c&#243;don 250<span class="elsevierStyleHsp" style=""></span>da prote&#237;na traduzida&#44; que foi descrita como patog&#234;nica no banco de dados Infervers e Clinvar &#40;rs28939089&#41; quando associada &#224; s&#237;ndrome de PAPA &#40;MIM 604416&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discuss&#227;o</span><p id="par0040" class="elsevierStylePara elsevierViewall">A Hz&#47;Hc &#233; uma rara condi&#231;&#227;o autoinflamat&#243;ria caracterizada clinicamente por les&#245;es cut&#226;neas inflamat&#243;rias pustulosas e ulcerativas&#44; artrite recorrente&#44; hepatoesplenomegalia&#44; pancitopenia e d&#233;ficit de crescimento&#44; sem predile&#231;&#227;o por sexo&#44; geralmente diagnosticada na juventude&#46; A doen&#231;a apresenta achados laboratoriais caracter&#237;sticos&#44; como n&#237;veis s&#233;ricos extremamente altos do zinco e principalmente da calprotectina &#40;500&#8211;12&#46;000 vezes os n&#237;veis normais&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">A calprotectina &#233; formada por um complexo de duas prote&#237;nas MRP8&#47;14&#44; ativadores end&#243;genos do receptor Toll&#8208;<span class="elsevierStyleItalic">like</span> 4 &#40;TLR&#8208;4&#41; e pertencentes &#224; fam&#237;lia das alarminas&#46; &#201; encontrada no citoplasma de neutr&#243;filos e apresenta intensa atividade pr&#243;&#8208;inflamat&#243;ria&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">5&#44;6</span></a> Recentemente&#44; identificaram&#8208;se nesses pacientes muta&#231;&#245;es espec&#237;ficas com altera&#231;&#227;o de um &#250;nico amino&#225;cido na PSTPIP1&#44; prote&#237;na associada ao citoesqueleto respons&#225;vel pela ativa&#231;&#227;o de c&#233;lulas&#160;T e libera&#231;&#227;o de IL&#8208;1b&#46; Outras muta&#231;&#245;es nesse mesmo gene j&#225; foram associadas a outras doen&#231;as autoinflamat&#243;rias&#44; como a s&#237;ndrome PAPA &#40;artrite piog&#234;nica&#44; PG e acne&#41;&#44; com algumas semelhan&#231;as cl&#237;nicas com a Hz&#47;Hc&#44; por&#233;m nenhuma apresentava n&#237;veis t&#227;o elevados de calprotectina e zinco&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">At&#233; o momento&#44; nenhum tratamento mostrou&#8208;se totalmente eficaz&#44; com relatos de uso de corticosteroides&#44; ciclosporina&#44; tacrolimus&#44; inibidores de TNF e IL&#8208;1&#46; A Hz&#47;Hc &#233; uma doen&#231;a multissist&#234;mica com sintomatologia inespec&#237;fica&#44; por&#233;m cr&#244;nica&#44; e j&#225; se apresenta desde a inf&#226;ncia na maioria dos casos&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2&#44;4&#8211;7</span></a> Os n&#237;veis extremamente elevados de zinco e calprotectina s&#233;ricos favorecem fortemente o diagn&#243;stico&#44; portanto devem ser considerados em casos suspeitos&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">As altera&#231;&#245;es cut&#226;neas na Hz&#47;Hc foram relatadas como vasculite&#44; eczemas&#44; &#250;lceras furunculoides e les&#245;es necr&#243;ticas&#44; por&#233;m ressalta&#8208;se que tendem a ser inflamat&#243;rias&#44; ulceradas&#44; por vezes pruriginosas&#44; com cl&#237;nica e histopatologia semelhantes ao PG&#44; tendem a acometer extremidades inferiores simetricamente&#44; com relatos de les&#245;es faciais&#44; particularmente nas p&#225;lpebras&#46; A observa&#231;&#227;o de tais les&#245;es cr&#244;nicas em crian&#231;as e adultos jovens com hepatoesplenomegalia&#44; artralgia&#47;artrite&#44; PCR elevado e anemia microc&#237;tica devem levar &#224; suspeita diagn&#243;stica de Hz&#47;Hc&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Suporte financeiro</span><p id="par0065" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Contribui&#231;&#227;o dos autores</span><p id="par0075" class="elsevierStylePara elsevierViewall">Ludimila Oliveira Resende&#58; Elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Marilia Formentini Scotton Jorge&#58; Elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Juliano Vilaverde Schmitt&#58; Participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflitos de interesse</span><p id="par0095" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hiperzinquemia e hipercalprotectinemia s&#227;o doen&#231;as inflamat&#243;rias raras causadas por muta&#231;&#227;o no gene PSTPIP1&#44; com desregula&#231;&#227;o no metabolismo da calprotectina&#44; que &#233; uma prote&#237;na quelante de zinco com propriedades antimicrobianas e pr&#243;&#8208;inflamat&#243;rias&#46; Reportamos o caso de uma mulher de 20 anos com &#250;lceras cut&#226;neas persistentes&#44; compat&#237;veis com pioderma gangrenoso&#44; d&#233;ficit de crescimento e anemia cr&#244;nica&#44; que levaram ao diagn&#243;stico de hiperzinquemia e hipercalprotectinemia&#46; Sugere&#8208;se a dosagem de zinco e calprotectina em casos compat&#237;veis&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Como citar este artigo&#58; Resende LO&#44; Jorge MFS&#44; Schmitt JV&#46; Extensive pyoderma gangrenosum&#8208;like lesions revealing a case of hyperzinquemia and hypercalprotectinemia&#58; when to suspect it&#63; An Bras Dermatol&#46; 2019&#59;94&#58;713&#8211;6&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Trabalho realizado no Hospital das Cl&#237;nicas&#44; Faculdade de Medicina de Botucatu&#44; Universidade Estadual Paulista&#44; Botucatu&#44; SP&#44; Brasil&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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  " align="left" valign="\n
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                  \t\t\t\t">M&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">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
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                  \t\t\t\t">M&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\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Reduzido&nbsp;\t\t\t\t\t\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">Normal&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Normal&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">Reduzido&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\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">Sim&nbsp;\t\t\t\t\t\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">Sim&nbsp;\t\t\t\t\t\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">Sim&nbsp;\t\t\t\t\t\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">Sim&nbsp;\t\t\t\t\t\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">Sim&nbsp;\t\t\t\t\t\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">Sim&nbsp;\t\t\t\t\t\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">Sim&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">Altera&#231;&#245;es dermatol&#243;gicas&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  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Altera&#231;&#245;es reumatol&#243;gicas&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  " align="left" valign="\n
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                  \t\t\t\t">Artrite&#44; uve&#237;te&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Hemoglobina &#40;g&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">Zinco &#40;10&#8211;18<span class="elsevierStyleHsp" style=""></span>&#956;m&#47;L&#41;&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">180&#8211;200&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  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">175&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  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \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
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                  \t\t\t\t">Calprotectina &#40;&#60; 0&#44;001 g&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;5&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">1&#44;4&#8211;2&#44;55&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">9&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  " align="left" valign="\n
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                  \t\t\t\t">6&#44;1&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  " align="left" valign="\n
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                  \t\t\t\t">1&#44;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">12&#44;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">2&#44;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">0&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2218755.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Relatos de casos de Hz&#47;Hc descritos na literatura com avalia&#231;&#227;o dermatol&#243;gica<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#44;3&#44;4</span></a></p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Tabela 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Tabela "
            "rol" => "short"
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        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Caracter&#237;stica&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
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                  \t\t\t\t">6&#47;6 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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Caso Clínico
Lesões extensas tipo pioderma gangrenoso revelando um caso de hiperzinquemia e hipercalprotectinemia: quando suspeitar?
Ludimila Oliveira Resendea,
Autor para correspondência
ludi.lor07@gmail.com

Autor para correspondência.
, Marilia Formentini Scotton Jorgeb, Juliano Vilaverde Schmittb
a Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brasil
b Departamento de Dermatologia, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brasil
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normal&#58; &#60;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; e hepatoesplenomegalia &#224; ultrassonografia&#44; revelaram par&#234;nquima preservado com hematopoiese extramedular na histopatologia de bi&#243;psia hep&#225;tica&#46; Apresentava hipertens&#227;o portal com varizes esof&#225;gicas e osteoporose pronunciada com fratura patol&#243;gica em T12&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Considerando a hip&#243;tese diagn&#243;stica de Hz&#47;Hc&#44; foram feitas dosagens s&#233;ricas de zinco e calprotectina&#44; obtiveram&#8208;se os valores de 869<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L &#40;normal&#58; 70&#8211;120<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#41; e 642<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L &#40;normal&#58; &#60;<span class="elsevierStyleHsp" style=""></span>1&#44;6<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#41;&#44; 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por&#233;m parcial&#44; das les&#245;es cut&#226;neas&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Em estudo gen&#233;tico da paciente encontrou&#8208;se a variante c&#46;748G<span class="elsevierStyleHsp" style=""></span>&#62;A&#160;p&#46; &#40;Glu250Lys&#41; no &#233;xon 1 do gene PSTPIP1&#44; em heterozigose&#46; Essa variante substitui um &#225;cido glut&#226;mico por uma lisina no c&#243;don 250<span class="elsevierStyleHsp" style=""></span>da prote&#237;na traduzida&#44; que foi descrita como patog&#234;nica no banco de dados Infervers e Clinvar &#40;rs28939089&#41; quando associada &#224; s&#237;ndrome de PAPA &#40;MIM 604416&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discuss&#227;o</span><p id="par0040" class="elsevierStylePara elsevierViewall">A Hz&#47;Hc &#233; uma rara condi&#231;&#227;o autoinflamat&#243;ria caracterizada clinicamente por les&#245;es cut&#226;neas inflamat&#243;rias pustulosas e ulcerativas&#44; artrite recorrente&#44; hepatoesplenomegalia&#44; pancitopenia e d&#233;ficit de crescimento&#44; sem predile&#231;&#227;o por sexo&#44; geralmente diagnosticada na juventude&#46; A doen&#231;a apresenta achados laboratoriais caracter&#237;sticos&#44; como n&#237;veis s&#233;ricos extremamente altos do zinco e principalmente da calprotectina &#40;500&#8211;12&#46;000 vezes os n&#237;veis normais&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">A calprotectina &#233; formada por um complexo de duas prote&#237;nas MRP8&#47;14&#44; ativadores end&#243;genos do receptor Toll&#8208;<span class="elsevierStyleItalic">like</span> 4 &#40;TLR&#8208;4&#41; e pertencentes &#224; fam&#237;lia das alarminas&#46; &#201; encontrada no citoplasma de neutr&#243;filos e apresenta intensa atividade pr&#243;&#8208;inflamat&#243;ria&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">5&#44;6</span></a> Recentemente&#44; identificaram&#8208;se nesses pacientes muta&#231;&#245;es espec&#237;ficas com altera&#231;&#227;o de um &#250;nico amino&#225;cido na PSTPIP1&#44; prote&#237;na associada ao citoesqueleto respons&#225;vel pela ativa&#231;&#227;o de c&#233;lulas&#160;T e libera&#231;&#227;o de IL&#8208;1b&#46; Outras muta&#231;&#245;es nesse mesmo gene j&#225; foram associadas a outras doen&#231;as autoinflamat&#243;rias&#44; como a s&#237;ndrome PAPA &#40;artrite piog&#234;nica&#44; PG e acne&#41;&#44; com algumas semelhan&#231;as cl&#237;nicas com a Hz&#47;Hc&#44; por&#233;m nenhuma apresentava n&#237;veis t&#227;o elevados de calprotectina e zinco&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">At&#233; o momento&#44; nenhum tratamento mostrou&#8208;se totalmente eficaz&#44; com relatos de uso de corticosteroides&#44; ciclosporina&#44; tacrolimus&#44; inibidores de TNF e IL&#8208;1&#46; A Hz&#47;Hc &#233; uma doen&#231;a multissist&#234;mica com sintomatologia inespec&#237;fica&#44; por&#233;m cr&#244;nica&#44; e j&#225; se apresenta desde a inf&#226;ncia na maioria dos casos&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2&#44;4&#8211;7</span></a> Os n&#237;veis extremamente elevados de zinco e calprotectina s&#233;ricos favorecem fortemente o diagn&#243;stico&#44; portanto devem ser considerados em casos suspeitos&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">As altera&#231;&#245;es cut&#226;neas na Hz&#47;Hc foram relatadas como vasculite&#44; eczemas&#44; &#250;lceras furunculoides e les&#245;es necr&#243;ticas&#44; por&#233;m ressalta&#8208;se que tendem a ser inflamat&#243;rias&#44; ulceradas&#44; por vezes pruriginosas&#44; com cl&#237;nica e histopatologia semelhantes ao PG&#44; tendem a acometer extremidades inferiores simetricamente&#44; com relatos de les&#245;es faciais&#44; particularmente nas p&#225;lpebras&#46; A observa&#231;&#227;o de tais les&#245;es cr&#244;nicas em crian&#231;as e adultos jovens com hepatoesplenomegalia&#44; artralgia&#47;artrite&#44; PCR elevado e anemia microc&#237;tica devem levar &#224; suspeita diagn&#243;stica de Hz&#47;Hc&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Suporte financeiro</span><p id="par0065" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Contribui&#231;&#227;o dos autores</span><p id="par0075" class="elsevierStylePara elsevierViewall">Ludimila Oliveira Resende&#58; Elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Marilia Formentini Scotton Jorge&#58; Elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Juliano Vilaverde Schmitt&#58; Participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflitos de interesse</span><p id="par0095" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hiperzinquemia e hipercalprotectinemia s&#227;o doen&#231;as inflamat&#243;rias raras causadas por muta&#231;&#227;o no gene PSTPIP1&#44; com desregula&#231;&#227;o no metabolismo da calprotectina&#44; que &#233; uma prote&#237;na quelante de zinco com propriedades antimicrobianas e pr&#243;&#8208;inflamat&#243;rias&#46; Reportamos o caso de uma mulher de 20 anos com &#250;lceras cut&#226;neas persistentes&#44; compat&#237;veis com pioderma gangrenoso&#44; d&#233;ficit de crescimento e anemia cr&#244;nica&#44; que levaram ao diagn&#243;stico de hiperzinquemia e hipercalprotectinemia&#46; Sugere&#8208;se a dosagem de zinco e calprotectina em casos compat&#237;veis&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Como citar este artigo&#58; Resende LO&#44; Jorge MFS&#44; Schmitt JV&#46; Extensive pyoderma gangrenosum&#8208;like lesions revealing a case of hyperzinquemia and hypercalprotectinemia&#58; when to suspect it&#63; An Bras Dermatol&#46; 2019&#59;94&#58;713&#8211;6&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Trabalho realizado no Hospital das Cl&#237;nicas&#44; Faculdade de Medicina de Botucatu&#44; Universidade Estadual Paulista&#44; Botucatu&#44; SP&#44; Brasil&#46;</p>"
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">M&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  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Reduzido&nbsp;\t\t\t\t\t\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">Normal&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">Normal&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Reduzido&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduzido&nbsp;\t\t\t\t\t\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 ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\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\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\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">Sim&nbsp;\t\t\t\t\t\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">Sim&nbsp;\t\t\t\t\t\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">Sim&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">Altera&#231;&#245;es dermatol&#243;gicas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Vasc&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  " align="left" valign="\n
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                  \t\t\t\t">Les&#245;es p&#225;lpebras&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Altera&#231;&#245;es reumatol&#243;gicas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Artrite&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Artrite&#44; uve&#237;te&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Artrite&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Artrite&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Artrite&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">PCR &#40;&#60; 10 mg&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Hemoglobina &#40;g&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Zinco &#40;10&#8211;18<span class="elsevierStyleHsp" style=""></span>&#956;m&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">180&#8211;200&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Calprotectina &#40;&#60; 0&#44;001 g&#47;L&#41;&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  " align="left" valign="\n
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                  \t\t\t\t">6&#44;1&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">1&#44;5&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">12&#44;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;3&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">0&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2218755.png"
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Relatos de casos de Hz&#47;Hc descritos na literatura com avalia&#231;&#227;o dermatol&#243;gica<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#44;3&#44;4</span></a></p>"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Masculino&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">4&#47;7 &#40;57&#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"><span class="elsevierStyleItalic">Hepatoesplenomegalia</span>&nbsp;\t\t\t\t\t\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;6 &#40;100&#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"><span class="elsevierStyleItalic">D&#233;ficit de crescimento</span>&nbsp;\t\t\t\t\t\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">5&#47;7 &#40;71&#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"><span class="elsevierStyleItalic">Artrite</span>&nbsp;\t\t\t\t\t\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;6 &#40;100&#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"><span class="elsevierStyleItalic">Anemia</span>&nbsp;\t\t\t\t\t\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">5&#47;6 &#40;83&#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">Hemoglobina &#40;g&#47;L&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;2 &#40;2&#44;1&#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">Zinco s&#233;rico &#40;&#956;m&#47;L&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">153&#44;4 &#40;35&#44;4&#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
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                  \t\t\t\t">Calprotectina &#40;g&#47;L&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</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="left" valign="\n
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                  \t\t\t\t">4&#44;9 &#40;1&#44;5&#8211;6&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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