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em associa&#231;&#227;o com fatores metab&#243;licos e oxidativos&#46; O mais prov&#225;vel &#233; que haja uma soma dos fatores de maneira heterog&#234;nea&#44; contribuindo para as diferentes apresenta&#231;&#245;es&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">O vitiligo caracteriza&#8208;se clinicamente pela despigmenta&#231;&#227;o da pele e dos fol&#237;culos pilosos&#59; &#233; comum o surgimento em &#225;reas de trauma &#40;fen&#244;meno de Koebner&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a> Em geral&#44; a doen&#231;a poupa os melan&#243;citos residentes dentro do fol&#237;culo piloso em virtude do do contexto imunol&#243;gico nesse local&#44; semelhante a outros locais que cont&#234;m melan&#243;citos&#44; como c&#233;rebro&#44; olhos e ouvido interno&#46; &#193;reas com pelos brancos ou sem pelos apresentam maior dificuldade de recupera&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">O vitiligo pode ser classificado em segmentar e n&#227;o segmentar&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">2</span></a> Os segmentares costumam surgir na inf&#226;ncia e caracterizam&#8208;se por manchas acr&#244;micas unilaterais em padr&#245;es lineares ou em blocos&#44; com leucotriquia precoce e pouca resposta aos tratamentos&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">5&#44;6&#44;8&#44;9</span></a> As formas n&#227;o segmentares podem ser localizadas&#44; generalizadas&#44; universais e mistas&#46; As localizadas s&#227;o subdivididas em focais e mucosos&#46; O vitiligo focal &#233; caracterizado por uma pequena mancha acr&#244;mica &#40;10&#8211;15 cm<span class="elsevierStyleSup">2</span>&#41;&#59; o vitiligo mucoso ocorre quando pelo menos um local de acometimento &#233; a mucosa oral ou genital&#46; As variantes acrofaciais s&#227;o formas localizadas mais resistentes aos tratamentos&#46; As formas generalizadas apresentam m&#225;culas acr&#244;micas em diversas partes do corpo &#40;&#225;rea corporal acometida &#60;<span class="elsevierStyleHsp" style=""></span>80&#37;&#41; e&#44; nas formas universais&#44; h&#225; despigmenta&#231;&#227;o completa ou quase completa da pele &#40;acometimento &#62;<span class="elsevierStyleHsp" style=""></span>80&#37; da &#225;rea corporal&#41;&#46; A forma mista pode apresentar les&#245;es compat&#237;veis com vitiligo segmentar e n&#227;o segmentar&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">2&#44;6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">O impacto psicol&#243;gico &#233; importante&#59;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">10&#44;11</span></a> a ansiedade &#233; um sintoma comum&#44; o que afeta a vida social e sexual desses pacientes&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">1</span></a> Embora se trate de doen&#231;a com acometimento predominantemente cut&#226;neo&#44; novos estudos mostram envolvimento sist&#234;mico com maior frequ&#234;ncia de resist&#234;ncia &#224; insulina&#44; s&#237;ndrome metab&#243;lica&#44; doen&#231;as cardiovasculares e autoimunes&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">11&#8208;14</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Estudos recentes t&#234;m salentado o papel das quimiocinas inflamat&#243;rias como CXCL9&#44; CXCL10 e CXCL12&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">15&#44;16</span></a> Essas quimiocinas est&#227;o relacionadas com a resposta Th1&#44; e se mostraram importantes no processo de recrutamento e ativa&#231;&#227;o dos linf&#243;citos TCD8<span class="elsevierStyleSup">&#43;</span> citot&#243;xicos&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">17&#44;18</span></a> Nos tecidos inflamados&#44; os linf&#243;citos otimizam a produ&#231;&#227;o de interferona gama &#40;IFN&#947;&#41; e de fator de necrose tumoral alfa &#40;TNF&#945;&#41;&#44; que&#44; por sua vez&#44; estimulam a secre&#231;&#227;o de CXCL10&#46; Essa quimiocina se liga ao seu receptor nas c&#233;lulas &#40;CXCR3&#41; e desencadeia uma cascata inflamat&#243;ria com ativa&#231;&#227;o e maior recrutamento de linf&#243;citos T&#44; contribuindo para a destrui&#231;&#227;o dos melan&#243;citos&#46; A CXCL10 tamb&#233;m est&#225; aumentada em outras doen&#231;as autoimunes&#44; como l&#237;quen escleroso e atr&#243;fico&#44; tireoidite autoimune&#44; doen&#231;a de Graves&#44; alopecia areata e artrite reumatiide&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">19</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">A teoria autoimune vem sendo refor&#231;ada pelos seguintes achados mais recentes&#58;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">13&#44;14</span></a> 1&#41; os linf&#243;citos T CD8<span class="elsevierStyleSup">&#43;</span> e o eixo da IFN&#947; parecem desempenhar papel crucial na inibi&#231;&#227;o da melanog&#234;nese e na indu&#231;&#227;o da apoptose dos melan&#243;citos&#59;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a> e 2&#41; quimiocinas como CXCL10 podem exercer papel na progress&#227;o e manuten&#231;&#227;o do vitiligo&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">21</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">No entanto&#44; ainda existem muitas lacunas com rela&#231;&#227;o a par&#226;metros imunol&#243;gicos e inflamat&#243;rios que possibilitem melhor entendimento de sua patog&#234;nese e o desenvolvimento de estrat&#233;gias terap&#234;uticas mais eficazes&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="par0045" class="elsevierStylePara elsevierViewall">Estudo de corte transversal com portadores de vitiligo do servi&#231;o de dermatologia&#44; com o objetivo de avaliar perfil cl&#237;nico&#44; citocinas e par&#226;metros inflamat&#243;rios&#46; Para a caracteriza&#231;&#227;o do perfil cl&#237;nico&#44; foram avaliados&#44; entre fevereiro de 2019 e janeiro de 2022&#44; todos os pacientes entre 18 e 60 anos cadastrados &#40;total de 98&#41;&#46; O banco de dados de pacientes incluiu informa&#231;&#245;es sobre identifica&#231;&#227;o&#44; dados da doen&#231;a &#40;tempo de surgimento&#44; hist&#243;rico pessoal ou familiar de vitiligo ou outras doen&#231;as autoimunes&#44; tratamentos pr&#233;vios&#41;&#44; tipo de vitiligo&#44; extens&#227;o da doen&#231;a e tratamentos prescritos&#46; Para a avalia&#231;&#227;o dos par&#226;metros inflamat&#243;rios e imunol&#243;gicos&#44; foram recrutados 30 pacientes no per&#237;odo de mar&#231;o de 2021 a janeiro de 2022&#46; A sele&#231;&#227;o foi realizada por demanda espont&#226;nea de pacientes que compareciam ao servi&#231;o e que estavam cadastrados previamente no banco de dados&#44; de maneira aleat&#243;ria e sob consentimento&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Avalia&#231;&#227;o cl&#237;nica</span><p id="par0050" class="elsevierStylePara elsevierViewall">Os pacientes foram avaliados por um &#250;nico dermatologista&#44; que classificou a forma cl&#237;nica do vitiligo&#44; assim como a extens&#227;o da doen&#231;a&#44; de acordo com o Vitiligo Extent Tensity Index &#40;VETI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a> C&#225;lculo do VETI&#58; &#40;porcentagem de envolvimento da cabe&#231;a &#215; est&#225;gio de despigmenta&#231;&#227;o&#41; &#43; &#40;porcentagem de envolvimento do tronco &#215; est&#225;gio de despigmenta&#231;&#227;o&#41; 4 &#43; &#40;porcentagem de envolvimento dos MMSS &#215; est&#225;gio de despigmenta&#231;&#227;o&#41; 2 &#43; &#40;porcentagem de envolvimento dos MMII &#215; est&#225;gio de despigmenta&#231;&#227;o&#41; 4 &#43; &#40;porcentagem de envolvimento da genit&#225;lia &#215; est&#225;gio de despigmenta&#231;&#227;o&#41; 0&#44;1&#46; O valor m&#225;ximo do VETI &#233; de 55&#44;5&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Avalia&#231;&#227;o laboratorial</span><p id="par0055" class="elsevierStylePara elsevierViewall">Os dados do hemograma e de prote&#237;na C reativa &#40;PCR&#41; do subgrupo de 30 pacientes foram obtidos do prontu&#225;rio da &#250;ltima consulta&#44; com o prazo de no m&#225;ximo tr&#234;s meses antes da dosagem de citocinas&#47;quimiocinas&#46; A raz&#227;o neutr&#243;filo linf&#243;cito &#40;RNL&#41; foi calculada por meio da divis&#227;o do n&#250;mero absoluto de neutr&#243;filos pelo de linf&#243;citos&#44; obtidos do hemograma&#46; Foram dosadas as citocinas e quimiocinas de 10 controles saud&#225;veis&#44; como grupo de compara&#231;&#227;o&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Para dosagem de citocinas&#47;quimiocinas &#40;TNF&#945;&#44; IFN&#947;&#44; IL10&#44; IL15&#44; CXCL10&#41; foram coletados 10<span class="elsevierStyleHsp" style=""></span>mL de sangue processados pela t&#233;cnica de ELISA&#46; Para todas as aferi&#231;&#245;es&#44; foram usados os <span class="elsevierStyleItalic">kits</span> BD Bioscience &#40;BD OptEIA<span class="elsevierStyleSup">TM</span> Set&#41;&#46; Os resultados foram calculados no programa InStat &#40;GraphPad&#44; San Diego&#44; CA&#44; EUA&#41; e expressos em pg&#47;mL&#46; Foram exclu&#237;dos pacientes que se recusaram a participar do estudo&#44; portadores de doen&#231;as virais ou bacterianas em atividade&#44; uso de terapia imunossupressora sist&#234;mica nos &#250;ltimos 30 dias e portadores de outras doen&#231;as autoimunes&#44; como tireoidopatias&#44; artrite reumatoide e l&#250;pus eritematoso sist&#234;mico&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">An&#225;lise estat&#237;stica</span><p id="par0065" class="elsevierStylePara elsevierViewall">Os dados cl&#237;nicos e laboratoriais foram analisados pelo <span class="elsevierStyleItalic">software</span> livre R &#40;R version 4&#46;1&#46;1 &#91;2021&#8208;08&#8208;10&#93;&#41;&#46; O valor de p foi considerado significante quando &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#46; As vari&#225;veis quantitativas foram resumidas em tabelas descritivas utilizando m&#233;dia e desvio&#8208;padr&#227;o&#46; Para compara&#231;&#227;o das vari&#225;veis entre os grupos&#44; foram utilizados os testes Anova de uma via e o teste <span class="elsevierStyleItalic">t</span> de <span class="elsevierStyleItalic">Student</span> para as vari&#225;veis categ&#243;ricas que seguiam a distribui&#231;&#227;o normal&#46; Para compara&#231;&#227;o das vari&#225;veis categ&#243;ricas que n&#227;o seguiram o padr&#227;o da normalidade&#44; foram utilizados os testes de Kruskal Wallis e de Mann Whitney&#46; A correla&#231;&#227;o de Spearman foi usada para compara&#231;&#227;o das vari&#225;veis quantitativas intervalares que n&#227;o seguiram esse padr&#227;o&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Aspectos &#233;ticos</span><p id="par0070" class="elsevierStylePara elsevierViewall">O estudo foi conduzido de acordo com as diretrizes da Resolu&#231;&#227;o 466&#47;2012&#44; tendo aprova&#231;&#227;o do Comit&#234; de &#201;tica e Pesquisa &#40;parecer n&#176; 4&#46;886&#46;709&#41;&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Resultados</span><p id="par0075" class="elsevierStylePara elsevierViewall">Conforme <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#44; pode&#8208;se observar que a m&#233;dia de idade dos pacientes foi de 43&#44;3 anos&#44; com predom&#237;nio do sexo feminino &#40;78&#44;6&#37;&#41;&#46; Fototipo IV ou V esteve presente em 71&#44;3&#37;&#59; o fototipo IV &#40;43&#44;8&#37;&#41; foi o mais comum&#46; O subtipo de vitiligo mais comum foi o generalizado &#40;54&#37;&#41;&#44; seguido pelo focal &#40;17&#44;3&#37;&#41; e acrofacial &#40;10&#44;2&#37;&#41;&#46; Na avalia&#231;&#227;o da extens&#227;o da doen&#231;a&#44; observou&#8208;se VETI m&#233;dio de 3&#44;11&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a> Na amostra de 30 participantes&#44; a m&#233;dia de idade foi de 45&#44;2 anos&#46; Prevaleceram o sexo feminino &#40;86&#44;6&#37;&#41;&#44; fototipo IV &#40;43&#44;3&#37;&#41; e o subtipo generalizado &#40;63&#44;3&#37;&#41;&#44; dados semelhantes ao grupo de 98 participantes&#44; sem diferen&#231;as estatisticamente significante entre os grupos&#46; Mais de 70&#37; dos entrevistados n&#227;o apresentavam comorbidades nem hist&#243;rico familiar de vitiligo&#46; Dentre as doen&#231;as autoimunes associadas mais comuns estavam o hipotireoidismo&#44; seguido pelo hipertireoidismo&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a> encontram&#8208;se a m&#233;dia e o desvio&#8208;padr&#227;o dos valores obtidos dos marcadores imunoinflamat&#243;rios dosados na amostra de 30 participantes e 10 controles sadios&#46; Dentro do grupo localizado foram inclu&#237;das as formas focais&#44; acrofaciais e segmentares&#59; no grupo generalizado&#44; as formas generalizadas e universais&#46; Foram realizados os testes <span class="elsevierStyleItalic">t</span> de <span class="elsevierStyleItalic">Student</span> e Anova de uma via para os marcadores que seguiram o padr&#227;o da normalidade &#40;RNL e CXCL10&#41; e&#44; para os demais&#44; os testes de Mann Whitney e o de Kruskal Wallis &#40;valores de p na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Na <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a>&#44; observam&#8208;se n&#237;veis mais elevados da quimiocina CXCL10 em pacientes com menor tempo de vitiligo&#46; Realizado teste de correla&#231;&#227;o de Spearman com valor de p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#44; indicando rela&#231;&#227;o inversa entre as vari&#225;veis&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Foram feitas an&#225;lises entre RNL&#44; PCR&#44; n&#237;veis de TNF&#945;&#44; IFN&#947;&#44; IL10 e IL15 e o tempo da doen&#231;a&#46; Todas demostraram tend&#234;ncia de valores mais altos em pacientes com menor tempo da doen&#231;a&#59; entretanto&#44; o valor de p n&#227;o foi estatisticamente significante&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discuss&#227;o</span><p id="par0095" class="elsevierStylePara elsevierViewall">O estudo demonstra maior preval&#234;ncia de vitiligo entre mulheres &#40;78&#44;5&#37;&#41;&#44; achado compat&#237;vel com a metan&#225;lise realizada por Zhang et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">23</span></a> mas diferente de outros estudos pr&#233;vios&#44; em que a preval&#234;ncia entre homens e mulheres se demonstrou igualit&#225;ria&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">24&#44;25</span></a> Esse resultado provavelmente se deve &#224; maior preocupa&#231;&#227;o cultural com a despigmenta&#231;&#227;o cut&#226;nea no g&#234;nero feminino&#46; A m&#233;dia de idade encontrada em nosso estudo&#44; de 43 anos&#44; difere da metan&#225;lise de Zhang et al&#46;&#44; na qual a preval&#234;ncia foi mais comum em pacientes acima de 60 anos&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">23</span></a> Essa diverg&#234;ncia pode ter ocorrido em virtude do menor acesso dos idosos durante a vig&#234;ncia da pandemia de COVID&#8208;19&#46; Pela escala de Fitzpatrick&#44; a maioria dos pacientes apresentaram fototipos IV e V &#40;71&#44;3&#37;&#41;&#46; No estudo brasileiro de Cerci et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a> houve predomin&#226;ncia do fototipo IV&#46; J&#225; o tempo m&#233;dio de doen&#231;a foi maior que 15 anos&#44; demonstrando a cronicidade da doen&#231;a&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">A maioria dos pacientes n&#227;o apresentava comorbidades nem hist&#243;rico familiar de vitiligo&#46; Estudos epidemiol&#243;gicos mostram que os casos de vitiligo tendem a ser mais comuns em um mesmo n&#250;cleo familiar&#59; entretanto&#44; o risco gen&#233;tico n&#227;o &#233; absoluto&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a> Quando h&#225; hist&#243;rico em parente de primeiro grau&#44; o risco de desenvolvimento de vitiligo &#233; de 6&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Dados mais recentes v&#234;m demostrando que o vitiligo pode estar associado a maior risco cardiovascular&#44; resist&#234;ncia &#224; insulina e s&#237;ndrome metab&#243;lica&#44;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">12&#44;28</span></a> como revela o estudo com 96 pacientes de Karadag et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a> no qual os pacientes com vitiligo tinham maior preval&#234;ncia de resist&#234;ncia &#224; insulina&#44; maiores n&#237;veis de LDL e n&#237;veis mais baixos de HDL&#46; Associa&#231;&#227;o de vitiligo com diabetes <span class="elsevierStyleItalic">mellitus</span> juvenil&#44; diabetes <span class="elsevierStyleItalic">mellitus</span> tipo 2&#44; acantose nigricans e como componente da s&#237;ndrome hiperandrogenismo&#44; resist&#234;ncia &#224; insulina e acantose nigricante &#40;HAIR&#8208;NA&#41; tem sido descrita&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">30&#8208;32</span></a> Fato interessante &#233; que os melan&#243;citos presentes no tecido adiposo parecem desempenhar papel importante na neutraliza&#231;&#227;o de radicais livres de oxig&#234;nio&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">12&#44;28&#44;33</span></a> Desse modo&#44; questiona&#8208;se o conceito de doen&#231;a puramente cut&#226;nea que traz impactos psicol&#243;gicos em decorr&#234;ncia da desfigura&#231;&#227;o cosm&#233;tica&#44; em favorecimento de uma tese mais ampla&#44; que a posiciona como autoinflamat&#243;ria e com repercuss&#245;es sist&#234;micas&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Poucos estudos avaliaram marcadores inflamat&#243;rios sist&#234;micos no vitiligo&#46; A RNL vem sendo considerada marcador de maior risco cardiovascular&#46; Solak et al&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a> conclu&#237;ram que a RNL &#233; relacionada &#224; disfun&#231;&#227;o endotelial&#44; tem valor progn&#243;stico e poderia prever desfechos cardiovasculares independentes&#46; Nossos dados mostraram que a m&#233;dia da RNL dos pacientes foi de 2&#44;24&#44; semelhante &#224; m&#233;dia encontrada nos pacientes de vitiligo do estudo de Solak et al&#46;&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a> Observaram&#8208;se maiores valores de RNL em pacientes com vitiligo generalizado em compara&#231;&#227;o &#224;queles com vitiligo localizado&#46; Contudo&#44; como a amostra foi pequena&#44; nosso dado n&#227;o foi significante&#44; por&#233;m coerente com a hip&#243;tese que vincula doen&#231;a extensa com repercuss&#227;o sist&#234;mica&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">No presente estudo&#44; a m&#233;dia da PCR foi de 2&#44;92<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; Badimon et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a> mostraram que dosagens acima de 1<span class="elsevierStyleHsp" style=""></span>mg&#47;dL eram consideradas de m&#233;dio risco cardiovascular&#44; e acima de 3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; de alto risco&#46; Em rela&#231;&#227;o aos n&#237;veis de PCR e tipo de vitiligo&#44; tamb&#233;m observamos tend&#234;ncia para valores mais altos nos casos generalizados&#44; conforme demonstrado por Solak et al&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Embora os valores de citocinas e quimiocinas no sangue perif&#233;rico dos controles saud&#225;veis e dos portadores de vitiligo subdivididos de acordo com o tipo n&#227;o apresentem diferen&#231;as estatisticamentes significantes &#40;talvez em virtude do tamanho amostral&#41;&#44; apenas o CXCL10 est&#225; nitidamente aumentado nos portadores de vitiligo em compara&#231;&#227;o com os controles&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Um achado relevante deste estudo &#233; a correla&#231;&#227;o inversa entre os n&#237;veis da quimiocina CXCL10 com o tempo da doen&#231;a&#44; na qual os valores mais elevados se encontram nos pacientes com menos tempo de doen&#231;a &#8211; ou seja&#44; na fase mais inicial e aguda&#44; corroborando os resultados de Wang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a> Vitiligo ativo e em progress&#227;o costuma ser mais comum em pacientes com menor tempo de evolu&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">17</span></a> Essa foi uma tend&#234;ncia tamb&#233;m observada nas dosagens das outras citocinas &#40;TNF&#945;&#44; IFN&#947;&#44; IL10 e IL15&#41;&#44; apesar da aus&#234;ncia de signific&#226;ncia estat&#237;stica&#46; Tamb&#233;m foram observados maiores n&#237;veis de CXCL10 em pacientes com as formas acrofaciais e generalizadas em rela&#231;&#227;o aos pacientes com formas universais&#44; compat&#237;veis com os resultados do estudo de Gharib et al&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">17</span></a> &#201; poss&#237;vel que a estabilidade cl&#237;nica do vitiligo universal explique esse achado&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">O recrutamento dos pacientes foi dificultado pela pandemia da COVID&#8208;19&#44; pois a acessibilidade e o atendimento ficaram reduzidos por um per&#237;odo de dois anos&#46; Dessa maneira&#44; a amostra foi pequena para as an&#225;lises comparativas&#44; mas permitiu tra&#231;ar um perfil cl&#237;nico dos portadores de vitiligo do servi&#231;o de refer&#234;ncia e obter dados importantes&#44; corroborando o papel da CXCL10 na patog&#234;nese da doen&#231;a&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">O vitiligo &#233; doen&#231;a autoimune com participa&#231;&#227;o importante dos linf&#243;citos TCD4<span class="elsevierStyleSup">&#43;</span> e TCD8<span class="elsevierStyleSup">&#43;</span> citot&#243;xicos&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">17&#44;36&#44;37</span></a> Tanto no sangue perif&#233;rico quanto nas les&#245;es cut&#226;neas&#44; h&#225; aumento de linf&#243;citos T citot&#243;xicos que infiltram a epiderme e se acumulam ao redor dos melan&#243;citos&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">17</span></a> A literatura salienta o papel das quimiocinas inflamat&#243;rias como CXCL9&#44; CXCL10 e CXCL12&#44; com destaque para o CXCL10&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">15&#44;16</span></a> A produ&#231;&#227;o de CXCL10 &#233; regulada pela IFN&#947; &#40;secretada por linf&#243;citos CD8<span class="elsevierStyleSup">&#43;</span>&#41;&#44; que induz a transcri&#231;&#227;o de fatores via NF&#8208;kB&#44; Janus Kinase e STAT1 &#40;JAK&#47;STAT&#41;&#44; ativando a cascata de sinaliza&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a> Essa ativa&#231;&#227;o estimula maior produ&#231;&#227;o de CXCL10&#44; levando a um ciclo que se autoalimenta&#46; Essa via da IFN&#947; tamb&#233;m &#233; importante na manuten&#231;&#227;o das les&#245;es j&#225; existentes&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a> Isso sugere que os tratamentos mais promissores devem envolver n&#227;o s&#243; o bloqueio de CXCL10 e da via da IFN&#947;&#44; mas tamb&#233;m o controle ou a destrui&#231;&#227;o das c&#233;lula T residentes de mem&#243;ria&#46; Nessa linha&#44; os inibidores da JAK que bloqueiam a via de sinaliza&#231;&#227;o da IFN&#947; t&#234;m se mostrado promissores para algumas doen&#231;as dermatol&#243;gicas como dermatite at&#243;pica&#44; alopecia areata e vitiligo&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a> Mais recentemente&#44; inibidores da JAK t&#243;picos t&#234;m sido usados com algum sucesso no vitiligo&#44; a exemplo do tofacitinibe &#40;inibidor da JAK1&#47;3&#41; e ruxolitinibe &#40;inibidor JAK1&#47;2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">40</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclus&#227;o</span><p id="par0140" class="elsevierStylePara elsevierViewall">Nosso trabalho contribui para confirmar papel relevante do eixo IFN&#947;&#47;CXCL10 e&#44; consequentemente&#44; da via JAK&#47;STAT na patog&#234;nese do vitiligo&#44; destacando o CXCL10 como poss&#237;vel marcador para atividade da doen&#231;a&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">21&#44;36</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Suporte financeiro</span><p id="par0145" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Contribui&#231;&#227;o dos autores</span><p id="par0150" class="elsevierStylePara elsevierViewall">Marta Regina Machado Mascarenhas&#58; An&#225;lise estat&#237;stica&#59; concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; revis&#227;o cr&#237;tica da literatura&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Mariana de Castro Oliveira&#58; Elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados</p><p id="par0160" class="elsevierStylePara elsevierViewall">Luise Fonseca de Oliveira&#58; Elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados</p><p id="par0165" class="elsevierStylePara elsevierViewall">Andr&#233;a Santos Magalh&#227;es&#58; Obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Paulo Roberto Lima Machado&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; 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&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflito de interesses</span><p id="par0175" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">O vitiligo &#233; a mais comum das desordens pigmentares&#44; considerado doen&#231;a cr&#244;nica&#44; cumulativa e multifatorial&#46; Em sua patog&#234;nese&#44; tem sido demonstrado o papel crucial dos linf&#243;citos TCD8<span class="elsevierStyleSup">&#43;</span> citot&#243;xicos e do eixo IFN&#947;&#47;CXCL10&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Avaliar o perfil cl&#237;nico e os marcadores imunoinflamat&#243;rios nos pacientes com vitiligo em um servi&#231;o de refer&#234;ncia&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Estudo de corte transversal no qual foram avaliados todos os pacientes com vitiligo do servi&#231;o no per&#237;odo de 2019 a 2022&#44; para tra&#231;ar o perfil cl&#237;nico&#46; Al&#233;m disso&#44; foram dosados biomarcadores de risco cardiovascular &#40;rela&#231;&#227;o neutr&#243;filo&#47;linf&#243;cito e prote&#237;na C reativa&#41;&#44; assim como citocinas e quimiocinas &#40;TNF&#945;&#44; IFN&#947;&#44; IL&#8208;10&#44; IL&#8208;15 e CXCL10&#41; no soro de um subgrupo de 30 pacientes&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Entre os pacientes&#44; houve predom&#237;nio do sexo feminino&#44; com m&#233;dia de idade de 43 anos&#46; A maioria apresentou fototipos IV ou V &#40;71&#44;3&#37;&#41;&#44; sem comorbidades &#40;77&#44;55&#37;&#41; e sem hist&#243;rico familiar de vitiligo &#40;70&#44;41&#37;&#41;&#46; N&#237;veis mais elevados da rela&#231;&#227;o neutr&#243;filo&#47;linf&#243;cito&#44; prote&#237;na C reativa e citocinas&#47;quimiocinas inflamat&#243;rias foram documentados nos pacientes com vitiligo em compara&#231;&#227;o com o grupo controle &#40;n&#227;o significante&#41;&#46; Como dado relevante&#44; os maiores valores de CXCL10 foram detectados nos pacientes com vitiligo em compara&#231;&#227;o com os controles&#44; assim como nos pacientes com menor tempo de doen&#231;a &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">O n&#250;mero de pacientes avaliados foi reduzido em virtude das dificuldades de recrutamento decorrentes da pandemia de COVID&#8208;19&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#227;o</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Nossos dados contribuem para confirmar o papel relevante do eixo IFN&#947;&#47;CXCL10 na patog&#234;nese do vitiligo&#44; destacando o CXCL10 como poss&#237;vel marcador de atividade&#46;</p></span>"
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                  \t\t\t\t">43 &#40;43&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Marcadores imunoinflamat&#243;rios e tipo de vitiligo &#40;subgrupo de 30 participantes e 10 controles sadios&#41;</p>"
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                            0 => "L&#46;S&#46;C&#46; Nogueira"
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                      "titulo" => "Vitiligo Global Issue Consensus Conference Panelists &#40;2012&#41;&#46; Revised classification&#47;nomenclature of vitiligo and related issues&#58; the Vitiligo Global Issues Consensus Conference"
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