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muito mais raro&#44; como calv&#237;cie completa &#40;alopecia total&#41; ou perda total de pelos corporais &#40;alopecia universal&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">2</span></a> A gravidade da doen&#231;a &#233; avaliada utilizando os escores da ferramenta <span class="elsevierStyleItalic">Severity of Alopecia Tool</span> &#40;SALT&#41;&#46; <a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A etiopatogenia da AA ainda n&#227;o foi totalmente esclarecida&#46; Em seu estudo&#44; Petukhova et al&#46; mostraram que a base gen&#233;tica tem um papel na patog&#234;nese da AA&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">4</span></a> Al&#233;m do hist&#243;rico gen&#233;tico&#44; considera&#8208;se que fatores ambientais e imunol&#243;gicos desempenhem um papel na doen&#231;a&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">5&#44;6</span></a> H&#225; evid&#234;ncias crescentes de que esta seja uma doen&#231;a autoimune polig&#234;nica&#46; Estudos anteriores demonstraram uma rela&#231;&#227;o entre AA e alelos HLA&#44; alguns alelos DQB e DR e <span class="elsevierStyleItalic">cluster</span> de genes da interleucina &#40;IL&#41;&#8208;1&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">No tratamento da AA grave&#44; a resposta &#224;s abordagens tradicionais &#233; limitada e a busca por um tratamento eficaz ainda est&#225; em andamento&#46; Tratamentos que t&#234;m como alvo diferentes vias do sistema imunol&#243;gico est&#227;o sendo introduzidos como novas op&#231;&#245;es terap&#234;uticas&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a> Relatos de casos&#44; s&#233;ries de casos e estudos <span class="elsevierStyleItalic">open&#8208;label</span> sobre o uso de tofacitinibe&#44; um inibidor da Janus quinase &#40;JAK&#41; 1 e 3&#44; foram publicados nos &#250;ltimos anos&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">8</span></a> Estudos anteriores mostraram que as IL&#44; especialmente IL&#8208;2&#44; IL&#8208;4 e IL&#8208;15&#44; podem ter um papel na patog&#234;nese da AA&#46; Os estudos atuais tamb&#233;m mencionam a IL&#8208;17 como uma potencial citocina pr&#243;&#8208;inflamat&#243;ria com um papel no mecanismo da doen&#231;a&#46; O tofacitinibe &#233; um inibidor de JAK que interfere com a JAK1 e JAK3&#46; A JAK3 interage com o receptor de citocina&#44; o cyc&#44; utilizado especificamente para alguns receptores de IL&#44; incluindo IL&#8208;2&#44; IL&#8208;4&#44; IL15&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">9</span></a> Al&#233;m disso&#44; o tofacitinibe inibe as c&#233;lulas Th17 que produzem IL&#8208;17&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">O presente estudo teve como objetivo determinar os n&#237;veis s&#233;ricos de IL &#40;IL&#8208;2&#44; IL&#8208;4&#44; IL&#8208;15 e IL&#8208;17&#41;&#44; que provavelmente desempenham um papel na patog&#234;nese em pacientes com diagn&#243;stico de AA&#46; Em compara&#231;&#227;o com os estudos anteriores&#44; a rela&#231;&#227;o dos n&#237;veis de IL com a dura&#231;&#227;o e a gravidade de AA &#40;escore SALT&#41; e a resposta &#224; terapia com tofacitinibe tamb&#233;m foi investigada&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="par0025" class="elsevierStylePara elsevierViewall">Foram inclu&#237;dos no estudo pacientes com idade &#8805; 16 anos&#44; com diagn&#243;stico cl&#237;nico de AA entre 09&#47;01&#47;2019 e 06&#47;01&#47;2020 em nossa institui&#231;&#227;o&#46; Alguns pacientes apresentavam queda de pelos no corpo&#44; al&#233;m de queda de cabelo no couro cabeludo&#46; Pacientes com doen&#231;as cr&#237;ticas agudas ou cr&#244;nicas que pudessem dificultar o estudo&#44; 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Os n&#237;veis basais de IL foram medidos no soro dos pacientes e controles&#46; No grupo de pacientes recebendo terapia com tofacitinibe&#44; os n&#237;veis s&#233;ricos de IL foram medidos novamente ap&#243;s seis meses de tratamento&#46; Os pacientes com AA resistentes &#224; terapia t&#243;pica iniciaram a terapia com tofacitinibe ap&#243;s terem dado o consentimento informado&#46; Antes de iniciar o tratamento com tofacitinibe&#44; hemograma&#44; testes de fun&#231;&#227;o hep&#225;tica&#44; testes de fun&#231;&#227;o renal&#44; n&#237;veis de amilase&#44; lipase&#44; sorologia viral&#44; teste de quantiferon e radiografia de t&#243;rax foram solicitados para todos os pacientes&#46; Os exames de sangue foram repetidos a cada m&#234;s&#44; e os pacientes foram acompanhados em nossa cl&#237;nica&#46; A dose di&#225;ria de tofacitinibe foi de 10<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A gravidade da AA foi avaliada utilizando a ferramenta SALT&#46; No sistema de escore SALT&#44; o couro cabeludo &#233; dividido em quatro &#225;reas&#59; o v&#233;rtice corresponde a 40&#37;&#44; o perfil direito corresponde a 18&#37;&#44; o perfil esquerdo corresponde a 18&#37; e a regi&#227;o occipital corresponde a 24&#37; da superf&#237;cie do couro cabeludo&#46; Ap&#243;s determinar a porcentagem de queda de cabelo nessas quatro regi&#245;es&#44; ela &#233; multiplicada pelo valor percentual correspondente &#224; &#225;rea em quest&#227;o&#44; e o escore SALT &#233; obtido como a soma dos escores obtidos em cada uma das quatro &#225;reas&#46; Escores mais altos indicam doen&#231;a grave&#59; a perda total de cabelos no couro cabeludo corresponde a 100 pontos&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">3</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Amostras de sangue perif&#233;rico obtidas dos pacientes e controles para an&#225;lise dos n&#237;veis s&#233;ricos de IL foram centrifugadas a 3&#46;000<span class="elsevierStyleHsp" style=""></span>rpm por 10 minutos e&#44; em seguida&#44; o soro foi separado e armazenado a<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>&#176;C at&#233; o momento da an&#225;lise&#46; Os n&#237;veis s&#233;ricos de IL&#8208;2&#44; IL&#8208;4&#44; IL&#8208;15 e IL&#8208;17 foram medidos pelo m&#233;todo ELISA&#46; Os valores foram apresentados como ng&#47;L&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">An&#225;lise estat&#237;stica</span><p id="par0045" class="elsevierStylePara elsevierViewall">Os dados foram analisados usando o <span class="elsevierStyleItalic">software</span> SPSS&#44; vers&#227;o 18&#46;0 &#40;SPSS Inc&#46;&#44; Chicago&#44; IL&#44; EUA&#41;&#46; A adequa&#231;&#227;o das vari&#225;veis &#224; distribui&#231;&#227;o normal foi analisada por m&#233;todos visuais &#40;histograma e gr&#225;ficos de probabilidade&#41; e anal&#237;ticos &#40;testes de Kolmogorov&#8208;Smirnov&#47;Shapiro&#8208;Wilk&#41;&#46; As estat&#237;sticas descritivas foram apresentadas como n&#250;meros e porcentagens para vari&#225;veis categ&#243;ricas e como mediana&#44; percentil 25 &#40;Q1&#41; e percentil 75 &#40;Q3&#41; para as vari&#225;veis num&#233;ricas&#46; Para as vari&#225;veis categ&#243;ricas&#44; a compara&#231;&#227;o de grupos pareados foi realizada por meio do teste de Qui&#8208;quadrado&#46; Como a condi&#231;&#227;o de distribui&#231;&#227;o normal n&#227;o foi fornecida&#44; o teste U de Mann&#8208;Whitney foi utilizado na compara&#231;&#227;o de grupos pareados para vari&#225;veis num&#233;ricas&#46; As an&#225;lises pr&#233;&#8208;p&#243;s para cada grupo foram realizadas utilizando o teste de postos sinalizados de Wilcoxon&#46; A rela&#231;&#227;o entre as vari&#225;veis num&#233;ricas foi analisada pelo teste rho de Spearman&#46; As situa&#231;&#245;es em que o erro do tipo 1 foi inferior a 5&#37; foram interpretadas como estatisticamente significativas&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Resultados</span><p id="par0050" class="elsevierStylePara elsevierViewall">O estudo incluiu 61 pacientes com AA e 30 volunt&#225;rios saud&#225;veis como grupo controle&#46; O grupo de pacientes e o grupo controle eram compar&#225;veis em termos de idade e sexo &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46; A dura&#231;&#227;o m&#233;dia da doen&#231;a para AA foi de 7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6 anos e o escore SALT basal m&#233;dio foi 71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>30 &#40;varia&#231;&#227;o&#44; 20&#8208;100&#41;&#46; O tratamento com tofacitinibe foi usado em 52&#44;5&#37; dos pacientes&#46; No grupo restante&#44; 36&#44;1&#37; dos pacientes iniciaram outros tratamentos&#44; incluindo imunoterapia t&#243;pica e tratamento sist&#234;mico com esteroides&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">As concentra&#231;&#245;es s&#233;ricas de IL dos pacientes e do grupo controle s&#227;o mostradas na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46; Os n&#237;veis basais de IL&#8208;2&#44; IL&#8208;4 e IL&#8208;15 foram significativamente maiores no grupo de pacientes em compara&#231;&#227;o com os do grupo controle&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Os n&#237;veis de IL foram analisados de acordo com o sexo no grupo de pacientes e no grupo controle&#46; Nenhuma diferen&#231;a significativa foi determinada entre homens e mulheres em rela&#231;&#227;o aos n&#237;veis de IL&#44; tanto no grupo de pacientes quanto no grupo controle &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Nenhuma correla&#231;&#227;o estatisticamente significativa foi encontrada entre os n&#237;veis basais de IL e a dura&#231;&#227;o ou gravidade da doen&#231;a &#40;escore SALT basal&#44; <a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Havia 32 pacientes em tratamento com tofacitinibe&#46; Os n&#237;veis de IL pr&#233; e p&#243;s&#8208;tratamento e os escores SALT foram comparados em 22 desses pacientes&#44; nos quais as medidas foram repetidas no sexto m&#234;s&#46; Uma diminui&#231;&#227;o significativa foi encontrada nos n&#237;veis de todas as IL ap&#243;s o tratamento quando comparados &#224;queles antes do tratamento &#40;basal&#41;&#46; Al&#233;m disso&#44; foi observada uma diminui&#231;&#227;o significativa na gravidade da doen&#231;a avaliada pelo escore SALT &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabela 5</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">N&#227;o houve rela&#231;&#227;o significativa entre a mudan&#231;a nos n&#237;veis de IL e a mudan&#231;a nos escores SALT ap&#243;s o tratamento em compara&#231;&#227;o com aqueles observados antes do tratamento nos pacientes que receberam tofacitinibe &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">tabela 6</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Discuss&#227;o</span><p id="par0080" class="elsevierStylePara elsevierViewall">Dependendo da gravidade da doen&#231;a&#44; o estado psicossocial dos pacientes com AA &#233; influenciado e sua qualidade de vida &#233; prejudicada&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">11</span></a> A falta de tratamento curativo para esta doen&#231;a leva &#224; continua&#231;&#227;o da busca por um tratamento eficaz e de estudos que esclare&#231;am sua patog&#234;nese&#46; Acredita&#8208;se que os mecanismos imunol&#243;gicos estejam envolvidos na patog&#234;nese da AA e que v&#225;rias citocinas&#44; como interferon &#40;IFN&#41;&#44; fator de necrose tumoral &#40;TNF&#41; e IL tamb&#233;m desempenhem um papel&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">12&#44;13</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">H&#225; um n&#250;mero limitado de estudos cl&#237;nicos que investigam a rela&#231;&#227;o das IL com a gravidade da doen&#231;a e seu papel na patog&#234;nese da AA&#46; No presente estudo&#44; avaliamos os n&#237;veis de IL&#8208;2&#44; IL&#8208;4&#44; IL&#8208;15 e IL&#8208;17&#46; Os n&#237;veis basais de IL&#8208;2&#44; IL&#8208;4 e IL&#8208;15 foram significativamente maiores no grupo de pacientes do que no grupo controle &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001 para cada uma&#41;&#46; Nenhuma correla&#231;&#227;o significativa foi encontrada entre os n&#237;veis basais de IL e a dura&#231;&#227;o ou gravidade da doen&#231;a&#46; N&#227;o houve diferen&#231;a estatisticamente significativa nos n&#237;veis de IL&#8208;17 entre o grupo de pacientes e o grupo controle e nenhuma correla&#231;&#227;o significativa entre os n&#237;veis de IL&#8208;17 e a dura&#231;&#227;o ou gravidade da AA&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">A IL&#8208;2 &#233; uma citocina que desempenha um papel na mem&#243;ria imunol&#243;gica&#44; que tem uma rela&#231;&#227;o comprovada com doen&#231;as autoimunes&#44; e o uso de IL&#8208;2 ou de seus receptores na imunoterapia &#233; discut&#237;vel&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">14</span></a> Kasumagi&#263;&#8208;Halilovic et al&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">15</span></a> encontraram n&#237;veis mais elevados de IL&#8208;2 em pacientes com AA em compara&#231;&#227;o com os controles&#46; Nenhuma correla&#231;&#227;o foi encontrada entre os n&#237;veis de IL&#8208;2 e o tipo cl&#237;nico de AA ou dura&#231;&#227;o da doen&#231;a&#46; Do mesmo modo&#44; tamb&#233;m encontramos n&#237;veis mais elevados de IL&#8208;2 em pacientes com AA do que nos controles&#46; N&#227;o encontramos correla&#231;&#227;o significativa entre os n&#237;veis de IL&#8208;2 e a dura&#231;&#227;o ou gravidade da AA&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">A IL&#8208;4 &#233; uma IL que participa de v&#225;rios processos fisiol&#243;gicos e patol&#243;gicos e desempenha um papel na ades&#227;o e inflama&#231;&#227;o dos tecidos&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">16</span></a> Kalkan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">17</span></a> conclu&#237;ram que o polimorfismo VNTR da IL&#8208;4 pode ser um fator de risco para o desenvolvimento de AA&#46; No presente estudo&#44; os n&#237;veis de IL&#8208;4 foram maiores nos pacientes com AA quando comparados aos controles &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; N&#227;o houve correla&#231;&#227;o significativa entre os n&#237;veis de IL&#8208;4 e a dura&#231;&#227;o ou gravidade da AA&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">A IL&#8208;15 &#233; uma citocina multifuncional com rela&#231;&#227;o documentada com doen&#231;as autoimunes&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">18</span></a> Ebrahim et al&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">19</span></a> relataram n&#237;veis s&#233;ricos de IL&#8208;15 mais elevados em pacientes com AA em compara&#231;&#227;o com os controles e uma correla&#231;&#227;o significativamente positiva entre os escores SALT e os n&#237;veis de IL&#8208;15&#46; Eles conclu&#237;ram que a IL&#8208;15 pode ser um marcador de gravidade da AA&#46; Do mesmo modo&#44; no presente estudo&#44; os n&#237;veis de IL&#8208;15 foram maiores nos pacientes com AA em compara&#231;&#227;o aos controles &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Entretanto&#44; nenhuma correla&#231;&#227;o significativa foi encontrada entre os n&#237;veis de IL&#8208;15 e a dura&#231;&#227;o ou gravidade da AA&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">A IL&#8208;17 &#233; uma citocina que desempenha um papel cr&#237;tico na barreira epitelial das partes do corpo que s&#227;o frequentemente expostas a microrganismos&#44; bem como na imunopatologia&#44; defesa do hospedeiro e inflama&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">20</span></a> El&#8208;Morsy et al&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">21</span></a> observaram n&#237;veis s&#233;ricos mais elevados de IL&#8208;17A em pacientes com AA em compara&#231;&#227;o com os controles&#59; entretanto&#44; eles relataram a aus&#234;ncia de uma correla&#231;&#227;o significativa entre os n&#237;veis de IL&#8208;17A e sexo&#44; dura&#231;&#227;o da doen&#231;a&#44; escore SALT ou gravidade da doen&#231;a&#46; Com base nesses achados&#44; eles conclu&#237;ram que a IL&#8208;17A potencialmente desempenha um papel na patog&#234;nese&#44; mas n&#227;o afeta a gravidade da doen&#231;a&#46; Em outro estudo&#44; n&#227;o foi encontrada diferen&#231;a entre os n&#237;veis de IL&#8208;17A de pacientes com AA e dos controles&#59; no entanto&#44; os n&#237;veis de IL&#8208;17A dos pacientes mostraram uma diminui&#231;&#227;o significativa ap&#243;s o tratamento com ultravioleta B de banda estreita&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">22</span></a> Loh et al&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">23</span></a> relataram n&#237;veis s&#233;ricos de IL&#8208;17 mais elevados em pacientes com AA em compara&#231;&#227;o com os controles em seu estudo&#46; Em sua revis&#227;o&#44; Ramot et al&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">24</span></a> conclu&#237;ram que n&#227;o h&#225; uma rela&#231;&#227;o clara entre os n&#237;veis de IL&#8208;17 e a gravidade ou dura&#231;&#227;o da doen&#231;a&#44; apesar dos n&#237;veis mais elevados de IL&#8208;17 relatados em pacientes com AA&#46; No presente estudo&#44; embora o n&#237;vel de IL&#8208;17 tenha sido maior em pacientes com AA do que nos controles&#44; a diferen&#231;a n&#227;o foi estatisticamente significativa&#46; Al&#233;m disso&#44; n&#227;o houve correla&#231;&#227;o significativa entre os n&#237;veis de IL&#8208;17 e a dura&#231;&#227;o ou gravidade da AA&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">A sele&#231;&#227;o de medicamentos para o tratamento de AA depende de v&#225;rios fatores&#44; como idade do paciente&#44; extens&#227;o&#47;dura&#231;&#227;o da doen&#231;a&#44; expectativa do paciente&#44; custo do tratamento e presen&#231;a de comorbidades&#46; Embora ainda n&#227;o exista tratamento curativo&#44; v&#225;rias terapias est&#227;o sendo implementadas para obter a remiss&#227;o&#46; Corticosteroides&#44; minoxidil t&#243;pico&#44; imunoterapia t&#243;pica &#40;DPCP&#44; SADBE&#41;&#44; antralina&#44; fototerapia&#44; agentes imunossupressores&#44; an&#225;logos de prostaglandinas&#44; agentes biol&#243;gicos e inibidores de JAK est&#227;o entre as terapias que t&#234;m sido implementadas atualmente e consideradas ben&#233;ficas&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">25</span></a> Recentemente&#44; junto com o aumento das informa&#231;&#245;es sobre a patog&#234;nese e a introdu&#231;&#227;o do papel da via JAK&#44; o potencial terap&#234;utico dos inibidores de JAK &#40;tofacitinibe&#44; ruxolitinibe e baricitinibe&#41; na AA come&#231;ou a atrair aten&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">26</span></a> Os efeitos ben&#233;ficos do tofacitinibe no tratamento da AA moderada a grave foram relatados em s&#233;ries de casos e estudos cl&#237;nicos&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">27&#8211;31</span></a> Guo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">32</span></a> realizaram uma revis&#227;o sistem&#225;tica e uma metan&#225;lise e relataram que o tofacitinibe &#233; ben&#233;fico no tratamento de pacientes com AA e causa apenas eventos adversos leves&#44; e recomendaram a verifica&#231;&#227;o desses dados em futuros ensaios cl&#237;nicos randomizados de grande escala&#46; No presente estudo&#44; os n&#237;veis de interleucina foram reestudados e o escore SALT foi medido novamente no sexto m&#234;s de tratamento em 22 dos pacientes com AA que receberam tofacitinibe&#46; Embora a mediana do escore SALT &#40;Q1&#8208;Q3&#41; dos pacientes tenha sido 100 &#40;50&#8208;100&#41; na linha de base&#44; ela apresentou um valor de 40 &#40;24&#8208;50&#41; no sexto m&#234;s de terapia com tofacitinibe&#46; Essa diminui&#231;&#227;o na gravidade da doen&#231;a foi considerada estatisticamente significativa &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Os n&#237;veis de interleucina dos pacientes estudados no presente estudo demonstraram redu&#231;&#227;o significativa ap&#243;s terapia com tofacitinibe&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Em conclus&#227;o&#44; os n&#237;veis elevados de interleucina em pacientes com AA e a diminui&#231;&#227;o significativa com o tratamento corroboram a ideia de que as IL t&#234;m um papel na patog&#234;nese&#46; No entanto&#44; nenhuma rela&#231;&#227;o foi demonstrada entre os n&#237;veis de IL e a dura&#231;&#227;o ou gravidade da doen&#231;a&#46; Mais estudos com popula&#231;&#245;es maiores de pacientes s&#227;o necess&#225;rios&#46; Compreender o papel das IL na patog&#234;nese da AA contribuir&#225; para o desenvolvimento de novas terapias direcionadas&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conclus&#227;o</span><p id="par0120" class="elsevierStylePara elsevierViewall">N&#237;veis elevados de IL em pacientes com AA e a diminui&#231;&#227;o significativa ap&#243;s o tratamento com tofacitinibe apoiam a ideia de que as IL tenham um papel na patog&#234;nese da AA&#46; Mais estudos s&#227;o necess&#225;rios para investigar o papel das IL na patog&#234;nese da AA&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Suporte financeiro</span><p id="par0125" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Contribui&#231;&#227;o dos autores</span><p id="par0130" class="elsevierStylePara elsevierViewall">&#214;zge a&#351;k&#305;n&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o de dados&#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&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; an&#225;lise estat&#237;stica&#59; concep&#231;&#227;o e planejamento do estudo&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Sera Nur Y&#252;cesoy&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o de dados&#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&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Erkam Co&#351;kun&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o de dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Burhan Engin&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o de dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Server Serdaro&#287;lu&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o de dados&#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&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflito de interesses</span><p id="par0155" 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">Alopecia areata &#40;AA&#41; &#233; uma doen&#231;a dos fol&#237;culos pilosos que causa perda de cabelos sem deixar cicatrizes&#46; A etiopatogenia da AA ainda n&#227;o foi totalmente compreendida&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Determinar os n&#237;veis s&#233;ricos de interleucinas &#40;IL&#8208;2&#44; IL&#8208;4&#44; IL&#8208;15 e IL&#8208;17&#41; em pacientes com diagn&#243;stico de AA e investigar a rela&#231;&#227;o dos n&#237;veis de IL com a dura&#231;&#227;o e gravidade da AA e a resposta &#224; terapia com tofacitinibe&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Pacientes &#40;&#8805; 16 anos&#41; com diagn&#243;stico de AA e indiv&#237;duos saud&#225;veis como grupo controle foram inclu&#237;dos&#46; Os n&#237;veis s&#233;ricos basais de IL dos pacientes e controles foram medidos&#46; No grupo de pacientes que recebeu terapia com tofacitinibe&#44; os n&#237;veis s&#233;ricos de IL foram medidos novamente ap&#243;s seis meses&#46; A gravidade da AA foi avaliada utilizando a ferramenta <span class="elsevierStyleItalic">Severity of Alopecia Tool</span>&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Sessenta e um pacientes com AA e 30 indiv&#237;duos saud&#225;veis foram inclu&#237;dos&#59; eles eram compar&#225;veis em rela&#231;&#227;o &#224; idade e sexo&#46; A dura&#231;&#227;o m&#233;dia da AA foi de 7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6 anos e o escore m&#233;dio inicial na ferramenta <span class="elsevierStyleItalic">Severity of Alopecia Tool</span> foi de 71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>30 &#40;varia&#231;&#227;o&#44; 20&#8208;100&#41;&#46; Os n&#237;veis basais de IL&#8208;2&#44; IL&#8208;4 e IL&#8208;15 foram significativamente maiores no grupo de pacientes do que no grupo controle &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001 para cada um&#41;&#46; Nenhuma correla&#231;&#227;o significativa foi encontrada entre os n&#237;veis basais de IL e a dura&#231;&#227;o ou gravidade da doen&#231;a &#40;escore basal da ferramenta <span class="elsevierStyleItalic">Severity of Alopecia Tool</span>&#41;&#46; Entre os pacientes que receberam tofacitinibe &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>22&#41;&#44; os n&#237;veis de todas as IL diminu&#237;ram significativamente ap&#243;s o tratamento&#46; Entretanto&#44; nenhuma rela&#231;&#227;o significativa entre a mudan&#231;a nos n&#237;veis de IL e a mudan&#231;a nos escores da <span class="elsevierStyleItalic">Severity of Alopecia Tool</span> foi observada ap&#243;s o tratamento com tofacitinibe&#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">Trata&#8208;se de um estudo monoc&#234;ntrico&#44; realizado em um &#250;nico hospital universit&#225;rio&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#227;o</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Os n&#237;veis elevados de IL em pacientes com AA e a diminui&#231;&#227;o significativa com o tratamento corroboram a ideia de que as IL t&#234;m um papel na patog&#234;nese&#46; Entretanto&#44; nenhuma rela&#231;&#227;o pode ser demonstrada entre os n&#237;veis de IL e a dura&#231;&#227;o ou gravidade da doen&#231;a&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Como citar este artigo&#58; A&#351;k&#305;n &#214;&#44; Y&#252;cesoy SN&#44; Co&#351;kun E&#44; Engin B&#44; Serdaro&#287;lu S&#46; Evaluation of the level of serum Interleukins &#40;IL&#8208;2&#44; IL&#8208;4&#44; IL&#8208;15 and IL&#8208;17&#41; and its relationship with disease severity in patients with alopecia areata&#46; An Bras Dermatol&#46; 2021&#59;96&#58;551&#8211;7&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Trabalho realizado no Istanbul University Cerrahpasa&#44; Istambul&#44; Turquia&#46;</p>"
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;6&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&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="elsevierStyleHsp" style=""></span>DPCP&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 &#40;1&#44;6&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&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">&#8211;&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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Nenhum&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">7 &#40;11&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8211;&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">&#8211;&nbsp;\t\t\t\t\t\t\n
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        ]
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                  \t\t\t\t" scope="col">Interleucinas&#44; ng&#47;L&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col">M&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DP&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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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">359&#44;53 &#40;306&#44;34&#8208;709&#44;42&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">324&#44;99 &#40;273&#44;87&#8208;648&#44;9&#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">150&#44;08 &#40;99&#44;1716&#8208;251&#44;26&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " rowspan="2" align="left" valign="\n
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                  \t\t\t\t">IL&#8208;15</td><td class="td" title="\n
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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">195&#44;1 &#40;136&#44;39&#8208;496&#44;33&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">134&#44;66 &#40;65&#44;46&#8208;170&#44;49&#41;&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL&#8208;17</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;723&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">80&#44;66 &#40;60&#44;27&#8208;162&#44;38&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">83&#44;56 &#40;56&#44;69&#8208;171&#44;12&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">M&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DP&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">M&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DP&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mediana &#40;Q1&#8208;Q3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mediana &#40;Q1&#8208;Q3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">303&#44;53 &#40;262&#44;56&#8208;536&#44;01&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " rowspan="2" align="left" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">193&#44;78 &#40;130&#44;28&#8208;590&#44;95&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">200&#44;42 &#40;139&#44;63&#8208;446&#44;04&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " rowspan="2" align="left" valign="\n
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                  \t\t\t\t">IL&#8208;17</td><td class="td" title="\n
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                  \t\t\t\t">30&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="" valign="\n
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                  \t\t\t\t">85&#44;03 &#40;57&#44;33&#8208;192&#44;49&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">78&#44;97 &#40;62&#44;49&#8208;124&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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          "pt" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">N&#237;veis de interleucinas de acordo com o sexo</p>"
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                  \t\t\t\t" scope="col">N&#237;veis basais da IL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">IL&#8208;15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>0&#44;109&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">0&#44;404&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">61&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;059&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;650&nbsp;\t\t\t\t\t\t\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">IL&#8208;17&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>0&#44;073&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">Pr&#233;&#8208;tratamento &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>22&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col">P&#243;s&#8208;tratamento &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>22&#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="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mediana &#40;Q1&#8208;Q3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mediana &#40;Q1&#8208;Q3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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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  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">N&#237;vel de IL</span></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"><span class="elsevierStyleHsp" style=""></span>IL&#8208;2&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">346&#44;92 &#40;314&#44;08&#8208;462&#44;66&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">248&#44;96 &#40;174&#44;55&#8208;298&#44;89&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>IL&#8208;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;016&nbsp;\t\t\t\t\t\t\n
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          "pt" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Rela&#231;&#227;o entre a mudan&#231;a nos n&#237;veis das interleucinas e a mudan&#231;a nos escores na ferramenta SALT em pacientes recebendo tratamento com tofacitinibe</p>"
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    ]
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      "titulo" => "Refer&#234;ncias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:32 [
            0 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Alopecia areata"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "K&#46;L&#46;E&#46; Hon"
                            1 => "A&#46;K&#46;C&#46; Leung"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2174/187221311795399291"
                      "Revista" => array:6 [
                        "tituloSerie" => "Recent Pat Inflamm Allergy Drug Discov&#46;"
                        "fecha" => "2011"
                        "volumen" => "5"
                        "paginaInicial" => "98"
                        "paginaFinal" => "107"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21453266"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Alopecia Areata&#58; a Comprehensive Review of Pathogenesis and Management"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46;M&#46; Tr&#252;eb"
                            1 => "M&#46;F&#46;R&#46;G&#46; Dias"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12016-017-8620-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Rev Allergy Immunol&#46;"
                        "fecha" => "2018"
                        "volumen" => "54"
                        "paginaInicial" => "68"
                        "paginaFinal" => "87"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28717940"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "National Alopecia Areata Foundation Alopecia areata investigational assessment guidelines &#8211; Part II&#46; National Alopecia Areata Foundation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;A&#46; Olsen"
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