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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">Prurigo &#233; condi&#231;&#227;o cut&#226;nea hiperpl&#225;sica reativa caracterizada por p&#225;pulas&#44; placas e&#47;ou n&#243;dulos&#44; isolados ou m&#250;ltiplos&#44; com prurido intenso&#46; Alguns autores classificam o prurigo de acordo com o tipo &#40;agudo&#44; subagudo ou cr&#244;nico&#41; ou forma cl&#237;nica ou agente causador&#47;doen&#231;a associada&#46; H&#225; vasta sinon&#237;mia e descri&#231;&#227;o de quadros superpon&#237;veis&#44; sob a mesma denomina&#231;&#227;o&#44; o que dificulta a revis&#227;o da informa&#231;&#227;o dispon&#237;vel&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">1&#8211;3</span></a>O termo &#8220;prurigo&#8221; foi originado do latim <span class="elsevierStyleItalic">pruire</span>&#44; que significa coceira&#44; nominado por Ferdinand von Hebra ao caracterizar p&#225;pulas e n&#243;dulos com prurido intenso&#44; em Viena&#44; em 1850&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">3&#44;4</span></a> Outros autores&#44; por&#233;m&#44; atribuem a Robert Willan&#44; h&#225; mais de 200 anos&#44; a descri&#231;&#227;o de p&#225;pulas pruriginosas sob o termo prurigo&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Este manuscrito revisa os principais tipos de prurigo&#44; doen&#231;as associadas&#44; suas bases imunol&#243;gicas&#44; diagn&#243;stico e tratamento&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Formas cl&#237;nicas de prurigo</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Prurigo agudo&#47;subagudo</span><p id="par0015" class="elsevierStylePara elsevierViewall">O prurigo agudo compreende les&#245;es com dura&#231;&#227;o ef&#234;mera &#40;&#8804; 6 semanas&#41;&#44; podendo haver surtos de reagudiza&#231;&#227;o&#46; Compreende uma variedade de manifesta&#231;&#245;es cl&#237;nicas como p&#225;pulas eritematosas intensamente pruriginosas&#44; frequentemente exibindo ves&#237;cula central&#44; em &#225;reas cobertas por roupas &#40;t&#243;rax&#44; abdome&#41;&#44; ou principalmente n&#227;o cobertas&#44; como antebra&#231;os&#44; bra&#231;os&#44; pernas&#44; m&#227;os e p&#233;s &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#44; dependendo do agente indutor&#46; Les&#245;es at&#237;picas podem estar associadas&#44; como ves&#237;culas&#44; bolhas&#44; crostas e les&#245;es urticariformes&#44; em que a superinfec&#231;&#227;o estafiloc&#243;cica &#233; comum&#46; O prurigo agudo geralmente ocorre em virtude de picada de artr&#243;podes&#59; &#233; comumente referido na literatura pedi&#225;trica como prurigo estr&#243;fulo&#44; que privilegia crian&#231;as de 2 a 7 anos&#44; em &#225;reas tropicais&#44; com fundo imunol&#243;gico at&#243;pico e baixo n&#237;vel socioecon&#244;mico&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">2&#44;6</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">A reativa&#231;&#227;o de les&#245;es antigas ap&#243;s novas picadas de insetos em outras topografias &#233; descrita&#44; assim como a forma&#231;&#227;o de bolhas e ves&#237;culas nos locais das novas picadas &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Les&#245;es mais exuberantes aparecem em indiv&#237;duos predispostos&#44; principalmente em at&#243;picos&#46; O conte&#250;do das les&#245;es geralmente &#233; citrino&#44; refletindo o plasma exsudado das les&#245;es&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Em geral&#44; o prurigo agudo n&#227;o requer exames complementares extensos&#46; Seu tratamento deve ser orientado de acordo com o agente causador&#46; O tratamento &#233; sintom&#225;tico&#58; anti&#8208;histam&#237;nicos &#40;anti&#8208;H1&#41; n&#227;o sedantes de dia e sedantes &#224; noite&#44; cuidados antiss&#233;pticos di&#225;rios&#44; corte de unhas para evitar superinfec&#231;&#227;o bacteriana e corticosteroides t&#243;picos&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">No entanto&#44; a exposi&#231;&#227;o a picadas intermitentes de artr&#243;podes pode conduzir a uma forma de prurido agudo referido como urtic&#225;ria papular &#40;UP&#41;&#44; que &#233; induzida principalmente por picada de pulga&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">A UP &#233; condi&#231;&#227;o al&#233;rgica cr&#244;nica em que a melhora cl&#237;nica pode ocorrer em torno dos 7 anos&#44; representando um modelo natural de toler&#226;ncia imunol&#243;gica adquirida&#46; Em pacientes com UP&#44; estudos imunol&#243;gicos demonstraram mais c&#233;lulas&#8208;T CLA4<span class="elsevierStyleSup">&#43;</span> espec&#237;ficas da pele para ant&#237;genos de pulgas secretando IFN&#8208;&#947;&#44; IL&#8208;4&#44; IL&#8208;10 e IL&#8208;17&#44; quando comparadas a controles saud&#225;veis&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">8&#44;9</span></a> Curiosamente&#44; ap&#243;s mais de cinco anos de dura&#231;&#227;o da doen&#231;a&#44; as c&#233;lulas T CLA4<span class="elsevierStyleSup">&#43;</span> da pele perdem sua capacidade de produzir IL&#8208;4&#44; enquanto mant&#234;m em grande parte sua capacidade de secre&#231;&#227;o de IL&#8208;10 e IL&#8208;17&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">8&#44;9</span></a> Alinhado com essa hip&#243;tese&#44; a frequ&#234;ncia de c&#233;lulas T positivas para IFN&#8208;&#947; &#233; reduzida tanto em linf&#243;citos residentes ou n&#227;o&#44; na pele nesses pacientes&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Celiksoy et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">10</span></a> estudaram 130 pacientes com UP &#40;idade mediana&#58; 60 meses&#41;&#46; A preval&#234;ncia de sibilos recorrentes e dermatite at&#243;pica &#40;DA&#41; foi maior no grupo &#60;<span class="elsevierStyleHsp" style=""></span>5 anos com UP do que no grupo controle da mesma idade&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">10</span></a> A preval&#234;ncia de asma&#44; rinite al&#233;rgica e DA foi maior no grupo &#62;<span class="elsevierStyleHsp" style=""></span>5 anos com UP do que o grupo controle da mesma idade&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">10</span></a> Esses pacientes devem ser avaliados n&#227;o apenas em termos de UP&#44; mas tamb&#233;m em termos de doen&#231;as at&#243;picas com&#243;rbidas&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">8&#44;10</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Prurigo cr&#244;nico</span><p id="par0045" class="elsevierStylePara elsevierViewall">O prurigo cr&#244;nico &#40;PGC&#41; tem sua dura&#231;&#227;o definida por mais de 6 semanas&#44; e pode ser classificado em tr&#234;s subtipos&#44; se associado&#47;causado por outras dermatoses ou n&#227;o&#58; a&#41; PGC com les&#245;es cut&#226;neas associadas&#59; b&#41; PGC sem les&#245;es cut&#226;neas associadas&#59; ou c&#41; PGC de origem indeterminada&#46; Um consenso japon&#234;s classificou os tipos de prurigo de acordo com sua causa relacionada&#44; conforme demonstrado na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">1</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">O PGC sem associa&#231;&#227;o com outras les&#245;es cut&#226;neas pode estar relacionado a doen&#231;as internas ou sist&#234;micas&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">2&#44;11&#44;12</span></a> Na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#44; demonstramos doen&#231;as dermatol&#243;gicas associadas ao PGC com ou sem les&#245;es cut&#226;neas de outras dermatoses&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Morfologicamente&#44; o PGC pode ser designado como prurigo nodular cr&#244;nico &#40;predominam os n&#243;dulos&#41;&#44; prurigo papular cr&#244;nico &#40;predominam as p&#225;pulas&#41;&#44; PGC em placas &#40;predominam as placas&#41;&#44; PGC umbilicado &#40;predominam as les&#245;es pruriginosas ulceradas&#41; ou linear &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46; Entretanto&#44; como morfologias distintas podem estar presentes no mesmo paciente simultaneamente e suas caracter&#237;sticas podem evoluir e mudar ao longo do tempo&#44; todos esses fen&#243;tipos ser&#227;o tratados como PGC&#44; nesse texto&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">4&#44;13&#44;14</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Dados epidemiol&#243;gicos sobre o PGC s&#227;o escassos na literatura&#46; Alguns autores estimam 72 casos por 100&#46;000 pessoas&#44; o que provavelmente sejam subestimados por subnotifica&#231;&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">4&#44;14</span></a> Docampo&#8208;Sim&#243;n et al&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">13</span></a> relataram que&#44; em sua pr&#225;tica cl&#237;nica&#44; o PGC &#233; mais frequente em pacientes com idade entre 50 e 60 anos e entre afro&#8208;americanos&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">14</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Zeidler et al&#46; estudaram 1&#46;128 pacientes de PGC na Alemanha entre 2004 e 2018&#44; dos quais 61&#44;4&#37; eram do sexo feminino&#59; a preval&#234;ncia aumenta com a idade&#44; e a dura&#231;&#227;o mediana do PGC foi de 2&#44;9 anos antes do diagn&#243;stico pelo estudo&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">15</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Especialistas europeus e americanos em prurido desenvolveram a diretriz do F&#243;rum Internacional sobre o Estudo do Prurido &#40;IFSI&#41; sobre PGC&#44; incluindo prurigo nodular como seu sin&#244;nimo&#59; foram estabelecidos crit&#233;rios diagn&#243;sticos para PGC &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a> As defini&#231;&#245;es japonesas s&#227;o alinhadas&#44; embora ligeiramente diferentes&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">1</span></a> De acordo com a classifica&#231;&#227;o etiol&#243;gica do IFSI&#44; o PGC pode ainda ser de origem dermatol&#243;gica&#44; sist&#234;mica&#44; neurol&#243;gica&#44; psiqui&#225;trica&#47;psicossom&#225;tica&#44; multifatorial ou desconhecida&#44; atentando para a relev&#226;ncia da investiga&#231;&#227;o etiol&#243;gica em seu tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">O PGC induz um ciclo prurido&#8208;co&#231;adura&#44; bem como fen&#244;menos de sensibiliza&#231;&#227;o neuronal&#44; que contribuem para o desenvolvimento e perpetua&#231;&#227;o do PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a> Esses mecanismos s&#227;o independentes da origem do prurido&#44; uma vez que o desenvolvimento do PGC &#233; observado em diferentes etiologias subjacentes do prurido &#8211; p&#46; ex&#46;&#44; na DA&#44; prurido nefrog&#234;nico ou s&#237;ndromes de compress&#227;o neurol&#243;gica&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a> Em idosos&#44; muitas comorbidades independentes podem estar presentes&#44; mas sem representar causa desencadeante do PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a> Portanto&#44; a doen&#231;a subjacente do PGC n&#227;o &#233; f&#225;cil de estabelecer&#44; e alguns termos&#44; como &#8220;dermatite at&#243;pica prurigoide&#8221;&#44; devem ser evitados em favor de afirmar que existem duas entidades distintas&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a></p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Patog&#234;nese do prurigo cr&#244;nico</span><p id="par0080" class="elsevierStylePara elsevierViewall">Em pacientes at&#243;picos&#44; estudos imunol&#243;gicos e gen&#233;ticos delinearam vias inflamat&#243;rias al&#233;rgicas comuns a diversas condi&#231;&#245;es&#44; como DA&#44; asma&#44; alergia alimentar&#44; entre outras&#44; das quais a patog&#234;nese central &#233; a via do receptor da interleucina 4 &#40;IL&#8208;4R&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">17</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">O eixo IL&#8208;4&#47;IL&#8208;13&#47;IL&#8208;4R promove a diferencia&#231;&#227;o das c&#233;lulas T helper tipo 2 &#40;TH2&#41;&#44; que medeiam a resposta imune adaptativa pr&#243;&#8208;al&#233;rgica&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">17</span></a> Uma vez que a IL&#8208;4 ou IL&#8208;13 se liga aos receptores&#44; elas desencadeiam a transfosforila&#231;&#227;o e a ativa&#231;&#227;o das prote&#237;nas quinases da fam&#237;lia Janus &#40;JAKs&#41; associadas &#224; subunidade do receptor&#44; incluindo JAK1&#44; JAK3 e JAK2&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">17</span></a> No entanto&#44; v&#225;rias outras condi&#231;&#245;es est&#227;o relacionadas ao PGC&#44; e sua patog&#234;nese &#233; baseada na sensibiliza&#231;&#227;o do prurido e nas intera&#231;&#245;es entre pruriceptores e c&#233;lulas da pele&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">18</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">O prurido envolve estruturas e c&#233;lulas com origem em tecidos neuroectod&#233;rmicos&#46; Existem dois principais envolvidos na patog&#234;nese do PGC&#58; o sistema nervoso central e as c&#233;lulas imunes da pele&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">18</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Ocorrem altera&#231;&#245;es funcionais encef&#225;licas associadas &#224; sensibiliza&#231;&#227;o ao prurido que mostram ativa&#231;&#227;o aumentada de algumas &#225;reas associadas a altera&#231;&#245;es estruturais&#44; como diminui&#231;&#227;o da massa cinzenta em algumas regi&#245;es do c&#233;rebro&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Na medula espinal&#44; a regula&#231;&#227;o anormal das vias inibit&#243;rias do prurido pode explicar a sensibiliza&#231;&#227;o central&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">18</span></a> A sensibiliza&#231;&#227;o perif&#233;rica tem sido atribu&#237;da ao aumento da excitabilidade do nervo sensorial em virtude da hiperinerva&#231;&#227;o &#40;na derme&#41; e&#47;ou &#224; perda de inerva&#231;&#227;o &#40;fibras nervosas intraepid&#233;rmicas de pequeno di&#226;metro&#44; FNIPD&#41;&#44; bem como ao aumento da express&#227;o&#44; sensibilidade e&#47;ou capacidade de resposta de pruriceptores&#44; que contribuem para a hipersensibilidade dos neur&#244;nios sensoriais aos pruritog&#234;nicos&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">10</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Na pele&#44; os queratin&#243;citos interagem com termina&#231;&#245;es nervosas sensoriais&#44; especialmente pruriceptores das FNIPD&#44; por meio de contatos sin&#225;pticos&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">18</span></a> A percep&#231;&#227;o da coceira e o aparecimento de les&#245;es de prurigo est&#227;o relacionados a essas intera&#231;&#245;es e com outras c&#233;lulas do seu ambiente&#44; como mast&#243;citos&#44; eosin&#243;filos&#44; c&#233;lulas dendr&#237;ticas ou linf&#243;citos T&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">18</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Em camundongos&#44; foram identificados tr&#234;s tipos de termina&#231;&#245;es nervosas pruriceptivas&#58; a&#41; neur&#244;nios D&#43; MRGPR &#40;receptor acoplado &#224; prote&#237;na G relacionada a Mas&#41;&#59; b&#41; neur&#244;nios que expressam MRGPRA3&#44; MMRGPRC11&#44; receptores de histamina e o receptor de IL&#8208;33&#59; e c&#41; termina&#231;&#245;es nervosas que expressam receptores de serotonina e o receptor de IL&#8208;31&#46; Muitos genes MRGPR s&#227;o expressos exclusivamente em subconjuntos de neur&#244;nios do g&#226;nglio da raiz dorsal &#40;GRD&#41; de pequeno di&#226;metro e&#44; em humanos&#44; as prote&#237;nas derivadas desses genes s&#227;o denominadas MRGPRX1 a MRGPRX4&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">19</span></a> Em humanos&#44; o gene MRGPR&#8208;X2 &#233; altamente expresso em les&#245;es de PGC&#44; e os mast&#243;citos s&#227;o as principais c&#233;lulas que expressam mRNA de MRGPRX2 na maioria dos pacientes &#40;70&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">20</span></a> Os receptores de IL&#8208;4 e IL&#8208;13 s&#227;o detectados em todas as tr&#234;s categorias&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">18</span></a> Em camundongos&#44; foi demonstrado que os comportamentos do ato de co&#231;ar variam de acordo com a ativa&#231;&#227;o desses diferentes subtipos&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">18</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">No PGC&#44; a express&#227;o d&#233;rmica de IL&#8208;31&#44; IL&#8208;31RA e oncostatina M &#40;OSM&#41; e periostina est&#227;o bem correlacionadas com a intensidade da coceira&#46; Al&#233;m disso&#44; a express&#227;o de OSMR&#946; na derme est&#225; aumentada&#44; apesar de n&#227;o estar correlacionada com a intensidade do prurido&#46; A IL&#8208;31 est&#225; envolvida na coceira em v&#225;rias doen&#231;as&#44; incluindo DA&#44; psor&#237;ase&#44; linfoma cut&#226;neo de c&#233;lulas T&#44; dermatite de estase&#44; penfigoide bolhoso&#44; escabiose e amiloidose cut&#226;nea prim&#225;ria localizada&#46; O PGC expressa 50 vezes mais o mRNA da IL&#8208;31 na pele lesionada&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">21</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">A IL&#8208;31 &#233; produzida principalmente por c&#233;lulas Th2 ativadas&#46; Queratin&#243;citos epid&#233;rmicos&#44; gl&#226;ndulas sudor&#237;paras &#233;crinas&#44; mast&#243;citos&#44; bas&#243;filos&#44; eosin&#243;filos e mon&#243;citos&#47;macr&#243;fagos s&#227;o capazes de liberar IL&#8208;31&#44; pois macr&#243;fagos CD68<span class="elsevierStyleSup">&#43;</span>&#44; al&#233;m de c&#233;lulas T CD3<span class="elsevierStyleSup">&#43;</span>&#44; s&#227;o as principais fontes celulares de IL&#8208;31 em les&#245;es de PGC&#46; Os macr&#243;fagos M2 expressam IL&#8208;31 e podem ser respons&#225;veis pelo prurido em diversas dermatoses&#44; como a dermatite de estase e a escabiose&#46; Portanto&#44; os macr&#243;fagos&#44; juntamente com as c&#233;lulas T&#44; podem ser potencial alvo terap&#234;utico para o prurido associado ao PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">21</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">A intensidade do prurido tamb&#233;m est&#225; intimamente relacionada &#224; express&#227;o d&#233;rmica de IL&#8208;31RA e OSMR&#946; &#40;receptor beta da oncostatina M&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">21</span></a> A maior popula&#231;&#227;o de c&#233;lulas d&#233;rmicas IL&#8208;31RA<span class="elsevierStyleSup">&#43;</span> s&#227;o macr&#243;fagos e mast&#243;citos&#46; As c&#233;lulas d&#233;rmicas OSMR&#946;<span class="elsevierStyleSup">&#43;</span> s&#227;o principalmente macr&#243;fagos&#44; enquanto os mast&#243;citos mal expressavam OSMR&#946;&#46; Isso indica que os macr&#243;fagos podem responder &#224; IL&#8208;31&#44; mas os mast&#243;citos n&#227;o&#46; A maioria das c&#233;lulas infiltradas nas les&#245;es de PGC consiste em macr&#243;fagos&#44; c&#233;lulas T e mast&#243;citos&#46; Considera&#8208;se que essas c&#233;lulas causam inflama&#231;&#227;o e prurido na pele ao secretar citocinas&#47;quimiocinas e pruritog&#234;nios &#40;incluindo IL&#8208;31&#41; e&#44; para macr&#243;fagos&#44; parcialmente em resposta &#224; sinaliza&#231;&#227;o de IL&#8208;31 envolvendo IL&#8208;31RA e OSMR&#946;&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">21</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">A OSM atua nos fibroblastos d&#233;rmicos para liberar a prote&#237;na quimioatrativa de mon&#243;citos 1 &#40;MCP&#8208;1&#41;&#44; o que pode levar &#224; infiltra&#231;&#227;o de mon&#243;citos&#47;macr&#243;fagos com capacidade de liberar IL&#8208;31&#46; Essas fun&#231;&#245;es da OSM podem estar envolvidas na patog&#234;nese do PGC e contribuir para sua associa&#231;&#227;o com o prurido&#46; Relata&#8208;se que os queratin&#243;citos epid&#233;rmicos medeiam o prurido induzido pela IL&#8208;31 pela secre&#231;&#227;o de estimuladores pruritog&#234;nicos quando estimulados pela IL&#8208;31 por meio de seu complexo receptor&#46; A menor express&#227;o de OSMR&#946; epid&#233;rmico pode estar relacionada &#224; redu&#231;&#227;o de FNIPD&#44; pois a insufici&#234;ncia de OSMR&#946; poderia levar &#224; apoptose das fibras nervosas epid&#233;rmicas&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">21</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">O meio d&#233;rmico complexo de c&#233;lulas imunes&#47;citocinas&#47;rede receptora incluindo IL&#8208;31&#44; OSM&#44; IL&#8208;31RA e OSMR&#946; pode desempenhar papel importante na patog&#234;nese do prurido no PGC&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">21&#44;22</span></a> No entanto&#44; em contraste com a DA&#44; a ativa&#231;&#227;o de macr&#243;fagos M1&#47;M2&#44; produ&#231;&#227;o de fator de necrose tumoral&#44; fibrose d&#233;rmica&#44; revasculariza&#231;&#227;o e desregula&#231;&#227;o neural s&#227;o caracter&#237;sticas &#250;nicas do PGC at&#243;pico&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">23</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Uma imunopolariza&#231;&#227;o sist&#234;mica e cut&#226;nea Th22 do PGC leva a outros participantes a interagirem em sua patog&#234;nese&#44; bem como a hiperplasia neuronal d&#233;rmica proeminente&#44; na qual a neurite expressa CGRP e subst&#226;ncia P&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">21</span></a> A IL&#8208;4 induz a prolifera&#231;&#227;o e migra&#231;&#227;o de fibroblastos e estimula a produ&#231;&#227;o de prote&#237;nas da matriz extracelular&#46; A sinaliza&#231;&#227;o hiperativa de IL&#8208;4 e IL&#8208;13 tem sido implicada na patog&#234;nese de doen&#231;as fibr&#243;ticas da pele&#46; IL&#8208;4 e IL&#8208;13 regulam positivamente a atividade do promotor e a transcri&#231;&#227;o de genes pr&#243;&#8208;fibr&#243;ticos&#44; como col&#225;geno tipo I e TGF&#8208;&#946;&#46; O aumento da periostina d&#233;rmica e a diminui&#231;&#227;o da periostina epid&#233;rmica tamb&#233;m foram encontrados em pacientes com PGC em compara&#231;&#227;o com controles saud&#225;veis&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">24</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Al&#233;m disso&#44; h&#225; alguma relev&#226;ncia na participa&#231;&#227;o do microbioma em pacientes com PGC&#44; especialmente o papel de <span class="elsevierStyleItalic">S&#46; aureus</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">25&#44;26</span></a> Al&#233;m disso&#44; a linfopoietina estromal t&#237;mica &#40;TSLP&#41; induz a hiperplasia da pele ativando c&#233;lulas imunes&#44; promovendo a prolifera&#231;&#227;o de queratin&#243;citos &#40;diretamente&#41;&#44; interrompendo a diferencia&#231;&#227;o de queratin&#243;citos e aumentando a express&#227;o de mediadores pr&#243;&#8208;inflamat&#243;rios&#44; contribuindo para o fen&#244;meno da hiperplasia&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">27</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">A IL&#8208;22 est&#225; envolvida em v&#225;rias condi&#231;&#245;es inflamat&#243;rias cr&#244;nicas&#44; como doen&#231;a arterial coronariana e diabetes tipo II &#40;DM2&#41;&#44; ambas comorbidades altamente associadas em pacientes com PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">23</span></a> Na epiderme&#44; n&#237;veis elevados de IL&#8208;22 promovem hiperplasia de queratin&#243;citos e acantose&#44; al&#233;m de atuar sinergicamente com a IL&#8208;17&#44; que promove hiperplasia de queratin&#243;citos e diferencia&#231;&#227;o epid&#233;rmica prejudicada no PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">23</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Observa&#8208;se aumento da express&#227;o de IL&#8208;31 em europeus quando comparados a afro&#8208;americanos&#59; no entanto&#44; a regula&#231;&#227;o positiva de citocinas relacionadas a Th22 no PGC pode ser independente da etnia&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">23</span></a> Em contraste&#44; observou&#8208;se aumento da express&#227;o de citocinas Th2&#44; incluindo IL&#8208;4&#44; IL&#8208;5 e IL&#8208;13&#44; bem como maior ativa&#231;&#227;o de Th2 entre os europeus&#44; mas n&#227;o entre os afro&#8208;americanos&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">23</span></a> Esse perfil de citocinas pode ser a chave para respostas bem&#8208;sucedidas ao tratamento com medicamentos espec&#237;ficos&#44; como o dupilumabe&#44; que pode ser mais eficaz em certos endotipos de pacientes com PGC com atopia associada&#44; envolvendo IL&#8208;4R&#945;&#44; e&#47;ou nemolizumabe em pacientes descendentes de europeus&#46; J&#225; o receptor de IL&#8208;31 &#233; composto de receptor alfa de IL&#8208;31 &#40;IL&#8208;31RA&#41; e receptor beta de oncostatina M &#40;OSMR&#946;&#41;&#44; que s&#227;o dependentes de JAK1&#47;2&#44;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">24</span></a> e indicam uma janela de oportunidade para f&#225;rmacos seletivos da JAK1&#44; como o abrocitinibe e o upadacitinibe&#44; no tratamento do PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">28</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Diagn&#243;stico do prurigo cr&#244;nico e sua avalia&#231;&#227;o</span><p id="par0160" class="elsevierStylePara elsevierViewall">O diagn&#243;stico do PGC &#233; feito clinicamente com base na hist&#243;ria cl&#237;nica&#44; exame cl&#237;nico&#44; histopatol&#243;gico&#44; laboratorial e radiol&#243;gico&#44; que auxiliam na confirma&#231;&#227;o do diagn&#243;stico e determinam a gravidade do PGC&#44; a doen&#231;a subjacente e um plano de tratamento individual&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">A anamnese de pacientes com PGC deve envolver v&#225;rias quest&#245;es objetivas&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a> O exame f&#237;sico geral&#44; dermatol&#243;gico sugerido para o PGC&#44; exames laboratoriais e de imagem complementares recomendados pela diretriz IFSI no PGC&#44;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a> com adapta&#231;&#245;es&#44; com base na pr&#225;tica cl&#237;nica&#44; est&#227;o listados na <a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Variantes de prurigo cr&#244;nico</span><p id="par0170" class="elsevierStylePara elsevierViewall">Em pacientes japoneses&#44; al&#233;m do PGC&#47;prurigo nodular &#40;Hyde&#41;&#44; &#233; referido o prurigo cr&#244;nico multiforme &#40;PCM&#41;&#44; descrito pela primeira vez por Lutz em 1957&#44; como uma desordem cut&#226;nea cr&#244;nica&#44; intensamente pruriginosa&#44; que acomete principalmente indiv&#237;duos idosos&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">29</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Sempre houve confus&#227;o na sinon&#237;mia e classifica&#231;&#227;o das les&#245;es pruriginosas&#44; e Greither incluiu o PCM como variante do prurigo subagudo apresentando um tra&#231;o de neurodermatite&#46;<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">20&#44;30</span></a> A morfologia caracter&#237;stica&#44; o local de predile&#231;&#227;o&#44; a idade e os achados histopatol&#243;gicos do PCM indicam que se trata de dermatose distinta e n&#227;o de variante do prurigo simples subagudo ou cr&#244;nico &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">29</span></a> O &#8220;sinal da borboleta&#8221; &#233; um exemplo de &#8220;fen&#244;meno poupador&#8221; que denota uma &#225;rea de pele normal ou relativamente hipopigmentada toracolombar que &#233; poupada da co&#231;adura em virtude de sua inacessibilidade &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#44; em pacientes com prurido generalizado decorrente de muitos dist&#250;rbios&#44; como doen&#231;a hepatobiliar&#44; dermatite at&#243;pica e PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">31</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">Fujii et al&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">29</span></a> coletaram mais de 30 casos de PCM de 1997 a 2000&#44; seguindo os seguintes crit&#233;rios&#58; i&#41; a les&#227;o prim&#225;ria come&#231;a como les&#227;o intensamente pruriginosa&#44; papular solit&#225;ria ou pruriginosa que se desenvolve na lateral do t&#243;rax&#44; regi&#227;o lombar&#44; n&#225;degas e superf&#237;cies extensoras das coxas&#59; ii&#41; a parte superior das costas&#44; ombros&#44; superf&#237;cies extensoras das extremidades superiores&#44; abdome inferior&#44; t&#243;rax anterior e panturrilhas tamb&#233;m podem ser afetadas&#59; iii&#41; as les&#245;es papulares pruriginosas prim&#225;rias frequentemente se expandem ou coalescem para formar uma placa eritematosa infiltrada&#59; iv&#41; a natureza coalescente da erup&#231;&#227;o prim&#225;ria diferencia o PCM do PGC usual ou do prurigo subagudo&#59; v&#41; o prurido intenso muitas vezes causa &#225;reas focais de eczema agudo sobre e ao redor das les&#245;es em placa&#44; mas componentes seropapulares e&#47;ou descamativos nunca dominam as manifesta&#231;&#245;es cut&#226;neas&#59; vi&#41; uma les&#227;o tipo placa infiltrada se estende al&#233;m do confinamento da &#225;rea cut&#226;nea&#44; que &#233; clinicamente diferente da liquenifica&#231;&#227;o do eczema cr&#244;nico ou da neurodermatite&#59; vii&#41; no exame histopatol&#243;gico&#44; tanto as les&#245;es papulares pruriginosas prim&#225;rias quanto as les&#245;es em placa mostram graus moderados de infiltra&#231;&#227;o perivascular de c&#233;lulas mononucleares contendo popula&#231;&#245;es variadas de eosin&#243;filos na derme reticular e papilar superior&#59; viii&#41; ao contr&#225;rio das les&#245;es prim&#225;rias de prurigo simples subagudo&#44; a epiderme nem sempre apresenta espongiose com exocitose&#44; sugerindo que a espongiose epid&#233;rmica n&#227;o deva ser a principal altera&#231;&#227;o patol&#243;gica da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">29</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Ent&#227;o&#44; essa variante singular de PGC &#233; caracterizada por p&#225;pulas pruriginosas urticariformes ou s&#243;lidas&#44; que &#224;s vezes se juntam para formar placas liquenificadas&#59; as les&#245;es est&#227;o espalhadas pelo tronco e extremidades&#44; e cada erup&#231;&#227;o dura v&#225;rias semanas &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">32</span></a> O PCM ocorre mais frequentemente em homens e em pacientes com idade mais avan&#231;ada&#44; ao contr&#225;rio do PGC&#44; que ocorre mais em mulheres e pacientes de meia&#8208;idade&#44; no Jap&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">32</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Inui et al&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">32</span></a> estudaram 168 casos de prurigo cr&#244;nico no Jap&#227;o &#40;103 com PGC e 65 com PCM&#41; e demonstraram que tanto no PGC quanto no PCM&#44; os n&#237;veis s&#233;ricos de IgE tendiam a ser elevados &#40;&#62; 256 UI&#47;mL&#41;&#44; sugerindo o envolvimento das respostas imunes Th2 no prurigo cr&#244;nico&#46; Esses autores descobriram que os n&#237;veis s&#233;ricos de TARC&#47;CCL17 e o n&#250;mero de eosin&#243;filos no sangue eram maiores no PCM do que no PGC&#46; Al&#233;m disso&#44; a distribui&#231;&#227;o de eosin&#243;filos tamb&#233;m era distinta no PGC e no PCM&#44; mas sua densidade foi compar&#225;vel em ambos os grupos&#46; Esses achados sugerem que o aumento dos n&#237;veis de eosin&#243;filos no sangue perif&#233;rico e o recrutamento dessas c&#233;lulas para &#225;reas com col&#225;geno na derme podem ser importantes para a patog&#234;nese do PCM&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">32</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">O PCM &#233; frequentemente resistente ao tratamento com uma combina&#231;&#227;o de esteroides t&#243;picos e anti&#8208;histam&#237;nicos&#44; particularmente quando a les&#227;o cut&#226;nea est&#225; se expandindo ativamente&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">32</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Todas as formas de PGC apresentam a marca registrada de prurido intenso e les&#245;es secund&#225;rias ao ato de co&#231;ar&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">10</span></a> Embora o PGC seja entidade cl&#237;nica espec&#237;fica&#44; tamb&#233;m pode ser secund&#225;rio a v&#225;rias condi&#231;&#245;es subjacentes&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">33</span></a> O PGC tem impacto significante na qualidade de vida&#44;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">11</span></a> maior do que outras condi&#231;&#245;es de pele em que o prurido &#233; uma caracter&#237;stica marcante&#44; como psor&#237;ase ou DA&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">14</span></a> A ansiedade ocorre em 37&#37; dos pacientes&#44; a depress&#227;o em 29&#37; e a idea&#231;&#227;o suicida em 19&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">13&#44;14</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Especialistas do European Prurigo Project publicaram um consenso em 2018 para propor defini&#231;&#245;es&#44; classifica&#231;&#245;es e terminologia&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">4&#44;13</span></a> O artigo afirma que o PGC &#233; &#8220;uma doen&#231;a distinta definida pela presen&#231;a de prurido cr&#244;nico e m&#250;ltiplas les&#245;es pruriginosas localizadas ou generalizadas&#8221;&#46; A sensibiliza&#231;&#227;o &#224; coceira e o desenvolvimento de um ciclo prurido&#8208;co&#231;adura podem ser de origem dermatol&#243;gica&#44; sist&#234;mica&#44; neurol&#243;gica e psiqui&#225;trica&#47;psicossom&#225;tica&#44; multifatorial ou indeterminada&#8221;&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">4&#44;13</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Histopatologia do prurigo cr&#244;nico</span><p id="par0210" class="elsevierStylePara elsevierViewall">O exame histopatol&#243;gico das les&#245;es cut&#226;neas nodulares do PGC sob microscopia &#243;ptica pode variar dependendo do est&#225;gio e gravidade da les&#227;o e da resposta individual do paciente ao ato de co&#231;ar e &#224; irrita&#231;&#227;o cr&#244;nica&#46; Hiperceratose&#44; escoria&#231;&#227;o&#44; acantose &#40;&#224;s vezes psoriasiforme&#41;&#44; espongiose leve&#44; fibrose d&#233;rmica e infiltrado perivascular leve &#40;linf&#243;citos e eosin&#243;filos escassos&#41; s&#227;o a base da doen&#231;a &#40;<a class="elsevierStyleCrossRef" href="#fig0020">fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0215" class="elsevierStylePara elsevierViewall">Um aumento da densidade de fibras nervosas d&#233;rmicas e altera&#231;&#245;es em muitos tipos de c&#233;lulas da pele&#44; incluindo mast&#243;citos&#44; c&#233;lulas de Merkel&#44; queratin&#243;citos epid&#233;rmicos&#44; c&#233;lulas dendr&#237;ticas&#44; c&#233;lulas endoteliais e fibras de col&#225;geno tamb&#233;m s&#227;o relatados&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">34</span></a> Essas c&#233;lulas causam inflama&#231;&#227;o e prurido por meio da libera&#231;&#227;o de triptase&#44; IL&#8208;31&#44; prostaglandinas&#44; prote&#237;na cati&#244;nica eosin&#243;fila&#44; histamina e outros mediadores como neuropept&#237;deos&#44; incluindo subst&#226;ncia P&#44; pept&#237;deo relacionado ao gene da calcitonina &#40;CGRP&#41; e fator de crescimento&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">34&#44;35</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Tratamento do prurigo cr&#244;nico</span><p id="par0220" class="elsevierStylePara elsevierViewall">O tratamento dos prurigos pode ser desafiador pela hist&#243;ria recorrente das les&#245;es&#44; em virtude de doen&#231;as subjacentes &#40;p&#46; ex&#46;&#44; DA&#44; uremia&#41; ou por limita&#231;&#227;o do uso de medicamentos sist&#234;micos em pacientes suscet&#237;veis a efeitos adversos &#40;p&#46; ex&#46;&#44; idosos&#41;&#46; A <a class="elsevierStyleCrossRef" href="#tbl0025">tabela 5</a> lista uma s&#233;rie de abordagens&#44; farmacol&#243;gicas ou n&#227;o&#44; referidas na literatura para o tratamento de les&#245;es prurigoides&#59; entretanto&#44; somente a correta classifica&#231;&#227;o diagn&#243;stica&#44; identifica&#231;&#227;o de condi&#231;&#245;es subjacentes&#44; investigada criteriosamente &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#41; pode levar ao maior sucesso terap&#234;utico dos casos&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0225" class="elsevierStylePara elsevierViewall">De modo geral&#44; a prescri&#231;&#227;o de emolientes&#44; antipruriginosos t&#243;picos&#44; corticosteroides t&#243;picos&#44; inibidores de calcineurina e anti&#8208;histam&#237;nicos n&#227;o sedantes s&#227;o pouco eficientes no PGC&#44; enquanto anti&#8208;histam&#237;nicos sedantes podem levar a efeitos adversos&#44; especialmente em pacientes que demandem aten&#231;&#227;o profissional &#40;p&#46; ex&#46;&#44; motoristas&#41; ou idosos&#44; que acumulam efeitos anticolin&#233;rgicos&#46; Ademais&#44; a patog&#234;nese do PGC &#233; complexa&#44; e a histamina n&#227;o est&#225; entre as principais mediadoras envolvidas&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Usualmente&#44; o tratamento do PGC depende de medicamentos sist&#234;micos como os corticosteroides&#44; ciclosporina&#44; micofenolato de mofetila&#44; azatioprina&#44; talidomida e neuromoduladores &#40;p&#46; ex&#46;&#44; gabapentina ou pregabalina&#41;&#44; al&#233;m de fototerapia &#40;especialmente <span class="elsevierStyleItalic">narrow&#8208;band</span> UVB&#41;&#46; Mas a demanda pelo uso prolongado dessas op&#231;&#245;es maximiza efeitos adversos&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">O dupilumabe &#233; um anticorpo monoclonal humano IgG4 &#40;mAb&#41; que se liga a IL&#8208;4Ra e inibe a sinaliza&#231;&#227;o de IL&#8208;4R induzida por IL&#8208;4 e IL&#8208;13&#44; e regula negativamente a inflama&#231;&#227;o TH2 na DA e em outras doen&#231;as inflamat&#243;rias e at&#243;picas&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">17</span></a> O dupiluma apresenta efeito antipruriginoso em pacientes com PGC&#46; Dois estudos recentes de fase 3 tamb&#233;m demonstraram que o tratamento com dupilumabe reduziu o prurido e as les&#245;es cut&#226;neas em pacientes com PGC&#59; no Brasil&#44; a indica&#231;&#227;o &#8220;prurigo nodular&#8221; foi incorporada &#224; bula do medicamento&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">36</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">A terapia com dupilumabe reduziu a assinatura de mais de 800 genes afetados na DA&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">37</span></a> Dupilumabe diminui a express&#227;o de mRNA de genes relacionados &#224; hiperplasia epid&#233;rmica &#40;K16 e MKI67&#41;&#44; c&#233;lulas T e c&#233;lulas dendr&#237;ticas &#40;CD1b e CD1c&#41;&#44; e uma inibi&#231;&#227;o potente de quimiocinas associadas &#224; via TH2 &#40;CCL17&#44; CCL18&#44; CCL22 e CCL26&#41; foi observada sem modula&#231;&#227;o significante de genes associados &#224; via TH1 &#40;IFNG&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">37</span></a> Essas a&#231;&#245;es podem explicar a boa resposta do dupilumabe no tratamento do PGC &#40;<a class="elsevierStyleCrossRef" href="#fig0025">fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0245" class="elsevierStylePara elsevierViewall">As les&#245;es cut&#226;neas da DA cr&#244;nica incluem aumento da infiltra&#231;&#227;o por c&#233;lulas T&#44; c&#233;lulas dendr&#237;ticas &#40;DCs&#41; e eosin&#243;filos&#44;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">17</span></a> semelhante ao encontrado nas les&#245;es de PGC&#46; Embora a DA tenha sido classificada como doen&#231;a dominada por TH2&#44; outros subconjuntos de c&#233;lulas T &#40;c&#233;lulas TH22&#44; TH17 e TH1&#41; tamb&#233;m podem contribuir para a patog&#234;nese&#46; Como mencionado&#44; alguns autores encontraram no PGC um <span class="elsevierStyleItalic">upregulation</span> de mRNA da IL&#8208;31&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">35</span></a> A liga&#231;&#227;o da IL&#8208;31 aos seus receptores ativa vias de sinaliza&#231;&#227;o poderosas &#40;ou seja&#44; a ativa&#231;&#227;o de JAK1 e JAK2 e o in&#237;cio da via JAK&#8208;STAT&#41;&#46; Assim&#44; a IL&#8208;31 foi considerada um novo participante na inflama&#231;&#227;o do tipo 2&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Essa teoria foi corroborada pela descoberta de que as c&#233;lulas Th2 s&#227;o uma das principais produtoras de IL&#8208;31&#44; havendo uma correla&#231;&#227;o positiva entre IL&#8208;31 e a gravidade da DA&#46; Al&#233;m disso&#44; n&#237;veis elevados de IL&#8208;31 contribuem para sintomas espec&#237;ficos como prurido&#44; les&#245;es cut&#226;neas e irrita&#231;&#227;o&#47;inflama&#231;&#227;o localizada da DA<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">17</span></a> e eixos de endotelina na pele lesional e perilesional no PGC&#46; Zhong et al&#46; observaram maior express&#227;o do mRNA da IL&#8208;31 nas les&#245;es de cinco pacientes at&#243;picos do que em seis pacientes n&#227;o at&#243;picos&#46; Esses resultados sugerem papel muito mais importante da IL&#8208;31 em pacientes com PGC at&#243;pico <span class="elsevierStyleItalic">versus</span> n&#227;o at&#243;pico&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">38</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">O PGC &#233; doen&#231;a &#243;rf&#227;&#44; com altas taxas associadas a ansiedade&#44; depress&#227;o e alto impacto na qualidade de vida&#46; O prurido cr&#244;nico tamb&#233;m prejudica negativamente o sono e a qualidade de vida&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">39</span></a> Zhai et al&#46;&#44; em um estudo retrospectivo envolvendo 20 pacientes com prurido recalcitrante cr&#244;nico &#40;nove com PGC&#59; cinco com prurido ur&#234;mico&#59; quatro com prurido idiop&#225;tico cr&#244;nico&#59; um com l&#237;quen plano e um com dermatose eosinof&#237;lica relacionada a malignidade hematol&#243;gica&#41;&#44; demonstraram o uso <span class="elsevierStyleItalic">off&#8208;label</span> do dupilumabe e desfecho bem&#8208;sucedido&#44; reduzindo o prurido em todos os pacientes&#44; levando &#224; resolu&#231;&#227;o completa em 12&#47;20 pacientes e m&#233;dia geral da intensidade de prurido na escala de classifica&#231;&#227;o num&#233;rica &#40;NRSi&#41; de 7&#44;55&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">40</span></a> Em idosos&#44; o dupilumabe foi bem tolerado sem grandes efeitos adversos&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">41</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">Entre 90 pacientes adultos com DA tratados com dupilumabe<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">41</span></a> em dois hospitais universit&#225;rios italianos&#44; 10&#44;0&#37; apresentavam PGC generalizado e eram afetados por uma ou mais comorbidades at&#243;picas &#40;rinite al&#233;rgica&#44; asma e conjuntivite al&#233;rgica&#41;&#46; O n&#237;vel s&#233;rico de IgE estava acima do normal em todos os pacientes&#46; Os nove pacientes de PGC foram tratados com dupilumabe com o regime de dosagem padr&#227;o&#46; Ap&#243;s 16 semanas de tratamento&#44; todos os pacientes apresentaram melhora cl&#237;nica acentuada&#46; Nenhum paciente abandonou o tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">41</span></a></p><p id="par0265" class="elsevierStylePara elsevierViewall">A abordagem terap&#234;utica para o PGC tamb&#233;m &#233; baseada em casu&#237;stica e experi&#234;ncia cl&#237;nica&#58; corticosteroides&#44; fototerapia&#44; imunomoduladores t&#243;picos &#40;inibidores t&#243;picos de calcineurina&#41; e imunossupressores &#40;ciclosporina&#44; azatioprina&#44; micofenolato de mofetila e metotrexato&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">42</span></a> neuromoduladores&#44; talidomida que&#44; no entanto&#44; t&#234;m efeitos colaterais indesej&#225;veis potenciais significantes&#44; especialmente em pacientes idosos&#46; Agentes sist&#234;micos s&#227;o frequentemente necess&#225;rios&#44; incluindo corticoides intralesionais&#44; agentes antipruriginosos como anti&#8208;histam&#237;nicos orais&#44; neuromoduladores como gabapentina e pregabalina&#44; al&#233;m de fototerapia&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">43&#8211;45</span></a>Em casos mais graves&#44; os agentes imunossupressores t&#234;m sido usados com sucesso vari&#225;vel e apresentam diversos efeitos colaterais indesej&#225;veis&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">43&#44;44</span></a> Outro aspecto do uso de imunossupressores sist&#234;micos em pa&#237;ses tropicais s&#227;o as doen&#231;as infecciosas end&#234;micas&#44; como as parasitoses gastrintestinais &#40;a profilaxia da estrongiloid&#237;ase &#233; obrigat&#243;ria&#41;&#44; e o risco de pacientes idosos desenvolverem doen&#231;as infecciosas end&#234;micas graves comodengue&#44; Zika e Chikungunya<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">46</span></a> ou novos v&#237;rus epid&#234;micos&#44; como o COVID&#8208;19&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">47</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">De modo geral&#44; uma abordagem racional para o tratamento do PGC pode ser feita levando em considera&#231;&#227;o cinco passos&#46; O primeiro &#233; utilizar corticoides t&#243;picos&#44; inibidores de calcineurina &#40;tacrolimus e pimecrolimus&#41; e fototerapia ultravioleta &#40;<span class="elsevierStyleItalic">narrowband</span> 311<span class="elsevierStyleHsp" style=""></span>nm&#44; Excimer <span class="elsevierStyleItalic">laser</span> e PUVA terapia&#41;&#46; O segundo passo compreende o uso da capsaicina t&#243;pica na concentra&#231;&#227;o que varia de 0&#44;025&#37; a 0&#44;3&#37; de 4 a 6&#215;&#47;dia&#44; al&#233;m do uso oral de gabapentina 300&#8208;900<span class="elsevierStyleHsp" style=""></span>mg&#47;dia at&#233; 3&#215;&#47;dia ou pregabalina 150&#8208;600<span class="elsevierStyleHsp" style=""></span>mg&#47;dia dividida em 2&#8208;3 doses&#46; O terceiro passo consiste no uso de antidepressivos&#44; como a paroxetina 20&#8208;50<span class="elsevierStyleHsp" style=""></span>mg&#47;dia ou a mirtazapina 15<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#46; O quarto passo&#44; para casos em que o controle t&#243;pico e com antidepressivos e&#47;ou gabapentinoides n&#227;o obtiveram melhora&#44; &#233; o uso de imunossupressores como a ciclosporina e o metotrexato&#46; Para casos mais refrat&#225;rios&#44; o quinto passo incluiria tamb&#233;m o uso de antagonistas dos receptores opioides &#956;&#44; como a naltrexona&#59; antagonistas dos receptores da neuroquinina 1&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">48</span></a> Como em metade dos casos de PGC&#44; a DA est&#225; associada&#44; h&#225; uma concord&#226;ncia dos tratamentos entre essas duas entidades&#44; inclusive com o uso de biol&#243;gicos como o dupilumabe e o nemolizumabe&#44; e pequenas mol&#233;culas&#44; como os inibidores de JAK&#44; como upadacitinibe&#44; baricitinibe&#44; tofacitinibe abrocitinibe&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">49</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">O dupilumabe &#233; bem tolerado em crian&#231;as&#44; adultos e idosos&#44; com poucos eventos adversos graves&#44; que incluem nasofaringite&#44; cefaleia&#44; conjuntivite e rea&#231;&#245;es no local da inje&#231;&#227;o&#44; rubor alco&#243;lico em um caso&#44; eritema cut&#226;neo transit&#243;rio e descama&#231;&#227;o&#44; rea&#231;&#245;es locais no local&#44; infec&#231;&#245;es por herpes simples e alopecia&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">50</span></a> Aten&#231;&#227;o especial deve ser dada &#224; prescri&#231;&#227;o de dupilumabe em pacientes com linfoma cut&#226;neo de c&#233;lulas T &#40;micose fungoide&#41;&#44; em virtude do risco de evolu&#231;&#227;o desfavor&#225;vel da doen&#231;a de base&#46;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">51</span></a></p><p id="par0280" class="elsevierStylePara elsevierViewall">Novos f&#225;rmacos emergentes surgem como op&#231;&#245;es promissoras&#44; como o nemolizumabe&#44; um anticorpo humanizado contra o receptor IL&#8208;31 &#945; &#40;IL&#8208;31R&#945;&#41;&#46; A IL&#8208;31 &#233; uma citocina pr&#243;&#8208;inflamat&#243;ria elevada em v&#225;rias dermatoses pruriginosas cr&#244;nicas&#44; e o bloqueio de seu receptor recentemente mostrou redu&#231;&#227;o do escore de prurido em pacientes com PGC&#44; melhora na qualidade de vida e do sono&#44; em compara&#231;&#227;o com o placebo em um estudo duplo&#8208;cego randomizado de 12 semanas&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">52</span></a> Os eventos adversos relatados nesse estudo foram leves e incomuns&#44; principalmente diarreia&#44; dor abdominal e sintomas musculoesquel&#233;ticos&#46; Outro estudo avaliou o transcriptoma de pacientes com PGC ap&#243;s a terapia com nemolizumabe&#44; mostrando fatores inflamat&#243;rios a jusante&#44; ap&#243;s 12 semanas de tratamento&#44; bem como altera&#231;&#245;es no transcriptoma&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">53</span></a> Em decorr&#234;ncia dessas evid&#234;ncias&#44; o FDA considerou recentemente o nemolizumabe uma &#8220;terapia inovadora&#8221; para pacientes com PGC&#46; Mais estudos s&#227;o necess&#225;rios para garantir a efic&#225;cia e seguran&#231;a do inibidor de IL&#8208;31R&#945; em pacientes com PGC e&#44; nesse momento&#44; existem quatro ensaios cl&#237;nicos em andamento&#46;<a class="elsevierStyleCrossRefs" href="#bib0605"><span class="elsevierStyleSup">54&#8211;57</span></a>Outros biol&#243;gicos e pequenas mol&#233;culas est&#227;o atualmente sendo investigados&#44; como os inibidores de IL&#8208;4 e IL&#8208;13&#44; antirreceptores OSM&#946;&#44; inibidores do receptor de tirosina quinase KIT e inibidores da JAK&#46;<a class="elsevierStyleCrossRefs" href="#bib0625"><span class="elsevierStyleSup">58&#8211;61</span></a> O traloquinumabe&#44; um inibidor de IL&#8208;13&#44; mostrou melhora&#44; em um estudo aberto&#44; em pacientes at&#243;picos com PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">61</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">Os inibidores de JAK surgiram mais recentemente como op&#231;&#227;o para o PGC recalcitrante&#44; inibindo a via JAK&#8208;STAT&#44; bloqueando a transcri&#231;&#227;o de IL&#8208;4 e IL&#8208;31&#44; aumentando a densidade das fibras nervosas epid&#233;rmicas e reduzindo o prurido &#40;<a class="elsevierStyleCrossRef" href="#fig0030">fig&#46; 6</a>&#41;&#46; A via JAK&#8208;STAT regula positivamente numerosas citocinas e c&#233;lulas CD4 e j&#225; foi reconhecida pela patog&#234;nese em outras condi&#231;&#245;es cut&#226;neas inflamat&#243;rias&#44; como DA&#46;<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">62&#44;63</span></a> Relatos de casos da efic&#225;cia do tofacitinibe&#44; um inibidor n&#227;o seletivo de JAK1 e JAK3&#44; foram descritos&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">64</span></a> O tofacitinibe t&#243;pico a 2&#37; tamb&#233;m demonstrou redu&#231;&#227;o substancial no prurido em dois pacientes com PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">65</span></a> O abrocitinibe&#44; um inibidor de JAK1 estudado pela primeira vez na DA&#44; est&#225; atualmente sendo estudado para PGC em ensaios cl&#237;nicos&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">66</span></a> Um estudo recente comparou 36 e 13 pacientes &#40;com ou sem DA&#41; em uso de dupilumabe e inibidores orais de JAK &#40;baricitinibe e upadacitinibe&#41;&#44; respectivamente&#46; Ambos os grupos obtiveram respostas semelhantes em rela&#231;&#227;o ao prurido &#40;WI&#8208;NRS&#41;&#44; enquanto os escores IGA PN&#8208;S de 0 ou 1 foram alcan&#231;ados por 40&#44;0&#37; dos pacientes com dupilumabe e 25&#44;0&#37; dos inibidores de JAK&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">67</span></a></p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0290" class="elsevierStylePara elsevierViewall">O melhor conhecimento da patog&#234;nese&#44; associado &#224; disponibilidade de uma gama de novos tratamentos&#44; deve modificar a hist&#243;ria da doen&#231;a e o panorama dos pacientes com PGC&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclus&#245;es</span><p id="par0295" class="elsevierStylePara elsevierViewall">Diversas entidades se manifestam clinicamente como les&#245;es prurigoides&#44; e o correto diagn&#243;stico cl&#237;nico deve preceder o tratamento intempestivo&#46; Al&#233;m disso&#44; os PGC representam dermatose recalcitrante e angustiante&#44; e pelo menos 50&#37; desses pacientes apresentam di&#225;tese at&#243;pica&#44; cujos tratamentos podem induzir efeitos adversos&#44; especialmente em idosos&#46; H&#225; importante comprometimento da qualidade de vida&#44; e&#44; muitas vezes&#44; tratamentos t&#243;picos n&#227;o s&#227;o capazes de controlar os sintomas e as les&#245;es cut&#226;neas&#46; Imunossupressores sist&#234;micos&#44; imunobiol&#243;gicos e inibidores de JAK&#44; apesar do custo e potenciais efeitos adversos&#44; podem ser necess&#225;rios para o controle do PGC e oferecer melhoria cl&#237;nica e na qualidade de vida para esses pacientes&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Suporte financeiro</span><p id="par0300" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Contribui&#231;&#227;o dos autores</span><p id="par0305" class="elsevierStylePara elsevierViewall">Paulo Ricardo Criado&#58; Idealiza&#231;&#227;o do estudo&#44; escrita e aprova&#231;&#227;o do texto final&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">Roberta Fachini Jardim Criado&#58; Idealiza&#231;&#227;o do estudo&#44; escrita e aprova&#231;&#227;o do texto final&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">Mayra Ianhez&#58; Idealiza&#231;&#227;o do estudo&#44; escrita e aprova&#231;&#227;o do texto final&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">Juliana Nakano&#58; Idealiza&#231;&#227;o do estudo&#44; escrita e aprova&#231;&#227;o do texto final&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">Daniel Lorenzini&#58; Idealiza&#231;&#227;o do estudo&#44; escrita e aprova&#231;&#227;o do texto final&#46;</p><p id="par0330" class="elsevierStylePara elsevierViewall">H&#233;lio Amante Miot&#58; Idealiza&#231;&#227;o do estudo&#44; escrita e aprova&#231;&#227;o do texto final&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflito de interesses</span><p id="par0335" class="elsevierStylePara elsevierViewall">Paulo Criado&#58; <span class="elsevierStyleItalic">Advisory board</span> &#8211; Pfizer&#44; Galderma&#44; Takeda&#44; Hypera&#44; Novartis&#44; Sanofi&#59; <span class="elsevierStyleItalic">Pesquisa cl&#237;nica</span> &#8211; Pfizer&#44; Novartis&#44; Sanofi&#44; Amgen e Lilly&#59; <span class="elsevierStyleItalic">Palestrantre</span> &#8211; Pfizer&#44; Abbvie&#44; Sanofi&#8208;Genzyme&#44; Hypera&#44; Takeda&#44; Novartis&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">Roberta Fachini Jardim Criado&#58; <span class="elsevierStyleItalic">Advisory board</span> &#8211; Pfizer&#44; Takeda&#44; Hypera&#44; Novartis&#44; Sanofi&#59; <span class="elsevierStyleItalic">Pesquisa cl&#237;nica</span> &#8211; Pfizer&#44; Novartis&#44; Sanofi e Lilly&#59; <span class="elsevierStyleItalic">Palestrantre</span> &#8211; Pfizer&#44; Abbvie&#44; Sanofi&#8208;Genzyme&#44; Hypera&#44; Takeda&#44; Novartis&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">Mayra Ianhez&#58; <span class="elsevierStyleItalic">Advisory Board</span> &#8211; Galderma&#44; Sanofi&#44; Pfizer&#44; Novartis&#44; Abbvie&#44; Janssen&#44; UCB&#8208;Biopharma&#44; Boehringer&#8208;Ingelheim&#59; <span class="elsevierStyleItalic">Palestrante</span> &#8211; Galderma&#44; Sanofi&#44; Pfizer&#44; Theraskin&#44; Novartis&#44; Abbvie&#44; Janssen&#44; Leopharma&#44; FQM&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">Juliana Nakano&#58; <span class="elsevierStyleItalic">Advisory Board</span> &#8211; Novartis&#44; Abbvie&#44; Janssen&#44; Boehringer&#8208;Ingelheim&#59; <span class="elsevierStyleItalic">Palestrante</span> &#8211; Sanofi&#44; LeoPharma&#44; Lilly&#44; Novartis&#44; Abbvie&#44; Janssen&#44; Boehringer&#8208;Ingelheim&#46;</p><p id="par0355" class="elsevierStylePara elsevierViewall">Daniel Lorenzini&#58; <span class="elsevierStyleItalic">Advisory Board</span> &#8211; Abbvie&#44; Sanofi&#44; Galderma&#59; <span class="elsevierStyleItalic">Palestrante</span> &#8211; Sanofi&#44; Abbvie&#44; Pfizer&#44; Lilly&#44; Leopharma&#46;</p><p id="par0360" class="elsevierStylePara elsevierViewall">H&#233;lio Miot&#58; <span class="elsevierStyleItalic">Advisory Board</span> &#8211; Johnson &#38; Johnson&#44; L&#8217;Or&#233;al&#44; Theraskin&#44; Sanofi e Pfizer&#59; P<span class="elsevierStyleItalic">esquisa cl&#237;nica</span> &#8211; Abbvie&#44; Galderma e Merz&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Prurigo &#233; condi&#231;&#227;o reativa hiperpl&#225;sica da pele caracterizada por p&#225;pulas&#44; placas e&#47;ou n&#243;dulos pruriginosos&#46; Temporalmente&#44; s&#227;o classificados como agudo&#47;subagudo e cr&#244;nico &#40;&#8805; 6 semanas&#41;&#44; com diferentes variantes cl&#237;nicas&#44; sinon&#237;mias&#44; e fatores etiol&#243;gicos subjacentes&#46; A imunologia do prurigo cr&#244;nico mostra semelhan&#231;as com a dermatite at&#243;pica em virtude do envolvimento de IL&#8208;4 e IL&#8208;13&#44; IL&#8208;22 e IL&#8208;31&#46; O tratamento varia desde anti&#8208;histam&#237;nicos&#44; esteroides t&#243;picos&#44; dupilumabe e inibidores de Janus Quinases &#40;JAK&#41;&#46; Diversas entidades se manifestam clinicamente como les&#245;es prurigoides&#44; e o correto diagn&#243;stico cl&#237;nico deve preceder o tratamento intempestivo&#46; Al&#233;m disso&#44; prurigos cr&#244;nicos representam dermatose recalcitrante e angustiante&#44; e pelo menos 50&#37; desses pacientes apresentam di&#225;tese at&#243;pica&#44; cujo tratamento pode induzir efeitos adversos&#44; especialmente em idosos&#46; H&#225; importante comprometimento da qualidade de vida&#44; e&#44; muitas vezes&#44; os tratamentos t&#243;picos n&#227;o s&#227;o capazes de controlar os sintomas e as les&#245;es cut&#226;neas&#46; Imunossupressores sist&#234;micos&#44; imunobiol&#243;gicos e inibidores de JAK&#44; apesar do custo e de potenciais efeitos adversos&#44; podem ser necess&#225;rios para obter melhoria cl&#237;nica e na qualidade de vida&#46; Este manuscrito revisa os principais tipos de prurigo&#44; doen&#231;as associadas&#44; suas bases imunol&#243;gicas&#44; diagn&#243;stico e tratamento&#46;</p></span>"
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                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Doen&#231;as dermatol&#243;gicas associadas ao prurigo cr&#244;nico</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prurigo cr&#244;nico sem les&#245;es cut&#226;neas de outras dermatoses</th></tr></thead><tbody title="tbody"><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">Doen&#231;as inflamat&#243;rias ou parasit&#225;rias da pele&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">Dermatite at&#243;pica&#44; l&#237;quen plano&#44; escabiose&#44; l&#237;quen simples cr&#244;nico&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">Condi&#231;&#245;es infecciosas&#47;parasit&#225;rias&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">Parasitoses gastrintestinais&#44; hepatites cr&#244;nicas&#44; infec&#231;&#227;o por HIV&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">Prurigo relacionado a f&#225;rmaco&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">Eczema de contato&#44; rea&#231;&#245;es adversas a f&#225;rmaco&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">Doen&#231;as metab&#243;licas ou endocrinopatias&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">Dermatoses adquiridas perfurantes&#44; insufici&#234;ncia renal cr&#244;nica&#44; doen&#231;as colest&#225;ticas hep&#225;ticas&#44; hiper&#47;hipotiroidismo&#44; amiloidose nodular&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">Doen&#231;as autoimunes&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">Dermatoses bolhosas autoimunes &#40;dermatite herpetiforme&#44; penfigoide bolhoso&#44; dermatose por IgA linear&#44; p&#234;nfigo vegetante&#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">F&#225;rmacos&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">Inibidores da enzima conversora de angiotensina &#40;IECA&#41;&#44; antagonistas do receptor da angiotensina&#44; morfina&#44; amiodarona&#44; hidroclorotiazida&#44; alopurinol&#44; entre outras&#46;&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">Genodermatoses&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">Dermatose acantol&#237;tica transit&#243;ria &#40;doen&#231;a de Grover&#41;&#44; doen&#231;a de Darier&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">Psiqui&#225;tricas&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">Condi&#231;&#245;es psic&#243;ticas ou neur&#243;ticas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;as neopl&#225;sicas</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Linfoma cut&#226;neo de c&#233;lulas T ou B&#44; <span class="elsevierStyleItalic">leukaemia cutis</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Causas neurop&#225;ticas</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">Prurido braquiorradial&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">Neuralgia p&#243;s&#8208;herp&#233;tica&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">Polineuropatia ou mononeurite&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">Doen&#231;as psiqui&#225;tricas&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">Prurido associado a ansiedade&#44; depress&#227;o ou outras condi&#231;&#245;es psiqui&#225;tricas&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">Estase venosa&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"><span class="elsevierStyleItalic">Prurigo nodularis</span> em virtude do prurido e ato de co&#231;ar das veias varicosas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3644940.png"
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        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Doen&#231;as dermatol&#243;gicas associadas a prurido e prurigo cr&#244;nico&#44; e prurido&#47;prurigo cr&#244;nico sem les&#245;es cut&#226;neas de outras dermatoses<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">1&#44;21</span></a></p>"
        ]
      ]
      8 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Tabela 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Crit&#233;rios maiores&#58;</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">i&#41; Prurido cr&#244;nico &#40;&#8805; 6 semanas&#41;&#59;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ii&#41; Hist&#243;ria e&#47;ou sinais de prurido repetidos&#59;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">iii&#41; Presen&#231;a de m&#250;ltiplas les&#245;es pruriginosas localizadas ou generalizadas<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="17" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Crit&#233;rios associados&#58;</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">i&#41; Sinais cl&#237;nicos</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">Les&#245;es pruriginosas&#58; simetricamente distribu&#237;das&#44; raramente afetando a face e palmas&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">Sinais do ato de co&#231;ar&#58; escoria&#231;&#245;es&#44; cicatrizes&#44; liquenifica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ii&#41; Diversidade de manifesta&#231;&#245;es cl&#237;nicas</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">Tipo papular&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">Tipo nodular&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">Tipo placa&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">Tipo umbilicado&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">Tipo linear&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">iii&#41; Sintomas</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">Usualmente&#44; as les&#245;es pruriginosas se desenvolvem ap&#243;s o in&#237;cio do prurido&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">Qualidade&#58; prurido&#44; queima&#231;&#227;o&#44; dor ou pinica&#231;&#227;o&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">Sinais de cronicidade&#58; intensidade importante do prurido&#44; alocinesia&#44; hipercinesia&#44; aumento cont&#237;nuo no n&#250;mero de les&#245;es&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">Qualidade de vida prejudicada&#44; perda de sono&#44; dias de absente&#237;smo ao trabalho e&#47;ou comportamento obsessivo&#8208;compulsivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">iv&#41; Emo&#231;&#245;es</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">Depress&#227;o&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">Ansiedade&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">Raiva&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">Desgosto&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">Vergonha&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">Desamparo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab3644939.png"
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          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Defini&#231;&#227;o de les&#245;es pruriginosas&#58; escoriadas&#44; p&#225;pulas e&#47;ou n&#243;dulos e&#47;ou placas descamativas e crostosas&#44; frequentemente com um centro esbranqui&#231;ado ou r&#243;seo e borda hiperpigmentada&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Diretriz do F&#243;rum Internacional sobre o Estudo do Prurido &#40;IFSI&#41; sobre crit&#233;rios diagn&#243;sticos de prurigo cr&#244;nico&#46; Os tr&#234;s crit&#233;rios maiores s&#227;o necess&#225;rios para estabelecer o diagn&#243;stico de prurigo cr&#244;nico&#46; Os crit&#233;rios menores est&#227;o frequentemente presentes&#44; mas n&#227;o s&#227;o obrigat&#243;rios<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a></p>"
        ]
      ]
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        "identificador" => "tbl0020"
        "etiqueta" => "Tabela 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
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            "identificador" => "at4"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">I&#46; EXAME F&#205;SICO&#58;</span>&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="elsevierStyleBold">1&#46; Exame dermatol&#243;gico&#58;</span>&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>&#8208; Distribui&#231;&#227;o cl&#237;nica das les&#245;es pruriginosas &#40;p&#46; ex&#46;&#44; localizadas&#47;generalizadas&#59; sim&#233;tricas&#47;assim&#233;tricas&#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="elsevierStyleHsp" style=""></span>&#8208; Morfologia dermatol&#243;gica das les&#245;es pruriginosas&#59;&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>&#8208; N&#250;mero de regi&#245;es do corpo afetadas&#59; n&#250;mero de les&#245;es pruriginosas&#47;com escoria&#231;&#245;es no topo&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>&#8208; <span class="elsevierStyleItalic">Sinal da borboleta</span> &#40;&#225;rea poupada de les&#245;es ou escoria&#231;&#245;es no dorso&#44; onde as m&#227;os do paciente n&#227;o alcan&#231;am&#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="elsevierStyleBold">2&#46; M&#233;todos objetivos&#58;</span>&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>&#8208; Medida das les&#245;es pruriginosas &#40;com r&#233;gua ou outro equipamento&#41;&#59;&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>&#8208; Monitoramento de les&#227;o alvo quando for poss&#237;vel &#40;clinicamente ou por fotos&#41;&#59;&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>&#8208; Documenta&#231;&#227;o fotogr&#225;fica&#59;&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>&#8208; Escores&#58; IGA<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&#44; para o estadiamento do prurigo cr&#244;nico&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="elsevierStyleBold">3&#46; Exame f&#237;sico geral&#58;</span>&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>&#8208; Palpa&#231;&#227;o abdominal&#44; avalia&#231;&#227;o de linfadenopatias&#44; avalia&#231;&#227;o da for&#231;a muscular&#44; ausculta &#40;pulm&#227;o&#44; cora&#231;&#227;o&#44; abdome&#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="elsevierStyleHsp" style=""></span>&#8208; Exame neurol&#243;gico simples&#59;&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>&#8208; Exame dermatol&#243;gico&#58; presen&#231;a de doen&#231;as de pele concomitantes&#44; xerose&#44; inspe&#231;&#227;o das mucosas&#59;&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>&#8208; Dermatoscopia das les&#245;es pruriginosas &#40;em busca de ectoparasitas como o <span class="elsevierStyleItalic">Sarcoptes scabiei</span>&#41;&#59;&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>&#8208; Pesquisa de dermografismo&#59; pesquisa do sinal de Nikolsky&#59; pesquisa do sinal de Darier&#46;&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="elsevierStyleBold">II&#46; BIOPSIAS DE PELE&#47;FLUIDOS &#47;SANGUE&#58;</span>&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">1&#46; Biopsias de pele&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46; Fluidos&#47;cultura microbiol&#243;gica se sinais de infec&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46; Avalia&#231;&#227;o microsc&#243;pica direta&#58; pesquisa de <span class="elsevierStyleItalic">Sarcoptes scabiei</span>&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>&#8208; Imunofluoresc&#234;ncia direta e indireta &#40;se h&#225; suspei&#231;&#227;o de condi&#231;&#245;es autoimunes como penfigoide bolhoso&#44; dermatite herpetiforme&#44; dermatose por IgA linear&#44; p&#234;nfigo paraneopl&#225;sico etc&#46;&#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="elsevierStyleHsp" style=""></span>&#8208; Histopatologia &#40;colora&#231;&#227;o com hematoxilina &#38; eosina ou colora&#231;&#245;es histoqu&#237;micas para dep&#243;sito de subst&#226;ncia amiloide&#44; mucina&#44; e outras desordens cut&#226;neas de dep&#243;sito&#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="elsevierStyleBold">III&#46; EXAMES DIAGN&#211;STICOS COMPLEMENTARES</span>&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="elsevierStyleBold">1&#46; Evitar procedimentos diagn&#243;sticos invasivos&#44; se desnecess&#225;rios&#44; para&#58;</span>&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>&#8208; PGC com prurido de leve intensidade ou pequena extens&#227;o&#59;&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>&#8208; PGC de origem n&#227;o dermatol&#243;gica&#59;&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"><span class="elsevierStyleHsp" style=""></span>&#8208; Pacientes idosos ou pedi&#225;tricos e fr&#225;geis&#46;&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="elsevierStyleBold">2&#46; Grupos de pacientes nos quais estudos de imagem e laborat&#243;rio s&#227;o recomendados&#58;</span>&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"><span class="elsevierStyleHsp" style=""></span>&#8208; Dependendo da hist&#243;ria familiar&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>&#8208; Dependendo do hist&#243;rico m&#233;dico &#40;p&#46; ex&#46;&#44; presen&#231;a de escarro com sangue&#44; mudan&#231;a do perfil de tosse&#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="elsevierStyleHsp" style=""></span>&#8208; Em todos os pacientes com PGC&#44; descartar doen&#231;as subjacentes&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>&#8208; Em todos os pacientes com PGC cuja doen&#231;a tem dura&#231;&#227;o de&#44; pelo menos&#44; um ano&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>&#8208; Em pacientes com PGC que relatam sudorese noturna ou perda ponderal&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>&#8208; Em pacientes com PGC de origem indeterminada&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>&#8208; Em pacientes com PGC com prurido desproporcional&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>&#8208; Quando os pacientes demandam realizar exames laboratoriais&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="elsevierStyleBold">3&#46; Exames laboratoriais regularmente realizados&#58;</span>&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>&#8208; Hemograma&#59; eletr&#243;litos&#44; VHS&#44; PCR&#44; glicemia de jejum&#44; hemoglobina glicada &#40;HbA1c&#41;&#44; ferro&#44; ferritina&#44; LDH&#44; TSH&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>&#8208; IgE s&#233;rica total&#44; IgE espec&#237;fica &#40;se alergia respirat&#243;ria ou ocular forem suspeitas&#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="elsevierStyleHsp" style=""></span>&#8208; Par&#226;metros de reten&#231;&#227;o renal &#40;p&#46; ex&#46;&#44; pot&#225;ssio&#44; creatinina&#44; ureia&#44; taxa de filtra&#231;&#227;o glomerular&#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="elsevierStyleHsp" style=""></span>&#8208; Enzimas hep&#225;ticas &#40;p&#46; ex&#46;&#44; gama&#8208;GT&#44; TGO&#44; TGP&#44; fosfatase alcalina&#44; bilirrubinas&#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="elsevierStyleBold">4&#46; Exames laboratoriais &#8211; com base nos achados patol&#243;gicos ou hist&#243;ria m&#233;dica&#58;</span>&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\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8208; Eletroforese de prote&#237;nas s&#233;ricas e urin&#225;rias&#44; imunofixa&#231;&#227;o &#40;maior sensibilidade se gamopatia monoclonal for suspeita&#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="elsevierStyleHsp" style=""></span>&#8208; Imunofenotipagem por citometria de fluxo para neoplasias hematol&#243;gicas no sangue perif&#233;rico<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">b</span></a>&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
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Prurigo: revisão de sua patogênese, diagnóstico e tratamento
Paulo Ricardo Criadoa,b,
Autor para correspondência
prcriado@uol.com.br

Autor para correspondência.
, Mayra Ianhezc, Roberta Fachini Jardim Criadoa,d, Juliana Nakanoe, Daniel Lorenzinif, Hélio Amante Miotg
a Centro Universitário Faculdade de Medicina do ABC, Santo André, SP, Brasil
b Faculdade de Ciências Médicas de Santos (Fundação Lusíada), Santos, SP, Brasil
c Departamento de Dermatologia, Hospital de Doenças Tropicais de Goiás, Goiânia, GO, Brasil
d Alergoskin Alergia e Dermatologia, UCARE Center and ADCARE, Santo André, SP, Brasil
e Ambulatório de Dermatologia, Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brasil
f Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
g Departamento de Infectologia, Dermatologia, Diagnóstico por Imagem e Radioterapia, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP, Brasil
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          "pt" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Prurigo cr&#244;nico &#40;PGC&#41; e a morfologia elementar de les&#245;es&#46; &#40;A&#41; P&#225;pula &#40;&#60; 1<span class="elsevierStyleHsp" style=""></span>cm de di&#226;metro&#41; e n&#243;dulos &#40;&#62; 1<span class="elsevierStyleHsp" style=""></span>cm de di&#226;metro&#41;&#46; &#40;B&#41; Coalesc&#234;ncia de p&#225;pulas e n&#243;dulos &#40;placa&#41; e les&#245;es em arranjo linear&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">Prurigo &#233; condi&#231;&#227;o cut&#226;nea hiperpl&#225;sica reativa caracterizada por p&#225;pulas&#44; placas e&#47;ou n&#243;dulos&#44; isolados ou m&#250;ltiplos&#44; com prurido intenso&#46; Alguns autores classificam o prurigo de acordo com o tipo &#40;agudo&#44; subagudo ou cr&#244;nico&#41; ou forma cl&#237;nica ou agente causador&#47;doen&#231;a associada&#46; H&#225; vasta sinon&#237;mia e descri&#231;&#227;o de quadros superpon&#237;veis&#44; sob a mesma denomina&#231;&#227;o&#44; o que dificulta a revis&#227;o da informa&#231;&#227;o dispon&#237;vel&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">1&#8211;3</span></a>O termo &#8220;prurigo&#8221; foi originado do latim <span class="elsevierStyleItalic">pruire</span>&#44; que significa coceira&#44; nominado por Ferdinand von Hebra ao caracterizar p&#225;pulas e n&#243;dulos com prurido intenso&#44; em Viena&#44; em 1850&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">3&#44;4</span></a> Outros autores&#44; por&#233;m&#44; atribuem a Robert Willan&#44; h&#225; mais de 200 anos&#44; a descri&#231;&#227;o de p&#225;pulas pruriginosas sob o termo prurigo&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Este manuscrito revisa os principais tipos de prurigo&#44; doen&#231;as associadas&#44; suas bases imunol&#243;gicas&#44; diagn&#243;stico e tratamento&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Formas cl&#237;nicas de prurigo</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Prurigo agudo&#47;subagudo</span><p id="par0015" class="elsevierStylePara elsevierViewall">O prurigo agudo compreende les&#245;es com dura&#231;&#227;o ef&#234;mera &#40;&#8804; 6 semanas&#41;&#44; podendo haver surtos de reagudiza&#231;&#227;o&#46; Compreende uma variedade de manifesta&#231;&#245;es cl&#237;nicas como p&#225;pulas eritematosas intensamente pruriginosas&#44; frequentemente exibindo ves&#237;cula central&#44; em &#225;reas cobertas por roupas &#40;t&#243;rax&#44; abdome&#41;&#44; ou principalmente n&#227;o cobertas&#44; como antebra&#231;os&#44; bra&#231;os&#44; pernas&#44; m&#227;os e p&#233;s &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#44; dependendo do agente indutor&#46; Les&#245;es at&#237;picas podem estar associadas&#44; como ves&#237;culas&#44; bolhas&#44; crostas e les&#245;es urticariformes&#44; em que a superinfec&#231;&#227;o estafiloc&#243;cica &#233; comum&#46; O prurigo agudo geralmente ocorre em virtude de picada de artr&#243;podes&#59; &#233; comumente referido na literatura pedi&#225;trica como prurigo estr&#243;fulo&#44; que privilegia crian&#231;as de 2 a 7 anos&#44; em &#225;reas tropicais&#44; com fundo imunol&#243;gico at&#243;pico e baixo n&#237;vel socioecon&#244;mico&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">2&#44;6</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">A reativa&#231;&#227;o de les&#245;es antigas ap&#243;s novas picadas de insetos em outras topografias &#233; descrita&#44; assim como a forma&#231;&#227;o de bolhas e ves&#237;culas nos locais das novas picadas &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Les&#245;es mais exuberantes aparecem em indiv&#237;duos predispostos&#44; principalmente em at&#243;picos&#46; O conte&#250;do das les&#245;es geralmente &#233; citrino&#44; refletindo o plasma exsudado das les&#245;es&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Em geral&#44; o prurigo agudo n&#227;o requer exames complementares extensos&#46; Seu tratamento deve ser orientado de acordo com o agente causador&#46; O tratamento &#233; sintom&#225;tico&#58; anti&#8208;histam&#237;nicos &#40;anti&#8208;H1&#41; n&#227;o sedantes de dia e sedantes &#224; noite&#44; cuidados antiss&#233;pticos di&#225;rios&#44; corte de unhas para evitar superinfec&#231;&#227;o bacteriana e corticosteroides t&#243;picos&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">No entanto&#44; a exposi&#231;&#227;o a picadas intermitentes de artr&#243;podes pode conduzir a uma forma de prurido agudo referido como urtic&#225;ria papular &#40;UP&#41;&#44; que &#233; induzida principalmente por picada de pulga&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">A UP &#233; condi&#231;&#227;o al&#233;rgica cr&#244;nica em que a melhora cl&#237;nica pode ocorrer em torno dos 7 anos&#44; representando um modelo natural de toler&#226;ncia imunol&#243;gica adquirida&#46; Em pacientes com UP&#44; estudos imunol&#243;gicos demonstraram mais c&#233;lulas&#8208;T CLA4<span class="elsevierStyleSup">&#43;</span> espec&#237;ficas da pele para ant&#237;genos de pulgas secretando IFN&#8208;&#947;&#44; IL&#8208;4&#44; IL&#8208;10 e IL&#8208;17&#44; quando comparadas a controles saud&#225;veis&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">8&#44;9</span></a> Curiosamente&#44; ap&#243;s mais de cinco anos de dura&#231;&#227;o da doen&#231;a&#44; as c&#233;lulas T CLA4<span class="elsevierStyleSup">&#43;</span> da pele perdem sua capacidade de produzir IL&#8208;4&#44; enquanto mant&#234;m em grande parte sua capacidade de secre&#231;&#227;o de IL&#8208;10 e IL&#8208;17&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">8&#44;9</span></a> Alinhado com essa hip&#243;tese&#44; a frequ&#234;ncia de c&#233;lulas T positivas para IFN&#8208;&#947; &#233; reduzida tanto em linf&#243;citos residentes ou n&#227;o&#44; na pele nesses pacientes&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Celiksoy et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">10</span></a> estudaram 130 pacientes com UP &#40;idade mediana&#58; 60 meses&#41;&#46; A preval&#234;ncia de sibilos recorrentes e dermatite at&#243;pica &#40;DA&#41; foi maior no grupo &#60;<span class="elsevierStyleHsp" style=""></span>5 anos com UP do que no grupo controle da mesma idade&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">10</span></a> A preval&#234;ncia de asma&#44; rinite al&#233;rgica e DA foi maior no grupo &#62;<span class="elsevierStyleHsp" style=""></span>5 anos com UP do que o grupo controle da mesma idade&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">10</span></a> Esses pacientes devem ser avaliados n&#227;o apenas em termos de UP&#44; mas tamb&#233;m em termos de doen&#231;as at&#243;picas com&#243;rbidas&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">8&#44;10</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Prurigo cr&#244;nico</span><p id="par0045" class="elsevierStylePara elsevierViewall">O prurigo cr&#244;nico &#40;PGC&#41; tem sua dura&#231;&#227;o definida por mais de 6 semanas&#44; e pode ser classificado em tr&#234;s subtipos&#44; se associado&#47;causado por outras dermatoses ou n&#227;o&#58; a&#41; PGC com les&#245;es cut&#226;neas associadas&#59; b&#41; PGC sem les&#245;es cut&#226;neas associadas&#59; ou c&#41; PGC de origem indeterminada&#46; Um consenso japon&#234;s classificou os tipos de prurigo de acordo com sua causa relacionada&#44; conforme demonstrado na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">1</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">O PGC sem associa&#231;&#227;o com outras les&#245;es cut&#226;neas pode estar relacionado a doen&#231;as internas ou sist&#234;micas&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">2&#44;11&#44;12</span></a> Na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#44; demonstramos doen&#231;as dermatol&#243;gicas associadas ao PGC com ou sem les&#245;es cut&#226;neas de outras dermatoses&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Morfologicamente&#44; o PGC pode ser designado como prurigo nodular cr&#244;nico &#40;predominam os n&#243;dulos&#41;&#44; prurigo papular cr&#244;nico &#40;predominam as p&#225;pulas&#41;&#44; PGC em placas &#40;predominam as placas&#41;&#44; PGC umbilicado &#40;predominam as les&#245;es pruriginosas ulceradas&#41; ou linear &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46; Entretanto&#44; como morfologias distintas podem estar presentes no mesmo paciente simultaneamente e suas caracter&#237;sticas podem evoluir e mudar ao longo do tempo&#44; todos esses fen&#243;tipos ser&#227;o tratados como PGC&#44; nesse texto&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">4&#44;13&#44;14</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Dados epidemiol&#243;gicos sobre o PGC s&#227;o escassos na literatura&#46; Alguns autores estimam 72 casos por 100&#46;000 pessoas&#44; o que provavelmente sejam subestimados por subnotifica&#231;&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">4&#44;14</span></a> Docampo&#8208;Sim&#243;n et al&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">13</span></a> relataram que&#44; em sua pr&#225;tica cl&#237;nica&#44; o PGC &#233; mais frequente em pacientes com idade entre 50 e 60 anos e entre afro&#8208;americanos&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">14</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Zeidler et al&#46; estudaram 1&#46;128 pacientes de PGC na Alemanha entre 2004 e 2018&#44; dos quais 61&#44;4&#37; eram do sexo feminino&#59; a preval&#234;ncia aumenta com a idade&#44; e a dura&#231;&#227;o mediana do PGC foi de 2&#44;9 anos antes do diagn&#243;stico pelo estudo&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">15</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Especialistas europeus e americanos em prurido desenvolveram a diretriz do F&#243;rum Internacional sobre o Estudo do Prurido &#40;IFSI&#41; sobre PGC&#44; incluindo prurigo nodular como seu sin&#244;nimo&#59; foram estabelecidos crit&#233;rios diagn&#243;sticos para PGC &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a> As defini&#231;&#245;es japonesas s&#227;o alinhadas&#44; embora ligeiramente diferentes&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">1</span></a> De acordo com a classifica&#231;&#227;o etiol&#243;gica do IFSI&#44; o PGC pode ainda ser de origem dermatol&#243;gica&#44; sist&#234;mica&#44; neurol&#243;gica&#44; psiqui&#225;trica&#47;psicossom&#225;tica&#44; multifatorial ou desconhecida&#44; atentando para a relev&#226;ncia da investiga&#231;&#227;o etiol&#243;gica em seu tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">O PGC induz um ciclo prurido&#8208;co&#231;adura&#44; bem como fen&#244;menos de sensibiliza&#231;&#227;o neuronal&#44; que contribuem para o desenvolvimento e perpetua&#231;&#227;o do PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a> Esses mecanismos s&#227;o independentes da origem do prurido&#44; uma vez que o desenvolvimento do PGC &#233; observado em diferentes etiologias subjacentes do prurido &#8211; p&#46; ex&#46;&#44; na DA&#44; prurido nefrog&#234;nico ou s&#237;ndromes de compress&#227;o neurol&#243;gica&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a> Em idosos&#44; muitas comorbidades independentes podem estar presentes&#44; mas sem representar causa desencadeante do PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a> Portanto&#44; a doen&#231;a subjacente do PGC n&#227;o &#233; f&#225;cil de estabelecer&#44; e alguns termos&#44; como &#8220;dermatite at&#243;pica prurigoide&#8221;&#44; devem ser evitados em favor de afirmar que existem duas entidades distintas&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a></p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Patog&#234;nese do prurigo cr&#244;nico</span><p id="par0080" class="elsevierStylePara elsevierViewall">Em pacientes at&#243;picos&#44; estudos imunol&#243;gicos e gen&#233;ticos delinearam vias inflamat&#243;rias al&#233;rgicas comuns a diversas condi&#231;&#245;es&#44; como DA&#44; asma&#44; alergia alimentar&#44; entre outras&#44; das quais a patog&#234;nese central &#233; a via do receptor da interleucina 4 &#40;IL&#8208;4R&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">17</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">O eixo IL&#8208;4&#47;IL&#8208;13&#47;IL&#8208;4R promove a diferencia&#231;&#227;o das c&#233;lulas T helper tipo 2 &#40;TH2&#41;&#44; que medeiam a resposta imune adaptativa pr&#243;&#8208;al&#233;rgica&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">17</span></a> Uma vez que a IL&#8208;4 ou IL&#8208;13 se liga aos receptores&#44; elas desencadeiam a transfosforila&#231;&#227;o e a ativa&#231;&#227;o das prote&#237;nas quinases da fam&#237;lia Janus &#40;JAKs&#41; associadas &#224; subunidade do receptor&#44; incluindo JAK1&#44; JAK3 e JAK2&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">17</span></a> No entanto&#44; v&#225;rias outras condi&#231;&#245;es est&#227;o relacionadas ao PGC&#44; e sua patog&#234;nese &#233; baseada na sensibiliza&#231;&#227;o do prurido e nas intera&#231;&#245;es entre pruriceptores e c&#233;lulas da pele&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">18</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">O prurido envolve estruturas e c&#233;lulas com origem em tecidos neuroectod&#233;rmicos&#46; Existem dois principais envolvidos na patog&#234;nese do PGC&#58; o sistema nervoso central e as c&#233;lulas imunes da pele&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">18</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Ocorrem altera&#231;&#245;es funcionais encef&#225;licas associadas &#224; sensibiliza&#231;&#227;o ao prurido que mostram ativa&#231;&#227;o aumentada de algumas &#225;reas associadas a altera&#231;&#245;es estruturais&#44; como diminui&#231;&#227;o da massa cinzenta em algumas regi&#245;es do c&#233;rebro&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Na medula espinal&#44; a regula&#231;&#227;o anormal das vias inibit&#243;rias do prurido pode explicar a sensibiliza&#231;&#227;o central&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">18</span></a> A sensibiliza&#231;&#227;o perif&#233;rica tem sido atribu&#237;da ao aumento da excitabilidade do nervo sensorial em virtude da hiperinerva&#231;&#227;o &#40;na derme&#41; e&#47;ou &#224; perda de inerva&#231;&#227;o &#40;fibras nervosas intraepid&#233;rmicas de pequeno di&#226;metro&#44; FNIPD&#41;&#44; bem como ao aumento da express&#227;o&#44; sensibilidade e&#47;ou capacidade de resposta de pruriceptores&#44; que contribuem para a hipersensibilidade dos neur&#244;nios sensoriais aos pruritog&#234;nicos&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">10</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Na pele&#44; os queratin&#243;citos interagem com termina&#231;&#245;es nervosas sensoriais&#44; especialmente pruriceptores das FNIPD&#44; por meio de contatos sin&#225;pticos&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">18</span></a> A percep&#231;&#227;o da coceira e o aparecimento de les&#245;es de prurigo est&#227;o relacionados a essas intera&#231;&#245;es e com outras c&#233;lulas do seu ambiente&#44; como mast&#243;citos&#44; eosin&#243;filos&#44; c&#233;lulas dendr&#237;ticas ou linf&#243;citos T&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">18</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Em camundongos&#44; foram identificados tr&#234;s tipos de termina&#231;&#245;es nervosas pruriceptivas&#58; a&#41; neur&#244;nios D&#43; MRGPR &#40;receptor acoplado &#224; prote&#237;na G relacionada a Mas&#41;&#59; b&#41; neur&#244;nios que expressam MRGPRA3&#44; MMRGPRC11&#44; receptores de histamina e o receptor de IL&#8208;33&#59; e c&#41; termina&#231;&#245;es nervosas que expressam receptores de serotonina e o receptor de IL&#8208;31&#46; Muitos genes MRGPR s&#227;o expressos exclusivamente em subconjuntos de neur&#244;nios do g&#226;nglio da raiz dorsal &#40;GRD&#41; de pequeno di&#226;metro e&#44; em humanos&#44; as prote&#237;nas derivadas desses genes s&#227;o denominadas MRGPRX1 a MRGPRX4&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">19</span></a> Em humanos&#44; o gene MRGPR&#8208;X2 &#233; altamente expresso em les&#245;es de PGC&#44; e os mast&#243;citos s&#227;o as principais c&#233;lulas que expressam mRNA de MRGPRX2 na maioria dos pacientes &#40;70&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">20</span></a> Os receptores de IL&#8208;4 e IL&#8208;13 s&#227;o detectados em todas as tr&#234;s categorias&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">18</span></a> Em camundongos&#44; foi demonstrado que os comportamentos do ato de co&#231;ar variam de acordo com a ativa&#231;&#227;o desses diferentes subtipos&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">18</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">No PGC&#44; a express&#227;o d&#233;rmica de IL&#8208;31&#44; IL&#8208;31RA e oncostatina M &#40;OSM&#41; e periostina est&#227;o bem correlacionadas com a intensidade da coceira&#46; Al&#233;m disso&#44; a express&#227;o de OSMR&#946; na derme est&#225; aumentada&#44; apesar de n&#227;o estar correlacionada com a intensidade do prurido&#46; A IL&#8208;31 est&#225; envolvida na coceira em v&#225;rias doen&#231;as&#44; incluindo DA&#44; psor&#237;ase&#44; linfoma cut&#226;neo de c&#233;lulas T&#44; dermatite de estase&#44; penfigoide bolhoso&#44; escabiose e amiloidose cut&#226;nea prim&#225;ria localizada&#46; O PGC expressa 50 vezes mais o mRNA da IL&#8208;31 na pele lesionada&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">21</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">A IL&#8208;31 &#233; produzida principalmente por c&#233;lulas Th2 ativadas&#46; Queratin&#243;citos epid&#233;rmicos&#44; gl&#226;ndulas sudor&#237;paras &#233;crinas&#44; mast&#243;citos&#44; bas&#243;filos&#44; eosin&#243;filos e mon&#243;citos&#47;macr&#243;fagos s&#227;o capazes de liberar IL&#8208;31&#44; pois macr&#243;fagos CD68<span class="elsevierStyleSup">&#43;</span>&#44; al&#233;m de c&#233;lulas T CD3<span class="elsevierStyleSup">&#43;</span>&#44; s&#227;o as principais fontes celulares de IL&#8208;31 em les&#245;es de PGC&#46; Os macr&#243;fagos M2 expressam IL&#8208;31 e podem ser respons&#225;veis pelo prurido em diversas dermatoses&#44; como a dermatite de estase e a escabiose&#46; Portanto&#44; os macr&#243;fagos&#44; juntamente com as c&#233;lulas T&#44; podem ser potencial alvo terap&#234;utico para o prurido associado ao PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">21</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">A intensidade do prurido tamb&#233;m est&#225; intimamente relacionada &#224; express&#227;o d&#233;rmica de IL&#8208;31RA e OSMR&#946; &#40;receptor beta da oncostatina M&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">21</span></a> A maior popula&#231;&#227;o de c&#233;lulas d&#233;rmicas IL&#8208;31RA<span class="elsevierStyleSup">&#43;</span> s&#227;o macr&#243;fagos e mast&#243;citos&#46; As c&#233;lulas d&#233;rmicas OSMR&#946;<span class="elsevierStyleSup">&#43;</span> s&#227;o principalmente macr&#243;fagos&#44; enquanto os mast&#243;citos mal expressavam OSMR&#946;&#46; Isso indica que os macr&#243;fagos podem responder &#224; IL&#8208;31&#44; mas os mast&#243;citos n&#227;o&#46; A maioria das c&#233;lulas infiltradas nas les&#245;es de PGC consiste em macr&#243;fagos&#44; c&#233;lulas T e mast&#243;citos&#46; Considera&#8208;se que essas c&#233;lulas causam inflama&#231;&#227;o e prurido na pele ao secretar citocinas&#47;quimiocinas e pruritog&#234;nios &#40;incluindo IL&#8208;31&#41; e&#44; para macr&#243;fagos&#44; parcialmente em resposta &#224; sinaliza&#231;&#227;o de IL&#8208;31 envolvendo IL&#8208;31RA e OSMR&#946;&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">21</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">A OSM atua nos fibroblastos d&#233;rmicos para liberar a prote&#237;na quimioatrativa de mon&#243;citos 1 &#40;MCP&#8208;1&#41;&#44; o que pode levar &#224; infiltra&#231;&#227;o de mon&#243;citos&#47;macr&#243;fagos com capacidade de liberar IL&#8208;31&#46; Essas fun&#231;&#245;es da OSM podem estar envolvidas na patog&#234;nese do PGC e contribuir para sua associa&#231;&#227;o com o prurido&#46; Relata&#8208;se que os queratin&#243;citos epid&#233;rmicos medeiam o prurido induzido pela IL&#8208;31 pela secre&#231;&#227;o de estimuladores pruritog&#234;nicos quando estimulados pela IL&#8208;31 por meio de seu complexo receptor&#46; A menor express&#227;o de OSMR&#946; epid&#233;rmico pode estar relacionada &#224; redu&#231;&#227;o de FNIPD&#44; pois a insufici&#234;ncia de OSMR&#946; poderia levar &#224; apoptose das fibras nervosas epid&#233;rmicas&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">21</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">O meio d&#233;rmico complexo de c&#233;lulas imunes&#47;citocinas&#47;rede receptora incluindo IL&#8208;31&#44; OSM&#44; IL&#8208;31RA e OSMR&#946; pode desempenhar papel importante na patog&#234;nese do prurido no PGC&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">21&#44;22</span></a> No entanto&#44; em contraste com a DA&#44; a ativa&#231;&#227;o de macr&#243;fagos M1&#47;M2&#44; produ&#231;&#227;o de fator de necrose tumoral&#44; fibrose d&#233;rmica&#44; revasculariza&#231;&#227;o e desregula&#231;&#227;o neural s&#227;o caracter&#237;sticas &#250;nicas do PGC at&#243;pico&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">23</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Uma imunopolariza&#231;&#227;o sist&#234;mica e cut&#226;nea Th22 do PGC leva a outros participantes a interagirem em sua patog&#234;nese&#44; bem como a hiperplasia neuronal d&#233;rmica proeminente&#44; na qual a neurite expressa CGRP e subst&#226;ncia P&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">21</span></a> A IL&#8208;4 induz a prolifera&#231;&#227;o e migra&#231;&#227;o de fibroblastos e estimula a produ&#231;&#227;o de prote&#237;nas da matriz extracelular&#46; A sinaliza&#231;&#227;o hiperativa de IL&#8208;4 e IL&#8208;13 tem sido implicada na patog&#234;nese de doen&#231;as fibr&#243;ticas da pele&#46; IL&#8208;4 e IL&#8208;13 regulam positivamente a atividade do promotor e a transcri&#231;&#227;o de genes pr&#243;&#8208;fibr&#243;ticos&#44; como col&#225;geno tipo I e TGF&#8208;&#946;&#46; O aumento da periostina d&#233;rmica e a diminui&#231;&#227;o da periostina epid&#233;rmica tamb&#233;m foram encontrados em pacientes com PGC em compara&#231;&#227;o com controles saud&#225;veis&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">24</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Al&#233;m disso&#44; h&#225; alguma relev&#226;ncia na participa&#231;&#227;o do microbioma em pacientes com PGC&#44; especialmente o papel de <span class="elsevierStyleItalic">S&#46; aureus</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">25&#44;26</span></a> Al&#233;m disso&#44; a linfopoietina estromal t&#237;mica &#40;TSLP&#41; induz a hiperplasia da pele ativando c&#233;lulas imunes&#44; promovendo a prolifera&#231;&#227;o de queratin&#243;citos &#40;diretamente&#41;&#44; interrompendo a diferencia&#231;&#227;o de queratin&#243;citos e aumentando a express&#227;o de mediadores pr&#243;&#8208;inflamat&#243;rios&#44; contribuindo para o fen&#244;meno da hiperplasia&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">27</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">A IL&#8208;22 est&#225; envolvida em v&#225;rias condi&#231;&#245;es inflamat&#243;rias cr&#244;nicas&#44; como doen&#231;a arterial coronariana e diabetes tipo II &#40;DM2&#41;&#44; ambas comorbidades altamente associadas em pacientes com PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">23</span></a> Na epiderme&#44; n&#237;veis elevados de IL&#8208;22 promovem hiperplasia de queratin&#243;citos e acantose&#44; al&#233;m de atuar sinergicamente com a IL&#8208;17&#44; que promove hiperplasia de queratin&#243;citos e diferencia&#231;&#227;o epid&#233;rmica prejudicada no PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">23</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Observa&#8208;se aumento da express&#227;o de IL&#8208;31 em europeus quando comparados a afro&#8208;americanos&#59; no entanto&#44; a regula&#231;&#227;o positiva de citocinas relacionadas a Th22 no PGC pode ser independente da etnia&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">23</span></a> Em contraste&#44; observou&#8208;se aumento da express&#227;o de citocinas Th2&#44; incluindo IL&#8208;4&#44; IL&#8208;5 e IL&#8208;13&#44; bem como maior ativa&#231;&#227;o de Th2 entre os europeus&#44; mas n&#227;o entre os afro&#8208;americanos&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">23</span></a> Esse perfil de citocinas pode ser a chave para respostas bem&#8208;sucedidas ao tratamento com medicamentos espec&#237;ficos&#44; como o dupilumabe&#44; que pode ser mais eficaz em certos endotipos de pacientes com PGC com atopia associada&#44; envolvendo IL&#8208;4R&#945;&#44; e&#47;ou nemolizumabe em pacientes descendentes de europeus&#46; J&#225; o receptor de IL&#8208;31 &#233; composto de receptor alfa de IL&#8208;31 &#40;IL&#8208;31RA&#41; e receptor beta de oncostatina M &#40;OSMR&#946;&#41;&#44; que s&#227;o dependentes de JAK1&#47;2&#44;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">24</span></a> e indicam uma janela de oportunidade para f&#225;rmacos seletivos da JAK1&#44; como o abrocitinibe e o upadacitinibe&#44; no tratamento do PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">28</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Diagn&#243;stico do prurigo cr&#244;nico e sua avalia&#231;&#227;o</span><p id="par0160" class="elsevierStylePara elsevierViewall">O diagn&#243;stico do PGC &#233; feito clinicamente com base na hist&#243;ria cl&#237;nica&#44; exame cl&#237;nico&#44; histopatol&#243;gico&#44; laboratorial e radiol&#243;gico&#44; que auxiliam na confirma&#231;&#227;o do diagn&#243;stico e determinam a gravidade do PGC&#44; a doen&#231;a subjacente e um plano de tratamento individual&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">A anamnese de pacientes com PGC deve envolver v&#225;rias quest&#245;es objetivas&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a> O exame f&#237;sico geral&#44; dermatol&#243;gico sugerido para o PGC&#44; exames laboratoriais e de imagem complementares recomendados pela diretriz IFSI no PGC&#44;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a> com adapta&#231;&#245;es&#44; com base na pr&#225;tica cl&#237;nica&#44; est&#227;o listados na <a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Variantes de prurigo cr&#244;nico</span><p id="par0170" class="elsevierStylePara elsevierViewall">Em pacientes japoneses&#44; al&#233;m do PGC&#47;prurigo nodular &#40;Hyde&#41;&#44; &#233; referido o prurigo cr&#244;nico multiforme &#40;PCM&#41;&#44; descrito pela primeira vez por Lutz em 1957&#44; como uma desordem cut&#226;nea cr&#244;nica&#44; intensamente pruriginosa&#44; que acomete principalmente indiv&#237;duos idosos&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">29</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Sempre houve confus&#227;o na sinon&#237;mia e classifica&#231;&#227;o das les&#245;es pruriginosas&#44; e Greither incluiu o PCM como variante do prurigo subagudo apresentando um tra&#231;o de neurodermatite&#46;<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">20&#44;30</span></a> A morfologia caracter&#237;stica&#44; o local de predile&#231;&#227;o&#44; a idade e os achados histopatol&#243;gicos do PCM indicam que se trata de dermatose distinta e n&#227;o de variante do prurigo simples subagudo ou cr&#244;nico &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">29</span></a> O &#8220;sinal da borboleta&#8221; &#233; um exemplo de &#8220;fen&#244;meno poupador&#8221; que denota uma &#225;rea de pele normal ou relativamente hipopigmentada toracolombar que &#233; poupada da co&#231;adura em virtude de sua inacessibilidade &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#44; em pacientes com prurido generalizado decorrente de muitos dist&#250;rbios&#44; como doen&#231;a hepatobiliar&#44; dermatite at&#243;pica e PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">31</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">Fujii et al&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">29</span></a> coletaram mais de 30 casos de PCM de 1997 a 2000&#44; seguindo os seguintes crit&#233;rios&#58; i&#41; a les&#227;o prim&#225;ria come&#231;a como les&#227;o intensamente pruriginosa&#44; papular solit&#225;ria ou pruriginosa que se desenvolve na lateral do t&#243;rax&#44; regi&#227;o lombar&#44; n&#225;degas e superf&#237;cies extensoras das coxas&#59; ii&#41; a parte superior das costas&#44; ombros&#44; superf&#237;cies extensoras das extremidades superiores&#44; abdome inferior&#44; t&#243;rax anterior e panturrilhas tamb&#233;m podem ser afetadas&#59; iii&#41; as les&#245;es papulares pruriginosas prim&#225;rias frequentemente se expandem ou coalescem para formar uma placa eritematosa infiltrada&#59; iv&#41; a natureza coalescente da erup&#231;&#227;o prim&#225;ria diferencia o PCM do PGC usual ou do prurigo subagudo&#59; v&#41; o prurido intenso muitas vezes causa &#225;reas focais de eczema agudo sobre e ao redor das les&#245;es em placa&#44; mas componentes seropapulares e&#47;ou descamativos nunca dominam as manifesta&#231;&#245;es cut&#226;neas&#59; vi&#41; uma les&#227;o tipo placa infiltrada se estende al&#233;m do confinamento da &#225;rea cut&#226;nea&#44; que &#233; clinicamente diferente da liquenifica&#231;&#227;o do eczema cr&#244;nico ou da neurodermatite&#59; vii&#41; no exame histopatol&#243;gico&#44; tanto as les&#245;es papulares pruriginosas prim&#225;rias quanto as les&#245;es em placa mostram graus moderados de infiltra&#231;&#227;o perivascular de c&#233;lulas mononucleares contendo popula&#231;&#245;es variadas de eosin&#243;filos na derme reticular e papilar superior&#59; viii&#41; ao contr&#225;rio das les&#245;es prim&#225;rias de prurigo simples subagudo&#44; a epiderme nem sempre apresenta espongiose com exocitose&#44; sugerindo que a espongiose epid&#233;rmica n&#227;o deva ser a principal altera&#231;&#227;o patol&#243;gica da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">29</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Ent&#227;o&#44; essa variante singular de PGC &#233; caracterizada por p&#225;pulas pruriginosas urticariformes ou s&#243;lidas&#44; que &#224;s vezes se juntam para formar placas liquenificadas&#59; as les&#245;es est&#227;o espalhadas pelo tronco e extremidades&#44; e cada erup&#231;&#227;o dura v&#225;rias semanas &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">32</span></a> O PCM ocorre mais frequentemente em homens e em pacientes com idade mais avan&#231;ada&#44; ao contr&#225;rio do PGC&#44; que ocorre mais em mulheres e pacientes de meia&#8208;idade&#44; no Jap&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">32</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Inui et al&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">32</span></a> estudaram 168 casos de prurigo cr&#244;nico no Jap&#227;o &#40;103 com PGC e 65 com PCM&#41; e demonstraram que tanto no PGC quanto no PCM&#44; os n&#237;veis s&#233;ricos de IgE tendiam a ser elevados &#40;&#62; 256 UI&#47;mL&#41;&#44; sugerindo o envolvimento das respostas imunes Th2 no prurigo cr&#244;nico&#46; Esses autores descobriram que os n&#237;veis s&#233;ricos de TARC&#47;CCL17 e o n&#250;mero de eosin&#243;filos no sangue eram maiores no PCM do que no PGC&#46; Al&#233;m disso&#44; a distribui&#231;&#227;o de eosin&#243;filos tamb&#233;m era distinta no PGC e no PCM&#44; mas sua densidade foi compar&#225;vel em ambos os grupos&#46; Esses achados sugerem que o aumento dos n&#237;veis de eosin&#243;filos no sangue perif&#233;rico e o recrutamento dessas c&#233;lulas para &#225;reas com col&#225;geno na derme podem ser importantes para a patog&#234;nese do PCM&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">32</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">O PCM &#233; frequentemente resistente ao tratamento com uma combina&#231;&#227;o de esteroides t&#243;picos e anti&#8208;histam&#237;nicos&#44; particularmente quando a les&#227;o cut&#226;nea est&#225; se expandindo ativamente&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">32</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Todas as formas de PGC apresentam a marca registrada de prurido intenso e les&#245;es secund&#225;rias ao ato de co&#231;ar&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">10</span></a> Embora o PGC seja entidade cl&#237;nica espec&#237;fica&#44; tamb&#233;m pode ser secund&#225;rio a v&#225;rias condi&#231;&#245;es subjacentes&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">33</span></a> O PGC tem impacto significante na qualidade de vida&#44;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">11</span></a> maior do que outras condi&#231;&#245;es de pele em que o prurido &#233; uma caracter&#237;stica marcante&#44; como psor&#237;ase ou DA&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">14</span></a> A ansiedade ocorre em 37&#37; dos pacientes&#44; a depress&#227;o em 29&#37; e a idea&#231;&#227;o suicida em 19&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">13&#44;14</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Especialistas do European Prurigo Project publicaram um consenso em 2018 para propor defini&#231;&#245;es&#44; classifica&#231;&#245;es e terminologia&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">4&#44;13</span></a> O artigo afirma que o PGC &#233; &#8220;uma doen&#231;a distinta definida pela presen&#231;a de prurido cr&#244;nico e m&#250;ltiplas les&#245;es pruriginosas localizadas ou generalizadas&#8221;&#46; A sensibiliza&#231;&#227;o &#224; coceira e o desenvolvimento de um ciclo prurido&#8208;co&#231;adura podem ser de origem dermatol&#243;gica&#44; sist&#234;mica&#44; neurol&#243;gica e psiqui&#225;trica&#47;psicossom&#225;tica&#44; multifatorial ou indeterminada&#8221;&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">4&#44;13</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Histopatologia do prurigo cr&#244;nico</span><p id="par0210" class="elsevierStylePara elsevierViewall">O exame histopatol&#243;gico das les&#245;es cut&#226;neas nodulares do PGC sob microscopia &#243;ptica pode variar dependendo do est&#225;gio e gravidade da les&#227;o e da resposta individual do paciente ao ato de co&#231;ar e &#224; irrita&#231;&#227;o cr&#244;nica&#46; Hiperceratose&#44; escoria&#231;&#227;o&#44; acantose &#40;&#224;s vezes psoriasiforme&#41;&#44; espongiose leve&#44; fibrose d&#233;rmica e infiltrado perivascular leve &#40;linf&#243;citos e eosin&#243;filos escassos&#41; s&#227;o a base da doen&#231;a &#40;<a class="elsevierStyleCrossRef" href="#fig0020">fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0215" class="elsevierStylePara elsevierViewall">Um aumento da densidade de fibras nervosas d&#233;rmicas e altera&#231;&#245;es em muitos tipos de c&#233;lulas da pele&#44; incluindo mast&#243;citos&#44; c&#233;lulas de Merkel&#44; queratin&#243;citos epid&#233;rmicos&#44; c&#233;lulas dendr&#237;ticas&#44; c&#233;lulas endoteliais e fibras de col&#225;geno tamb&#233;m s&#227;o relatados&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">34</span></a> Essas c&#233;lulas causam inflama&#231;&#227;o e prurido por meio da libera&#231;&#227;o de triptase&#44; IL&#8208;31&#44; prostaglandinas&#44; prote&#237;na cati&#244;nica eosin&#243;fila&#44; histamina e outros mediadores como neuropept&#237;deos&#44; incluindo subst&#226;ncia P&#44; pept&#237;deo relacionado ao gene da calcitonina &#40;CGRP&#41; e fator de crescimento&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">34&#44;35</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Tratamento do prurigo cr&#244;nico</span><p id="par0220" class="elsevierStylePara elsevierViewall">O tratamento dos prurigos pode ser desafiador pela hist&#243;ria recorrente das les&#245;es&#44; em virtude de doen&#231;as subjacentes &#40;p&#46; ex&#46;&#44; DA&#44; uremia&#41; ou por limita&#231;&#227;o do uso de medicamentos sist&#234;micos em pacientes suscet&#237;veis a efeitos adversos &#40;p&#46; ex&#46;&#44; idosos&#41;&#46; A <a class="elsevierStyleCrossRef" href="#tbl0025">tabela 5</a> lista uma s&#233;rie de abordagens&#44; farmacol&#243;gicas ou n&#227;o&#44; referidas na literatura para o tratamento de les&#245;es prurigoides&#59; entretanto&#44; somente a correta classifica&#231;&#227;o diagn&#243;stica&#44; identifica&#231;&#227;o de condi&#231;&#245;es subjacentes&#44; investigada criteriosamente &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#41; pode levar ao maior sucesso terap&#234;utico dos casos&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0225" class="elsevierStylePara elsevierViewall">De modo geral&#44; a prescri&#231;&#227;o de emolientes&#44; antipruriginosos t&#243;picos&#44; corticosteroides t&#243;picos&#44; inibidores de calcineurina e anti&#8208;histam&#237;nicos n&#227;o sedantes s&#227;o pouco eficientes no PGC&#44; enquanto anti&#8208;histam&#237;nicos sedantes podem levar a efeitos adversos&#44; especialmente em pacientes que demandem aten&#231;&#227;o profissional &#40;p&#46; ex&#46;&#44; motoristas&#41; ou idosos&#44; que acumulam efeitos anticolin&#233;rgicos&#46; Ademais&#44; a patog&#234;nese do PGC &#233; complexa&#44; e a histamina n&#227;o est&#225; entre as principais mediadoras envolvidas&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Usualmente&#44; o tratamento do PGC depende de medicamentos sist&#234;micos como os corticosteroides&#44; ciclosporina&#44; micofenolato de mofetila&#44; azatioprina&#44; talidomida e neuromoduladores &#40;p&#46; ex&#46;&#44; gabapentina ou pregabalina&#41;&#44; al&#233;m de fototerapia &#40;especialmente <span class="elsevierStyleItalic">narrow&#8208;band</span> UVB&#41;&#46; Mas a demanda pelo uso prolongado dessas op&#231;&#245;es maximiza efeitos adversos&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">O dupilumabe &#233; um anticorpo monoclonal humano IgG4 &#40;mAb&#41; que se liga a IL&#8208;4Ra e inibe a sinaliza&#231;&#227;o de IL&#8208;4R induzida por IL&#8208;4 e IL&#8208;13&#44; e regula negativamente a inflama&#231;&#227;o TH2 na DA e em outras doen&#231;as inflamat&#243;rias e at&#243;picas&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">17</span></a> O dupiluma apresenta efeito antipruriginoso em pacientes com PGC&#46; Dois estudos recentes de fase 3 tamb&#233;m demonstraram que o tratamento com dupilumabe reduziu o prurido e as les&#245;es cut&#226;neas em pacientes com PGC&#59; no Brasil&#44; a indica&#231;&#227;o &#8220;prurigo nodular&#8221; foi incorporada &#224; bula do medicamento&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">36</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">A terapia com dupilumabe reduziu a assinatura de mais de 800 genes afetados na DA&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">37</span></a> Dupilumabe diminui a express&#227;o de mRNA de genes relacionados &#224; hiperplasia epid&#233;rmica &#40;K16 e MKI67&#41;&#44; c&#233;lulas T e c&#233;lulas dendr&#237;ticas &#40;CD1b e CD1c&#41;&#44; e uma inibi&#231;&#227;o potente de quimiocinas associadas &#224; via TH2 &#40;CCL17&#44; CCL18&#44; CCL22 e CCL26&#41; foi observada sem modula&#231;&#227;o significante de genes associados &#224; via TH1 &#40;IFNG&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">37</span></a> Essas a&#231;&#245;es podem explicar a boa resposta do dupilumabe no tratamento do PGC &#40;<a class="elsevierStyleCrossRef" href="#fig0025">fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0245" class="elsevierStylePara elsevierViewall">As les&#245;es cut&#226;neas da DA cr&#244;nica incluem aumento da infiltra&#231;&#227;o por c&#233;lulas T&#44; c&#233;lulas dendr&#237;ticas &#40;DCs&#41; e eosin&#243;filos&#44;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">17</span></a> semelhante ao encontrado nas les&#245;es de PGC&#46; Embora a DA tenha sido classificada como doen&#231;a dominada por TH2&#44; outros subconjuntos de c&#233;lulas T &#40;c&#233;lulas TH22&#44; TH17 e TH1&#41; tamb&#233;m podem contribuir para a patog&#234;nese&#46; Como mencionado&#44; alguns autores encontraram no PGC um <span class="elsevierStyleItalic">upregulation</span> de mRNA da IL&#8208;31&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">35</span></a> A liga&#231;&#227;o da IL&#8208;31 aos seus receptores ativa vias de sinaliza&#231;&#227;o poderosas &#40;ou seja&#44; a ativa&#231;&#227;o de JAK1 e JAK2 e o in&#237;cio da via JAK&#8208;STAT&#41;&#46; Assim&#44; a IL&#8208;31 foi considerada um novo participante na inflama&#231;&#227;o do tipo 2&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Essa teoria foi corroborada pela descoberta de que as c&#233;lulas Th2 s&#227;o uma das principais produtoras de IL&#8208;31&#44; havendo uma correla&#231;&#227;o positiva entre IL&#8208;31 e a gravidade da DA&#46; Al&#233;m disso&#44; n&#237;veis elevados de IL&#8208;31 contribuem para sintomas espec&#237;ficos como prurido&#44; les&#245;es cut&#226;neas e irrita&#231;&#227;o&#47;inflama&#231;&#227;o localizada da DA<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">17</span></a> e eixos de endotelina na pele lesional e perilesional no PGC&#46; Zhong et al&#46; observaram maior express&#227;o do mRNA da IL&#8208;31 nas les&#245;es de cinco pacientes at&#243;picos do que em seis pacientes n&#227;o at&#243;picos&#46; Esses resultados sugerem papel muito mais importante da IL&#8208;31 em pacientes com PGC at&#243;pico <span class="elsevierStyleItalic">versus</span> n&#227;o at&#243;pico&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">38</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">O PGC &#233; doen&#231;a &#243;rf&#227;&#44; com altas taxas associadas a ansiedade&#44; depress&#227;o e alto impacto na qualidade de vida&#46; O prurido cr&#244;nico tamb&#233;m prejudica negativamente o sono e a qualidade de vida&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">39</span></a> Zhai et al&#46;&#44; em um estudo retrospectivo envolvendo 20 pacientes com prurido recalcitrante cr&#244;nico &#40;nove com PGC&#59; cinco com prurido ur&#234;mico&#59; quatro com prurido idiop&#225;tico cr&#244;nico&#59; um com l&#237;quen plano e um com dermatose eosinof&#237;lica relacionada a malignidade hematol&#243;gica&#41;&#44; demonstraram o uso <span class="elsevierStyleItalic">off&#8208;label</span> do dupilumabe e desfecho bem&#8208;sucedido&#44; reduzindo o prurido em todos os pacientes&#44; levando &#224; resolu&#231;&#227;o completa em 12&#47;20 pacientes e m&#233;dia geral da intensidade de prurido na escala de classifica&#231;&#227;o num&#233;rica &#40;NRSi&#41; de 7&#44;55&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">40</span></a> Em idosos&#44; o dupilumabe foi bem tolerado sem grandes efeitos adversos&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">41</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">Entre 90 pacientes adultos com DA tratados com dupilumabe<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">41</span></a> em dois hospitais universit&#225;rios italianos&#44; 10&#44;0&#37; apresentavam PGC generalizado e eram afetados por uma ou mais comorbidades at&#243;picas &#40;rinite al&#233;rgica&#44; asma e conjuntivite al&#233;rgica&#41;&#46; O n&#237;vel s&#233;rico de IgE estava acima do normal em todos os pacientes&#46; Os nove pacientes de PGC foram tratados com dupilumabe com o regime de dosagem padr&#227;o&#46; Ap&#243;s 16 semanas de tratamento&#44; todos os pacientes apresentaram melhora cl&#237;nica acentuada&#46; Nenhum paciente abandonou o tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">41</span></a></p><p id="par0265" class="elsevierStylePara elsevierViewall">A abordagem terap&#234;utica para o PGC tamb&#233;m &#233; baseada em casu&#237;stica e experi&#234;ncia cl&#237;nica&#58; corticosteroides&#44; fototerapia&#44; imunomoduladores t&#243;picos &#40;inibidores t&#243;picos de calcineurina&#41; e imunossupressores &#40;ciclosporina&#44; azatioprina&#44; micofenolato de mofetila e metotrexato&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">42</span></a> neuromoduladores&#44; talidomida que&#44; no entanto&#44; t&#234;m efeitos colaterais indesej&#225;veis potenciais significantes&#44; especialmente em pacientes idosos&#46; Agentes sist&#234;micos s&#227;o frequentemente necess&#225;rios&#44; incluindo corticoides intralesionais&#44; agentes antipruriginosos como anti&#8208;histam&#237;nicos orais&#44; neuromoduladores como gabapentina e pregabalina&#44; al&#233;m de fototerapia&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">43&#8211;45</span></a>Em casos mais graves&#44; os agentes imunossupressores t&#234;m sido usados com sucesso vari&#225;vel e apresentam diversos efeitos colaterais indesej&#225;veis&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">43&#44;44</span></a> Outro aspecto do uso de imunossupressores sist&#234;micos em pa&#237;ses tropicais s&#227;o as doen&#231;as infecciosas end&#234;micas&#44; como as parasitoses gastrintestinais &#40;a profilaxia da estrongiloid&#237;ase &#233; obrigat&#243;ria&#41;&#44; e o risco de pacientes idosos desenvolverem doen&#231;as infecciosas end&#234;micas graves comodengue&#44; Zika e Chikungunya<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">46</span></a> ou novos v&#237;rus epid&#234;micos&#44; como o COVID&#8208;19&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">47</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">De modo geral&#44; uma abordagem racional para o tratamento do PGC pode ser feita levando em considera&#231;&#227;o cinco passos&#46; O primeiro &#233; utilizar corticoides t&#243;picos&#44; inibidores de calcineurina &#40;tacrolimus e pimecrolimus&#41; e fototerapia ultravioleta &#40;<span class="elsevierStyleItalic">narrowband</span> 311<span class="elsevierStyleHsp" style=""></span>nm&#44; Excimer <span class="elsevierStyleItalic">laser</span> e PUVA terapia&#41;&#46; O segundo passo compreende o uso da capsaicina t&#243;pica na concentra&#231;&#227;o que varia de 0&#44;025&#37; a 0&#44;3&#37; de 4 a 6&#215;&#47;dia&#44; al&#233;m do uso oral de gabapentina 300&#8208;900<span class="elsevierStyleHsp" style=""></span>mg&#47;dia at&#233; 3&#215;&#47;dia ou pregabalina 150&#8208;600<span class="elsevierStyleHsp" style=""></span>mg&#47;dia dividida em 2&#8208;3 doses&#46; O terceiro passo consiste no uso de antidepressivos&#44; como a paroxetina 20&#8208;50<span class="elsevierStyleHsp" style=""></span>mg&#47;dia ou a mirtazapina 15<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#46; O quarto passo&#44; para casos em que o controle t&#243;pico e com antidepressivos e&#47;ou gabapentinoides n&#227;o obtiveram melhora&#44; &#233; o uso de imunossupressores como a ciclosporina e o metotrexato&#46; Para casos mais refrat&#225;rios&#44; o quinto passo incluiria tamb&#233;m o uso de antagonistas dos receptores opioides &#956;&#44; como a naltrexona&#59; antagonistas dos receptores da neuroquinina 1&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">48</span></a> Como em metade dos casos de PGC&#44; a DA est&#225; associada&#44; h&#225; uma concord&#226;ncia dos tratamentos entre essas duas entidades&#44; inclusive com o uso de biol&#243;gicos como o dupilumabe e o nemolizumabe&#44; e pequenas mol&#233;culas&#44; como os inibidores de JAK&#44; como upadacitinibe&#44; baricitinibe&#44; tofacitinibe abrocitinibe&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">49</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">O dupilumabe &#233; bem tolerado em crian&#231;as&#44; adultos e idosos&#44; com poucos eventos adversos graves&#44; que incluem nasofaringite&#44; cefaleia&#44; conjuntivite e rea&#231;&#245;es no local da inje&#231;&#227;o&#44; rubor alco&#243;lico em um caso&#44; eritema cut&#226;neo transit&#243;rio e descama&#231;&#227;o&#44; rea&#231;&#245;es locais no local&#44; infec&#231;&#245;es por herpes simples e alopecia&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">50</span></a> Aten&#231;&#227;o especial deve ser dada &#224; prescri&#231;&#227;o de dupilumabe em pacientes com linfoma cut&#226;neo de c&#233;lulas T &#40;micose fungoide&#41;&#44; em virtude do risco de evolu&#231;&#227;o desfavor&#225;vel da doen&#231;a de base&#46;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">51</span></a></p><p id="par0280" class="elsevierStylePara elsevierViewall">Novos f&#225;rmacos emergentes surgem como op&#231;&#245;es promissoras&#44; como o nemolizumabe&#44; um anticorpo humanizado contra o receptor IL&#8208;31 &#945; &#40;IL&#8208;31R&#945;&#41;&#46; A IL&#8208;31 &#233; uma citocina pr&#243;&#8208;inflamat&#243;ria elevada em v&#225;rias dermatoses pruriginosas cr&#244;nicas&#44; e o bloqueio de seu receptor recentemente mostrou redu&#231;&#227;o do escore de prurido em pacientes com PGC&#44; melhora na qualidade de vida e do sono&#44; em compara&#231;&#227;o com o placebo em um estudo duplo&#8208;cego randomizado de 12 semanas&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">52</span></a> Os eventos adversos relatados nesse estudo foram leves e incomuns&#44; principalmente diarreia&#44; dor abdominal e sintomas musculoesquel&#233;ticos&#46; Outro estudo avaliou o transcriptoma de pacientes com PGC ap&#243;s a terapia com nemolizumabe&#44; mostrando fatores inflamat&#243;rios a jusante&#44; ap&#243;s 12 semanas de tratamento&#44; bem como altera&#231;&#245;es no transcriptoma&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">53</span></a> Em decorr&#234;ncia dessas evid&#234;ncias&#44; o FDA considerou recentemente o nemolizumabe uma &#8220;terapia inovadora&#8221; para pacientes com PGC&#46; Mais estudos s&#227;o necess&#225;rios para garantir a efic&#225;cia e seguran&#231;a do inibidor de IL&#8208;31R&#945; em pacientes com PGC e&#44; nesse momento&#44; existem quatro ensaios cl&#237;nicos em andamento&#46;<a class="elsevierStyleCrossRefs" href="#bib0605"><span class="elsevierStyleSup">54&#8211;57</span></a>Outros biol&#243;gicos e pequenas mol&#233;culas est&#227;o atualmente sendo investigados&#44; como os inibidores de IL&#8208;4 e IL&#8208;13&#44; antirreceptores OSM&#946;&#44; inibidores do receptor de tirosina quinase KIT e inibidores da JAK&#46;<a class="elsevierStyleCrossRefs" href="#bib0625"><span class="elsevierStyleSup">58&#8211;61</span></a> O traloquinumabe&#44; um inibidor de IL&#8208;13&#44; mostrou melhora&#44; em um estudo aberto&#44; em pacientes at&#243;picos com PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">61</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">Os inibidores de JAK surgiram mais recentemente como op&#231;&#227;o para o PGC recalcitrante&#44; inibindo a via JAK&#8208;STAT&#44; bloqueando a transcri&#231;&#227;o de IL&#8208;4 e IL&#8208;31&#44; aumentando a densidade das fibras nervosas epid&#233;rmicas e reduzindo o prurido &#40;<a class="elsevierStyleCrossRef" href="#fig0030">fig&#46; 6</a>&#41;&#46; A via JAK&#8208;STAT regula positivamente numerosas citocinas e c&#233;lulas CD4 e j&#225; foi reconhecida pela patog&#234;nese em outras condi&#231;&#245;es cut&#226;neas inflamat&#243;rias&#44; como DA&#46;<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">62&#44;63</span></a> Relatos de casos da efic&#225;cia do tofacitinibe&#44; um inibidor n&#227;o seletivo de JAK1 e JAK3&#44; foram descritos&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">64</span></a> O tofacitinibe t&#243;pico a 2&#37; tamb&#233;m demonstrou redu&#231;&#227;o substancial no prurido em dois pacientes com PGC&#46;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">65</span></a> O abrocitinibe&#44; um inibidor de JAK1 estudado pela primeira vez na DA&#44; est&#225; atualmente sendo estudado para PGC em ensaios cl&#237;nicos&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">66</span></a> Um estudo recente comparou 36 e 13 pacientes &#40;com ou sem DA&#41; em uso de dupilumabe e inibidores orais de JAK &#40;baricitinibe e upadacitinibe&#41;&#44; respectivamente&#46; Ambos os grupos obtiveram respostas semelhantes em rela&#231;&#227;o ao prurido &#40;WI&#8208;NRS&#41;&#44; enquanto os escores IGA PN&#8208;S de 0 ou 1 foram alcan&#231;ados por 40&#44;0&#37; dos pacientes com dupilumabe e 25&#44;0&#37; dos inibidores de JAK&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">67</span></a></p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0290" class="elsevierStylePara elsevierViewall">O melhor conhecimento da patog&#234;nese&#44; associado &#224; disponibilidade de uma gama de novos tratamentos&#44; deve modificar a hist&#243;ria da doen&#231;a e o panorama dos pacientes com PGC&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclus&#245;es</span><p id="par0295" class="elsevierStylePara elsevierViewall">Diversas entidades se manifestam clinicamente como les&#245;es prurigoides&#44; e o correto diagn&#243;stico cl&#237;nico deve preceder o tratamento intempestivo&#46; Al&#233;m disso&#44; os PGC representam dermatose recalcitrante e angustiante&#44; e pelo menos 50&#37; desses pacientes apresentam di&#225;tese at&#243;pica&#44; cujos tratamentos podem induzir efeitos adversos&#44; especialmente em idosos&#46; H&#225; importante comprometimento da qualidade de vida&#44; e&#44; muitas vezes&#44; tratamentos t&#243;picos n&#227;o s&#227;o capazes de controlar os sintomas e as les&#245;es cut&#226;neas&#46; Imunossupressores sist&#234;micos&#44; imunobiol&#243;gicos e inibidores de JAK&#44; apesar do custo e potenciais efeitos adversos&#44; podem ser necess&#225;rios para o controle do PGC e oferecer melhoria cl&#237;nica e na qualidade de vida para esses pacientes&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Suporte financeiro</span><p id="par0300" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Contribui&#231;&#227;o dos autores</span><p id="par0305" class="elsevierStylePara elsevierViewall">Paulo Ricardo Criado&#58; Idealiza&#231;&#227;o do estudo&#44; escrita e aprova&#231;&#227;o do texto final&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">Roberta Fachini Jardim Criado&#58; Idealiza&#231;&#227;o do estudo&#44; escrita e aprova&#231;&#227;o do texto final&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">Mayra Ianhez&#58; Idealiza&#231;&#227;o do estudo&#44; escrita e aprova&#231;&#227;o do texto final&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">Juliana Nakano&#58; Idealiza&#231;&#227;o do estudo&#44; escrita e aprova&#231;&#227;o do texto final&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">Daniel Lorenzini&#58; Idealiza&#231;&#227;o do estudo&#44; escrita e aprova&#231;&#227;o do texto final&#46;</p><p id="par0330" class="elsevierStylePara elsevierViewall">H&#233;lio Amante Miot&#58; Idealiza&#231;&#227;o do estudo&#44; escrita e aprova&#231;&#227;o do texto final&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflito de interesses</span><p id="par0335" class="elsevierStylePara elsevierViewall">Paulo Criado&#58; <span class="elsevierStyleItalic">Advisory board</span> &#8211; Pfizer&#44; Galderma&#44; Takeda&#44; Hypera&#44; Novartis&#44; Sanofi&#59; <span class="elsevierStyleItalic">Pesquisa cl&#237;nica</span> &#8211; Pfizer&#44; Novartis&#44; Sanofi&#44; Amgen e Lilly&#59; <span class="elsevierStyleItalic">Palestrantre</span> &#8211; Pfizer&#44; Abbvie&#44; Sanofi&#8208;Genzyme&#44; Hypera&#44; Takeda&#44; Novartis&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">Roberta Fachini Jardim Criado&#58; <span class="elsevierStyleItalic">Advisory board</span> &#8211; Pfizer&#44; Takeda&#44; Hypera&#44; Novartis&#44; Sanofi&#59; <span class="elsevierStyleItalic">Pesquisa cl&#237;nica</span> &#8211; Pfizer&#44; Novartis&#44; Sanofi e Lilly&#59; <span class="elsevierStyleItalic">Palestrantre</span> &#8211; Pfizer&#44; Abbvie&#44; Sanofi&#8208;Genzyme&#44; Hypera&#44; Takeda&#44; Novartis&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">Mayra Ianhez&#58; <span class="elsevierStyleItalic">Advisory Board</span> &#8211; Galderma&#44; Sanofi&#44; Pfizer&#44; Novartis&#44; Abbvie&#44; Janssen&#44; UCB&#8208;Biopharma&#44; Boehringer&#8208;Ingelheim&#59; <span class="elsevierStyleItalic">Palestrante</span> &#8211; Galderma&#44; Sanofi&#44; Pfizer&#44; Theraskin&#44; Novartis&#44; Abbvie&#44; Janssen&#44; Leopharma&#44; FQM&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">Juliana Nakano&#58; <span class="elsevierStyleItalic">Advisory Board</span> &#8211; Novartis&#44; Abbvie&#44; Janssen&#44; Boehringer&#8208;Ingelheim&#59; <span class="elsevierStyleItalic">Palestrante</span> &#8211; Sanofi&#44; LeoPharma&#44; Lilly&#44; Novartis&#44; Abbvie&#44; Janssen&#44; Boehringer&#8208;Ingelheim&#46;</p><p id="par0355" class="elsevierStylePara elsevierViewall">Daniel Lorenzini&#58; <span class="elsevierStyleItalic">Advisory Board</span> &#8211; Abbvie&#44; Sanofi&#44; Galderma&#59; <span class="elsevierStyleItalic">Palestrante</span> &#8211; Sanofi&#44; Abbvie&#44; Pfizer&#44; Lilly&#44; Leopharma&#46;</p><p id="par0360" class="elsevierStylePara elsevierViewall">H&#233;lio Miot&#58; <span class="elsevierStyleItalic">Advisory Board</span> &#8211; Johnson &#38; Johnson&#44; L&#8217;Or&#233;al&#44; Theraskin&#44; Sanofi e Pfizer&#59; P<span class="elsevierStyleItalic">esquisa cl&#237;nica</span> &#8211; Abbvie&#44; Galderma e Merz&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Prurigo &#233; condi&#231;&#227;o reativa hiperpl&#225;sica da pele caracterizada por p&#225;pulas&#44; placas e&#47;ou n&#243;dulos pruriginosos&#46; Temporalmente&#44; s&#227;o classificados como agudo&#47;subagudo e cr&#244;nico &#40;&#8805; 6 semanas&#41;&#44; com diferentes variantes cl&#237;nicas&#44; sinon&#237;mias&#44; e fatores etiol&#243;gicos subjacentes&#46; A imunologia do prurigo cr&#244;nico mostra semelhan&#231;as com a dermatite at&#243;pica em virtude do envolvimento de IL&#8208;4 e IL&#8208;13&#44; IL&#8208;22 e IL&#8208;31&#46; O tratamento varia desde anti&#8208;histam&#237;nicos&#44; esteroides t&#243;picos&#44; dupilumabe e inibidores de Janus Quinases &#40;JAK&#41;&#46; Diversas entidades se manifestam clinicamente como les&#245;es prurigoides&#44; e o correto diagn&#243;stico cl&#237;nico deve preceder o tratamento intempestivo&#46; Al&#233;m disso&#44; prurigos cr&#244;nicos representam dermatose recalcitrante e angustiante&#44; e pelo menos 50&#37; desses pacientes apresentam di&#225;tese at&#243;pica&#44; cujo tratamento pode induzir efeitos adversos&#44; especialmente em idosos&#46; H&#225; importante comprometimento da qualidade de vida&#44; e&#44; muitas vezes&#44; os tratamentos t&#243;picos n&#227;o s&#227;o capazes de controlar os sintomas e as les&#245;es cut&#226;neas&#46; Imunossupressores sist&#234;micos&#44; imunobiol&#243;gicos e inibidores de JAK&#44; apesar do custo e de potenciais efeitos adversos&#44; podem ser necess&#225;rios para obter melhoria cl&#237;nica e na qualidade de vida&#46; Este manuscrito revisa os principais tipos de prurigo&#44; doen&#231;as associadas&#44; suas bases imunol&#243;gicas&#44; diagn&#243;stico e tratamento&#46;</p></span>"
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          "pt" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Prurigo agudo no antebra&#231;o em virtude de picadas de percevejos em morfologia de padr&#227;o linear t&#237;pico semelhante ao caf&#233; da manh&#227;&#44; almo&#231;o e jantar&#46; &#40;B&#41; Prurigo agudo decorrente de picada de inseto &#40;prurigo estr&#243;fulo&#41;&#46; &#40;C&#41; Prurigo agudo extenso por escabiose&#46; &#40;D&#41; Bolha ap&#243;s prurigo agudo em virtude de picadas de insetos&#46;</p>"
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          "pt" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Prurigo cr&#244;nico &#40;PGC&#41; e a morfologia elementar de les&#245;es&#46; &#40;A&#41; P&#225;pula &#40;&#60; 1<span class="elsevierStyleHsp" style=""></span>cm de di&#226;metro&#41; e n&#243;dulos &#40;&#62; 1<span class="elsevierStyleHsp" style=""></span>cm de di&#226;metro&#41;&#46; &#40;B&#41; Coalesc&#234;ncia de p&#225;pulas e n&#243;dulos &#40;placa&#41; e les&#245;es em arranjo linear&#46;</p>"
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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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prurigo no diabetes <span class="elsevierStyleItalic">mellitus</span>&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">Prurigo na insufici&#234;ncia renal&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">Prurigo na insufici&#234;ncia hep&#225;tica&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">Prurigo na malignidade interna&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">Prurigo na malignidade hematol&#243;gica&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">Prurigo associado a doen&#231;as eczematosas&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">Prurigo na infec&#231;&#227;o pelo HIV&#47;erup&#231;&#227;o papulopruriginosa do HIV &#40;preval&#234;ncia de 24&#37; a 36&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prurigo na gesta&#231;&#227;o&#47;<span class="elsevierStyleItalic">Prurigo gestationis</span> &#40;forma especial&#58; erup&#231;&#227;o polimorfa da gravidez&#41;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prurigo na alergia a f&#225;rmacos</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prurigo na alergia a metais</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prurigo nas doen&#231;as psiqui&#225;tricas</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prurigo idiop&#225;tico &#40;causa indeterminada&#41;</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3644937.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Classifica&#231;&#227;o do prurigo de acordo com sua causa subjacente&#46; Frequentemente&#44; a maioria dessas formas evolui para prurigo cr&#244;nico<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a></p>"
        ]
      ]
      7 => 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"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Doen&#231;as dermatol&#243;gicas associadas ao prurigo cr&#244;nico</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prurigo cr&#244;nico sem les&#245;es cut&#226;neas de outras dermatoses</th></tr></thead><tbody title="tbody"><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">Doen&#231;as inflamat&#243;rias ou parasit&#225;rias da pele&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">Dermatite at&#243;pica&#44; l&#237;quen plano&#44; escabiose&#44; l&#237;quen simples cr&#244;nico&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">Condi&#231;&#245;es infecciosas&#47;parasit&#225;rias&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">Parasitoses gastrintestinais&#44; hepatites cr&#244;nicas&#44; infec&#231;&#227;o por HIV&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">Prurigo relacionado a f&#225;rmaco&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">Eczema de contato&#44; rea&#231;&#245;es adversas a f&#225;rmaco&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">Doen&#231;as metab&#243;licas ou endocrinopatias&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">Dermatoses adquiridas perfurantes&#44; insufici&#234;ncia renal cr&#244;nica&#44; doen&#231;as colest&#225;ticas hep&#225;ticas&#44; hiper&#47;hipotiroidismo&#44; amiloidose nodular&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">Doen&#231;as autoimunes&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">Dermatoses bolhosas autoimunes &#40;dermatite herpetiforme&#44; penfigoide bolhoso&#44; dermatose por IgA linear&#44; p&#234;nfigo vegetante&#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">F&#225;rmacos&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">Inibidores da enzima conversora de angiotensina &#40;IECA&#41;&#44; antagonistas do receptor da angiotensina&#44; morfina&#44; amiodarona&#44; hidroclorotiazida&#44; alopurinol&#44; entre outras&#46;&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">Genodermatoses&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">Dermatose acantol&#237;tica transit&#243;ria &#40;doen&#231;a de Grover&#41;&#44; doen&#231;a de Darier&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">Psiqui&#225;tricas&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">Condi&#231;&#245;es psic&#243;ticas ou neur&#243;ticas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;as neopl&#225;sicas</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Linfoma cut&#226;neo de c&#233;lulas T ou B&#44; <span class="elsevierStyleItalic">leukaemia cutis</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Causas neurop&#225;ticas</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">Prurido braquiorradial&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">Neuralgia p&#243;s&#8208;herp&#233;tica&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">Polineuropatia ou mononeurite&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">Doen&#231;as psiqui&#225;tricas&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">Prurido associado a ansiedade&#44; depress&#227;o ou outras condi&#231;&#245;es psiqui&#225;tricas&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">Estase venosa&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"><span class="elsevierStyleItalic">Prurigo nodularis</span> em virtude do prurido e ato de co&#231;ar das veias varicosas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3644940.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Doen&#231;as dermatol&#243;gicas associadas a prurido e prurigo cr&#244;nico&#44; e prurido&#47;prurigo cr&#244;nico sem les&#245;es cut&#226;neas de outras dermatoses<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">1&#44;21</span></a></p>"
        ]
      ]
      8 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Tabela 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Crit&#233;rios maiores&#58;</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">i&#41; Prurido cr&#244;nico &#40;&#8805; 6 semanas&#41;&#59;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ii&#41; Hist&#243;ria e&#47;ou sinais de prurido repetidos&#59;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">iii&#41; Presen&#231;a de m&#250;ltiplas les&#245;es pruriginosas localizadas ou generalizadas<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="17" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Crit&#233;rios associados&#58;</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">i&#41; Sinais cl&#237;nicos</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">Les&#245;es pruriginosas&#58; simetricamente distribu&#237;das&#44; raramente afetando a face e palmas&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">Sinais do ato de co&#231;ar&#58; escoria&#231;&#245;es&#44; cicatrizes&#44; liquenifica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ii&#41; Diversidade de manifesta&#231;&#245;es cl&#237;nicas</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">Tipo papular&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">Tipo nodular&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">Tipo placa&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">Tipo umbilicado&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">Tipo linear&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">iii&#41; Sintomas</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">Usualmente&#44; as les&#245;es pruriginosas se desenvolvem ap&#243;s o in&#237;cio do prurido&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">Qualidade&#58; prurido&#44; queima&#231;&#227;o&#44; dor ou pinica&#231;&#227;o&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">Sinais de cronicidade&#58; intensidade importante do prurido&#44; alocinesia&#44; hipercinesia&#44; aumento cont&#237;nuo no n&#250;mero de les&#245;es&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">Qualidade de vida prejudicada&#44; perda de sono&#44; dias de absente&#237;smo ao trabalho e&#47;ou comportamento obsessivo&#8208;compulsivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">iv&#41; Emo&#231;&#245;es</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">Depress&#227;o&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">Ansiedade&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">Raiva&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">Desgosto&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">Vergonha&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">Desamparo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            ]
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          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Diretriz do F&#243;rum Internacional sobre o Estudo do Prurido &#40;IFSI&#41; sobre crit&#233;rios diagn&#243;sticos de prurigo cr&#244;nico&#46; Os tr&#234;s crit&#233;rios maiores s&#227;o necess&#225;rios para estabelecer o diagn&#243;stico de prurigo cr&#244;nico&#46; Os crit&#233;rios menores est&#227;o frequentemente presentes&#44; mas n&#227;o s&#227;o obrigat&#243;rios<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a></p>"
        ]
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        "etiqueta" => "Tabela 4"
        "tipo" => "MULTIMEDIATABLA"
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          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Tabela "
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><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="elsevierStyleBold">I&#46; EXAME F&#205;SICO&#58;</span>&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="elsevierStyleBold">1&#46; Exame dermatol&#243;gico&#58;</span>&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>&#8208; Distribui&#231;&#227;o cl&#237;nica das les&#245;es pruriginosas &#40;p&#46; ex&#46;&#44; localizadas&#47;generalizadas&#59; sim&#233;tricas&#47;assim&#233;tricas&#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="elsevierStyleHsp" style=""></span>&#8208; Morfologia dermatol&#243;gica das les&#245;es pruriginosas&#59;&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>&#8208; N&#250;mero de regi&#245;es do corpo afetadas&#59; n&#250;mero de les&#245;es pruriginosas&#47;com escoria&#231;&#245;es no topo&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>&#8208; <span class="elsevierStyleItalic">Sinal da borboleta</span> &#40;&#225;rea poupada de les&#245;es ou escoria&#231;&#245;es no dorso&#44; onde as m&#227;os do paciente n&#227;o alcan&#231;am&#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="elsevierStyleBold">2&#46; M&#233;todos objetivos&#58;</span>&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>&#8208; Medida das les&#245;es pruriginosas &#40;com r&#233;gua ou outro equipamento&#41;&#59;&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>&#8208; Monitoramento de les&#227;o alvo quando for poss&#237;vel &#40;clinicamente ou por fotos&#41;&#59;&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>&#8208; Documenta&#231;&#227;o fotogr&#225;fica&#59;&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>&#8208; Escores&#58; IGA<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&#44; para o estadiamento do prurigo cr&#244;nico&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="elsevierStyleBold">3&#46; Exame f&#237;sico geral&#58;</span>&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>&#8208; Palpa&#231;&#227;o abdominal&#44; avalia&#231;&#227;o de linfadenopatias&#44; avalia&#231;&#227;o da for&#231;a muscular&#44; ausculta &#40;pulm&#227;o&#44; cora&#231;&#227;o&#44; abdome&#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="elsevierStyleHsp" style=""></span>&#8208; Exame neurol&#243;gico simples&#59;&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>&#8208; Exame dermatol&#243;gico&#58; presen&#231;a de doen&#231;as de pele concomitantes&#44; xerose&#44; inspe&#231;&#227;o das mucosas&#59;&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>&#8208; Dermatoscopia das les&#245;es pruriginosas &#40;em busca de ectoparasitas como o <span class="elsevierStyleItalic">Sarcoptes scabiei</span>&#41;&#59;&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>&#8208; Pesquisa de dermografismo&#59; pesquisa do sinal de Nikolsky&#59; pesquisa do sinal de Darier&#46;&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="elsevierStyleBold">II&#46; BIOPSIAS DE PELE&#47;FLUIDOS &#47;SANGUE&#58;</span>&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">1&#46; Biopsias de pele&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46; Fluidos&#47;cultura microbiol&#243;gica se sinais de infec&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46; Avalia&#231;&#227;o microsc&#243;pica direta&#58; pesquisa de <span class="elsevierStyleItalic">Sarcoptes scabiei</span>&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>&#8208; Imunofluoresc&#234;ncia direta e indireta &#40;se h&#225; suspei&#231;&#227;o de condi&#231;&#245;es autoimunes como penfigoide bolhoso&#44; dermatite herpetiforme&#44; dermatose por IgA linear&#44; p&#234;nfigo paraneopl&#225;sico etc&#46;&#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="elsevierStyleHsp" style=""></span>&#8208; Histopatologia &#40;colora&#231;&#227;o com hematoxilina &#38; eosina ou colora&#231;&#245;es histoqu&#237;micas para dep&#243;sito de subst&#226;ncia amiloide&#44; mucina&#44; e outras desordens cut&#226;neas de dep&#243;sito&#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="elsevierStyleBold">III&#46; EXAMES DIAGN&#211;STICOS COMPLEMENTARES</span>&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="elsevierStyleBold">1&#46; Evitar procedimentos diagn&#243;sticos invasivos&#44; se desnecess&#225;rios&#44; para&#58;</span>&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>&#8208; PGC com prurido de leve intensidade ou pequena extens&#227;o&#59;&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>&#8208; PGC de origem n&#227;o dermatol&#243;gica&#59;&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>&#8208; Pacientes idosos ou pedi&#225;tricos e fr&#225;geis&#46;&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="elsevierStyleBold">2&#46; Grupos de pacientes nos quais estudos de imagem e laborat&#243;rio s&#227;o recomendados&#58;</span>&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>&#8208; Dependendo da hist&#243;ria familiar&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>&#8208; Dependendo do hist&#243;rico m&#233;dico &#40;p&#46; ex&#46;&#44; presen&#231;a de escarro com sangue&#44; mudan&#231;a do perfil de tosse&#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="elsevierStyleHsp" style=""></span>&#8208; Em todos os pacientes com PGC&#44; descartar doen&#231;as subjacentes&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>&#8208; Em todos os pacientes com PGC cuja doen&#231;a tem dura&#231;&#227;o de&#44; pelo menos&#44; um ano&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>&#8208; Em pacientes com PGC que relatam sudorese noturna ou perda ponderal&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\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8208; Em pacientes com PGC de origem indeterminada&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>&#8208; Em pacientes com PGC com prurido desproporcional&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>&#8208; Quando os pacientes demandam realizar exames laboratoriais&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"><span class="elsevierStyleBold">3&#46; Exames laboratoriais regularmente realizados&#58;</span>&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>&#8208; Hemograma&#59; eletr&#243;litos&#44; VHS&#44; PCR&#44; glicemia de jejum&#44; hemoglobina glicada &#40;HbA1c&#41;&#44; ferro&#44; ferritina&#44; LDH&#44; TSH&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>&#8208; IgE s&#233;rica total&#44; IgE espec&#237;fica &#40;se alergia respirat&#243;ria ou ocular forem suspeitas&#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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8208; Par&#226;metros de reten&#231;&#227;o renal &#40;p&#46; ex&#46;&#44; pot&#225;ssio&#44; creatinina&#44; ureia&#44; taxa de filtra&#231;&#227;o glomerular&#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"><span class="elsevierStyleHsp" style=""></span>&#8208; Enzimas hep&#225;ticas &#40;p&#46; ex&#46;&#44; gama&#8208;GT&#44; TGO&#44; TGP&#44; fosfatase alcalina&#44; bilirrubinas&#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\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">4&#46; Exames laboratoriais &#8211; com base nos achados patol&#243;gicos ou hist&#243;ria m&#233;dica&#58;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8208; Eletroforese de prote&#237;nas s&#233;ricas e urin&#225;rias&#44; imunofixa&#231;&#227;o &#40;maior sensibilidade se gamopatia monoclonal for suspeita&#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"><span class="elsevierStyleHsp" style=""></span>&#8208; Imunofenotipagem por citometria de fluxo para neoplasias hematol&#243;gicas no sangue perif&#233;rico<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">b</span></a>&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"><span class="elsevierStyleHsp" style=""></span>&#8208; Triptase s&#233;rica &#40;se houver suspeita de mastocitose sist&#234;mica&#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"><span class="elsevierStyleHsp" style=""></span>&#8208; Diagn&#243;stico de tiroidopatia em situa&#231;&#245;es especiais &#40;p&#46; ex&#46;&#44; paratorm&#244;nio&#44; fosfato&#44; Ca2<span class="elsevierStyleSup">&#43;</span>&#44; fT3&#44; fT4&#41;&#46;&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"><span class="elsevierStyleHsp" style=""></span>&#8208; Vitamina B12&#44; &#225;cido f&#243;lico &#40;se anemia estiver presente&#41;&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">5&#46; Exames de imagem&#44; se a anamnese e o exame f&#237;sico forem sugestivos de neoplasia ou doen&#231;as sist&#234;micas&#58;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8208; Tomografia computadorizada &#40;TC&#41; de cr&#226;nio&#44; t&#243;rax e abdome&#59; endoscopia digestiva&#44; conoloscopia&nbsp;\t\t\t\t\t\t\n
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">A imunofenotipagem por citometria de fluxo est&#225; indicada nas seguintes situa&#231;&#245;es cl&#237;nicas&#58; citopenia&#44; especialmente bicitopenia e pancitopenia&#59; contagem elevada de leuc&#243;citos&#44; incluindo linfocitose&#44; monocitose e eosinofilia&#59; presen&#231;a de c&#233;lulas at&#237;picas ou blastos na periferia sangue&#44; medula &#243;ssea ou fluidos corporais&#59; plasmocitose ou gamopatia monoclonal&#59; e organomegalia e massas teciduais&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">21</span></a></p>"
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          "pt" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Proposta de exames dermatol&#243;gico e laboratoriais para pacientes com prurigo cr&#244;nico<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">16</span></a></p>"
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                  \t\t\t\t">Emolientes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Inibidores da calcineurina &#40;tacrolimus&#47;pimecrolimus&#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">Fototerapia UV &#40;UVB <span class="elsevierStyleItalic">narrow band</span>&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Gabapentina&#44; pregabalina<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Antidepressivos &#40;p&#46; ex&#46;&#44; mirtazapina&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Canabinoides&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Imunossupressores &#40;metotrexato&#44; ciclosporina A&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Antagonista da neurocinina 1 &#40;NK1 &#8208; aprepitanto&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Antagonista dos receptores opioides &#956; &#40;naloxona&#44; naltrexona&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Inibidores de JAK &#40;abrocitinibe&#44; tofacitinibe&#44; upadacitinibe&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Anti IL&#8208;4&#47;13&#58; dupilumabe<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Anti&#8208;IL&#8208;31&#58; nemolizumabe<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Antirreceptor de antioncostatina &#40;OSMR&#946;&#47;IL&#8208;13&#41;&#58; vixarelimabe<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Antirreceptores KIT &#40;CDX&#8208;0159&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                      "titulo" => "2020 guidelines for the diagnosis and treatment of prurigo"
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                          "autores" => array:6 [
                            0 => "T&#46; Satoh"
                            1 => "H&#46; Yokozeki"
                            2 => "H&#46; Murota"
                            3 => "Y&#46; Tokura"
                            4 => "K&#46; Kabashima"
                            5 => "K&#46; Takamori"
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                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Presse Med&#46;"
                        "fecha" => "2009"
                        "volumen" => "38"
                        "paginaInicial" => "1099"
                        "paginaFinal" => "1105"
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Informação do artigo
ISSN: 26662752
Idioma original: Português
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