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causada pela bact&#233;ria espiroqueta n&#227;o cultiv&#225;vel <span class="elsevierStyleItalic">Treponema pallidum</span> subsp&#46; <span class="elsevierStyleItalic">pallidum</span>&#46; O diagn&#243;stico requer correla&#231;&#227;o entre dados cl&#237;nicos&#44; incluindo infec&#231;&#245;es pr&#233;vias e exposi&#231;&#227;o recente&#44; e testes laboratoriais&#46; O m&#233;todo diagn&#243;stico mais &#250;til para s&#237;filis &#233; o teste sorol&#243;gico&#46; No entanto&#44; considerando as manifesta&#231;&#245;es cl&#237;nicas multifacetadas&#44; o exame histopatol&#243;gico &#233; muito importante quando a s&#237;filis n&#227;o &#233; considerada inicialmente&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Treponema pallidum</span> &#233; classicamente reportado como sendo identificado pelas t&#233;cnicas de impregna&#231;&#227;o por prata como Warthin&#8208;Starry&#44; Levaditi ou Dieterle modificada por Steiner&#46; Entretanto&#44; fundos de marca&#231;&#227;o inespec&#237;fica ou artefatual de elementos teciduais&#44; como fibras reticulares e melanina&#44; representam dificuldades de interpreta&#231;&#227;o que podem originar resultados falso&#8208;positivos ou falso&#8208;negativos&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">4&#8211;7</span></a> Recentemente&#44; a marca&#231;&#227;o por imunoperoxidase com anticorpo policlonal anti&#8208;<span class="elsevierStyleItalic">Treponema pallidum</span> tem mostrado ser um m&#233;todo sens&#237;vel e &#250;til para real&#231;ar e identificar a espiroqueta&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">6&#8211;11</span></a> Este estudo foi realizado para avaliar a contribui&#231;&#227;o da imuno&#8208;histoqu&#237;mica &#40;IHQ&#41; e t&#233;cnica de Warthin&#8208;Starry &#40;WS&#41; na visualiza&#231;&#227;o da espiroqueta em amostras de bi&#243;psias de pele&#46; A correla&#231;&#227;o dessa visualiza&#231;&#227;o com achados cl&#237;nicos e histopatol&#243;gicos tamb&#233;m foi investigada&#44; a fim de definir o desempenho esperado em diferentes cen&#225;rios&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="par0020" class="elsevierStylePara elsevierViewall">Um estudo de acur&#225;cia diagn&#243;stica foi conduzido usando IHQ e t&#233;cnica de WS para detec&#231;&#227;o de espiroquetas nas amostras de bi&#243;psias de pele&#46; Dados cl&#237;nicos e sorol&#243;gicos de pacientes vistos em dois hospitais terci&#225;rios no Rio de Janeiro entre&#160;os anos de 2000 e&#160;2019 foram recuperados de registros m&#233;dicos&#46; Os pacientes foram classificados com s&#237;filis quando os achados cl&#237;nicos foram consistentes e os testes sorol&#243;gicos foram positivos &#40;<span class="elsevierStyleItalic">Veneral Disease Research Laboratory Test</span> &#91;VDRL&#93; com t&#237;tulos maiores que&#160;1&#47;8&#160;ou teste trepon&#234;mico positivo&#41;&#44; ou VDRL foi reagente no l&#237;quor em qualquer titula&#231;&#227;o no momento da bi&#243;psia de pele e da investiga&#231;&#227;o diagn&#243;stica&#46; Os pacientes com uma ou mais amostras de pele foram inclu&#237;dos&#46; Um grupo controle foi formado por amostras de pele de pacientes com testes sorol&#243;gicos n&#227;o reagentes para s&#237;filis e diagnosticados com outras dermatoses que poderiam ser consideradas nos diagn&#243;sticos diferenciais cl&#237;nicos e histopatol&#243;gicos da s&#237;filis&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Cortes histol&#243;gicos de 4<span class="elsevierStyleHsp" style=""></span>&#956;m de espessura foram obtidos de blocos de parafina para colora&#231;&#227;o de hematoxilina &#38; eosina e WS&#44; de acordo com protocolo de Luna&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">12</span></a> Os laudos histopatol&#243;gicos foram revisados e as l&#226;minas&#44; reavaliadas&#46; Padr&#227;o de rea&#231;&#227;o inflamat&#243;ria&#44; distribui&#231;&#227;o do infiltrado&#44; hiperplasia endotelial e semiquantifica&#231;&#227;o dos plasm&#243;citos foram considerados na avalia&#231;&#227;o das amostras de pele de pacientes com s&#237;filis&#46; Plasm&#243;citos foram codificados como &#43;&#43;&#47;&#43;&#43; quando compunham mais de&#160;30&#37; do infiltrado&#59; &#43;&#47;&#43;&#43;&#44; menos do que&#160;30&#37;&#59; e zero quando eram ausentes ou raros&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Cortes histopatol&#243;gicos adicionais foram obtidos para o estudo imuno&#8208;histoqu&#237;mico realizado com pr&#233;&#8208;tratamento de recupera&#231;&#227;o de ep&#237;topo induzido pelo calor&#44; anticorpo prim&#225;rio policlonal contra <span class="elsevierStyleItalic">T&#46; pallidum</span> &#40;BIOCARE Medical&#44; Calif&#243;rnia&#44; EUA&#41; em dilui&#231;&#227;o de&#160;1&#58;200 e sistema de detec&#231;&#227;o polim&#233;rica &#40;Novolink Max Polymer Detection System&#44; Leica Biosystems&#44; Illinois&#44; EUA&#41;&#46; A an&#225;lise IHQ foi cega para o diagn&#243;stico e realizada simult&#226;nea e consensualmente por dois patologistas com ampla experi&#234;ncia em diagn&#243;stico histopatol&#243;gico e imuno&#8208;histoqu&#237;mico de doen&#231;as infecciosas&#44; em microsc&#243;pio &#243;ptico Nikon <span class="elsevierStyleItalic">dual head</span> E200&#46; A an&#225;lise da carga bacteriana foi feita com escala semiquantitativa considerando &#40;3&#43;&#41; numerosas bact&#233;rias em todos os campos&#59; &#40;2&#43;&#41; numerosas bact&#233;rias em alguns campos&#59; e &#40;1&#43;&#41; raras bact&#233;rias&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">As an&#225;lises estat&#237;sticas foram realizadas usando o <span class="elsevierStyleItalic">software</span> SPSS vers&#227;o&#160;20&#46; Raz&#245;es de preval&#234;ncia &#40;RP&#41; e seus respectivos intervalos de confian&#231;a &#40;IC&#41; de 95&#37; foram calculados para medir a associa&#231;&#227;o entre a positividade da IHQ e as vari&#225;veis cl&#237;nico&#8208;histopatol&#243;gicas&#46; Os testes de Qui&#8208;quadrado &#40;&#967;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">2</span></a>&#41; e exato de Fisher foram usados para determinar a signific&#226;ncia estat&#237;stica&#46; O n&#237;vel de signific&#226;ncia de&#160;0&#44;05 foi definido&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="par0040" class="elsevierStylePara elsevierViewall">Trinta e oito pacientes &#40;29&#160;homens e 9&#160;mulheres&#41; com idades entre&#160;19&#160;e&#160;66&#160;anos &#40;m&#233;dia&#58;&#160;42&#160;anos&#44; mediana&#58;&#160;39&#160;anos&#41; com s&#237;filis e suas&#160;40&#160;amostras de pele foram inclu&#237;dos no estudo&#46; A sorologia anti&#8208;HIV foi positiva em 22 pacientes&#59; 10 pacientes demonstravam carga viral<span class="elsevierStyleHsp" style=""></span>&#62; 1&#46;000&#160;c&#243;pias&#47;mL&#59; sete pacientes apresentavam contagem de CD4 &#60;<span class="elsevierStyleHsp" style=""></span>200&#160;c&#233;lulas&#47;mm<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">3</span></a>&#44; e seis pacientes tinham ambos&#46; As les&#245;es de pele eram predominantes nos membros superiores&#160;&#40;32&#47;38&#41;&#46; Vinte e seis pacientes exibiam les&#245;es papulares&#44; e 22&#160;em placas&#46; Outras les&#245;es de pele descritas foram exantemas &#40;10&#47;38&#41;&#44; n&#243;dulos &#40;10&#47;38&#41; e p&#250;stulas ou crostas &#40;8&#47;38&#41;&#46; Vinte e nove amostras &#40;72&#44;5&#37;&#41; vieram de pacientes com s&#237;filis secund&#225;ria&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Os laudos histopatol&#243;gicos de 30&#47;40&#160;&#40;75&#37;&#41; amostras de pacientes com s&#237;filis foram considerados compat&#237;veis com o diagn&#243;stico&#46; Farmacodermia&#44; psor&#237;ase&#44; s&#237;ndrome de Reiter e xantogranuloma foram outros diagn&#243;sticos histopatol&#243;gicos sugeridos&#46; Em cinco laudos&#160;&#40;12&#44;5&#37;&#41;&#44; nenhuma sugest&#227;o de diagn&#243;stico histopatol&#243;gico foi feita&#46; Os padr&#245;es de rea&#231;&#227;o tecidual mais comuns foram dermatite perivascular superficial e profunda e de interface &#40;27&#44;5&#37;&#41;&#44; e o achado mais comum foi hiperplasia endotelial &#40;75&#37;&#41; &#8211; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Vinte e seis amostras de pele formaram o grupo controle e eram de pacientes diagnosticados com outras dermatoses &#40;10 farmacodermias&#44; 10 com psor&#237;ase&#44; quatro de l&#250;pus eritematoso&#44; quatro eczemas&#44; duas de hansen&#237;ase&#44; duas eritrodermias&#44; duas vasculites&#44; uma s&#237;ndrome de Sweet&#44; e uma l&#237;quen plano&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">A impregna&#231;&#227;o pelo WS foi negativa ou inconclusiva em todas as amostras&#46; Um fundo com impregna&#231;&#227;o de estruturas inespec&#237;ficas e de melanina nos dendritos dos melan&#243;citos tornou imposs&#237;vel identificar definitivamente as espiroquetas &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">A IHQ foi positiva em&#160;24&#160;das&#160;40&#160;amostras de pele de pacientes com s&#237;filis&#44; e foi negativa em todas&#160;as 36 amostras do controle sem s&#237;filis&#44; produzindo sensibilidade de 60&#37; &#40;95&#37;&#160;IC&#160;44&#44;8&#8208;75&#44;2&#41;&#44; especificidade de 100&#37;&#44; valor preditivo positivo de 100&#37;&#44; valor preditivo negativo de 69&#44;2&#37; &#40;95&#37;&#160;IC&#160;56&#44;7&#8208;81&#44;8&#41;&#46; A acur&#225;cia do teste foi de&#160;78&#44;9&#37; &#40;95&#37;&#160;IC&#160;69&#44;8&#8208;88&#44;1&#41;&#46; Os diagn&#243;sticos histol&#243;gicos propostos nas amostras positivas de IHQ foram s&#237;filis&#160;&#40;17&#47;24&#41;&#59; farmacodermia apenas&#160;&#40;4&#47;24&#41;&#59; farmacodermia e s&#237;filis como hip&#243;tese adicional&#160;&#40;2&#47;24&#41;&#59; s&#237;ndrome de Reiter&#160;&#40;1&#47;24&#41;&#59; e nenhuma sugest&#227;o histopatol&#243;gica foi feita em&#160;duas&#160;amostras&#46; A maioria dos nossos casos apresentava espiroquetas tanto na derme &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>A&#41; quanto na epiderme &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>B&#41;&#46; A <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a> demonstra os resultados da IHQ&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Os resultados da revis&#227;o dos dados cl&#237;nicos e dos achados histopatol&#243;gicos e suas correla&#231;&#245;es com a IHQ s&#227;o apresentados nas <a class="elsevierStyleCrossRefs" href="#tbl0010">tabelas 2 e 3</a>&#46; A IHQ foi frequentemente positiva nas amostras de pacientes com s&#237;filis secund&#225;ria &#40;RP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;441&#41; ou com s&#237;filis terci&#225;ria &#40;RP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;286&#41;&#44; com sorologia anti&#8208;HIV n&#227;o reagente &#40;RP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;444&#41; ou em imunossupress&#227;o pelo HIV com CD4&#160;&#60;<span class="elsevierStyleHsp" style=""></span>200&#160;c&#233;lulas&#47;mm<span class="elsevierStyleSup">3</span> e CV<span class="elsevierStyleHsp" style=""></span>&#62;1&#46;000&#160;c&#243;pias&#47;mL &#40;RP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;133&#41;&#46; Os resultados positivos tamb&#233;m foram mais prevalentes em amostras com dermatite perivascular superficial&#44; profunda e de interface &#40;RP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;582&#41; ou com plasm&#243;citos abundantes &#43;&#43;&#47;&#43;&#43; &#40;RP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;547&#41;&#46; Amostras com dermatite perivascular superficial e profunda &#40;RP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;304&#41; ou plasm&#243;citos &#43;&#47;&#43;&#43; &#40;RP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;619&#41; apresentaram mais resultados negativos na IHQ&#46; Entretanto&#44; essas associa&#231;&#245;es n&#227;o foram consideradas significantes &#40;p<span class="elsevierStyleHsp" style=""></span>&#62; 0&#44;05&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discuss&#227;o</span><p id="par0070" class="elsevierStylePara elsevierViewall">Uma descri&#231;&#227;o cl&#237;nica e histopatol&#243;gica dos casos de s&#237;filis e estudo de acur&#225;cia diagn&#243;stica da IHQ com anticorpo anti&#8208;<span class="elsevierStyleItalic">T&#46; pallidum</span> foi realizada&#46; Nosso estudo mostrou alta frequ&#234;ncia de s&#237;filis adquirida em homens &#40;76&#44;3&#37;&#41;&#44; assim como reportado pela literatura&#44;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">1&#8211;3</span></a> especialmente com relatos entre homens que fazem sexo com homens&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">1&#44;13</span></a> S&#237;filis tamb&#233;m foi observada em adolescentes e pacientes mais velhos&#44; grupos comumente considerados sem risco ou com baixo risco para a infec&#231;&#227;o&#46; A fase secund&#225;ria da doen&#231;a foi predominante&#44; provavelmente em decorr&#234;ncia da alta frequ&#234;ncia de bi&#243;psias de pele realizadas nessa fase&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">A dermatite de interface associada &#224; dermatite perivascular superficial e profunda&#160;&#40;27&#44;5&#37;&#41; e &#224; dermatite perivascular superficial e profunda e perianexial&#160;&#40;20&#37;&#41; destacou a mistura de padr&#245;es de rea&#231;&#227;o tecidual j&#225; reportada&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">14</span></a> Hiperplasia endotelial tamb&#233;m foi frequente&#160;&#40;75&#37;&#41;&#44; como nos estudos anteriores&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">14&#44;15</span></a> Plasm&#243;citos foram raros ou ausentes em sete amostras de pele&#160;&#40;17&#44;5&#37;&#41;&#44; concordando com relatos da literatura de escassez e aus&#234;ncia de plasm&#243;citos em at&#233;&#160;25&#37;&#8208;33&#37; das amostras&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">16&#8211;18</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">As espiroquetas e sua morfologia t&#237;pica foram facilmente visualizadas pelo m&#233;todo imuno&#8208;histoqu&#237;mico&#46; Resultados semelhantes s&#227;o relatados com os mesmos anticorpos&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">9</span></a> ou anticorpos semelhantes&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">6&#44;8</span></a> A IHQ como teste diagn&#243;stico forneceu diagn&#243;stico espec&#237;fico de s&#237;filis em 60&#37; dos casos&#44; n&#250;mero que se aproxima de estudos anteriores &#40;71&#37;&#8208;100&#37; de sensibilidade&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">6&#44;9</span></a> N&#227;o foi poss&#237;vel determinar a positividade pela&#160;t&#233;cnica&#160;de Warthin&#8208;Starry &#40;WS&#41;&#46; Quatresooz e Pi&#233;rard&#44; em 2009&#44; mostraram achados semelhantes com resultados inconclusivos ou negativos com a t&#233;cnica WS devido ao fundo de melanina na epiderme e fibrilas de reticulina na derme&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">9</span></a> Outros autores&#44; entretanto&#44; encontraram taxas de sensibilidade de 9&#37; e 60&#37; em amostras de pele&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">8&#44;10</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">As espiroquetas podem predominar na derme<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">6</span></a> ou na epiderme de les&#245;es de pele da s&#237;filis secund&#225;ria&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">7&#44;8</span></a> A maioria dos nossos casos apresentava espiroquetas tanto na derme quanto na epiderme&#44; e a alta carga bacteriana &#40;3&#43;&#41; foi predominante&#46; Esses resultados indicam que os micro&#8208;organismos ainda est&#227;o difusamente disseminados na pele durante a fase secund&#225;ria da doen&#231;a&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Na epiderme&#44; as espiroquetas localizaram&#8208;se principalmente na camada basal ou suprabasal&#44; e em&#160;62&#44;5&#37; das amostras n&#227;o foram observadas na parte mais alta&#44; ao contr&#225;rio dos resultados de Phelps et al&#46;&#44; que raramente observaram espiroquetas nas por&#231;&#245;es mais baixas da epiderme&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a> O achado de espiroquetas no epit&#233;lio folicular e ao redor dos anexos em&#160;58&#44;3&#37; das amostras positivas apoiam ainda mais a teoria de epiteliotropismo do micro&#8208;organismo&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">As altera&#231;&#245;es vasculares s&#227;o componentes importantes da resposta inflamat&#243;ria tecidual na s&#237;filis&#46; Hiperplasia endotelial foi achado comum e evidente&#44; e numerosas espiroquetas imunomarcadas foram detectadas nas paredes dos vasos&#46; Martin&#8208;Ezquerra et al&#46; tamb&#233;m encontraram um padr&#227;o vasculotr&#243;pico &#8211; por&#233;m&#44; principalmente nas les&#245;es de s&#237;filis prim&#225;ria&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Nenhuma correla&#231;&#227;o significante entre IHQ e caracter&#237;sticas cl&#237;nicas ou histopatol&#243;gicas foi observada&#46; No entanto&#44; a preval&#234;ncia de resultados positivos pela IHQ foi alta em amostras de pacientes sem coinfec&#231;&#227;o pelo HIV &#40;RP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;444&#41; e naqueles com imunossupress&#227;o pelo HIV com CD4&#160;&#60;<span class="elsevierStyleHsp" style=""></span>200&#160;c&#233;lulas&#47;mm<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">3</span></a> e CV<span class="elsevierStyleHsp" style=""></span>&#62; 1&#44;000&#160;c&#243;pias&#47;mL &#40;RP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;133&#41;&#46; Esses resultados sugerem que a infec&#231;&#227;o pelo HIV por si s&#243; n&#227;o teve impacto principal na detec&#231;&#227;o de espiroquetas&#44; mas o estado de imunossupress&#227;o pode influenciar a dissemina&#231;&#227;o de espiroquetas nas amostras de s&#237;filis&#46; Similar aos nossos achados&#44; pesquisas anteriores reportaram alta carga bacteriana em amostras de pele de pacientes com contagem de CD4 &#60;<span class="elsevierStyleHsp" style=""></span>250&#160;c&#233;lulas<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">10</span></a> ou em estados de imunossupress&#227;o associados com s&#237;filis maligna precoce&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">As amostras cut&#226;neas de s&#237;filis com dermatite perivascular superficial e profunda e de interface e com plasm&#243;citos vis&#237;veis no infiltrado &#40;&#43;&#43;&#47;&#43;&#43;&#41; mostraram alta preval&#234;ncia de resultados positivos na IHQ em compara&#231;&#227;o com amostras sem esses achados &#40;RP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;582&#59; RP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;547&#44; respectivamente&#41;&#46; Ao contr&#225;rio&#44; amostras com dermatite perivascular superficial e profunda &#40;RP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;304&#41; ou poucos plasm&#243;citos &#40;&#43;&#47;&#43;&#43;&#59; RP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;619&#41; sugerem que mesmo com resultados negativos na IHQ&#44; o diagn&#243;stico da s&#237;filis n&#227;o pode ser exclu&#237;do&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclus&#227;o</span><p id="par0110" class="elsevierStylePara elsevierViewall">A detec&#231;&#227;o de ant&#237;genos no protocolo de IHQ real&#231;ou espiroquetas de <span class="elsevierStyleItalic">Treponema pallidum</span> e possibilitou diagn&#243;stico indubit&#225;vel de s&#237;filis nas amostras teciduais&#46; A impregna&#231;&#227;o por WS foi considerada ineficiente na detec&#231;&#227;o da bact&#233;ria e n&#227;o ofereceu nenhuma contribui&#231;&#227;o para o diagn&#243;stico espec&#237;fico da doen&#231;a&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Comit&#234;s &#233;ticos</span><p id="par0115" class="elsevierStylePara elsevierViewall">Os comit&#234;s &#233;ticos do Hospital Clementino Fraga Filho &#40;HUCFF&#41; da Universidade Federal do Rio de Janeiro &#40;UFRJ&#41; e do Instituto Nacional de Doen&#231;as Infecciosas Evandro Chagas &#40;INI&#41;&#44; Funda&#231;&#227;o Oswaldo Cruz &#40;Fiocruz&#41;&#44; Brasil&#44; aprovaram o estudo&#46; Os comit&#234;s dispensaram informe de consentimento porque nenhuma informa&#231;&#227;o de identifica&#231;&#227;o pessoal foi inclu&#237;da no conjunto de dados usado para an&#225;lise&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Suporte financeiro</span><p id="par0120" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Contribui&#231;&#227;o dos autores</span><p id="par0125" class="elsevierStylePara elsevierViewall">Mariana Freitas de Assis Pereira Rosa&#58; Concep&#231;&#227;o e o desenho do estudo&#59; levantamento dos dados&#44; ou an&#225;lise e interpreta&#231;&#227;o dos dados&#59; an&#225;lise estat&#237;stica&#59; reda&#231;&#227;o do artigo ou revis&#227;o cr&#237;tica do conte&#250;do intelectual importante&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; revis&#227;o cr&#237;tica da literatura&#59; aprova&#231;&#227;o final da vers&#227;o final do manuscrito&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Leonardo Pereira Quintella&#58; Concep&#231;&#227;o e o desenho do estudo&#59; levantamento dos dados&#44; ou an&#225;lise e interpreta&#231;&#227;o dos dados&#59; an&#225;lise estat&#237;stica&#59; reda&#231;&#227;o do artigo ou revis&#227;o cr&#237;tica do conte&#250;do intelectual importante&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; revis&#227;o cr&#237;tica da literatura&#59; aprova&#231;&#227;o final da vers&#227;o final do manuscrito&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Luiz Claudio Ferreira&#58; Levantamento dos dados&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Tullia Cuzzi&#58; Concep&#231;&#227;o e o desenho do estudo&#59; levantamento dos dados&#44; ou an&#225;lise e interpreta&#231;&#227;o dos dados&#59; an&#225;lise estat&#237;stica&#59; reda&#231;&#227;o do artigo ou revis&#227;o cr&#237;tica do conte&#250;do intelectual importante&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; revis&#227;o cr&#237;tica da literatura&#59; aprova&#231;&#227;o final da vers&#227;o final do manuscrito&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflito de interesses</span><p id="par0145" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A s&#237;filis&#44; em suas diferentes fases&#44; pode ser diagn&#243;stico dif&#237;cil na &#225;rea cl&#237;nica e histopatol&#243;gica&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Avaliar a detec&#231;&#227;o e a distribui&#231;&#227;o tecidual de <span class="elsevierStyleItalic">Treponema pallidum</span> nas les&#245;es de pele de s&#237;filis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todo</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Estudo cego de acur&#225;cia diagn&#243;stica foi realizado com imuno&#8208;histoqu&#237;mica e impregna&#231;&#227;o por prata de Warthin&#8208;Starry nas amostras de pele de pacientes com s&#237;filis e outras doen&#231;as&#46; Os pacientes foram atendidos em dois hospitais terci&#225;rios entre os anos de&#160;2000&#160;e&#160;2019&#46; Raz&#245;es de preval&#234;ncia &#40;RP&#41; e intervalos de confian&#231;a &#40;IC&#41; de 95&#37; foram calculados para avaliar associa&#231;&#227;o entre positividade da imuno&#8208;histoqu&#237;mica e vari&#225;veis cl&#237;nicas&#8208;histopatol&#243;gicas&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Trinta e oito pacientes com s&#237;filis e suas&#160;40&#160;amostras de bi&#243;psias foram inclu&#237;das para o estudo&#46; Trinta e seis amostras de pele formaram os controles sem s&#237;filis&#46; A t&#233;cnica de Warthin&#8208;Starry foi incapaz de demonstrar de maneira acurada a bact&#233;ria em todas as amostras&#46; A imuno&#8208;histoqu&#237;mica mostrou espiroquetas apenas em amostras de pele de pacientes de s&#237;filis &#40;24&#47;40&#41; com sensibilidade de 60&#37; &#40;95&#37;&#160;IC&#160;44&#44;8&#8208;75&#44;2&#41;&#46; A especificidade foi de 100&#37; e a acur&#225;cia de 78&#44;9&#37; &#40;95&#37;&#160;IC&#160;69&#44;8&#8208;88&#44;1&#41;&#46; A maioria dos nossos casos teve espiroquetas tanto na derme quanto na epiderme&#44; com alta carga bacteriana&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">As correla&#231;&#245;es entre imuno&#8208;histoqu&#237;mica e caracter&#237;sticas cl&#237;nico&#8208;histopatol&#243;gicas foram observadas&#44; mas foram limitadas estatisticamente em decorr&#234;ncia do pequeno tamanho da amostra&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#227;o</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Espiroquetas foram prontamente vistas no protocolo de imuno&#8208;histoqu&#237;mica&#44; o que pode contribuir para o diagn&#243;stico de s&#237;filis em amostras de bi&#243;psias cut&#226;neas&#46; Por outro lado&#44; a t&#233;cnica de Warthin&#8208;Starry mostrou ser de nenhum valor pr&#225;tico&#46;</p></span>"
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                  \t\t\t\t" scope="col">n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</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
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                  \t\t\t\t">Epiderme e derme&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">18 &#40;75&#44;0&#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\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5 &#40;20&#44;8&#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">Epiderme &#40;apenas&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1 &#40;4&#44;2&#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\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4 &#40;16&#44;6&#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">Basal&#44; suprabasal e por&#231;&#245;es altas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;12&#44;5&#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">Suprabasal &#40;apenas&#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">2 &#40;8&#44;3&#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">Basal e por&#231;&#245;es altas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;4&#44;2&#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">Localiza&#231;&#227;o d&#233;rmica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;95&#44;8&#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">Extracelular&#44; no infiltrado inflamat&#243;rio&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">21 &#40;87&#44;5&#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">Parede de vasos d&#233;rmicos&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">20 &#40;83&#44;3&#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">Intracelular&#44; no infiltrado inflamat&#243;rio&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">18 &#40;75&#44;0&#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">Epit&#233;lio anexial&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;41&#44;6&#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">Dentro do vaso d&#233;rmico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;8&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Perianexial&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;16&#44;6&#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
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#43;3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;62&#44;5&#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>&#43;2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;12&#44;5&#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\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#43;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;25&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">Vari&#225;veis cl&#237;nicas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">S&#237;filis secund&#225;ria</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">29 &#40;72&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">19 &#40;47&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">10 &#40;25&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;213<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;694 &#40;0&#44;345&#8208;1&#44;396&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#237;filis secundo&#8208;terci&#225;ria</span></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>Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#44;286 &#40;0&#44;685&#8208;2&#44;413&#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">0&#44;471<a class="elsevierStyleCrossRef" href="#tblfn0010"><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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                  \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">36 &#40;90&#44;0&#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">21 &#40;52&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;37&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;778 &#40;0&#44;414&#8208;1&#44;460&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#237;filis terci&#225;ria</span></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>Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#44;0&#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">1 &#40;2&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&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">NA&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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                  \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">39 &#40;97&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;60&#44;0&#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">15 &#40;37&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#237;filis maligna precoce</span></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>Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;7&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;5&#44;0&#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">0&#44;536 &#40;0&#44;106&#8208;2&#44;709&#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">0&#44;348<a class="elsevierStyleCrossRef" href="#tblfn0010"><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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                  \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">37 &#40;92&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;57&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;35&#44;0&#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">1&#44;865 &#40;0&#44;369&#8208;9&#44;423&#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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#237;filis indeterminada</span></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>Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;7&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#44;5&#41;&#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">2 &#40;5&#44;0&#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">0&#44;536 &#40;0&#44;106&#8208;2&#44;709&#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">0&#44;348<a class="elsevierStyleCrossRef" href="#tblfn0010"><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
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;92&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;57&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;35&#44;0&#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">1&#44;865 &#40;0&#44;369&#8208;9&#44;423&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Coinfec&#231;&#227;o HIV</span></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>Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;55&#44;0&#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">11 &#40;27&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;27&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;692 &#40;0&#44;417&#8208;1&#44;149&#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">0&#44;154&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>N&#227;o&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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;45&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;32&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;12&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;444 &#40;0&#44;870&#8208;2&#44;397&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \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="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">CD4 &#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">200 c&#233;lulas&#47;mm</span><span class="elsevierStyleSup">3</span></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>Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;17&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;10&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3 &#40;7&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">CV</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#62; 1&#46;000 c&#243;pias</span></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>Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4 &#40;10&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2 &#40;5&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;882 &#40;0&#44;469&#8208;1&#44;660&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">Amostras de pele &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>40&#41; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IHQ &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>40&#41; &#40;&#37;&#41;</th><th class="td" title="\n
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                  \t\t\t\t" scope="col">RP &#40;95&#37;&#160;IC&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Positiva &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24&#41; &#40;60&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Negativa &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41; &#40;40&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Padr&#245;es de rea&#231;&#245;es teciduais perivasculares superficiais apenas</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3 &#40;7&#44;5&#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">4 &#40;10&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">33 &#40;82&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">21 &#40;52&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12 &#40;30&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#44;485 &#40;0&#44;608&#8208;3&#44;628&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Dermatite perivascular superficial e de interface</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;2&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Padr&#245;es de rea&#231;&#245;es teciduais perivasculares superficiais e profundas</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">33 &#40;82&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">NA&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>N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">39 &#40;97&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;57&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">16 &#40;40&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Dermatite perivascular superficial&#44; profunda&#44; de interface e psoriasiforme</span></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>Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2 &#40;5&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&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>N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">38 &#40;95&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">24 &#40;60&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">14 &#40;35&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&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="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Dermatite perivascular superficial&#44; profunda&#44; de interface&#44; perianexial e psoriasiforme</span></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>Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;5&#44;0&#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">2 &#40;5&#44;0&#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">0&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">NA&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">NA&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>N&#227;o&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">38 &#40;95&#44;0&#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">22 &#40;55&#44;0&#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">16 &#40;40&#44;0&#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="" valign="\n
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                  \t\t\t\t">&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="" valign="\n
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                  \t\t\t\t">&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="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Dermatite espongi&#243;tica&#44; de interface e nodular</span></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>Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1 &#40;2&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&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">NA&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">NA&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>N&#227;o&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">39 &#40;97&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;57&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">16 &#40;40&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \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="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Melan&#243;fagos</span></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>Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">20 &#40;50&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;27&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">9 &#40;22&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#44;845 &#40;0&#44;508&#8208;1&#44;410&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;519&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>N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">20 &#40;50&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">13 &#40;32&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">7 &#40;17&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1&#44;182 &#40;0&#44;709&#8208;1&#44;969&#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="" valign="\n
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                  \t\t\t\t">&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="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Plasm&#243;citos</span> &#43;&#43;&#47;&#43;&#43;</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>Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">19 &#40;47&#44;5&#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">14 &#40;35&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5 &#40;12&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;547 &#40;0&#44;917&#8208;2&#44;610&#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
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Journal Information
Vol. 98. Issue 4.
Pages 480-486 (1 July 2023)
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6441
Vol. 98. Issue 4.
Pages 480-486 (1 July 2023)
Artigo original
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Detecção imuno‐histoquímica de Treponema pallidum em amostras de pele com correlações clínicas e histopatológicas e análise crítica do Warthin‐Starry
Visits
6441
Mariana Freitas de Assis Pereira Rosaa,
Corresponding author
marianafaprosa@ufrj.br

Autor para correspondência.
, Leonardo Pereira Quintellab, Luiz Claudio Ferreirab, Tullia Cuzzic
a Programa de Pós-Graduação em Anatomia Patológica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
b Serviço de Anatomia Patológica, Instituto Nacional de Doenças Infecciosas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil
c Departamento de Patologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
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Abstract
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Tables (3)
Tabela 1. Distribuição e carga bacteriana das espiroquetas nas amostras de pele positivas na imuno‐histoquímica com anticorpo anti‐T. pallidum
Tabela 2. Associação entre resultados da imuno‐histoquímica com anticorpo anti‐T. pallidum e variáveis clínicas de pacientes com sífilis
Tabela 3. Associação entre resultados da imuno‐histoquímica com anticorpo anti‐T. pallidum e alterações histopatológicas nas amostras de pele de pacientes com sífilis
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Resumo
Fundamentos

A sífilis, em suas diferentes fases, pode ser diagnóstico difícil na área clínica e histopatológica.

Objetivos

Avaliar a detecção e a distribuição tecidual de Treponema pallidum nas lesões de pele de sífilis.

Método

Estudo cego de acurácia diagnóstica foi realizado com imuno‐histoquímica e impregnação por prata de Warthin‐Starry nas amostras de pele de pacientes com sífilis e outras doenças. Os pacientes foram atendidos em dois hospitais terciários entre os anos de 2000 e 2019. Razões de prevalência (RP) e intervalos de confiança (IC) de 95% foram calculados para avaliar associação entre positividade da imuno‐histoquímica e variáveis clínicas‐histopatológicas.

Resultados

Trinta e oito pacientes com sífilis e suas 40 amostras de biópsias foram incluídas para o estudo. Trinta e seis amostras de pele formaram os controles sem sífilis. A técnica de Warthin‐Starry foi incapaz de demonstrar de maneira acurada a bactéria em todas as amostras. A imuno‐histoquímica mostrou espiroquetas apenas em amostras de pele de pacientes de sífilis (24/40) com sensibilidade de 60% (95% IC 44,8‐75,2). A especificidade foi de 100% e a acurácia de 78,9% (95% IC 69,8‐88,1). A maioria dos nossos casos teve espiroquetas tanto na derme quanto na epiderme, com alta carga bacteriana.

Limitações do estudo

As correlações entre imuno‐histoquímica e características clínico‐histopatológicas foram observadas, mas foram limitadas estatisticamente em decorrência do pequeno tamanho da amostra.

Conclusão

Espiroquetas foram prontamente vistas no protocolo de imuno‐histoquímica, o que pode contribuir para o diagnóstico de sífilis em amostras de biópsias cutâneas. Por outro lado, a técnica de Warthin‐Starry mostrou ser de nenhum valor prático.

Palavras‐chave:
Diagnóstico
Histologia
Imuno‐histoquímica
Sífilis
Treponema pallidum
Full Text
Introdução

A sífilis é infecção sexualmente transmissível (IST) curável, em reemergência global nos últimos anos,1 e um grande desafio de saúde pública, particularmente em grupos com comportamento sexual de alto risco. No Brasil, a frequência da sífilis adquirida tem aumentado progressivamente nos últimos 10 anos. Esse aumento atingiu 30,2% em um único ano, entre 2017 e 2018. Entre 2010 e 2018, a taxa de detecção de sífilis em grávidas aumentou de 3,5 a 21,5 casos por mil nascidos vivos.2,3

A doença é causada pela bactéria espiroqueta não cultivável Treponema pallidum subsp. pallidum. O diagnóstico requer correlação entre dados clínicos, incluindo infecções prévias e exposição recente, e testes laboratoriais. O método diagnóstico mais útil para sífilis é o teste sorológico. No entanto, considerando as manifestações clínicas multifacetadas, o exame histopatológico é muito importante quando a sífilis não é considerada inicialmente.

Treponema pallidum é classicamente reportado como sendo identificado pelas técnicas de impregnação por prata como Warthin‐Starry, Levaditi ou Dieterle modificada por Steiner. Entretanto, fundos de marcação inespecífica ou artefatual de elementos teciduais, como fibras reticulares e melanina, representam dificuldades de interpretação que podem originar resultados falso‐positivos ou falso‐negativos.4–7 Recentemente, a marcação por imunoperoxidase com anticorpo policlonal anti‐Treponema pallidum tem mostrado ser um método sensível e útil para realçar e identificar a espiroqueta.6–11 Este estudo foi realizado para avaliar a contribuição da imuno‐histoquímica (IHQ) e técnica de Warthin‐Starry (WS) na visualização da espiroqueta em amostras de biópsias de pele. A correlação dessa visualização com achados clínicos e histopatológicos também foi investigada, a fim de definir o desempenho esperado em diferentes cenários.

Métodos

Um estudo de acurácia diagnóstica foi conduzido usando IHQ e técnica de WS para detecção de espiroquetas nas amostras de biópsias de pele. Dados clínicos e sorológicos de pacientes vistos em dois hospitais terciários no Rio de Janeiro entre os anos de 2000 e 2019 foram recuperados de registros médicos. Os pacientes foram classificados com sífilis quando os achados clínicos foram consistentes e os testes sorológicos foram positivos (Veneral Disease Research Laboratory Test [VDRL] com títulos maiores que 1/8 ou teste treponêmico positivo), ou VDRL foi reagente no líquor em qualquer titulação no momento da biópsia de pele e da investigação diagnóstica. Os pacientes com uma ou mais amostras de pele foram incluídos. Um grupo controle foi formado por amostras de pele de pacientes com testes sorológicos não reagentes para sífilis e diagnosticados com outras dermatoses que poderiam ser consideradas nos diagnósticos diferenciais clínicos e histopatológicos da sífilis.

Cortes histológicos de 4μm de espessura foram obtidos de blocos de parafina para coloração de hematoxilina & eosina e WS, de acordo com protocolo de Luna.12 Os laudos histopatológicos foram revisados e as lâminas, reavaliadas. Padrão de reação inflamatória, distribuição do infiltrado, hiperplasia endotelial e semiquantificação dos plasmócitos foram considerados na avaliação das amostras de pele de pacientes com sífilis. Plasmócitos foram codificados como ++/++ quando compunham mais de 30% do infiltrado; +/++, menos do que 30%; e zero quando eram ausentes ou raros.

Cortes histopatológicos adicionais foram obtidos para o estudo imuno‐histoquímico realizado com pré‐tratamento de recuperação de epítopo induzido pelo calor, anticorpo primário policlonal contra T. pallidum (BIOCARE Medical, Califórnia, EUA) em diluição de 1:200 e sistema de detecção polimérica (Novolink Max Polymer Detection System, Leica Biosystems, Illinois, EUA). A análise IHQ foi cega para o diagnóstico e realizada simultânea e consensualmente por dois patologistas com ampla experiência em diagnóstico histopatológico e imuno‐histoquímico de doenças infecciosas, em microscópio óptico Nikon dual head E200. A análise da carga bacteriana foi feita com escala semiquantitativa considerando (3+) numerosas bactérias em todos os campos; (2+) numerosas bactérias em alguns campos; e (1+) raras bactérias.

As análises estatísticas foram realizadas usando o software SPSS versão 20. Razões de prevalência (RP) e seus respectivos intervalos de confiança (IC) de 95% foram calculados para medir a associação entre a positividade da IHQ e as variáveis clínico‐histopatológicas. Os testes de Qui‐quadrado (χ2) e exato de Fisher foram usados para determinar a significância estatística. O nível de significância de 0,05 foi definido.

Resultados

Trinta e oito pacientes (29 homens e 9 mulheres) com idades entre 19 e 66 anos (média: 42 anos, mediana: 39 anos) com sífilis e suas 40 amostras de pele foram incluídos no estudo. A sorologia anti‐HIV foi positiva em 22 pacientes; 10 pacientes demonstravam carga viral> 1.000 cópias/mL; sete pacientes apresentavam contagem de CD4 <200 células/mm3, e seis pacientes tinham ambos. As lesões de pele eram predominantes nos membros superiores (32/38). Vinte e seis pacientes exibiam lesões papulares, e 22 em placas. Outras lesões de pele descritas foram exantemas (10/38), nódulos (10/38) e pústulas ou crostas (8/38). Vinte e nove amostras (72,5%) vieram de pacientes com sífilis secundária.

Os laudos histopatológicos de 30/40 (75%) amostras de pacientes com sífilis foram considerados compatíveis com o diagnóstico. Farmacodermia, psoríase, síndrome de Reiter e xantogranuloma foram outros diagnósticos histopatológicos sugeridos. Em cinco laudos (12,5%), nenhuma sugestão de diagnóstico histopatológico foi feita. Os padrões de reação tecidual mais comuns foram dermatite perivascular superficial e profunda e de interface (27,5%), e o achado mais comum foi hiperplasia endotelial (75%) – (fig. 1).

Figura 1.

Pele, achados histopatológicos. (A) Dermatite de interface (Hematoxilina & eosina, 400×). (B) Hiperplasia endotelial e plasmócitos em abundância ao redor dos vasos dérmicos (Hematoxilina & eosina, 400×).

(0.52MB).

Vinte e seis amostras de pele formaram o grupo controle e eram de pacientes diagnosticados com outras dermatoses (10 farmacodermias, 10 com psoríase, quatro de lúpus eritematoso, quatro eczemas, duas de hanseníase, duas eritrodermias, duas vasculites, uma síndrome de Sweet, e uma líquen plano).

A impregnação pelo WS foi negativa ou inconclusiva em todas as amostras. Um fundo com impregnação de estruturas inespecíficas e de melanina nos dendritos dos melanócitos tornou impossível identificar definitivamente as espiroquetas (fig. 2).

Figura 2.

(A) Marcação de fundo da camada basal (Warthin‐Starry, 1000×). (B) Estruturas inespecíficas na derme (setas, Warthin‐Starry, 1.000×).

(0.51MB).

A IHQ foi positiva em 24 das 40 amostras de pele de pacientes com sífilis, e foi negativa em todas as 36 amostras do controle sem sífilis, produzindo sensibilidade de 60% (95% IC 44,8‐75,2), especificidade de 100%, valor preditivo positivo de 100%, valor preditivo negativo de 69,2% (95% IC 56,7‐81,8). A acurácia do teste foi de 78,9% (95% IC 69,8‐88,1). Os diagnósticos histológicos propostos nas amostras positivas de IHQ foram sífilis (17/24); farmacodermia apenas (4/24); farmacodermia e sífilis como hipótese adicional (2/24); síndrome de Reiter (1/24); e nenhuma sugestão histopatológica foi feita em duas amostras. A maioria dos nossos casos apresentava espiroquetas tanto na derme (fig. 3A) quanto na epiderme (fig. 3B). A tabela 1 demonstra os resultados da IHQ.

Figura 3.

Pele, achados imuno‐histoquímicos. (A) Espiroquetas na dermoepidérmica e derme papilar (imuno‐histoquímica com anticorpo anti‐Treponema pallidum, 100×). (B) Detalhe da localização das espiroquetas na epiderme baixa (imuno‐histoquímica com anticorpo anti‐Treponema pallidum, 1.000×, ver texto para detalhes técnicos).

(0.47MB).
Tabela 1.

Distribuição e carga bacteriana das espiroquetas nas amostras de pele positivas na imuno‐histoquímica com anticorpo anti‐T. pallidum

Localização  n (%) 
  Total (n=24) 
Epiderme e derme  18 (75,0) 
Derme (apenas)  5 (20,8) 
Epiderme (apenas)  1 (4,2) 
Localização epidérmica  19 (79,1) 
Basal e suprabasal  9 (37,5) 
Basal (apenas)  4 (16,6) 
Basal, suprabasal e porções altas  3 (12,5) 
Suprabasal (apenas)  2 (8,3) 
Basal e porções altas  1 (4,2) 
Localização dérmica  23 (95,8) 
Extracelular, no infiltrado inflamatório  21 (87,5) 
Parede de vasos dérmicos  20 (83,3) 
Intracelular, no infiltrado inflamatório  18 (75,0) 
Epitélio anexial  10 (41,6) 
Dentro do vaso dérmico  2 (8,3) 
Perianexial  4 (16,6) 
Carga bacteriana
+3  15 (62,5) 
+2  3 (12,5) 
+1  6 (25,0) 

Os resultados da revisão dos dados clínicos e dos achados histopatológicos e suas correlações com a IHQ são apresentados nas tabelas 2 e 3. A IHQ foi frequentemente positiva nas amostras de pacientes com sífilis secundária (RP=1,441) ou com sífilis terciária (RP=1,286), com sorologia anti‐HIV não reagente (RP=1,444) ou em imunossupressão pelo HIV com CD4 <200 células/mm3 e CV>1.000 cópias/mL (RP=1,133). Os resultados positivos também foram mais prevalentes em amostras com dermatite perivascular superficial, profunda e de interface (RP=1,582) ou com plasmócitos abundantes ++/++ (RP=1,547). Amostras com dermatite perivascular superficial e profunda (RP=0,304) ou plasmócitos +/++ (RP=0,619) apresentaram mais resultados negativos na IHQ. Entretanto, essas associações não foram consideradas significantes (p> 0,05).

Tabela 2.

Associação entre resultados da imuno‐histoquímica com anticorpo anti‐T. pallidum e variáveis clínicas de pacientes com sífilis

Variáveis clínicas  Amostras de pele (n=40) (%)  IHQ (n=40) (%)RP (95% IC)  p‐valora 
    Positiva (n=24) (60,0)  Negativa (n=16) (40,0)     
Sífilis secundária
Sim  29 (72,5)  19 (47,5)  10 (25,0)  1,441 (0,716‐2,900)  0,213b 
Não  11 (27,5)  5 (12,5)  6 (15,0)  0,694 (0,345‐1,396)   
Sífilis secundo‐terciária
Sim  4 (10,0)  3 (7,5)  1 (2,5)  1,286 (0,685‐2,413)  0,471b 
Não  36 (90,0)  21 (52,5)  15 (37,5)  0,778 (0,414‐1,460)   
Sífilis terciária
Sim  1 (2,5)  0 (0,0)  1 (2,5)  NA  NA 
Não  39 (97,5)  24 (60,0)  15 (37,5)     
Sífilis maligna precoce
Sim  3 (7,5)  1 (2,5)  2 (5,0)  0,536 (0,106‐2,709)  0,348b 
Não  37 (92,5)  23 (57,5)  14 (35,0)  1,865 (0,369‐9,423)   
Sífilis indeterminada
Sim  3 (7,5)  1 (2,5))  2 (5,0)  0,536 (0,106‐2,709)  0,348b 
Não  37 (92,5)  23 (57,5)  14 (35,0)  1,865 (0,369‐9,423)   
Coinfecção HIV
Sim  22 (55,0)  11 (27,5)  11 (27,5)  0,692 (0,417‐1,149)  0,154 
Não  18 (45,0)  13 (32,5)  5 (12,5)  1,444 (0,870‐2,397)   
CD4 <200 células/mm3
Sim  7 (17,5)  4 (10,0)  3 (7,5)  0,943 (0,469‐1,895)  0,592b 
Não  33 (82,5)  20 (50,0)  13 (32,5)  1,061 (0,528‐2,132)   
CV> 1.000 cópias
Sim  10 (25,0)  6 (15,0)  4 (10,0)  1,000 (0,557‐1,794)  0,64b 
Não  30 (75,0)  18 (45,0)  12 (30,0)  1,000 (0,557‐1,794)   
CD4 <200 e CV> 1.000 cópias
Sim  6 (15,0)  4 (10,0)  2 (5,0)  1,133 (0,602‐2,132)  0,544b 
Não  34 (85,0)  20 (50,0)  14 (35,0)  0,882 (0,469‐1,660)   

IHQ, imuno‐histoquímica; CV, carga viral HIV; RP, razão de prevalência; 95% IC, intervalo de confiança de 95%; NA, não aplicável, poucos casos.

a

p‐valor por teste Qui‐Quadrado (χ2).

b

Teste exato de Fisher.

Tabela 3.

Associação entre resultados da imuno‐histoquímica com anticorpo anti‐T. pallidum e alterações histopatológicas nas amostras de pele de pacientes com sífilis

  Amostras de pele (n=40) (%)  IHQ (n=40) (%)RP (95% IC)  p‐valora 
    Positiva (n=24) (60,0)  Negativa (n=16) (40,0)     
Padrões de reações teciduais perivasculares superficiais apenas
Sim  7 (17,5)  3 (7,5)  4 (10,0)  0,673 (0,276‐1,646)  0,273b 
Não  33 (82,5)  21 (52,5)  12 (30,0)  1,485 (0,608‐3,628)   
Dermatite perivascular superficial
Sim  1 (2,5)  1 (2,5)  NA  NA 
Não  39 (97,5)  24 (60,0)  15 (37,5)     
Dermatite perivascular superficial e de interface
Sim  4 (10,0)  2 (5,0)  2 (5,0)  0,818 (0,297‐2,255)  0,529b 
Não  36 (90,0)  22 (55,0)  14 (35,0)  1,222 (0,443‐3,369)   
Dermatite perivascular superficial, espongiótica e psoriasiforme
Sim  1 (2,5)  1 (2,5)  NA  NA 
Não  39 (97,5)  23 (57,5)  16 (40,0)     
Dermatite psoriasiforme e de interface
Sim  1 (2,5)  1 (2,5)  NA  NA 
Não  39 (97,5)  24 (60,0)  15 (37,5)     
Padrões de reações teciduais perivasculares superficiais e profundas
Sim  33 (82,5)  21 (52,5)  12 (30,0)  1,485 (0,608‐3,628)  0,273b 
Não  7 (17,5)  3 (7,5)  4 (10,0)  0,673 (0,276‐1,646)   
Dermatite perivascular superficial e profunda
Sim  5 (12,5)  1 (2,5)  4 (10,0)  0,304 (0,052‐1,786)  0,073b 
Não  35 (87,5)  23 (57,5)  12 (30,0)  3,286 (0,560‐19,276)   
Dermatite perivascular superficial, profunda e perianexial
Sim  3 (7,5)  2 (5,0)  1 (2,5)  1,121 (0,482‐2,606)  0,652b 
Não  37 (92,5)  22 (55,0)  15 (37,5)  0,892 (0,384‐2,073)   
Dermatite perivascular superficial, profunda e de interface
Sim  11 (27,5)  9 (22,5)  2 (5,0)  1,582 (1,010‐2,477)  0,083b 
Não  29 (72,5)  15 (37,5)  14 (35,0)  0,632 (0,404‐0,990)   
Dermatite perivascular superficial, profunda, de interface e perianexial
Sim  8 (20,0)  5 (12,5)  3 (7,5)  1,053 (0,573‐1,934)  0,601b 
Não  32 (80,0)  19 (47,5)  13 (32,5)  0,950 (0,517‐1,746)   
Dermatite de interface e nodular
Sim  1 (2,5)  1 (2,5)  NA  NA 
Não  39 (97,5)  23 (57,5)  16 (40,0)     
Dermatite perivascular superficial, profunda, de interface e psoriasiforme
Sim  2 (5,0)  2 (5,0)  NA  NA 
Não  38 (95,0)  24 (60,0)  14 (35,0)     
Dermatite perivascular superficial, profunda, de interface, perianexial e psoriasiforme
Sim  2 (5,0)  2 (5,0)  NA  NA 
Não  38 (95,0)  22 (55,0)  16 (40,0)     
Dermatite espongiótica, de interface e nodular
Sim  1 (2,5)  1 (2,5)  NA  NA 
Não  39 (97,5)  23 (57,5)  16 (40,0)     
Melanófagos
Sim  20 (50,0)  11 (27,5)  9 (22,5)  0,845 (0,508‐1,410)  0,519 
Não  20 (50,0)  13 (32,5)  7 (17,5)  1,182 (0,709‐1,969)   
Plasmócitos ++/++
Sim  19 (47,5)  14 (35,0)  5 (12,5)  1,547 (0,917‐2,610)  0,093 
Não  21 (52,5)  10 (25,0)  11 (27,5)  0,646 (0,383‐1,090)   
Plasmócitos +/++
Sim  14 (35,0)  6 (15,0)  8 (20,0)  0,619 (0,321‐1,194)  0,104 
Não  26 (65,0)  18 (45,0)  8 (20,0)  1,615 (0,838‐3,116)   
Ausência de plasmócitos
Sim  7 (17,5)  4 (10,0)  3 (7,5)  0,943 (0,469‐1,895)   
Não  33 (82,5)  20 (50,0)  13 (32,5)  1,061 (0,528‐2,132)   
Granulomas
Sim  17 (42,5)  11 (27,5)  6 (15,0)  1,145 (0,693‐1,891)  0,601 
Não  23 (57,5)  13 (32,5)  10 (25,0)  0,874 (0,529‐1,443)   
Hiperplasia endotelial
Sim  30 (75,0)  18 (45,0)  12 (30,0)  1,000 (0,557‐1,794)  0,640b 
Não  10 (25,0)  6 (15,0)  4 (10,0)  1,000 (0,557‐1,794)   

IHQ, imuno‐histoquímica; (++/++),> 30% do infiltrado inflamatório; (+/++), <30% do infiltrado inflamatório; RP, razão de prevalência; IC 95%, intervalo de confiança de 95%; NA, não aplicável, poucos casos.

a

p‐valor por Qui‐Quadrado (χ2).

b

Teste exato de Fischer.

Discussão

Uma descrição clínica e histopatológica dos casos de sífilis e estudo de acurácia diagnóstica da IHQ com anticorpo anti‐T. pallidum foi realizada. Nosso estudo mostrou alta frequência de sífilis adquirida em homens (76,3%), assim como reportado pela literatura,1–3 especialmente com relatos entre homens que fazem sexo com homens.1,13 Sífilis também foi observada em adolescentes e pacientes mais velhos, grupos comumente considerados sem risco ou com baixo risco para a infecção. A fase secundária da doença foi predominante, provavelmente em decorrência da alta frequência de biópsias de pele realizadas nessa fase.

A dermatite de interface associada à dermatite perivascular superficial e profunda (27,5%) e à dermatite perivascular superficial e profunda e perianexial (20%) destacou a mistura de padrões de reação tecidual já reportada.14 Hiperplasia endotelial também foi frequente (75%), como nos estudos anteriores.14,15 Plasmócitos foram raros ou ausentes em sete amostras de pele (17,5%), concordando com relatos da literatura de escassez e ausência de plasmócitos em até 25%‐33% das amostras.16–18

As espiroquetas e sua morfologia típica foram facilmente visualizadas pelo método imuno‐histoquímico. Resultados semelhantes são relatados com os mesmos anticorpos,9 ou anticorpos semelhantes.6,8 A IHQ como teste diagnóstico forneceu diagnóstico específico de sífilis em 60% dos casos, número que se aproxima de estudos anteriores (71%‐100% de sensibilidade).6,9 Não foi possível determinar a positividade pela técnica de Warthin‐Starry (WS). Quatresooz e Piérard, em 2009, mostraram achados semelhantes com resultados inconclusivos ou negativos com a técnica WS devido ao fundo de melanina na epiderme e fibrilas de reticulina na derme.9 Outros autores, entretanto, encontraram taxas de sensibilidade de 9% e 60% em amostras de pele.8,10

As espiroquetas podem predominar na derme6 ou na epiderme de lesões de pele da sífilis secundária.7,8 A maioria dos nossos casos apresentava espiroquetas tanto na derme quanto na epiderme, e a alta carga bacteriana (3+) foi predominante. Esses resultados indicam que os micro‐organismos ainda estão difusamente disseminados na pele durante a fase secundária da doença.

Na epiderme, as espiroquetas localizaram‐se principalmente na camada basal ou suprabasal, e em 62,5% das amostras não foram observadas na parte mais alta, ao contrário dos resultados de Phelps et al., que raramente observaram espiroquetas nas porções mais baixas da epiderme.8 O achado de espiroquetas no epitélio folicular e ao redor dos anexos em 58,3% das amostras positivas apoiam ainda mais a teoria de epiteliotropismo do micro‐organismo.7

As alterações vasculares são componentes importantes da resposta inflamatória tecidual na sífilis. Hiperplasia endotelial foi achado comum e evidente, e numerosas espiroquetas imunomarcadas foram detectadas nas paredes dos vasos. Martin‐Ezquerra et al. também encontraram um padrão vasculotrópico – porém, principalmente nas lesões de sífilis primária.7

Nenhuma correlação significante entre IHQ e características clínicas ou histopatológicas foi observada. No entanto, a prevalência de resultados positivos pela IHQ foi alta em amostras de pacientes sem coinfecção pelo HIV (RP=1,444) e naqueles com imunossupressão pelo HIV com CD4 <200 células/mm3 e CV> 1,000 cópias/mL (RP=1,133). Esses resultados sugerem que a infecção pelo HIV por si só não teve impacto principal na detecção de espiroquetas, mas o estado de imunossupressão pode influenciar a disseminação de espiroquetas nas amostras de sífilis. Similar aos nossos achados, pesquisas anteriores reportaram alta carga bacteriana em amostras de pele de pacientes com contagem de CD4 <250 células10 ou em estados de imunossupressão associados com sífilis maligna precoce.11

As amostras cutâneas de sífilis com dermatite perivascular superficial e profunda e de interface e com plasmócitos visíveis no infiltrado (++/++) mostraram alta prevalência de resultados positivos na IHQ em comparação com amostras sem esses achados (RP=1,582; RP=1,547, respectivamente). Ao contrário, amostras com dermatite perivascular superficial e profunda (RP=0,304) ou poucos plasmócitos (+/++; RP=0,619) sugerem que mesmo com resultados negativos na IHQ, o diagnóstico da sífilis não pode ser excluído.

Conclusão

A detecção de antígenos no protocolo de IHQ realçou espiroquetas de Treponema pallidum e possibilitou diagnóstico indubitável de sífilis nas amostras teciduais. A impregnação por WS foi considerada ineficiente na detecção da bactéria e não ofereceu nenhuma contribuição para o diagnóstico específico da doença.

Comitês éticos

Os comitês éticos do Hospital Clementino Fraga Filho (HUCFF) da Universidade Federal do Rio de Janeiro (UFRJ) e do Instituto Nacional de Doenças Infecciosas Evandro Chagas (INI), Fundação Oswaldo Cruz (Fiocruz), Brasil, aprovaram o estudo. Os comitês dispensaram informe de consentimento porque nenhuma informação de identificação pessoal foi incluída no conjunto de dados usado para análise.

Suporte financeiro

Nenhum.

Contribuição dos autores

Mariana Freitas de Assis Pereira Rosa: Concepção e o desenho do estudo; levantamento dos dados, ou análise e interpretação dos dados; análise estatística; redação do artigo ou revisão crítica do conteúdo intelectual importante; obtenção, análise e interpretação dos dados; participação efetiva na orientação da pesquisa; revisão crítica da literatura; aprovação final da versão final do manuscrito.

Leonardo Pereira Quintella: Concepção e o desenho do estudo; levantamento dos dados, ou análise e interpretação dos dados; análise estatística; redação do artigo ou revisão crítica do conteúdo intelectual importante; obtenção, análise e interpretação dos dados; participação efetiva na orientação da pesquisa; revisão crítica da literatura; aprovação final da versão final do manuscrito.

Luiz Claudio Ferreira: Levantamento dos dados; obtenção, análise e interpretação dos dados.

Tullia Cuzzi: Concepção e o desenho do estudo; levantamento dos dados, ou análise e interpretação dos dados; análise estatística; redação do artigo ou revisão crítica do conteúdo intelectual importante; obtenção, análise e interpretação dos dados; participação efetiva na orientação da pesquisa; revisão crítica da literatura; aprovação final da versão final do manuscrito.

Conflito de interesses

Nenhum.

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Como citar este artigo: Rosa MFAP, Quintella LP, Ferreira LC, Cuzzi T. Immunohistochemical detection of Treponema pallidum in skin samples with clinical and histopathological correlations and Warthin‐Starry staining critical analysis. An Bras Dermatol. 2023;98:480–6.

Trabalho realizado no Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro e Instituto Nacional de Doenças Infecciosas Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.

Copyright © 2023. Sociedade Brasileira de Dermatologia
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