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e 3 &#40;IIQ&#160;1&#8211;16&#41;&#44; respectivamente&#46; Em 66&#44;9&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>237&#41; dos casos n&#227;o foi poss&#237;vel identificar o f&#225;rmaco causador&#46; A carbamazepina foi o mais comumente relacionado ao diagn&#243;stico definitivo &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>18&#59;&#160;15&#44;4&#37;&#41;&#44; seguido por fenito&#237;na &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#59;&#160;13&#44;7&#37;&#41; e dipirona &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#59;&#160;9&#44;4&#37;&#41;&#46; Os principais grupos foram os anticonvulsivantes arom&#225;ticos &#40;31&#44;6&#37;&#59;&#160;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>37&#41;&#44; 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entre os casos com etiologia definida ou n&#227;o &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; Os pacientes cujo f&#225;rmaco causador n&#227;o foi encontrado utilizavam maior n&#250;mero de medicamentos &#40;mediana&#160;8&#44; IIQ 0&#8211;27&#41; e maior n&#250;mero de f&#225;rmacos suspeitos &#40;mediana&#160;3&#44; IIQ&#160;1&#8211;16&#41;&#44; em rela&#231;&#227;o aos pacientes que apresentavam defini&#231;&#227;o etiol&#243;gica &#40;medianas de 4&#44; IIQ&#160;0&#8211;26 e 1&#44; IIQ&#160;1&#8211;7&#44; respectivamente&#41;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;000 &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; Os pacientes com farmacodermias graves tiveram maior propor&#231;&#227;o de identifica&#231;&#227;o dos f&#225;rmacos causadores do que as n&#227;o graves &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#46; Podemos observar uma compara&#231;&#227;o geral entre os pacientes com e sem etiologia definida na <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Foram avaliados os fatores que poderiam estar relacionadas a uma maior probabilidade de ser realizado o diagn&#243;stico etiol&#243;gico&#46; Os seguintes fatores apresentaram signific&#226;ncia estat&#237;stica para a obten&#231;&#227;o de uma defini&#231;&#227;o da etiologia para as farmacodermias&#58; menor n&#250;mero de medicamentos em uso &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41;&#44; menor n&#250;mero de f&#225;rmacos suspeitos &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41; e rea&#231;&#245;es farmacod&#233;rmicas graves &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#46; Os dois primeiros fatores s&#227;o caracter&#237;sticos dos pacientes em polifarm&#225;cia&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Utilizando a an&#225;lise por regress&#227;o log&#237;stica&#44; e ap&#243;s ajustes devidos&#44; verificou&#8208;se que o menor n&#250;mero de f&#225;rmacos suspeitos &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;29&#59; 95&#37;&#160;IC&#160;0&#44;22&#8208;0&#44;38&#41; &#233; definitivamente importante para a defini&#231;&#227;o etiol&#243;gica das farmacodermias&#46; Ressalta&#8208;se que nessa etapa da avalia&#231;&#227;o n&#227;o foi inclu&#237;do o n&#250;mero total de f&#225;rmacos em uso&#44; pois em an&#225;lise multivariada evita&#8208;se incluir fatores muito relacionados entre si ou que utilizem par&#226;metros semelhantes &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">J&#225; se suspeitava que a polifarm&#225;cia &#233; um importante fator contribuinte para o n&#227;o diagn&#243;stico das farmacodermias&#44; o que foi corroborado por nossos resultados&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">2&#8211;4</span></a> &#201; conhecido que o uso m&#250;ltiplo de medicamentos &#233; um dos principais entraves para definir o f&#225;rmaco causador&#46; Em nossa amostra&#44; 79&#44;7&#37; dos pacientes utilizavam mais de um f&#225;rmaco no momento da rea&#231;&#227;o e&#44; consequentemente&#44; apresentavam mais de um f&#225;rmaco suspeito&#46; Isso se mostrou similar ao estudo de Beniwal et al&#46;&#44; que mostrou que 74&#37; dos pacientes estavam em uso de m&#250;ltiplas subst&#226;ncias no momento da farmacodermia&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">2</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">A maioria dos pacientes avaliados n&#227;o teve o f&#225;rmaco causador identificado&#44; correspondendo a 66&#44;9&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>237&#41; dos casos&#46; Isso esteve relacionado ao alto percentual de uso de m&#250;ltiplas subst&#226;ncias 79&#44;7&#37;&#160;&#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>282&#41; e uma maior mediana de f&#225;rmacos em uso do que as descritas em outros trabalhos&#46; A mediana de medicamentos em uso pelos pacientes de nosso estudo foi de&#160;7 &#40;IIQ&#160;0&#8211;27&#41;&#44; e a m&#233;dia de f&#225;rmacos suspeitos foi de&#160;3&#160;&#40;IIQ&#160;1&#8211;16&#41;&#46; Tais dados s&#227;o superiores aos de outros estudos&#44; como o de Beniwal et al&#46;&#44; que foi de&#160;2&#44;09&#160;&#40;IIQ&#160;1&#8211;6&#41;&#44; e o de Thakkar et al&#46;&#44; que observou uma m&#233;dia de&#160;1&#44;52 &#40;&#177; 0&#44;80&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">2&#44;3</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">H&#225; poucos estudos na literatura que descrevem os casos nos quais n&#227;o foi estabelecido diagn&#243;stico etiol&#243;gico&#44; pois a aus&#234;ncia de diagn&#243;stico do medicamento precipitador &#233; um crit&#233;rio de exclus&#227;o na maioria dos protocolos&#46; No caso do estudo de Zhao J et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">4</span></a> o f&#225;rmaco causador n&#227;o foi estabelecido em apenas 13&#37; dos pacientes&#44; os quais estavam em uso de mais de um medicamento&#46; No entanto&#44; foram exclu&#237;dos&#44; ainda na sele&#231;&#227;o&#44; os casos que n&#227;o apresentavam subst&#226;ncias causais definidas ou que n&#227;o apresentavam subst&#226;ncias suspeitas e se os pacientes estavam em uso de mais de cinco medicamentos&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">4</span></a> Isso contrasta com nosso estudo&#44; tendo em vista que a mediana de uso de f&#225;rmacos foi superior a cinco&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Em conclus&#227;o&#44; em um hospital terci&#225;rio de refer&#234;ncia no sul do Brasil&#44; as farmacodermias s&#227;o frequentes&#44; e &#233; alta a possibilidade de n&#227;o serem definidas etiologicamente&#46; A polifarm&#225;cia &#233; o principal fator associado &#224; indefini&#231;&#227;o etiol&#243;gica das farmacodermias&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Suporte financeiro</span><p id="par0060" class="elsevierStylePara elsevierViewall">Funaderm&#47;Sociedade Brasileira de Dermatologia&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Contribui&#231;&#227;o dos autores</span><p id="par0065" class="elsevierStylePara elsevierViewall">Fabiana Bazanella de Oliveira&#58; An&#225;lise estat&#237;stica&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; 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; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Paula Chiamenti&#58; Obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Roberta de Freitas Horn&#58; Obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Renan Rangel Bonamigo&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflito de interesses</span><p id="par0085" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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                  \t\t\t\t">0&#44;6 &#40;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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Eritrodermia&#44; &#37;&#160;&#40;n&#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"><span class="elsevierStyleItalic">Farmacodermias n&#227;o graves&#44; &#37;&#160;&#40;n&#41;</span>&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">72&#44;3 &#40;256&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Exantema&#44; &#37;&#160;&#40;n&#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">59&#44;9 &#40;212&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Eritema pigmentar fixo&#44; &#37;&#160;&#40;n&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&#44;5 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fotossensibilidade&#44; &#37;&#160;&#40;n&#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">3&#44;4&#40;12&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Erup&#231;&#227;o liquen&#243;ide&#44; &#37;&#160;&#40;n&#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;3 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>SRIFE&#44; &#37;&#160;&#40;n&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;8 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sindrome diest&#233;sica de m&#227;os e p&#233;s&#44; &#37;&#160;&#40;n&#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;3 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rea&#231;&#227;o acneiforme&#44; &#37;&#160;&#40;n&#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;8 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Vasculite cut&#226;nea de pequenos vasos&#44; &#37;&#160;&#40;n&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Acometimento extra cut&#226;neo&#44; &#37;&#160;&#40;n&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Eosinofilia&#44; &#37;&#160;&#40;n&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Altera&#231;&#227;o de fun&#231;&#227;o hep&#225;tica&#44; &#37;&#160;&#40;n&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Altera&#231;&#227;o de fun&#231;&#227;o renal&#44; &#37;&#160;&#40;n&#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">4 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pneumonite&#44; &#37;&#160;&#40;n&#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;3 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Linfonodomegalia&#44; &#37;&#160;&#40;n&#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;1 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pancitopenia&#44; &#37;&#160;&#40;n&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;3 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Presen&#231;a de comorbidade&#44; &#37;&#160;&#40;n&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">88&#44;7 &#40;314&#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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HAS&#44; &#37;&#160;&#40;n&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diabetes <span class="elsevierStyleItalic">mellitus</span>&#44; &#37;&#160;&#40;n&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14&#44;4 &#40;51&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cardiopatia isqu&#234;mica&#44; &#37; &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>DPOC&#44; &#37; &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&#44;2 &#40;15&#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>Asma&#44; &#37; &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#44;7 &#40;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Neoplasia&#44; &#37; &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">23&#44;7 &#40;84&#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>HIV&#44; &#37; &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11 &#40;39&#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>Doen&#231;a renal cr&#244;nica&#44; &#37; &#40;n&#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">7&#44;1 &#40;25&#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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Epilepsia&#44; &#37; &#40;n&#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">4&#44;8 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a psiqui&#225;trica&#44; &#37; &#40;n&#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">6&#44;5 &#40;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Insufici&#234;ncia card&#237;aca&#44; &#37; &#40;n&#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&#44;8 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cirrose&#44; &#37; &#40;n&#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&#44;5 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Acidente vascular cerebral&#44; &#37; &#40;n&#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&#44;6 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2658523.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;stica dos pacientes com farmacodermia &#8211; Hospital de Cl&#237;nicas de Porto Alegre&#44; 2011&#8208;2019</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Tabela 2"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Anticonvulsivantes arom&#225;ticos&#58; carbamazepina&#44; fenitoina&#44; fenobarbital&#44; lamotrigina&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Anti&#8208;inflamat&#243;rios n&#227;o esteroides&#58; ibuprofeno&#44; nimesulida&#44; diclofenaco&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Antirretrovirais&#58; ritonavir&#44; etratina&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Corticoide&#58; prednisona&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Penicilinas&#58; amoxicilina&#8208;clavulanato&#44; amoxicilina&#44; ampicilina&#44; ampicilina&#8208;sulbactam&#44; oxacilina&#46; Sulfonamidas&#58; sulfametoxazol&#8208;trimetropim&#44; sulfassadiazina&#59; cefalosporinas&#58; cefepime&#44; cefuroxima&#59; fluorquinolonas&#58; levofloxacino&#44; ciprofloxacino&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grupos de medicamentos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37; &#40;n&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anticonvulsivantes arom&#225;ticos&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">31&#44;6 &#40;37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antimicrobianos&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">29 &#40;34&#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">Penicilinas&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&#44;1 &#40;13&#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">Sulfonamidas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;5 &#40;10&#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">Cefalosporinas&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&#44;2 &#40;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">Vancomicina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;5 &#40;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">Fluorquinolonas&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;7 &#40;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">Macrodantina&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;8 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hidroxicloroquina&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;7 &#40;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">Alopurinol&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;7 &#40;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">Clopidrogel&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;8 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Contraste&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;8 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fluconazol&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;8 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genfibrozil&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;8 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Homeopatia&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;8 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#193;cido valproico&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;8 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total&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">100&#37; &#40;117&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2658524.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Grupos de medicamentos identificados como causadores das farmacodermias</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Tabela 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Farmacodermias com etiologia definida&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Farmacodermias com etiologia n&#227;o definida&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&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" 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" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">Idade &#40;&#177; DP&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">40&#44;49 &#40;&#177; 22&#44;069&#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" style="border-bottom: 2px solid black">46&#44;86 &#40;&#177; 20&#44;924&#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" style="border-bottom: 2px solid black">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;429<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="elsevierStyleItalic">Sexo &#37;&#40;n&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" 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><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-with-role" title="\n
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                  \t\t\t\t">34&#44;5 &#40;50&#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
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">N&#250;mero de medicamentos em uso no momento da erup&#231;&#227;o &#8211; mediana &#40;IIQ&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;0&#8211;26&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;0&#8211;27&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">36&#44;8 &#40;43&#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">23&#44;2 &#40;55&#41;&nbsp;\t\t\t\t\t\t\n
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Journal Information
Vol. 96. Issue 4.
Pages 508-510 (1 July 2021)
Visits
6247
Vol. 96. Issue 4.
Pages 508-510 (1 July 2021)
Carta ‐ Investigação
Open Access
Fatores associados à indefinição etiológica das farmacodermias: estudo transversal no sul do Brasil
Visits
6247
Fabiana Bazanella de Oliveiraa,
Corresponding author
fabibazanella@gmail.com

Autor para correspondência.
, Paula Chiamentib, Roberta de Freitas Hornc, Renan Rangel Bonamigoc
a Universidade Federal de Ciências da Saúde, Porto Alegre, RS, Brazil
b Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
c Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
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Tables (3)
Tabela 1. Característica dos pacientes com farmacodermia – Hospital de Clínicas de Porto Alegre, 2011‐2019
Tabela 2. Grupos de medicamentos identificados como causadores das farmacodermias
Tabela 3. [ll1]Perfil dos pacientes com farmacodermias definidas e não definidas etiologicamente
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Reportamos um estudo retrospectivo e transversal, realizado por análise de prontuários de pacientes internados e avaliados pelo Serviço de Dermatologia do Hospital de Clínicas de Porto Alegre, com diagnóstico clínico ou histopatológico de farmacodermia no período entre janeiro de 2011 e janeiro de 2019. Foram incluídos todos os padrões de farmacodermia, independente se o fármaco causador tenha sido ou não identificado. Foram excluídos os casos nos quais o diagnóstico de farmacodermia (RAD) não foi completamente estabelecido (quando o quadro poderia corresponder também a doenças infecciosas, autoimunes ou de cunho reacional não medicamentoso). As RAD consideradas graves foram as seguintes: síndrome de Stevens‐Johnson (SJS), sobreposição SJS/necrólise epidérmica tóxica (NET), NET, síndrome de hipersensibilidade a medicamentos tipo síndrome da farmacodermia com eosinofilia e sintomas sistêmicos (DRESS), eritrodermia e pustulose exantemática generalizada aguda (PEGA) e eritrodermia.1

Foram descritas as frequências de cada variável demográfica e clínica. A análise estatística foi realizada pelo programa SPSS v18.0. Foram utilizados testes não paramétricos para avaliação das variáveis contínuas, visto que a distribuição de dados não era linear, de acordo com teste de Kolmogorov‐Smirnov. Utilizou‐se teste U de Mann Whitney para essas variáveis. Para as variáveis categóricas, foram avaliadas associações por meio do teste de Qui‐Quadrado. Uma regressão logística múltipla foi realizada para avaliação dos fatores que poderiam estar associados ou não a uma maior probabilidade de diagnóstico etiológico. Foi considerado significativo um resultado com p ˂ 0,05.

O estudo identificou 354 pacientes com farmacodermia, com média de 44,25 novos casos por ano, incidência anual de 1,4 caso por 1.000 internações gerais. A idade média foi de 46,08 (± 21,307) anos, e 209 (59%) participantes eram mulheres. A maioria apresentava alguma comorbidade (88,7%; n=314) (tabela 1). Houve maior número de farmacodermias não graves (72,3%; n=256); o exantema maculopapular foi a forma mais comum (58,9%; n=212). A maior parte dos pacientes não apresentou achados sistêmicos (72,3%; n=256) (tabela 1).

Tabela 1.

Característica dos pacientes com farmacodermia – Hospital de Clínicas de Porto Alegre, 2011‐2019

Idade média (± DP)  46,08 (± 21,307) 
Sexo, % (n)   
Feminino  59% (209) 
Masculino  41% (145) 
Número de fármacos em uso, mediana (IIQ)  7 (IIQ 0–27) 
Número de fármacos suspeitos (IIQ)  3 (IIQ 1–16) 
Medicamento causador da farmacodermia identificado, % (n)  33,3 (117) 
Farmacodermias graves, % (n)  27,6 (98) 
SJS/Overlap/NET, % (n)  8,5 (30) 
Eritema multiforme, % (n)  6,5 (23) 
DRESS, % (n)  11 (39) 
PEGA, % (n)  0,6 (2) 
Eritrodermia, % (n)  1,1(4) 
Farmacodermias não graves, % (n)  72,3 (256) 
Exantema, % (n)  59,9 (212) 
Eritema pigmentar fixo, % (n)  4,5 (16) 
Fotossensibilidade, % (n)  3,4(12) 
Erupção liquenóide, % (n)  0,3 (1) 
SRIFE, % (n)  0,8 (3) 
Sindrome diestésica de mãos e pés, % (n)  0,3 (1) 
Reação acneiforme, % (n)  0,8 (3) 
Vasculite cutânea de pequenos vasos, % (n)  1,1 (4) 
Urticária, % (n)  1,1 (4) 
Acometimento extra cutâneo, % (n)  27,7 (98) 
Eosinofilia, % (n)  18,1 (64) 
Alteração de função hepática, % (n)  13,3 (47) 
Febre, % (n)  11,6 (41) 
Alteração de função renal, % (n)  4 (14) 
Pneumonite, % (n)  0,3 (1) 
Linfonodomegalia, % (n)  1,1 (4) 
Pancitopenia, % (n)  0,3 (1) 
Presença de comorbidade, % (n)  88,7 (314) 
HAS, % (n)  33,1 (117) 
Diabetes mellitus, % (n)  14,4 (51) 
Cardiopatia isquêmica, % (n)  5,6 (20) 
DPOC, % (n)  4,2 (15) 
Asma, % (n)  1,7 (6) 
Neoplasia, % (n)  23,7 (84) 
HIV, % (n)  11 (39) 
Doença renal crônica, % (n)  7,1 (25) 
Epilepsia, % (n)  4,8 (17) 
Doença psiquiátrica, % (n)  6,5 (23) 
Insuficiência cardíaca, % (n)  4,8 (17) 
Cirrose, % (n)  2,5 (9) 
Acidente vascular cerebral, % (n)  5,6 (20) 

%, porcentagem; DP, desvio padrão; DPOC, doença pulmonar obstrutiva crônica; DRESS, síndrome da farmacodermia com eosinofilia e sintomas sistêmicos; HAS, hipertensão arterial sistêmica; HIV, vírus da imunodeficiência humana; IIQ, intervalo interquartil; n, número; NET, necrólise epidérmica tóxica; PEGA, pustulose exantemática generalizada aguda; SJS, síndrome de Stevens‐Johnson.

A maioria das farmacodermias ocorreu durante o uso de mais de um medicamento (79,7%; n=282). As medianas do número de fármacos utilizados no momento da erupção e de fármacos suspeitos foram de 7 (IIQ 0–27) e 3 (IIQ 1–16), respectivamente. Em 66,9% (n=237) dos casos não foi possível identificar o fármaco causador. A carbamazepina foi o mais comumente relacionado ao diagnóstico definitivo (n=18; 15,4%), seguido por fenitoína (n=16; 13,7%) e dipirona (n=11; 9,4%). Os principais grupos foram os anticonvulsivantes aromáticos (31,6%; n=37), seguidos dos antimicrobianos (29%; n=34). Dentre os antimicrobianos, as penicilinas foram a principal classe (n=13) (tabela 2).

Tabela 2.

Grupos de medicamentos identificados como causadores das farmacodermias

Grupos de medicamentos  % (n) 
Anticonvulsivantes aromáticos  31,6 (37) 
Antimicrobianos  29 (34) 
Penicilinas  11,1 (13) 
Sulfonamidas  8,5 (10) 
Cefalosporinas  4,2 (5) 
Vancomicina  2,5 (3) 
Fluorquinolonas  1,7 (2) 
Macrodantina  0,8 (1) 
Hidroxicloroquina  1,7 (2) 
Alopurinol  1,7 (2) 
Clopidrogel  0,8 (1) 
Contraste  0,8 (1) 
Fluconazol  0,8 (1) 
Genfibrozil  0,8 (1) 
Homeopatia  0,8 (1) 
Ácido valproico  0,8 (1) 
Total  100% (117) 

Anticonvulsivantes aromáticos: carbamazepina, fenitoina, fenobarbital, lamotrigina.

Anti‐inflamatórios não esteroides: ibuprofeno, nimesulida, diclofenaco.

Antirretrovirais: ritonavir, etratina.

Corticoide: prednisona.

Penicilinas: amoxicilina‐clavulanato, amoxicilina, ampicilina, ampicilina‐sulbactam, oxacilina. Sulfonamidas: sulfametoxazol‐trimetropim, sulfassadiazina; cefalosporinas: cefepime, cefuroxima; fluorquinolonas: levofloxacino, ciprofloxacino.

Não houve diferença estatística em relação a idade (p=0,429), sexo (p=0,633) e presença de comorbidades (p=0,321) entre os casos com etiologia definida ou não (tabela 3). Os pacientes cujo fármaco causador não foi encontrado utilizavam maior número de medicamentos (mediana 8, IIQ 0–27) e maior número de fármacos suspeitos (mediana 3, IIQ 1–16), em relação aos pacientes que apresentavam definição etiológica (medianas de 4, IIQ 0–26 e 1, IIQ 1–7, respectivamente), p<0,000 (tabela 3). Os pacientes com farmacodermias graves tiveram maior proporção de identificação dos fármacos causadores do que as não graves (p=0,007). Podemos observar uma comparação geral entre os pacientes com e sem etiologia definida na tabela 3.

Tabela 3.

[ll1]Perfil dos pacientes com farmacodermias definidas e não definidas etiologicamente

  Farmacodermias com etiologia definida  Farmacodermias com etiologia não definida 
Idade (± DP)  40,49 (± 22,069)  46,86 (± 20,924)  p=0,429b 
Sexo %(n)       
Feminino  32,1 (67)  67,9 (142)  p=0,633c 
Masculino  34,5 (50)  65,5 (95)   
Número de medicamentos em uso no momento da erupção – mediana (IIQ)  4 (0–26)  8 (0–27)  p<0,000b 
Número de medicamentos suspeitos (IIQ)  1 (1–7)  3 (1–16)  p < 0,000b 
Farmacodermia gravea  36,8 (43)  23,2 (55)  p=0,007c 
Farmacodermia não grave  63,2 (74)  76,8 (182)  p=0,007c 
Coomorbidades       
Sim  32,2 (101)  67,8 (213)  p=0,321c 
Não  40 (16)  60 (24)   
a

Farmacodermia grave: DRESS, STS/Overlap/NET, AGEP, eritrodermia, eritema multiforme.

b

Teste U de Mann‐Whitney.

c

Qui‐Quadrado.

DP, desvio padrão; IIQ, intervalo interquartil.

Foram avaliados os fatores que poderiam estar relacionadas a uma maior probabilidade de ser realizado o diagnóstico etiológico. Os seguintes fatores apresentaram significância estatística para a obtenção de uma definição da etiologia para as farmacodermias: menor número de medicamentos em uso (p<0,0001), menor número de fármacos suspeitos (p<0,0001) e reações farmacodérmicas graves (p=0,007). Os dois primeiros fatores são característicos dos pacientes em polifarmácia.

Utilizando a análise por regressão logística, e após ajustes devidos, verificou‐se que o menor número de fármacos suspeitos (OR=0,29; 95% IC 0,22‐0,38) é definitivamente importante para a definição etiológica das farmacodermias. Ressalta‐se que nessa etapa da avaliação não foi incluído o número total de fármacos em uso, pois em análise multivariada evita‐se incluir fatores muito relacionados entre si ou que utilizem parâmetros semelhantes (tabela 3).

Já se suspeitava que a polifarmácia é um importante fator contribuinte para o não diagnóstico das farmacodermias, o que foi corroborado por nossos resultados.2–4 É conhecido que o uso múltiplo de medicamentos é um dos principais entraves para definir o fármaco causador. Em nossa amostra, 79,7% dos pacientes utilizavam mais de um fármaco no momento da reação e, consequentemente, apresentavam mais de um fármaco suspeito. Isso se mostrou similar ao estudo de Beniwal et al., que mostrou que 74% dos pacientes estavam em uso de múltiplas substâncias no momento da farmacodermia.2

A maioria dos pacientes avaliados não teve o fármaco causador identificado, correspondendo a 66,9% (n=237) dos casos. Isso esteve relacionado ao alto percentual de uso de múltiplas substâncias 79,7% (n=282) e uma maior mediana de fármacos em uso do que as descritas em outros trabalhos. A mediana de medicamentos em uso pelos pacientes de nosso estudo foi de 7 (IIQ 0–27), e a média de fármacos suspeitos foi de 3 (IIQ 1–16). Tais dados são superiores aos de outros estudos, como o de Beniwal et al., que foi de 2,09 (IIQ 1–6), e o de Thakkar et al., que observou uma média de 1,52 (± 0,80).2,3

Há poucos estudos na literatura que descrevem os casos nos quais não foi estabelecido diagnóstico etiológico, pois a ausência de diagnóstico do medicamento precipitador é um critério de exclusão na maioria dos protocolos. No caso do estudo de Zhao J et al.,4 o fármaco causador não foi estabelecido em apenas 13% dos pacientes, os quais estavam em uso de mais de um medicamento. No entanto, foram excluídos, ainda na seleção, os casos que não apresentavam substâncias causais definidas ou que não apresentavam substâncias suspeitas e se os pacientes estavam em uso de mais de cinco medicamentos.4 Isso contrasta com nosso estudo, tendo em vista que a mediana de uso de fármacos foi superior a cinco.

Em conclusão, em um hospital terciário de referência no sul do Brasil, as farmacodermias são frequentes, e é alta a possibilidade de não serem definidas etiologicamente. A polifarmácia é o principal fator associado à indefinição etiológica das farmacodermias.

Suporte financeiro

Funaderm/Sociedade Brasileira de Dermatologia.

Contribuição dos autores

Fabiana Bazanella de Oliveira: Análise estatística; aprovação da versão final do manuscrito; concepção e planejamento do estudo; elaboração e redação do manuscrito; obtenção, análise e interpretação dos dados; participação efetiva na orientação da pesquisa; participação intelectual em conduta propedêutica e/ou terapêutica de casos estudados; revisão crítica da literatura; revisão crítica do manuscrito.

Paula Chiamenti: Obtenção, análise e interpretação dos dados.

Roberta de Freitas Horn: Obtenção, análise e interpretação dos dados.

Renan Rangel Bonamigo: Aprovação da versão final do manuscrito; concepção e planejamento do estudo; participação efetiva na orientação da pesquisa; participação intelectual em conduta propedêutica e/ou terapêutica de casos estudados; revisão crítica do manuscrito.

Conflito de interesses

Nenhum.

Referências
[1]
L.A. Drake, S.M. Dinehart, E.R. Farmer, R.W. Goltz, G.F. Graham, M.K. Hordinsky, et al.
Guidelines of care for cutaneous adverse drug reactions. American Academy of Dermatology.
J Am Acad Dermatol., 35 (1996), pp. 458-461
[2]
R. Beniwal, L.K. Gupta, A.K. Khare, A. Mittal, S. Mehta, M. Balai.
Clinical Profile and Comparison of Causality Assessment Tools in Cutaneous Adverse Drug Reactions.
Indian Dermatol Online J., 10 (2019), pp. 27-33
[3]
S. Thakkar, T.K. Patel, R. Vahora, P. Bhabhor, R. Patel.
Cutaneous adverse drug reactions in a tertiary care teaching hospital in India: An intensive monitoring study.
Indian J Dermatol., 62 (2017), pp. 618-625
[4]
J. Zhao, L. Hu, L. Zhang, M. Zhou, L. Gao, L. Cheng.
Causative drugs for drug‐induced cutaneous reactions in central China: a 608‐case analysis.
An Bras Dermatol., 94 (2019), pp. 664-670

Como citar este artigo: Oliveira FB, Chiamenti P, Horn RF, Bonamigo RR. Factors associated with the etiological uncertainty of drug reactions: a cross‐sectional study in southern Brazil. An Bras Dermatol. 2021;96:508–10.

Trabalho realizado no Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brasil.

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