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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">cVrWqLzDjSy6Jr8Kmjqt3hQ</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2025000700501</article-id>
      <article-id pub-id-type="other">00501</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20240207</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Carta Cient&#237;fica</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Doen&#231;a de Whipple como Diagn&#243;stico Diferencial de Endocardite com Hemocultura Negativa: Um Relato de Caso</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0000-1745-8382</contrib-id>
          <name>
            <surname>Soares</surname>
            <given-names>Carolina Kuchenbecker</given-names>
          </name>
          <role>Obten&#231;&#227;o de dados</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Silva</surname>
            <given-names>Rafaela Clara Resende da</given-names>
          </name>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Brasileiro</surname>
            <given-names>Geraldo</given-names>
            <suffix>Filho</suffix>
          </name>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gelape</surname>
            <given-names>Claudio Leo</given-names>
          </name>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rosa</surname>
            <given-names>J&#233;sus Faria</given-names>
            <suffix>J&#250;nior</suffix>
          </name>
          <role>Obten&#231;&#227;o de dados</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-8260-9212</contrib-id>
          <name>
            <surname>Passaglia</surname>
            <given-names>Luiz Guilherme</given-names>
          </name>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgdiv1">Hospital das Cl&#237;nicas</institution>
        <institution content-type="orgname">Universidade Federal de Minas Gerais</institution>
        <addr-line>
          <named-content content-type="city">Belo Horizonte</named-content>
          <named-content content-type="state">MG</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Hospital das Cl&#237;nicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG &#8211; Brasil</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Faculdade de Medicina da UFMG</institution>
        <institution content-type="orgdiv1">Departamento de Cl&#237;nica M&#233;dica</institution>
        <addr-line>
          <named-content content-type="city">Belo Horizonte</named-content>
          <named-content content-type="state">MG</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Faculdade de Medicina da UFMG &#8211; Departamento de Cl&#237;nica M&#233;dica, Belo Horizonte, MG &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"><label>Correspond&#234;ncia</label>: Carolina Kuchenbecker Soares &#8226; Hospital das Cl&#237;nicas da Universidade Federal de Minas Gerais &#8211; Cardiologia &#8211; Av. Prof. Alfredo Balena, 110. CEP 30130-100, Santa Efig&#234;nia, Belo Horizonte, MG &#8211; Brasil E-mail: <email>carolinakuchenbecker@gmail.com</email> </corresp>
        <fn fn-type="conflict">
          <label>Potencial conflito de interesse:</label>
          <p>N&#227;o h&#225; conflito com o presente artigo.</p>
        </fn>
        <fn fn-type="edited-by">
          <label>Editor respons&#225;vel pela revis&#227;o:</label>
          <p> Gl&#225;ucia Maria Moraes de Oliveira</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>18</day>
        <month>08</month>
        <year>2025</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>07</month>
        <year>2025</year>
      </pub-date>
      <volume>122</volume>
      <issue>7</issue>
      <elocation-id>e20240207</elocation-id>
      <history>
        <date date-type="received">
          <day>26</day>
          <month>03</month>
          <year>2024</year>
        </date>
        <date date-type="rev-recd">
          <day>24</day>
          <month>04</month>
          <year>2025</year>
        </date>
        <date date-type="accepted">
          <day>07</day>
          <month>05</month>
          <year>2025</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>Este &#233; um artigo de acesso aberto distribu&#237;do sob os termos da licen&#231;a de atribui&#231;&#227;o pelo Creative Commons</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Resumo</title>
        <p>A endocardite de Whipple &#233; uma condi&#231;&#227;o infecciosa rara causada pela bact&#233;ria <italic>Tropheryma whipplei</italic>. Apesar da forma generalizada ser a mais conhecida, a infec&#231;&#227;o tem um amplo espectro de apresenta&#231;&#245;es extraintestinais, sendo a endocardite infecciosa com hemocultura negativa a forma mais frequente de comprometimento card&#237;aco. Este caso exemplifica a import&#226;ncia da suspei&#231;&#227;o da enfermidade para o estabelecimento de tratamento adequado.</p>
      </abstract>
      <kwd-group xml:lang="pt">
        <kwd>Doen&#231;a de Whipple</kwd>
        <kwd>Endocardite Bacteriana</kwd>
        <kwd>Acidente Vascular Cerebral</kwd>
      </kwd-group>
      <counts>
        <fig-count count="4"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="7"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>A doen&#231;a de Whipple, causada pelo <italic>Tropheryma whipplei,</italic> &#233; uma enfermidade rara, cr&#244;nica e sist&#234;mica que afeta comumente o trato gastrointestinal. Embora exista um amplo espectro de manifesta&#231;&#245;es extraintestinais, neste relato apresentaremos um caso da principal forma de acometimento card&#237;aco: a endocardite de Whipple.</p>
      <sec>
        <title>Descri&#231;&#227;o</title>
        <p>Paciente feminina, 64 anos, previamente h&#237;gida e sem sinais ou sintomas de doen&#231;a subaguda (febre ou manifesta&#231;&#245;es inespec&#237;ficas, manifesta&#231;&#245;es articulares ou do trato digestivo), apresentou, em 17/01/2022, hemiplegia esquerda e desvio da comissura labial &#224; direita, de in&#237;cio s&#250;bito. A tomografia de cr&#226;nio mostrou hipodensidade aguda em corona radiata direita, confirmando o diagn&#243;stico de acidente vascular cerebral isqu&#234;mico. A angioresson&#226;ncia do enc&#233;falo revelou aus&#234;ncia de fluxo na art&#233;ria cerebral m&#233;dia direita, sem ateromatose obstrutiva nos vasos intracranianos, e o doppler de art&#233;rias car&#243;tidas e vertebrais n&#227;o evidenciou ateromatose obstrutiva desses vasos.</p>
        <p>O ecocardiograma transtor&#225;cico mostrou estrutura m&#243;vel aderida &#224; valva a&#243;rtica, motivando transfer&#234;ncia a hospital com servi&#231;o especializado de cardiologia e cirurgia cardiovascular em 01/02/2022. Em avalia&#231;&#227;o pela equipe, apresentava-se normotensa, sem sopros percept&#237;veis &#224; ausculta inicial, pulsos perif&#233;ricos sim&#233;tricos e carot&#237;deo de conforma&#231;&#227;o habitual. Ecocardiograma transesof&#225;gico demonstrou c&#226;maras de tamanho normal, fra&#231;&#227;o de eje&#231;&#227;o de 68%, valvas normais, exceto pela presen&#231;a de estrutura filamentar aderida a face ventricular do folheto coronariano direito da valva a&#243;rtica, de 9,3 mm, associada a regurgita&#231;&#227;o moderada (<xref ref-type="fig" rid="f01">Figura 1</xref>). Eletrocardiograma sem altera&#231;&#245;es significativas.</p>
        <p>
          <fig id="f01">
            <label>Figura 1</label>
            <caption>
              <title>&#8211; A) massa vis&#237;vel ao ecoTT, janela paraesternal eixo longo; B) regurgita&#231;&#227;o a&#243;rtica associada &#224; les&#227;o em janela paraesternal eixo longo; C) regurgita&#231;&#227;o a&#243;rtica em janela apical 5 c&#226;maras.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-122-07-e20240207-40207-gf01.tif"/></fig>
        </p>
        <p>Considerado diagn&#243;stico inicial de endocardite infecciosa, por&#233;m hemoculturas e fator reumatoide negativos, prote&#237;na C-reativa em baixos t&#237;tulos, exame de urina tipo 1 e ultrassonografia do abdome sem altera&#231;&#245;es significativas. Frente a isso, e ap&#243;s discuss&#227;o com equipe de ecocardiografia, visto que a imagem n&#227;o era t&#237;pica de vegeta&#231;&#227;o, entendeu-se que havia apenas o evento isqu&#234;mico como crit&#233;rio menor de Duke e que havia diagn&#243;stico diferencial mais prov&#225;vel (fibroelastoma), justificando a op&#231;&#227;o da equipe por n&#227;o iniciar antibioticoterapia emp&#237;rica. Dada a possibilidade de tumor com emboliza&#231;&#227;o e disfun&#231;&#227;o valvar, optou-se por cirurgia card&#237;aca pela preocupa&#231;&#227;o com novas emboliza&#231;&#245;es. Ap&#243;s cerca de quatro semanas do evento isqu&#234;mico, foi realizada a troca valvar a&#243;rtica com implante de pr&#243;tese biol&#243;gica.</p>
        <p>Durante o ato cir&#250;rgico, observou-se destrui&#231;&#227;o tecidual e perfura&#231;&#227;o nas por&#231;&#245;es semilunares da valva a&#243;rtica. Microscopicamente, fragmentos das v&#225;lvulas mostraram fibrose, agress&#227;o endotelial e microtrombos de fibrina, al&#233;m de discreto infiltrado mononuclear com macr&#243;fagos espumosos contendo granula&#231;&#245;es PAS (&#225;cido peri&#243;dico-Schiff) positivas (<xref ref-type="fig" rid="f02">Figura 2</xref>), tornando prov&#225;vel o diagn&#243;stico retrospectivo de endocardite de Whipple. A confirma&#231;&#227;o por imuno-histoqu&#237;mica (IHQ) ou exames moleculares n&#227;o foi realizada, no entanto, por indisponibilidade dos m&#233;todos no servi&#231;o.</p>
        <p>
          <fig id="f02">
            <label>Figura 2</label>
            <caption>
              <title>&#8211; Histologia da valva a&#243;rtica nativa mostrando macr&#243;fagos contendo granula&#231;&#245;es PAS positivas.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-122-07-e20240207-40207-gf02.tif"/></fig>
        </p>
        <p>A paciente foi acionada em domic&#237;lio e recebeu antibioticoterapia venosa por seis semanas, com boa resposta, e, posteriormente, foi prescrita a terapia de manuten&#231;&#227;o com sulfametoxazol-trimetropima oral por 12 meses.</p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>A endocardite de Whipple &#233; uma condi&#231;&#227;o infecciosa rara causada pelo <italic>Tropheryma whipplei</italic>, uma bact&#233;ria intracelular gram-positiva.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup> O bacilo tornou-se mais conhecido pela forma generalizada (cl&#225;ssica) da doen&#231;a, mas a infec&#231;&#227;o apresenta um amplo espectro de formas extraintestinais (localizadas), como envolvimento neurol&#243;gico, pleural, articular ou card&#237;aco.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
      <p>Em caso de acometimento card&#237;aco, sua principal forma &#233; a endocardite infecciosa; no entanto, pericardite constritiva, miocardite, arterite coron&#225;ria e insufici&#234;ncia card&#237;aca congestiva tamb&#233;m s&#227;o pass&#237;veis de ocorr&#234;ncia.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup> Os mais afetados s&#227;o homens de meia-idade (&gt;80%). Ao contr&#225;rio de outras endocardites infecciosas, endocardite de Whipple n&#227;o tem predile&#231;&#227;o por valvas doentes e a maioria dos casos ocorre naquelas sem altera&#231;&#245;es subjacentes (at&#233; 88%). A principal valva acometida &#233; a a&#243;rtica (43%), seguida pela mitral (20%) e tric&#250;spide (3%), respectivamente, sendo poss&#237;veis combina&#231;&#245;es.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B4">4</xref></sup></p>
      <p>O <italic>Tropheryma whipplei</italic> foi detectado em amostras de fezes e saliva de indiv&#237;duos saud&#225;veis (1% a 11% e 0% a 2%, respectivamente), principalmente em trabalhadores de esta&#231;&#245;es de tratamento de esgoto (12% a 26% e 2%, respectivamente), sendo a ingest&#227;o a rota mais prov&#225;vel de transmiss&#227;o. Mesmo nos portadores que desenvolvem a doen&#231;a, a replica&#231;&#227;o &#233; insidiosa, com in&#237;cio dos sintomas ap&#243;s anos ou d&#233;cadas.</p>
      <p>Sua apresenta&#231;&#227;o pode ser subaguda ou cr&#244;nica e as principais manifesta&#231;&#245;es s&#227;o artralgia (52% a 75%), insufici&#234;ncia card&#237;aca (41% a 71%) e perda de peso (25%). Tamb&#233;m podem ocorrer sintomas gastrointestinais, como diarreia ou desconforto abdominal (21%), febre (21% a 24%), acidente vascular cerebral (17% a 25%) e emboliza&#231;&#227;o perif&#233;rica (11%).<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup> Assim como no caso apresentado &#8211; em que a suspeita ocorreu apenas ap&#243;s a avalia&#231;&#227;o anatomopatol&#243;gica &#8211; cogitar essa condi&#231;&#227;o &#233; um desafio, uma vez que as apresenta&#231;&#245;es cl&#237;nica e laboratorial s&#227;o inespec&#237;ficas, sem resposta inflamat&#243;ria evidente. Al&#233;m disso, o <italic>Tropheryma whipplei</italic> n&#227;o pode ser cultivado usando t&#233;cnicas padr&#227;o, portanto, frequentemente n&#227;o atende aos crit&#233;rios de Duke para endocardite.</p>
      <p>Na doen&#231;a de Whipple, o diagn&#243;stico &#233; feito principalmente por endoscopia digestiva com an&#225;lise histol&#243;gica do duodeno. Uma vez que o paciente apresente sintomas gastrointestinais, a maioria ter&#225; histologia com macr&#243;fagos contendo granula&#231;&#245;es PAS positivas.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Outras possibilidades s&#227;o a IHQ ou PCR (rea&#231;&#227;o em cadeia da polimerase) com amplifica&#231;&#227;o do gene T<italic>ropheryma whipplei</italic> 16S rRNA na amostra tecidual. Por&#233;m, este &#250;ltimo carece de especificidade (devido ao risco de contamina&#231;&#227;o do DNA, &#224; falta de controles visuais e &#224; dificuldade de realiza&#231;&#227;o em cortes de parafina) e deve ser interpretado com cautela, sem confirma&#231;&#227;o histol&#243;gica.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup></p>
      <p>Por outro lado, em formas localizadas, o diagn&#243;stico s&#243; pode ser feito por an&#225;lise histol&#243;gica, IHQ ou PCR do &#243;rg&#227;o afetado. Por isso, at&#233; hoje dependemos do exame direto da valva;<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> outros exames podem, entretanto, ser realizados para corroborar a decis&#227;o pela ressec&#231;&#227;o cir&#250;rgica. A PCR em amostras de sangue mostrou sensibilidade insatisfat&#243;ria; j&#225; em amostras de fezes, saliva ou urina, &#233; uma op&#231;&#227;o, desde que guiada por manifesta&#231;&#245;es cl&#237;nicas.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> A bi&#243;psia do intestino delgado pode ser realizada para apoiar o diagn&#243;stico, considerando o envolvimento intestinal assintom&#225;tico, comum em apresenta&#231;&#245;es extraintestinais. Por fim, o cultivo &#233; uma possibilidade ainda com escassa disponibilidade, dependendo de laborat&#243;rios especializados.</p>
      <p>Como demonstrado no caso, o acometimento valvar mostra vegeta&#231;&#245;es (observadas ao ecocardiograma em 75% a 84% dos casos) de tamanho intermedi&#225;rio, fibrose e destrui&#231;&#227;o valvular com pouca inflama&#231;&#227;o, sugerindo um processo lento.<sup><xref ref-type="bibr" rid="B6">6</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup> A avalia&#231;&#227;o microsc&#243;pica mostra macr&#243;fagos PAS positivos, por&#233;m, estes n&#227;o s&#227;o patognom&#244;nicos da doen&#231;a, devendo ser associados a outros m&#233;todos que elevem sua especificidade.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup></p>
      <p>O tratamento sugerido &#233; baseado em estudos observacionais e consiste em um esquema prolongado de antibi&#243;tico para favorecer a erradica&#231;&#227;o completa da bact&#233;ria, reduzindo o risco de recidiva.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Em caso de acometimento card&#237;aco, &#233; sugerida uma fase inicial intravenosa com penicilina G (2 UI IV a cada 4 horas) ou ceftriaxona (2 g IV uma vez ao dia) por quatro semanas, seguida por uma fase de manuten&#231;&#227;o oral com sulfametoxazol-trimetoprima (160/800 mg duas vezes por dia) por pelo menos 12 meses.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B4">4</xref></sup></p>
      <p>Em caso de alergia &#224; ceftriaxona ou &#224; penicilina, o meropenem &#233; uma alternativa. Em caso de alergia &#224; sulfametoxazol-trimetoprima, as op&#231;&#245;es s&#227;o (1) clotrimazol em combina&#231;&#227;o com sulfametoxazol ou (2) doxiciclina em combina&#231;&#227;o com hidroxicloroquina.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup></p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#227;o</title>
      <p>O diagn&#243;stico da endocardite de Whipple &#233; um desafio, seja por sua apresenta&#231;&#227;o at&#237;pica, pela dificuldade nas vias diagn&#243;sticas ou mesmo pelo desconhecimento da condi&#231;&#227;o. Sua suspeita deve ocorrer diante de um quadro de endocardite com hemoculturas persistentemente negativas, sintomas associados (como gastrintestinais ou artralgia) e achados morfol&#243;gicos caracter&#237;sticos da doen&#231;a.</p>
      <p>A colora&#231;&#227;o PAS deve ser feita rotineiramente no tecido biopsiado e, se a endocardite de Whipple for uma possibilidade, outro m&#233;todo diagn&#243;stico deve ser associado em um laborat&#243;rio especializado para confirmar a condi&#231;&#227;o e permitir o tratamento. Sua ocorr&#234;ncia &#233; muito provavelmente subestimada e, em vista do risco de recorr&#234;ncia e do tratamento diferenciado, seu reconhecimento &#233; fundamental para o adequado tratamento.</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <title>Refer&#234;ncias</title>
      <ref id="B1">
        <label>1</label>
        <mixed-citation>1. McGee M, Brienesse S, Chong B, Levendel A, Lai K. Tropheryma Whipplei Endocarditis: Case Presentation and Review of the Literature. Open Forum Infect Dis. 2018;6(1):ofy330. doi: 10.1093/ofid/ofy330.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>McGee</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Brienesse</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Chong</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Levendel</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Lai</surname>
              <given-names>K</given-names>
            </name>
          </person-group>
          <article-title>Tropheryma Whipplei Endocarditis: Case Presentation and Review of the Literature</article-title>
          <source>Open Forum Infect Dis</source>
          <year>2018</year>
          <volume>6</volume>
          <issue>1</issue>
          <elocation-id>ofy330</elocation-id>
          <pub-id pub-id-type="doi">10.1093/ofid/ofy330</pub-id>
        </element-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <mixed-citation>2. Lepidi H, Fenollar F, Dumler JS, Gauduchon V, Chalabreysse L, Bammert A, et al. Cardiac Valves in Patients with Whipple Endocarditis: Microbiological, Molecular, Quantitative Histologic, and Immunohistochemical Studies of 5 Patients. J Infect Dis. 2004;190(5):935-45. doi: 10.1086/422845.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lepidi</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Fenollar</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Dumler</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Gauduchon</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Chalabreysse</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Bammert</surname>
              <given-names>A</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Cardiac Valves in Patients with Whipple Endocarditis: Microbiological, Molecular, Quantitative Histologic, and Immunohistochemical Studies of 5 Patients</article-title>
          <source>J Infect Dis</source>
          <year>2004</year>
          <volume>190</volume>
          <issue>5</issue>
          <fpage>935</fpage>
          <lpage>945</lpage>
          <pub-id pub-id-type="doi">10.1086/422845</pub-id>
        </element-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <mixed-citation>3. Duss F-R, Jaton K, Vollenweider P, Troillet N, Greub G. Whipple disease: a 15-year retrospective study on 36 patients with positive polymerase chain reaction for Tropheryma whipplei. Clinical Microbiology and Infection. 2020; S1198-743X(20)30519-X. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.cmi.2020.08.036">https://doi.org/10.1016/j.cmi.2020.08.036</ext-link> </mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Duss</surname>
              <given-names>F-R</given-names>
            </name>
            <name>
              <surname>Jaton</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Vollenweider</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Troillet</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Greub</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
          <article-title>Whipple disease: a 15-year retrospective study on 36 patients with positive polymerase chain reaction for Tropheryma whipplei</article-title>
          <source>Clinical Microbiology and Infection</source>
          <year>2020</year>
          <comment>S1198-743X(20)30519-X</comment>
          <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.cmi.2020.08.036">https://doi.org/10.1016/j.cmi.2020.08.036</ext-link>
        </element-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <mixed-citation>4. Fenollar F, Lepidi H, Raoult D. Whipple's Endocarditis: Review of the Literature and Comparisons with Q Fever, Bartonella Infection, and Blood Culture-Positive Endocarditis. Clin Infect Dis. 2001;33(8):1309-16. doi: 10.1086/322666.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Fenollar</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Lepidi</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Raoult</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
          <article-title>Whipple's Endocarditis: Review of the Literature and Comparisons with Q Fever, Bartonella Infection, and Blood Culture-Positive Endocarditis</article-title>
          <source>Clin Infect Dis</source>
          <year>2001</year>
          <volume>33</volume>
          <issue>8</issue>
          <fpage>1309</fpage>
          <lpage>1316</lpage>
          <pub-id pub-id-type="doi">10.1086/322666</pub-id>
        </element-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <mixed-citation>5. Kim MJ, Jung HO. Anatomic Variants Mimicking Pathology on Echocardiography: Differential Diagnosis. J Cardiovasc Ultrasound. 2013;21(3):103-12. doi: 10.4250/jcu.2013.21.3.103.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kim</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Jung</surname>
              <given-names>HO</given-names>
            </name>
          </person-group>
          <article-title>Anatomic Variants Mimicking Pathology on Echocardiography: Differential Diagnosis</article-title>
          <source>J Cardiovasc Ultrasound</source>
          <year>2013</year>
          <volume>21</volume>
          <issue>3</issue>
          <fpage>103</fpage>
          <lpage>112</lpage>
          <pub-id pub-id-type="doi">10.4250/jcu.2013.21.3.103</pub-id>
        </element-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <mixed-citation>6. Fenollar F, C&#233;lard M, Lagier JC, Lepidi H, Fournier PE, Raoult D. Tropheryma Whipplei Endocarditis. Emerg Infect Dis. 2013;19(11):1721-30. doi: 10.3201/eid1911.121356.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Fenollar</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>C&#233;lard</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Lagier</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Lepidi</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Fournier</surname>
              <given-names>PE</given-names>
            </name>
            <name>
              <surname>Raoult</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
          <article-title>Tropheryma Whipplei Endocarditis</article-title>
          <source>Emerg Infect Dis</source>
          <year>2013</year>
          <volume>19</volume>
          <issue>11</issue>
          <fpage>1721</fpage>
          <lpage>1730</lpage>
          <pub-id pub-id-type="doi">10.3201/eid1911.121356</pub-id>
        </element-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <mixed-citation>7. Marth T, Moos V, M&#252;ller C, Biagi F, Schneider T. Tropheryma Whipplei Infection and Whipple's Disease. Lancet Infect Dis. 2016;16(3):e13-22. doi: 10.1016/S1473-3099(15)00537-X.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Marth</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Moos</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>M&#252;ller</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Biagi</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Schneider</surname>
              <given-names>T</given-names>
            </name>
          </person-group>
          <article-title>Tropheryma Whipplei Infection and Whipple's Disease</article-title>
          <source>Lancet Infect Dis</source>
          <year>2016</year>
          <volume>16</volume>
          <issue>3</issue>
          <fpage>e13</fpage>
          <lpage>e22</lpage>
          <pub-id pub-id-type="doi">10.1016/S1473-3099(15)00537-X</pub-id>
        </element-citation>
      </ref>
    </ref-list>
    <fn-group>
      <fn fn-type="other">
        <label>Aprova&#231;&#227;o &#233;tica e consentimento informado:</label>
        <p> Este artigo n&#227;o cont&#233;m estudos com humanos ou animais realizados por nenhum dos autores.</p>
      </fn>
      <fn fn-type="other">
        <label>Uso de Intelig&#234;ncia Artificial:</label>
        <p> Os autores n&#227;o utilizaram ferramentas de intelig&#234;ncia artificial no desenvolvimento deste trabalho.</p>
      </fn>
      <fn fn-type="other">
        <label>Vincula&#231;&#227;o acad&#234;mica:</label>
        <p> N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
      </fn>
      <fn fn-type="data-availability" specific-use="data-in-article">
        <label>Disponibilidade de Dados:</label>
        <p> Os conte&#250;dos subjacentes ao texto da pesquisa est&#227;o contidos no manuscrito.</p>
      </fn>
      <fn fn-type="financial-disclosure">
        <label>Fontes de financiamento:</label>
        <p> O presente estudo n&#227;o teve fontes de financiamento externas.</p>
      </fn>
    </fn-group>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-id pub-id-type="doi">10.36660/abc.20240207i</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Research Letter</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Whipple&#8217;s Disease as a Differential Diagnosis of Blood Culture-Negative Endocarditis: A Case Report</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0000-1745-8382</contrib-id>
          <name>
            <surname>Soares</surname>
            <given-names>Carolina Kuchenbecker</given-names>
          </name>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Silva</surname>
            <given-names>Rafaela Clara Resende da</given-names>
          </name>
          <role>Analysis and interpretation of the data</role>
          <role>Writing of the manuscript</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Brasileiro</surname>
            <given-names>Geraldo</given-names>
            <suffix>Filho</suffix>
          </name>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gelape</surname>
            <given-names>Claudio Leo</given-names>
          </name>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rosa</surname>
            <given-names>J&#233;sus Faria</given-names>
            <suffix>J&#250;nior</suffix>
          </name>
          <role>Acquisition of data</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-8260-9212</contrib-id>
          <name>
            <surname>Passaglia</surname>
            <given-names>Luiz Guilherme</given-names>
          </name>
          <role>Analysis and interpretation of the data</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Hospital das Cl&#237;nicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG &#8211; Brazil</institution>
      </aff>
      <aff id="aff2001">
        <label>2</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Faculdade de Medicina da UFMG &#8211; Departamento de Cl&#237;nica M&#233;dica, Belo Horizonte, MG &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001"><label>Mailing Address:</label> Carolina Kuchenbecker Soares &#8226; Hospital das Cl&#237;nicas da Universidade Federal de Minas Gerais &#8211; Cardiologia &#8211; Av. Prof. Alfredo Balena, 110. Postal Code 30130-100, Santa Efig&#234;nia, Belo Horizonte, MG &#8211; Brazil E-mail: carolinakuchenbecker@gmail.com </corresp>
        <fn fn-type="conflict">
          <label>Potential conflict of interest:</label>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
        <fn fn-type="edited-by">
          <label>Editor responsible for the review:</label>
          <p> Gl&#225;ucia Maria Moraes de Oliveira</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Abstract</title>
        <p>Whipple&#8217;s endocarditis is a rare infectious condition caused by the bacterium <italic>Tropheryma whipplei</italic>. Although its systemic form is the most widely recognized, the infection exhibits a broad spectrum of extraintestinal manifestations, with blood culture-negative infective endocarditis being the most common form of cardiac involvement. The case presented in this study underscores the importance of clinical investigation for accurate diagnosis and the application of appropriate treatment.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Whipple Disease</kwd>
        <kwd>Bacterial Endocarditis</kwd>
        <kwd>Stroke</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Whipple&#8217;s disease, caused by <italic>Tropheryma whipplei</italic>, is a rare, chronic, and systemic disease that commonly affects the gastrointestinal tract. Although a wide spectrum of extraintestinal manifestations exists, this report presents a case with the principal form of cardiac involvement: Whipple&#8217;s endocarditis.</p>
        <sec>
          <title>Description</title>
          <p>A previously healthy 64-year-old female patient, presenting no signs or symptoms of subacute disease (e.g., fever, nonspecific manifestations, or joint or gastrointestinal symptoms), presented a sudden left hemiplegia and rightward deviation of the labial commissure on January 17, 2022. Cranial computed tomography revealed an acute hypodensity in the right corona radiata, confirming the diagnosis of ischemic stroke. Cerebral magnetic resonance angiography revealed absent flow in the right middle cerebral artery, with no evidence of obstructive atheromatosis in the intracranial vessels. Doppler ultrasound of the carotid and vertebral arteries did not evidence obstructive atheromatosis in these vessels.</p>
          <p>A transthoracic echocardiogram revealed a mobile structure attached to the aortic valve, which led to a referral to a hospital specialized in cardiology and cardiovascular surgery on February 1, 2022. The evaluation of the team found that the patient was normotensive, with no audible heart murmurs on initial auscultation, symmetric peripheral pulses, and normally configured carotid arteries. Transesophageal echocardiography presented normal-sized chambers, an ejection fraction of 68%, and structurally normal valves except for a filamentous structure adhered to the ventricular side of the right coronary cusp of the aortic valve, measuring 9.3 mm, associated with moderate regurgitation (<xref ref-type="fig" rid="f01001">Figure 1</xref>). The electrocardiogram presented no significant abnormalities.</p>
          <p>
            <fig id="f01001">
              <label>Figure 1</label>
              <caption>
                <title>&#8211; A) Visible mass on transthoracic echocardiography (parasternal long-axis view); B) Aortic regurgitation associated with the lesion in the parasternal long-axis view; C) Aortic regurgitation in the apical five-chamber view.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-122-07-e20240207-40207-gf01-en.tif"/></fig>
          </p>
          <p>Although a diagnosis of infectious endocarditis was considered, blood cultures and rheumatoid factor tests were negative, levels of C-reactive protein were low, and urinalysis and abdominal ultrasound results showed no significant abnormalities. Considering these findings, and after discussion with the echocardiography team, as the imaging was not typical of vegetation, it was concluded that the only minor Duke criterion present was the ischemic event, and a more probable differential diagnosis (fibroelastoma) was considered. Therefore, the team decided not to initiate empirical antibiotic therapy. Given the possibility of a tumor with embolic potential and valvular dysfunction, surgical intervention was chosen due to concerns about further embolization. About four weeks after the ischemic event, the patient underwent aortic valve replacement with biological prosthesis implantation.</p>
          <p>Tissue destruction and perforation of the semilunar portions of the aortic valve were observed during surgery. A microscopic examination of the valve fragments revealed fibrosis, endothelial damage, fibrin microthrombi, and a mild mononuclear infiltrate with foamy macrophages containing positive periodic acid-Schiff (PAS) granules (<xref ref-type="fig" rid="f02001">Figure 2</xref>), supporting a retrospective diagnosis of Whipple&#8217;s endocarditis. Confirmation by immunohistochemistry or molecular testing was not performed due to unavailability at the facility.</p>
          <p>
            <fig id="f02001">
              <label>Figure 2</label>
              <caption>
                <title>&#8211; Histology of the native aortic valve showing macrophages containing PAS-positive granules.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-122-07-e20240207-40207-gf02-en.tif"/></fig>
          </p>
          <p>The patient was contacted at home and received six weeks of intravenous antibiotic therapy, resulting in a good clinical response. Then, oral maintenance therapy with sulfamethoxazole-trimethoprim was prescribed for 12 months.</p>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>Whipple&#8217;s endocarditis is a rare infectious condition caused by <italic>Tropheryma whipplei</italic>, a Gram-positive intracellular bacterium.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup>The bacillus became widely known for its generalized (classic) form of the disease; however, the infection presents a broad spectrum of extraintestinal (localized) forms, such as neurological, pleural, articular, or cardiac involvement.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <p>In cases of cardiac involvement, its main manifestation is infectious endocarditis; however, constrictive pericarditis, myocarditis, coronary arteritis, and congestive heart failure may also occur.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup>The most affected individuals are middle-aged men (&gt; 80%). Unlike other forms of infectious endocarditis, Whipple&#8217;s endocarditis has no predilection for previously diseased valves, and most cases occur on structurally normal valves (up to 88%). The aortic valve is most affected (43%), followed by the mitral (20%) and tricuspid (3%) valves, with combinations also possible.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B4">4</xref></sup></p>
        <p><italic>T. whipplei</italic> has been detected in stool and saliva samples of healthy individuals (1% to 11% and 0% to 2%, respectively), particularly in sewage treatment workers (12% to 26% and 2%, respectively); the most probable route of transmission was ingestion. Even among those infected who develop the disease, replication is insidious, and symptoms may not manifest for years or decades later.</p>
        <p>Its presentation may be subacute or chronic, with the main manifestations being arthralgia (52% to 75%), heart failure (41% to 71%), and weight loss (25%). Gastrointestinal symptoms, such as diarrhea or abdominal discomfort (21%), fever (21% to 24%), stroke (17% to 25%), and peripheral embolization (11%),<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup> may also occur. As in the presented case, in which the condition was considered only after histopathological evaluation, the diagnosis of this condition is challenging since clinical and laboratory findings are nonspecific, and it does not present an evident inflammatory response. Additionally, <italic>T. whipplei</italic> cannot be cultured using standard techniques, often failing to meet Duke criteria for endocarditis.</p>
        <p>The diagnosis of Whipple&#8217;s disease is primarily made via digestive endoscopy with histological analysis of the duodenum. When patients manifest gastrointestinal symptoms, most will have histology showing PAS-positive granule-containing macrophages.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Other options include immunohistochemistry or polymerase chain reaction (PCR) amplification of the <italic>T. whipplei</italic> 16S rRNA gene from tissue samples. However, the latter lacks specificity due to risks of DNA contamination, a lack of visual controls, and difficulty in performing the test on paraffin-embedded sections, and must be interpreted cautiously without histological confirmation.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup></p>
        <p>On the other hand, in localized forms, diagnosis can only be made through histological analysis, immunohistochemistry, or PCR of the affected organ. Therefore, to this day, direct examination of the valve is often required; however, other tests may be conducted to support the decision for surgical resection.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> PCR from blood samples has shown unsatisfactory sensitivity, whereas stool, saliva, or urine samples are acceptable options when guided by clinical manifestations.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> A small bowel biopsy can be performed to support the diagnosis, considering that asymptomatic intestinal involvement is common in extraintestinal presentations. Last, culture is possible besides the limited method availability, which requires specialized laboratories.</p>
        <p>As demonstrated in this case, valvular involvement typically exhibits intermediate-sized vegetations (observed by echocardiography in 75% to 84% of cases), fibrosis, and valve destruction, accompanied by minimal inflammation, suggesting a slow progression of the disease.<sup><xref ref-type="bibr" rid="B6">6</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup> Microscopic examination reveals PAS-positive macrophages; however, these are not pathognomonic and must be correlated with other diagnostic methods to increase specificity.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup></p>
        <p>The suggested treatment is based on observational studies and consists of prolonged antibiotic therapy to promote complete bacterial eradication and reduce the risk of recurrence.<sup><xref ref-type="bibr" rid="B3">3</xref></sup>An initial intravenous phase is recommended in cases of cardiac involvement, using either penicillin G (2 IU IV every 4 hours) or ceftriaxone (2 g IV once a day) for four weeks, followed by a maintenance phase with oral sulfamethoxazole-trimethoprim (160/800 mg, respectively, twice daily) for at least 12 months.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B4">4</xref></sup></p>
        <p>In cases of allergy to ceftriaxone or penicillin, meropenem is an alternative. If the patient is allergic to sulfonamides, options include (1) clotrimazole combined with sulfamethoxazole or (2) doxycycline combined with hydroxychloroquine.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup></p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusion</title>
        <p>The diagnosis of Whipple&#8217;s endocarditis is challenging due to its atypical presentation, difficult diagnosis, and lack of knowledge about the condition. Cases of endocarditis with persistently negative blood cultures, associated symptoms (e.g., gastrointestinal complaints or arthralgia), and morphological findings characteristic may raise suspicion of the disease.</p>
        <p>PAS staining should be routinely performed on biopsied tissue. If Whipple&#8217;s endocarditis is a possibility, an additional diagnostic method should be performed by a specialized laboratory to confirm the condition and initiate the appropriate treatment. The true incidence of the disease is likely underestimated; recognition is essential for proper management, given the risk of recurrence and the need for targeted therapy.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <label>Ethics approval and consent to participate:</label>
          <p> This article does not contain any studies with human participants or animals performed by any of the authors.</p>
        </fn>
        <fn fn-type="other">
          <label>Use of Artificial Intelligence:</label>
          <p> The authors did not use any artificial intelligence tools in the development of this work.</p>
        </fn>
        <fn fn-type="other">
          <label>Study association:</label>
          <p> This study is not associated with any thesis or dissertation work.</p>
        </fn>
        <fn fn-type="data-availability" specific-use="data-in-article">
          <label>Data Availability:</label>
          <p> The underlying content of the research text is contained within the manuscript.</p>
        </fn>
        <fn fn-type="financial-disclosure">
          <label>Sources of funding:</label>
          <p> There were no external funding sources for this study.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
