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      <text:p text:style-name="P199"><text:span text:style-name="T7">pediátrico.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">Correa Borit JM</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">, Bellón Heredia T</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">, Ramírez García E</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">, Adrianzen Alvarez F</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">, Colque Bayona M</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">, Gomez Traseira C</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">1Servicio de Alergología, Hospital Universitario La Paz, Madrid</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">2Grupo de Hipersensibilidad a Medicamentos, Instituto de Investigación Sanitaria Hospital Universitario La Paz (IdiPAZ), Madrid </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">3Servicio de Farmacología Clínica, Instituto de Investigación Sanitaria Hospital Universitario La Paz (IdiPAZ), Madrid </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">4Servicio de Alergología, Instituto de Investigación Sanitaria Hospital Universitario La Paz (IdiPAZ), Madrid</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">*Corresponding author: Jorge M. Correa Borit, Servicio de Alergología, Hospital Universitario La Paz, Madrid, España.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">E-mail: <text:s/></text:span><text:span text:style-name="T11">jorgemauricio.correa@salud.madrid.org </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Introducción:</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">La necrólisis epidérmica tóxica (NET) y el síndrome de DRESS (Drug Reaction With Eosinophilia and Systemic Symptoms) son </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">dos tipos de reacciones cutáneas graves producidas por reacciones de hipersensibilidad de tipo IV. Son enfermedades raras, </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">más aún en población pediátrica. Los antibióticos, anticonvulsivantes y sulfamidas son los fármacos más implicados.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Paciente y método:</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Varón de 10 años con malformación de Dandy-Walker, y epilepsia multifocal que, 2 semanas después de añadir lamotrigina a </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">su tratamiento crónico habitual, presentó fiebre, numerosas lesiones pápulo-vesiculo-ampollosas y costras hemorrágicas en </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">cara, tronco y extremidades, con aftas en mucosa oral y ocular que progresaron a eritrodermia generalizada. Ante la sospe-</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">cha de NET, se suspendió lamotrigina, se pautó tratamiento con ciclosporina, y se incluyó en el Registro de Piel en Red de </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">reacciones de hipersensibilidad graves, iniciándose estudio según protocolo. </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">El cuadro evolucionó hacia la resolución, sin embargo, tras 19 días de tratamiento en pauta descendente con ciclosporina, </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">ésta se suspendió y ese mismo día reinició fiebre, eosinofilia, e hipertransaminasemia, con estudio microbiológico normal </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">(Tabla I). Ante la sospecha de Síndrome de DRESS tras retirada de ciclosporina, se pautó corticoterapia con mejoría clínica y </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">analítica en 72 horas. </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Finalmente, el cuadro clínico fue diagnosticado de un solapamiento entre NET y síndrome DRESS secundario a sensibilización </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">a lamotrigina.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Resultados:</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Anatomía patológica (biopsia cutánea): infiltrado linfocitario subepitelial, numerosos queratinocitos necróticos que confluyen </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="17.02cm" svg:height="0.336cm" svg:x="1.977cm" svg:y="23.881cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">en una ampolla (compatible con NET). Evaluación de causalidad medicamentosa según algoritmo ALDEN (Algorithm for Drug </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="17.024cm" svg:height="0.336cm" svg:x="1.977cm" svg:y="24.283cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Causality for Epidermal Necrolysis): MUY PROBABLE: lamotrigina (+6). Test de transformación Linfocitaria (TTL) con lamotrigi-</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="8.452cm" svg:height="0.336cm" svg:x="1.977cm" svg:y="24.685cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">na: positivo en todas las concentraciones probadas (Tabla II). <text:s/></text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T6">2022 | Volume 1 | S. Issue4 | e00001</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T6">www.ibjournals.com</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T6">3</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Keywords: </text:span><text:span text:style-name="T15">Toxic epidermal necrolysis, Stevens-Johnson Syndrome, DRESS, Lamotrigine.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Published </text:span><text:span text:style-name="T15">October 21, 2022</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Copyright: </text:span><text:span text:style-name="T15">© 2022 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License, </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Editor: </text:span><text:span text:style-name="T15">Alberto Borobia</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Cite as: </text:span><text:span text:style-name="T15">Correa Borit JM, Bellón Heredia T, Ramírez García E, Adrianzen Alvarez F, Colque Bayona M, Gomez Traseira C. Solapamiento </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">entre Necrólisis epidérmica tóxica y Síndrome DRESS inducido por lamotrigina en un paciente pediátrico. IBJ Clin Pharmacol 2022 </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">(S4):e0001 doi: 10.24217/2530-4984.22s4v1s1.00001</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Funding: </text:span><text:span text:style-name="T15">Without funding.</text:span></text:p>
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      <text:p/>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T14">Competing Interests: </text:span><text:span text:style-name="T15">Without competing interest.</text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="1.81cm" svg:height="0.336cm" svg:x="2.007cm" svg:y="6.993cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Conclusiones</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.406cm" svg:height="0.336cm" svg:x="2.007cm" svg:y="7.595cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">Presentamos un caso de solapamiento entre NET y síndrome DRESS secundario a lamotrigina en un niño de 10 años con </text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="6.661cm" svg:height="0.336cm" svg:x="2.007cm" svg:y="7.998cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">buena respuesta al tratamiento con ciclosporina.</text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="8.926cm" svg:height="0.336cm" svg:x="2.007cm" svg:y="8.6cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">El TTL fue útil para confirmar lamotrigina como el fármaco causal.</text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr204" draw:text-style-name="P204" draw:layer="layout" svg:width="5.26cm" svg:height="0.331cm" svg:x="13.584cm" svg:y="28.144cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T6">2022 | Volume 1 | S. Issue4 | e00001</text:span></text:p>
     </draw:text-box>
    </draw:frame>
   </draw:page>
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      <text:p text:style-name="P199"><text:span text:style-name="T6">4</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T7">Tratamiento en el síndrome de Stevens-Johnson y </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T7">necrólisis epidérmica tóxica: serie de casos</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">Carmen Arrieta-Pey, Irene Vázquez-Barrera, Pilar Tornero-Molina</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Departamento de Alergología, Hospital General Universitario Gregorio Marañón (HGUGM), Madrid, España</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Introducción:</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">El síndrome de Stevens-Johnson y la necrólisis epidérmica tóxica (SJS/NET) son reacciones cutáneas graves. Los fármacos </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">constituyen una de sus principales causas. Se han empleado diversos medicamentos inmunosupresores o inmunomodulado-</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">res sin establecer un tratamiento específico.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Material y métodos:</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Se realizó un estudio observacional retrospectivo del 2020 al 2022 en el HGU Gregorio Marañón recogiendo 10 casos. Se </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">clasificaron en tres grupos según el tratamiento administrado (corticoides, etanercept y gammaglobulina). Se valoró median-</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">te estudio estadístico (T Student) la influencia del tratamiento en la duración del cuadro y en la modificación del riesgo de </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">mortalidad calculado mediante la escala SCORTEN (Score for Toxic Epidermal Necrolysis) al inicio de la enfermedad y tras 5 </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">días de tratamiento. Se registraron complicaciones, secuelas y se analizó el impacto de las infecciones virales en la duración </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">del cuadro. Se recogieron los fármacos más probablemente implicados según la escala ALDEN (Algorithm of Drug Causality </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">for Epidermal Necrolysis).</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Resultados</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Tres pacientes (SCORTEN 5,3,3) iniciaron tratamiento con metilprednisolona 60mg/24h el día 1 (D1) y 3 (D3) tras el inicio </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.77cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="13.081cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">de las lesiones con duración del cuadro entre 7 y 10 días. El SCORTEN tras tratamiento se redujo a 3,3,2. Dos pacientes con </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">infección por VIH iniciaron corticoides en D5 y D18 con duración del cuadro de 29 días sin cambios del SCORTEN (4,1) presen-</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="11.415cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="13.885cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">tando uno shock hipovolémico por deshidratación y otro bacteriemia por Klebsiella.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Tres pacientes (SCORTEN 5,4,1) recibieron etanercept 50mg en D5 y D7. Uno recibió solo etanercept (SCORTEN 5) y los otros </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">dos asociaron corticoides. El SCORTEN tras el tratamiento se redujo a 4,3,1. El paciente con SCORTEN 4 desarrolló sinequias </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.901cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="15.292cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">peneanas y membranas conjuntivales y el de SCORTEN 5 falleció el D19 por fallo multiorgánico por sepsis. Los tres presenta-</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">ron bacteriemia por Serratia y Estafilococo Aureus.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Dos pacientes (SCORTEN 2,2) recibieron gammaglobulina iv (1g/Kg/día 3 días) en D2 y D3. Uno recibió únicamente gammag-</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.91cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="16.698cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">lobulina sin cambios en el SCORTEN. El otro asoció corticoides aumentando el SCORTEN a 3. El cuadro cedió en 13 y 10 días. </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.969cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="17.1cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">El primero presentó mucositis orofaríngea requiriendo asistencia en UCI y el segundo sobreinfección cutánea por microorga-</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="3.85cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="17.503cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">nismos coagulasa negativos.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Los fármacos más implicados fueron los betalactámicos (50%) y antiinflamatorios no esteroideos (AINES) (50%) seguidos de </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">antiepilépticos (20%) y ciprofloxacino (20%). Otros fármacos implicados (10%) fueron los macrólidos, inhibidores de la bomba </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">de protones, alopurinol, metronidazol y metoclopramida.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Conclusión</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">El añadir gammaglobulina o etanercept al tratamiento con corticoides no acorta la evolución del cuadro clínico ni mejora </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.631cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="20.516cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">el SCORTEN en nuestros pacientes respecto al uso aislado de corticoides. La infección por VIH fue signo de mal pronóstico </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">prolongando la resolución del cuadro clínico (p&lt;0,001). Los betalactámicos y AINES fueron los fármacos más frecuentemente </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">implicados en estas reacciones.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Keywords: </text:span><text:span text:style-name="T15">Tratamiento del síndrome de Stevens Johnson y necrólisis epidérmica tóxica, reacción cutánea grave, SCORTEN, </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">gammaglobulina, etanercept, corticoides. </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Published </text:span><text:span text:style-name="T15">October 21, 2022</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Copyright: </text:span><text:span text:style-name="T15">© 2022 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License, </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Editor: </text:span><text:span text:style-name="T15">Alberto Borobia</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Cite as: </text:span><text:span text:style-name="T15">Carmen Arrieta-Pey, Irene Vázquez-Barrera, Pilar Tornero-Molina. Tratamiento en el síndrome de Stevens-Johnson y </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">necrólisis epidérmica tóxica: serie de casos. IBJ Clin Pharmacol 2022 (S4):e0002 doi: 10.24217/2530-4984.22s4v1s1.00002.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Funding: </text:span><text:span text:style-name="T15">Without funding.</text:span></text:p>
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    <draw:frame draw:style-name="gr212" draw:text-style-name="P210" draw:layer="layout" svg:width="6.492cm" svg:height="0.319cm" svg:x="2cm" svg:y="25.972cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Competing Interests: </text:span><text:span text:style-name="T15">Without competing interest.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T6">2022 | Volume 1 | S. Issue4 | e00002</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T6">5</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T6">2022 | Volume 1 | S. Issue4 | e00003</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Keywords: </text:span><text:span text:style-name="T15">Stevens-Johnson, Toxic Epidermal Necrolysis, Immune Checkpoint Inhibitors.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Published </text:span><text:span text:style-name="T15">October 21, 2022</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Copyright: </text:span><text:span text:style-name="T15">© 2022 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License, </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Editor: </text:span><text:span text:style-name="T15">Alberto Borobia</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Cite as: </text:span><text:span text:style-name="T15">Kiril Magaletskyy Kharachko, Elena Sendagorta Cudos, Esther Fiz Benito, Rafaela de Moraes Souza, Ander Mayor Ibarguren, </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">Herranz Pinto. Un caso para replantear lo que sabemos y no sabemos: NET e inmunoterapia. IBJ Clin Pharmacol 2022 (S4):e0003 </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">doi: 10.24217/2530-4984.22s4v1s1.00003.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Funding:</text:span><text:span text:style-name="T15"> Without funding.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Competing Interests: </text:span><text:span text:style-name="T15">Without competing interest.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T7">Un caso para replantear lo que sabemos y no sabemos: </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T7">NET e inmunoterapia.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">Kiril Magaletskyy Kharachko*, Elena Sendagorta Cudos, Esther Fiz Benito, Rafaela de Moraes Souza, Ander Mayor </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">Ibarguren, Herranz Pinto.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Dermatología del Hospital Universitario La Paz.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T16">*Corresponding author: <text:s/>Kiril Magaletyskyy Kharachko. E-mail: </text:span><text:span text:style-name="T17">dr.kirilmk@gmail.com</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Debido al uso creciente de inmunoterapia se van describiendo nuevos casos de síndrome de Stevens-Johnson y Necrolisis </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Epidermolítica Tóxica en relación a estos tratamientos. Pero, ¿acaso es la misma patología que conocimos antes?</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.906cm" svg:height="0.336cm" svg:x="2cm" svg:y="8.624cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Presentamos el caso de un varón de 71 años con cáncer de células claras en tratamiento con nivolumab y aparición de lesio-</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">nes cutáneas de forma progresiva de dos meses de evolución que evoluciona a un síndrome overlap SSJ-NET con despega-</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">miento asociado.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Se realiza el diagnóstico diferencial del pénfigo paraneoplásico siendo descartado mediante la ausencia de acantolisis, la </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">ausencia de depósitos de anticuerpos en la IFD y la ausencia de autoanticuerpos en ELISA frente a desmogleina 1, desmog-</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">leina 3, envoplaquina y periplaquina. El diagnóstico de SSJ/NET sería obvio excepto por la evolución retardada del cuadro, la </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">afectación clínica moderada y la ausencia de afectación ocular lo que es compatible con una variante de SSJ/NET descrita en <text:s/></text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">inmunoterapia llamada PIRME (Progressive Immunotherapy-Related Mucocutaenous Eruption). Esta variante presentaría un </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">curso más benigno con una estancia hospitalaria más corta y que podría ser proclive a reiniciar la inmunoterapia de forma </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">más pronta debido a que su fisiopatología se basaría en un mecanismo de intolerancia inmunológica exacerbada por los </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">inhibidores de checkpoint hacia otros fármacos. Se postula por tanto que <text:s/>serían estos fármacos introducidos posteriormente </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">los que causarían el cuadro en vez de la inmunoterapia por sí mismo.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">La baja incidencia de casos de toxicidad cutánea grado IV a inhibidores de checkpoint con algo más de 50 casos descritos </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">en la literatura hace que la fisiopatología, el diagnóstico, el tratamiento y el pronóstico se hayan asociado a la presentación </text:span></text:p>
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    </draw:frame>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">clásica de SSJ/NET. Sin embargo, las últimas series nos muestran que existen diferencias entre los distintos pacientes, lo que </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">no hace más que poner el foco en nuestra ignorancia respecto a las reacciones SSJ/NET-like de la inmunoterapia. Hacen falta </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">más estudios que hagan hincapié en la historia del uso de fármacos asociados a inmunoterapia al igual que investigaciones </text:span></text:p>
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    </draw:frame>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">alergológicas buscando demostrar la causalidad de estos fármacos para así verificar el modelo propuesto de doble impacto </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">en el que la inmunoterapia fuera solo un facilitador de una reacción de toxicidad que necesitaría otro fármaco. </text:span><text:span text:style-name="T12"><text:s text:c="2"/></text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T6">www.ibjournals.com</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T7">Síndrome de DRESS inducido por tuberculostáticos: </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T7">manejo multidisciplinar complejo.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">Emilio Narváez Fernández</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">, Antonio Martínez Verdasco</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Servicio de Alergología, Hospital La Paz, Madrid, España.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">*Corresponding author:</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Emilio Narváez Fernández, Servicio de Alergología, Hospital La Paz, Madrid, España. E-mail: </text:span><text:span text:style-name="T19">emilionarvaez2015@hotmail.com</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">El síndrome DRESS inducido por tuberculostáticos (anti-TBC) es una reacción cutánea grave de muy difícil manejo en el que la </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">reintroducción controlada con fármacos implicados puede estar indicada.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Mujer de 27 años diagnosticada de tuberculosis pulmonar extensa cavitada, inicia tratamiento con isoniazida, rifampicina, </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">pirazinamida y etambutol. Al 26º día de tratamiento presenta exantema pruriginoso generalizado con fiebre y afectación </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">hepática. Es valorada en urgencias donde se diagnostica de DRESS (RegiSCAR +4). Se realiza TTL antes de iniciar corticotera-</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">pia con resultado positivo a isoniazida y negativo para el resto de anti-TBC. Tras sesión clínica multidisciplinar (Dermatología, </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Farmacología, Neumología y Alergología) se decide la introducción controlada de anti-TBC con resultado negativo en TTL y </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">monitorización desde el punto de vista clínico y analítico del paciente. Iniciamos etambutol, introducción controlada en 3 </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">días. Tras 48 horas añadimos pirazinamida 187,5 mg y a las 48 horas 500mg (3 dosis) pero fue suspendida debido al desarro-</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">llo de artritis reactiva. Pasadas 24 horas de su suspensión incorporamos rifampicina 225mg y a las 48 horas 450mg, pero fue </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">interrumpida debido a la detección de nuevas alteraciones hepáticas. Se aumentó la dosis de corticoide y se objetivó control </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">de los parámetros séricos a las 72 horas. Introducción posterior de rifabutina, moxifloxacino y linezolid con buena tolerancia. </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Resultados y discusión:</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">- La reintroducción controlada con etambutol bien tolerada pero la de pirazinamida y rifampicina no tuvo éxito. Como facto-</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">res de confusión: tratamiento concomitante con corticoides y manifestaciones retardadas del síndrome DRESS. No habiendo </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">sido posible discriminar si la alteración hepática tras la reintroducción controlada de pirazinamida y rifampicina se debió a </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="2.737cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="16.402cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">uno u otro fármaco.</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="10.192cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="17.004cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">- Ha sido necesario el tratamiento con fármacos anti-TBC de segunda línea.</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.99cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="17.606cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">- El manejo multidisciplinar del DRESS inducido por anti-TBC es muy complejo y requiere de realización de guías clínicas para </text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">su estandarización.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Keywords: </text:span><text:span text:style-name="T15">DRESS/tuberculostáticos/eosinofilia.</text:span></text:p>
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    </draw:frame>
    <draw:frame draw:style-name="gr212" draw:text-style-name="P210" draw:layer="layout" svg:width="3.605cm" svg:height="0.319cm" svg:x="2cm" svg:y="22.924cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Published </text:span><text:span text:style-name="T15">October 21, 2022</text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T14">Copyright: </text:span><text:span text:style-name="T15">© 2022 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License, </text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T15">which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T14">Editor: </text:span><text:span text:style-name="T15">Alberto Borobia</text:span></text:p>
     </draw:text-box>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T14">Cite as: </text:span><text:span text:style-name="T15">Emilio Narváez Fernández, Elena Ramirez García, Teresa Bellón, Elena Sendagorta, Antonio Martínez Verdasco, Rosario </text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T15">Cabañas. Síndrome de DRESS inducido por tuberculostáticos: manejo multidisciplinar complejo. IBJ Clin Pharmacol 2022 (S4):e0004 </text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T15">doi: 10.24217/2530-4984.22s4v1s1.00004.</text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T14">Funding: </text:span><text:span text:style-name="T15">Without funding.</text:span></text:p>
     </draw:text-box>
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    <draw:frame draw:style-name="gr212" draw:text-style-name="P210" draw:layer="layout" svg:width="6.492cm" svg:height="0.319cm" svg:x="2cm" svg:y="25.972cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T14">Competing Interests: </text:span><text:span text:style-name="T15">Without competing interest.</text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T6">2022 | Volume 1 | S. Issue4 | e00004</text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T6">www.ibjournals.com</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T9">1,2,3,4.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T18">1</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Servicio de Alergología, Hospital Universitario La Paz, Madrid, Madrid, España.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T18">2</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Servicio de Alergia. Instituto de Investigación Hospital La Paz (IdiPAZ)., Madrid, Madrid, España.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T18">3</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">PIELenRed Consortium.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T18">4</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Centro de Investigación en Red de Enfermedades Raras (CIBERER, U754)</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">*Autor correspondiente: Gabriela Leon Zambrana, Servicio de Alergología, Hospital Universitario La Paz, Madrid, Madrid, España. </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">E-mail: </text:span><text:span text:style-name="T19">gabriela.leon@salud.madrid.org</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Introducción:</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">El síndrome de hipersensibilidad inducido por fármacos es una reacción adversa a medicamentos (hipersensibilidad tipo IVb). </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">A menudo son erupciones cutáneas, anomalías hematológicas (eosinofilia, linfocitosis atípica), linfadenopatía y afectación </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">de órganos internos. Su diagnóstico y manejo son difíciles y requieren la participación de diversos especialistas. La mayoría </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">de los casos ocurren en adultos, sin diferencias por género [1]. Según el estudio multicéntrico de Barbaud (Barbaud, British </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Journal of Dermatology 2013) en un 18% de los casos hay hipersensibilidad a más de un fármaco [2].</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Los fármacos implicados con mayor frecuencia suelen ser los anticonvulsivantes, el alopurinol, las sulfonamidas, la minocicli-</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.859cm" svg:height="0.336cm" svg:x="2cm" svg:y="12.74cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">na y la vancomicina, también se han reportado casos de piperacilina/tazobactam [3]. En Europa los agentes más frecuentes </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="3.266cm" svg:height="0.336cm" svg:x="2cm" svg:y="13.142cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">son los beta-lactámicos.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Caso clínico:</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Varón de 29 años con antecedente de astrocitoma con derivación ventrículo-peritoneal (DVP), quien inicia con fiebre (39ºC), </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.664cm" svg:height="0.336cm" svg:x="2cm" svg:y="14.749cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">malestar general y odinofagia el día 18/03/2011 por lo que su médico de familia prescribe amoxicilina/clavulánico, ibupro-</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">feno, metamizol y paracetamol. A las 48 horas presenta fiebre y máculas eritematosas faciales por lo que acude nuevamen-</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.546cm" svg:height="0.336cm" svg:x="2cm" svg:y="15.553cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">te a su centro de salud donde suspenden antibioterapia y prescriben pantomicina (sospecha de mononucleosis). Acude a </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="17.143cm" svg:height="0.336cm" svg:x="2cm" svg:y="15.956cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">urgencias de HULP el 22/03 con exantema maculopapular confluente en cara, tronco y muslos, adenopatías supraclaviculares </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.745cm" svg:height="0.336cm" svg:x="2cm" svg:y="16.358cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">&lt; 1 cm, leucopenia, trombopenia e hipertransaminasemia (ALT 670), PCR 29.37, con función renal normal. Serologías nega-</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.868cm" svg:height="0.336cm" svg:x="2cm" svg:y="16.76cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">tivas o de infección pasada (Epstein-barr). El día 26/03 presenta alteración neurológica (rigidez de nuca) con estudio de LCR </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="17.007cm" svg:height="0.336cm" svg:x="2cm" svg:y="17.162cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">negativo. Es valorado por Dermatología objetivando exantema petequial equimótico que respeta palmas y plantas, asociado </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.597cm" svg:height="0.336cm" svg:x="2cm" svg:y="17.564cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">a úlceras corneales (sin etiología clara). Ingresa en medicina interna el 28/03 ante la sospecha de neumonía LID, probable </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.889cm" svg:height="0.336cm" svg:x="2cm" svg:y="17.966cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">meningitis bacteriana en paciente con DVP y síndrome de hipersensibilidad sistémico inducido por fármacos, se pauta trata-</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="17.033cm" svg:height="0.336cm" svg:x="2cm" svg:y="18.369cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">miento con rifampicina, ciprofloxacino y vancomicina por 15 días. Durante todo el ingreso se evitaron los betalactámicos y el </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">metamizol, recibió paracetamol y dexketoprofeno. La clínica fue evolucionando favorablemente. Presentó mejoría y resolu-</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">ción de las lesiones cutáneas, sin descamación en 10 días tras el alta hospitalaria. </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Resultados:</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Los resultados de la biopsia cutánea concluían exantema vírico vs erupción medicamentosa. Estudio alergológico: intradermo </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">positiva para amoxicilina y muy positiva para metamizol, las epicutáneas negativas y los TTL fueron positivos para amoxicilina </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">y metamizol (Tabla I y II). Diagnóstico de “Síndrome de DRESS probable(puntuación RegiSCAR de 4)”. </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T6">8</text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T14">Keywords: </text:span><text:span text:style-name="T15">DRESS, Amoxiciline, Metamizol</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Published </text:span><text:span text:style-name="T15">October 21, 2022</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Copyright: </text:span><text:span text:style-name="T15">© 2022 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License, </text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T15">which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Editor: </text:span><text:span text:style-name="T15">Alberto Borobia</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Cite as: </text:span><text:span text:style-name="T15">Gabriela Leon Zambrana, Katherine Pose, Ana Fiandor, Rosario Cabañas. Síndrome de hipersensibilidad inducida </text:span></text:p>
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    <draw:frame draw:style-name="gr212" draw:text-style-name="P210" draw:layer="layout" svg:width="15.543cm" svg:height="0.319cm" svg:x="1.977cm" svg:y="11.877cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T15">por fármacos en simultáneo Amoxicilina y Metamizol: comunicación de un caso. IBJ Clin Pharmacol 2022 (S4):e0005 doi: </text:span></text:p>
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    </draw:frame>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T15">10.24217/2530-4984.22s4v1s1.00005.</text:span></text:p>
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    <draw:frame draw:style-name="gr212" draw:text-style-name="P210" draw:layer="layout" svg:width="3.41cm" svg:height="0.319cm" svg:x="1.977cm" svg:y="12.639cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Funding: </text:span><text:span text:style-name="T15">Without funding.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Competing Interests: </text:span><text:span text:style-name="T15">Without competing interest.</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="1.903cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="2.858cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Conclusiones:</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Presentamos un caso de hipersensibilidad inducida por fármacos con pruebas cutáneas y TTL positivo para dos medicamen-</text:span></text:p>
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    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="15.818cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="3.862cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">tos (amoxicilina y metamizol). El diagnóstico y tratamiento de nuestro paciente precisó un trabajo multidisciplinario.</text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T12">Referencias:</text:span></text:p>
     </draw:text-box>
    </draw:frame>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">1.Cabañas R, Ramírez E, Sendagorta E, et al. Spanish Guidelines for Diagnosis, Management, Treatment, and Prevention of </text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="9.734cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="6.071cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">DRESS Syndrome. J Investig Allergol Clin Immunol. 2020;30(4):229-253. </text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.918cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="6.673cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">2.Barbaud, A., et al. “A multicentre study to determine the value and safety of drug patch tests for the three main classes of </text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="13.189cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="7.075cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">severe cutaneous adverse drug reactions.” British Journal of Dermatology 168.3 (2013): 555-562.</text:span></text:p>
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    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.961cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="7.677cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">3.Choudhary S, McLeod M, Torchia D, Romanelli P. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndro-</text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="6.195cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="8.08cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">me. J Clin Aesthet Dermatol. 2013;6(6):31-37.</text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr204" draw:text-style-name="P204" draw:layer="layout" svg:width="5.26cm" svg:height="0.331cm" svg:x="13.579cm" svg:y="28.144cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T6">2022 | Volume 1 | S. Issue4 | e00005</text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T6">www.ibjournals.com</text:span></text:p>
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    </draw:frame>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Málaga, Spain.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T18">2</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">UGC Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Spain.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T18">3</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Biomedical Research Network Center for Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute, Madrid, Spain.</text:span></text:p>
     </draw:text-box>
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      <text:p text:style-name="P199"><text:span text:style-name="T18">4</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Platform for Clinical Research and Clinical Trials IBIMA, Plataforma ISCiii de Investigación Clínica, Madrid, Spain.</text:span></text:p>
     </draw:text-box>
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    <draw:frame draw:style-name="gr209" draw:text-style-name="P208" draw:layer="layout" svg:width="2.584cm" svg:height="0.268cm" svg:x="1.988cm" svg:y="10.02cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T10">*Corresponding author:</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Villanueva-Paz M. UGC Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Málaga, Málaga, Spain. E-mail: </text:span><text:span text:style-name="T19">marvp75@gmail.com</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Introduction: </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Drug-induced liver injury (DILI) may develop in the context of an immune-mediated severe cutaneous adverse reaction, </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">including drug reaction with eosinophilia and systemic symptoms (DRESS). However, the characterization of DILI in the setting </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">of DRESS is a subject yet undefined.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Objectives: </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">We aimed to comprehensively assess the clinical characteristics, outcomes, and causative agents in a cohort of well-defined </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">DILI cases with DRESS from the Spanish DILI Registry and the LATINDILI Network.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Methods: </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Data from 55 well-characterized DILI cases with DRESS enrolled in the Spanish DILI Registry (N=31) and LATINDILI Network </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">(N=24) between 1994 and 2020 were retrieved. DRESS was defined according to the European Registry of Severe Cutaneous </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Adverse Reactions (RegiSCAR) diagnostic criteria. Steven Johnson syndrome and toxic epidermal necrolysis cases, and cases </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">with missing or incomplete information of any of the hypersensitivity features were excluded.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Results: </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">DILI-DRESS patients were aged 48±20 years, and 51% were female. Hepatocellular damage was predominant (44%). Most </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">patients (80%) had eosinophilia and were hospitalized. Over half of the patients showed a moderate liver injury (55%), while </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">the 15% developed a severe damage. Only one patient progressed to acute liver failure and died. DILI-DRESS cases showed a </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">distinctive causative agent pattern compared to DILI cases included in the registries. The most frequent drugs were antiepi-</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">leptic drugs (carbamazepine, lamotrigine, and phenytoin, 24%), amoxicillin-clavulanate (13%), anti-tuberculosis drugs (9.1%) </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">and allopurinol (7.3%). Antiepileptic drug-induced cases were younger and predominantly women. In allopurinol cases, </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.876cm" svg:height="0.336cm" svg:x="2cm" svg:y="21.312cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">mixed pattern of liver injury was distinctive. Anti-tuberculosis drugs were associated with a more severe liver injury and the </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">fatal outcome, and a prolonged time to resolution. </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Conclusion: </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Obtaining a complete clinical picture of DRESS represents a major challenge. In this well-characterized cohort, DILI-DRESS </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">cases coursed with great severity, but low mortality. Antiepileptic drugs were the leading causative agent, causing predo-</text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">minantly a hepatocellular pattern of liver injury. These findings represent a major step to understand the distinctive clinical </text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">features and outcomes of DRESS in the context of DILI.</text:span></text:p>
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    <draw:frame draw:style-name="gr204" draw:text-style-name="P204" draw:layer="layout" svg:width="5.26cm" svg:height="0.331cm" svg:x="13.584cm" svg:y="28.144cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T6">2022 | Volume 1 | S. Issue4 | e00006</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T6">www.ibjournals.com</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T6">2022 | Volume 1 | S. Issue4 | e00006</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Keywords: </text:span><text:span text:style-name="T15">Hepatotoxicity, drug reaction with eosinophilia and systemic symptoms, immunoallergic, antiepileptic drugs, </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">phenotyping.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Published </text:span><text:span text:style-name="T15">October 21, 2022</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Copyright: </text:span><text:span text:style-name="T15">© 2022 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License, </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Editor: </text:span><text:span text:style-name="T15">Alberto Borobia</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Cite as: </text:span><text:span text:style-name="T15">Sanabria-Cabrera J, Villanueva-Paz M, Niu H, Alvarez-Alvarez I, Andrade RJ, Lucena MI, on behalf of the Spanish DILI </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">Registry &amp; the LATINDILI Network.IN-DEPTH CHARACTERIZATION OF DRUG-INDUCED LIVER INJURY CASES WITH DRUG REACTION </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS: <text:s/>DEMOGRAPHICS, CLINICAL FEATURES AND CULPRIT DRUGS. IBJ Clin Pharmacol </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">2022 (S4):e0006 doi: 10.24217/2530-4984.22s4v1s1.00006.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Funding: </text:span><text:span text:style-name="T15">grants of the Andalusian Health Service (SAS)(PI-0310-2018), Instituto de Salud Carlos III– FEDER (PI18/00901, PI18/01804, </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">PI21/01248), and AEMPS. CIBERehd is funded by ISCIII. HN (POSTDOC_21_00780). IAA (CD20/00083). MVP (CD21/00198). JSC </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T15">(JR21/00066).</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Competing Interests: </text:span><text:span text:style-name="T15">The authors have no conflicts of interest to declare.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">, Rodríguez-Jiménez C</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">, Boada Fernández del Campo C</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">, Velázquez-Perelló C</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">, Fernández-Quintana E</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10"><text:s/></text:span><text:span text:style-name="T10">Complejo Hospitalario Universitario de Canarias, c/ofra s/n La Cuesta, La Laguna, Spain. </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">*Corresponding author:</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10"><text:s/></text:span><text:span text:style-name="T10">Consuelo Rodríguez Jiménez, Complejo Hospitalario Universitario de Canarias, c/ofra s/n La Cuesta, La Laguna, Spain. E-mail: </text:span><text:span text:style-name="T19">conrodjim@gmail.com</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Case report of a 53-year-old man who came to the emergency department because of pharyngotonsillitis.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">A type 2 diabetic patient, came to the emergency department with a sore throat and fever. He was diagnosed <text:s/>with pharyn-</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">gotonsillitis and started treatment with azithromycin. He started with skin lesions, so he returned to the emergency depart-</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">back with swallowing problems. No known allergies.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Physical examination:</text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">Conscious, haemodynamically stable, with lesions on thoracic centre and back composed of habonoid, vesicular and bliste-</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.588cm" svg:height="0.336cm" svg:x="2cm" svg:y="11.5cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">red elements. He also had lesions on the back of the hands and in the flexor area of the forearm, some of them bull’s-eye </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="17.134cm" svg:height="0.336cm" svg:x="2cm" svg:y="11.902cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">type, and similar elements on the lower limbs. Also, we found an erosive lesion on the soft palate about 2 cm in diameter. No </text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="4.883cm" svg:height="0.336cm" svg:x="2cm" svg:y="12.304cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">ocular or other mucosal alterations.</text:span></text:p>
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    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="4.362cm" svg:height="0.336cm" svg:x="2cm" svg:y="12.906cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T12">Results / Complementary tests:</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.847cm" svg:height="0.336cm" svg:x="2cm" svg:y="13.509cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T20">CBC:</text:span><text:span text:style-name="T12"> </text:span><text:span text:style-name="T13">Hb: 15.1 g/dL leukocytes: 16.98 x10E3/mm3 Absolute neutrophils: 13.24 Platelets: 291 x10E3/mm3 INR: 1.10 Glucose: </text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="5.797cm" svg:height="0.336cm" svg:x="2cm" svg:y="13.911cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">261 mg/dL GFR (CKD-EPI) &gt;90ml/min/sup. </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.292cm" svg:height="0.336cm" svg:x="2cm" svg:y="14.513cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T20">Biopsy-punch:</text:span><text:span text:style-name="T12"> </text:span><text:span text:style-name="T13">lesion of left upper limb about 0.4cm in surface with 0.7 in depth: Skin structure consisting of epidermis, </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.842cm" svg:height="0.336cm" svg:x="2cm" svg:y="14.915cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">dermis and hypodermis. Epidermis with some neutrophils. Mitoses in stratum basale. Dermal oedema with fibrin forming a </text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="17.088cm" svg:height="0.336cm" svg:x="2cm" svg:y="15.317cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">blister and under this, mixed inflammatory infiltrates with abundant neutrophils and eosinophils, perivascular and interstitial </text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="15.123cm" svg:height="0.336cm" svg:x="2cm" svg:y="15.72cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">with focal extension to the hypodermis. With PAS technique, it appears to be a Sweet’s syndrome-type picture.</text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="12.875cm" svg:height="0.336cm" svg:x="2cm" svg:y="16.322cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T20">Differential diagnosis:</text:span><text:span text:style-name="T12"> </text:span><text:span text:style-name="T13">Erythema Multiforme Major vs Steven-Johson secondary to Amoxicillin.</text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="7.22cm" svg:height="0.336cm" svg:x="2cm" svg:y="16.924cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T20">Definitive diagnosis after biopsy:</text:span><text:span text:style-name="T12"> </text:span><text:span text:style-name="T13">Sweet’s Syndrome.</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="3.545cm" svg:height="0.336cm" svg:x="2cm" svg:y="17.526cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T12">Treatment and evolution:</text:span></text:p>
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    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.614cm" svg:height="0.336cm" svg:x="2cm" svg:y="18.129cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">Amoxicillin was discontinued and treatment was started with intravenous corticosteroids (1mg/kg), antihistamine (polara-</text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.741cm" svg:height="0.336cm" svg:x="2cm" svg:y="18.531cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">mine) and insulin control. After 3 days with intravenous corticosteroids, lesions and swallowing improved. The patient was </text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="8.773cm" svg:height="0.336cm" svg:x="2cm" svg:y="18.933cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">discharged with oral corticosteroids with a descending regimen. </text:span></text:p>
     </draw:text-box>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.889cm" svg:height="0.336cm" svg:x="2cm" svg:y="19.535cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">The case was reported to the Centro Autonómico de Farmacovigilancia de Canarias, which, after evaluation of the temporal </text:span></text:p>
     </draw:text-box>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="7.63cm" svg:height="0.336cm" svg:x="2cm" svg:y="19.937cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">relationship, established a POSSIBLE causal relationship.</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="1.598cm" svg:height="0.336cm" svg:x="2cm" svg:y="20.54cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T12">Conclusion:</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.643cm" svg:height="0.336cm" svg:x="2cm" svg:y="21.142cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">If any of these antibiotics were the causative agent, we still can not conclude that there is a greater causal relationship for </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">one than for the other. Adverse drug reactions account for 5-10% of admissions or trips to hospital emergency departments. </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">They are often overlooked in initial differential diagnoses and the drug is only considered when the lesions are really serious </text:span></text:p>
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     <text:p/>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">and life-threatening. </text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T14">Keywords: </text:span><text:span text:style-name="T15">antibiotics, Sweet Syndrome, cutaneous drug reaction</text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr212" draw:text-style-name="P210" draw:layer="layout" svg:width="3.605cm" svg:height="0.319cm" svg:x="2.007cm" svg:y="23.679cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T14">Published </text:span><text:span text:style-name="T15">October 21, 2022</text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T14">Copyright: </text:span><text:span text:style-name="T15">© 2022 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License, </text:span></text:p>
     </draw:text-box>
    </draw:frame>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T15">which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T14">Editor: </text:span><text:span text:style-name="T15">Alberto Borobia</text:span></text:p>
     </draw:text-box>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T14">Cite as: </text:span><text:span text:style-name="T15">Rolinson-Landaeta L1, Rodríguez-Jiménez C2, Boada Fernández del Campo C3,6, Velázquez-Perelló C4, Fondevilla-Batista D5, </text:span></text:p>
     </draw:text-box>
    </draw:frame>
    <draw:frame draw:style-name="gr212" draw:text-style-name="P210" draw:layer="layout" svg:width="16.965cm" svg:height="0.319cm" svg:x="2.007cm" svg:y="25.584cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T15">Fernández-Quintana E6. SWEET Syndrome, who was to blame?. IBJ Clin Pharmacol 2022 (S4):e0007 doi: 10.24217/2530-4984.22s4v</text:span></text:p>
     </draw:text-box>
    </draw:frame>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T15">1s1.00007.</text:span></text:p>
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    </draw:frame>
    <draw:frame draw:style-name="gr212" draw:text-style-name="P210" draw:layer="layout" svg:width="3.41cm" svg:height="0.319cm" svg:x="2.007cm" svg:y="26.346cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T14">Funding:</text:span><text:span text:style-name="T15"> Without funding.</text:span></text:p>
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     <text:p/>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T14">Competing Interests: </text:span><text:span text:style-name="T15">Without competing interest.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T6">www.ibjournals.com</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T6">12</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T7">Necrolisis epidérmica tóxica fatal por Ciprofloxacino. </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T7">Un caso ilustrativo.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T8">Cristina Pesántez¹, María Cruz Torres¹, Gerard Pitarch², Ana Pitarch², María Jesús Nicolau³, Ernesto Enrique¹.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T18">1</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Allergy Service. Hospital General Universitario de Castellón, Castellón de la Plana, Spain. <text:s text:c="8"/></text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T18">2</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Dermatology Service, Hospital General Universitario de Castellón, Castellón de la Plana, Spain. </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T18">3</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Anatomical Pathology Service, Hospital General Universitario de Castellón, Castellón de la Plana, Spain.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">*Corresponding author: </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T10">Cristina Pesántez, Allergy Service. Hospital General Universitario de Castellón, Castellón de la Plana. Spain. E-mail: </text:span><text:span text:style-name="T19">crissap_17@hotmail.com</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Caso clínico:</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Varón pluripatológico que presenta episodios de otitis media aguda (OMA) de repetición.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">En el 2011 (87 años) se pauta Ciprofloxacino oral por OMA, presentando tras 48h lesiones <text:s/>generalizadas pustulares y má-</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.978cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="10.307cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">culas eritematosas con signo de Nikolsky positivo, afectación de mucosas y deterioro del estado general. Tras valoración por </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="17.105cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="10.709cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">Dermatología, ingresa, se retira ciprofloxacino y se instaura fluidoterapia iv y analgesia. Se realiza biopsia compatible con SSJ. </text:span></text:p>
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    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="12.503cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="11.111cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">Evoluciona favorablemente, es dado de alta y se recomienda evitación de fluoroquinolonas.</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.52cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="11.713cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">En el 2018 (93 años) presenta nuevamente OMA y por indicación de ORL se pauta Ciprofloxacino oral. A las 72h presenta </text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">lesiones generalizadas eritemato-descamativas y ampollosas en piel y mucosas, deterioro de la función renal y elevación </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.647cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="12.518cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">de reactantes de fase aguda. Ingresa, se retira ciprofloxacino e inicia tratamiento parenteral con esteroides, fluidoterapia, </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.774cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="12.92cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">antibiótico y analgesia. La biopsia es compatible con NET. Evoluciona desfavorablemente, presenta sobreinfección cutánea </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">extensa, insuficiencia respiratoria aguda, fallo multiorgánico y exitus.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Discusión:</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">La causa más frecuente de SSJ/NET son los medicamentos. La mortalidad es 3 veces superior en el NET debido a la extensión </text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.745cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="15.531cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">cutánea y las complicaciones sistémicas, además, la edad avanzada y el deterioro de la función renal constituyen signos de </text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">mal pronóstico. </text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">Entre 10-20% de pacientes con afectación pulmonar requieren soporte ventilatorio. </text:span></text:p>
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    </draw:frame>
    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.88cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="17.137cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">El tratamiento inicial incluye fluidoterapia IV, analgesia IV y cuidados de la piel. El estudio alergológico de las reacciones gra-</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="13.841cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="17.54cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">ves por medicamentos puede realizarse mediante pruebas epicutáneas valorando el riesgo/beneficio.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T12"><text:s text:c="84"/></text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="1.598cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="18.744cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T12">Conclusión:</text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">Es vital la identificación precoz del fármaco implicado y su retirada permanente.</text:span></text:p>
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    <draw:frame draw:style-name="gr210" draw:text-style-name="P209" draw:layer="layout" svg:width="16.533cm" svg:height="0.336cm" svg:x="2.012cm" svg:y="19.949cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T13">El abordaje de esta patología precisa de la creación de unidades multidisciplinares (dermatología, alergología, intensivos, </text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T13">medicina interna, anatomía patológica, farmacia, etc) para lograr un diagnóstico y tratamiento integral.</text:span></text:p>
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     <text:p/>
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     <text:p/>
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      <text:p text:style-name="P199"><text:span text:style-name="T13">El caso presentado remarca la importancia de crear alertas medicamentosas visibles en todos niveles asistenciales sanitarios.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Keywords: </text:span><text:span text:style-name="T15">Drug reaction; Stevens-Johnson syndrome; Toxic epidermal necrolysis.</text:span></text:p>
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    <draw:frame draw:style-name="gr212" draw:text-style-name="P210" draw:layer="layout" svg:width="3.605cm" svg:height="0.319cm" svg:x="2cm" svg:y="22.924cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Published </text:span><text:span text:style-name="T15">October 21, 2022</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Copyright: </text:span><text:span text:style-name="T15">© 2022 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License, </text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T15">which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</text:span></text:p>
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    <draw:frame draw:style-name="gr212" draw:text-style-name="P210" draw:layer="layout" svg:width="3.004cm" svg:height="0.319cm" svg:x="2cm" svg:y="24.067cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Editor: </text:span><text:span text:style-name="T15">Alberto Borobia</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Cite as: </text:span><text:span text:style-name="T15">Cristina Pesántez, María Cruz Torres, Gerard Pitarch, Ana Pitarch, María Jesús Nicolau, Ernesto Enrique.Necrolisis epidérmica </text:span></text:p>
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     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T15">tóxica fatal por Ciprofloxacino. Un caso ilustrativo. IBJ Clin Pharmacol 2022 (S4):e0008 doi: 10.24217/2530-4984.22s4v1s1.00008.</text:span></text:p>
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    <draw:frame draw:style-name="gr212" draw:text-style-name="P210" draw:layer="layout" svg:width="3.41cm" svg:height="0.319cm" svg:x="2cm" svg:y="25.21cm">
     <draw:text-box>
      <text:p text:style-name="P199"><text:span text:style-name="T14">Funding: </text:span><text:span text:style-name="T15">Without funding.</text:span></text:p>
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    <draw:frame draw:style-name="gr212" draw:text-style-name="P210" draw:layer="layout" svg:width="6.492cm" svg:height="0.319cm" svg:x="2cm" svg:y="25.591cm">
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      <text:p text:style-name="P199"><text:span text:style-name="T14">Competing Interests: </text:span><text:span text:style-name="T15">Without competing interest.</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T6">2022 | Volume 1 | S. Issue4 | e00008</text:span></text:p>
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      <text:p text:style-name="P199"><text:span text:style-name="T1">ISSN: 2530-4984</text:span></text:p>
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