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3-LUPUS ERITEMATOSO.P65 REVISTA COLOMBIANA DE REUMATOLOGÍA Vol. 18 Núm. 3, septiembre 2011, pp. 175-186 Vol.© 2011, 18 Núm. Asociación 3 - 2011 Colombiana de Reumatología LUPUS ERITEMATOSO SISTÉMICO Y EMBARAZO ARTÍCULO DE REVISIÓN Lupus eritematoso sistémico y embarazo Systemic lupus erythematosus and pregnancy Luis Alonso González Naranjo1, Mauricio Restrepo Escobar2 Resumen El lupus eritematoso sistémico (LES) se asocia con diversos eventos adversos en el embarazo como parto prematuro, pre-eclampsia y pérdidas gestacionales. Gracias a los avances terapéuticos el pronóstico del embarazo en mujeres con LES ha mejorado. Además de las complicaciones relacionadas con el emba- razo, las mujeres con LES tienen un alto riesgo de complicaciones médicas durante la gestación como hipertensión, enfermedad renal, síndrome antifosfolípido, diabetes pregestacional o actividad lúpica, las cuales afectan el curso de la enfermedad y empeoran los resultados del embarazo. El embarazo au- menta la probabilidad de recaídas del LES. Aunque no es posible predecir cuándo se presentará una recaída en una paciente, esta es más probable si la enfermedad ha permanecido activa en los seis meses previos a la concepción. Palabras clave: lupus eritematoso sistémico, embarazo, resultados obstétricos. Summary Systemic lupus erythematosus (SLE) is associated with multiple adverse pregnancy outcomes, including fetal loss, preterm birth, and pre-eclampsia. With treatment advances, the prognosis of pregnancy in women with SLE has improved. In addition to complications related to pregnancy, SLE women are at increased risk for medical complications during pregnancy such as hypertension, renal disease, antiphospholipid syndrome, pregestational diabetes or active SLE which affect the course of the disease and worse the outcome of pregnancy. Pregnancy increases the likelihood of a lupus flare. It is not possible to predict when an individual patient will flare, although flare is more likely if disease has been active within six months of conception. Key words: systemic lupus erythematosus, pregnancy, obstetric outcome. El lupus eritematoso sistémico (LES) es una vamente la frecuencia de embarazos exitosos, con enfermedad autoinmune multisistémica que afec- una disminución en la tasa de pérdida de emba- ta especialmente a mujeres en edad reproductiva. razos de un 43% en los años sesenta a un 17% en En el pasado, no se recomendaba a las mujeres el 20001. Sin embargo, el embarazo en estas pa- con LES embarazarse por temor a complicacio- cientes debe ser considerado de alto riesgo por nes graves tanto para ellas como para el feto. el gran número de complicaciones maternas y Sin embargo, a través de los años, gracias a un fetales causadas por actividad de la enfermedad mayor conocimiento de la enfermedad y a la o por los anticuerpos antifosfolípidos (aFL) que atención simultánea y coordinada de obstetras, influyen en la evolución de la enfermedad y en el nefrólogos y especialistas en lupus para la ma- desenlace final del embarazo. Por ende, requie- dre y el feto, se ha logrado mejorar significati- ren una evaluación completa antes, durante y des- 1. Profesor asistente. Sección de Reumatología, Departamento de Medici- Los autores declaran no presentar ningún conflicto de interés al momento na Interna, Facultad de Medicina, Universidad de Antioquia, Medellín, de la redacción del manuscrito. Colombia. Correo electrónico: [email protected] 2. Profesor auxiliar. Sección de Reumatología, Departamento de Medicina In- Recibido: Abril 18 de 2011 terna, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia. Aceptado: Junio 16 de 2011 175 LUIS A. GONZÁLEZ N. & MAURICIO RESTREPO E. Rev.Colomb.Reumatol. pués de su embarazo. Además, algunos de los para producir anticuerpos contra el HLA7,8. Diver- medicamentos antirreumáticos utilizados en el sas alteraciones tanto locales como sistémicas tratamiento del LES son teratogénicos. acontecen en el sistema inmunológico durante la En este artículo se revisan los cambios fisioló- gestación, evitando así el rechazo fetal. La gicos normales en el embarazo, los riesgos para placenta provee un microambiente inmunológico la madre y el feto y las medidas preventivas, donde existe un estado de tolerancia mutua en- diagnósticas y terapéuticas con el fin de minimi- tre dos tejidos antigénicamente diferentes y cons- zar las complicaciones y mejorar los resultados tituye el sitio de interfase materno-fetal. El lado en el embarazo de mujeres con LES. materno corresponde a la decidua que es endometrio hipertrófico y el lado fetal al Cambios fisiológicos normales durante el trofoblasto. La unidad feto-placentaria es un si- embarazo tio inmunológicamente privilegiado ya que po- see diversos mecanismos de protección contra el El embarazo normal es un estado fisiológico rechazo del embarazo: 1) expresa una combina- caracterizado por cambios hormonales y signos ción de tres moléculas poco usuales de HLA de y síntomas particulares que pueden simular acti- clase I (HLA-C, HLA-E y HLA-G) las cuales son vidad lúpica. El volumen intravascular aumenta ligandos dominantes para receptores inhibitorios de un 30% a 50% en un embarazo normal; por en las células asesinas naturales (NK), macró- ende, las pacientes con LES con compromiso en fagos y células dentríticas de la madre; 2) una la función renal o cardíaca pueden tolerar mal alta expresión de Fas ligando (FasL) por el 2 este incremento . El embarazo genera un estado sincitiotrofoblasto materno, el cual induce la protrombótico ya que hay un aumento en los ni- apoptosis de linfocitos activados que expresan veles de fibrinógeno, protrombina, factores VII y Fas al unirse a FasL y 3) la expresión de proteí- X de la coagulación y disminución en los niveles nas reguladoras del complemento, las cuales de la proteína S; asimismo, el sistema fibrinolítico protegen la unidad feto-placentaria de la lisis se encuentra inhibido, especialmente en el tercer mediada por el complemento9,10. trimestre del embarazo3. Además de los cambios El embarazo normal conlleva a un cambio de en la coagulación, la estasis venosa, la compre- una respuesta Th1 o celular a una respuesta hu- sión venosa por el útero grávido y el reposo en moral Th2 de forma dominante en la cual pre- cama contribuyen a un alto riesgo de trombo- dominan citoquinas como interleuquina 10 embolismo venoso4, el cual, es cinco veces ma- (IL-10), IL-4, IL-5, IL-6 e IL-13. Los abortos espon- yor en la mujer embarazada que en la mujer no táneos de etiología desconocida son mediados embarazada de la misma edad5. por una respuesta Th1, donde el interferón γ, el Usualmente las mujeres embarazadas están factor de necrosis tumoral α y ß, la IL-2 y la IL-12 ligeramente anémicas en el tercer trimestre de- predominan. La progesterona en la interfase bido a la hemodilución fisiológica2. Aunque la materno-fetal, a través del factor bloqueador in- producción de plaquetas normalmente aumen- ducido por progesterona, inhibe la función de las ta en forma compensatoria, una leve tromboci- células NK uterinas y promueve una respuesta Th2 topenia (alrededor de 100.000 plaquetas/mm3) dominante10. se produce en el 8% de los embarazos no La inmunidad celular comúnmente se encuen- 6 complicados . tra deprimida en el embarazo, presentándose una En el embarazo existe una tolerancia local disminución en la relación célula T/célula B, en persistente del sistema inmune de la madre a los la relación linfocitos/monocitos y un incremento antígenos leucocitarios humanos (HLA) del padre en la relación célula T supresora/célula T expresados por el feto. Esta tolerancia inmune ayudadora3. La respuesta inmune humoral, inclu- local no se asocia con una disminución en la res- so la respuesta a antígenos microbianos, está puesta inmunológica de la madre a los estímu- deprimida. La quimiotaxis y adhesión de los los exógenos, o con incapacidad de la madre leucocitos también está disminuida. La produc- 176 Vol. 18 Núm. 3 - 2011 LUPUS ERITEMATOSO SISTÉMICO Y EMBARAZO ción de autoanticuerpos no parece estar induci- embarazo13,17,18. Metotrexate, mofetil micofeno- da específicamente por el embarazo11. En em- lato y ciclofosfamida son teratogénicos y deben barazos normales, los niveles del complemento suspenderse al menos tres meses antes del em- se encuentran usualmente elevados en relación barazo. Debido a que la suspensión de estos con los niveles séricos encontrados en mujeres no inmunosupresores puede ser suficiente para el embarazadas, lo cual indica un aumento de su desencadenamiento de nuevas exacerbaciones síntesis3. del LES durante el embarazo, se recomienda re- emplazarlos con un inmunosupresor que no esté Asesoramiento antes del embarazo contraindicado durante el embarazo, como por 12 Es necesario informar sobre el riesgo de even- ejemplo, la azatioprina . tos adversos, tanto para la madre como para el Con la excepción de los compuestos fluorados bebé, y establecer la planificación de la atención (dexametasona y betametasona), los GCs son prenatal. Es importante evaluar el riesgo de com- inactivados por hidrolasas placentarias. Aunque plicaciones maternas y fetales12. Por tanto, en la son considerados como seguros en el embarazo, visita preconcepcional es necesario conocer las existe un aumento de dos veces en el riesgo de complicaciones presentadas en embarazos an- paladar hendido tras la exposición a GCs sisté- teriores, la positividad de los autoanticuerpos, micos. Además, dosis de prednisona o su equiva- especialmente de los aFL (anticuerpos anti- lente mayores de 20 mg/día pueden causar cardiolipinas [aCL]
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