Mielitis longitudinal asociada a lupus eritematoso ?· Debido a que la mielitis transversa es un hallazgo…

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r e v c o l o m b r e u m a t o l . 2 0 1 5;2 2(2):140143Documento descargado de http://www.elsevier.es el 01/03/2016. Copia para uso personal, se prohbe la transmisin de este documento por cualquier medio o formato.www.elsev ier .es / rc reumaInforme de casoMielitis longitudinal asociada a lupus eritematososistmicoJos Antonio de Jess Batn Garridoa,, ufrates Hernndez Nnezb y Francisco Olnba Medicina Interna, Hospital Regional de Alta Especialidad Dr. Gustavo A. Rovirosa Prez, Villahermosa, Tabasco, Mxicob Servicio de Medicina Interna y Reumatologa, Hospital Regional de Alta Especialidad Dr. Gustavo A. Rovirosa, Villahermosa, Tabasco,Mxicoinformacin del artculoHistoria del artculo:Recibido el 8 de enero de 2015Aceptado el 12 de mayo de 2015On-line el 19 de junio de 2015Palabras clave:Lupus neuropsiquitricoMielitis longitudinalLupus eritematoso sistmicor e s u m e nSe presenta el caso de una mujer de 33 anos de edad con el diagnstico de mielitis lon-gitudinal secundaria a lupus eritematoso sistmico. Present parapleja e hipoestesia parasensibilidad trmica y dolorosa a nivel del dermatoma T6, recibi manejo con pulsos demetilprednisolona y ciclofosfamida con respuesta parcial al tratamiento. La mielitis es unaenfermedad inflamatoria que produce una lesin en la mdula espinal, la mielitis longitu-dinal hace referencia a la participacin continua de la mdula espinal, con implicacin de 3o ms segmentos medulares contiguos. El tratamiento consiste en dosis altas de glucocor-ticoides combinados o no con inmunosupresores o plasmafresis. 2015 Asociacin Colombiana de Reumatologa. Publicado por Elsevier Espaa, S.L.U.Todos los derechos reservados.Longitudinal myelitis associated with systemic lupus erythematosusKeywords:Neuropsychiatric lupusLongitudinal myelitisSystemic lupus erythematosusa b s t r a c tA case is presented of a 33 year-old woman diagnosed with longitudinal myelitis secon-dary to systemic lupus erythematosus. She presented with paraplegia and hypoesthesia topain, and temperature sensitivity to dermatome level T6. She was treated with pulses ofmethylprednisolone and cyclophosphamide, with partial response to treatment. Myelitis isan inflammatory disease that causes injury to the spinal cord. Longitudinal myelitis refersto the continued involvement of the spinal cord, with the involvement of three or more adja-cent spinal segments. The treatment consists of high steroid doses, sometimes combinedwith immunosuppressants and/or plasmapheresis. Colo 2015 Asociacin Autor para correspondencia.Correo electrnico: antonio bg1986@hotmail.com (J.A.d.J. Batn Garhttp://dx.doi.org/10.1016/j.rcreu.2015.05.0020121-8123/ 2015 Asociacin Colombiana de Reumatologa. Publicado mbiana de Reumatologa. Published by Elsevier Espaa, S.L.U. Allrights reserved.rido).por Elsevier Espaa, S.L.U. Todos los derechos reservados.dx.doi.org/10.1016/j.rcreu.2015.05.002http://www.elsevier.es/rcreumahttp://crossmark.crossref.org/dialog/?doi=10.1016/j.rcreu.2015.05.002&domain=pdfmailto:antonio_bg1986@hotmail.comdx.doi.org/10.1016/j.rcreu.2015.05.002o l . 2 0 1 5;2 2(2):140143 141IEd(masepuliloCPLpcgphpydnc(tts(1drdlrspihldmr(emdupFigura 1 Resonancia magntica nuclear de mdulaespinal torcica y lumbar en secuencia T1, donde podemosanticuerpos IgG anti-acuaporina 4 (anti-AQP4) en suero, conresultado negativo.Documento descargado de http://www.elsevier.es el 01/03/2016. Copia para uso personal, se prohbe la transmisin de este documento por cualquier medio o formato.r e v c o l o m b r e u m a t ntroduccinn 1999 el Colegio Americano de Reumatologa public 19 sn-romes neurolgicos asociados a lupus eritematoso sistmicoLES), dividindolos en 2 categoras: centrales y perifricos1. Laielopata es una manifestacin de tipo central, que afecta menos del 1% de los pacientes con LES2,3. Es muy grave ye suele presentar en los primeros 5 anos de evolucin de lanfermedad, con una recurrencia del 21-55%, y el 21% de losacientes no presenta mejora e incluso presenta deteriorona vez instaurado el tratamiento4,5. El manejo consiste ena combinacin de metilprednisolona y ciclofosfamida por vantravenosa, siendo ms eficaz mientras ms rpido se inicie,a terapia de intercambio de plasma se emplea en casos graves refractarios al tratamiento inicial6.aso clnicoaciente femenino de 33 anos de edad con el diagnstico deES desde hace un ano (poliartritis no erosiva, eritema malar,ancitopenia, afectacin de mucosas y anticuerpos antinu-leares y anticuerpos anti-ADN positivos) en tratamiento conlucocorticoide, azatioprina e hidroxicloroquina. Ingresa porresentar prdida del estado de alerta, as como fiebre de 72oras de evolucin y cefalea de predominio occipital, 2 dasrevios haba presentado evacuaciones diarreicas, nuseas vmitos. A la exploracin fsica presenta eritema malar,esorientacin, presencia de signos menngeos (rigidez deuca, signos de Kernig y Brudzinski positivos). Los paraclni-os a su ingreso reportan anemia normoctica, normocrmicaHb 10 g/dL, Hto 35,8%, VCM 87,8 fL, HCM 27,1 pg), leucoci-os 10,2 103/, bioqumica sangunea, electrolitos sricos yiempos de coagulacin dentro de los parmetros normales.Debido al cuadro clnico se sospecha una meningitis ye realiza puncin lumbar que reporta hiperproteinorraquia198 mg/dL), hipoglucorraquia (24 mg/dL), recuento celular.500 cel/mm3, 74% polimorfonucleares, tincin de Gram ye BAAR negativas. Con el diagnstico de meningitis bacte-iana se inicia tratamiento con ceftriaxona 2 g, cada 12 horase manera emprica, en espera del resultado del cultivo delquido cefalorraqudeo (LCR).Despus de 24 horas de tratamiento, la paciente presentaecuperacin del estado de alerta, ausencia de cefalea y deignos menngeos. A las 48 horas de inicio del tratamientoresenta parestesias y debilidad ascendente en extremidadesnferiores, as como retencin urinaria y de heces, esfnter analipotnico. A las 72 horas presenta parapleja, fuerza muscu-ar de extremidades inferiores 0/5 en escala de Daniels, nivele hipoestesia para sensibilidad trmica y dolorosa inicial-ente en dermatoma L1, en 24 horas asciende hasta T6.Ante la sospecha clnica de una mielitis asociada a LES, seealiza de manera urgente una resonancia magntica nuclearRMN) de mdula espinal la cual reporta en secuencia T1nsanchamiento medular (fig. 1) y en secuencia T2 ensancha-iento medular con senal hiperintensa en toda la extensine la mdula dorsal y lumbar (fig. 2), con la confirmacin dena mielitis longitudinal se inician pulsos con 1 g de metil-rednisolona por va intravenosa, cada 24 horas, por 3 dosis,observar el ensanchamiento medular en toda su extensin.seguida de 1 g de ciclofosfamida por va intravenosa, previaadministracin de mesna. Debido a que la mielitis transversaes un hallazgo tpico de la neuromielitis ptica, se solicitanFigura 2 Resonancia magntica nuclear de mdulaespinal torcica y lumbar en secuencia T2 en la cual seobserva ensanchamiento medular y senal hiperintensa entoda la extensin. t o l Documento descargado de http://www.elsevier.es el 01/03/2016. Copia para uso personal, se prohbe la transmisin de este documento por cualquier medio o formato.142 r e v c o l o m b r e u m aSe recaba resultado de cultivo de LCR para bacterias, hon-gos y Mycobacterium tuberculosis con resultados negativos.Se solicitan anticuerpos antifosfolpidos (aFL), los cualesreportan anticuerpos anti-cardiolipina (aCL) IgG de 40 U/mL,aCL IgM 25 U/mL, anticuerpos anti-2 glicoprotena (2GPI) IgGde 90 U/mL, los anti-2GPI IgM 115 U/mL. Se agrega al manejoaspirina en bajas dosis.Despus de los pulsos se mantiene con prednisona a dosisde 75 mg/da, va oral y 50 mg de azatioprina.Siete das despus del inicio de los pulsos la paciente recu-pera sensibilidad a nivel de L1, pero persiste con incontinenciade esfnteres y parapleja. Despus de 6 ciclos de ciclofosfa-mida, uno mensual, la paciente recupera control de esfnteres,pero se mantiene con parapleja. Sin presentar recada des-pus de 7 meses de seguimiento.DiscusinSe presenta el caso de una mujer de 33 anos de edad conmielitis longitudinal secundaria a LES, inicialmente se pensen meningitis bacteriana por la presencia de signos menn-geos y las caractersticas del LCR, sin embargo, al presentar laparapleja se realiz RMN de mdula espinal confirmando eldiagnstico de mielitis longitudinal.Se denomina mielitis longitudinal cuando existe una par-ticipacin continua de la mdula espinal o bien cuando seinvolucran 3 o ms segmentos medulares contiguos, afectacentralmente el cordn medular y, en ocasiones, se extiendehasta el bulbo, observndose con mejor definicin en secuen-cias T2 y STIR de la RMN. Si el compromiso medular se observahipointenso en T1 est indicando necrosis y cavitacin (lesinsecuelar), mientras que si muestra refuerzo con gadolinioindica inflamacin activa7,8.EL lupus neuropsiquitrico (LESNP) se presenta hasta en el80% de los pacientes, sin embargo, la mielitis es poco frecuentey se presenta en el 1%. Hasta el 2009 se haban reportado 105casos de mielitis asociada a LES en la literatura3.El LESNP es una de las principales causas de mor-bimortalidad en los pacientes con LES, es multifactorial,implicando citoquinas inflamatorias, autoanticuerpos y com-plejos inmunes. En las autopsias de los pacientes con LESNPse observan infartos multifocales, hemorragia cerebral, atrofiacortical, desmielinizacin e isquemia. Desempenan un papelimportante en su fisiopatogenia la integridad de la barrerahematoenceflica y la presencia de autoanticuerpos9.Se han descrito numerosos autoanticuerpos en el suero depacientes con LES, sin embargo, en el LESNP, solo 3 se han aso-ciado con manifestaciones clnicas: los aFL, anti-P-ribosomaly los anticuerpos contra la subunidad NR2 del receptor gluta-mato N-metil-D-aspartato9. Los aFL se encuentran presenteshasta en el 60% de los pacientes con mielitis asociada a LES3,8.Debido a la presencia de estos anticuerpos se piensa que elmecanismo fisiopatolgico es consecuencia de trombosis arte-rial, lo cual produce necrosis de la mdula espinal, as comouna interaccin directa entre los anticuerpos y los fosfolpidos10espinales .Su presentacin clnica puede ser como una mielitis agudao subaguda, cuando evoluciona en ms de 4 horas y menosde 4 semanas, o puede ser una mielitis crnica progresiva con. 2 0 1 5;2 2(2):140143sndrome de remisin y recadas de afectacin medular4,6. Enla forma aguda y subaguda el paciente presenta dolor intensoa nivel del cuello y en la regin interescapular, posteriormentese presenta dficit sensorial y motor debajo del nivel medularde la lesin, la forma subaguda y la crnica suelen asociarsems a la incontinencia urinaria y dificultad para la marcha,que puede progresar hasta una parapleja espstica. La mieli-tis asociada a LES suele presentar parapleja hasta en el 70%de los casos, tumefaccin de la regin afectada, retencin uri-naria y dolor abdominal o lumbar6,8.El diagnstico puede hacerse mediante estudios de ima-gen de la mdula espinal y del LCR. La RMN muestra senaleshiperintensas en T2 entre 70-93% de los casos, realce con gado-linio y edema del cordn medular, as mismo, es til paraexcluir compresin del cordn6. Si se presentan otros signos osntomas de LESNP se debe realizar RMN cerebral. Las anorma-lidades del LCR de leves a moderadas son comunes (50-70%),pero no especficas, suele haber pleocitosis, hipoglucorraquiae hiperproteinorraquia, se deben realizar estudios microbio-lgicos para excluir mielitis infecciosa3,6.El diagnstico diferencial se debe hacer con infeccionesvirales, compresin medular debido a las fracturas vertebra-les, lipomatosis epidural o subdural, abscesos paravertebrales,subluxacin atlanto-axoidea y neuromielitis ptica o enfer-medad de Devic811.Le enfermedad de Devic se caracteriza por ataques agu-dos de neuritis ptica y mielitis, el proceso agudo que afectael nervio ptico y la mdula espinal puede ser simultneo oestar separado por semanas o meses, es tpico hallar duranteel episodio agudo de mielitis una afectacin longitudinal enlas imgenes de RMN en T2 y FLAIR, por lo que el diagns-tico definitivo lo establece la presencia de anti-AQP4 con unasensibilidad y especificidad elevadas11,12.A pesar de que el LCR presente caractersticas infecciosas(meningitis bacteriana o viral), se recomienda iniciar terapiacon glucocorticoides debido a los beneficios de su empleo tem-prano, mientras se confirma el diagnstico y continuar si sedescarta un proceso infeccioso6. El tratamiento consiste enla combinacin de 3 ciclos de 1 g de metilprenisolona porva intravenosa y un ciclo de ciclofosfamida en la fase aguda,seguido de prednisona por va oral y ciclofosfamida en bolosmensuales de 3 a 12 meses. La respuesta neurolgica en para-lelo con la mejora en la RMN se produce dentro de unospocos das a 3 semanas2,6. Las recadas son comunes (50-60%)durante la reduccin de la dosis de glucocorticoides, lo quesubraya la necesidad de terapia inmunosupresora de man-tenimiento. La plasmafresis se emplea en casos refractarioso graves. Si existe la presencia de aFL positivos la terapia deanticoagulacin tiene buenos resultados2,9.ConclusinLa mielitis longitudinal es un sndrome neurolgico asociadoa LES poco frecuente, sin embargo, se debe sospechar en lospacientes que presentan un cuadro compatible con menin-gitis, paraparesia o parapleja, debido a que el pronsticodepende del tratamiento oportuno. Es importante descartar lapresencia de aFL, para determinar el empleo de terapia anti-trombtica.o l . 2 RPpsCeDapCLb11Rodrguez D, et al. Neuromielitis ptica: actualizacin clnica.Documento descargado de http://www.elsevier.es el 01/03/2016. Copia para uso personal, se prohbe la transmisin de este documento por cualquier medio o formato.r e v c o l o m b r e u m a t esponsabilidades ticasroteccin de personas y animales. Los autores declaran queara esta investigacin no se han realizado experimentos eneres humanos ni en animales.onfidencialidad de los datos. Los autores declaran que enste artculo no aparecen datos de pacientes.erecho a la privacidad y consentimiento informado. Losutores declaran que en este artculo no aparecen datos deacientes.onflicto de interesesos autores declaran no tener ningn conflicto de intereses. i b l i o g r a f a1. Borchers A, Aokia C, Naguwa S, Keen C, Shoenfeld Y,Gershwin M. Neuropsychiatric features of systemic lupuserythematosus. Autoimmunity Reviews. 2005;4:32944.2. Rodrguez F, Freire M, Grana J, Atanes A. Evolucin yrespuesta al tratamiento de un caso de mielitis. Rev Clin Esp.2002;202(6):35863.3. Tristano A. Mielitis transversa asociada a enfermedadesautoinmunes. Revisin. Invest Clin. 2009;50(2):25170.4. Schulz S, Shenin M, Mehta A, Kebede A, Fluerant M, Derk C.Initial presentation of acute transverse myelitis in systemic10 1 5;2 2(2):140143 143lupus erythematosus: demographics, diagnosis, managementand comparison to idiopathic cases. Rheumatol Int.2012;32:26237.5. Birnbaum J, Petri M, Thompson R, Izbudak I, Kerr D. Distinctsubtypes of myelitis in systemic lupus erythematosus.Arthritis Rheum. 2009;60:337887.6. Bertsias G, Ioannidis J, Aringer M, Bollen E, Bombardieri S,Bruce I, et al. EULAR recommendations for the managementof systemic lupus erythematosus with neuropsychiatricmanifestations: report of a task force of the EULAR standingcommittee for clinical affairs. Ann Rheum Dis.2010;69(12):207482.7. Tllez J, Remes J, Negrete R, Dvila L. Longitudinal myelitisassociated with systemic lupus erythematosus: clinicalfeatures and magnetic resonance imaging of six cases. Lupus.2001;10:8516.8. Celebisoy N, Gulec F, Bayrakcl A, Yargucu F. Longitudinalmyelitis as the first manifestation of systemic lupuserythematosus. J Neurol Sci. 2009;26(4):4924.9. Fregoso H, Cabiedes J, Orozco A, Dvila L, Atisha Y, DiamondB, et al. Serum and cerebrospinal fluid autoantibodies inpatients with neuropsychiatric lupus erythematosus.Implications for diagnosis and pathogenesis. Plos One.2008;3(10):334754.0. DCruz D, Mellor S, Joven B, Sanna G, Allanson J, Taylor J, et al.Transverse myelitis as the first manifestation of systemiclupus erythematosus or lupus-like disease: Good functionaloutcome and relevance of anti-phospholipid antibodies. JRheumatol. 2004;31:2805.1. Chiquete E, Navarro J, Ayala R, Gutirrez N, Solrzano A,Rev Neurol. 2010;51:28994.2. Pinzn A, Echeverry T, Bibiana A. 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