Tratamiento de Granulomatosis de Wegener, Complicaciones Relacionadas

El 50% de los pacientes con ciclofosfamida oral presenta hematuria no glomerular, de los cuales el 70% presentan cambios de toxicidad en la cistoscopia29. Es más frecuente cuando la dosis excede 100 gr. dosis total (2.7 años en promedio). El desarrollo de cáncer de vejiga es otro riesgo potencial. La probabilidad es de un 5% en 10 años, y 16% en 15 años167. Se sugiere que ante la presencia de hematuria es mandatoria la cistoscopia. Un factor coadyuvante para el desarrollo de cistitis hemorrágica es el tabaquismo67.

Las infecciones oportunistas, son una situación que aumenta la morbimortalidad. Los gérmenes comúnmente presentes son: virus Varicela zoster, Pseudomonas, Staphylococcus, Aspergillus, Cándidas, Haemophilus influenzae, P. carinni, Streptococcus, bacilo tuberculoso y las micobacterias atípicas29.

Otros efectos notorios a tener en cuenta en cada control clínico y paraclínico son depresión de médula ósea, hepatitis medicamentosa, síndromes mielodisplásicos, alopecia (17% de los casos ), efectos por Cushing yatrogénico, miopatía esteroide (hasta en un 18% principalmente en viejos), diabetes mellitus (8%), cataratas (21%), necrosis aséptica de la cabeza del fémur (3%), insuficiencia gonadal, con casos de amenorrea franca, y desarrollo de otras neoplasias diferentes a las de vejiga como son los linfomas (riesgo de 2.4 mayor que población general)29.

Trimetoprim – sulfametoxazol

Basados en un informe anecdótico de DeRemme168, en el cual observó mejoría en pacientes con GW tratados con T-S, y recaídas con su retiro, se ha motivado una gran controversia, si en realidad tiene un papel en el tratamiento de la GW102. Es evidente que faltan más estudios controlados, de difícil ejecución, dadas las implicaciones éticas que plantearía. Sin embargo, hay estudios que demuestran su utilidad en formas benignas de la enfermedad, al igual que disminuir el índice de recaídas si se utiliza en forma permanente una vez obtenida la remisión169. El mecanismo de acción es desconocido. Quizá sirva como inmunomodulador, o por qué no controla gérmenes implicados en la exacerbación o perpetuación del proceso inflamatorio. Un punto a favor de su uso sería como profiláctico para infecciones oportunistas160. Varios autores recomiendan dar una tableta de T-S “F” de 800-160 mg tres veces a la semana160.

Metotrexate

Se utiliza como terapia combinada con corticosteroides en casos pocos severos, a razón de 0.3 mg /kg /una vez a la semana, dando un índice de remisión hasta del 75%170-171. También puede indicarse en casos con intolerancia o contraindicación para el uso de ciclofosfamida. También se han diseñado esquemas para mantenimiento, una vez lograda la remisión con ciclofosfamida, con la ventaja de ser un esquema menos tóxico101.

Tratamiento quirúrgico

En caso de presentarse estenosis traqueal, se puede intentar si no hay una obstrucción muy grande que pone en inminente peligro la vida, infiltración con esteroide. De persistir o ser más severa se impone la instalación de Stent o la terapia con láser93. Un grupo de pacientes a los que se han aplicado estas modalidades terapéuticas tienen el inconveniente posterior de desarrollar traqueomalasia. Otras complicaciones relacionadas con los Stent son la migración, la formación de granulomas y las infecciones172. Por último se impone la resección quirúrgica78. Si hay inminente peligro de la vida por obstrucción se debe realizar traqueostomía. Esta última plantea el problema de que se forma una fístula cutánea de muy difícil cierre posterior.

Las deformidades nasales se tratan de corregir una vez controlada la enfermedad desde el punto de vista farmacológico por lo menos durante un año. Existen diferentes técnicas de reconstrucción cosmética de la nariz, donde puede requerirse injerto de hueso.

La lobectomía o la neumonectomía, puede llegar a ser necesaria cuando existen síntomas locales recurrentes, como son las neumonías postobstructivas y una terapia bajo broncoscopia no es exitosa93.

Otras modalidades terapéuticas

En casos muy severos, se ha indicado la gamaglobulina173-174 y la plasmaféresis175-176, como terapia concomitante con buenos resultados. La azatioprina177 y la ciclosporina178-180 pueden indicarse en casos en los cuales no exista respuesta o tolerancia a las indicaciones clásicas de tratamiento. Recientemente se ha estudiado el micofenolato, inmunosupresor de la inmunidad celular de baja toxicidad aprobado para la profilaxis de rechazo en transplante renal, con respuesta adecuado en el mantenimiento de 11 pacientes con GW en un período de 15 meses. Faltan estudios a largo plazo y con un mayor número de pacientes, además de ser comparado con las terapias tradicionalmente aceptada181.

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