[Rituximab for treatment of patients with systemic autoimmune diseases]. / Utilidad del rituximab en el tratamiento de pacientes con enfermedades sistémicas autoinmunitarias.

BACKGROUND AND OBJECTIVE: To assess the value of rituximab in systemic autoimmune diseases which are refractory to others treatments. PATIENTS AND METHOD: Prospective study on 12 patients -7 with systemic lupus erythematosus (SLE), 4 with Wegener's granulomatosis (WG), and 1 with overlapping connective disease and autoimmune thrombocytopenia-, controlled in a specialized unit of a tertiary hospital. Four weekly doses of rituximab, 2 biweekly doses of cyclophosphamide, and glucocorticoids were administered to all patients, and other immunosuppressants were also administered as considered necessary in each case. RESULTS: Mean follow up after treatment with rituximab was 12.8 moths for SLE patients and 12.3 for WG patients. In SLE patients, proteinuria was reduced below 1 g daily in 5 cases (83%), with a clear parallel improvement in the urinary sediment. Serositis was resolved in both cases. One patient required 3 treatment cycles to obtain an adequate response and another required a second cycle for relapse. Only one patient with WG had a favorable response. The patient treated for autoimmune thrombocytopenia had a favorable response, with no relapses, and creatine-kinase levels also tended to return to normal. There were 2 serious adverse events (terminal renal failure and serious colitis in a patient with SLE, and death of one patient with WG), that were not adjudicated directly to rituximab. Immunoglobulin levels did not change substantially. There were no infusion reactions or associated infections. CONCLUSIONS: Rituximab was useful in patients with SLE refractory to other immunosuppressants. On the contrary, its efficacy in WG was limited. The response of thrombocytopenia was complete and maintained.

Utilidad del rituximab en el tratamiento de pacientes con enfermedades sistémicas autoinmunitarias / Rituximab for treatment of patients with systemic autoimmune diseases

Fundamento y objetivo: Evaluar la utilidad del rituximab en el tratamiento de enfermedades autoinmunitarias sistémicas refractarias a otros tratamientos. Pacientes y método: Se ha realizado un estudio prospectivo de 12 pacientes: 7 con lupus eritematoso sistémico (LES), 4 con granulomatosis de Wegener (GW) y 1 con conectivopatía de superposición y trombocitopenia autoinmunitaria. Se administraron 4 dosis semanales de rituximab y 2 quincenales de ciclofosfamida, además de glucocorticoides y otros inmunodepresores según se estimó necesario en cada caso. Resultados: El tiempo de seguimiento medio tras finalizar el tratamiento con rituximab fue de 12,8 meses para los pacientes con LES y de 12,3 para los pacientes con GW. Entre los casos de LES, la proteinuria se redujo por debajo de 1 g al día en 5 pacientes (83%), con mejoría paralela evidente en el sedimento urinario. La serositis se resolvió en los 2 casos. Un paciente requirió 3 ciclos de tratamiento antes de obtener una respuesta adecuada y otro requirió un segundo ciclo por recaída. Sólo un paciente con GW tuvo una respuesta favorable. El paciente tratado por trombocitopenia autoinmunitaria tuvo una respuesta favorable, sin recurrencias, y además sus valores de creatincinasa tendieron a normalizarse. Hubo 2 acontecimientos adversos graves (insuficiencia renal terminal y colitis grave en una paciente con LES, y fallecimiento de un paciente con GW), que no se atribuyeron directamente al rituximab. Los valores de inmunoglobulinas no se modificaron sustancialmente. No hubo reacciones infusionales ni infecciones asociadas. Conclusiones: El rituximab resultó útil en pacientes con LES resistente a otros inmunodepresores. Por el contrario, su eficacia en la GW resultó limitada. La respuesta de la trombocitopenia fue completa y mantenida

Background and objective: To assess the value of rituximab in systemic autoimmune diseases which are refractory to others treatments. Patients and method: Prospective study on 12 patients ­7 with systemic lupus erythematosus (SLE), 4 with Wegener's granulomatosis (WG), and 1 with overlapping connective disease and autoimmune thrombocytopenia­, controlled in a specialized unit of a tertiary hospital. Four weekly doses of rituximab, 2 biweekly doses of cyclophosphamide, and glucocorticoids were administered to all patients, and other immunosuppressants were also administered as considered necessary in each case. Results: Mean follow up after treatment with rituximab was 12.8 moths for SLE patients and 12.3 for WG patients. In SLE patients, proteinuria was reduced below 1 g daily in 5 cases (83%), with a clear parallel improvement in the urinary sediment. Serositis was resolved in both cases. One patient required 3 treatment cycles to obtain an adequate response and another required a second cycle for relapse. Only one patient with WG had a favorable response. The patient treated for autoimmune thrombocytopenia had a favorable response, with no relapses, and creatine-kinase levels also tended to return to normal. There were 2 serious adverse events (terminal renal failure and serious colitis in a patient with SLE, and death of one patient with WG), that were not adjudicated directly to rituximab. Immunoglobulin levels did not change substantially. There were no infusion reactions or associated infections. Conclusions: Rituximab was useful in patients with SLE refractory to other immunosuppressants. On the contrary, its efficacy in WG was limited. The response of thrombocytopenia was complete and maintained

Bloqueo auriculoventricular completo en pacientes adultos con lupus eritematoso sistémico. Casuística propia y revisión de la bibliografía / Complete auriculoventricular blockage in adult patients with systemic lupus erythematosus. Case series and a review of the literature

Fundamento y objetivo: El bloqueo auriculoventricular completo (BAVC) congénito se debe, en la mayoría de los pacientes, a lesión del sistema de conducción por anticuerpos trasplacentarios de origen materno (lupus neonatal). En el adulto con lupus eritematoso sistémico (LES) es muy dudosa la cardiotoxicidad por dichos anticuerpos y se ha relacionado con el tratamiento con antipalúdicos de síntesis (APS). Se valora, en nuestro medio, la presencia de BAVC (no congénito) en pacientes adultos con LES y su posible asociación con el tratamiento con APS. Pacientes y métodos: Se ha estudiado la frecuencia de BAVC en una serie de 595 pacientes afectados de LES controlados en una unidad de enfermedades sistémicas. Resultados: Cinco mujeres (0,8% del total) presentaron un BAVC (desarrollado en una crisis lúpica en 2 pacientes). Todas estaban en tratamiento con APS (el 100 frente al 60% en el resto de la serie) y mantuvieron una dosis de 250 mg/día (excepto una, con dosis de 500 mg/día) por un tiempo medio de 90 meses. La dosis media acumulada de APS fue de 753 g. Tres pacientes desarrollaron insuficiencia cardíaca; 2, nefropatía; 2, miopatía; y una, maculopatía. Como procesos acompañantes se constató síndrome de Sjögren (2) e hipotiroidismo (3). La frecuencia de HLA DR3, 80% de los casos, es superior a la observada en la serie total, 34% (p = 0,053). Conclusiones: Constatamos la presencia de BAVC en el 0,8% de pacientes con LES. Todos ellos en tratamiento con APS. No hemos comprobado relación con anticuerpos anti-ENA (anti-Ro y anti-RNP) comunicada en algunos casos, pero sí una tendencia a la asociación con HLA DR3 (en el límite de significación estadística)(AU)

Background and objective: Congenital complete atrioventricular heart block (CHB) is due to the lesion of the cardiac conduction system by specific transplacental antibodies of maternal origin. In adults with systemic lupus erythematosus (SLE), cardiac toxicity is very questionable and has been related to treatment with synthetic antimalarial drugs (AM). Here we evaluate, in our geographic area, the presence of non congenital CHB in adult patients with SLE and its possible association with AM treatment. Patients and methods: The frequency of CHB has been studied revising the clinical records of 595 SLE patients followed at the Unit for Systemic Diseases. Results: Five women (0.8% of the total series) suffered from CHB (2 patients developed it during a lupic crisis). All were on treatment with AM (100 versus 60% of the rest of the series) and maintained a dose of 250 mg/day (except one, with a dose of 500 mg/day) for a mean period of 90 months. The accumulated mean dose of AM was 753 g. Three patients developed cardiac insufficiency; 2 nephropathy; 2 myopathy; and one maculopathy. As accompanying processes we detected Sjögren’s syndrome (2) and hypothyroidism (3). The frequency of HLA DR3, positive in 80% of the cases, is higher than observed in the total series, 34% (p = 0.053). Conclusions: We detected the presence of CHB in 0.8% of SLE patients. They were all treated with AM. We did not verify any relationship with anti-ENA (anti-Ro/La and anti-RNP) antibodies, as communicated by others, but rather a trend to the association with HLA DR3 (at the limit of statistical significance)(AU)

[Complete auriculoventricular blockage in adult patients with systemic lupus erythematosus. Case series and a review of the literature]. / Bloqueo auriculoventricular completo en pacientes adultos con lupus eritematoso sistémico. Casuística propia y revisión de la bibliografía.

BACKGROUND AND OBJECTIVE: Congenital complete atrioventricular heart block (CHB) is due to the lesion of the cardiac conduction system by specific transplacental antibodies of maternal origin. In adults with systemic lupus erythematosus (SLE), cardiac toxicity is very questionable and has been related to treatment with synthetic antimalarial drugs (AM). Here we evaluate, in our geographic area, the presence of non congenital CHB in adult patients with SLE and its possible association with AM treatment. PATIENTS AND METHODS: The frequency of CHB has been studied revising the clinical records of 595 SLE patients followed at the Unit for Systemic Diseases. RESULTS: Five women (0.8% of the total series) suffered from CHB (2 patients developed it during a lupic crisis). All were on treatment with AM (100 versus 60% of the rest of the series) and maintained a dose of 250 mg/day (except one, with a dose of 500 mg/day) for a mean period of 90 months. The accumulated mean dose of AM was 753 g. Three patients developed cardiac insufficiency; 2 nephropathy; 2 myopathy; and one maculopathy. As accompanying processes we detected Sjögren's syndrome (2) and hypothyroidism (3). The frequency of HLA DR3, positive in 80% of the cases, is higher than observed in the total series, 34% (p = 0.053). CONCLUSIONS: We detected the presence of CHB in 0.8% of SLE patients. They were all treated with AM. We did not verify any relationship with anti-ENA (anti-Ro/La and anti-RNP) antibodies, as communicated by others, but rather a trend to the association with HLA DR3 (at the limit of statistical significance).