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Background: Rituximab is a chimeric anti-CD20 monoclonal antibody used in various clinical scenarios for the treatment of SAD, especially when immunocomplexes and/or limphocyte B proliferation plays a central role. Objectives: The objective of this study was to retrospectively assess the efficacy and safety of use of rituximab in a cohort of patients with SAD in a tertiary hospital within the last 12 years. Methods: We carry out a retrospective study of 48 patients with a diagnosis of SAD in our Autoimmune and Minority Diseases Department using Google Sheets. Results: Our cohort is mostly female (48 women and 8 men). The mean age is 40.9 ±13.1 years (median 38 years). It is composed of different SAD: erythematous systemic lupus (22), granulomatosis with polyangiitis (6), dermatomyositis (6), eosinophilic granulomatosis with polyangiitis (3), rheumatoid arthritis (2), Takayasu’s arteritis (1), Kikuchi-Fujimoto disease (1), mixed connective tissue disease (i), dermatomyositis with scleroderma overlap (1), systemic sclerosis (1) foliaceus pemphigus (1), gangrenosum pyoderma, (1) polimyositis (1) and orbital pseudotumor (1). The mean time from diagnosis to rituximab was 7.7±7.1years. the efficacy of RTX in reducing disease activity after 6 month was 64.6% patients -according to the disease recommended scales-. Nevertheless, 39% maintained 1 year remission. The indications for rituximab were: persistant activity despite improvement of clasical immunosuppressive strategies (36), corticodependency (4), new relapses (3), corticoresistance (3) and toxicity (others immunosuppressant) (2). The drugs used when rituximab was used: cyclophosphamide (24), hydroxychloroquine (21), mycophenolate mofetil or mycophenolic acid (20); cyclosporine (7), immunoglobulines (7), leflunomide (4), and methotrexate (6). 5 patients did not receive any immunosuppressant. 61.3% were taking at least 2 drugs. All of them were taking glucocorticoids. In terms of security and side effects, we observed 11 (22.9%) adverse reactions related to the administration. We detect 3 infusion reactions (mild severity), 1 severe mucocutaneous reaction, 1 moderate herpes zoster, 1 fungic invasive infection and 5 severe bacterial infections (1 of them lead to rituximab suspension). We did not detect any hepatitis B virus reactivation, multifocal progressive leukoencephalopathy, cytomegalovirus infections nor herpes simplex infections. We observed 65 different haematologic adverse events: lymphopenia (34), anemia (15), neutropenia (12) and hrombocytopenia (4). No one needed specific treatment. Conclusion: Rituximab is a second line therapeutic alternative in patients with SAD in whom other treatments have failed. It is a effective drug that rescues a 65% of patients in whom other treatments have failed. Furthermore, rituximab is a safe immunosuppressant. References [1] Oon S, Huq M, Godfrey T, Nikpour M. Systematic review, and meta-analysis of steroid-sparing effect, of biologic agents in randomized, placebo-controlled phase 3 trials for systemic lupus erythematosus. Semin Arthritis Rheum. 2018 Jan 6. pii: 0049-0172(17)30579-6 [2] Tesfa D, Ajeganova S, Hagglund H, Sander B, Fadeel B, Hafstrom I, Palmblad J. Late-onset neutropenia following rituximab therapy in rheumatic diseases: association with B lymphocyte depletion and infections. Arthritis Rheum. 2011;63(8):2209 Disclosure of Interests: None declared

Resumen Fundamento y objetivo La hipertension arterial pulmonar (HAP) es causa importante de morbimortalidad en la esclerosis sistemica (ES). Su evolucion es peor que en la HAP idiopatica, pero el pronostico mejora si se diagnostica precozmente. El objetivo de este trabajo es describir el resultado de un programa de cribado para el diagnostico de hipertension pulmonar (HP) desarrollado en una cohorte de pacientes espanoles con ES. Pacientes y metodo Se realizo cribado de HP mediante ecocardiografia-doppler transtoracica (EDTT) en 184 pacientes con ES. Los pacientes con valor de presion arterial pulmonar sistolica estimada por EDTT > 35 mmHg se evaluaron de forma protocolizada para establecer o no el diagnostico de certeza de HP y su tipo. Resultados Se diagnostico HAP en 25 pacientes (13,6%). Los pacientes con ES difusa y limitada desarrollaron HAP en proporciones semejantes: 9 de 60 (15%) frente a 16 de 100 (16%). No se registraron casos entre pacientes con ES «sine esclerodermia» o «preesclerodermia» (p Conclusiones La prevalencia de HAP en ES resulto elevada y apoya la implantacion de programas de cribado sistematico.

Objective.Behçet disease (BD) is a multifactorial disease in which infectious agents have been proposed as triggers in genetically predisposed individuals. The aim of our study was to investigate the role of innate immunity receptors, specifically the nucleic acid sensors, in susceptibility to BD.Methods.Seventy-four tag single nucleotide polymorphisms (tSNP) selected in 9 candidate genes (DDX58, IFIH1, TLR3, TLR7, TLR8, AIM2, IFI16, ZBP1, and TLR9) were genotyped in 371 patients and 854 controls. Assays of mRNA expression and allele-specific transcript quantification (ASTQ) were performed in 110 and 50 controls, respectively.Results.Patients and controls were genotyped and 2 tSNP (rs6940 in IFI16 and rs855873 in AIM2) were associated with BD. To confirm this association, these tSNP were genotyped in 850 additional controls, and the total cohort was randomly divided into 2 cohorts. The association of these 2 tSNP with the disease remained in both cohorts. One haplotype (rs6940T-rs855873G) was identified as a risk factor (OR 1.41, 95% CI 1.06–1.86, p = 0.015), and another (rs6940A-rs855873A) as a protective factor (OR 0.65, 95% CI 0.47–0.90, p = 0.009). Samples with the risk haplotype had lower IFI16 expression levels than samples with the protective (0.99 ± 0.29 vs 1.23 ± 0.50, p = 0.022). Consistently, in the ASTQ assays performed with the nonsynonymous rs6940 SNP, the risk allele had lower IFI16 expression levels than the protective (p = 0.027).Conclusion.Our findings suggest association of IFI16, a cytosolic sensor of dsDNA and mediator of the AIM2 inflammasome-dependent pathway, in susceptibility to BD. Differences genetically determined in the levels of this molecule could be the cause of this association.

To assess the clinical manifestations and prognosis of Spanish patients with systemic sclerosis (SSc) according to their immunological profile.From the Spanish Scleroderma Study Group or RESCLE (Registro de ESCLErodermia as Spanish nomenclature) Registry we selected those patients in which anti-centromere (ACA), anti-topoisomerase I (ATA), and anti-RNA polymerase III (ARA) antibodies had been determined, and a single positivity for each SSc specific antibody was detected. Demographic, clinical, laboratory, and survival data were compared according to the serologic status of these antibodies.Overall, 209 SSc patients were included. In 128 (61%) patients ACA was the only positive antibody, 46 (22%) were only positive for ATA, and 35 (17%) for ARA. Of note, the three groups were mutually exclusive. In univariate analysis, patients with ACA presented more frequently limited cutaneous SSc (lcSSc) (p0.001), whereas diffuse cutaneous SSc (dcSSc) was the most frequent subtype in patients with ATA (54%) and ARA (62%) (both p0.001). Positive patients for ARA showed the highest prevalence of joint involvement (p0.001) and those from ATA group had a higher prevalence of interstitial lung disease (ILD) (p0.001). Scleroderma renal crisis was more frequent in the ARA group (p0.001). In multivariate analysis, ACA were associated with female gender and were protective for dcSSc and ILD. ATA were found to be protective for lcSSc and they were independently associated with interstitial reticular pattern. ARA positivity was independently associated with dcSSc. We did not find differences in mortality between the three groups.In Spanish SSc patients, the presence of SSc specific antibodies conferred a distinctive clinical profile.

The low overall prevalence of systemic sclerosis (SSc) and the low proportion of male patients have resulted in a scarcity of studies assessing sex differences in Ssc patients, and contradictory results have often been show among those studies that have been performed.A prospective study was conducted with the Spanish RESCLE register to analyse the influence of gender on survival of SSc patients.In total, 1506 SSc patients (1341 women, 165 men) were recruited from 21 centres. Older age at onset (OR 1.02), shorter time from onset to diagnosis (OR 0.96), smoking (OR 2.57), interstitial lung disease (ILD) (OR 1.58), less predisposition to sicca syndrome and to antinuclear antibody positivity (OR 0.29 and 0.43, respectively), and higher compliance with the ACR 1980 criteria (OR 1.79) were independently associated with the male sex. During follow-up, 30.4% of men versus 14.6% of women died (p0.001). Survival at 10 years from the onset of symptoms was 75.3% for men and 92.9% for women (p0.001), and the difference remained after selecting only SSc-related deaths (85.6% vs. 96.1%, p0.001). The mortality predictive factors were diffuse SSc (OR 2.26), ILD (OR 1.82), digital ulcers (OR 1.38), tendon friction rubs (OR 1.74), male sex (OR 1.53), increased age at onset (OR 1.13) and isolated PH (considering only deaths from diagnosis), both in the overall (OR 3.63) and female cohorts (OR 3.97). The same risk factors were observed in the male cohort, except for isolated PH and ILD.The present study confirms the existence of epidemiological, clinical, laboratory and prognostic gender differences in systemic sclerosis patients.

Internet has become a widely used tool by patients seeking information on different diseases. The information regarding lupus patients' Internet use is scarce. This study aims to explore the attitudes and practices of lupus patients in southern Spain, regarding Internet use to find health-related information. A survey was carried out including 150 patients from six Andalusian Hospitals. To search for information, 67.3 % of the patients used Internet. The proportion of female Internet users was higher (69.3 vs 46.2 %), particularly those belonging to a patients' association (81.8 vs 32.7 %), and are regular users of Internet (80.2 vs 44.4 %); 37.5 % thought the information found in the Internet was of little use or not useful at all, and 58 % of the respondents stated that the information found caused them concern while for 27 %, it was a relief. Most patients preferred the information given by their physicians (63.6 %); 33.9 % considered that the information from both sources was complementary, and 2.5 % preferred the information obtained from the Internet. A percentage of 85.3 of the patients would like their physicians to provide them with information on high-quality sites regarding their illness. Lupus patients make frequent use of the Internet to look for information on their disease. Considering this, and because better-informed patients follow more precisely the indications given by the physician, medical staff should collaborate in the development of high-quality sites for the patient to have additional sources of information.

A biological marker can be defined as any substance that can be objectively measured and evaluated as an indicator of a normal biological process, a pathogenic process or pharmacological responses to a therapeutic intervention. In pulmonary hypertension (PH), in addition to routine markers (hemodynamic and functional), there are a growing number of biomarkers that allow an increasingly comprehensive approach to knowledge of susceptibility to this disease and to diagnosis, prognosis and treatment response. These markers can be both constitutive (genetic) and disease-related (related to right ventricular failure, such as BMP/NT-proBNP, endothelial dysfunction, such as endothelin-1, or inflammation, such as certain cytokines and chemokines). Novel insights in genomics and proteomics may allow major advances in this field.

Objetivos Analizar los casos de tuberculosis (TB) en una cohorte de pacientes con lupus eritematoso sistemico (LES) y comparar la frecuencia y caracteristicas de la TB en nuestra serie con las de otras series publicadas; identificar caracteristicas diferenciales entre los pacientes que presentaron TB y los que no la presentaron, y evaluar si las formas mas graves se relacionaron con dosis mas altas de glucocorticoides (GC) u otros inmunosupresores. Material y metodo Analisis descriptivo de 13 pacientes con TB de una serie de 789 pacientes con LES. Revision de las historias clinicas de los casos. Busqueda bibliografica en MEDLINE-PubMed de las series LES/TB publicadas, utilizando los terminos «infection», «tuberculosis», «lupus erythematosus». Estudio comparativo de casos (LES/TB+) y controles (LES/TB�) en cuanto a las caracteristicas clinicas, de laboratorio y el tratamiento realizado, mediante test ?2 y test exacto de Fisher. Resultados Trece pacientes estuvieron afectados por TB (10 mujeres, con edad media de 36 anos; DE de 11,2, y prevalencia del 1,6%). Se diagnosticaron 9 primoinfecciones (69,2%) y 4 reactivaciones (30,8%). El diagnostico se confirmo mediante aislamiento microbiologico (baciloscopia y/o cultivo) en 11 casos (84,6%). La afectacion pulmonar fue la mas frecuente (69,2%). Ocho pacientes (61,5%) presentaron formas extrapulmonares, de las que 6 (46%) fueron diseminadas. En el momento del diagnostico, 9 pacientes (69,2%) recibian tratamiento con GC. Fallecieron 4 pacientes (30,8%). La afectacion muscular fue mas frecuente en el grupo casos (p < 0,05). Conclusiones La TB en nuestra serie supuso una alta mortalidad (30,8%) en los enfermos con LES. Las formas extrapulmonares representaron el doble con respecto a la observada en la poblacion general. Los pacientes que recibieron dosis mayores de GC fueron los que presentaron formas mas graves de TB. Los datos son similares a los publicados en la mayoria de las series nacionales y extranjeras.

Resumen Fundamento y objetivo Comunicamos nuestra experiencia con rituximab mas ciclofosfamida en el tratamiento de pacientes con miopatia inflamatoria idiopatica refractaria. Pacientes y metodo Estudio prospectivo abierto no controlado sobre 17 pacientes. Resultados Evaluacion cumplimentada tras 1, 6 y 12 meses en el 95,2, el 85,7 y el 52,4% de los ciclos, respectivamente. Remision total o parcial tras 1, 6 y 12 meses en el 65, el 100 y el 63,6% de los ciclos evaluados, respectivamente. Deplecion absoluta de linfocitos B en sangre periferica en los 18 casos con datos disponibles, con tendencia a la normalizacion tras 6 a 12 meses. Hubo 5 recaidas; la mediana de tiempo hasta la recaida fue de 11 meses; hubo repeticion del tratamiento en 4 casos. Cuatro pacientes tenian afectacion respiratoria; uno (etiologia multifactorial) no mejoro, pero si los otros 3, con neumopatia intersticial aislada o asociada a debilidad muscular respiratoria. Hubo 5 pacientes con anticuerpos anti-Jo-1 positivos (6 ciclos), con respuesta al tratamiento superponible al resto. Se observaron escasos efectos adversos; solo cabe destacar un caso de meningitis por Corynebacterium, con buena evolucion. Conclusiones El rituximab parece una alternativa valida en el tratamiento de pacientes con polimiositis o dermatomiositis resistentes.

Objectives 1) To study tuberculosis (TB) infection in a cohort of patients with systemic lupus erythematosus (SLE) and to compare its frequency and characteristics with that of others series. 2) To look for differential characteristic among SLE patients with and without TB. 3) To investigate if there was any relationship between TB's most severe forms and higher doses of glucocorticoids (GC) or other immunosuppressants. Patients and method Retrospective review of medical records of 789 SLE patients and description of the clinical characteristics of 13 cases of active TB infection among them. Bibliographical search in MEDLINE-PubMed of the SLE/TB series published, using the terms: infection, tuberculosis, systemic lupus erythematosus. Comparative study of clinical, biological and therapeutic differences between cases (SLE/ TB+) and controls (SLE/TB) using χ 2 and Fisher exact test. Results Thirteen patients with active tuberculosis were detected (10 women, average age 36 years/SD 11.2/prevalence 1.6%). Nine (69.2%) of them were primary infections and 4 (30.8%) reactivations. Microbiological diagnosis (smear examination for acid-fast bacilli and/or culture on Lowestein-Jensen medium) was established in 11 patients (84.6%). TB Pulmonary manifestations was present in 9 patients (69.2%) and extrapulmonary manifestations were found in 8 [(61.5%); 6 of them (46%) were disseminated forms]. Nine (69.2%) patients were on GC therapy at the moment TB was diagnosed. Four of the TB patients died (30.8%). Myositis was more frequent in TB cases (P Conclusions In our series, TB mortality was high (30.8%) in a patients with SLE. Frequency of extrapulmonary forms was double than that described in the Spanish population. Patients with higher GC dose had more severe forms of TB

Resumen Fundamento y objetivo La patologia tiroidea (PT) es mas frecuente en pacientes con hipertension arterial pulmonar (HAP) que en la poblacion general. No estan bien establecidas la frecuencia ni la causa de esta asociacion. El objetivo de este trabajo es cuantificar y analizar la incidencia y las caracteristicas de la PT en una cohorte de pacientes con HAP (idiopatica o asociada preferentemente a enfermedades sistemicas) y realizar una revision de la literatura cientifica. Pacientes y metodo Se estudio a 58 pacientes con HAP prospectivamente segun un protocolo preestablecido (incluido cateterismo cardiaco derecho) y se determinaron la tirotropina (TSH), la tiroxina libre (T 4 l) y los anticuerpos antitiroglobulinicos y anticuerpos antiperoxidasa. Se definio la PT como alteracion de la TSH o elevacion de cualquiera de los 2 anticuerpos antitiroideos (AcAT). Se compararon las variables clinicas, biologicas y hemodinamicas entre los grupos con y sin PT. Resultados Habia PT en 30 pacientes (51%): TSH elevada en 21 (36,21%), hipertiroidismo en 2 pacientes (3,45%) y AcAT elevados en 16 de los 54 pacientes (27,59%), 7 de los cuales eran eutiroideos. En el grupo con PT el tiempo de evolucion de la HAP fue mayor (4,62 frente a 2,61 anos; intervalo de confianza [IC] del 95%: 0,63 a 3,38; p=0,005), hubo mas pacientes en clase funcional iv (13 frente a 5, el 43,3 frente al 15,8%; IC del 95%: 0,05 a 11,75; p=0,046), el gasto cardiaco fue menor (IC del 95%: 3,16 a 4,89; p=0,032) y fue mas frecuente el tratamiento con epoprostenol (14 frente a 4, el 46 frente al 14,3%; IC del 95%: 1,46 a 18,85; odds ratio de 5,25; p=0,008) que en el grupo sin PT. Conclusiones La frecuencia de PT en esta cohorte de pacientes con HAP alcanza un 51% y solo se relaciono con mayor tiempo de evolucion de la enfermedad y con peor situacion hemodinamica. Aunque el epoprostenol se utilizo mas en el grupo con PT, no puede establecerse una relacion causal con la PT.

Objetivo La mielitis transversa aguda (MTA) es una rara complicacion en los pacientes con lupus eritematoso sistemico (LES). Revisamos nuestra serie de pacientes con LES para determinar la prevalencia de MTA y analizar las caracteristicas clinicas, las pruebas complementarias, la evolucion y la respuesta al tratamiento. Pacientes y metodo Se identifico a 6 pacientes con MTA que se sometieron a valoracion clinico-neurologica, resonancia magnetica y estudio electrofisiologico y recibieron el mismo tratamiento. Realizamos un estudio estadistico descriptivo. Resultados Observamos una prevalencia de MTA del 0,92% de nuestros pacientes con LES. El 83,3% Presentaba anticuerpos antifosfolipidicos y/o anticoagulante lupico. La resonancia magnetica confirmo el diagnostico en 5 de los 6 casos; 3 de los 5 pacientes con anticuerpos antifosfolipidicos fueron anticoagulados o antiagregados, con buena evolucion neurologica; 2 de ellos han quedado sin secuelas. Conclusiones Encontramos una prevalencia similar a la observada en otras series, en torno al 1%. La alta prevalencia de anticuerpos antifosfolipidicos en los pacientes, con buen resultado en los antiagregados o anticoagulados, indica un importante papel patogenico en el desarrollo de la MTA, y nos hace plantearnos la importancia de anadir al tratamiento estandar terapia antiagregante o anticoagulante.

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.

Objective Transverse myelitis (TM) is a rare complication in patients with systemic lupus erithematosus (SLE). We reviewed a series of our SLE patients to determine the prevalence of TM, and evaluate the clinical characteristics, medical tests, evolution, and response to the treatment. Patients and method Six patients with TM were identified and underwent a neurological evaluation, MRI, electrophysiologic study, and were all subjected to the same treatment. A descriptive statistical study was conducted. Results We observed a prevalence of 0.92% in our patients with SLE. Eighty-three point three per cent had antiphospholipid antibodies and/or lupus anticoagulant. The MRI confirmed the diagnosis in 5 cases. Of the 5 patients with antiphospholypid antibodies, 3 were anticoagulated or took aspirin with a good neurological outcome, leaving 2 of them without posterior complications. Conclusions We found a prevalence similar to that observed in other series, around 1%. The high prevalence of antiphospholypid antibodies in these patients, with good outcome in those anticoagulated or treated with antiplatelet agents suggests an important pathogenic role in the development of TM, and emphasized the possibility of adding to the standard treatment, antiplatelet agents, or anticoagulation.

Fundamento y objetivo: El bloqueo auriculoventricular completo (BAVC) congenito se debe, en la mayoria de los pacientes, a lesion del sistema de conduccion por anticuerpos trasplacentarios de origen materno (lupus neonatal). En el adulto con lupus eritematoso sistemico (LES) es muy dudosa la cardiotoxicidad por dichos anticuerpos y se ha relacionado con el tratamiento con antipaludicos de sintesis (APS). Se valora, en nuestro medio, la presencia de BAVC (no congenito) en pacientes adultos con LES y su posible asociacion con el tratamiento con APS. Pacientes y metodos: Se ha estudiado la frecuencia de BAVC en una serie de 595 pacientes afectados de LES controlados en una unidad de enfermedades sistemicas. Resultados: Cinco mujeres (0,8% del total) presentaron un BAVC (desarrollado en una crisis lupica 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/dia (excepto una, con dosis de 500 mg/dia) por un tiempo medio de 90 meses. La dosis media acumulada de APS fue de 753 g. Tres pacientes desarrollaron insuficiencia cardiaca; 2, nefropatia; 2, miopatia; y una, maculopatia. Como procesos acompanantes se constato sindrome de Sjogren (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 relacion con anticuerpos anti-ENA (anti-Ro y anti-RNP) comunicada en algunos casos, pero si una tendencia a la asociacion con HLA DR3 (en el limite de significacion estadistica).

Objetivo Analizar la efectividad y tolerancia a corto plazo de la terapia con rituximab (RTX) en pacientes con lupus eritematoso sistemico (LES) y diferentes manifestaciones clinicas. Pacientes y metodos Se estudio a un total de 13 pacientes. El RTX fue indicado en 6 ocasiones para el tratamiento de nefritis refractaria, en 5 para el tratamiento de trombocitopenia grave, en 1 para el tratamiento de aplasia medular y en 1 para el tratamiento de vasculitis peritoneal asociada a nefritis. Los 13 pacientes fueron tratados con 4 dosis semanales de 375 mg/m2 de RTX. El tiempo medio de seguimiento fue 12 ± 8,5 meses. Nueve pacientes experimentaron una respuesta favorable; 3 con nefropatia, 5 con trombocitopenia y 1 con vasculitis peritoneal y nefritis. El SLEDAI medio paso de 11 a 6,5. Dos pacientes con trombocitopenia presentaron recidivas; y la respuesta al retratamiento fue buena. Conclusiones El presente estudio demuestra que RTX es un farmaco efectivo y seguro, a corto plazo, en el tratamiento de diferentes manifestaciones clinicas asociadas al LES.

Fundamento y objetivo Evaluar la eficacia a largo plazo del iloprost por via intravenosa en el tratamiento del fenomeno de Raynaud (FR) y las ulceras isquemicas asociados a enfermedades sistemicas autoinmunitarias Pacientes y metodo Estudio observacional prospectivo de 2 anos de duracion con iloprost (perfusion intravenosa mensual en dosis entre 0,5 y 2 ng/kg/min, con una duracion del primer ciclo de 5 dias y ciclos posteriores de 24 h, prolongados cuando se requirio) en pacientes con FR grave o ulceras isquemicas en miembros inferiores sin respuesta adecuada al tratamiento convencional. Se interrumpio el tratamiento en los pacientes con evolucion optima tras 1 ano, con mantenimiento de controles clinicos Resultados Se trato a 23 pacientes. Con iloprost se redujeron significativamente el numero medio (DE) de episodios mensuales de FR (150,38 [102,04] al inicio y 40,05 [78,06] al final; p Conclusiones El iloprost resulto eficaz en el tratamiento a largo plazo del FR grave y de las ulceras isquemicas en extremidades inferiores en pacientes con enfermedades sistemicas

Fundamento Establecer el papel de la tomografia computarizada por emision de foton simple(SPECT) y los tests psicologicos en el diagnostico del neuro-Behcet (NB) y evaluar la significacionde los sintomas neurologicos de dificil interpretacion y las alteraciones asintomaticas enlas pruebas diagnosticas. Pacientes y metodo Se estudio a 40 pacientes con enfermedad de Behcet (EB) mediante resonanciamagnetica (RM), SPECT y tests psicologicos. Resultados La RM estaba alterada en el 52,9% de los pacientes con clinica neurologica y enel 23,1% sin sintomas neurologicos (p Conclusiones La SPECT parece mas sensible y menos especifica que la RM en el diagnosticodel NB. Aunque la SPECT estaba frecuentemente alterada en pacientes con EB sin antecedentesneurologicos o con clinica de dificil interpretacion, ninguno desarrollo clinica neurologicadefinida tras su seguimiento prolongado. Se encontro un perfil de personalidad caracteristicode los pacientes con EB.

Pulmonary arterial hypertension (PAH) is an important cause of morbimortality in systemic sclerosis (SSc). Evolution is worse than that of subjects with idiopathic PAH, but prognosis improves when PAH is diagnosed early. The aim of this research is to describe results of a screening program for diagnosis of pulmonary hypertension (PH) carried out in a cohort of Spanish patients with SSc.PH screening was performed by transthoracic doppler echocardiography (TTDE) in 184 patients with SSc. Patients with systolic pulmonary arterial pressure estimated by TTDE35 mmHg were evaluated per protocol to confirm diagnosis and type of PH.PAH was diagnosed in 25 patients (13.6%). Patients with diffuse and limited SSc developed PAH in a similar degree, 9/60 (15%) vs. 16/100 (16%), with no cases among patients with SSc "sine scleroderma" or "pre-scleroderma" (P.001). The only clinical or epidemiological data characterizing patients with PAH were older age (mean age 67 years for patients with PAH vs. 56 years for those without PAH, P=.007), limited SSc, a trend toward shorter evolution of the underlying disease (median 8 years for patients with PAH vs. 10 years for those without PAH, P=.73), and a higher frequency of positive anticentromere antibodies (16 patients [64%] with PAH vs. 70 (48,3%) without PAH, P=.19).Prevalence of PAH in SSc was high and supports the implementation of a regular screening program.

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.

Peritoneal vasculitis is a rare and severe clinical manifestation of systemic lupus erythematosus. We report a patient who presented with ascites due to peritoneal vasculitis and cutaneous, articular, hematological and renal inflammatory activity. Treatment with glucocorticoids and immunosuppressive drugs was ineffective. In view of the resistance to different therapies, 4 weekly infusions of 375 mg/m2 of rituximab (RTX) were started, in association with cyclophosphamide pulses during the first and the third weeks. With this treatment strategy, the patient reached a complete response which was achieved in later flares of inflammatory activity (the second and third flares were multisystemic and with ascites again, and the fourth flare with nephritis).

Peritoneal vasculitis is a rare and severe clinical manifestation of systemic lupus erythematosus. We report a patient who presented with ascites due to peritoneal vasculitis and cutaneous, articular, hematological and renal inflammatory activity. Treatment with glucocorticoids and immunosuppressive drugs was ineffective. In view of the resistance to different therapies, 4 weekly infusions of 375mg/m2 of rituximab (RTX) were started, in association with cyclophosphamide pulses during the first and the third weeks. With this treatment strategy, the patient reached a complete response which was achieved in later flares of inflammatory activity (the second and third flares were multisystemic and with ascites again, and the fourth flare with nephritis).

A pesar de los avances en el tratamiento de los pacientes con hipertension arterial pulmonar (HAP), su supervivencia sigue estando muy afectada. El imatinib, un antagonista del factor de crecimiento derivado de las plaquetas con accion antiproliferativa, ha sido eficaz en modelos experimentales y en algunos casos comunicados. Se describe el resultado del tratamiento con imatinib en 4 pacientes con HAP en clase funcional IV y refractarios al tratamiento con asociaciones de medicamentos para la HAP. La respuesta final fue favorable solo en uno de los 4 casos, que 5 meses despues de iniciado el tratamiento estaba en clase funcional III y con mejoria significativa de los parametros hemodinamicos. Sin embargo, el paciente fallecio por hepatitis toxica grave en la que el imatinib pudo haber participado. Estos resultados se anaden a la escasa experiencia clinica comunicada (solo otros 4 casos) e indican que debemos mantener la cautela sobre la utilidad del imatinib en el tratamiento de la HAP.

Fundamento y objetivo Se describe la experiencia con el tratamiento combinado con prostaciclina intravenosa y sildenafilo oral en pacientes con hipertension arterial pulmonar grave con mala respuesta a prostaciclina sola. Pacientes y metodo Se asocio sildenafilo al tratamiento en 4 pacientes con hipertension arterial pulmonar (primaria en dos y secundaria a colagenosis en dos) sin respuesta favorable a prostaciclina intravenosa. Se valoro la evolucion clinica, la prueba de caminar durante 6 min y el ecocardiograma. Resultados La dosis inicial de sildenafilo fue 12,5 mg tres veces al dia, con incremento hasta 50 mg tres veces al dia en un paciente y 50 mg 4 veces al dia en los otros tres. Se controlaron los sintomas de insuficiencia cardiaca derecha en todos los casos. Antes de iniciar la administracion de sildenafilo, dos pacientes tenian disnea de clase III y dos de clase IV. Dos pacientes (antes clases III y IV, respectivamente) pasaron a clase I y los otros dos pasaron a clase II. Tras alcanzar la dosis final, la distancia caminada en 6 min aumento (incremento medio del 55%) y la presion arterial pulmonar se redujo (porcentaje medio de reduccion del 27% para la sistolica) en todos los pacientes, efecto que se mantuvo durante el seguimiento. El unico efecto secundario observado fue cefalea leve. Conclusiones Nuestra experiencia apoya la posible utilidad del sildenafilo en el tratamiento de la hipertension arterial pulmonar y sugiere su utilidad en tratamiento combinado para rescatar a pacientes que no responden al tratamiento inicial con prostaciclina intravenosa.

To study severe infectious complications in a cohort of patients with systemic lupus erythematosus (SLE).Retrospective study of 705 patients followed from January 1980 to January 2008. Data are expressed in percentages.The frequency of severe infectious was 38.6%. The etiology was bacterial 54.4%, viric 30.4% and opportunist in 15.2% patients. Involved organs were: Lung 38.2%, kidney 48.9%, central nervous system 43%. 43.75% patients received pulsed ciclofosfamide therapy and 88.6% received glucocorticoids (39.7% pulsed). The mortality was 27.7%.At present, infection is an important cause of mortality in patients with SLE. Early diagnosis of infectious complications is very important in SLE.

We report our experience with rituximab plus cyclophosphamide in the treatment of patients with resistant idiopathic inflammatory myopathies.Open-label uncontrolled prospective study on 17 patients.Evaluation was completed after 1, 6 and 12 months in 95'2, 85'7 y 52'4% of cycles, respectively. Total or partial remission was achieved after 1, 6 and 12 months in 65, 100 y 63'6% of evaluated cycles, respectively. Absolute depletion of B lymphocites from peripheral blood was found in the 18 cases with available data. There were 5 relapses; median of time to relapse: 11 months; treatment was repeated in 4. Four patients (6 cycles) had impaired pulmonary function; one (with a multifactorial etiology) did not improve but the other 3, with interstitial pneumonia associated or not with respiratory muscle weakness, did. Five patients with positive anti-Jo-1 antibodies (6 cycles) displayed similar results. The only adverse event observed was a case of meningitis caused by Corynebacterium, with good results.Rituximab seems a valid alternative for the treatment of patients with resistant polymyositis or dermatomyosytis.

Despite advances in the treatment of patients with pulmonary arterial hypertension (PAH), survival has not improved greatly (is still very affected). Imatinib, an antagonist of platelet-derived growth factor with antiproliferative activity, has been effective in experimental models and clinically in several published reports. We report the results of imatinib therapy in 4 patients with PAH (functional class IV) who were refractory to treatment with drug combinations for this condition. The final outcome was favorable in only 1 of the 4 cases. In this case, the patient was in functional class III and his hemodynamic parameters had improved significantly within 5 months after starting therapy. However, the patient died as a result of severe toxic hepatitis in which imatinib may have played a role. The present report adds to the few already in the literature (4 cases) and suggests that care should continue to be shown when using imatinib to treat PAH.

Thyroid disease (TD) is more prevalent in patients with pulmonary arterial hypertension (PAH) than in the general population. The frequency and the cause of this association are not well established. We aimed to quantify and analyze the incidence and characteristics of TD in a cohort of PAH patients (idiopathic or preferentially associated with systemic diseases) and review the literature.Fifty eight PAH patients were prospectively studied, according to a previously established protocol (that included right heart catheterization); TSH, T(4), and antithyroglobulin and antiperoxidase antibodies were determined. TD was defined as an abnormal TSH level and/or elevated antithyroid antibodies (TAbs). Clinical, biological and hemodynamic variables were compared between patients with and without TD.TD was detected in 30 patients (51%): high TSH levels were observed in 21 (36,21%); hyperthyroidism in 2 (3,45%); and TAbs in 16 of 54 (27,59%), 7 of whom were euthyroid. In the TD group, PAH evolution time was longer (4,62 vs 2,61 years; P=.005, CI 95%, 0,63-3,38), more patients were in functional class IV (13;43,3% vs 5;15,8%, P=.046, CI 95% ,0,05-11,75), cardiac output was lower (P=.032, CI 95%, 3,16-4,89) and epoprostenol treatment was more frequently used (14;46,6% vs 4;14,3%, P=.008, CI 95%, 1,46-18,85; OR=5,25).The frequency of TD detected in this PAH cohort reaches 51% and it was associated with a longer evolution time of PAH and worse hemodynamic situation. Although epoprostenol was used more frequently in TD patients, a causal relationship with TD could not be established.

To assess the value of rituximab in systemic autoimmune diseases which are refractory to others treatments.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.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.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.

Background Antisynthetase syndrome (ASS) can be a life-threatening condition. Patients with ASS in the context of idiopathic inflammatory myositis (IIM) have been described to have a worse prognosis compared to patients either with dermatomyositis (DM) or polymyositis (PM) alone. Objectives To evaluate survival and mortality in a large cohort of Spanish patients with anti-Jo1 ASS and compare it with mortality rates of Spanish general population. Methods From March 2011 to June 2014 we conducted a national multicentre study, including retrospective and prospective data, among members of the GEAS-IIM Group of the SEMI. Clinicians from 18 Spanish centers participated in the development of a registry of patients with Anti-Jo1 ASS. For data collection a specific electronic database including broad information about demographic and clinical data was developed. Continuous variables were compared by the t-student or non-parametric Mann-Whitney tests when appropriated, while X2 test were used to compare categorical variables. The Kaplan-Meier method and long-rank tests were used to compare survival between groups. The standardized mortality ratio (SMR) was calculated using the Spanish mortality registry. Results were expressed with its 95% interval confiance (IC). Results A total of 148 anti-Jo1 ASS patients, 90 women (60.8%), were included in the study. Mean (SD) age at diagnosis was 50.8 (16) years. Range follow-up was 1.3 to 412 months [mean (SD) 95 (76.4) months], with only 12 patients with a follow-up fewer than 12 months. Fifteen percent of patients had ILD as the unique main ASS clinical manifestation, other 15% had myositis and 69.3% had both ILD and myositis. Thirty seven patients (25%) died after a median follow-up of 70.3 months (range 4.9 – 308 months). The SMR (95%IC) was 4.77 (3.31-6.67). Main causes of death included respiratory failure (6.8%), cancer (6.1%), infection (4.1%), myositis (2.7%) and acute cardiovascular events (1.3%). A directly ASS-related death were considered in 18 patients (46.6%). Estimated survival rate (95% IC) was 87.5% (81.6% - 93.4%) and 75.4% (66.4% - 84.4%) at 5 and 10 years respectively. Median survival rate (95% IC) was 20.3 years (13.8-26.8 years). No difference in survival was found between patients with myositis (DM or PM) and those with ILD without associated myopathy. The presence of cancer (p=0.02) and an advanced age at ASS diagnosis (p Conclusions Mortality in ASS patients is four-fold and a half higher than in the general population. Mortality can be directly attributed to ASS in near a half of the cases. Respiratory failure, cancer and infection are the main causes of death. Estimated survival rate at 10 years is around 75%. References Marie I. Morbidity and mortality in adult polymyositis and dermatomyositis. Curr Rheumatol Rep.2012;14:275-285. Disclosure of Interest None declared

To evaluate the long term efficacy of treatment with intravenous iloprost for severe Raynaud's phenomenon (RP) and ischemic leg ulcers in patients with autoimmune systemic diseases.Prospective observational study over 2 years with iloprost (intravenous infusions, 0.5 to 2 ng/kg/min, initial cycle of 5 consecutive days and maintenance infusions during 24 h monthly, lengthened when it was needed) in patients with severe RP and ischemic leg ulcers whithout response to conventional therapy. Treatment was halted in patients with a good response after one year of treatment, with regular clinical controls.We treated 23 patients. Iloprost reduced significantly the mean number (SD) of monthly episodes of RP (150.38 [102.04] initially and 40.05 [78.06] at the end; p0.0005), the mean highest duration of episodes of RP (21.86 [26.96] min initially and 7.14 [9.87] min at the end; p = 0.013), the associated pain (p = 0.005), and the mean number of ischemic digital (4.25 [2.86] initially and 0.63 [2.25] at the end; p = 0.003) and leg ulcers (1.67 [0.52] initially and 0.33 [0.52] at the end; p = 0.01). Articular symptoms and inflammatory markers did not improve. Treatment was stopped in 8 patients (in 5 for a very good evolution and in 3 for other causes), and only 1 of them needed to be treated again. Side effects were seen in all cases but always disappeared after slowing infusion.Iloprost was effective in the long term treatment of severe RP and ischemic leg ulcers in patients with autoimmune systemic diseases.

Here we report the experience obtained from a combined treatment with intravenous (i.v) prostacyclin and oral sildenafil in patients with severe pulmonary hypertension (PHT) who had a poor response to prior treatment with prostacyclin alone.Sildenafil was added to the treatment in four patients with PHT (primary in two patients and secondary to collagenosis in the other two) with no adequate response to i.v. prostacyclin treatment. The clinical course, 6minutes walking test and echocardiogram were evaluated.Initial sildenafil dose was 12.5 mg three times daily, which was increased up to 50 mg three times daily in one patient and up to 50 mg four times daily in the other three. The symptoms of right heart failure were controlled in all cases. Before the start of sildenafil administration, two patients had class III dyspnea and two patients had class IV dyspnea. Two patients converted to class I (previously class III and IV), and the other two converted to class II. The distance walked within 6 minutes increased (average increase 55%) and systolic pulmonary artery pressure decreased in all patients (average reduction 27%). Effects of sildenafil were substained. The only side effect seen was mild headache.Our experience supports the value of sildenafil in the treatment of PHT and suggests that combined treatment is useful for rescuing patients who fail to respond to initial treatment with i.v. prostacyclin.

The purpose of this study was to establish the usefulness of single photon emission computed tomography (SPECT) and psychological tests for diagnostic of neuro-Behçet (NB) and to evaluate the clinical significance of neurological symptoms that are difficult to interpret and asymptomatic abnormalities in diagnostic tests.Forty patients with Behçet's disease (BD) were enrrolled for being studied with magnetic resonance imaging (MRI), SPECT and psychological tests.MRI findings were abnormal in 52,9% of patients with neurological involvement and 23.1% without it (p0.1), whereas SPECT findings were abnormal in 82.3% and 61.5%, respectively (no significant difference). The difference between MRI and SPECT findings was significant (p0.02 for the complete group; p0.05 for patients without neurological symptoms; p0.08 for patients with them). The mean follow-up period was 42.6 months, and no patient without neurological involvement or those only with neurological symptoms that are difficult to interprete developed definite neurological involvement. The results of cognitive tests were not significantly different among patients with or without neurological involvement, neither among patients and controls. The scale 2 (depression) of the personality test was more frequent in patients with definite neurological involvement (p0.05).SPECT seems more sensible and less specific than MRI for diagnostic of NB. Although SPECT findings were frequently abnormal in patients with BD without neurological involvement or with neurological symptoms hard to interpret, no patient from this group developed a NB flare after a long follow-up period. A characteristic personality was found for patients with BD.