Pregnancy outcomes in 1869 pregnancies in a large cohort from the Spanish Society of Rheumatology Lupus Register (RELESSER).

INTRODUCTION: Obstetric complications are more common in women with systemic lupus erythematosus (SLE) than in the general population. OBJECTIVE: To assess pregnancy outcomes in women with SLE from the RELESSER cohort after 12 years of follow-up. METHODS: A multicentre retrospective observational study was conducted. In addition to data from the RELESSER register, data were collected on obstetric/gynaecological variables and treatments received. The number of term pregnancies was compared between women with pregnancies before and after the diagnosis of SLE. Further, clinical and laboratory characteristics were compared between women with pregnancies before and after the diagnosis, on the one hand, and with and without complications during pregnancy, on the other. Bivariate and multivariate analyses were carried out to identify factors potentially associated with complications during pregnancy. RESULTS: A total of 809 women were included, with 1869 pregnancies, of which 1395 reached term. Women with pregnancies before the diagnosis of SLE had more pregnancies (2.37 vs 1.87) and a higher rate of term pregnancies (76.8% vs 69.8%, p < 0.001) compared to those with pregnancies after the diagnosis. Women with pregnancies before the diagnosis were diagnosed at an older age (43.4 vs 34.1 years) and had more comorbidities. No differences were observed between the groups with pregnancies before and after diagnosis in antibody profile, including anti-dsDNA, anti-Sm, anti-Ro, anti-La, lupus anticoagulant, anticardiolipin or anti-beta-2-glycoprotein. Overall, 114 out of the 809 women included in the study experienced complications during pregnancy, including miscarriage, preeclampsia/eclampsia, foetal death, and/or preterm birth. Women with complications had higher rates of antiphospholipid syndrome (40.5% vs 9.9%, p < 0.001) and higher rates of positivity for IgG anticardiolipin (33.9% vs 21.3%, p = 0.005), IgG anti-beta 2 glycoprotein (26.1% vs 14%, p = 0.007), and IgM anti-beta 2 glycoprotein (26.1% vs 16%, p = 0.032) antibodies, although no differences were found regarding lupus anticoagulant. Among the treatments received, only heparin was more commonly used by women with pregnancy complications. We did not find differences in corticosteroid or hydroxychloroquine use. CONCLUSIONS: The likelihood of term pregnancy is higher before the diagnosis of SLE. In our cohort, positivity for anticardiolipin IgG and anti-beta-2- glycoprotein IgG/IgM, but not lupus anticoagulant, was associated with a higher risk of poorer pregnancy outcomes.

Macitentan for the Treatment of Refractory Digital Ulcers in Patients With Connective Tissue Diseases.

Systemic sclerosis (SSc) is a chronic autoimmune disease with complex pathogenesis, characterized by vascular dysfunction and fibrosis. Digital ulcers (DUs) are a common and severe complication in SSc patients, negatively impacting their quality of life. This retrospective study evaluates the use of macitentan, an endothelin receptor antagonist, in six female patients with connective tissue disease (CTD) and sclerodermiform features (five SSc and one mixed connective tissue disease) for the treatment of refractory DUs. Macitentan demonstrated a safe and effective alternative to bosentan, reducing DU relapses, hospitalizations, and the use of systemic prostaglandin therapy. The findings suggest that macitentan may be a valuable therapeutic option in specific cases of recurrent or refractory DUs and warrant further investigation in larger, long-term studies.

Central nervous system involvement in systemic lupus erythematosus: Data from the Spanish Society of Rheumatology Lupus Register (RELESSER).

OBJECTIVES: To analyze the prevalence, incidence, survival and contribution on mortality of major central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). METHODS: Patients fulfilling the SLE 1997 ACR classification criteria from the multicentre, retrospective RELESSER-TRANS (Spanish Society of Rheumatology Lupus Register) were included. Prevalence, incidence and survival rates of major CNS neuropsychiatric (NP)-SLE as a group and the individual NP manifestations cerebrovascular disease (CVD), seizure, psychosis, organic brain syndrome and transverse myelitis were calculated. Furthermore, the contribution of these manifestations on mortality was analysed in Cox regression models adjusted for confounders. RESULTS: A total of 3591 SLE patients were included. Of them, 412 (11.5%) developed a total of 522 major CNS NP-SLE manifestations. 61 patients (12%) with major CNS NP-SLE died. The annual mortality rate for patients with and without ever major CNS NP-SLE was 10.8% vs 3.8%, respectively. Individually, CVD (14%) and organic brain syndrome (15.5%) showed the highest mortality rates. The 10% mortality rate for patients with and without ever major CNS NP-SLE was reached after 12.3 vs 22.8 years, respectively. CVD (9.8 years) and organic brain syndrome (7.1 years) reached the 10% mortality rate earlier than other major CNS NP-SLE manifestations. Major CNS NP-SLE (HR 1.85, 1.29-2.67) and more specifically CVD (HR 2.17, 1.41-3.33) and organic brain syndrome (HR 2.11, 1.19-3.74) accounted as independent prognostic factors for poor survival. CONCLUSION: The presentation of major CNS NP-SLE during the disease course contributes to a higher mortality, which may differ depending on the individual NP manifestation. CVD and organic brain syndrome are associated with the highest mortality rates.

Prevalencia y características clínicas de la enfermedad pulmonar intersticial difusa sintomática en la artritis reumatoide en una población española / Prevalence and clinical characteristics of symptomatic diffuse interstitial lung disease in rheumatoid arthritis in a Spanish population

Antecedentes y objetivos: En España, los estudios epidemiológicos de prevalencia de enfermedad pulmonar intersticial difusa (EPID) en artritis reumatoide (AR) son escasos y limitados. Nuestro objetivo fue estimar la prevalencia de EPID sintomática en AR y sus características en nuestra área. Materiales y métodos: Se diseñó un estudio observacional longitudinal prospectivo en la consulta interdisciplinar de Reumatología y Neumología, en el que incluimos AR con síntomas respiratorios y EPID confirmada por tomografía computarizada de alta resolución. Resultados: De las 2.729 personas con AR de nuestra área, 47 presentaban EPID sintomática, estimándose una prevalencia de EPID sintomática en AR del 1,72% (intervalo de confianza del 95%: 1,26-2,29) con una edad al diagnóstico de AR de 57,3±13,3 años. Fue más frecuente en hombres, el 60,6% tenía antecedente de tabaquismo y el 84,3 y el 84,7% factor reumatoide y anticuerpos antipéptidos cíclicos citrulinados, respectivamente. El patrón más frecuente fue neumonía intersticial usual (NIU) en 28 (31,1%), la neumonía intersticial no específica (NINE) fue más frecuente en mujeres y el síndrome combinado enfisema-fibrosis (SCEF) exclusivamente en hombres. Conclusiones: En este estudio hemos analizado la prevalencia de AR-EPID sintomática en nuestra área, la cual está por debajo de lo esperado, probablemente en relación con las definiciones utilizadas. Así mismo, hemos descrito que el patrón NIU es el más frecuente en la AR, seguido del NINE y analizado por primera vez la prevalencia de SCEF en la AR, que alcanza el 13% (AU)

Background and objectives: In Spain, epidemiological studies of the prevalence of diffuse interstitial lung disease (ILD) in rheumatoid arthritis (RA) are limited. Our objective was to estimate the prevalence of symptomatic ILD in RA and its characteristics in our area. Materials and methods: In our hospital's interdisciplinary rheumatology and pulmonology clinic, a prospective longitudinal observational study was designed in which we included RA with respiratory symptoms and ILD confirmed by high resolution computed tomography. Results: Of the 2,729 people with RA in our area, 47 had symptomatic ILD, estimating a prevalence of symptomatic ILD in RA of 1.72% (95% CI 1.26 - 2.29) with an age at diagnosis of RA of 57.3±13.3 years. It was more frequent in men, 60.6% had a history of smoking, and 84.3% and 84.7% had rheumatoid factor (RF) and anti-cyclic citrullinated peptide (Anti-CCP) antibodies, respectively. The most frequent pattern was usual interstitial pneumonitis (UIP), appearing in 28 (31.1%). Nonspecific interstitial pneumonia (NSIP) was more frequent in women, while the combined pulmonary fibrosis-emphysema (CPFE) syndrome presented exclusively in men. Conclusions: We have analysed the prevalence of symptomatic RA-ILD in our area, which is lower than expected, probably in relation to the definitions used. We have also described that the UIP pattern is the most frequent in RA in our environment, followed by the NSIP. Lastly, we have analysed the prevalence of CPFE in RA, which reaches 13%, for the first time (AU)

Prevalence and clinical characteristics of symptomatic diffuse interstitial lung disease in rheumatoid arthritis in a Spanish population.

BACKGROUND AND OBJECTIVES: In Spain, epidemiological studies of the prevalence of diffuse interstitial lung disease (ILD) in rheumatoid arthritis (RA) are limited. Our objective was to estimate the prevalence of symptomatic ILD in RA and its characteristics in our area. MATERIALS AND METHODS: In our hospital's interdisciplinary rheumatology and pulmonology clinic, a prospective longitudinal observational study was designed in which we included RA with respiratory symptoms and ILD confirmed by high resolution computed tomography. RESULTS: Of the 2729 people with RA in our area, 47 had symptomatic ILD, estimating a prevalence of symptomatic ILD in RA of 1.72% (95% CI 1.26-2.29) with an age at diagnosis of RA of 57.3 ±â€¯13.3 years. It was more frequent in men, 60.6% had a history of smoking, and 84.3% and 84.7% had rheumatoid factor (RF) and anti-cyclic citrullinated peptide (Anti-CCP) antibodies, respectively. The most frequent pattern was usual interstitial pneumonitis (UIP), appearing in 28 (31.1%). Nonspecific interstitial pneumonia (NSIP) was more frequent in women, while the combined pulmonary fibrosis-emphysema (CPFE) syndrome presented exclusively in men. CONCLUSIONS: We have analysed the prevalence of symptomatic RA-ILD in our area, which is lower than expected, probably in relation to the definitions used. We have also described that the UIP pattern is the most frequent in RA in our environment, followed by the NSIP. Lastly, we have analysed the prevalence of CPFE in RA, which reaches 13%, for the first time.

Fracturas vertebrales múltiples tras la suspensión de tratamiento con denosumab: serie de diez casos / Multiple vertebral fractures following discontinuation of denosumab treatment: ten clinical cases report

OBJETIVOS: Analizar las características clínicas y de metabolismo óseo de una serie de pacientes con fracturas vertebrales tras la suspensión de denosumab (DMab). MÉTODOS: Estudio observacional retrospectivo de 10 pacientes con fracturas vertebrales tras suspender DMab atendidas en el Servicio de Reumatología de un hospital español de tercer nivel entre 2015 y 2018. RESULTADOS: Se registraron un total de 49 fracturas espontáneas tras una media de 6 dosis de DMab y transcurridos 10,9 meses desde la suspensión del fármaco. El 90% había recibido tratamiento previo, 7 de 10 bisfosfonatos orales. Tras la suspensión, CTX y P1NP estaban elevados y la media de T-score en cuello femoral y columna lumbar fue menor que previo a DMab. Las vértebras más afectadas fueron L3, L5, D6, D7, D9 y D11. CONCLUSIÓN: La descripción de nuevos casos de fracturas vertebrales múltiples en los meses posteriores a la suspensión de DMab subraya la preocupación emergente en la comunidad científica siendo preciso apoyar en evidencias sólidas las nuevas recomendaciones sobre su manejo

OBJECTIVES: Analyse clinical and bone metabolism features in a case series of patients with multiple vertebral fractures after discontinuation of denosumab (DMab). METHODS: An observational descriptive study analysing data from ten patients with multiple vertebral fractures after DMab discontinuation that were admitted to our rheumatology department between 2015 and 2018. RESULTS: There were a total of 49 spontaneous fractures after an average of 6 DMab doses and 10.9 months from discontinuation. Ninety percent had already received treatment other than DMab 7 of 10 oral bisphosphonates. After discontinuation, CTX and P1NP remained elevated and mean T-score for femoral neck and lumbar spine was lower than before treatment. The most affected vertebrae were L3, L5, D6, D7, D9 and D11. CONCLUSION: This report of ten new cases suffering multiple vertebral fractures early after discontinuation of DMab highlights the emerging concern on the subject in the scientific community and the need to clarify its pathogenic mechanism, and to support by solid evidence the new recommendations on its management

Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients.

OBJECTIVE: To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD). METHODS: This was an observational, multicentre study of RA-ILD patients treated with at least one dose of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect. RESULTS: We studied 263 RA-ILD patients [150 women/113 men; mean (s.d.) age 64.6 (10) years]. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25-3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6-36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P < 0.001) and a CS-sparing effect from a median 7.5 (5-10) to 5 (2.5-7.5) mg/day at the end of follow-up (P < 0.001) was also observed. ABA was withdrawn in 62 (23.6%) patients due to adverse events (n = 30), articular inefficacy (n = 27), ILD worsening (n = 3) and other causes (n = 2). CONCLUSION: ABA may be an effective and safe treatment for patients with RA-ILD.

Multiple vertebral fractures following discontinuation of denosumab treatment: Ten clinical cases report. / Fracturas vertebrales múltiples tras la suspensión de tratamiento con denosumab: serie de diez casos.

OBJECTIVES: Analyse clinical and bone metabolism features in a case series of patients with multiple vertebral fractures after discontinuation of denosumab (DMab). METHODS: An observational descriptive study analysing data from ten patients with multiple vertebral fractures after DMab discontinuation that were admitted to our rheumatology department between 2015 and 2018. RESULTS: There were a total of 49 spontaneous fractures after an average of 6 DMab doses and 10.9 months from discontinuation. Ninety percent had already received treatment other than DMab 7 of 10 oral bisphosphonates. After discontinuation, CTX and P1NP remained elevated and mean T-score for femoral neck and lumbar spine was lower than before treatment. The most affected vertebrae were L3, L5, D6, D7, D9 and D11. CONCLUSION: This report of ten new cases suffering multiple vertebral fractures early after discontinuation of DMab highlights the emerging concern on the subject in the scientific community and the need to clarify its pathogenic mechanism, and to support by solid evidence the new recommendations on its management.

Association of apolipoprotein B/apolipoprotein A1 ratio and cardiovascular events in rheumatoid arthritis: results of the CARMA study.

OBJECTIVES: To assess the plasma apolipoprotein B/apolipoprotein A1 ratio and its potential association with cardiovascular events (CVE) in patients with rheumatoid arthritis (RA). METHODS: A baseline analysis was made of the CARdiovascular in rheuMAtology Project (CARMA), a 10-year prospective study evaluating the presence of at least one CVE in 775 Spanish patients with RA. Of them, 29 had already experienced CVE prior to the inclusion in the study. We assessed the association between the elevation of the apoB/apoA1 ratio with the presence of CVE according to a logistic regression model for possible confounding factors. We also analysed the main parameters of activity of RA and parameters related to lipid metabolism. RA patients were classified according to treatment: patients treated with disease-modifying anti-rheumatic drugs without biologics and those undergoing biologic therapy (anti-TNF-α, anti-IL-6 receptor, and other biologic agents). RESULTS: The apoB/apoA1 ratio of patients who had experienced CVE was higher than that of patients without previous CVE (0.65 vs. 0.60). However, the difference between both subgroups did not reach statistical significance (p=0.197). It was also the case after the multivariate analysis [OR: 1.48 (95% CI: 0.15-14.4); p=0.735]. RA patients from the group with CVE were more commonly receiving lipid-lowering treatment with statins than those without CVE history (41.4% vs. 20%, p=0.005). High HAQ and high atherogenic index were significantly associated with the presence of CVE. There was no statistical association between the type of biologic therapy used in RA and the presence of CVE. CONCLUSIONS: No association between ApoB/apoA1 ratio and CVE was found at the baseline visit of patients with RA from the CARMA study.

Artritis gonocócica y déficit de C2 / Gonococcal arthritis and C2 deficiency

La enfermedad gonocócica diseminada es una manifestación infrecuente de la afectación por Neisseria gonorrhoeae, que presenta una clínica variada y no bien definida, siendo la afectación articular un hallazgo característico. Presentamos el caso de una mujer de 64 años con enfermedad gonocócica diseminada de inicio agudo, que comenzó con deterioro generalizado y oligoartritis. Se realizó artrocentesis de carpo, obteniéndose un líquido sinovial de aspecto purulento, cuyo estudio microbiológico identificó Neisseira gonorrhoeae. En el estudio se objetivó un complemento hemolítico total (CH50) de cero, no detectándose la fracción C2 del complemento. Son muy pocos los casos descritos en la literatura de enfermedad gonocócica diseminada asociada a déficit de C2. Presentamos un nuevo caso y revisamos los previamente publicados

Disseminated gonococcal infection is a rare presentation of the sexually transmitted pathogen, Neisseria gonorrhoeae. Here, we report the case of a 64-year-old woman with disseminated gonococcal infection, which started with symptoms of oligoarthritis and malaise. Neisseria gonorrhoeae was identified in the carpal synovial fluid. The follow-up study revealed an absence of total hemolytic complement and complement C2 was not detected. Being relatively common, C2 deficiency has been associated with disseminated gonococcal infection in a few cases. We present a new case and discuss those previously published

Gonococcal Arthritis and C2 Deficiency. / Artritis gonocócica y déficit de C2.

Disseminated gonococcal infection is a rare presentation of the sexually transmitted pathogen, Neisseria gonorrhoeae. Here, we report the case of a 64-year-old woman with disseminated gonococcal infection, which started with symptoms of oligoarthritis and malaise. Neisseria gonorrhoeae was identified in the carpal synovial fluid. The follow-up study revealed an absence of total hemolytic complement and complement C2 was not detected. Being relatively common, C2 deficiency has been associated with disseminated gonococcal infection in a few cases. We present a new case and discuss those previously published.

Preliminary Report of Microcephaly Potentially Associated with Zika Virus Infection During Pregnancy - Colombia, January-November 2016.

In Colombia, approximately 105,000 suspected cases of Zika virus disease (diagnosed based on clinical symptoms, regardless of laboratory confirmation) were reported during August 9, 2015-November 12, 2016, including nearly 20,000 in pregnant women (1,2). Zika virus infection during pregnancy is a known cause of microcephaly and serious congenital brain abnormalities and has been associated with other birth defects related to central nervous system damage (3). Colombia's Instituto Nacional de Salud (INS) maintains national surveillance for birth defects, including microcephaly and other central nervous system defects. This report provides preliminary information on cases of congenital microcephaly identified in Colombia during epidemiologic weeks 5-45 (January 31-November 12) in 2016. During this period, 476 cases of microcephaly were reported, compared with 110 cases reported during the same period in 2015. The temporal association between reported Zika virus infections and the occurrence of microcephaly, with the peak number of reported microcephaly cases occurring approximately 24 weeks after the peak of the Zika virus disease outbreak, provides evidence suggesting that the period of highest risk is during the first trimester of pregnancy and early in the second trimester of pregnancy. Microcephaly prevalence increased more than fourfold overall during the study period, from 2.1 per 10,000 live births in 2015 to 9.6 in 2016. Ongoing population-based birth defects surveillance is essential for monitoring the impact of Zika virus infection during pregnancy on birth defects prevalence and measuring the success in preventing Zika virus infection and its consequences, including microcephaly.

Constitutively altered frequencies of circulating follicullar helper T cell counterparts and their subsets in rheumatoid arthritis.

INTRODUCTION: Circulating CD4 T cells expressing CXCR5, ICOS and/or PD-1 are counterparts of follicular helper T cells (Tfh). There are three subpopulations of circulating Tfh (cTfh): CXCR5 + CXCR3 + CCR6- (Tfh-Th1), CXCR5 + CXCR3-CCR6- (Tfh-Th2) and CXCR5 + CXCR3-CCR6+ (Tfh-Th17). Our objective was to study the B cell helping capacity of cTfh subsets, and examine their frequency in Rheumatoid Arthritis (RA) patients, together with the frequency of circulating plasmablasts (CD19 + CD20-CD38high). METHODS: Peripheral blood was drawn from RA patients with active disease (RA-a, DAS28 >2.6) (n = 17), RA in remission (RA-r, DAS28 <2.6) (n = 17) and healthy controls (HC) (n = 34). cTfh and plasmablast frequencies were determined by flow cytometry. Cocultures of sorted CD4 + CXCR5+ T cell subpopulations were established with autologous CD19 + CD27- naïve B cells of HC, and concentrations of IgG, A and M were measured in supernatants. RESULTS: Isolated Tfh-Th2 and Tfh-Th17 but not Tfh-Th1 cells, induced naïve B cells to secrete IgG and IgA. The frequency of CXCR5+ cells gated for CD4+ T cells was not different among HC, RA-a and RA-r. In contrast, both RA-a and RA-r patients demonstrated an increased frequency of CD4 + CXCR5 + ICOS+ T cells and augmented (%Tfh-Th2 + %Tfh-Th17)/%Tfh-Th1 ratio as compared with HC. In addition, RA-a but not RA-r patients, showed an increased frequency of circulating plasmablasts. CONCLUSION: Both RA-a and RA-r patients demonstrate an increased frequency of cTfh and overrepresentation of cTfh subsets bearing a B cell helper phenotype, suggesting that altered germinal center dynamics play a role in RA pathogenesis. In contrast, only RA-a patients show an increased proportion of circulating plasmablasts.

Manifestaciones pulmonares de las enfermedades del colágeno / Pulmonary Manifestations of Collagen Diseases

Las enfermedades del colágeno constituyen un gran grupo de enfermedades inflamatorias sistémicas de etiología autoinmune. La etiopatogenia de las enfermedades del colágeno es multifactorial. Existe una susceptibilidad genética, y muchos trastornos del tejido conectivo muestran una agregación familiar, sobre la que actúan factores ambientales que desencadenan la enfermedad. En las enfermedades del colágeno se pueden afectar casi todos los órganos del cuerpo. El sistema respiratorio es uno de los más frecuentemente afectados, aunque no se conoce con exactitud la prevalencia de enfermedad pulmonar en las diferentes enfermedades del colágeno. Cualquier estructura del aparato respiratorio puede estar afectada. Quizá lo más frecuente sea la enfermedad del parénquima pulmonar en forma de neumonitis, que puede manifestarse como cualquiera de los patrones de neumonitis intersticiales idiopáticas. Pero también pueden afectarse la pleura, los vasos pulmonares, la vía aérea y la musculatura respiratoria. La frecuencia de enfermedad pulmonar asociada a las enfermedades del colágeno está aumentando, por una parte gracias a los mejores métodos de diagnóstico de que disponemos hoy en día, como la tomografía computarizada de alta resolución, y también por la aparición de nuevas formas de neumonitis asociadas a los nuevos tratamientos empleados en la actualidad. El objetivo de este artículo es ofrecer una visión en conjunto de cómo las enfermedades del colágeno pueden afectar el pulmón, de acuerdo con las nuevas evidencias científicas (AU)

Collagen diseases are a large group of systemic inflammatory diseases of autoimmune etiology. The etiopathogenesis of collagen diseases is multifactorial. There is genetic susceptibility, as many connective tissue disorders show family history, and environmental factors may trigger the disease. Collagen diseases can affect almost all the organs of the body. The respiratory system is one of the most frequently affected, although the prevalence of pulmonary disease is not precisely known for the different collagen disorders. Any structure of the respiratory tract can be affected, but perhaps the most frequent is pulmonary parenchymal disease in the form of pneumonitis, which can be produced in any of the idiopathic interstitial pneumonitis patterns. The pleura, pulmonary vessels, airways and respiratory muscles may also be affected. The frequency of lung disease associated with collagen diseases is on the rise. This is in due part to the better diagnostic methods that are available to us today (such as high-resolution computed tomography) and also to the appearance of new forms of pneumonitis associated with the new treatments that are currently used. The objective of this article is to offer a global vision of how collagen diseases can affect the lungs according to the latest scientific evidence (AU)

Pulmonary manifestations of collagen diseases.

Collagen diseases are a large group of systemic inflammatory diseases of autoimmune etiology. The etiopathogenesis of collagen diseases is multifactorial. There is genetic susceptibility, as many connective tissue disorders show family history, and environmental factors may trigger the disease. Collagen diseases can affect almost all the organs of the body. The respiratory system is one of the most frequently affected, although the prevalence of pulmonary disease is not precisely known for the different collagen disorders. Any structure of the respiratory tract can be affected, but perhaps the most frequent is pulmonary parenchymal disease in the form of pneumonitis, which can be produced in any of the idiopathic interstitial pneumonitis patterns. The pleura, pulmonary vessels, airways and respiratory muscles may also be affected. The frequency of lung disease associated with collagen diseases is on the rise. This due in part to the better diagnostic methods that are available to us today (such as high-resolution computed tomography) and also to the appearance of new forms of pneumonitis associated with the new treatments that are currently used. The objective of this article is to offer a global vision of how collagen diseases can affect the lungs according to the latest scientific evidence.

Frequency of Th17 CD4+ T cells in early rheumatoid arthritis: a marker of anti-CCP seropositivity.

OBJECTIVE: To examine the frequency and phenotype of Th17 cells in the peripheral blood of early RA (eRA) patients. METHODS: CD4+ T cells were isolated from the peripheral blood of 33 eRA patients, 20 established RA patients and 53 healthy controls (HC), and from the synovial fluid of 20 established RA patients (RASF), by ficoll-hypaque gradient and magnetical negative selection. After polyclonal stimulation, the frequency of Th17 and Th1 cells was determined by flow cytometry and concentrations of IL-17, IFN-γ, TNF-α and IL-10 were measured by ELISA in cell-free supernatants. RESULTS: When all of our eRA patients were analyzed together, a significantly lower percentage of circulating Th17 cells and a lower CD4-derived IL-17 secretion were observed in comparison with HC. However, after stratifying by anti-CCP antibody status, circulating Th17 cells were decreased in anti-CCP(+) but not in anti-CCP(-)-eRA. All Th17 cells were CD45RO+CD45RA- and CCR6+. Dual Th17/Th1 cells were also exclusively decreased in anti-CCP(+)-eRA. Circulating Th17 and Th17/Th1 cells were negatively correlated with anti-CCP titres. When anti-CCP(+)-eRA patients were retested one year after initiating treatment with oral methotrexate, their circulating Th17 frequency was no longer different from HC. Of note, the percentage of circulating Th1 cells and the secretion of CD4-derived IFN-γ, TNF-α and IL-10 were not different between eRA patients and HC. In established RA patients, circulating Th17 and T17/Th1 cell frequencies were comparable to HC. In RASF, both Th17 and Th1 cells were increased when compared with blood of eRA patients, established RA patients and HC. CONCLUSION: Decreased circulating Th17 levels in eRA seem to be a marker of anti-CCP seropositivity, and return to levels observed in healthy controls after treatment with methotrexate.

IL-15 expression on RA synovial fibroblasts promotes B cell survival.

INTRODUCTION: The purpose of this study was to examine the role of RA Synovial Fibroblast (RASFib) IL-15 expression on B cell survival. METHODS: Magnetically sorted peripheral blood memory B cells from 15 healthy subjects were cocultured with RASFib. RESULTS: RASFib constitutively expressed membrane IL-15. Survival of isolated B cells cultured for 6 days, below 5%, was extended in coculture with RASFib to 52+/-8% (p<0.001). IL-15 neutralizing agents but not isotype controls, reduced this rate to 31+/-6% (p<0.05). Interestingly, rhIL-15 had no effect on isolated B cells but significantly increased their survival in coculture with RASFib. In parallel, B cell IL-15R chains were upregulated in cocultures. BAFF and VCAM-1, that are expressed on RASFib, were tested as potential candidates involved in upregulating B cell IL-15R. Culture of B cells in the presence of rhBAFF or rhVCAM-1 resulted in significantly increased survival, together with upregulation of all three IL-15R chains; in parallel, rhIL-15 potentiated the anti-apoptotic effect of BAFF and VCAM-1. Both BAFF and VCAM-1 neutralizing agents downmodulated the effect of RASFib on B cell survival and IL-15R expression. In parallel, rhIL-15 had a lower effect on the survival of B cells cocultured with RASFib in the presence of BAFF or VCAM-1 neutralizing agents. Peripheral blood B cells from 15 early RA patients demonstrated an upregulated IL-15R and increased survival in cocultures. CONCLUSION: IL-15 expression on RASFib significantly contributes to the anti-apoptotic effect of RASFib on B cells. IL-15 action is facilitated by BAFF and VCAM-1 expressed on RASFib, through an upregulation of IL-15R chains.

New drugs beyond biologics in rheumatoid arthritis: the kinase inhibitors.

Orally available small molecule compounds have recently been developed for the treatment of RA, and inhibitors of signalling cascades, specifically inhibitors of kinases, have reached advanced stages of clinical development. The p38 mitogen-activated protein kinase blockers have shown poor clinical response despite encouraging preclinical data. In contrast, inhibitors of the non-receptor tyrosine kinases, spleen tyrosine kinase and janus kinase 3, have demonstrated a significant clinical efficacy together with an acceptable safety profile. We herein present a review on published preclinical and clinical data on these new drugs.

Clinical and ultrasonographic findings related to knee pain in osteoarthritis.

OBJECTIVES: To determine clinical and sonographic factors associated with painful episodes in patients with knee osteoarthritis (OA). METHODS: In this cross-sectional controlled study, patients with primary knee OA (ACR criteria) were prospectively placed into two groups. Group A: 81 patients with knee pain during physical activity >or=30 mm in visual analogue scale (VAS) for pain for at least 48 h prior to inclusion; Group B: 20 patients without knee pain from at least 1 month prior to inclusion. Clinical parameters, knee radiographic and ultrasonographic findings were collected. The sonographic study assessed joint effusion in the suprapatellar pouch, infrapatellar superficial and deep bursitis, meniscal lesions, anserine tendinobursitis, and Baker's cyst. RESULTS: Group A patients tended to be older and heavier women than group B (P<0.05). The most frequent radiographic stage was III (57%) in group A, and I (35%) and II (35%) in group B, showing differences in the distribution of each radiographic stage (P<0.005). The most frequent ultrasonographic finding in group A was suprapatellar effusion (79%), and in group B it was meniscal lesions (40%). Ultrasonographic findings showed in group A a significant increase of suprapatellar effusion (P<0.001) and a tendency towards an increase of Baker's cyst (P=0.06). Suprapatellar effusion, Baker's cyst, and body mass index (BMI) were the factors associated with the appearance of pain after the logistic regression analysis. CONCLUSIONS: Suprapatellar effusion, Baker's cyst, and higher BMI are more frequent and seem to be risk factors of painful flare in OA of the knee.

[Infliximab (anti-TNF-alpha) treatment in patients with adult Still's disease. Experience in 2 cases]. / Tratamiento con infliximab (anti-TNF alfa) en pacientes con enfermedad de Still del adulto. Experiencia de dos casos.

Adult Still's disease is a systemic inflammatory disorder of unknown etiology. First-line treatment for Still's disease includes nonsteroidal anti-inflammatory drugs and corticosteroids. In refractory cases o when the dose of corticosteroid is unacceptably high, other disease modifying antirheumatic drugs have been used. But recent study showed the efficacy anti-TNF therapy in adult Sill's disease refractory to conventional therapy. We report a favourable response to infliximab in two patients who has proved resistant to conventional therapy.