Primary Sjögren's syndrome: Extraglandular manifestations and hydroxychloroquine therapy.

The use of hydroxychloroquine (HCQ) in Primary Sjögren's Syndrome (pSS) has been assessed in different studies over the last years, with conflicting results regarding its efficacy in sicca syndrome and extraglandular manifestations (EGM). The goal of this study was to compare the incidence rate of EGM in pSS patients with and without HCQ therapy.We performed a multicenter retrospective study, including patients with pSS (European classification criteria) with at least 1 year of follow-up. Subjects with concomitant fibromyalgia, autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis were excluded. Demographics and pSS characteristics were recorded. The EGM were defined by EULAR-SS disease activity index (ESSDAI). Patients were divided into two groups according to their use or not of HCQ therapy. We evaluated the use of HCQ and its relationship to EGM. HCQ therapy was defined as the continuous use of the drug for at least 3 months. A descriptive analysis of demographics and pSS characteristics was performed. We compared the incidence of EGM between groups defined by HCQ therapy using chi2 test or Fisher's exact test. A total of 221 patients were included (97.3% women), mean age, 55.7 years (SD 14). Mean age at diagnosis, 48.8 years (SD 15); median disease duration, 60 months (IQR 35-84). One hundred and seventy patients (77%) received HCQ. About half of the patients had at least one EGM during the course of the disease, 20% of them developed an EGM before the onset of the sicca syndrome and 26% simultaneously with dryness symptom. Overall, EGM were less frequent in those on HCQ therapy (36.5% vs 63.5%, p < 0.001). Considering each EGM individually, the following manifestations were more frequent in the non-treated group: arthritis (p < 0.001), fatigue (p < 0.001), purpura (p = 0.01), Raynaud phenomenon (p = 0.003), and hypergammaglobulinemia (p = 0.006). Immunosuppressive treatment was indicated on 28 patients (12.7%), 13 of which were receiving also HCQ. The first reason for those treatments was the presence of arthritis in 12/28 patients (42.8%), and the drug used in all the cases was methotrexate. Only three patients required immunosuppressive therapy with cyclophosphamide, due to the presence of glomerulonephritis, vasculitis, and interstitial lung disease. None of the patients received biologic therapy. The lower incidence of EGM was observed in patients on HCQ therapy supports its efficacy in pSS. However, further large scale prospective studies are needed to confirm these findings.

Perfil lipídico e inflamación en pacientes con artritis reumatoidea: una contradicción? / Lipid profile and inflammatory state in patients with rheumatoid arthritis

INTRODUCCIÓN: Los pacientes con artritis reumatoidea (AR) presentan una mobimortalidad cardiovascular (CV) 50-60% más alta comparada con la población general. En este grupo poblacional, la carga inflamatoria acumulada, medida por los niveles de VSG y PCR durante un período prolongado, se ha asociado con aterosclerosis subclínica, riesgo cardiovascular y mortalidad. En contrapartida, la presencia de un estado pro-inflamatorio conduciría a una disminución del colesterol total (CT), colesterol HDL y colesterol LDL, por lo que la contribución de los lípidos como factor de riesgo CV es, ciertamente, contradictorio. OBJETIVO Correlacionar los reactantes de fase aguda (VSG-PCR) y los valores de lípidos (CT, HDL, LDL) en una muestra de pacientes con AR. PACIENTES Y METODO: Estudio observacional, retrospectivo, analítico, en el que se incluyeron pacientes con diagnóstico de AR según criterios ACR/EULAR 2010. La relación entre los valores de CT, HDL, LDL con la PCR y VSG se analizó con correlación de Pearson. Dada la distribución no simétrica de los valores de PCR, se obtuvo una transformación logarítmica (logaritmo normal) de la misma. En un segundo modelo, los valores de CT, HDL y LDL se correlacionaron con el logaritmo normal de la PCR realizando distintos cortes de la misma (concentración de PCR ≤5 mg/l, > 5 a 10 mg/l). Finalmente, las correlaciones significativas, se incluyeron en un modelo de regresión lineal multivariado ajustado por edad, género, tiempo de evolución de la enfermedad, uso de hipolipemiantes, medicamentos biológicos y dosis de glucocorticoides. RESULTADOS El análisis de este estudio incluyó 449 mediciones del perfil de lípidos y reactantes de fase aguda (PCR y VSG) correspondientes a 318 pacientes. Los pacientes fueron predominantemente mujeres (79.5%), con una edad media (desviación estándar) de 57.7 (12.3) años. La mediana (rango intercuartilo) del tiempo de evolución de la enfermedad fue de 74.0 (108.0) meses. La mayoría de los pacientes eran seropositivos (67%). La correlación entre PCR y CT (r= 0.16; p= 0.60), así como sus fracciones HDL (0.09; p= 0.30) y LDL (r= 0.09; p= 0.36), fueron débiles. En el sub-análisis de la PCR dividida en tres valores de corte, tanto el CT (r= -0.18 a 0.09) y la fracción LDL (r= -0.34 a 0.11) mostraron correlaciones débiles, independientemente del valor de corte analizado de PCR. Por el contrario, se observó una correlación positiva moderada entre los valores positivos intermedios de PCR y HDL (r= 0.53; p= 0.01). Las correlación entre VSG y CT (r=- 0.03; p= 0.58), así como su fracción LDL (r= 0.10; p= 0.88), fueron débiles. Se observó una correlación negativa débil, pero estadísticamente significativa entre VSG y la fracción HDL (r=-0.14; p= 0.02). En el análisis multivariado de regresión lineal la VSG mantuvo una asociación negativa y significativa con los valores de colesterol HDL (coeficiente ß= -0.179, IC95% -0.28 -0.07; p= 0.001). CONCLUSION: En este estudio pudimos corroborar una relación inversa, aunque débil, entre la VSG y la fracción HDLcolesterol, por el contrario, no pudimos reproducir los hallazgos previamente publicados sobre la relación inversa entre la PCR y los niveles séricos de colesterol y sus fracciones. (AU)

INTRODUCTION: Cardiovascular disease (CVD) is the main cause of premature mortality in patients with rheumatoid arthritis (RA). The risk of CVD mortality is increased by approximately 50% compared to the general population. In patients with RA, the cumulative inflammatory burden, as measured by the levels of the globular sedimentation rate (GSR) and the Creactive protein (CRP), has been associated with sub-clinical atherosclerosis, CV risk and mortality. On the contrary, the presence of a proinflammatory state, as observed in patients with RA, may lead to a decline of the total cholesterol (TC) and HDL fraction. This observation suggests that inflammation may play a confounding role in the association of lipids with CVD. OBJETIVO: To correlate acute phase reactants (GSR and CRP) with the lipid measurements (TC, HDL and LDL) in a sample of patients with RA. PATIENTS Y METHOD: In this observational, retrospective and analytic study, we included 318 patients fulfilling the CR/EULAR 2010 criteria for RA. The relationship between the TC, HDL, LDL and the CRP (normal logarithm) and GSR was analyzed with the Pearson´s correlation. In a second model, the relationship of the TC, HDL and LDL with the normal logarithm of CRP was analyzed using different cutoff values (CRP ≤5 mg/l, > 5 a <10 mg/l y >10 mg/l). Finally, all the significant correlations were included in a multivariate linear regression model adjusting for age, gender, disease duration, use of lipid lowering drugs, biologic disease modifying antirheumatic drugs and glucocorticoid doses. RESULTS: The study included 449 measurements of the lipid profile and acute phase reactants. Patients were predominantly women (79.5%) with mean (SD) age of 57.7 (12.3) years. Median (IQR) disease duration was 74.0 (108.0) months. Most of the patients (67%) were either positive for the rheumatoid factor and/or anti-citrullinated antibodies. The correlation of the CRP and TC (r= 0.16; p= 0.6) and their fractions HDL (0.09; p= 0.30) and LDL (r= 0.09; p= 0.36) were positive and weak. In the sub-analyses using the three cut-off values of the CRP, the correlations of both, TC (r= -0.18 to 0.09) and LDL (r= -0.34 to 0.11) were also weak. On the contrary, the correlation between the intermediate values of CRP and HDL was positive and moderate (r= 0.53; p= 0.01). The correlation of the GSR and TC (r=-0.03; p= 0.58) and LDL (r= 0.10; p= 0.88) were weak. There was, however, a negative and significant, although weak correlation between the GSR and HDL (r=-0.14; p= 0.02). In the multivariate analyses, the GSR had a negative and significant association with the levels of HDL (ß coefficient = -0.179, 95%CI - 0.28 -0.07; p= 0.001). CONCLUSION: In this study we confirmed an inverse, although weak, relationship between the GSR and HDL-cholesterol. On the contrary, we were not able to reproduce previous published data regarding the inverse relationship between the CRP values and the levels of the TC or their fractions. (AU)