Serum uric acid is associated with damage in patients with systemic lupus erythematosus.

Introduction: Serum uric acid levels have been reported as predictors of cardiovascular, pulmonary, neurological and renal morbidity in patients with SLE. However, their role in cumulative global damage in these patients has not yet been determined. Objective: To determine whether serum uric acid levels are associated with new damage in patients with SLE. Methods: This is a longitudinal study of patients with SLE from the Almenara Lupus Cohort, which began in 2012. At each visit, demographic and clinical characteristics were evaluated, such as activity (Systemic Lupus Erythematosus Disease Activity Index-2K or SLEDAI-2K) and cumulative damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index or SDI). Treatment (glucocorticoids, immunosuppressive drugs and antimalarials) was also recorded. Univariable and multivariable Cox regression models were used to determine the impact of serum uric acid levels on the risk of new damage. Results: We evaluated 237 patients, with a mean age (SD) at diagnosis of 35.9 (13.1) years; 220 patients (92.8%) were women, and the duration of the disease was 7.3 (6.6) years. The mean SLEDAI-2K and SDI scores were 5.1 (4.2) and 0.9 (1.3), respectively. Serum uric acid level was 4.5 (1.4) mg/dL. Follow-up time was 3.1 (1.3) years, and 112 (47.3%) patients accrued damage during follow-up. In univariable and multivariable analyses, serum uric acid levels were associated with new damage (HR=1.141 (95% CI 1.016 to 1.282), p=0.026; HR=1.189 (95% CI 1.025 to 1.378), p=0.022, respectively). Conclusion: Higher serum uric acid levels are associated with global damage in patients with SLE.

Factores asociados a infecciones serias en pacientes hospitalizados con lupus eritematoso sistémico / Factors associated with serious infections in patients hospitalized with systemic lupus erythematosus

RESUMEN Introducción. En pacientes con lupus eritematoso sistémico (LES) existe incremento de infecciones debido a la propia enfermedad, al uso de inmunosupresores y corticoides. Objetivo. Identificar los factores asociados a infecciones serias en pacientes lúpicos en un hospital de referencia nacional. Estudio retrospectivo, analítico, de casos y controles en el Servicio de Reumatología del Hospital Nacional Guillermo Almenara Irigoyen, Lima, Perú. Métodos. Se analizó el registro de pacientes hospitalizados en el periodo de estudio, los casos fueron pacientes en los que se demostró la etiología de la primera infección durante su hospitalización. Los controles fueron pacientes lúpicos hospitalizados sin infecciones en el mismo periodo de estudio. Se analizaron variables asociadas al desarrollo de infecciones. Resultados. 61 pacientes de 390 hospitalizados desarrollaron infecciones durante su hospitalización. 48 desarrollaron 1 solo evento infeccioso (en 40 se demostró etiología). Los casos tuvieron mayor actividad, daño y comorbilidad en comparación con los controles. En el análisis univariado, el salario (p=0,031), el uso de inmunosupresores a la admisión (previo: p=0,004 y actual: p=0,004), el uso de glucocorticoides (<30 días: p=0,015 y >30-360 días: p=0,028), la actividad (p=0,029) y el daño (p=0,026) producido por la enfermedad, y el tiempo de hospitalización (p=0,045) tuvieron asociación estadísticamente significativa. En el análisis multivariado, los días de hospitalización se asociaron al desarrollo de infecciones. Conclusiones. Existió asociación entre días de hospitalización y el desarrollo de infecciones serias en pacientes lúpicos durante el periodo de estudio.

ABSTRACT Introduction. Lupus patients have an increased risk of developing infections due to the disease, use of immunosuppressants and corticosteroids. Objective. To identify the associated factors for serious infections in lupus patients in a national referral hospital. Retrospective, analytical, case-control study in the Rheumatology Service of the Guillermo Almenara Irigoyen National Hospital, Lima, Peru. Methods. The registry of hospitalized patients in the study period was analyzed, the cases were patients in whom the etiology of the first infection developed their hospitalization. Controls were hospitalized lupus patients without infections in the same study period. Variables predisposing to the development of infections were analyzed. Results. 61 patients out of 390 hospitalized developed infections during their hospitalization. 48 developed 1 only infectious event (in 40 an etiology developed). The cases had higher damage, activity and comorbidity compared to the controls. In the univariate analysis, salary (p = 0.031), use of immunosuppressants upon admission (previous: p = 0.004 and current: p = 0.004), use of glucocorticoids (<30 days: p = 0.015 and> 30-360 days: p = 0.028), activity (p = 0.029) and damage (p = 0.026) produced by the disease and length of hospitalization (p = 0.045), had a statistically significant association. In the multivariate analysis, the days of hospitalization were associated with the development of infections. Conclusions. There is an association between days of hospitalization and the development of serious infections in lupus patients in the study period.

Genome-Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a strong genetic component. We undertook the present work to perform the first genome-wide association study on individuals from the Americas who are enriched for Native American heritage. METHODS: We analyzed 3,710 individuals from the US and 4 countries of Latin America who were diagnosed as having SLE, and healthy controls. Samples were genotyped with HumanOmni1 BeadChip. Data on out-of-study controls genotyped with HumanOmni2.5 were also included. Statistical analyses were performed using SNPtest and SNPGWA. Data were adjusted for genomic control and false discovery rate. Imputation was performed using Impute2 and, for classic HLA alleles, HiBag. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: The IRF5-TNPO3 region showed the strongest association and largest OR for SLE (rs10488631: genomic control-adjusted P [Pgcadj ] = 2.61 × 10(-29), OR 2.12 [95% CI 1.88-2.39]), followed by HLA class II on the DQA2-DQB1 loci (rs9275572: Pgcadj = 1.11 × 10(-16), OR 1.62 [95% CI 1.46-1.80] and rs9271366: Pgcadj = 6.46 × 10(-12), OR 2.06 [95% CI 1.71-2.50]). Other known SLE loci found to be associated in this population were ITGAM, STAT4, TNIP1, NCF2, and IRAK1. We identified a novel locus on 10q24.33 (rs4917385: Pgcadj = 1.39 × 10(-8)) with an expression quantitative trait locus (eQTL) effect (Peqtl = 8.0 × 10(-37) at USMG5/miR1307), and several new suggestive loci. SLE risk loci previously identified in Europeans and Asians were corroborated. Local ancestry estimation showed that the HLA allele risk contribution is of European ancestral origin. Imputation of HLA alleles suggested that autochthonous Native American haplotypes provide protection against development of SLE. CONCLUSION: Our results demonstrate that studying admixed populations provides new insights in the delineation of the genetic architecture that underlies autoimmune and complex diseases.

Riesgo de enfermedad tuberculosa en pacientes con artritis reumatoide / Tuberculosis risk in patients with rheumatoid arthritis

Antecedentes: Los estudios sobre riesgo de enfermedad tuberculosa (ET) en artritis reumatoide (AR) en pacientes no usuarios de terapia biológica son controversiales. Objetivo: Evaluar AR como factor de riesgo independiente para ET. Diseño: Estudio de cohortes no concurrente. Lugar: Red asistencial Hospital Guillermo Almenara Irigoyen, Lima-Perú, hospital docente. Participantes: Pacientes con AR no usuarios de terapia biológica. Intervenciones: Una cohorte de pacientes con AR no usuarios de terapia biológica (cumplimiento de criterios 1987 del ACR) fue pareada por edad y género con una cohorte control (pacientes con trastornos no inmunológicos). Se realizó una entrevista personal. El seguimiento para la cohorte AR se inició en el diagnostico de AR y culminó en el momento de la entrevista o en el diagnóstico de ET (los controles fueron seguidos el mismo periodo de tiempo). Se calculó la densidad de incidencia (DI) para ET en cada cohorte y el riesgo relativo (RR). La probabilidad de ET de acuerdo al tiempo de enfermedad fue comparada mediante curvas de Kaplan Meier. Se aplicó un modelo de Cox para ajustar drogas y patologías predisponentes (hazard ratio -HR). Principales medidas de resultados: Enfermedad tuberculosa en pacientes con artritis reumatoide. Resultados: La cohorte AR y los controles (667 y 664 pacientes, respectivamente) tuvieron 6 940,75 y 6 666,53 personas-año de seguimiento. La edad al diagnóstico...

Background: Studies on tuberculosis (TB) risk in patients with rheumatoid arthritis (RA) non-users of biological therapy show contradictory results. Objetives: To determine RA as independent risk factor for TB. Design: Non concurrent cohort study. Setting: Guillermo Almenara Asistential Net, Lima-Peru, a teaching hospital. Participants: Biological therapy non-users RA patients. Interventions: RA patients fulfilled the ARA 1987 diagnosis criteria and were biological therapy non-users. Control group was paired by age and sex to RA patients. Patients in control groups had non immunological disorders. Clinical information was completed by interviews. RA patients follow-up was started at the time of diagnosis and ended at the time of interview and/or TB diagnosis. Density incidence (DI) was found for each cohort and TB relative risk (RR) was calculated. To evaluate time length to TB evolution a Kaplan Meier curve was graphed and compared both groups with log-rank test. Drugs and predisposing TB pathologies were analyzed. Main outcome measures: Tuberculosis in patients with rheumatoid arthritis. Results: Six hundred and seventy six out of 808 RA patients and 664 controls qualified for inclusion criteriaÆs. RA and control groups reached 6 940,75 and 6 666,53 follow-up patients-year, respectively. RA cohort mean age was 46,65 at RA diagnosis. Only 29,7 per cent of RA patients had a positive tuberculin reaction. Fifteen TB cases were identified in the RA cohort and 8 at the control group, yielding a mean DI of 216,1/100 000 and 122,1/ 100 000 patients-year respectively. TB RR was 1,8 (IC 95 per cent=0,8- 4,2), and after adjusting drugs and co-morbidity the HR was 1,69 (IC 95 per cent =0,26-10,93). Statistically significant difference was not found with Kaplan Meier curves comparison (p=0,19). Conclusions: We did not find a higher risk of rheumatoid arthritis patients to develop tuberculosis.