Predictors of severe hemolytic anemia and its impact on major outcomes in systemic lupus erythematosus: Data from a multiethnic Latin American cohort.

OBJECTIVE: To determine the predictors of the occurrence of severe autoimmune hemolytic anemia (AIHA) and its impact on damage accrual and mortality in SLE patients. METHODS: Factors associated with time to severe AIHA (hemoglobin level ≤7 g/dL) occurring from the onset of SLE symptoms were examined by Cox proportional hazards regressions. The association of severe AIHA with mortality was examined by logistic regression analyses while its impact on damage was by negative binomial regression. RESULTS: Of 1,349 patients, 49 (3.6%) developed severe AIHA over a mean (SD) follow-up time of 5.4 (3.8) years. The median time from the first clinical manifestation to severe AIHA was 111 days (IQR 43-450). By multivariable analysis, male sex (HR 2.26, 95% CI 1.02-4.75, p = 0.044), and higher disease activity at diagnosis (HR 1.04, 95% CI 1.01-1.08, p = 0.025) were associated with a shorter time to severe AIHA occurrence. Of the SLEDAI descriptors, only hematologic (leukopenia and/or thrombocytopenia) showed a certain trend toward significance in the multivariable analysis (HR 2.36, 95% CI 0.91-6.13, p = 0.0772). Severe AIHA contributed neither to damage nor to mortality. CONCLUSIONS: Severe AIHA occurs during the early course of SLE. Male sex and higher disease activity at diagnosis emerged as independent predictors of a shorter time to severe AIHA occurrence. Although not statistically significant, hematological abnormalities at SLE diagnosis could predict the occurrence of severe AIHA in a shorter time. Damage and mortality did not seem to be impacted by the occurrence of severe AIHA.

Predictors of Remission and Low Disease Activity in Rheumatoid Arthritis Patients: Results From the Follow-up of a Real-World Peruvian Cohort.

BACKGROUND: Clinical remission is the goal in rheumatoid arthritis (RA) management; however, this can be difficult to achieve in several parts of the world. Our objective was to determine predictors of remission and remission/low disease activity (LDA) in RA. METHODS: A longitudinal real-setting RA cohort was followed up (January 2016-2020). Predictors examined were sex, age at diagnosis, disease duration, socioeconomic status, tobacco use, rheumatoid factor titer, comorbidities (Charlson index), Simple Disease Activity Index (SDAI) score, disability (Multidimensional Disease Health Assessment Questionnaire), health-related quality of life (Short Form-36 questionnaire), glucocorticoid dose, biological/target synthetic disease-modifying antirheumatic drugs, and conventional DMARD (c-DMARD) use. Univariable and multivariable generalized estimating equation models were done to determine predictors of remission (at a given visit) and sustained remission (2 consecutives visits), using the SDAI definition (0 or <3.3). Similarly, remission/LDA (SDAI <11) predictors were examined. RESULTS: Five hundred thirty RA patients included the following: 160 patients (30.2%) achieved remission in at least 1 visit, and 126 patients (23.77%) achieved sustained remission. On the multivariable analysis glucocorticoid dose (odds ratio [OR], 1.060; 95% confidence interval [CI], 1.027-1.094; p = 0.004) and current (OR, 2.293; 95% CI, 1.811-2.903; p < 0.001) or past (OR, 1.383; 95% CI, 1.127-1.698; p = 0.002) use of c-DMARDs predicted remission/LDA in at least 1 visit, whereas the SDAI (OR, 0.951; 95% CI, 0.942-0.959; p < 0.001), Multidimensional Disease Health Assessment Questionnaire (OR, 0.648; 95% CI, 0.549-0.764; p < 0.001), and age at diagnosis (OR, 0.994; 95% CI, 0.990-0.998; p = 0.004) were negative predictors. As to sustained remission/LDA, current (OR, 2.012; 95% CI, 1.458-2.776: p < 0.001) or past (OR, 1.517; 95% CI, 1.155-1.993; p = 0.003) use of c-DMARDs, having a better Short Form-36 questionnaire physical component summary (OR, 1.022; 95% CI, 1.014-1.029; p < 0.001), and older age at diagnosis (OR, 1.013; 95% CI, 1.003-1.022; p = 0.008) predicted it, whereas SDAI (OR, 0.949; 95% CI, 0.933-0.965; p < 0.001) and medium low/low socioeconomic status (OR, 0.674; 95% CI, 0.500-0.909; p = 0.010) were negative predictors. CONCLUSION: During follow-up of this real-world RA cohort, c-DMARD use predicted remission and remission/LDA. In contrast, disease activity was a negative predictor.

Metabolic syndrome predicts new damage in systemic lupus erythematosus patients: Data from the Almenara Lupus Cohort.

OBJECTIVES: This study aims to determine whether the MetS predicts damage accrual in SLE patients. METHODS: This longitudinal study was conducted in a cohort of consecutive SLE patients seen since 2012 at one single Peruvian institution. Patients had a baseline visit and then follow-up visits every 6 months. Patients with ≥ 2 visits were included. Evaluations included interview, medical records review, physical examination, and laboratory tests. Damage accrual was ascertained with the SLICC/ACR damage index (SDI) and disease activity with the SLEDAI-2K. Univariable and multivariable Cox-regression survival models were carried out to determine the risk of developing new damage. The multivariable model was adjusted for age at diagnosis; disease duration; socioeconomic status; SLEDAI; baseline SDI; the Charlson Comorbidity Index; daily dose; and time of exposure of prednisone (PDN), antimalarials, and immunosuppressive drugs. RESULTS: Two hundred and forty-nine patients were evaluated; 232 of them were women (93.2%). Their mean (SD) age at diagnosis was 35.8 (13.1) years; nearly all patients were Mestizo. Disease duration was 7.4 (6.6) years. The SLEDAI-2K was 5.2 (4.3) and the SDI, 0.9 (1.3). One hundred and eight patients (43.4%) had MetS at baseline. During follow-up, 116 (46.6%) patients accrued at least one new point in the SDI damage index. In multivariable analyses, the presence of MetS was a predictor of the development of new damage (HR: 1.54 (1.05-2.26); p < 0.029). CONCLUSIONS: The presence of MetS predicts the development of new damage in SLE patients, despite other well-known risk factors for such occurrence.

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.

Performance of the 2017 American College of Rheumatology/European League Against Rheumatism Provisional Classification Criteria for Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in a Peruvian Tertiary Care Center.

AIM: To validate the new classification criteria for antineutrophil cytoplasmic antibody-associated vasculitis in a real-life Peruvian cohort of antineutrophil cytoplasmic antibody-associated vasculitis patients. METHODS: We reviewed medical records from a Peruvian tertiary care center from January 1990 to December 2019. Antineutrophil cytoplasmic antibody-associated vasculitis was diagnosed based on the 1990 American College of Rheumatology (ACR) criteria, the 2012 Chapel Hill Consensus Conference definitions, the European Medicines Agency (EMEA) algorithm, and the clinical acumen of the treating rheumatologists. We classified all patients using the "former criteria" (the 1990 ACR criteria for granulomatosis with polyangiitis [GPA] and eosinophilic GPA [EGPA] and the 1994 Chapel Hill Consensus Conference definition for microscopic polyangiitis [MPA]), the EMEA algorithm, and the "new criteria" (the 2017 ACR/European League Against Rheumatism Provisional Criteria). The level of agreement (using Cohen κ) was calculated using the clinical diagnosis as the criterion standard. RESULTS: We identified 212 patients, 12 of whom were excluded. One hundred fifty-four (77%) had MPA, 41 (20.5%) GPA, and 5 (2.5%) EGPA. The new criteria performed well for MPA (κ = 0.713) and EGPA (κ = 0.659), whereas the EMEA algorithm performed well for GPA (κ = 0.938). In the overall population, the new criteria showed better agreement (κ = 0.653) than the EMEA algorithm (κ = 0.506) and the former criteria (κ = 0.305). CONCLUSIONS: The 2017 ACR/European League Against Rheumatism Provisional Criteria showed better agreement for the clinical diagnosis of all the patients overall and had the best performance for MPA and EGPA. The EMEA algorithm had the best performance for GPA.

Guía de práctica clínica para el diagnóstico y manejo inicial de artritis reumatoide en el Seguro Social del Perú (EsSalud) / Clinical Practice Guideline for the diagnosis and initial management of Rheumatoid Arthritis in the Social Security of Peru (EsSalud)

La Artritis Reumatoide (AR) tiene adversas consecuencias en la salud su diagnóstico temprano y manejo óptimo requiere recomendaciones basadas en evidencia de alta calidad adaptadas a cada sistema de salud. Objetivo: Proveer recomendaciones clínicas basadas en evidencia para el diagnóstico y manejo inicial de la AR. Material y Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos. El GEG formuló 10 preguntas clínicas a ser respondidas por la presente GPC. Se realizaron búsquedas sistemáticas de la evidencia publicada en PubMed y CENTRAL entre diciembre 2017 a julio 2019 (revisiones sistemáticas y ­cuando fue considerado pertinente­ estudios primarios). Se seleccionó la evidencia de mayor calidad para responder cada una de las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE) y en reuniones de trabajo periódicas, el GEG usó dicha metodología para revisar la evidencia y formular las recomendaciones, los puntos de buena práctica clínica y los flujogramas. Finalmente, la GPC fue aprobada con Resolución N° 132 ­ IETSI ­ ESSALUD ­ 2019. Resultados: La presente GPC abordó 10 preguntas clínicas, divididas en dos temas: diagnóstico y manejo. En base a dichas preguntas se formularon 16 recomendaciones (5 fuertes y 11 condicionales), 45 puntos de buena práctica clínica, y 3 flujogramas. Conclusión: El presente artículo resume la metodología y las conclusiones basadas en evidencias de la GPC para el diagnóstico y manejo inicial de la AR en EsSalud.

Rheumatoid arthritis (RA) has adverse health consequences its early diagnosis and optimal management requires high quality evidence-based recommendations tailored to each health system. Objective: To provide evidence-based clinical recommendations for the diagnosis and initial management of RA. Material and Methods: A guideline development group (GDG) was formed that included medical specialists and methodologists. The GEG formulated 10 clinical questions to be answered by this CPG. Systematic searches of the evidence published in PubMed and CENTRAL were performed between December 2017 and July 2019 (systematic reviews and -when considered relevant- primary studies). The highest quality evidence was selected to answer each of the clinical questions posed. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, and in periodic working meetings, the GEG used this methodology to review the evidence and formulate the recommendations, good clinical practice points, and flowcharts. Finally, the CPG was approved by Resolution No. 132 - IETSI - ESSALUD - 2019. Results: This CPG addressed 10 clinical questions, divided into two topics: diagnosis and management. Based on these questions, 16 recommendations (5 strong and 11 conditional), 45 points of good clinical practice, and 3 flowcharts were formulated. Conclusion: This article summarizes the methodology and evidence-based conclusions of the CPG for the diagnosis and initial management of RA in EsSalud.

Health-Related Quality of Life and fatigue are associated with a higher work productivity impairment in systemic lupus erythematosus patients: Data from the Almenara Lupus Cohort.

Objectives: This study aims to determine the factors associated with absenteeism, presenteeism, and overall work impairment in patients with systemic lupus erythematosus (SLE).Methods: A total of 133 consecutive working patients with SLE were assessed between October 2017 and December 2018, using a standardized data collection form. Sociodemographic, disease, and work-related variables were collected. Work productivity and activity impairment (WPAI) was assessed with the respective questionnaire; absenteeism and presenteeism due to overall health and symptoms during the past 7 days were scored. Linear regression models were performed to determine the factors associated with absenteeism, presenteeism, and overall work impairment. Potential factors included were age at diagnosis, gender, socioeconomic status, educational level, SLEDAI, SLICC/ACR damage index (SDI), FACIT-Fatigue, and the domains of the LupusQoLResults: The mean age at diagnosis was 32.2 years (11.8); 121 (91.7%) were female. Nearly all patients were Mestizo. The mean percent of time for absenteeism was 5.0 (12.9), it was 28.5 (26.4) for presenteeism, and it was 31.3 (27.2) for overall work impairment. In the multiple regression analysis, factors associated with absenteeism were disease duration (B = -0.34; SE = 0.12; p = 0.007), pain (B = -0.14; SE = 0.06; p = 0.046), intimate relationship (B = -0.07; SE = 0.03; p = 0.046), and emotional health (B = 0.16; SE = 0.06; p = 0.006); factors associated with presenteeism were physical health (B = -0.43; SE = 0.14; p = 0.002) and FACIT (B = -0.87; SE = 0.30; p = 0.005); and factors associated with overall work impairment were pain (B = -0.40; SE = 0.11; p = 0.001) and FACIT-Fatigue (B = -0.74; SE = 0.28; p = 0.010).Conclusion: A poor HRQoL and higher levels of fatigue were associated with a higher percentage of absenteeism, presenteeism, and overall work impairment in SLE patients.

Survival in ANCA-Associated Vasculitides in a Peruvian Center: 28 Years of Experience.

AIM: The aim of this study was to identify demographic and clinical risk factors for mortality in patients with antineutrophil cytoplasmic antibodies-associated vasculitides (AAVs) in a Peruvian tertiary referral hospital. METHODS: Medical records of patients with AAV according to classification criteria or diagnosed by an experienced rheumatologist, covering the period between January 1990 and December 2018, were reviewed. Granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited vasculitis were included. Potential predictors of mortality were demographic factors, clinical manifestations, antineutrophil cytoplasmic antibodies status, diagnosis, disease categorization, the 2009 Five Factor Score (FFS), and treatment. Cox regression models were used to determine the risk factors for mortality. Univariable and multivariable analyses using a backward selection method were performed. RESULTS: One hundred ninety-six patients were included; female-to-male ratio was 2:1. The median (interquartile range) age at diagnosis and follow-up were 60.0 (51.0-68.0) and 4.8 (1.3-11.6) years, respectively. One hundred forty-eight patients (75.5%) had microscopic polyangiitis, 37 (18.9%) granulomatosis with polyangiitis, 5 (2.6%) eosinophilic granulomatosis with polyangiitis, and 6 (3.0%) renal-limited vasculitis. Overall survival rates at 1, 5, and 10 years were 83.4%, 68.2%, and 51.7%, respectively. Ocular involvement was protective (hazards ratio [HR], 0.36; 95% confidence interval [CI], 0.17-0.74; p = 0.006), whereas renal (HR, 2.09; 95% CI, 1.33-3.28; p = 0.001) and lung involvement (HR, 2.07; 95% CI, 1.31-3.28; p = 0.002) and the 2009 FFSs were predictive of mortality (2009 FFS = 1: HR, 2.46; 95% CI, 1.50-4.04; p < 0.001; 2009 FFS = 2: HR, 3.07; 95% CI, 1.54-6.10; p = 0.001; 2009 FFS = 3: HR, 13.29; 95% CI, 3.69-47.88; p < 0.001). CONCLUSIONS: Ocular involvement was protective, whereas 2009 FFS ≥ 1 and renal and lung involvement were predictive factors of mortality in Peruvian AAV patients.

Demographic and Clinical Features of ANCA-Associated Vasculitides in a Peruvian Tertiary Center.

AIM: The aim of this study was to identify the demographic and clinical features of patients with ANCA-associated vasculitides (AAVs) in a Peruvian tertiary referral hospital. METHODS: Medical records of patients with AAV according to classification criteria or diagnosed by an experienced rheumatologist, and covering the period between January 1990 and December 2019, were reviewed. Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and renal-limited vasculitis (RLV) were included. Demographic factors (age at diagnosis, sex), disease duration, clinical manifestations (per organ involvement), creatinine level at diagnosis (milligram per deciliter), ANCA status, diagnosis, 2009 Five Factor Score, disease categorization, and treatment were recorded. RESULTS: Two hundred twelve patients were included. Their female-to-male ratio was 1.9:1 (139 [65.6%]/73 [34.4%]), and their mean (SD) age at diagnosis was 59.2 (12.5) years. One hundred fifty-eight patients (74.5%) had MPA, 42 (19.8%) GPA, 7 (3.3%) RLV, and 5 (2.4%) EGPA. Neurological, lung, and renal involvements were the most frequently affected systems. Myeloperoxidase preferentially occurred in MPA (82.5%), whereas proteinase 3 did occur in GPA (79.5%). Microscopic polyangiitis patients were older (61.1 [11.5] years). Female sex predominated in MPA and RLV (2.4:1 and 6:1, respectively), but the opposite was the case for EGPA (1:4). Ear-nose-throat and ocular involvement were more frequent in GPA (both p's < 0.001), and neurological and cardiovascular involvement were more frequent in EGPA (p < 0.001 and p = 0.002, respectively). CONCLUSIONS: This is one of the largest series of AAV patients in Latin America. Overall, female sex predominated. Microscopic polyangiitis was the most frequent AAV, and myeloperoxidase-ANCA was the most frequent antibody in Peruvian AAV population.

Clinical features, damage accrual, and survival in patients with familial systemic lupus erythematosus: data from a multi-ethnic, multinational Latin American lupus cohort.

OBJECTIVES: This study aimed to compare the clinical features, damage accrual, and survival of patients with familial and sporadic systemic lupus erythematosus (SLE). METHODS: A multi-ethnic, multinational Latin American SLE cohort was studied. Familial lupus was defined as patients with a first-degree SLE relative; these relatives were interviewed in person or by telephone. Clinical variables, disease activity, damage, and mortality were compared. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. Hazard ratios (HR) were calculated using Cox proportional hazard adjusted for potential confounders for time to damage and mortality. RESULTS: A total of 66 (5.6%) patients had familial lupus, and 1110 (94.4%) had sporadic lupus. Both groups were predominantly female, of comparable age, and of similar ethnic distribution. Discoid lupus (OR = 1.97; 95% CI 1.08-3.60) and neurologic disorder (OR = 1.65; 95% CI 1.00-2.73) were significantly associated with familial SLE; pericarditis was negatively associated (OR = 0.35; 95% CI 0.14-0.87). The SLE Disease Activity Index and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) were similar in both groups, although the neuropsychiatric (45.4% vs. 33.5%; p = 0.04) and musculoskeletal (6.1% vs. 1.9%; p = 0.02) domains of the SDI were more frequent in familial lupus. They were not retained in the Cox models (by domains). Familial lupus was not significantly associated with damage accrual (HR = 0.69; 95% CI 0.30-1.55) or mortality (HR = 1.23; 95% CI 0.26-4.81). CONCLUSION: Familial SLE is not characterized by a more severe form of disease than sporadic lupus. We also observed that familial SLE has a higher frequency of discoid lupus and neurologic manifestations and a lower frequency of pericarditis.

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.

Correction to: Homocysteine levels are independently associated with damage accrual in systemic lupus erythematosus patients from a Latin-American cohort.

The affiliations of Manuel F. Ugarte-Gil, one of the author of the above article has a discrepancy between the online version of the publisher's internet portal ( Springerlink.com ) and the online pdf version.

Homocysteine levels are independently associated with damage accrual in systemic lupus erythematosus patients from a Latin-American cohort.

OBJECTIVE: To determine the impact of homocysteine levels on damage accrual in systemic lupus erythematosus (SLE) patients. METHODS: This longitudinal study was conducted in consecutive patients seen every 6 months at our Rheumatology Department since 2012. Patients with available homocysteine levels and who had at least one subsequent visit were included. Univariable and multivariable Cox regression models were done to determine if homocysteine levels were predictive of damage accrual as per the SLICC Damage Index (SDI). The multivariable model was adjusted for pertinent variables (age at diagnosis, gender, socioeconomic status, disease duration, disease activity (SLEDAI), Framingham score, antimalarial and immunosuppressive drug use, average daily dose, and exposure time to prednisone (PDN)). RESULTS: One hundred forty-five patients were included; their mean (SD) age at diagnosis was 43.70 (12.09) years, 136 (93.8%) were female, and nearly all were Mestizo. At baseline, disease duration was 7.55 (6.73) years; patients were followed for 3.54 (1.27) years. The SLEDAI was 5.60 (4.34), and the SDI 0.97 (1.35). The average daily PDN dose was 7.30 (5.78) mg/day and the time of PDN exposure was 7.36 (6.73) years. Mean homocysteine levels were 10.07 (3.71) µmol/L. The highest tertile of homocysteine levels predicted new damage accrual in the univariable and multivariable models [HR 1.78 (95% CI, 1.042-3.039); p = 0.035 and HR 2.045 (95% CI, 1.077-3.883); p = 0.029, respectively]. Increased levels (> 15 µmol/L) were found in 12 (8.3%) patients; 75 (51.7%) patients increased ≥ 1 SDI point. CONCLUSION: In SLE patients, homocysteine levels predicted damage accrual independently of other well-known risk factors for such occurrence.

Efecto de los antimaláricos sobre los diferentes dominios del índice de daño SLICC en pacientes de la cohorte GLADEL / Effect of antimalarials on the different domains of the SLICC damage index in patients of the GLADEL cohort

Objetivos: Estimar el efecto de los antimaláricos (AM) sobre los diferentes dominios del índice de daño SLICC (SDI). Métodos: Se estudiaron pacientes con diagnóstico clínico reciente (≤2 años) de lupus eritematoso sistémico (LES) de la cohorte GLADEL. Variable de estudio: aumento en los dominios del SDI desde el ingreso a la cohorte. Variables independientes: características sociodemográficas, clínicas, laboratorio y tratamientos. El efecto de los AM, como variable dependiente del tiempo, sobre los dominios más frecuentes del SDI (ajustado por factores de confusión) fue examinado con un modelo de regresión de Cox multivariado. Resultados: De 1466 pacientes estudiados, 1049 (72%) recibieron AM con un tiempo medio de exposición de 30 meses (Q1-Q3: 11-57) y 665 pacientes (45%) presentaron daño durante un seguimiento medio de 24 meses (Q1-Q3: 8-55); 301 eventos fueron cutáneos, 208 renales, 149 neuropsiquiátricos, 98 musculoesqueléticos, 88 cardiovasculares y 230 otros. Después de ajustar por factores de confusión, el uso de AM se asoció a un menor riesgo de daño renal (HR 0,652; IC 95%: 0,472-0,901) y en el límite de la significancia estadística (HR 0,701, IC 95%: 0,481-1,024) para el dominio neuropsiquiátrico. Conclusión: En GLADEL, el uso de AM se asoció independientemente a un menor riesgo de daño acumulado renal.

Objective: To assess the effects of antimalarials (AM) over the items of the SLICC Damage Index (SDI). Methods: Patients with recent (≤2 years) diagnosis of systemic lupus erythematosus (SLE) from the GLADEL cohort were studied. End-point: increase in items SDI since cohort entry. Independent variables (socio-demographic, clinical, laboratory and treatment) were included. The effect of AM as a time dependent variable on most frequent SDI items (adjusting for potential confounders) was examined with a multivariable Cox regression model. Results: Of the 1466 patients included in this analysis, 1049 (72%) received AM with a median exposure time of 30 months (Q1-Q3: 11-57). Damage occurred in 665 (45%) patients during a median follow-up time of 24 months (Q1-Q3: 8-55). There were 301 integument, 208 renal, 149 neuropsychiatric, 98 musculoskeletal, 88 cardiovascular and 230 others less frequently represented damages. After adjusting for potential confounders at any time during follow-up, a lower risk of renal damage (HR 0.652; 95% CI: 0.472-0.901) and borderline for neuropsychiatric damage (HR 0.701, 95% CI: 0.481-1.024) was found. Conclusion: In the GLADEL cohort, after adjustment for possible confounding factors, AM were independently associated with a reduced risk of renal damage accrual.

Peripheral CD4+CD28null T-cells as predictors of damage in systemic lupus erythematosus patients.

OBJECTIVES: To determine whether the CD4+CD28null T-cells subpopulation predicts the occurrence of damage in SLE. METHODS: This longitudinal study was conducted in consecutive SLE patients seen every six months in our Rheumatology Department since 2012. Patients in whom CD4+CD28null T-cells had been measured and who had at least one subsequent visit were included in the study. Survival analyses (univariable and multivariable Cox-regression models) were performed to determine the risk of overall and domain damage (as per the SLICC Damage Index - SDI) as a function of the frequency of this T-cell subpopulation. The multivariable model was adjusted for pertinent confounders. All analyses were performed using SPSS 21.0. RESULTS: One hundred and nineteen patients were evaluated; their mean (SD) age was 43.5 (11.9) years, 113 (95.0%) were female. Disease duration was 7.8 (7.0) years, the SLEDAI 5.3 (4.1) and the SDI 1.0 (1.4). The percentage of CD4+CD28null T-cells was 17.4 (14.0). The mean follow-up was 2.1 (0.8) years, and the mean number of visits per patient 3.5 (1.1). Forty-six (38.7%) patients increase at least one SDI point. In the univariable and multivariable analyses, the percentage of CD4+CD28null predicted the occurrence of lung damage [HR: 1.042 (CI95%: 1.001-1.085); p=0.047 and HR: 1.099 (CI95%1.020-1.184); p=0.013, respectively] but neither the total SDI score nor all other SDI domain scores were predicted by the percentage of CD4+CD28null cells. CONCLUSIONS: In SLE patients, CD4+CD28null T-cells predict the occurrence of new lung damage, independently of other risk factors but not of overall damage or damage on other domains.

Serum uric acid levels contribute to new renal damage in systemic lupus erythematosus patients.

This study aims to determine whether uric acid levels contribute to new renal damage in systemic lupus erythematosus (SLE) patients. This prospective study was conducted in consecutive patients seen since 2012. Patients had a baseline visit and follow-up visits every 6 months. Patients with ≥2 visits were included; those with end-stage renal disease (regardless of dialysis or transplantation) were excluded. Renal damage was ascertained using the SLICC/ACR damage index (SDI). Univariable and multivariable Cox-regression models were performed to determine the risk of new renal damage. Uric acid was included as a continuous and dichotomous (per receiving operating characteristic curve) variable. Multivariable models were adjusted for age at diagnosis, disease duration, socioeconomic status, SLEDAI, SDI, serum creatinine, baseline use of prednisone, antimalarials, and immunosuppressive drugs. One hundred and eighty-six patients were evaluated; their mean (SD) age at diagnosis was 36.8 (13.7) years; nearly all patients were mestizo. Disease duration was 7.7 (6.8) years. Follow-up time was 2.3 (1.1) years. The SLEDAI was 5.2 (4.3) and the SDI 0.8 (1.1). Uric acid levels were 4.5 (1.3) mg/dl. During follow-up, 16 (8.6%) patients developed at least one new point in the renal domain of the SDI. In multivariable analyses, uric acid levels (continuous and dichotomous) at baseline predicted the development of new renal damage (HR 3.21 (1.39-7.42), p 0.006; HR 18.28 (2.80-119.48), p 0.002; respectively). Higher uric acid levels contribute to the development of new renal damage in SLE patients independent of other well-known risk factors for such occurrence.

Features associated with hematologic abnormalities and their impact in patients with systemic lupus erythematosus: Data from a multiethnic Latin American cohort.

OBJECTIVE: To examine hematological manifestations' correlates and their impact on damage accrual and mortality in SLE patients from the multiethnic, Latin American, GLADEL cohort. METHODS: In patients with recent SLE diagnosis (≤2 years), the association between follow-up hematological manifestations (per ACR criteria) and socio-demographic and clinical variables was examined by univariable and multivariable logistic regressions; their impact on damage accrual and mortality was examined by Poisson and Cox proportional-hazards regression analyses, respectively. RESULTS: Of 1437 patients, 948 (66.0%) developed ≥1 hematological manifestation [5.5% hemolytic anemia (AHA), 16.3% thrombocytopenia, and 56.4% lymphopenia] over 4.3 (3.3) follow-up years. Younger age, Mestizo ethnicity, hematologic disorder (at/or before SLE diagnosis), and first damage recorded were associated with hematological manifestations while antimalarials were negatively associated. AHA (at/or before SLE diagnosis), anti-Sm, and anti-RNP antibodies were associated with subsequent AHA occurrence while musculoskeletal involvement was negatively associated. Thrombocytopenia (at/or before SLE diagnosis), AHA, anti-phospholipid antibodies (aPLs), anti-SSA/Ro, anti-SSB/La antibodies, and first damage recorded were associated with later thrombocytopenia occurrence. Lymphopenia (at/or before SLE diagnosis), younger age at diagnosis, Mestizo ethnicity, having medical insurance, and first damage recorded were associated with subsequent lymphopenia occurrence while antimalarials and azathioprine treatment were negatively associated. AHA was associated with damage accrual and mortality after adjusting for variables known to affect these outcomes. CONCLUSIONS: Mestizo ethnicity and early hematological manifestations are risk factors for their subsequent occurrence while antimalarials have a protective effect. The associations between AHA and aPLs and thrombocytopenia were corroborated. AHA contributes independently to damage accrual and diminished survival.

Garre's sclerosing osteomyelitis caused by salmonella group D in a patient with systemic lupus erythematosus: an unusual complication.

We report the case of a 35-year-old male, who was diagnosed with systemic lupus erythematosus (SLE) in 2010 based on the presence of articular, serous, renal, immune, and hematologic involvement. He also had secondary antiphospholipid syndrome (APS). He was treated with prednisone 10 mg per day, hydroxychloroquine 200 mg per day, methotrexate 12.5 mg per week, leflunomide 20 mg per day, and oral anticoagulation previous to the present event. He presented to emergency room with a 7 day disease duration characterized by pain in the left thigh, which increased with physical activity, resulting in claudication; he also had malaise and fever. The X-ray films showed periostitis of the lower half of the left femur with bone marrow narrowing; the scintigraphy showed marked increased uptake in the middle and distal thirds of the left femur, and magnetic resonance imaging (MRI) showed thickening and hyperintensity of the cortex of the diaphysis and distal epiphysis of the femur and endosteal irregularity. Empirical treatment was started with vancomycin for 3 weeks. Femur biopsy and cultures were performed, isolating Salmonella spp. group "D" Vi (-); treatment with cotrimoxazole and ceftazidime for 4 weeks followed by doxycycline and cotrimoxazole for 4 months were given with a favorable functional outcome. This is an unusual case of a young adult with Garre's sclerosing osteomyelitis associated to SLE and caused by salmonella. The literature is reviewed and the clinical conditions predisposing to this infection are discussed, particularly in patients with SLE.

Circulating naive and memory CD4+ T cells and metabolic syndrome in patients with systemic lupus erythematosus: data from a primarily Mestizo population.

OBJECTIVE: The aim of this study was to determine whether the proportions of naive and memory CD4(+) T cell are independently associated with the metabolic syndrome (MetS) in patients with SLE. METHODS: This cross-sectional study was conducted in SLE patients seen at our rheumatology department between September 2013 and April 2014. CD4(+) T cell subpopulations were examined by flow cytometry. The association of MetS and CD4(+) T cell subpopulations was examined by Mann-Whitney U-test and by multivariable analysis, adjusting for all possible confounding variables. RESULTS: One hundred and seventeen patients were evaluated. Their mean age was 44.6 years (S.D. 12.6), 109 (93.2%) were female and all patients were Mestizo (mixed Caucasian and Amerindian ancestry). Fifty-two patients (44.4%) presented with MetS. Disease duration was 7.6 years (S.D. 6.8). The percentage of naive CD4(+) T cells was 25.0 (S.D. 12.7) and memory CD4(+) T cells was 66.7 (S.D. 13.2) and the memory:naive CD4(+) T cell ratio was 4.3 (S.D. 5.6). In multivariable analysis, the percentage of naive CD4(+) T cells was negatively associated with the presence of MetS [odds ratio (OR) 0.959 (95% CI 0.923, 0.997), P = 0.033], whereas the percentage of memory CD4(+)T cells and the memory:naive CD4(+) T cell ratio were positively associated with its presence [OR 1.040 (95% CI 1.003, 1.078), P = 0.031 and OR 1.238 (95% CI 1.041, 1.472), P = 0.016, respectively]. CONCLUSION: In the SLE patients studied, a lower percentage of naive CD4(+) T cells, a higher percentage of memory CD4(+) T cells and the memory:naive CD4(+) T cell ratio were independently associated with the presence of MetS. This association could reflect the impact of immunosenescence among SLE patients with cardiovascular morbidity.