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Objective To estimate the prevalence of premature ovarian failure (POF) and its associated factors in patients with systemic lupus erythematosus (SLE). Methods Cross-sectional study including consecutive SLE women <60 years of age attending a rheumatology clinic. A face-to-face interview was undertaken to obtain demographic, gynaecological and lupus characteristics. Additional rheumatologic and endocrine data were retrieved from patients’ medical records. POF prevalence was estimated in the study sample and in a subgroup of patients aged <40 years at interview. Associations between POF and selected variables were assessed by logistic regression analyses. Results A total of 961 patients were analysed. Prevalence of POF, secondary amenorrhea of known cause, menopause and hysterectomy were 5.4%, 0.8%, 7.8% and 4.4%, respectively. In 674 (70%) patients who had not been exposed to cyclophosphamide (CYC) the prevalence of POF was 0.6%. Disease activity over time (OR 1.4 (CI 95% 1.0–1.8, p < 0.05)) and CYC treatment (OR 5.9 (CI 95% 1.8–18.8, p < 0.01)) were associated with higher prevalence. Association between POF and endocrine autoimmune diseases was not found. Conclusions In the absence of CYC treatment, the prevalence of POF in lupus patients is consistent with that reported in the general population. The existence of autoimmune processes at the ovary seems unlikely in most lupus patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the progression of coronary artery calcification (CAC) and associated risk factors in a systemic lupus erythematosus (SLE) cohort., Methods: We reassessed the presence of CAC in patients with SLE who were screened 9 years before, using multidetector computed tomography. Clinical variables (cumulated disease activity and damage accrual), antiphospholipid syndrome and SLE serology, and cardiovascular (CV) risk factors (hypertension, BMI [kg/m 2 ], modified Framingham risk score, lipid profile, menopausal status) were assessed longitudinally., Results: We included 104 patients from the parent study. Most of them were women (94.2%), with a mean age of 41.0 (SD 8.3) years and mean disease duration of 14.8 (SD 2.9) years. We documented CAC in 17 patients (16.3%). Seven cases were from the parent study and 10 were incident cases. The cumulative incidence of CAC was 9% and the incidence density was 1 per 100 person-years. CAC occurred more frequently in the age groups 30-39 years and 40-44 years. All patients with previous CAC had worsening of their calcium indexes, and none developed clinical CV events. When comparing prevalent CAC cases (n = 17) vs patients without calcification (n = 87), both groups were similar in traditional CV risk factors, disease duration, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) area under the curve (AUC), and Systemic Lupus International Collaborating Clinics (SLICC) score, but were more likely to be postmenopausal and have higher apolipoprotein B (apoB) levels. Patients with previous CAC had higher apoB levels, SLEDAI-2K AUC scores, and anticardiolipin IgG antibodies than incident cases., Conclusion: CAC in patients with SLE progressed over time but was not associated with adverse CV events during the first 9 years of follow-up. ApoB levels and postmenopausal status might be associated with this progression., (Copyright © 2024 by the Journal of Rheumatology.)

TNFAIP3 is a classical systemic lupus erythematosus (SLE)-associated risk locus identified by genome-wide association studies (GWASs) and replicated by candidate gene association studies primarily in Caucasians and Asians. However, in Latin American populations, its role on SLE susceptibility is not known. We conducted a case-control study to evaluate whether the TNFAIP3 rs2230926T/G (Phe127Cys) variant is associated with risk of developing SLE in a cohort of Mexican patients. The TNFAIP3 rs2230926T/G variant was analyzed in 561 patients with SLE and 499 control subjects, using TaqMan probes. We found that the G allele was associated with susceptibility to SLE under the allelic (OR 2.09, p = 0.005) and genotypic (OR 2.14, p = 0.004) models. In conclusion, our results show that TNFAIP3 rs2230926T/G is a risk factor for the development of SLE in the Mexican population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Objective: Variants in STAT4 are associated with systemic lupus erythematosus (SLE) and other autoimmune diseases. We undertook this study to investigate how disease-associated variants affect STAT4 expression, in particular in CD4+ T cells where STAT4 plays an essential role., Methods: We compared Th1 differentiation between naive CD4+ T cells from healthy donors homozygous for the risk (R/R) or nonrisk (NR/NR) alleles. We analyzed epigenetic marks in STAT4 and evaluated the relevance of its third intron, assessed the consequences of Stat4 overexpression in vivo in mice, and analyzed the effects of the STAT4 genotype in patients with lupus nephritis., Results: Naive CD4+ T cells from NR/NR healthy donors down-regulated STAT4 in response to interleukin-12 (IL-12). In contrast, cells from R/R healthy donors maintained high levels. R/R cells exhibited a higher abundance of transcriptionally active STAT4 and increased interferon-γ production. Accordingly, R/R healthy donors exhibited a stronger induction of local active enhancer marks. Genetic editing confirmed the presence of a negative regulatory region in the STAT4 third intron, where most of the SLE-associated STAT4 single-nucleotide polymorphisms (SNPs) are located. In vivo forced expression demonstrated that increases in Stat4 levels in T cells enhanced glomerulonephritis in mice. Accordingly, the R/R genotype was associated with suboptimal response to treatment and with worse clinical outcomes in patients with proliferative lupus nephritis., Conclusion: The SLE-associated STAT4 haplotype correlates with an abnormal IL-12-mediated STAT4 transcriptional regulation. Carriers of the risk variant exhibit exaggerated CD4+ proinflammatory capacities that, in the context of SLE, contribute to more severe disease. R/R patients may benefit from blockade of the IL-12/STAT4 pathway., (© 2022 American College of Rheumatology.)

Background: Repeated renal flares in lupus nephritis (LN) have been associated with worse long-term kidney function. This study aimed to assess the impact of repeated LN flares in response to therapy, kidney and patient prognosis., Methods: All patients from a biopsy-proven LN cohort between 2008 and 2018 were segregated into three groups according to the number of LN flares when they entered our cohort: first LN flare, second LN flare or third LN flare. The following outcomes were evaluated by unadjusted and adjusted time-to-event analyses: complete and partial response, disease relapses, progression to decline of 30% of the estimated glomerular filtration rate (eGFR), doubling of serum creatinine, end-stage kidney disease and patient survival., Results: A total of 441 patients were included: 257 (58%) in their first LN flare, 102 (23%) in their second LN flare and 82 (19%) in their third LN flare. There were significant differences in LN flare presentation in age, eGFR, serum albumin, pyuria and hematuria among groups. The National Institutes of Health chronicity indices and the percentage of patients with vascular lesions were higher in groups at progressive LN flares. In the adjusted analyses, complete and partial response rates decreased, as well as kidney and patient survival, at a progressive number of LN flares. No differences in the dynamic course of all surveillance laboratory parameters were observed in the first year after initial therapy among LN flare groups., Conclusions: A progressive number of LN flares is associated with a lower response to therapy and an adverse prognosis for kidney function and patient survival., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Introduction: Kidney survival rates in lupus nephritis (LN) remain suboptimal, with 10-20% of patients progressing to end-stage kidney disease by 10-20 years. Recently, the landscape of LN management has changed with the advent of new molecules that have demonstrated safety and efficacy in clinical trials., Areas Covered: In this review, we approach the current state of LN management, the unmet therapeutic needs, and deep dive into voclosporin, a novel calcineurin inhibitor (CNI) that has demonstrated improved efficacy when added to a mycophenolate mofetil (MMF) and glucocorticoid regimen, without an increase in adverse events. We focus on the characteristics of this new CNI and the studies that led to its approval by the US FDA., Expert Opinion: Voclosporin adds to therapeutic options for LN. This drug offers potential advantages over other CNIs. The addition of voclosporin to a standard-of-care regimen of MMF/glucocorticoids demonstrated higher and faster response rates. As other regimens, a combination of CNI, MMF, and glucocorticoids must be individualized and is not appropriate for all patients. Some questions remain to be answered for this regimen, such as the length of treatment, the tapering schedule, and its long-term safety and efficacy for preserving kidney function.

Systemic lupus erythematosus (SLE) is a heterogeneous disease with unpredictable patterns of activity. Patients with similar activity levels may have different prognosis and molecular abnormalities. In this study, we aimed to measure the main differences in drug-induced gene expression signatures across SLE patients and to evaluate the potential for clinical data to build a machine learning classifier able to predict the SLE subset for individual patients. SLE transcriptomic data from two cohorts were compared with drug-induced gene signatures from the CLUE database to compute a connectivity score that reflects the capability of a drug to revert the patient signatures. Patient stratification based on drug connectivity scores revealed robust clusters of SLE patients identical to the clusters previously obtained through longitudinal gene expression data, implying that differential treatment depends on the cluster to which patients belongs. The best drug candidates found, mTOR inhibitors or those reducing oxidative stress, showed stronger cluster specificity. We report that drug patterns for reverting disease gene expression follow the cell-specificity of the disease clusters. We used 2 cohorts to train and test a logistic regression model that we employed to classify patients from 3 independent cohorts into the SLE subsets and provide a clinically useful model to predict subset assignment and drug efficacy.

We compared the chemokine/receptor expression in skin biopsies of discoid (SLE/DLE) and subacute lupus (SLE/SCLE) and correlated it with tissue and circulating effector CD4 T cells/regulatory cells. Skin biopsies and peripheral blood from 9 active SLE/DLE patients, 9 SLE/SCLE patients, 5 control SLE patients without cutaneous lesions and 10 control healthy donors were included. Clinical skin activity was measured by Cutaneous Lupus Erythematosus Disease Area and Severity Index scoring, and systemic activity was measured by a modified SLEDAI-2K excluding the cutaneous items. Pain and pruritus were evaluated by a 10-point visual analogue scale. To determine the frequencies of CXCL-10/CXCR3-, CCL2/CCR2-, CCL17/CCR4-, CCL20/CCR6-, CCL27/CCR10-, CXCL8/CXCR1-, CXCL13/CXCR5-, IL-22-, CD4/IL-17A-, CD4/IL-4-, CD4/IFN-γ-, CD123/IDO-, CD25/Foxp3-, and CD20/IL-10-expressing cells, double immunostaining procedures were performed. Circulating CD4+/CD161-/IL-22+, CD4+/CD161+/IL-17+, CD4+/CD25-/IL-4+, CD4+/CD25-/IFN-γ+, CD4+/CD25hi/Foxp3+, CD3+/CD19+/CD38hi/IL-10+, and CD123+/CD196+/IDO + cells were analyzed by flow cytometry. RESULTS: In the tissue, CXCL10, CXCR5, and CCL20 expression and IL-22+, CD4+/IL-17+, CD4+/IFN-γ + and CD123+/IDO + cell percentages were increased in SLE/DLE versus SLE/SCLE. Circulating CD4+/CD161-/IL-22+, CD4+/CD161+/IL-17+, CD4+/CD25-/IFN-γ+, CD19+/CD38hi/IL-10 + and CD123+/CD196+/IDO + cell percentages were higher in SLE/DLE versus SLE/SCLE. In the tissue, we found positive correlations between CXCR3 and CD4+/IL-17 + cells; CCR2 and CD4+/IFN-γ + cells; and CCR10 and CD123+/IDO + cells in the SLE/DLE patients and between CXCL13 and CD20+/IL-10 + cells in the SLE/SCLE patients. In the peripheral blood, we determined positive correlations between CXCR5 and CD4+/CD25-/IFN-γ + cells; CCL17 and CD4+/CD161-/IL-22 + cells; and CCL17 and CD4+/CD161+/IL-17 + cells in the SLE/DLE patients and between CXCR5 and CD3+/CD19+/CD38hi/IL-10 + cells; CCR2 and CD4+/CD25hi/Foxp3 + cells; and CXCR1 and CD4+/CD25hi/Foxp3 + cells in the SLE/SCLE patients. Positive correlations between the pain score and the expression of CCL2 and CCR6 expression were found in the SLE/SCLE patients. In conclusion, the correlations between the expression of chemokines/receptors and subpopulations of effector/regulatory cells showed differential responses among the cutaneous pathologies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

To determine, among systemic lupus erythematosus patients, factors associated with active tuberculosis. We performed a case-control study, in a tertiary-care center in Mexico City. We defined cases as systemic lupus erythematosus patients with active tuberculosis and matched them 1:1 with systemic lupus erythematosus patients without tuberculosis (controls) by age, date of systemic lupus erythematosus diagnosis, and disease duration. We analyzed clinical variables, lupus disease activity (SLEDAI-2K), and accumulated damage (SLICC/ARC-DI). We performed a nonconditional logistic regression to determine factors associated with tuberculosis. We identified 72 tuberculosis cases among systemic lupus erythematosus patients, 58% were culture confirmed. Thirty-three percent (24/72) were pulmonary only, 47.2% (34/72) extrapulmonary only, and 19.4% both. After adjustment for age, gender, and socioeconomic status, SLEDAI-2K and SLICC/ARC-DI, a 1-year cumulative dose of prednisone ≥ 3 g (odds ratios (OR), 18.85; 95% confidence interval (95% CI), 6.91-51.45) was associated with tuberculosis, and the antimalarial treatment was protective (OR, 0.13; 95% CI, 0.04-0.36). Among systemic lupus erythematosus patients, cumulative dose of prednisone is associated with tuberculosis. Further research is required to elucidate the protective effect of antimalarial drugs for tuberculosis. Preventive strategies must be implemented in patients at risk.

To evaluate the association of C-reactive protein (CRP) polymorphisms with risk of development SLE in a group of Mexican individuals. Five CRP polymorphisms (rs3093059, rs3093062, rs1800947, rs1130864, and rs1205) were determined by PCR-restriction fragment length polymorphism and SNP rs3093061 by refractory mutation system PCR assay in 126 SLE patients and 131 controls. Four of the polymorphisms showed differences between patients and controls. rs3093061 polymorphism was associated with a lower risk of developing lupus principally in the codominant 2 (OR = 0.219, 95% CI 0.108-0.785, P = 0.015) model. rs1130864 was associated with decreased risk mainly under codominant 1 (OR = 0.288, 95% CI 0.143-0.581, P = 0.001) model. rs1205 was associated under the over-dominant model (OR = 0.504, 95% CI 0.270-0.942, P = 0.032). The rs3091244 polymorphism was associated with decreased risk of SLE mostly under additive (OR = 0.605, 95% CI 0.393-0.931. P = 0.022) model. Our study establishes that rs3093061, rs1130864, rs1205, and rs3091244 polymorphisms are associated with decreased risk of developing SLE.

Objectives: In 2004 and 1999, respectively, recent-onset rheumatoid arthritis (RA) and systemic lupus erythematous (SLE) cohorts were initiated; the 36 item Medical Outcome Study Short-Form survey (SF-36) was applied beginning from enrolment. The objectives were to compare the SF-36v2 scores between patients from both cohorts who achieved sustained remission and to define the role of disease diagnosis as associated to SF-36v2 normative data in remission patients., Methods: Sustained remission was considered when RA and SLE patients achieved at least 12 months of continuous follow-up with either SLE disease activity index 2000 update =0 or Disease Activity Score (28 joints) ≤2.4, respectively. Up to December 2015, data from 172 RA patients and 211 SLE patients were reviewed. SF-36v2 scores were available for the totality of remission assessments. Logistic regression models were used to investigate factors associated with normative SF-36v2. Written informed consent was obtained from all patients., Results: A higher proportion of patients achieved sustained remission sooner in the RA cohort than in the SLE cohort, 58% vs. 30.6% of the patients, after 30.8±23.9 vs. 59.4±37.5 months, respectively, p≤0.001. At sustained remission, RA patients scored better than SLE patients in 6 out of 8 domains of the SF-36v2 and the physical health component summary (PHCS); the opposite figure was true for the mental component. Age (ß: 1.06, 95% CI: 1.02-1.1, p=0.03) and SLE diagnosis (ß: 9.64, 95% CI: 3.61-25.75, p≤0.001) were predictors of not achieving normative PHCS., Conclusions: RA patients in sustained remission achieved better quality of life than SLE patients.

Objective: To determine if cognitive dysfunction in patients with systemic lupus erythematosus (SLE) derives from an inflammatory process with continuing disease activity, and increased levels of autoantibodies and inflammatory molecules in serum and cerebrospinal fluid (CSF)., Methods: 100 randomly selected patients participating in an inception SLE cohort were studied. At entry into the cohort, a standardized medical history and extensive laboratory tests profile, including autoantibodies were completed. Follow-up occurred every 3-6 months with assessment of lupus characteristics, comorbidities, and treatment. After a mean follow-up of six-years, cross-sectional evaluation of cognitive function was done with standardized tests, and in a subset of patients an extended profile of autoantibodies, cytokines and chemokines was measured in serum and CSF., Results: At enrollment into the cohort, patients were 26.4±8.2 years of age and lupus duration 5.3±3.7 months. Moderate/severe cognitive dysfunction was diagnosed in 16 patients; in comparison to patients with normal cognitive function, they had lower education 9 vs. 12 years (P = 0.006), higher body mass index 26.7 vs. 24.3 (P = 0.03), positive IgG anticardiolipin antibodies 50% vs 18% (P = 0.009), and a higher median number of concomitant NPSLE syndromes 3 vs. 1, (P = 0.04). The prevalence of cardiovascular-risk factors, other auto-antibodies, lupus activity, treatment, and incidence of critical events did not differ. In serum and CSF, the levels of autoantibodies, cytokines and chemokine were similar, only CCL2 was elevated in CSF [886.1 (374.9-1439.7) vs. 515.8 (3.2-1958.2) pg/mL, P = 0.04]., Conclusion: Scant evidence of inflammation in SLE patients with cognitive dysfunction was observed. Only a higher prevalence of IgG anticardiolipin antibodies in serum and increased levels of CCL2 in CSF were detected.

Objective: To determine whether the prevalence and extent of asymptomatic coronary artery atherosclerosis are increased in men with systemic lupus erythematosus (SLE) compared with age- and sex-matched controls, and to define the associated risk factors., Methods: Ninety-five patients with SLE (mean ± SD age, 34.7 ± 10.1 yrs) and 100 control subjects (age 34.8 ± 9.7 yrs) with no history of coronary artery disease were screened for coronary artery calcification using multidetector computed tomography. The extent of calcification was measured using the Agatston score. The frequency of risk factors for calcification was compared between patients and controls, and the relationship between clinical and immunological characteristics and the presence of coronary artery calcification was investigated., Results: Coronary artery calcification was more frequent in patients than controls [18% vs 7%, respectively (OR 2.89, 95% CI 1.07-8.65)]. These factors were independently associated with the presence of calcifications: age (OR 1.12, 95% CI 1.04-1.20), SLE diagnosis (OR 3.38, 95% CI 1.07-10.64), diabetes mellitus (OR 6.88, 95% CI 1.50-31.62), Framingham risk score (OR 1.12, 95% CI 1.00-1.23), and glomerular filtration rate (OR 0.98, 95% CI 0.96-1.00). Among patients with SLE, coronary artery calcifications were observed starting at age 32 years, within 2.3 years of diagnosis. Increasing age (OR 1.18, 95% CI 1.06-1.31), Systemic Lupus International Collaborating Clinics score (OR 2.85, 95% CI 1.21-6.73), and cumulative dose of prednisone (OR 1.04, 95% CI 1.01-1.08) were independent risk factors., Conclusion: Men with SLE are at an increased risk of coronary artery calcifications than age- and sex-matched controls. Among patients with SLE, the increased risk is associated to older age, increasing chronic damage, and cumulative dose of corticosteroids.

Objective: We aimed to evaluate the usefulness of anti-α-fodrin antibodies (AFA) in combination with rheumatoid factor (RF) and/or antinuclear antibodies (ANA) as an alternative immunological criterion for Sjögren syndrome (SS) among patients with negative anti-Ro/La serology., Methods: The study included 350 patients (100 with rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, and 50 with primary SS) randomly selected and assessed for SS. All patients were tested for ANA, RF, anti-SSA/SSB, and AFA antibodies. SS diagnosis was made on a clinical basis by 2 rheumatologists based on the 6-item screening questionnaire, Schirmer-I test, nonstimulated whole salivary flow rate, fluorescein staining test, autoantibodies, lip biopsy, and medical chart review. Non-SS was defined as lack of clinical diagnosis and not fulfilling the American-European Consensus Group classification criteria and the American College of Rheumatology (ACR) criteria. The ACR criteria were applied substituting the immunological criteria as follows: (1) RF plus ANA > 1:320, (2) RF plus AFA, (3) ANA > 1:320 plus AFA, (4) RF alone, and (5) 2 positive tests out of RF, ANA > 1:320, or AFA. We estimated the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio positivity with 95% CI for each criterion., Results: There were 236 patients (67%) who tested negative for anti-SSA/SSB antibodies, of whom 65 (27.5%) were clinically diagnosed as SS, and 149 (63%) with non-SS. RF + AFA and ANA + AFA performed similarly to RF + ANA > 1:320. The model 2 out of 3 of RF, ANA, or AFA improved the sensitivity from 56.9% to 70.7%, although the specificity decreased., Conclusion: The combination AFA + RF, AFA + ANA > 1:320, or at least 2 out of 3, performed well as a proxy immunological test for patients with SS and negative Ro/La serology.

Objective: The aim of this study was to evaluate the feasibility and performance of the American-European Consensus Group (AECG) and ACR Classification Criteria for SS in patients with systemic autoimmune diseases., Methods: Three hundred and fifty patients with primary SS, SLE, RA or scleroderma were randomly selected from our patient registry. Each patient was clinically diagnosed as probable/definitive SS or non-SS following a standardized evaluation including clinical symptoms and manifestations, confirmatory tests, fluorescein staining test, autoantibodies, lip biopsy and medical chart review. Using the clinical diagnosis as the gold standard, the degree of agreement with each criteria set and between the criteria sets was estimated., Results: One hundred fifty-four (44%) patients were diagnosed with SS. The AECG criteria were incomplete in 36 patients (10.3%) and the ACR criteria in 96 (27.4%; P < 0.001). Nevertheless, their ability to classify patients was almost identical, with a sensitivity of 61.6 vs 62.3 and a specificity of 94.3 vs 91.3, respectively. Either set of criteria was met by 123 patients (80%); 95 (61.7%) met the AECG criteria and 96 (62.3%) met the ACR criteria, but only 68 (44.2%) patients met both sets. The concordance rate between clinical diagnosis and AECG or ACR criteria was moderate (k statistic 0.58 and 0.55, respectively). Among 99 patients with definitive SS sensitivity was 83.3 vs 77.7 and specificity was 90.8 vs 85.6, respectively. A discrepancy between clinical diagnosis and criteria was seen in 59 patients (17%)., Conclusion: The feasibility of the SS AECG criteria is superior to that of the ACR criteria, however, their performance was similar among patients with systemic autoimmune diseases. A subset of SS patients is still missed by both criteria sets., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: The aim of this study was to estimate the age at natural menopause in women with SLE., Methods: One thousand and thirty-nine consecutive SLE patients <60 years of age were surveyed. Demographic and clinical data were queried by a single investigator. SLE characteristics and co-morbidities were retrieved from their medical records. Natural menopause was defined as amenorrhoea ≥12 months in the absence of previous hysterectomy, CYC exposure and severe chronic kidney disease (SCKD). Pregnant women and those with menses during the 12 months prior to interview were considered premenopausal. Median age at menopause was estimated by both logit and survival analyses. In addition, mean age at menopause was calculated for patients aged ≥40 years. Factors associated with age at natural menopause were assessed by Cox regression analysis., Results: A total of 961 SLE women were analysed. At interview, most patients (81.6%) were premenopausal, 7.9% had natural menopause, 6.3% were postmenopausal previously exposed to CYC, 4.1% had undergone hysterectomy before menopause and 0.1% presented with SCKD and amenorrhoea. The mean age at interview was 35.2 years (s.d. 10.1), the mean age at SLE diagnosis was 26.9 years (s.d. 8.6) and the mean duration of disease was 8.2 years (s.d. 7.1). The mean recalled age at menopause was 46.4 years (s.d. 4.7). Median age at menopause estimated by logit and survival analyses were 50.7 and 50.8 years, respectively. Only the age at SLE diagnosis was associated with age at natural menopause., Conclusion: Median age at natural menopause in women with lupus is 50 years. This is consistent with the age at menopause reported in the general population., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To determine the prevalence of SS in a cohort of recent-onset SLE patients and evaluate the clinical and immunological variables that may identify SLE patients prone to develop SS., Methods: A total of 103 patients participating in a prospective cohort of recent-onset SLE were assessed for fulfilment of the American European Consensus Group criteria for SS using a three-phase approach: screening (European questionnaire, Schirmer-I test and wafer test), confirmation (fluorescein staining test, non-stimulated whole-salivary flow and anti-Ro/La antibodies) and lip biopsy. Anti-Ro/SSA and anti-La/SSB antibodies and RF were measured at entry into the cohort and at SS assessment., Results: Ninety-three females and 10 males were included. Mean age at lupus diagnosis was 25.9 ± 8.9 years, and lupus duration at SS assessment was 30.9 ± 9.1 years. SS was diagnosed in 19 (18.5%) patients, all female, and the patients were older at SLE diagnosis than patients without SS (30.8 ± 9.3 vs 24 ± 8.8 years, P = 0.004). Anti-Ro/SSA antibody was more common in SLE-SS patients (84% vs 55%, P = 0.02, LR + 1.53, 95% CI 1.14, 2.04). In the multivariate analysis, age ≥25 years and anti-Ro/SSA antibodies at SLE diagnosis were identified as predictors of SLE-SS, while the absence of anti-Ro/SSA, anti-La/SSB and RF seems to be protective (LR- 0.14, 95% CI 0.02, 0.95)., Conclusion: The overlap of SLE and SS occurs in almost one-fifth of SLE patients and presents early during its evolution. SLE onset at age ≥25 years plus the presence of anti-Ro/SSA antibody at diagnosis are useful predictors, while the absence of anti-Ro/SSA, anti-La/SSB and RF identifies patients at lowest risk.

Objective: Premature atherosclerosis in patients with SLE is partially explained by traditional risk factors; therefore, we aimed to identify lupus-related risk factors for coronary artery calcifications., Methods: An inception cohort of 139 lupus patients (93% females) was screened for coronary artery calcifications using Multidetector CT, after 5.1 years of follow-up. Clinical and immunological variables and cardiovascular risk factors were assessed longitudinally. Also, 100 age- and sex-matched healthy subjects were studied. Correlates for calcifications were analysed in lupus patients, including levels of lipids and inflammatory molecules in samples obtained at enrolment, mid-term follow-up and at screening., Results: At enrolment, lupus patients were 27.2 (9.1) years of age and with a disease duration of 5.4 (3.8) months. Calcifications were detected in 7.2% of patients and 1% of controls [unadjusted odds ratio (OR) 7.7, 95% CI 1.05, 336.3, P = 0.02]. In lupus, calcifications were detected since the age of 23 years and from 3 years of diagnosis. Patients with calcifications were older, post-menopausal, and had higher levels of serum apolipoprotein B and Framingham risk scores (P < 0.05). Lupus-related factors identified included age at diagnosis, IgG aCLs, cumulative lupus activity, length of moderate/severe activity and cumulative dose of prednisone and CYC (P < 0.05). Use of anti-malarials was protective (P = 0.006). Logistic regression analysis showed as predictors of calcification: disease duration (OR 15.1, 95% CI 2.6, 87.2), age at enrolment (OR 8.5, 95% CI 1.7, 43.0) and SLEDAI 2000 update (SLEDAI-2K) mean area under the curve (OR 12.3, 95% CI 2.5, 61.8). Longitudinal analyses of lipids and inflammatory molecules did not differ between patients., Conclusions: Disease activity is a potentially modifiable risk factor for coronary artery calcifications in SLE. Therefore, management of traditional risk factors plus tight control of lupus activity, including the use of anti-malarials, is recommended.

Objective: To compare the socio-economic characteristics, clinical features and health-related quality of life in Hispanic SLE patients residing in Mexico and in the Southwest USA (Mexican and Texan, herein)., Methods: Mexican and Texan SLE patients (fulfilling ACR criteria) participating in separate longitudinal outcome studies were evaluated. Texan patients were randomly chosen to match total disease duration with the Mexican patients. Cross-sectional data for the Mexican patients were obtained by a US-trained investigator who had previously participated in data collection for the cohort to which the Texan patients belonged. Socio-economic and -demographic characteristics, clinical characteristics, disease activity (with SLAM-Revised), damage accrual (with SLICC/ACR Damage Index) and self-reported function (with Short Form-36) were compared between the two groups., Results: Seventy Mexican patients were matched with either one or two Texan patients (n = 94) for a total of 164 patients. Mexican patients were younger. In age-adjusted analyses, the Mexican patients were more educated, had better health-related quality of life and overall less systemic SLE manifestations. Mexican patients were exposed more frequently to AZA., Conclusions: Texan patients had more severe disease than the Mexican patients. In multivariable analyses, Texan Hispanic ethnicity was significantly associated with high disease activity, but significance was not reached for damage. The discrepant findings observed between these two Hispanic groups of SLE patients may reflect socio-economic or biological factors. Given the global phenomenon of immigration, rheumatologists should be aware of the overall course and outcome of immigrant SLE patients if undesirable outcomes are to be prevented.

Objective: To determine the risk of thrombosis in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases of recent onset., Methods: A retrospective cohort of 482 patients, mean age 28.3 years, with SLE or other autoimmune diseases was analyzed. Followup started at diagnosis or first appointment within 12 months since diagnosis until the development of thrombosis, end of study, loss to followup, or death. Thromboses were diagnosed upon clinical manifestations and confirmed by appropriate studies. Clinical variables were retrieved from the medical records, and SLE activity was assessed from the medical notes at onset of thrombosis, or at a dummy date for thrombosis, using the SLE Disease Activity Index-2K., Results: During 2936 patient-years of followup, thromboses occurred in 49 patients (20.3%) with SLE and 6 patients (2.5%) with other autoimmune diseases. The incidence rate of thrombosis was 36.3 and 3.8 per 1000 patient-years in SLE and in other autoimmune diseases, respectively; relative risk 9.6 (95% CI 4.1-27.4, p<0.0001). Throughout the disease course, the risk of thrombosis remained high in the SLE group, while in patients with other autoimmune diseases this risk was lower. The incidence of venous and arterial thrombosis was similar among SLE patients and patients with other autoimmune diseases. SLE and venous insufficiency were associated with thromboses in the total study population, and with venous insufficiency, vasculitis, and disease activity in the SLE group., Conclusion: Patients with autoimmune diseases, particularly SLE, are at an increased risk of thrombosis. In patients with SLE, the risk remains elevated throughout the course of the disease.

Objective: To evaluate the effects of menopause hormonal therapy on disease activity in women with systemic lupus erythematosus (SLE)., Methods: We conducted a double-blind, randomized clinical trial involving 106 women with SLE who were in the menopausal transition or in early or late postmenopause. Patients received a continuous-sequential estrogen-progestogen regimen (n = 52) or placebo (n = 54). Disease activity was assessed at baseline and at 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 months, according to the SLE Disease Activity Index (SLEDAI). The primary outcome measure was global disease activity, estimated by measuring the area under the SLEDAI curve. Secondary outcome measures included maximum SLEDAI score, change in SLEDAI score, incidence of lupus flares, median time to flare, medication use, and adverse events. Results were studied using intent-to-treat analysis., Results: At baseline, demographic and disease characteristics were similar in both groups. Mean +/- SD SLEDAI scores were 3.5 +/- 3.3 and 3.1 +/- 3.4 in the menopause hormonal therapy and placebo groups, respectively (P = 0.57). Disease activity remained mild and stable in both groups throughout the trial. There were no significant differences between the groups in global or maximum disease activity, incidence or probability of flares, or medication use. Median time to flare was 3 months in both groups. Thromboses occurred in 3 patients who received menopause hormonal therapy and in 1 patient who received placebo. One patient in each group died during the trial due to sepsis., Conclusion: Menopause hormonal therapy did not alter disease activity during 2 years of treatment. However, an apparently increased risk of thrombosis seems to be a real threat in women with SLE who receive menopausal hormone therapy.

Background: : Renal biopsy is an important tool in devising an adequate treatment plan for lupus nephritis. However, it is not always possible to perform a biopsy, and in many cases, treatment must rely exclusively on clinical data., Objective: : The aim of this study was to compare the 5-year course of patients treated without a biopsy with another group with histologic evidence of diffuse proliferative glomerulonephritis (DPGN)., Methods: : The no-biopsy group consisted of 30 patients with lupus with strong clinical and laboratory suspicion of proliferative glomerulonephritis in whom a renal biopsy was unavailable either because of medical contraindication or the patient's refusal. The biopsy group included 30 patients undergoing biopsy and a histologic diagnosis of DPGN. Patients were followed from the onset of nephritis and at 18, 36, and 60 months., Results: : At onset, the no-biopsy group showed lower C3 levels and higher proteinuria, although both groups showed evident deterioration of the renal function. No significant differences were found in treatment, outcome, survival, renal function tests, or in the development of kidney failure., Conclusions: : Proliferative glomerulonephritis deserves prompt diagnosis and treatment. This study demonstrates that experience in the management of lupus nephropathy, together with clinical and laboratory data, are often enough information to adequately treat proliferative glomerulonephritis even in the absence of a renal biopsy.

Purpose: Cyclophosphamide-induced ovarian failure has been reported to be protective against flares of systemic lupus erythematosus (SLE). We studied whether patients with SLE experience a decrease in disease activity after natural menopause., Subjects and Methods: We studied 30 SLE patients with natural menopause who had been observed at least 2 years before and after menopause and who did not receive hormone replacement therapy or danazol. Menopause was defined as the date of the last self-reported menstrual period. Disease activity was assessed retrospectively by medical chart review using standard measures (the SLE disease activity index) during the immediate premenopausal and postmenopausal periods, and 2 (n = 30 patients), 3 (n = 19), and 4 (n = 13) years before and after menopause. We also compared the use of health services and medications., Results: Patients were studied for a mean (+/- SD) of 6.4 +/- 1.7 years (premenopausal, 3.3 +/- 0.9 years; postmenopausal, 3.2 +/- 0.9 years). During the premenopausal periods, the mean disease activity score was 2.3 +/- 2.3 (range, 0 to 9 on a 0 to 105 scale), compared with 2.3 +/- 2.9 (range, 0 to 12; P = 0.37) after menopause. The maximum disease activity score was somewhat greater in the premenopausal period (7.9 +/- 6.0 [range, 0 to 22] vs. 5.8 +/- 5.1 [range, 0 to 22]; P = 0.04). The incidence rates of flares (0.56 per year vs. 0.43 per year, P = 0.20) and severe flares (0.17 per year vs. 0.12 per year, P = 0.33) were similar in the premenopausal and postmenopausal periods. Differences in disease activity scores (mean and maximum) and the number of visits to a rheumatologist's office were only significant when the fourth year before menopause was compared with the fourth year after menopause., Conclusions: Disease activity is mild during the premenopausal and postmenopausal periods in women with SLE. A modest decrease, especially in the maximum disease activity, is seen after natural menopause.

We present our experience in eighty patients with superficial bladder cancer stage T1. They have been randomized to receive BCG 27 mg weekly x 6 and monthly until complete one year (Group A) or the same schedule plus Tegafur 800 mg daily until complete one year. Results are similar in both groups. With a median follow up of two years and a half, 33% in Group A and 20% in Group B have had recurrence; 7.6% in group A and 3% in group B have had progression in stage. Differences are not significant in both cases. Tolerance of Tegafur is good with only 11% of secondary effects. We concluded that there are no differences in both treatments but there is a trend to better results with combinant therapy. It is necessary more patients to achieve definitive results.

We show our results in the diagnostic and follow-up of the bladder tumors comparing de BTA test with Void Cytology, in order to substitute this with the former. We performed BTA test, Void Cytology (of the same sample) and abdominal ultrasound to 133 patients. They are divided in three groups: 45 with bladder tumor, 16 healthy controls, 72 in follow-up with and without prophylaxis. The sensibility and specificity in tumor's group were similar. In controls' and follow-up's groups the void cytology specificity was superior. There is a high number of false positives in the follow-up group with a large number of "white" cystoscopes. A high number of false positives was seen if the BTA test was done in he first three months of follow-up. In the subgroup in prophylaxis with cystostatic there weren't false positives. We conclude that BTA test is useful in the diagnostic of bladder tumor but not in the follow-up, especially in the first three months.