Systemic Lupus Erythematosus Cohort Research Articles

Familial Aggregation of Childhood- and Adulthood-Onset Systemic Lupus Erythematosus.

To assess the familial occurrence of systemic lupus erythematosus (SLE) in a large Brazilian cohort. Consecutive patients with SLE were recruited and stratified according to age at disease onset into childhood-onset SLE or adult-onset SLE. Each patient was personally interviewed regarding the history of SLE across 3 generations (first-, second-, and third-degree relatives). Recurrence rates were analyzed for each degree of relation. We included 392 patients with SLE (112 with childhood-onset SLE and 280 with adult-onset SLE). We identified 2,574 first-degree relatives, 5,490 second-degree relatives, and 6,805 third-degree relatives. In the combined overall SLE cohort, we observed a familial SLE recurrence rate of 19.4 in first-degree relatives, 5.4 in second-degree relatives, and 3.0 in third-degree relatives. Recurrence rates were higher for first- and second-degree relatives of patients with childhood-onset SLE than for first- and second-degree relatives of patients with adult-onset SLE (25.2 versus 18.4 for first-degree, and 8.5 versus 4.5 for second-degree), while in third-degree relatives, recurrence rates were higher in adult-onset SLE than in childhood-onset SLE (P = 2.2 × 10-4 for differences in recurrence proportions between childhood-onset SLE and adult-onset SLE). There were no phenotypic differences in patients from multicase versus single-case families, and there was no sex-skewing observed in the offspring of patients with SLE. The greater decline in SLE recurrence rate by generation in childhood-onset SLE versus adult-onset SLE suggests a more polygenic and epistatic inheritance and suggests that adult-onset SLE may be characterized by fewer risk factors that are individually stronger. This finding suggests a higher genetic load in childhood-onset SLE versus adult-onset SLE and a difference in the genetic architecture of the disease based on age at onset.

Associated factors to serious infections in a large cohort of juvenile-onset systemic lupus erythematosus from Lupus Registry (RELESSER).

ObjectiveTo assess the incidence of serious infection (SI) and associated factors in a large juvenile-onset systemic lupus erythematosus (jSLE) retrospective cohort. MethodsAll patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ≥4 ACR-97 SLE criteria and disease onset <18 years old (jSLE), were retrospectively investigated for SI (defined as either the need for hospitalization with antibacterial therapy for a potentially fatal infection or death caused by the infection). Standardized SI rate was calculated per 100 patient years. Patients with and without SI were compared. Bivariate and multivariate logistic and Cox regression models were built to calculate associated factors to SI and relative risks. ResultsA total of 353 jSLE patients were included: 88.7% female, 14.3 years (± 2.9) of age at diagnosis, 16.0 years (± 9.3) of disease duration and 31.5 years (±10.5) at end of follow-up. A total of 104 (29.5%) patients suffered 205 SI (1, 55.8%; 2-5, 38.4%; and ≥6, 5.8%). Incidence rate was 3.7 (95%CI: 3.2–4.2) SI per 100 patient years. Respiratory location and bacterial infections were the most frequent. Higher number of SLE classification criteria, SLICC/ACR DI score and immunosuppressants use were associated to the presence of SI. Associated factors to shorter time to first infection were higher number of SLE criteria, splenectomy and immunosuppressants use. ConclusionsThe risk of SI in jSLE patients is significant and higher than aSLE. It is associated to higher number of SLE criteria, damage accrual, some immunosuppressants and splenectomy.

Urticarial vasculitis in pediatric systemic lupus erythematosus.

To determine the prevalence of urticarial vasculitis (UV) in a pediatric systemic lupus erythematosus (pSLE) cohort of Arab ethnicity from Oman and to describe their demographic, clinical, and laboratory features. We conducted a retrospective multicenter study among pediatric rheumatology centers in Oman over a 10-year period from 2008 to 2018. Analyses were performed using univariate statistics. A total of 148 pSLE under the age of 13years were included of which 30% (n=44) were men. The overall mean age at SLE diagnosis was 7.6±3.5years while the mean disease duration was 10.1±5.4years. UV was diagnosed in 36% (n=53) of pSLE patients. Patients with pSLE and UV were more likely to be male(57% vs 15%; P<.001), diagnosed at a younger age (5.9 vs 8.5years; P<.001), have a family history of SLE (53% vs 36%; P=.044), and have associated conjunctivitis, (32% vs 5.3%; P<.001) but less likely to have CNS involvement (7.6% vs 20%; P=.045) or hematological manifestations such as leukopenia (9.4% vs 24%; P=.028) and thrombocytopenia (5.7% vs 18%; P=.045). This subgroup was also more likely to be associated with low C3 complement count (94% vs 66%; P<.001) and positive cytoplasmic ANCA (11% vs 0%; P=.022). We report a high occurrence of UV in a pSLE cohort associated with unique demographic, clinical, and laboratory features.

Treatment patterns and medical cost of systemic lupus erythematosus patients in Japan: a retrospective claims database study

Aim: To describe the characteristics and medication treatment patterns, healthcare resource utilization (HRU), and associated costs in Japanese patients with systemic lupus erythematosus (SLE).Methods: Claims data from the Japan Medical Data Center (JMDC) database were used to identify patients with SLE-related claims from 2010 to 2017. Algorithms were developed to retrospectively categorize patients by disease severity, treatment experience, and SLE-related manifestations such as lupus nephritis and central nervous system lupus. Descriptive and multivariate analyses were used to describe treatment pattern and estimate HRU and associated costs for the SLE cohort overall and by disease severity and complications.Results: Among 4,733 eligible patients, 2,072 (43.8%) were treatment naïve, 2,214 (46.8%) were previously treated for SLE, and 447 (9.4%) did not receive any treatment. Mean (SD) age of the total SLE cohort was 45.2 (13.1) years and mean (SD) follow-up duration was 1,137.3 (758.0) d. Based on disease severity, 1,383 (29.2%) patients had mild, 2,619 (55.3%) patients had moderate, and 731 (15.4%) patients had severe SLE. Patients on glucocorticoids (both oral and parenteral) received add-on medications the most (35.5%, p < .001). Mean annual cost per SLE patient in the post-index period, inclusive of hospitalizations, outpatient visits, and pharmacy was ¥436,836; ¥1,010,772; and ¥2,136,780 for patients with mild, moderate, and severe SLE, respectively.Limitations: The database only captured information on patients up to 75 years of age. Due to the nature of the database, biases regarding conditions that attribute to the spectrum of SLE severity, flare incidences, or individual physical status cannot be ruled out.Conclusions: This study describes the treatment patterns and economic burden experienced by Japanese patients with SLE. The results highlight an unmet need to derive better treatment strategies for patients with SLE to effectively address the disease burden in Japan.

Deep Neck Infection in Systemic Lupus Erythematosus Patients: Real-World Evidence

Systemic lupus erythematosus (SLE) might increase deep neck infection (DNI) risk, but evidence supporting this hypothesis is limited. In this retrospective follow-up study, the SLE–DNI association was investigated using data from the Registry for Catastrophic Illness Patients, which is a subset of the Taiwan National Health Insurance Research Database. All patients newly diagnosed as having SLE in 1997–2011 were identified, and every SLE patient was individually matched to four patients without SLE according to sex, age, and socioeconomic status. The study outcome was DNI occurrence. DNI treatment modalities and prognoses in SLE and non-SLE patients, along with the association of steroid dose with DNI risk, were also studied. In total, 17,426 SLE and 69,704 non-SLE patients were enrolled. Cumulative DNI incidence was significantly higher in the SLE cohort than in the non-SLE cohort (p < 0.001). The Cox regression model demonstrated that SLE significantly increased DNI risk (hazard ratio: 4.70; 95% confidence interval: 3.50–6.32, p < 0.001). Moreover, in the sensitivity and subgroup analyses, the effect of SLE on DNI was stable. Relatively few SLE–DNI patients received surgical interventions (15.6% vs. 28.6%, p = 0.033). The between-group differences in tracheostomy use and hospitalisation duration were nonsignificant. In SLE patients, high steroid doses significantly increased DNI incidence (≥3 vs. <3 mg/day = 2.21% vs. 0.52%, p < 0.001). This is the first study demonstrating that SLE increases DNI risk by approximately five times and that high steroid dose increases DNI incidence in SLE patients.

No association of complement mannose-binding lectin deficiency with cardiovascular disease in patients with Systemic Lupus Erythematosus

Cardiovascular (CV) morbidity is the major cause of death in patients with Systemic Lupus Erythematosus (SLE). Previous studies on mannose-binding lectin (MBL) gene polymorphisms in SLE patients suggest that low levels of complement MBL are associated with cardiovascular disease (CVD). However, as large studies on MBL deficiency based on resulting MBL plasma concentrations are lacking, the aim of our study was to analyze the association of MBL concentrations with CVD in SLE patients. Plasma MBL levels SLE patients included in the Swiss SLE Cohort Study were quantified by ELISA. Five different CV organ manifestations were documented. Of 373 included patients (85.5% female) 62 patients had at least one CV manifestation. Patients with MBL deficiency (levels below 500 ng/ml or 1000 ng/ml) had no significantly increased frequency of CVD (19.4% vs. 15.2%, P = 0.3 or 17.7% vs. 15.7%, P = 0.7). After adjustment for traditional CV risk factors, MBL levels and positive antiphospholipid serology (APL+) a significant association of CVD with age, hypertension, disease duration and APL+ was demonstrated. In our study of a large cohort of patients with SLE, we could not confirm previous studies suggesting MBL deficiency to be associated with an increased risk for CVD.

Evolving phenotype of systemic lupus erythematosus in Caucasians: low incidence of lupus nephritis, high burden of neuropsychiatric disease and increased rates of late-onset lupus in the 'Attikon' cohort.

ObjectiveThis study aimed to analyse the phenotype of systemic lupus erythematosus (SLE) at first presentation and during follow-up in a newly established SLE cohort based at ‘Attikon’ University Hospital. The hospital combines primary, secondary and tertiary care for the region of Western Attica, Greece.MethodsThis study comprised a mixed prevalent and incident cohort of 555 Caucasian patients diagnosed with SLE according to American College of Rheumatology 1997 criteria and/or the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 criteria. Demographic and clinical characteristics, patterns of severity, treatments and SLICC damage index were recorded for each patient at the time of diagnosis and at last evaluation.ResultsThe mean age at lupus diagnosis was 38.3 years (standard deviation = 15.6 years), with a median disease duration at last follow-up of two years (interquartile range 1-11). At initial presentation, the most common ‘classification’ manifestations were arthritis (73.3%), acute cutaneous lupus (65%) and unexplained fever (25%), while among symptoms not included in any criteria set, Raynaud’s phenomenon (33%) was the most common. Kidney and neuropsychiatric involvement as presenting manifestations were present in 10.3% and 11.5% cases, respectively. Irreversible damage accrual was present in 17.8% within six months of disease diagnosis, attributed mainly to thrombotic and neuropsychiatric disease. At last evaluation, 202 (36.4%) patients had developed severe disease, of whom more than half were treated with pulse cyclophosphamide.ConclusionIn this cohort of Caucasian patients, lupus nephritis is not as common as in older cohorts, while neuropsychiatric disease is emerging as a major frontier in lupus prevention and care. These data may help to document changes in the natural history and treatment of SLE over time and may have implications for its early recognition and management.

Application of the 2019 European League Against Rheumatism/American College of Rheumatology systemic lupus erythematosus classification criteria in clinical practice: a single center experience.

Originally developed as research tools, different classification criteria sets for systemic lupus erythematosus (SLE) are also used to diagnose SLE in routine clinical care. The recently developed European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2019 criteria set is noted to perform better than previous SLE classification criteria. This study applied the new criteria schema to a tertiary center SLE cohort, ascertained its performance, and identified the clinical characteristics of patients who did not fulfill these criteria. From the 217 patients who were included, 11 (5%) did not meet the new criteria, mainly because of the antinuclear antibody entry criterion, resulting in a diagnostic sensitivity of 94%. Within this group, we found that constitutional and renal manifestations were unusual. Additionally, specific SLE antibodies as well as hypocomplementemia were less likely to be present. We did not observe a statistically significant difference in outcomes between the two groups of patients (fulfilling vs. unfulfilling the new criteria). We conclude that the EULAR/ACR criteria may misclassify a small subset of SLE patients with milder disease. It is important to be cognizant of key clinical and serologic features of these patients and treat them accordingly to prevent further irreversible damage.

Ocular involvement in systemic lupus erythematosus patients: a paradigm shift based on the experience of a tertiary referral center.

To evaluate ocular involvement in a cohort of systemic lupus erythematosus (SLE) patients of a tertiary referral center and to compare the results with the existing literature. Patients underwent a complete ophthalmological evaluation, including visual acuity, slit-lamp examination, fluorescein staining, Schirmer-I test, Goldmann applanation tonometry, fundoscopy, 10-2 automated threshold visual fields, fundus autofluorescence and spectral-domain optical coherence tomography to screen for hydroxychloroquine (HCQ) macular toxicity. A total of 161 patients (16 men and 145 women) were enrolled in this study. The mean age was 47.6 years and the mean disease duration was 11.5 years. Fifty patients (31.1%) had at least one ocular manifestation of SLE. The most frequent manifestation was dry eye syndrome (12.4%), immediately followed by cataracts (11.2%) and HCQ macular toxicity (11.2%). Among patients with HCQ maculopathy, two presented with an atypical spectral-domain optical coherence tomography pattern. Five patients (3.1%) presented with glaucoma, two patients (1.2%) presented with SLE retinopathy while only one presented with lupus choroidopathy (0.6%). Compared with previous studies, we conclude there has been a significant reduction in disease-related ocular complications, particularly those associated with poor systemic disease control. On the other hand, drug and age-related complications are assuming a prominent role in the ophthalmic care of these patients.

In an early SLE cohort the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria classify non-overlapping groups of patients: use of all three criteria ensures optimal capture for clinical studies while their modification earlier classification and treatment

ObjectivesClassification criteria are biased towards classifying long-standing disease. We compared the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR)-2019, Systemic Lupus International Collaborating Clinics (SLICC)-2012 and ACR-1997 criteria in...

Contribution of rare and predicted pathogenic gene variants to childhood-onset lupus: a large, genetic panel analysis of British and French cohorts.

Systemic lupus erythematosus (SLE) is a rare immunological disorder and genetic factors are considered important in its causation. Monogenic lupus has been associated with around 30 genotypes in humans and 60 in mice, while genome-wide association studies have identified more than 90 risk loci. We aimed to analyse the contribution of rare and predicted pathogenic gene variants in a population of unselected cases of childhood-onset SLE. For this genetic panel analysis we designed a next-generation sequencing panel comprising 147 genes, including all known lupus-causing genes in humans, and potentially lupus-causing genes identified through GWAS and animal models. We screened 117 probands fulfilling American College of Rheumatology (ACR) criteria for SLE, ascertained through British and French cohorts of childhood-onset SLE, and compared these data with those of 791 ethnically matched controls from the 1000 Genomes Project and 574 controls from the FREX Consortium. After filtering, mendelian genotypes were confirmed in eight probands, involving variants in C1QA, C1QC, C2, DNASE1L3, and IKZF1. Seven additional patients carried heterozygous variants in complement or type I interferon-associated autosomal recessive genes, with decreased concentrations of the encoded proteins C3 and C9 recorded in two patients. Rare variants that were predicted to be damaging were significantly enriched in the childhood-onset SLE cohort compared with controls; 25% of SLE probands versus 5% of controls were identified to harbour at least one rare, predicted damaging variant (p=2·98 × 10-11). Inborn errors of immunity were estimated to account for 7% of cases of childhood-onset SLE, with defects in innate immunity representing the main monogenic contribution. An accumulation of rare variants that are predicted to be damaging in SLE-associated genes might contribute to disease expression and clinical heterogeneity. European Research Council.

A review and meta-analysis of anti-ribosomal P autoantibodies in systemic lupus erythematosus.

The discovery of autoantibodies to ribosomal proteins (anti-RibP) dates back more than fifty years when antibodies to ribosomes were identified in systemic lupus erythematosus (SLE) sera. Over the years, anti-RibP autoantibodies have been the subject of extensive study and became known as a highly specific biomarker for the diagnosis of SLE and were associated with neuropsychiatric SLE (NPSLE), lupus nephritis (LN) and hepatitis (LH). As demonstrated by studies on cultured human cells and of murine models, there is evidence to suggest that anti-RibP may have a pathogenic role in LN and NPSLE. Despite a wealth of evidence, in comparison to other SLE autoantibodies such as anti-Sm and anti-dsDNA, anti-RibP has not been included in classification criteria for SLE. A significant challenge is the variability of assays used to detect anti-RibP, including the antigens and diagnostic platforms employed. This may account for the marked variation in frequencies (10-47%) in SLE and its association with clinical and demographic features reported in SLE cohorts. We performed a systematic literature review and meta-analysis to help clarify its prevalence, various clinical and serological associations in SLE based on the different RibP antigens and assay platforms used.

Neuropsychiatric events in systemic lupus erythematosus: a longitudinal analysis of outcomes in an international inception cohort using a multistate model approach

ObjectivesUsing a reversible multistate model, we prospectively examined neuropsychiatric (NP) events for attribution, outcome and association with health-related quality of life (HRQoL), in an international, inception cohort of systemic lupus...

Systemic lupus erythematosus in the setting of HIV-1 infection: a longitudinal analysis.

Patients with concomitant HIV-1 infection and systemic lupus erythematosus (SLE) followed longitudinally at an HIV outpatient clinic from 1994 to 2019 were examined. Patients met 1982 and 1997 ACR classification criteria for SLE at the Thomas Street clinic from 1994 to 2019. Clinical and demographic comparisons were made with a non HIV-SLE patient cohort, the Lupus in Minorities Studies, Nature versus Nurture (LUMINA) study. Twenty-two patients with concomitant HIV-1 infection and SLE were identified, including 18 females, 3 males, and 1 male to female transgender. Overall, 81.8% of SLE-HIV patients were African-American compared to 55.3% of the 5856 patients seen at the HIV clinic from 2016 to 2017 (p= 0.02, OR = 3.6). There were 12 patients that developed HIV-1 in the setting of SLE and 10 patients that developed SLE in the setting HIV-1. This demographic distribution was significant when compared with the 1604 unique patients in the HIV rheumatology clinic from 1994 to 2019 (p= 0.03, OR = 5.9) and also significant when compared with the 5856 patients attending the county HIV clinic overall in 2016-2017 (p= 0.008, OR = 7.2). When comparing with the non-HIV SLE cohort, anti-dsDNA antibodies were noted less frequently in all HIV-SLE patients (p= 0.0002) including all sub-cohorts of our patients. Skin/mucosal involvement (p= 0.0003) and cytopenias (p= 0.0001) occurred less frequently in the patients that were diagnosed with HIV after their SLE diagnosis compared to non-HIV SLE patients. In a large county HIV clinic setting, the prevalence of SLE was significantly higher in African American women. Anti-dsDNA antibodies were less frequent in HIV-1 positive SLE patients.Key Points• This paper presents clinical and laboratory data on the largest cohort of SLE patients with HIV-1 infection reported to date.• The prevalence of SLE in a large outpatient HIV-1 clinic was larger than reported in HIV negative population studies.• The prevalence of SLE was particularly high in black HIV-1 infected women.• Skin/mucosal involvement and anti-ds DNA antibodies were less common in patients with HIV-1 and SLE compared to patients with SLE without SLE>.

Role of Neutrophil Extracellular Traps Regarding Patients at Risk of Increased Disease Activity and Cardiovascular Comorbidity in Systemic Lupus Erythematosus.

Neutrophil extracellular traps (NET) are essential in host defense, but are also linked to inflammation and autoimmunity, including in systemic lupus erythematosus (SLE). We recently described that immune complexes (IC) induce NET formation, promoting SLE-like disease in mice. In the current study, we investigated, for the first time to our knowledge, the role of NET in human SLE and their association with disease activity and severity. Levels of NET (myeloperoxidase-DNA complexes) were analyzed in plasma from 4 cross-sectional SLE cohorts (n = 44-142), 1 longitudinal SLE cohort (n = 47), and healthy individuals (n = 100) using ELISA. Type I interferon activity was determined using a cell reporter system. Patients with SLE had elevated levels of NET in circulation compared to healthy controls (p < 0.01). NET levels identified patients with a severe disease phenotype characterized by IC-driven nephritis (p < 0.05). Though not associated with current disease activity (p = 0.20), levels of NET were associated with future increase in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) within 3 months (OR 1.75, p = 0.01), as well as an overall heightened SLEDAI over 1 year (p < 0.01). Finally, levels of NET were associated with arterial events (OR 5.0, p = 0.02) and endothelial cell activation (p < 0.001). NET levels are elevated in patients with SLE, associated with IC-driven disease. NET levels provide significant clinical value in identifying patients at risk of active disease and/or severe disease, including nephritis and cardiovascular disease, and may allow for early interventions.

Clinical characteristics and survival of 413 patients with systemic lupus erythematosus in southeastern areas of South Korea: A multicenter retrospective cohort study.

To investigate demographic, clinical, laboratory, and immunological characteristics of patients with systemic lupus erythematosus (SLE) in southeastern areas of South Korea, and to perform survival analysis. We retrospectively evaluated 413 patients with SLE diagnosed in 3 tertiary rheumatology centers in South Korea from 1992 to 2016 by reviewing their medical charts. All patients fulfilled the 1997 revised American College of Rheumatology classification criteria for SLE. Most patients were women (92%), and the mean (±standard deviation) age at diagnosis was 30.9 (±12.9) years. The most common clinical manifestation was leukopenia (74.3%), followed by lymphopenia (73.6%), arthritis (59.1%), malar rash (48.4%), thrombocytopenia (46.5%), oral ulcer (35.1%), and biopsy-proven lupus nephritis (31.2%). Anti-nuclear, anti-double-stranded DNA, anti-Smith, and anti-Ro antibodies were positive in 97.8%, 70.1%, 38.4%, and 63% of patients, respectively. Twenty (4.8%) patients died during a median follow-up of 83months, and the cumulative 5-year and 10-year survival rates were 96.9% and 95.5%, respectively. The major causes of death were infection (50%) and lupus flare-up (50%). Male (hazards ratio [HR]=7.19, P=.001), pleuritis and/or pericarditis (HR=3.28, P=.012), childhood-onset (HR=3.57, P=.012), and late-onset (HR=4.65, P=.011) were independent risk factors for death. Compared with SLE cohorts in other ethnicities or countries, our patients tended to have a higher frequency of anti-Ro antibodies and hematologic disorders. This study describes clinical features of SLE in South Korea and suggests a remarkable phenotypic heterogeneity of SLE.

Estimates of Responsiveness, Minimally Important Differences, and Patient Acceptable Symptom State in Five Patient-Reported Outcomes Measurement Information System Short Forms in Systemic Lupus Erythematosus.

ObjectiveExaminations of Patient‐Reported Outcomes Measurement Information System (PROMIS) measures in adult systemic lupus erythematosus (SLE) have provided support for their cross‐sectional validity in SLE. We estimated responsiveness to change, meaningful changes (minimally important differences [MIDs]), and the patient acceptable symptom state (PASS) for five PROMIS short forms to facilitate longitudinal use and interpretation of PROMIS scales in SLE.MethodsData from five administrations of PROMIS short forms in the FORWARD SLE cohorts were used. Pearson correlation coefficients were used to assess associations between changes in PROMIS measures and changes in anchor measures for responsiveness analyses. Worse, same, or better groups were defined for each anchor. Differences in PROMIS scores were calculated for each consecutive PROMIS administration; mean changes in PROMIS scores of individuals in the worse, same, and better groups were calculated. Both anchor‐based and distribution‐based methods were used to estimate MIDs. PASS was defined as the 75th‐percentile positive score among those who considered their health to be acceptable or who were somewhat or very satisfied with their health.ResultsAll PROMIS short forms showed adequate responsiveness to changes in related patient‐reported outcomes. However, only the fatigue and pain interference scales were responsive to self‐reported SLE activity. Taking into account all methods, we estimated MIDs for each scale to be approximately two points. All PASS values were better than the population mean T‐score of 50.ConclusionThese results support use and further study of PROMIS short forms in SLE and should facilitate interpretation of PROMIS scores and changes.

Peripheral Nervous System Disease in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study.

To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients. Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate. Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy. PNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution.

Susceptibility of BAFF-var allele carriers to severe SLE with occurrence of lupus nephritis

BackgroundDysregulation of the B-cell activating factor (BAFF) system is involved in the pathogenesis of systemic lupus erythematosus (SLE). Increased serum concentrations of BAFF are related to lupus nephritis and disease activity among SLE patients. Recently, a variant of the BAFF-encoding gene, BAFF-var, was identified to be associated with autoimmune diseases, in particular SLE, and to promote the production of soluble BAFF. The present study aimed to assess the prevalence of BAFF-var in a cohort of 195 SLE patients and to analyze the association of the BAFF-var genotype (TNSF13B) with various manifestations of SLE.MethodsA cohort of 195 SLE patients from Central Europe, including 153 patients from the Swiss SLE Cohort Study and 42 patients from the University Hospital Essen, Germany, underwent genotyping for detection of BAFF-var allele.ResultsOf the 195 patients, 18 (9.2%) tested positive for BAFF-var variant according to the minor allele frequency of 4.6%. The presence of BAFF-var was associated with the occurrence of lupus nephritis (p = 0.038) (p = 0.03 and p = 0.003). Among various organ manifestations of SLE, the presence of BAFF-var was associated with the occurrence of lupus nephritis (p = 0.038; odds ratio [OR], 2.4; 95% confidence interval [CI], 0.89–6.34) and renal activity markers such as proteinuria and hematuria (p = 0.03; OR, 2.4; 95% CI, 0.9–6.4 for proteinuria; p = 0.003; OR, 3.9; 95% CI, 1.43–10.76 for hematuria). SLE patients carrying the BAFF-var allele exhibited increased disease activity at study entry, as determined by the physician’s global assessment (PGA: p = 0.002; OR, 4.8; 95% CI, 1.54–14.93) and the SLE Disease Activity Index (p = 0.012; OR, 3.5; 95% CI, 1.12–11.18). Consistent with that, the percentage of patients treated with immunosuppressive agents at study entry was higher among those carrying the BAFF-var allele than among those tested negative for BAFF-var (p = 0.006; OR, 3.7; 95% CI, 1.27–10.84).ConclusionsOur results indicate an association between the BAFF-var genotype and increased severity of SLE. Determining the BAFF-var status of SLE patients may improve the risk stratification of patients for whom the development of lupus nephritis is more likely and thus may be helpful in the follow-up care and treatment of SLE patients.

Prevalence and incidence of systemic lupus erythematosus and associated outcomes in the 2009-2016 US Medicare population.

We aimed to update data on the prevalence and incidence of systemic lupus erythematosus (SLE) in the Medicare population and describe associated outcomes. This observational study used Medicare 20% random sample data 2007-2016 to estimate SLE prevalence and incidence 2009-2016. The study population included patients aged ≥18 years (stratified by <65 and ≥65 years) with Medicare fee-for-service coverage. The SLE definition was based on a published and validated algorithm. All-cause death, hospitalizations, and kidney disease incidence were defined for a prevalent SLE cohort 2011-2015. Unadjusted event rates during 5-year follow-up were reported per 100 patient-years. The study included > 5 million eligible patients for each year 2009-2016. There were 19,518 (10,898, aged ≥65; 8620, aged <65) in 2016, extrapolated to 97,590 (54,490 aged ≥65; 43,100 aged <65) in the overall 2016 Medicare population. Age- and sex-adjusted prevalence rates (per 100,000 Medicare population) ranged from 301.1 in 2009 to 366.6 in 2016, all ages, and 184.0-239.9, ≥65 years. There were 2614 (1844 aged ≥65; 770 aged <65) incident patients in 2016; age-/sex-adjusted incidence rates (per 100,000 Medicare population) ranged from 46.9 in 2009 to 49.0 in 2016, all ages, and 37.5-40.8, ≥65. Five-year unadjusted mortality, elderly vs. younger, was 8.8 vs. 3.8, morbidity 34.5 vs. 32.4, and kidney disease incidence 19.8 vs. 18.0 per 100 patient-years. Prevalence rates steadily increased while incidence was relatively stable 2009-2016. Our data should be interpreted with caution due to our elderly study population.