Systemic Lupus Erythematosus International Research Articles

Health Related Quality of Life in Juvenile-Onset Systemic Lupus Erythematosus: A Questionnaire-Based Study

ObjectivesThis study aimed to evaluate health related quality of life (HRQOL) in Egyptian children with systemic lupus erythematosus (SLE) using 3 different tools.MethodsIn this questionnaire-based study, 100 children with SLE were included. HRQOL was assessed using the Pediatric Quality of Life Inventory Generic Core Scales (PedsQL™ 4.0 GCS), PedsQL™ 3.0 Rheumatology Module (PedsQL3-RM) and the Simple Measure of the Impact of Lupus Erythematosus in Youngsters (SMILEY). SLE disease activity index (SLEDAI) was used to evaluate activity and SLE International Collaborating Clinics/ American College of Rheumatology Damage Index (SDI) was used to evaluate chronic damage.ResultsAll mean scores of PedsQLTM4.0 GCS domains in SLE patients were lower than published normative data and previously published results of Egyptian healthy controls (p < 0.001). All mean scores of PedsQL-3RM domains were significantly lower than published normative data except for the treatment and pain and hurt domains (p = 0.1, 0.2 respectively). SMILEY scores were low and the lowest domain scores was “Burden of SLE”. Longer duration of illness, higher cumulative steroid doses, higher SLEDAI and SDI scores and presence of obesity were associated with lower scores for all 3 tools (p < 0.001).Conclusion for PracticeThe Arabic copies of PedsQL™ 4.0 GCS, PedsQL3-RM and SMILEY are easily used for Arabic speaking subjects and easily interpreted by physician and can be implemented for frequent monitoring of SLE HRQOL. Controlling the disease activity and using lowest doses of steroids and other immunosuppressive drugs are the corner stone strategies for improving HRQOL in SLE children.

Relationship between the EULAR/ACR classification criteria and organ damage in systemic lupus erythematosus.

To study the relationship between the 2019 EULAR/ACR classification criteria and organ damage in patients with systemic lupus erythematosus (SLE). Patients involved in a cross-sectional validation study of the EULAR/ACR criteria and judged by a panel of rheumatologists to be clinical SLE were studied. Those who fulfilled the EULAR/ACR criteria at their last clinic visit were stratified into 2 groups based on a cutoff score of 20. The last SLE International Collaborating Clinic (SLICC) Organ Damage Index (SDI) was compared between these two groups. Relationship among the domains of the EULAR/ACR criteria and SDI in all patients was studied by using Spearman's rank correlation. A total of 562 SLE patients were studied (93.6% women; age 36.5 ± 14.1years; follow-up duration 11.6 ± 6.6years). The mean and median EULAR/ACR criteria scores in those who fulfilled the EULAR/ACR criteria (N = 542) were 24.6 ± 7.3 and 24 (interquartile range 19-30), respectively. A total of 392 patients had EULAR/ACR scores of ≥20 (group 1), and 150 patients had scores of 10-19 (group 2). Group 1 patients had significantly higher prevalence of fever, alopecia, oral ulcers, acute lupus skin lesions, arthritis, serositis, seizure, hemolytic anemia, leukopenia, and renal disease and so were the anti-dsDNA, anti-Sm, antiphospholipid antibodies, and low complement state. Organ damage (SDI score of ≥1) occurred in 232 (42.8%) patients. Patients in group 1 had significantly higher SDI scores in the renal, cardiovascular, dermatological, and gonadal domains than group 2. The renal, neuropsychiatric, and antiphospholipid antibody domain scores of the EULAR/ACR criteria correlated positively with the total SDI. The renal domain of the EULAR/ACR criteria had the strongest correlation with renal damage (Rho 0.30; p < 0.001). Patients who scored 10 points in the renal domain had significantly higher renal damage score than those scored 8 points or 4 points. Gonadal damage score was also significantly more common in the 10-point than in the 8-point group. In addition to disease classification, the EULAR/ACR SLE criteria may have value in predicting prognosis.

Predictors of Initial Hydroxychloroquine Receipt Among Medicaid Beneficiaries With Incident Systemic Lupus Erythematosus.

Although hydroxychloroquine/chloroquine (HCQ/CQ) form the cornerstone of systemic lupus erythematosus (SLE) treatment, not all patients receive this, which may contribute to disparities in outcomes. The present study was undertaken to investigate factors associated with first dispensing of HCQ/CQ. Using Medicaid insurance claims from 2000 to 2010, we identified individuals ages 18-65 years with incident SLE (≥3 SLE International Classification of Diseases, Ninth Revision codes separated by ≥30 days without prior SLE codes or HCQ/CQ use for 24 months). The primary outcome was first dispensing of HCQ/CQ within 24 months of the first SLE code. We used Cox proportional hazards regression models to examine the association between sociodemographic factors, comorbidities, health care utilization, and medication use and HCQ/CQ dispensing within 24 months of diagnosis. We identified 9,560 Medicaid beneficiaries with incident SLE; 41% received HCQ (n = 3,949) or CQ (n = 14) within 24 months of diagnosis. Younger patients were more likely to receive HCQ/CQ. Black, Asian, Hispanic, and American Indian/Alaska Native individuals were more likely to receive HCQ/CQ than White individuals. Alcohol and nicotine use, chronic pain, diabetes mellitus, and end-stage renal disease were associated with lower dispensing. Appointments and preventive care services were associated with higher rates, and more hospitalizations with lower rates. Only 41% of Medicaid beneficiaries with SLE received HCQ/CQ within 24 months of diagnosis. Greater outpatient and preventive care increased receipt. All non-White race/ethnicities had higher rates of first dispensing. Time to initial HCQ/CQ dispensing may not explain racial/ethnic disparities in adverse outcomes, highlighting the need to consider other care quality-related issues and medication adherence challenges.

Developing and Validating Methods to Assemble Systemic Lupus Erythematosus Births in the Electronic Health Record.

Electronic health records (EHRs) represent powerful tools to study rare diseases. Our objective was to develop and validate EHR algorithms to identify systemic lupus erythematosus (SLE) births across centers. We developed algorithms in a training set using an EHR with over 3 million subjects and validated the algorithms at 2 other centers. Subjects at all 3 centers were selected using ≥1 code for SLE International Classification of Diseases, Ninth Revision (ICD-9) or SLE International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification (ICD-10-CM) and ≥1 ICD-9 or ICD-10-CM delivery code. A subject was a case if diagnosed with SLE by a rheumatologist and had a birth documented. We tested algorithms using SLE ICD-9 or ICD-10-CM codes, antimalarial use, a positive antinuclear antibody ≥1:160, and ever checked double-stranded DNA or complement, using both rule-based and machine learning methods. Positive predictive values (PPVs) and sensitivities were calculated. We assessed the impact of case definition, coding provider, and subject race on algorithm performance. Algorithms performed similarly across all 3 centers. Increasing the number of SLE codes, adding clinical data, and having a rheumatologist use the SLE code all increased the likelihood of identifying true SLE patients. All the algorithms had higher PPVs in African American versus White SLE births. Using machine learning methods, the total number of SLE codes and an SLE code from a rheumatologist were the most important variables in the model for SLE case status. We developed and validated algorithms that use multiple types of data to identify SLE births in the EHR. Algorithms performed better in African American mothers than in White mothers.

Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Role of Fibroblast Growth Factor 23- Phosphate Axis.

PurposeDespite management advances, accelerated atherosclerotic cardiovascular disease (ACVD) remains a major cause of morbimortality in systemic lupus erythematosus (SLE) patients; that is not fully explained by traditional risk factors. Fibroblast growth factor-23 (FGF23) is a bone-derived phosphaturic hormone with multiple klotho-dependent and independent effects, including promotion of atherosclerosis and vascular calcification, particularly in the context of chronic kidney disease. Increased circulating FGF23 was reported in SLE patients, particularly with lupus nephritis (LN); but its atherogenic role in these disorders was not explored.Subjects and MethodsThree study groups of predominantly middle-aged females were categorized by the 2012 SLE International Collaborating Clinics (SLICC) criteria as SLE (without LN), LN, or controls matching for traditional CVD risk profile. Measures of SLE activity, damage, steroid therapy, and glomerular filtration rate were calculated. Fasting blood samples were checked for serum lipid profile, anti-DNA, urea, creatinine, uric acid, proteins, albumin, calcium, phosphorus, C3, C4, CRP, vitamin-D3, intact parathyroid hormone and FGF23 (iFGF23). By carotid ultrasonography, mean common carotid artery intima-media thickness (CC-IMT), plaque score (PS) and internal carotid resistive index (ICRI) were recorded.ResultsCC-IMT, ICRI and serum iFGF23 differed along the study groups (LN>SLE>controls). In both SLE and LN patients, serum iFGF23 had a significant positive correlation with serum phosphorus, CC-IMT and PS. On multivariate analysis, the strongest predictor of increased CC-IMT was cumulative steroid dose in SLE and serum iFGF23 in LN patients. Most significant independent predictors of increased serum iFGF23 were hyperphosphatemia in SLE and proteinuria in LN patients.ConclusionFGF23-phosphate axis has a key role in accelerated ACVD in SLE patients. Serum phosphorus and iFGF23 should be included in ACVD risk profile assessment of these patients. Prospective studies shall define the role of dietary and/or pharmacologic control of hyperphosphatemia and proteinuria in reducing circulating iFGF23 and ACVD in them.

The effect of smoking on cumulative damage in systemic lupus erythematosus: An incident cohort study.

To investigate the relationship between smoking history and pack-year exposure on the rate of end-organ damage in systemic lupus erythematosus (SLE). The SLE incident cohort included patients who met American College of Rheumatology (ACR) 1997 or SLE International Collaborating Clinics (SLICC) 2012 SLE criteria and had rheumatology encounters at a US academic institution (2008-16). The primary outcome was median time to SLICC/ACR damage index (SLICC/ACR-DI) increase or death. Main explanatory variables were smoking status and pack-years. Covariates included age, sex, race, ethnicity, receipt of Medicaid, neighborhood area deprivation index, and baseline SLE damage. Damage increase-free survival was evaluated by smoking status and pack-years using Kaplan-Meier and Cox proportional hazards methods. Patients of Black race and Medicaid recipients were more commonly current smokers (p's < 0.05). Former smokers were older and more likely to have late-onset SLE (54% versus 33% of never and 29% of current smokers, p = 0.001). Median time to SLICC/ACR-DI increase or death was earlier in current or former compared to never smokers (4.5 and 3.4 versus 9.0 yrs; p = 0.002). In multivariable models, the rate of damage accumulation was twice as fast in current smokers (HR 2.18; 1.33, 3.57) and smokers with a >10 pack-year history (HR 2.35; 1.15, 3.64) versus never smokers. In this incident SLE cohort, past or current smoking predicted new SLE damage 4-5 years earlier. After adjustment, current smokers and patients with a pack-year history of >10 years accumulated damage at twice the rate of never smokers.

Hydroxychloroquine Suppresses Interferon-inducible Genes and B Cell Activating Factor in Patients With Incomplete and New-onset Systemic Lupus Erythematosus.

Hydroxychloroquine (HCQ) is commonly used as first-line treatment for systemic lupus erythematosus (SLE). Interferon (IFN)-inducible gene expression, IFN-γ-induced protein 10 (IP-10) and B cell activating factor (BAFF) are early mediators in SLE. The purpose of this study was to analyze the effects of HCQ on these factors. Patients with incomplete SLE (iSLE; antinuclear antibody titer ≥ 1:80, symptoms < 5 years, ≥ 1 objectified clinical American College of Rheumatology or SLE International Collaborating Clinics criteria), or new-onset, mild SLE were included when HCQ treatment was started for clinical reasons. Blood samples were taken at start and after 16 weeks. Three SLE-related IFN-inducible genes were measured in whole blood by real-time PCR, and an IFN score was calculated. Serum levels of IP-10 and BAFF were measured using ELISA. In total, 9 patients were included: 7 with iSLE and 2 with new-onset SLE. The median SLE Disease Activity Index (SLEDAI) was 4. After 16 weeks of treatment with HCQ, the expression of IFN-inducible genes decreased in 8 of 9 patients, and the IFN-3 score decreased significantly (P = 0.012). There was a trend towards lower IP-10 levels (P = 0.055), and a significant decrease in BAFF levels (P = 0.023). HCQ suppresses IFN score and BAFF levels in patients with iSLE or new-onset SLE, and there is a trend towards lowering IP-10 levels. As these biomarkers are early mediators in SLE, this might support the hypothesis that HCQ could influence disease progression. However, prospective research with a larger sample size and longer follow-up is needed.

Cerebrovascular Events in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study.

To determine the frequency, characteristics, and outcomes of cerebrovascular events (CerVEs), as well as clinical and autoantibody associations in a multiethnic/racial inception cohort of patients with systemic lupus erythematosus (SLE). A total of 1,826 patients were assessed annually for 19 neuropsychiatric (NP) events, including 5 types of CerVEs: 1) stroke, 2) transient ischemia, 3) chronic multifocal ischemia, 4) subarachnoid/intracranial hemorrhage, and 5) sinus thrombosis. Global disease activity (Systemic Lupus Erythematosus Disease [SLE] Activity Index 2000), damage scores (SLE International Collaborating Clinics/American College of Rheumatology Damage Index), and Short Form 36 (SF-36) scores were collected. Time to event, linear and logistic regressions, and multistate models were used as appropriate. CerVEs were the fourth most frequent NP event: 82 of 1,826 patients had 109 events; of these events, 103 were attributed to SLE, and 44 were identified at the time of enrollment. The predominant events were stroke (60 of 109 patients) and transient ischemia (28 of 109 patients). CerVEs were associated with other NP events attributed to SLE, non-SLE-attributed NP events, African ancestry (at US SLICC sites), and increased organ damage scores. Lupus anticoagulant increased the risk of first stroke and sinus thrombosis and transient ischemic attack. Physician assessment indicated resolution or improvement in the majority of patients, but patients reported sustained reduction in SF-36 summary and subscale scores following a CerVE. CerVEs, the fourth most frequent NP event in SLE, are usually attributable to lupus. In contrast to good physician-reported outcomes, patients reported a sustained reduction in health-related quality of life following a CerVE.

Mannose binding lectin 2 promotor-221 X/Y gene polymorphism in Egyptian systemic lupus erythematosus patients

Aim of the workThe present study was undertaken to determine whether mannose binding lectin-2 (MBL2) promotor-221X/Y gene polymorphism had a possible association with systemic lupus erythematosus (SLE) in Mansoura city. Patients and methodsWe analyzed functional polymorphisms in the promoter of MBL2 gene in 106 Egyptian SLE patients and 99 healthy controls by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). SLE disease activity was evaluated using SLE Disease Activity Index (SLEDAI) and organ damage was evaluated using SLE International Collaborating Clinic Damage Index (SLICC/DI). ResultsThe patients were 95 females and 11 males with a mean age of 34.4±10.2years and disease duration of 4±3.03years. Genotype frequencies of MBL2 were significantly different between patients and controls. The YY genotype was significantly associated with SLE in 77 (72.6%) patients compared to the control in 59 (59.6%) (p=0.048). The XY genotype was in 29 (27.4%) patients and in 40 (40.4%) control. An association was found between the XY genotype and alopecia (p=0.048), central nervous system involvement (p=0.03), vasculitis (p=0.004) and anti-phospholipid syndrome (p=0.001) while the YY genotype was associated with discoid rash, low serum complement level (C3; p=0.014 and C4; p=0.008) and with the presence of anticardiolipin antibodies (p=0.032). MBL genotype did not show any correlation with SLEDAI or SLICC/DI. ConclusionOur results indicate that MBL2 promotor-221X/Y polymorphism is a possible key-player for SLE development as well as the occurrence of some clinical and laboratory features. Further longitudinal studies including other single nucleoproteins are needed to clarify the role of MBL2.

Case definitions in Swedish register data to identify systemic lupus erythematosus

ObjectiveTo develop and investigate the utility of several different case definitions for systemic lupus erythematosus (SLE) using national register data in Sweden.MethodsThe reference standard consisted of clinically confirmed SLE cases...

Systemic lupus erythematosus activity and beta two microglobulin levels.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a cyclical clinical course. Evaluation of the clinical activity of this disease is important for choosing the correct treatment. The objective of this study was to analyze the value of beta-2 microglobulin (β2M) serum levels in determining SLE clinical activity. Cross-sectional analytical study conducted at the rheumatology outpatient clinic of a private university hospital. 129 SLE patients were studied regarding disease activity using SLEDAI (SLE Disease Activity Index) and cumulative damage using SLICC ACR (SLE International Collaborating Clinics/American College of Rheumatology Damage Index for SLE). At the same time, the β2M serum level, ESR (erythrocyte sedimentation rate), anti-dsDNA (anti-double-stranded DNA) and C3 and C4 complement fractions were determined. β2M levels correlated positively with SLEDAI (P = 0.02) and ESR (P = 0.0009) and negatively with C3 (P = 0.007). Patients who were positive for anti-dsDNA had higher β2M serum levels (P = 0.009). β2M levels are elevated in SLE patients with active disease.

Study of bone mineral density in patients with systemic lupus erythematosus

ObjectiveThe aim of the study was to investigate bone mineral density (BMD) in systemic lupus erythematosus (SLE) patients, either newly diagnosed or treated.BackgroundAs a consequence of the chronic course of SLE, osteoporosis can be a further clinical challenge in these patients. SLE-related medications can increase bone turnover, which eventually weakens bone architecture, and subsequently reduces bone strength and increases the risk for fractures, but there is good evidence that the disease per se can lead to reduced bone mass through several mechanisms such as reduced motility, renal impairment, and the systemic effect of bone-resorbing cytokines.Materials and methodsIn this study, we examined 30 lupus patients diagnosed with SLE. Patients were divided into two groups. Group II included 15 newly diagnosed patients and group III included 15 treated lupus patients. Patients diagnosed with SLE met four or more criteria of the American College of Rheumatology (ACR) for SLE. SLE Disease Activity Index (SLEDAI) and SLE International Collaboration Clinics/ACR (SLICC/ACR) index were calculated for all patients. Ten healthy adults were included as the control group (group I). Dual-energy X-ray absorptiometry was performed in all studied patients in addition to routine investigations.ResultsThe total patient number was 30. Ninety-three percent of patients were female and in the age group of 17-30 years. There was a significant reduction in BMD in diagnosed lupus patients (groups II and III) compared with healthy adults of the same age and sex. Forty percent of newly diagnosed lupus patients had osteopenia. Sixty percent of treated patients had osteopenia and 20% had osteoporosis. There was no difference among lupus patients with low BMD as regards steroid dose, SLEDAI, and SLICC/ACR index.ConclusionBMD was reduced in SLE patients as compared with healthy age-matched and sex-matched controls. It decreased in both newly diagnosed (40%) and treated lupus patients (80%). BMD in lupus patients was not affected by the duration of disease, corticosteroid doses, or SLEDAI and SLICC/ACR index.

FRI0340 Prevalence and significance of thrombocytopenia in juvenile-onset systemic lupus erythematosus at presentation and one year follow-up

BackgroundThrombocytopenia is both common in adult-onset Systemic Lupus Erythematosus (SLE), prevalence ranging up to 40% and associated with increased disease activity, damage accrual and mortality (1). In juvenile-onset SLE (JSLE)...

Disease activity, damage and survival in Mexican patients with acute severe systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a clinical syndrome of varying severity. Although the survival and prognosis of SLE have steadily improved, there is a group of patients who present an acute fatal outcome despite aggressive therapy. We designed this study to evaluate the factors associated with mortality in patients with acute severe SLE. During 2004-06, 41 Mexican SLE patients that could not be managed in the out-patient clinic and with acute severe major organ system involvement [nephritis, severe thrombocytopenia (platelet count below 20 000 per microL) acute neuropsychiatric pulmonary, gastrointestinal or cardiac disease and generalized vasculitis] were studied. During the first admission, disease activity (SLE Disease Activity Index (SLEDAI), SLE Activity Measured), damage [SLE International Collaborating Clinics (SLICC)], and therapy were assessed. Survival using Kaplan-Meier curves, odd ratios with 95% confidence interval and logistic regression analysis were used to determine risk factors for mortality. Ninety percent were female with a mean age of 29 +/- 19 years and mean disease duration of 21 +/- 9 months. The principal causes of first admission were renal (27%), SNC (22%) and cardiopulmonary (15%). After a mean follow-up of 9.7 +/- 6 months, 16 (39%) patients died. Deceased patients had significantly higher SLEDAI (P = 0.004), and SLICC (P = 0.03) scores. The manifestations associated with mortality were renal disease activity (odds ratio, OR 4.6, confidence interval, CI 95% 1.0-20.6), infections (OR 3.2 CI 95% 2.0-5.3) and thrombocytopenia (OR 4.0, CI 95% 1.0-15.9). The survival at 9.7 months was 72, 62 and 50% in patients with an SLEDAI score of 3-10, 11-20 and > or =21, respectively. The SLEDAI score, the presence of damage and infection were associated with death in patients with acute severe SLE.

Foley-catheter induction of labour.

OBJECTIVE: To evaluate whether the polymorphism of Fas promoter -670 is associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and their clinical features. METHODS: A polymerase chain reaction of a genomic DNA-restriction fragment length polymorphism was used to determine genotypes of the Fas promoter -670 in 87 patients with SLE, 87 with RA, and 87 healthy controls. A second cohort of SLE patients (n = 85) was included. Clinical manifestations were analyzed in each patient and correlated with the genotypes. RESULTS: The genotype distribution of the Fas promoter -670 did not differ between patients with SLE and control subjects (AA, GA, GG genotypes 31, 54, 15% vs 30, 55, 15% controls, respectively; chi-squared = 0.03, 2 df, p = 0.99) and between RA patients and controls (AA, GA, GG genotypes 38, 44, 18% vs 30, 55, 15% controls, respectively; chi-squared = 2.30, 2 df, p = 0.32). Regarding the clinical status of lupus patients according to Fas promoter -670 genotypes, there was no significant difference in age at onset, anti-dsDNA titer, C3, C4 level, renal involvement, number of American College of Rheumatology (ACR) criteria met, SLE Disease Activity Index, SLE International Collaborating Clinics/ACR Damage Index, or autoantibody profiles. However, the frequency of anti-RNP antibody was significantly different in the AA, GA, and GG groups (71, 25, 30%; chi-squared = 13.29, 2 df, p = 0.001). To confirm this finding, the Fas promoter -670 genotype was examined in a second cohort of SLE patients (n = 85). The result in the second cohort replicated the association shown in the first. In patients with RA, there was no significant difference in clinical and laboratory findings according to the Fas promoter -670 genotypes. CONCLUSION: Our data suggest that the Fas promoter -670 polymorphism is associated with development of anti-RNP antibodies in SLE.