Systemic Lupus Erythematosus International Collaborating Clinics Research Articles

Diagnostic performance of classification criteria for systemic lupus erythematosus: A validation study from Singapore.

Classification criteria for systemic lupus erythematosus (SLE) include American College of Rheumatology (ACR) 1997, Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 and European Alliance of Associations for Rheumatology (EULAR)/ACR 2019 criteria. Their performance in an Asian childhood-onset SLE (cSLE) population remains unclear as the clinical manifestations differ. We aim to evaluate the diagnostic performance in a cSLE cohort in Singapore. Cases were physician-diagnosed cSLE, while controls were children with mixed and undifferentiated connective tissue disease that posed an initial diagnostic challenge. Data were retrospec-tively reviewed to establish the 3 criteria fulfilled at diagnosis and over time. The study population included 120 cSLE cases and 36 controls. At diagnosis, 102 (85%) patients fulfilled all criteria. SLICC-2012 had the highest sensitivity (97.5%, 95% confidence interval [CI] 92.3-99.5), while ACR-1997 had the highest specificity (91.7%, 95% CI 77.5-98.3). All criteria had diagnostic accuracies at more than 85%. Over time, 113 (94%) fulfilled all criteria. SLICC-2012 remained the criteria with the highest sensitivity (99.2%, 95% CI 95.4-99.9), while ACR-1997 had the highest specificity (75.0%, 95% CI 57.8-87.9). Only SLICC-2012 and ACR-1997 had more than 85% diagnostic accuracy over time. Using a cutoff score of ≥13 for EULAR/ACR-2019 criteria resulted in improved diagnostic performance. SLICC-2012 criteria had the highest sensitivity early in the disease course in this first study evaluating the SLE classification criteria performance in a Southeast Asian cSLE cohort, while the ACR-1997 criteria had the highest specificity. Using a cutoff score of ≥13 for EULAR/ACR-2019 improved the diagnostic performance.

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.

Factors Associated With Candidiasis in Systemic Lupus Erythematosus Patients in Cipto Mangunkusumo National General Hospital: A Single-Center Case-Control Study.

Background: Infection has been a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. One of the infections encountered in SLE patients is candidiasis. Therefore, we aimed to conduct a case-control study to explore the risk factors associated with candidiasis in SLE patients in our center.Methods: Medical records of 20 SLE patients with fungal infection were obtained, and a case-control study was conducted with an age and sex-matched control group of 20 patients. Data were obtained from the Cipto Mangunkusumo National General Hospital. SLE confirmatory diagnosis was based on Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 criteria. Patients with comorbidities of various chronic diseases (diabetes, HIV, and chronic kidney disease) were excluded. Statistical analysis was conducted using the Mann-Whitney U test with statistical significance defined as a p-value < 0.05.Result: Based on the analysis, a maximum corticosteroid dose of 24 (4-250) mg/day for the last one year was associated with the development of fungal infection (p = 0.047). Lower absolute lymphocyte count (748 cells/mm³ versus 1635 cells/mm³) was also associated with the occurrence of candidiasis in SLE patients (p = 0.008).Conclusion: Physicians should be aware that corticosteroid use in SLE patients may cause candidiasis. Monitoring of maximum corticosteroid dose and absolute lymphocyte count is important to help prevent candidiasis. Patients should also be educated regarding the risk of candidiasis from corticosteroid use.

Predisposing Factors of Tuberculosis Infection in Systemic Lupus Erythematosus Patients: A Single-Center Case-Control Study.

Introduction: Indonesia has the second-highest tuberculosis cases in the world, according to the global WHO tuberculosis report, amounting to approximately 10% of the world's tuberculosis cases. Systemic lupus erythematosus (SLE) patients are at an increased risk for tuberculosis infection. This research aims to analyze the association between corticosteroid pulse dose, corticosteroid cumulative dose, SLE disease duration, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and lupus nephritis status with the development of tuberculosis in SLE patients.Methods: This research was a matched case-control study to identify risk factors of tuberculosis infection in SLE patients. Data were taken from medical records of Cipto Mangunkusumo National General Hospital, a national tertiary hospital. Inclusion criteria were patients who meet the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 criteria of SLE in the period of 2012-2016 or patients who meet the SLICC 2012 SLE criteria and developed tuberculosis between 2012 and 2016. Statistical analyses used were bivariate analysis and correlation analysis. All statistical analyses were conducted using SPSS software (IBM Corp., Armonk, NY). All statistical analyses were defined as statistically significant when the p-value was less than 0.05.Results: A total of 48 SLE patients were included from medical records consisting of 24 SLE patients with tuberculosis infection and controls of 24 SLE patients without tuberculosis infection. In this study, it was observed that the presence of lupus nephritis (p = 0.001), administration of pulse corticosteroids (p = 0.048), high corticosteroid cumulative dose (p = 0.001), and high SLEDAI score (p = 0.003) were associated with tuberculosis infection. Correlation analysis showed that all of these variables had a weak positive correlation with tuberculosis infection in SLE patients.Conclusion: SLE patients with lupus nephritis, administration of pulse corticosteroids, high cumulative corticosteroid dose, and high SLEDAI score have a higher risk of tuberculosis infection. Clinicians and patients should be aware of these risk factors in SLE patients to prevent tuberculosis infection. Corticosteroid pulse dose should be avoided in SLE patients and if it is needed, tuberculosis prophylaxis may be considered.

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.

New Classification Criteria for Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with highly variable clinical and immunological manifestations. Classification and diagnosis of SLE are complicated by the multi-organ nature of the disease and by our incomplete understanding of its pathophysiology. The 1997 update of the 1982 American College of Rheumatology (ACR) criteria for SLE has been widely used for classification of SLE. In order to improve clinical relevance and early diagnosis, the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) group suggested the 2012 SLICC criteria. These sets of classification criteria have unweighted lists of various serological and clinical findings typical of SLE, can be fulfilled by reaching a sum score of points. The only exception is biopsy-proven lupus nephritis with autoantibodies in the 2012 SLICC criteria. In an attempt to overcome limitations of the previous sets of SLE classification criteria, the new 2019 SLE European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for SLE have been recently published. The 2019 EULAR/ACR criteria include positive ANA at least once as obligatory entry criterion; followed by additive hierarchically clustered and weighted criteria. The structure and weighting of criteria constitute a paradigm shift in the classification of SLE. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%. This review attempts to delineate the history, performance and limitations of the current sets of SLE criteria.

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.

Investigating lupus retention in care to inform interventions for disparities reduction: an observational cohort study

BackgroundSystemic lupus erythematous (SLE) disproportionately impacts patients of color and socioeconomically disadvantaged patients. Similar disparities in HIV were reduced through a World Health Organization-endorsed Care Continuum strategy targeting “retention in care,” defined as having at least two annual visits or viral load lab tests. Using similar definitions, this study aimed to examine predictors of lupus retention in care, to develop an SLE Care Continuum and inform interventions to reduce disparities. We hypothesized that Black patients and those residing in disadvantaged neighborhoods would have lower retention in care.Methodsors manually validated 545 potential adult cases with SLE codes in 2013–2014 using 1997 American College of Rheumatology (ACR) or 2012 Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria. We identified 397 SLE patients who met ACR or SLICC criteria for definite lupus, had at least one baseline rheumatology visit, and were alive through 2015. Retention in care was defined as having two ambulatory rheumatology visits or SLE labs (e.g., complement tests) during the outcome year 2015, analogous to HIV retention definitions. Explanatory variables included age, sex, race, ethnicity, smoking status, neighborhood area deprivation index (ADI), number of SLE criteria, and nephritis. We used multivariable logistic regression to test our hypothesis and model predictors of SLE retention in care.ResultsAmong 397 SLE patients, 91% were female, 56% White, 39% Black, and 5% Hispanic. Notably, 51% of Black versus 5% of White SLE patients resided in the most disadvantaged ADI neighborhood quartile. Overall, 60% met visit-defined retention and 27% met complement lab-defined retention in 2015. Retention was 59% lower for patients in the most disadvantaged neighborhood quartile (adjusted OR 0.41, CI 0.18, 0.93). No statistical difference was seen based on age, sex, race, or ethnicity. More SLE criteria and non-smoking predicted greater retention.ConclusionsDisadvantaged neighborhood residence was the strongest factor predicting poor SLE retention in care. Future interventions could geo-target disadvantaged neighborhoods and design retention programs with vulnerable populations to improve retention in care and reduce SLE outcome disparities.

Antibodies against carbamylated proteins and cyclic citrullinated peptides in systemic lupus erythematosus: results from two well-defined European cohorts.

BackgroundArticular manifestations are common in systemic lupus erythematosus (SLE) whereas erosive disease is not. Antibodies to cyclic citrullinated peptide (anti-CCP) are citrulline-dependent in rheumatoid arthritis (RA), whereas the opposite is suggested in SLE, as reactivity with cyclic arginine peptide (CAP) is typically present. Antibodies targeting carbamylated proteins (anti-CarP) may occur in anti-CCP/rheumatoid factor (RF)-negative cases long before clinical onset of RA. We analysed these antibody specificities in sera from European patients with SLE in relation to phenotypes, smoking habits and imaging data.MethodsCases of SLE (n = 441) from Linköping, Sweden, and Leiden, the Netherlands, were classified according to American College of Rheumatology (ACR) and/or Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria. IgG anti-CCP, anti-CAP and anti-CarP were analysed by immunoassays. Radiographic data from 102 Swedish patients were available.ResultsThere were 16 Linköping (6.8%) and 11 Leiden patients (5.4%) who were anti-CCP-positive, of whom approximately one third were citrulline-dependent: 40/441 (9.1%) were anti-CarP-positive, and 33% of the anti-CarP-positive patients were identified as anti-CCP-positive. No associations were found comparing anti-CCP or anti-CarP with ACR-defined phenotypes, immunologic abnormalities or smoking habits. Radiographically confirmed erosions were found in 10 patients, and were significantly associated with anti-CCP, anti-CarP and RF. Musculoskeletal ultrasonography scores were higher in anti-CCP-positive compared to anti-CCP-negative patients.ConclusionsIn the hitherto largest anti-CarP study in SLE, we demonstrate that anti-CarP is more prevalent than anti-CCP and that the overlap is limited. We obtained some evidence that both autoantibodies seem to be associated with erosivity. Similar pathogenetic mechanisms to those seen in RA may be relevant in a subgroup of SLE cases with a phenotype dominated by arthritis.

The New Classification Criteria of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a prototype for multi-system, autoimmune diseases of unknown etiology, characterized by the production of autoantibodies. SLE can involve any organ system of the body with constitutional symptoms, including musculoskeletal, skin, renal, neuropsychiatric, cardiovascular, respiratory and gastrointestinal systems. These wide spectra of disease manifestations have made disease classification difficult. American College of Rheumatology (ACR) proposed classification criteria for SLE for research purpose in 1982, which had been widely used for research purpose and not for diagnosis. In 1997, these criteria were updated with further recognition of antiphospholipid antibodies, but not validated. But ACR criteria didn``t still meet the necessity for earlier diagnosis of SLE. In order to improve clinical relevance and incorporate new knowledge to the field of lupus immunology, the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC), an international lupus expert group dedicated to clinical research on lupus, revised the ACR systemic lupus classification criteria in 2012. The new 2012 SLICC criteria were validated using a large set of patient scenarios rated by experts. The history and diagnostic utility of SLE criteria are covered in this review.

The SLICC inception cohort for atherosclerosis

The Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) is a group of rheumatologists and methodologists from 27 international centers who have a particular interest and expertise in systemic lupus erythematosus. Initially, its efforts focused on development and validation of disease activity and damage indices. In 2000, the SLICC Registry for Atherosclerosis was established to determine the incidence, prevalence, nature, and risk factors of atherosclerotic coronary artery disease in systemic lupus erythematosus. Risk factors for coronary artery disease at presentation to the cohort were reported, as well as their accumulation over the first few years. Development of the metabolic syndrome was also described. Among the first 1078 patients who entered the cohort, 61 vascular events have occurred in 47 patients who were older at diagnosis and more likely male and hypertensive than were the patients without vascular events. Additional studies using this cohort are ongoing.

Analysis of C1q polymorphisms suggests association with systemic lupus erythematosus, serum C1q and CH50 levels and disease severity

Background:Several findings link systemic lupus erythematosus (SLE) with C1q, the first molecule of the classical complement pathway. Polymorphisms of the C1qA gene are associated with low serum C1q levels in...

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.