SLICC Damage Index Research Articles

The Impacts of the Clinical and Genetic Factors on Chronic Damage in Caucasian Systemic Lupus Erythematosus Patients.

Objective: The purpose of this study was to determine the distribution of organ damage in a cohort of systemic lupus erythematosus (SLE) patients and to evaluate the roles of clinical and genetic factors in determining the development of chronic damage. Methods: Organ damage was assessed by the SLICC Damage Index (SDI). We analyzed a panel of 17 single-nucleotide polymorphism (SNPs) of genes already associated with SLE, and we performed a phenotype–genotype correlation analysis by evaluating specific domains of the SDI. Results: Among 175 Caucasian SLE patients, 105 (60%) exhibited damage (SDI ≥1), with a median value of 1.0 (IQR 3.0). The musculoskeletal (26.2%), neuropsychiatric (24.6%) and ocular domains (20.6%) were involved most frequently. The presence of damage was associated with higher age, longer disease duration, neuropsychiatric (NP) manifestations, anti-phospholipid syndrome and the positivity of anti-dsDNA. Concerning therapies, cyclophosphamide, mycophenolate mofetil and glucocorticoids were associated with the development of damage. The genotype–phenotype correlation analysis showed an association between renal damage, identified in 6.9% of patients, and rs2205960 of TNFSF4 (p = 0.001; OR 17.0). This SNP was significantly associated with end-stage renal disease (p = 0.018, OR 9.68) and estimated GFR < 50% (p = 0.025, OR 1.06). The rs1463335 of MIR1279 gene was associated with the development of NP damage (p = 0.029; OR 2.783). The multivariate logistic regression analysis confirmed the associations between TNFSF4 rs2205960 SNP and renal damage (p = 0.027, B = 2.47) and between NP damage and rs1463335 of MIR1279 gene (p = 0.014, B = 1.29). Conclusions: Our study could provide new insights into the role of genetic background in the development of renal and NP damage.

The association of urinary plasmin level with renal involvement and disease flare among systemic lupus erythematosus patients.

To explore the ability to use urinary level of plasmin as an indicator for renal affection and activity in systemic lupus erythematosus (SLE) patients. Between April 2020 and October 2020, urine samples from 50 SLE patients (2 males, 48 females; mean age: 35.5±8.1 years; range, 22 to 39 years) and 20 age- and sex-matched healthy controls (2 males, 18 females; mean age: 34.1±6.5 years; range, 27 to 38 years) were collected. The patients were divided into two groups according to the presence or absence of renal manifestations as those with renal disease (n=28) and those without renal disease (n=22). The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), renal activity (rSLEDAI), and Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) scores were calculated. Renal biopsy was performed to patients with active lupus nephritis (LN). The activity index (AI) and Chronicity Index (CI) were scored. There was a highly statistically significant difference in the mean urinary plasmin levels between SLE cases and the control group (88.9±42.6 ng/mL vs. 21.3±26.8 ng/mL, respectively; p<0.001). A significant elevation was observed (p<0.05) in patients with LN (97.9±46.6 ng/mL) than without (42.7±12.7 ng/mL), particularly in patients with active renal involvement (82.9±26.6 ng/mL) than patients with inactive renal disease (63.2±15.5 ng/mL). There were significant positive correlations between the mean urinary plasmin levels and inflammatory markers, SLEDAI, and rSLEDAI scores. Urinary level of plasmin is significantly elevated among SLE cases, particularly in those with active LN. The remarkable association between urinary plasmin level and various activity status implies that urinary plasmin can be used as a beneficial marker to monitor lupus nephritis flare.

Depression-, Pain-, and Health-Related Quality of Life in Patients with Systemic Lupus Erythematosus.

Objectives A significant number of patients with systemic lupus erythematosus (SLE) have depression, and many are untreated. We aim to assess the frequency of moderate to severe depression (MSD) in a multiethnic group of SLE patients with different sociodemographic backgrounds, identify modifiable factors associated with depression, and determine the impact of depression, disease activity, damage, cognitive function, and pain severity on health-related quality of life (HRQoL). Methods Ninety-nine patients with SLE were evaluated in a cross-sectional study. Sociodemographic data, Beck Depression Inventory (BDI II), SLE disease activity index (SLEDAI-2K), SLICC Damage Index (SLICC-DI), pain severity (10 cm visual analogue scale), cognitive function (Automated Neuropsychologic Assessment Metrics (ANAM)), and the physical (PCS) and mental (MCS) component scores of the Short Form Health Survey (SF-36) were recorded. Bivariate analysis identified potential associations of relevant variables with BDI II and SF-36. Regression analysis determined independent correlates with MSD, PCS, and MCS. Results Over 50% of subjects (50.5%) were African-American, 37.1% had a family income of ≤$20,000, and 31.3% had MSD. In the bivariate analysis, family income, SLEDAI-2K, cognitive function, and pain severity were associated with MSD. Using binary logistic regression, SLEDAI-2K and pain severity remained independently correlated with MSD (p = 0.004). In the multiple linear regression analysis, pain severity was the only independent correlate of PCS (p < 0.0001), while cognitive function and BDI II were the main factors associated with MCS (p = 0.020 and p < 0.0001, respectively). Conclusion Pain severity and disease activity are associated with MSD in our unique population, are potentially modifiable, and deserve further attention in the clinic. Depression and pain significantly affect HRQoL and should be aggressively managed.

Nailfold capillary scleroderma pattern may be associated with disease damage in childhood-onset systemic lupus erythematosus: important lessons from longitudinal follow-up

ObjectivesTo observe if capillary patterns in childhood-onset SLE (cSLE) change over time and find associations between a capillary scleroderma pattern with disease activity, damage or scleroderma-like features.MethodsClinical and (yearly) capillaroscopy...

Evaluation of lupus anticoagulant, damage, and remission as predictors of pregnancy complications in systemic lupus erythematosus: the French GR2 study.

ObjectivesThe specific roles of remission status, lupus low disease activity state (LLDAS), and damage accrual on the prognosis of pregnancies in women with SLE are unknown. We analysed their impact on maternal flares and adverse pregnancy outcomes (APOs).MethodsWe evaluated all women (≥18 years) with SLE enrolled in the prospective GR2 study with an ongoing singleton pregnancy at 12 weeks (one pregnancy/woman). Several sets of criteria were used to define remission, disease activity and damage. APOs included: foetal/neonatal death, placental insufficiency with preterm delivery and small-for-gestational-age birth weight. First trimester maternal and disease features were tested as predictors of maternal flares and APOs.ResultsThe study included 238 women (98.3% on hydroxychloroquine (HCQ)) with 230 live births. Thirty-five (14.7%) patients had at least one flare during the second/third trimester. At least one APOs occurred in 34 (14.3%) women. Hypocomplementemia in the first trimester was the only factor associated with maternal flares later in pregnancy (P=0.02), while several factors were associated with APOs. In the logistic regression models, damage by SLICC-Damage Index [odds ratio (OR) 1.8, 95% CI: 1.1, 2.9 for model 1 and OR 1.7, 95% CI: 1.1, 2.8 for model 2] and lupus anticoagulant (LA, OR 4.2, 95% CI: 1.8, 9.7 for model 1; OR 3.7, 95% CI: 1.6, 8.7 for model 2) were significantly associated with APOs.ConclusionLA and damage at conception were predictors of APOs, and hypocomplementemia in the first trimester was associated with maternal flares later in pregnancy in this cohort of pregnant patients mostly with well-controlled SLE treated with HCQ.Trial registrationClinicalTrials.gov, https://clinicaltrials.gov, NCT02450396.

Clinical significance of platelet-lymphocyte ratio in systemic lupus erythematosus patients: Relation to disease activity and damage

Aim of the workTo assess platelet–lymphocyte ratio (PLR) in systemic lupus erythematosus (SLE) patients and study its clinical significance, its relation to disease activity and damage. Patients and methodsThis study included 52 adult SLE patients and 50 matched control. All patients were subjected to full clinical examination, disease activity was measured by SLE disease activity index (SLEDAI), and damage was assessed by using Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI). Laboratory and immunology profiles included the complete blood count (CBC) with differential white blood cell (WBC) counts and estimation of PLR, erythrocyte sedimentation rate (ESR), liver and kidney function, alkaline phosphatase (ALP), serum calcium (Ca) and phosphorous (P), lipid profile, 24hr urinary protein, renal biopsy, anti-nuclear antibody (ANA), anti-double stranded deoxyribonucleic acid (anti-dsDNA), serum complements (C3,C4). ResultsThe mean age of SLE patients was 33.1 ± 9.2 years (20–58 years), with mean disease duration of 5.4 ± 5.02 years (0.25–20 years). The PLR was significantly higher in patients (189.9 ± 136.4; 23.9–782.9) than control (95 ± 29.9; p < 0.0001). The WBC and platelets count was comparable between patients and control (7.1 ± 1.7 x103/mm3 and 243.4 ± 51.3 x103/mm3; p = 0.3 and p = 0.51 respectively). The lymphocytic count was significantly lower in patient compared to control (1.9 ± 1.1 x103/mm3 vs 2.7 ± 0.8 x103/mm3)(p < 0.0001). PLR would significantly predict activity (p = 0.02) with a sensitivity of 94.3% and specificity of 100% at a cut-off value of 33.6. There was no association of PLR with the damage index. ConclusionPLR might be considered a valuable and un-expensive tool in assessment and prediction of SLE disease activity.

Fever in systemic lupus erythematosus: associated clinical features and genetic factors.

Fever has been recently included in the new 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE). Thus, we investigated the possible association of fever with other clinical disease manifestations. Then, we analysed a panel of 30 SNPs to verify their possible contribution to the pathogenesis of this constitutional symptom. In this retrospective study we collected clinical/laboratory features in a SLE cohort, including the occurrence of fever (body temperature >37.5°C, excluding infective aetiology). A phenotype-genotype correlation analysis was carried out. We evaluated 167 patients (M/F 12/155, median age at the disease diagnosis 30 years, IQR 17; median disease duration 240 months, IQR 156). Seventy patients (41.9%) reported fever, significantly associated with: serositis and haematological manifestations (p=0.02 and p=0.00001, respectively). A significant association between fever and leukopenia (p=0.003), haemolytic anaemia (p=0.04), and thrombocytopenia (p=0.04) was observed. In addition, significantly higher median SLICC Damage Index (SDI) values were observed in patients with fever in comparison with those without [2 (IQR 3) vs. 1 (IQR 2); p=0.005]. The genotype/phenotype analysis showed an association between fever and the rs13361189 of Immunity Related GTPase M (IRGM) gene (p=0.003; OR 3.89, CI 1.16-13.03), confirmed also in multivariate logistic regression analysis (p=0.028, B=1.39). The association between IRGM rs13361189 polymorphism and the occurrence of inflammatory fever, could provide new insights into the role of genetic background in the pathogenesis of this SLE-related feature.

Neuropsychiatric involvement in juvenile-onset systemic lupus erythematosus: Data from the UK Juvenile-onset systemic lupus erythematosus cohort study.

IntroductionJuvenile-onset systemic lupus erythematosus (JSLE) is a rare autoimmune/inflammatory disease with significant morbidity and mortality. Neuropsychiatric (NP) involvement is a severe complication, encompassing a heterogeneous range of neurological and psychiatric manifestations.MethodsDemographic, clinical, and laboratory features of NP-SLE were assessed in participants of the UK JSLE Cohort Study, and compared to patients in the same cohort without NP manifestations.ResultsA total of 428 JSLE patients were included in this study, 25% of which exhibited NP features, half of them at first visit. Most common neurological symptoms among NP-JSLE patients included headaches (78.5%), mood disorders (48.6%), cognitive impairment (42%), anxiety (23.3%), seizures (19.6%), movement disorders (17.7%), and cerebrovascular disease (14.9%). Peripheral nervous system involvement was recorded in 7% of NP-SLE patients. NP-JSLE patients more frequently exhibited thrombocytopenia (<100 × 109/L) (p = 0.04), higher C-reactive protein levels (p = 0.01), higher global pBILAG score at first visit (p < 0.001), and higher SLICC damage index score at first (p = 0.02) and last (p < 0.001) visit when compared to JSLE patients without NP involvement.ConclusionsA significant proportion of JSLE patients experience NP involvement (25%). Juvenile-onset NP-SLE most commonly affects the CNS and is associated with increased overall disease activity and damage.

Serum BDNF and cognitive dysfunction in SLE: findings from a cohort of 111 patients

The association between brain-derived neurotrophic factor (BDNF) and neuropsychiatric systemic lupus erythematosus (NPSLE) is controversial in the literature. Cognitive dysfunction (CD) is a common, underdiagnosed NPSLE manifestation, but its pathophysiology is unknown. Thus, we investigate serum BDNF as a potential biomarker of CD in a cohort of SLE patients. We included 63 SLE patients, 48 NPSLE, and 57 age- and gender-matched controls (CON). All participants underwent neuropsychological assessment. Data on cardiovascular comorbidities, SLE disease activity index (SLEDAI), and Systemic Lupus International Collaborating Clinics damage index (SLICC-DI) were compiled. Multiple regression analyses evaluated predictors of serum BDNF levels. Serum BDNF levels were lower in SLE and NPSLE patients than in CON (SLE 800.4 ± 502.7 vs. NPSLE 779.7 ± 426.3 vs. CON 1,345.5ng/mL ± 438.4; p < 0.001). In addition, hypertension (B: - 192.5, SE: 84.3, 95% CI: - 359.7 to - 25.3, p = 0.024) and SLICC-DI score (B: - 75.9, SE: 27.2, 95% CI: - 129.8 to - 22, p = 0.006) were predictors of serum BDNF levels in SLE. There was no relation between BDNF levels and CD. BDNF levels are lower in SLE patients than CON and inversely associated with hypertension and SLICC-DI scores. No association between BDNF levels and CD or NPSLE was observed in this cohort. These findings indicate that BDNF may be associated with overall burden in SLE rather than specific manifestations such as cognition impairment. Key Points • BDNF is associated with an overall burden in SLE rather than specific manifestations such as cognition dysfunction. • BDNF levels are reduced in patients with SLE, and higher SLICC-DI scores and hypertension are independent predictors of lower serum BDNF levels. • The cognitive dysfunction rate is elevated (46%) among Brazilian SLE patients.

POS0685 MYCOPHENOLATE MOFETIL IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: FIVE-YEARS DRUG SURVIVAL IN RENAL AND NON-RENAL INVOLVEMENT

Background:The updated EULAR recommendations for the management of systemic lupus erythematosus (SLE) underline the use of Mycophenolate Mofetil (MMF) in the treatment of different disease related manifestations (1). Several randomized controlled trials have demonstrated the efficacy of MMF in lupus nephritis (LN) patients but only case series and open-labelled trials have analyzed the use of this drug in other than LN features. Moreover, no data are available about the MMF retention rate in a real-life setting.Objectives:The present study aims at evaluating the 5-years drug retention rate (DRR) of MMF in a large monocentric SLE cohort. Secondly, we investigated the influence of MMF in disease activity changes and chronic damage progression.Methods:We performed a longitudinal study including all the SLE patients (ACR 1997 criteria) starting MMF treatment in our Lupus Clinic. Data about indications, mean dosage, duration of treatment and reasons for drug withdrawal were registered. The DRR was estimated using the Kaplan–Meier method. Disease activity and chronic damage were assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and SLICC Damage Index (SDI), respectively.Results:The present analysis included 162 SLE patients (M/F 22/140, median age at the disease diagnosis 25.5 years, IQR 13). At the beginning of MMF treatment, we registered a median age of 34 months (IQR 21) and a median disease duration of 72 months (IQR 123). The most frequent indications for prescribing MMF were LN (101 patients, 62.3%) and musculoskeletal manifestations (39, 24.1%), followed by neuropsychiatric involvement (10, 6.2%), and others disease related manifestations (12, 7.4%; in particular skin involvement, hematological features, myositis, vasculitis). MMF was administered at a mean daily dosage of 2.1±0.6 grams; no differences in dosage were found between the different indications (p=ns).At the longitudinal analysis, we registered a median treatment duration of 30 months (IQR 55). Figure 1 reported data about DRR: in particular, at 60 months follow-up we observed a DRR of 61.1% for LN patients, which was similar to that registered for patients without renal involvement (NLN) (60.5%; p=ns). Interestingly, the DRR at 60 months was higher in the subgroup of patients treated for joint involvement (75.4%), even without reaching a statistically significant difference. During the observation period, 92 patients (59.2%) discontinued MMF (median treatment duration at discontinuation 25 months, IQR 35). Interestingly, the main cause of withdrawal was the achievement of persistent remission, observed in 20 patients (21.7%), followed by loss of efficacy (19 patients, 20.5%), drug intolerance and pregnancy planning (17 patients for both reasons, 18,4%). Furthermore, our analysis confirmed MMF efficacy, as demonstrated by the significant reduction in SLEDAI-2k values after 4, 12 and 24 months of treatment (p&lt; 0.0001 for all the time-points in comparison with baseline). In addition, MMF resulted able to control chronic damage progression, as demonstrated by the lack of significant increase in SDI values (baseline: 0.6, IQR 1; last observation: 0.93, IQR 1; p=ns).Conclusion:The evaluation of a large SLE cohort demonstrated a good retention rate for MMF. In particular, our results demonstrated that MMF is also a safe and effective drug for SLE manifestation other than LN, in particular for joint involvement. Moreover, it is able to control disease activity and to prevent the progression of chronic damage.

Relevance of gastrointestinal manifestations in a large Spanish cohort of patients with systemic lupus erythematosus: what do we know?

SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil ≥4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage.

Biomarkers of myocardial injury in lupus nephritis

Background Cardiovascular disease (CVD) is the main cause of death in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN). This study aimed to evaluate the prevalence of myocardial injury among patients with SLE without nephritis and patients with LN, determine whether serum high-sensitivity cardiac troponin T and creatine phosphokinase-MB (CKMB) might help to identify patients with LN at risk for CVD, and identify LN as a risk factor for myocardial injury. Patients and methods This study was conducted on 50 patients (30 patients with LN and 20 patients with SLE without nephritis). The SLE disease activity index (SLEDAI) and Systemic Lupus International Collaborating Clinics Damage Index (SLICC/DI) were assessed. Laboratory investigations, cardiac enzymes (Hs-TnT and CKMB), and transthoracic echocardiography were performed. Results The results demonstrated a higher prevalence of CVD in patients with LN. A total of 28 patients with LN (93.3%) vs 10 patients with SLE (50%) had detectable high-sensitivity troponin (Hs-TnT) levels, with a mean 29.77±18.22 vs 7.2±6.21 ng/l, respectively. The mean value of CKMB was higher in patients with LN than patients with SLE (23.9±18.6 vs 14.8±9.4 μg/l, respectively). Multilinear regression analysis for Hs-TnT revealed that low estimated glomerular filtration rate, high urinary albumin-to-creatinine ratio, low ejection fraction, and different ECHO diameters were the most statistically significant predictors of troponin elevation, with a P value less than 0.05. The strongest renal predictors of CKMB were estimated glomerular filtration rate and proteinuria, with a P value less than 0.05. Conclusion CVD is more in patients with LN than patients with SLE. Hs-TnT levels is a signature of subclinical cardiac disease, which could be used to identify at-risk individuals. CKMB and echocardiography lack adequate sensitivity for the diagnosis of myocardial injury in patients with LN.

Medication adherence is influenced by resilience in patients with systemic lupus erythematosus.

Evidence on the relationship between resilience and medication adherence in systemic lupus erythematosus (SLE) patients is lacking. We aimed to examine the impact of resilience on medication adherence in SLE patients. In a cross-sectional analysis SLE outpatients were assessed for resilience (Connor-Davison Resilience Scale, CD-RISC), depressive symptoms (CES-D) and medication adherence (Compliance Questionnaire for Rheumatology [CQR]). The disease activity index (mexSLEDAI) and damage (SLICC Damage Index) were administered. Factors independently associated with adherence were identified using multivariate logistic regression. Of the 157 patients, 152 (96.8%) were female with a median age of 45.9 (IQR: 39.0-55.5) years and disease duration of 14 (IQR: 10.0-19.0) years. Medication adherence (CQR ≥80%) and depressive symptoms were found in 74.5% and 43.9% of patients, respectively. Adherent patients had a lower CES-D score and a higher CD-RISC score. In the multivariate analysis adjusting for demographic and clinical confounders, resilience and older age protected against non-adherence (OR 0.96, [95% CI 0.94-0.99] and OR 0.96 [95% CI 0.93-0.98], respectively). In SLE patients, resilience and older age, which possibly associated with better medication adherence, may protect against non-adherence.

Chinese SLE Treatment and Research Group (CSTAR) Registry 2009-2019: Major Clinical Characteristics of Chinese Patients with Systemic Lupus Erythematosus.

To describe the overall clinical characteristics of patients from the Chinese SLE Treatment and Research group (CSTAR) registry in the past 10 years. CSTAR registry originated as a multicenter, consecutive, and prospective design launched in 2009. The data were collected online from 304 rheumatology centers, which covered 30 provinces in China. All data were generated and uploaded in the clinic directly without secondary collection, including demographic, clinical manifestations, disease activity (SLEDAI-2K) and organ damage evaluation (SLICC Damage Index), and lab test results. Biological samples were preserved for future study. Meanwhile, data cleaning and validation were managed by a professional backstage statistician. A total of 25,147 SLE patients were registered up to Dec 2019. The mean age of disease onset was 31.2 years with the age of confirmed diagnosis at 32.1 years. The male to female rate was 1:11.9. 4.6% were pediatric patients. The most common clinical presentations at entry were oral ulcer (59.4%), arthritis (55.0%), alopecia (43.22%), skin rash (40.0%), and nephritis (33.5%). The mean SLEDAI score at entry was 4 and 32.6% were in moderate to severely active disease. 66.4% and 37.8% of patients were positive for anti-ds-DNA antibody or low complement level. Additionally, 1.1% of patients were with pulmonary arterial hypertension (PAH). The prevalence rate of cerebrovascular disease was 0.3%. A total of 58.2% of patients were in clinical remission when thery were registered. The CSTAR registry is the largest ongoing SLE registry in China so far. More than 25,000 SLE patients are registered and nearly 10,000 are in follow-up visits. This registry has provided high-quality data for future studies and will become an infrastructure for domestic and international collaborations.

Smoking exposure in pack-years predicts cutaneous manifestations and damage in systemic lupus erythematosus.

To examine the impact of cumulative smoking in pack-years on systemic lupus erythematosus (SLE) cutaneous manifestations and damage. Our cohort study included 632 adult SLE patients at an academic center, meeting 1997 ACR or 2012 SLICC classification criteria. Outcomes were: (1) cutaneous SLICC Damage Index (SDI), (2) ACR and SLICC criteria. Smoking exposure was defined as low (<5 pack-years), medium (5-10), and high (>10), compared to non-smokers. Analysis used multivariable logistic regression to calculate odds ratios and confidence intervals (OR, (95% CI)). Among 632 SLE patients, mean age 42 ± 14, 91% were female, 82% White, and 40% were ever smokers. Black patients were more likely to have smoked (51% vs. 41% White, 11% Other). Chronic SLICC and SDI cutaneous criteria showed linear pack-year trends, meeting significance with high smoking exposure (OR 2.2, (1.2, 4.2); OR 4.2, (1.9, 9.2)). Those with medium exposure were more likely to meet acute SLICC cutaneous criteria (OR 2.3, (1.1, 5.1)). Low exposure predicted any cutaneous SLICC and ACR criteria (OR 3.7, (1.3, 10.6); OR 2.0 (1.03, 3.8)). Patients of color had more chronic SLICC cutaneous criteria (Other Race OR 3.6 (1.6, 8.1)) and SDI skin damage (Black OR 2.6 (1.1, 5.9)) even controlling for smoking exposure. Smoking was an independent risk factor for cutaneous SLE. High pack-year exposure and non-White race increased chronic skin manifestations and SDI damage. Findings suggested a dose relationship between smoking and cutaneous SLE damage, making cessation messaging important to potentially improve outcomes and reduce some disparities.

Comprehensive disease control in systemic lupus erythematosus

ObjectivesWe evaluated a monocentric SLE cohort in order to assess the frequency of Lupus comprehensive disease control (LupusCDC), a condition defined by the achievement of remission and the absence of damage progression. MethodsOur longitudinal analysis included SLE patients with 5-years follow-up and at least one visit per year. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and three different remission levels were evaluated (Complete Remission, CR; Clinical remission off-corticosteroids; clinical remission on-corticosteroids). Chronic damage was assessed according to SLICC Damage Index (SDI). LupusCDC was defined as remission achievement for at least one year plus absence of chronic damage progression in the previous one year. A machine learning based analysis was carried out, applying and comparing Nonlinear Support Vector Machines (SVM) models and Decision Trees (DT), whereas features ranking was performed with the ReliefF algorithm. ResultsWe evaluated 172 patients [M/F 16/156, median age 49 years (IQR 16.7), median disease duration 180 months (IQR 156)]. SDI values (baseline mean±SD 0.7 ± 1.1) significantly increased during the follow-up period. In all time-points analyzed, LupusCDC including CR was the most frequently detected. The failure to reach this condition was significantly associated with renal involvement and with the intake of immunosuppressant drugs and glucocorticoid (GC). Ten patients (5.8%) have maintained LupusCDC during the whole 5-year follow-up: these patients had never presented renal involvement and showed lower prevalence of anti-phospholipid antibodies (p = 0.0001). Finally, the prevalence of GC intake was significantly lower (p = 0.0001). The application of machine learning models showed that the available features were able to provide significant information to build predictive models with an AUC score of 0.703 ± 0.02 for DT and 0.713 ± 0.02 for SVM. ConclusionsOur data on a monocentric cohort suggest that the LupusCDC can efficaciously merge into one outcome SLE-related disease activity and chronic damage in order to perform an all-around evaluation of SLE patients.

Myositis in systemic lupus erythematosus.

Myositis is an infrequent feature of SLE and may often be overlooked. We aimed to estimate the incidence of myositis in SLE, and to determine demographic and clinical factors associated with it. Within our lupus cohort, we identified potential myositis cases using the SLICC Damage Index for muscle atrophy or weakness, the SLEDAI-2K item for myositis, and annually measured serum creatinine kinase. Cases were confirmed through chart review. We performed descriptive analyses of prevalent myositis cases as of January 2000. From that point onward, we studies patients without myositis to determine risk of incident myositis, using cohort analyses adjusted for demographic variables (age, sex, race/ethnicity). As of January 2000, there were 5 prevalent myositis cases in our SLE cohort. Among 560 SLE patients with a study visit from January 2000 onward, with no history of myositis at baseline, 5 new cases (4 females, 1 male) were identified over an average follow-up of 8.5 years (incidence 1.05 cases per 1000 person-years). There was a higher proportion of Caucasians in the non-myositis group versus myositis group, with a trend for fewer females in the myositis cases. Arthritis, Raynaud's phenomenon, and anti-Smith antibodies were common pre-existing features, occurring in all incident myositis cases. In Cox regression analyses adjusting for age, race/ethnicity and sex, non-Caucasian patients had a markedly increased risk of developing myositis. We found a low incidence of myositis in our SLE cohort. A cluster of variables, particularly non-Caucasian race/ethnicity, arthritis, Raynaud's phenomenon, and anti-Smith antibodies were associated with risk of developing myositis in SLE. These variables may aid clinicians in identifying SLE patients at highest risk for this important complication.

The problem of fatigue in patients with systemic lupus erythematosus according to the data on a Russian RENAISSANCE cohort

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations. Numerous observations and surveys of patients have shown that the most common symptom of SLE is fatigue complaints in 51 to 90% of patients.Objective: to determine the significance of fatigue in the general health status of RENAISSANCE cohort patients with SLE who were hospitalized in the Clinic, V.A. Nasonova Research Institute of Rheumatology.Patients and methods. The investigation included SLE patients aged 18 years and older who met the 2012 SLICC criteria. The standard examination accepted in the management of patients with SLE was made. Disease activity was determined by SLEDAI-2K; irreversible lesions in various organs were identified using the SLICC damage index. The SF-36 and the LupusQoL questionnaires were used to assess health-related quality of life (HRQOL) and the FACIT-Fatigue scale was applied to measure fatigue.Results and discussion. The investigation enrolled 328 patients, mainly women (91%); the mean age was 34.4±11.5 years; the duration of the disease was 106.3±97.9 months. In this group, moderate and high disease activities (SLEDAI-2K scores of 6–10 and 11–19, respectively) were observed at approximately the same frequency. At the time of inclusion, more than half (56.5%) of the patients already had various irreversible organ lesions. At Visit 1, the FACIT-Fatigue scale showed that fatigue was present in 148 (45%) of the 328 patients. According to the presence of fatigue, the patients were divided into two groups. Group 1 included 148 patients with fatigue; Group 2 consisted of 180 patients without fatigue. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and anti-DNA antibody levels were significantly higher in the fatigue group (p=0.01 and p=0.02, respectively); the patients also had decreased HRQOL according to 7 LupusQol domains (p&lt;0.001). The patients with fatigue were significantly more likely to receive intravenous glucocorticoids and rituximab. At 12 months after the start of treatment, the patients with fatigue were found to have a statistically significant reduction in disease activity, as well as normalization of anti-DNA antibody levels, improvements in HRQOL according to the LupusQol domains, and less severity of fatigue according to the FACIT-Fatigue scale.Conclusion. Fatigue was detected in almost half (45–53%) of SLE patients. It is associated with a higher disease activity by SLEDAI-2K and with a high anti-DNA antibody level. The patients with fatigue are observed to have an obvious worsening of HRQOL according to all LupusQol domains.

Cytokines, 25-OH vit D and disease activity in patients with juvenile-onset systemic lupus erythematosus.

Juvenile onset systemic lupus erythematosus JO-SLE patients usually exhibit a more aggressive disease course compared to adult patients. Vitamin D deficiency is proposed to be associated with increased disease activity and flares of numerous autoimmune diseases like SLE, rheumatoid arthritis, and scleroderma. To evaluate the level of IL-17, IFN-γ, and 25-OH Vit D in JO-SLE patients versus healthy controls, and determine the correlation of those inflammatory mediators with SLE disease activity and damage scores. Furthermore, to analyze the relationship between 25-OH Vit D levels with the inflammatory cytokines (IFN-γ and IL-17) in JO-SLE patients. Fifty JO-SLE patients and 25 controls were included in this study. Clinical and laboratory data of patients at the time of the study were recorded. SLE disease activity and damage were assessed using the SLEDAI-2K disease score and SLICC damage index, respectively. Plasma 25-OH Vit D, IFN-γ, and IL-17 concentrations were determined using the human ELISA kit. Plasma 25-OH Vit D levels (20 ng/mL) were significantly lower in JO-SLE patients compared to (31 ng/mL) controls (P = 0.014). Plasma levels of IFN-γ and IL-17 were significantly higher (163.5 and 25.5 pg./mL) in JO-SLE patients than (68.3 and 3 pg./mL) that of controls (P = 0.016 and P = 0.013). There was a significant negative correlation between 25-OH Vit D levels and SLEDAI-2K (R= -0.431) as well as IFN-γ (R= -0.471) plasma level (P = 0.022 and P = 0.027). IFN-γ and IL-17 were significantly higher in JO-SLE patients, while 25-OH Vit D was significantly lower compared to controls. There was a negative correlation between 25-OH Vit D and each of SLEDAI-2K and IFN-γ.

Serum Levels of T Cell Immunoglobulin and Mucin-Domain Containing Molecule 3 in Patients with Systemic Lupus Erythematosus.

Objective: T cell immunoglobulin and mucin-domain-containing molecule 3 (TIM-3) is implicated in the development of various autoimmune diseases. We aimed to investigate the levels of soluble TIM-3 (sTIM-3) and their associations between clinical parameters in patients with systemic lupus erythematosus (SLE). Methods: Serum samples were collected from 65 patients with SLE and 35 age-matched healthy controls (HCs). The SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI) were used to assess SLE disease activity and SLE-related organ damage. British Isles Lupus Assessment Group (BILAG)-2004 index was also used to assess SLE disease activity. Soluble TIM-3 (sTIM-3) in sera from patients with SLE and HCs were evaluated by enzyme-linked immunosorbent assay (ELISA). The results were compared with the clinical parameters of SLE including SLE disease activity. Results: Serum sTIM-3 levels in patients with SLE (median 2123 pg/mL (interquartile range (IQR), 229–7235)) were significantly higher than those in HCs (1363 pg/mL; IQR, 1097–1673; p = 0.0015). Serum levels of sTIM-3 were correlated with disease activity of SLE using the SLEDAI-2K score (p < 0.001, r = 0.53). The serum sTIM-3 levels in SLE patients with active renal disease (BILAG renal index A-B) were significantly higher than those without the active renal disease (BILAG renal index C–E). However, no significant difference was observed in serum sTIM-3 levels between SLE patients with and without active involvement in other organs (BILAG index). Serum sTIM-3 levels were significantly elevated in SLE patients with organ damage (2710 pg/mL; IQR, 256–7235) compared to those without organ damage (1532 pg/mL; IQR, 228–5274), as assessed by the SDI (p = 0.0102). Conclusions: Circulating sTIM-3 levels are elevated in SLE patients, and serum sTIM-3 levels are associated with SLE disease activity and SLE-related organ damage. The data indicate a possible link between the TIM-3/Gal-9 pathway and SLE clinical phenotypes, and further investigation of the TIM-3 pathway in SLE pathophysiology is warranted.