Systemic Lupus International Collaborating Clinics Research Articles

Abnormal cerebral hemodynamics and blood-brain barrier permeability detected with perfusion MRI in systemic lupus erythematosus patients

ObjectiveDynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) has previously shown alterations in cerebral perfusion in patients with systemic lupus erythematosus (SLE). However, the results have been inconsistent, in particular regarding neuropsychiatric (NP) SLE. Thus, we investigated perfusion-based measures in different brain regions in SLE patients with and without NP involvement, and additionally, in white matter hyperintensities (WMHs), the most common MRI pathology in SLE patients. Materials and methodsWe included 3 T MRI images (conventional and DSC) from 64 female SLE patients and 19 healthy controls (HC). Three different NPSLE attribution models were used: the Systemic Lupus International Collaborating Clinics (SLICC) A model (13 patients), the SLICC B model (19 patients), and the American College of Rheumatology (ACR) case definitions for NPSLE (38 patients). Normalized cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were calculated in 26 manually drawn regions of interest and compared between SLE patients and HC, and between NPSLE and non-NPSLE patients. Additionally, normalized CBF, CBV and MTT, as well as absolute values of the blood-brain barrier leakage parameter (K2) were investigated in WMHs compared to normal appearing white matter (NAWM) in the SLE patients. ResultsAfter correction for multiple comparisons, the most prevalent finding was a bilateral significant decrease in MTT in SLE patients compared to HC in the hypothalamus, putamen, right posterior thalamus and right anterior insula. Significant decreases in SLE compared to HC were also found for CBF in the pons, and for CBV in the bilateral putamen and posterior thalamus. Significant increases were found for CBF in the posterior corpus callosum and for CBV in the anterior corpus callosum. Similar patterns were found for both NPSLE and non-NPSLE patients for all attributional models compared to HC. However, no significant perfusion differences were revealed between NPSLE and non-NPSLE patients regardless of attribution model. The WMHs in SLE patients showed a significant increase in all perfusion-based metrics (CBF, CBV, MTT and K2) compared to NAWM. ConclusionOur study revealed perfusion differences in several brain regions in SLE patients compared to HC, independently of NP involvement. Furthermore, increased K2 in WMHs compared to NAWM may indicate blood-brain barrier dysfunction in SLE patients. We conclude that our results show a robust cerebral perfusion, independent from the different NP attribution models, and provide insight into potential BBB dysfunction and altered vascular properties of WMHs in female SLE patients. Despite SLE being most prevalent in females, a generalization of our conclusions should be avoided, and future studies including all sexes are needed.

Cardiac tamponade revealing systemic lupus in an elderly subject: a rare case report

Systemic lupus erythematous (SLE) is a chronic autoimmune disease with a polymorphic clinical presentation that occurs mainly in young women. The particularity of this case report is that pericardial tamponade as the first manifestation of SLE and its late discovery in an elderly subject are rare. Few similar cases are reported in the literature. We report the case of a 60-year-old woman admitted to the cardiology department for dyspnoea evolving for 15 days, with a sensation of chest pressure. On admission, the patient was haemodynamically unstable. Echocardiography showed abundant circumferential pericardial effusion with variations in respiratory flow. A pericardiocentesis was performed with a sample of 900 ml of blood fluid. We started a symptomatic treatment of the pericardial effusion and an etiological assessment was carried out. The diagnosis of SLE was made according to the Systemic Lupus International Collaborating Clinics (SLICC) criteria for SLE. In our case, emergency pericardial puncture showed hematic-like pericardial effusion. Using the lab results and other investigations, we were able to make a diagnosis of SLE. The diagnosis of lupus allowed a curative treatment of the etiology of the pericardial effusion, to avoid the recurrence as well as to improve the prognosis. This case is interesting because lupus is rarely the cause of a very abundant pericardial effusion, even less so in an elderly subject. Cardiac tamponade is a life-threatening condition. Therefore, pericardiocentesis should be performed as soon as possible to avoid death. It should be kept in mind that SLE can be complicated by pericardial tamponade and know how to look for it after hemodynamic stabilization of the patient.

Carotid Intima Media Thickness as a Marker of Atherosclerotic Burden in Patients with Systemic Lupus Erythematosus: A Cross-sectional Study from a Tertiary Care Centre of Eastern India

Introduction: Systemic Lupus Erythematosus (SLE) patients have an increased burden of atherosclerosis leading to adverse Cardiovascular (CV) events. Alterations in endothelial function, dysregulated immune system and increased oxidative stress are implicated in their development and progression. Carotid artery ultrasound is recommended to assess and follow progression of subclinical atherosclerosis and correlate with traditional/non traditional CV risk factors in SLE. Aim: To study the correlation between Carotid Intima Media Thickness (CIMT), traditional/non traditional CV risk factors in SLE. Materials and Methods: The hospital-based, descriptive, cross-sectional study was conducted in the Department of Internal Medicine, Medical College Kolkata, Kolkata, West Bengal, India, from April 2019 to August 2020. Patients with SLE, diagnosed by Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria, aged >12 years, irrespective of therapy status, were recruited by consecutive sampling. Subjects were classified as Lupus Nephritis (LN) and Lupus without Nephritis (LWN). Demographic data, parameters to define SLE (SLICC 2012 criteria), blood parameters like lipid profile, fasting plasma glucose, anti-Double stranded Deoxyribose Nucleic Acid antibody (anti-dsDNA Ab), C3/C4 levels, 24 hour urine protein values, haemoglobin, C-reactive Protein (CRP), serum homocysteine and Carotid Intima Media thickness as measured by Ultrasonography (USG) doppler study, duration of disease and medication history were considered as study variables. Statistical analysis was done by using Z-test, t-test, Analysis of variance (ANOVA), Chi-square test (for categorical data) and other non parametric statistical tests and correlation tests wherever applicable. A p-value <0.05 was considered to be statistically significant. Results: Fifty five SLE patients were studied. Subgroup analysis was performed between LN (n=36) and LWN (n=19). The mean age of the study subjects was 33 years with mean disease duration of 4.6 years. LN patients had longer disease duration, younger age of disease onset and longer duration of steroid usage. The mean systolic Blood Pressure (BP) was significantly higher in LN subgroup. Framingham Risk Scores (FRS) was positively correlated with duration of SLE disease and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) scores and duration of steroid therapy. The mean CIMT of the study population is 0.91 mm with 10.9% plaque prevalence whereas, mean CIMT of the LN subgroup and LWN subgroup was 1.02±0.27 mm and 0.86±0.3 mm, respectively; however no statistically significant difference in CIMT was observed between two subgroups. CIMT positively correlated with anti-dsDNA Ab levels, FRSs, anaemia, SLE Disease activity scores, 24 hour urine protein, duration of steroid usage, serum creatinine and CRP. No correlation between CIMT and age of subjects, Fasting Plasma Glucose (FPG), Triglycerides (TG) serum homocysteine was observed. Conclusion: Systemic lupus erythematous patients have a high atherosclerosis burden and are at increased risk of adverse CV events. LN patients, early age of lupus onset, longer disease duration with prolonged steroid therapy, significant proteinuria, higher anti-dsDNA Ab levels and hypocomplementemia were observed to have higher mean CIMT and plaque formation.

A study of CD11b rs1143679 gene polymorphism in Egyptian systemic lupus erythematosus patients

Background/aim The exact cause of systemic lupus erythematosus (SLE), an autoimmune disorder, is still vague. However, it is believed that its pathogenesis could be a result of the interplay between genetics and the environment. One such genetic factor is a single-nucleotide polymorphism in the CD11b gene (rs1143679) that has been shown to potentially increase a person’s susceptibility to SLE. This study aims to investigate the possible link of CD11b rs1143679 gene polymorphism to the risk of developing SLE, as well as the different manifestations and the disease severity in the studied group of Egyptian SLE patients. Patients and methods The present study enrolled 50 patients with SLE from Benha University Hospitals, Egypt. In addition to 30 apparently healthy individuals served as control, the CD11b gene (rs1143679) genetic variant was investigated by real-time PCR. The individuals with SLE were based on the Systemic Lupus International Collaborating Clinics criteria. Results A significant association of GA genotype (odds ratio=1.908, 95% confidence interval=1.021–3.568, P<0.05) with the risk to develop SLE and A allele was also linked to an elevated risk for SLE in comparison to the G allele (odds ratio=1.881, 95% confidence interval=1.038–3.408, P<0.05). Conclusion The CD11b rs1143679 gene polymorphism might be a potential risk factor for SLE in Egyptians.

Mortality in a cohort of Egyptian systemic lupus erythematosus patients: A comparison with African, Arabic, and Mediterranean studies.

The study aimed to examine the frequency, causes, and predictors of mortality in a cohort of Egyptian systemic lupus erythematosus (SLE) patients and compare mortality causes and the survival rate in our cohort to African, Arabic, and Mediterranean studies. In this retrospective study, a review of medical records of 563 SLE patients (516 females, 47 males; median of age: 32 [IQR: 26-38 years]; range, 14 to 63 years) fulfilling the 1997 American College of Rheumatology (ACR) criteria between January 2015 and December 2019 was done. The data extracted included demographic, clinical, and laboratory features, treatments used, disease activity as measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and damage index as measured by Systemic Lupus International Collaborating Clinics (SLICC) damage index. Causes of mortality were also reported. Out of 563 reviewed medical records, 50 (8.9%) patients died. Infection (28%) and organ damage (18%) were the most commonly reported causes of death. Multivariate Cox regression analysis showed that patients with cardiac manifestations, renal failure, those receiving higher doses of either oral (in their last visit) or intravenous (higher cumulative pulse steroids) steroids were at increased risk of mortality (p=0.011, p<0.001, p=0.01, and p<0.001, respectively; 95% confidence intervals 7.2, 63.9, 1.2, and 1.09, respectively). The overall survival at 5, 10, 15, and 20 years was 96.6%, 93.3%, 91.0%, and 83.2%, respectively, and 56.2% at 25 years until the end of the follow-up. Cardiac manifestations, renal failure, and higher steroid doses were independent predictors of mortality in our cohort. As in most African countries, infection was the main cause of death in our study; however, the mortality rate and the five-year survival among our cohort were better than in African (sub-Saharan) countries and similar to Arabic and Mediterranean countries.

The impact of normal serum complement levels on the disease classification and clinical characteristics in systemic lupus erythematosus

BackgroundSome patients have normal levels of complement during the diagnosis of systemic lupus erythematosus (SLE), although decreased serum levels of complement are a hallmark of the active phase of the disease. This study investigated the clinical characteristics, impact on the classification of SLE, and the prognosis of patients with SLE who had normal serum complement levels at initial diagnosis (N-com).MethodsWe evaluated 21 patients with N-com and 96 patients with hypocomplementemia at the initial diagnosis of SLE (H-com). The classification rates among the American College of Rheumatology (ACR) 1997, Systemic Lupus International Collaborating Clinics (SLICC) 2012, European League Against Rheumatism (EULAR)/ACR 2019 criteria, and clinical and immunological involvements were compared between SLE patients with N-com and H-com. Relapse and organ damage based on the SLICC/ACR damage index were also evaluated.ResultsThe classification rates of SLE were not significantly different in the ACR, SLICC, and EULAR/ACR criteria between the N-com and H-com groups. Patients with N-com had no significant differences in the classification rates among the three criteria, whereas patients with H-com had lower classification rates in the ACR criteria than in the SLICC criteria. A lower incidence of renal manifestation, less positivity for anti-dsDNA antibody, and a higher incidence of fever were observed in patients with N-com than in those with H-com. The occurrence of relapse and organ damage was not significantly different between patients with N-com and H-com.ConclusionPatients with N-com were less involved in renal manifestation and anti-dsDNA antibody positivity but had a higher incidence of fever than those with H-com, while having no disadvantage in SLE classification processes. Serum complement levels at the initial diagnosis of SLE may not predict prognosis.

Evaluating the Construct of Damage in Systemic Lupus Erythematosus.

The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI. We conducted a 3-part qualitative study of international SLE experts. Facilitated small groups evaluated the construct underlying the concept of damage in SLE. A consensus meeting using nominal group technique was conducted to achieve agreement on aspects of the conceptual framework and scope of the revised damage index. The framework was finally reviewed and agreed upon by the entire group. Fifty participants from 13 countries were included. The 8 thematic clusters underlying the construct of SLE damage were purpose, items, weighting, reversibility, impact, time frame, attribution, and perspective. The revised SDI will be a discriminative index to measure morbidity in SLE, independent of activity or impact on the patient, and should be related to mortality. The SDI is primarily intended for research purposes and should take a life-course approach. Damage can occur before a diagnosis of SLE but should be attributable to SLE. Damage to an organ is irreversible, but the functional consequences on that organ may improve over time through physiological adaptation or treatment. We identified shifts in the paradigm of SLE damage and developed a unifying conceptual framework. These data form the groundwork for the next phases of SDI development.

EQ-5D full health state after therapy heralds reduced hazard to accrue subsequent organ damage in systemic lupus erythematosus.

To investigate whether self-reported EQ-5D full health state (FHS) after therapeutic intervention for active systemic lupus erythematosus (SLE) is associated with a reduced risk to accrue organ damage. In a separate analysis, we sought to investigate associations between experience of "no problems" in each one of the five dimensions of EQ-5D and the risk to accrue damage. Data from the open-label extension periods of the BLISS-52 and BLISS-76 trials of belimumab in SLE (NCT00724867; NCT00712933) were used (N = 973). FHS was defined as an experience of "no problems" in all five EQ-5D dimensions. Organ damage was assessed annually using the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). Associations between the three-level version of the EQ-5D (EQ-5D-3L) responses at open-label baseline and the first documented increase in organ damage were investigated using Cox regression accounting for age, sex, ancestry, SDI at baseline, and background therapy, and associations with SDI items were investigated using phi (φ) correlation analyses. A total of 147 patients (15.1%) accrued organ damage during follow-up, with the first increase in their SDI score occurring after a mean time of 29.1 ± 19.6 months. Lower proportions of FHS respondents accrued damage over a course of up to 7.9 years of open-label follow-up compared with no FHS respondents (p = 0.004; derived from the logrank test). FHS was associated with a reduced hazard to accrue subsequent organ damage (HR: 0.60; 95% CI: 0.38-0.96; p = 0.033) after adjustments, as was experience of "no problems" in mobility (HR: 0.61; 95% CI: 0.43-0.87; p = 0.006). "No problems" in mobility was negatively correlated with musculoskeletal damage accrual (φ = -0.08; p = 0.008) and associated with a lower hazard to accrue musculoskeletal damage in Cox regression analysis (HR: 0.38; 95% CI: 0.19-0.76; p = 0.006). Experience of EQ-5D-3L FHS and "no problems" in mobility after therapeutic intervention heralded reduced hazard to accrue subsequent organ damage, especially musculoskeletal damage, suggesting that optimisation of these health-related quality of life aspects constitutes a clinically relevant treatment target in patients with SLE, along with clinical and laboratory parameters.

Characteristics of Hearing Loss in Patients with Systemic Lupus Erythematosus.

To investigate the clinical characteristics of hearing loss (HL) in patients with systemic lupus erythematosus (SLE) and its related factors. Ninety-one hospitalized SLE patients and thirty healthy controls were enrolled. All subjects completed pure tone audiometry (PTA), extended high frequency audiometry (EHFA) and distortion product otoacoustic emission (DPOAE) to assess hearing function. SLE patients were divided into two groups according to the presence or absence of HL, and the risk factors of HL were determined by multivariate logistic regression. The incidence of HL was 27.47% in SLE patients, significantly higher than in the control group (3.3%) and most cases were mild-to-moderate, bilateral and predominantly sensorineural. Compared with the control group, the hearing thresholds of SLE patients increased significantly in the middle and high frequencies starting from 2000 Hz. Even though the PTA test results were normal, the EHFA test results showed significant differences in hearing impairment between SLE patients and normal controls. For patients with abnormal PTA results, the signal-to-noise ratio (SNR) in DPOAE was markedly reduced, and the pass rate was also decreased. The Systemic Lupus International Collaborating Clinics Damage Index (SDI, OR 9.13) and secondary Sjögren's syndrome (sSS, OR 8.20) were identified as independent associated factors for HL, and there was no difference in PTA and EHFA at all frequencies between hydroxychloroquine users and non-users. HL is not rare in SLE patients, and EHFA can help identify early hearing impairment. Having a high SDI score and secondary Sjögren's syndrome may predict the presence of HL in SLE.

Efficacy and Safety of the Bruton's Tyrosine Kinase Inhibitor Evobrutinib in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Trial.

Evobrutinib is a highly selective, orally administered Bruton's tyrosine kinase (BTK) inhibitor. The objective of this phase II, multicenter, randomized, double-blind, placebo-controlled trial was to evaluate the efficacy and safety of evobrutinib in patients with active autoantibody-positive systemic lupus erythematosus (SLE). Patients were diagnosed with SLE by either the Systemic Lupus International Collaborating Clinics criteria or at least four American College of Rheumatology criteria 6 months or more prior to screening, had an SLE Disease Activity Index-2000 score of 6 or more, were autoantibody-positive and on standard-of-care therapy. Randomization was 1:1:1:1 to oral evobrutinib 25 mg once daily (QD), 75 mg QD, 50 mg twice daily, or placebo. Primary efficacy endpoints were SLE responder index (SRI)-4 response at week 52 and SRI-6 response at week 52 in the high disease activity subpopulation. Safety endpoints included treatment-emergent adverse events (TEAEs). A total of 469 patients were randomized and received at least one dose of evobrutinib or placebo at the time of primary analysis. Mean (SD) age at baseline was 40.7 (±12.3) years; 94.9% of patients were female. Neither primary efficacy endpoint was met. All doses of evobrutinib were well tolerated, and there was no clear dose effect on the incidence of reported TEAEs, or serious TEAEs, including severe infections. This phase II, dose-ranging trial in SLE failed to show a treatment effect of evobrutinib versus placebo at any dose. Evobrutinib was generally well tolerated, with no dose effect observed for TEAEs. These results suggest that BTK inhibition does not appear to be an effective therapeutic intervention for patients with SLE.

Dysentery and leg ulcer as an atypical presentation of systemic lupus erythematosus: A case report

Due to heterogeneity in the organs involved and a variety of influencing factors, a wide range of clinical manifestations are possible in systemic lupus erythematosus (SLE). In our knowledge, a combination of leg ulcer and dysentery as presenting symptoms of SLE has never been reported previously. A 13-year-old female child presented with a chronic wound over right medial malleolus for 6 months, and passing of watery stool, later mixed with blood, for 4 days. On examination, she had a fever of 38.5°C. Lab reports revealed anemia, thrombocytopenia, proteinuria, and features of urinary tract infection. Renal biopsy showed membranous glomerulonephropathy. She was positive for antinuclear antibodies (ANA) and antidouble stranded DNA (anti-dsDNA). Immunofluorescence revealed reduced C4 and C3 levels. Abdominal ultrasound showed symmetrical circumscribed thickening, and edematous cecum and ascending colon. The patient was diagnosed with SLE based on the Systemic Lupus International Collaborating Clinics classification criteria. The patient was treated with prednisolone, hydroxychloroquine, metronidazole, ciprofloxacin, trypsin-chymotrypsin, zinc, calcium, and calcitriol tablets. Fever subsided within 3 days of treatment. Gastrointestinal symptoms subsided within 1 week of treatment. On 31 day of treatment, the wound had been reduced and showed features of healing. Dysentery and leg ulcers can be the manifestations of SLE. Therefore, SLE should also be considered when a patient presents with such symptoms. Any suspicion of infection in SLE should be treated aggressively with antibiotics.

Pulmonary involvement: A potential independent factor for quality of life in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic multi-systemic autoimmune disease. SLE patients may experience a wide range of physical, psychological, and social perception of well-being influenced by the patient illness that are not always fully captured by descriptions of the disease's physiological consequences alone. Nowadays, patients with SLE have a better survival than decades ago, nevertheless still experience a low health related quality of life (HRQoL). Assessing disease activity in SLE is crucial to the physician as it forms the basis for treatment decisions, moreover careful evaluation for respiratory involvement should be routinely considered. More chronic lung disease related to SLE can have a significant negative effect on patient well-being and physical performance status and are detrimental to quality of life. The aim of this study was to evaluate quality of life changes in SLE patients using Lupus QoL scale, assessing their correlation with different disease aspects particularly pulmonary manifestations and predictors for worse QoL. Total of 60 SLE patients, who fulfilled the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria, were enrolled in this study. Disease activity was measured by systemic lupus erythematosus disease activity index (SLEDAI) and quality of life was assessed by Lupus QoL. Pulmonary evaluation included pulmonary function tests parameters (PFTs), mMRC dyspnea scale, HRCT score, and pulmonary damage index. Lupus QoL had a strong significant correlations with PFTs FEV1, FVC, and DLCO (r = 0.79, 0.78, 0.76, p < .001), respectively}, while Lupus QoL had strong negative correlations with both mMRC dyspnea scale and HRCT score (r = -0.96, -0.85, p < .001), respectively, and moderate negative correlation with neuropsychiatric lupus (NPSLE) (r = -0.61, p < .001). Weak negative correlations were found between Lupus QoL, photosensitivity, alopecia, Raynaud's and renal affection (r = -0.29, -0.30, -0.30, 0.38, p = .03, .02, .02, .002), respectively. NPSLE and pulmonary involvement were the most consistent predictors of low HRQoL [contributing 36% and 18% of the variance of Lupus QoL], respectively. Lupus QoL is negatively correlated with different SLE clinical parameters particularly pulmonary manifestations. Neuropsychiatric, pulmonary, renal affection, and SLEDAI are the best determinants for worse Lupus QoL.

Lupus low disease activity state and remission and risk of mortality in patients with systemic lupus erythematosus: a prospective, multinational, longitudinal cohort study.

Treat-to-target goals for patients with systemic lupus erythematosus (SLE) have been validated to protect against organ damage and to improve quality of life. We aimed to investigate the association between lupus low disease activity state (LLDAS) and remission and risk of mortality in patients with SLE. We hypothesised that LLDAS has a protective association with mortality risk. In this prospective, multinational, longitudinal cohort study, we used data from patients with SLE in the Asia Pacific Lupus Collaboration cohort collected between May 1, 2013, and Dec 31, 2020. Eligible patients were adults (aged ≥18 years) who met either the 1997 American College of Rheumatology modified classification criteria for SLE or the 2012 Systemic Lupus International Collaborating Clinics classification criteria. The primary outcome was all-cause mortality, and LLDAS, remission, and variations of remission with lower glucocorticoid thresholds were the primary exposure variables. Survival analyses were used to examine longitudinal associations between these endpoints and risk of mortality. This study is registered with ClinicalTrials.gov, NCT03138941. Among a total of 4106 patients in the cohort, 3811 (92·8%) patients were included in the final analysis (median follow-up 2·8 years [IQR 1·0-5·3]; 3509 [92·1%] women and 302 [7·9%] men), of whom 80 died during the observation period (crude mortality rate 6·4 deaths per 1000 person-years). LLDAS was attained at least once in 43 (53·8%) of 80 participants who died and in 3035 (81·3%) of 3731 participants who were alive at the end of the study (p<0·0001); 22 (27·5%) participants who died versus 1966 (52·7%) who were alive at the end of the study attained LLDAS for at least 50% of observed time (p<0·0001). Remission was attained by 32 (40·0%) of 80 who died and in 2403 (64·4%) of 3731 participants who were alive at the end of the study (p<0·0001); 14 (17·5%) participants who died versus 1389 (37·2%) who were alive at the end of the study attained remission for at least 50% of observed time (p<0·0001). LLDAS for at least 50% of observed time (adjusted hazard ratio 0·51 [95% CI 0·31-0·85]; p=0·010) and remission for at least 50% of observed time (0·52 [0·29-0·93]; p=0·027) were associated with reduced risk of mortality. Modifying the remission glucocorticoid threshold (<5·0 mg/day prednisolone) was more protective against mortality than current remission definitions (0·31 [0·12-0·77]; p=0·012), and glucocorticoid-free remission was the most protective (0·13 [0·02-0·96]; p=0·046). LLDAS significantly reduced the risk of mortality in patients with SLE. Remission did not further reduce the risk of mortality compared with LLDAS, unless lower glucocorticoid thresholds were used. The Asia-Pacific Lupus Collaboration received funding from Janssen, Bristol Myers Squibb, Eli Lilly, and UCB for this study.

Correlation between neutrophil to lymphocyte and platelet to lymphocyte ratios and renal involvement in systemic lupus erythematosus in Central Vietnam

Background: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease with diverse clinical manifestations and relapsing - remitting disease course. Nephritis is a major cause of morbidity and mortality in patients with lupus. Many clinical parameters and laboratory markers can be used to evaluate disease activity and nephritis. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are positively associated with inflammatory disorders. Objectives: To evaluate the correlation between NLR and PLR in peripheral blood and renal involvement in systemic lupus erythematosus. Methods: 63 patients were diagnosed with SLE according to the criteria of the Systemic Lupus International Collaborating Clinics 2012 (SLICC 2012) and were treated at the Internal Medicine Department of Hue University of Medicine and Pharmacy Hospital, Thua Thien Hue province, in central Vietnam, from February 2020 to July 2021. This study included 41 SLE patients with lupus nephritis (LN) and 22 SLE patients without renal involvement. Results: The mean age of the study group was 31.67 ± 12.10. The most common age group was 21-50 years old, accounting for 69.8%. Females accounted for 90.5% and the female-to-male ratio stood at 9.5:1. Clinical and laboratory characteristics: acute cutaneous lupus 50.8%, subacute cutaneous lupus 11.1%, oral ulcers 27%, non - scarring alopecia 47.6%, arthritis 61.9%, pleural or pericardial effusion 30.2%, renal involvement 65.1%, neuropsychiatric damage 4.8%, anemia 81.0%, leukopenia 22.2%, neutropenia 11.1%, lymphopenia 41.3%, thrombocytopenia 15.9%, hemolytic anemia 15.9%, positive ANA antibody 61.9%, positive anti-ds DNA antibody 52.4%. Acute cutaneous lupus and arthritis in SLE patients without the nephritis group were higher than in the LN group (p &lt; 0.05). Anemia, lymphopenia, thrombocytopenia, positive ANA, anti-ds DNA in the LN group were higher than SLE patients without nephritis (p &lt; 0.05). SLE patients with LN had higher levels of NLR than those without nephritis. While PLR had no remarkable difference between these two groups. NLR was positively correlated with CRP, serum creatinine, and 24-hour urinary protein. PLR was positively correlated with the SLEDAI score. The best NLR to predict LN was 4.97 with a sensitivity of 51.2% and a specificity of 95.5% (AUC = 0.742, 95% CI, 0.617 - 0.866, p = 0.002). Conclusion: Most of the clinical manifestations in SLE patients according to SLICC 2012 criteria were lupus nephritis, arthritis, and acute cutaneous lupus. PLR was positively correlated with the SLEDAI score. NLR could predict renal involvement in SLE patients. Keywords: Lupus nephritis, ANA, anti-ds DNA, NLR, PLR.

Glucocorticoid tapering and associated outcome in patients with newly diagnosed systemic lupus erythematosus: the real-world GULP prospective observational study

ObjectiveA subanalysis of the multicentre Early Lupus inception cohort was performed to investigate the real-world Glucocorticoids (GCs) Use in newly diagnosed systemic lupus erythematosus (SLE) Patients (GULP).MethodsPatients starting prednisone (PDN)...

Validity of immunoglobulin-binding protein 1 as a biomarker for lupus nephritis.

Lupus nephritis (LN) is a major issue that adds a burden on patients with systemic lupus erythematosus (SLE). Immunoglobulin-binding protein 1 (IGBP1) is identified as a phosphoprotein that has been recently reported to be linked to the B-cell receptor complex and regulates differentiation, proliferation, apoptosis, and tolerance of B cells. Its diagnostic and/or prognostic role in LN has been highlighted only recently. This study aims to evaluate the relation between serum IGBP1 and SLE disease activity and/or renal activity and to investigate the validity of IGBP1 as a biomarker for LN. 96 participants were enrolled and divided into three groups: nephritis, nonnephritis, and control groups. The patients with SLE were diagnosed according to the Systemic Lupus International Collaborating Clinics classification (SLICC) criteria. The serum IGBP1 level was assayed using an enzyme-linked immunosorbent assay (ELISA). Assessments were conducted using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2k) and renal biopsy for LN patients. The nephritis and nonnephritis groups had higher IGBP1 levels than the controls; the nephritis group had the highest serum IGBP1 levels (p < .001). Significant correlations were found between IGBP1 levels and proteinuria (r = 0.568, p = .001) and renal SLEDAI (r = 0.475, p = .006) in the nephritis group; on the other hand, the correlation of serum IGBP1 levels with SLEDAI-2K was non-significant for both groups (nephritis and nonnephritis groups). The IGBP1 levels were significantly different among histopathologic classes (p < .001), with class V showing the highest level. Moreover, it showed a significant positive correlation with the pathologic activity index. Compared with renal SLEDAI for identifying active renal affection in patients with SLE, the serum IGBP1 level with a cut-off value of 547.45ng/mL is a valid biomarker for detecting active nephritis with 93.8% sensitivity and 96.9% specificity. The serum IGBP1 levels were high in patients with LN and were positively correlated with the pathologic activity index. The serum IGBP1 level of 547.45ng/mL is a valid biomarker for detecting active nephritis. Thus, we recommend that clinicians monitor the serum IGBP1 level of patients with SLE to detect LN.

Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine

ObjectiveTo evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.MethodsData were collected at annual study visits between 1999 and 2019. We followed patients with...

Evaluating the Threshold Score for Classification of Systemic Lupus Erythematosus Using the EULAR/ACR Criteria.

To evaluate whether a change in the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria threshold score affects accurate classification of SLE cases compared to disease-based control subjects. We evaluated a range of threshold scores to determine the score that maximizes the accurate classification of early SLE. We conducted a cross-sectional study comparing SLE cases and control patients. A EULAR/ACR criteria score was calculated using baseline information. Sensitivity, specificity, positive likelihood ratios (+LRs), and negative likelihood ratios (-LRs) with 95% CIs were used to evaluate operating characteristics. Threshold scores of 6 to 12 were evaluated in subjects with early disease (ie, disease duration of ≤ 5 years). +LRs > 10 and -LRs < 0.1 provide evidence to rule in or rule out SLE. A total of 2764 patients were included: 1980 SLE cases who fulfilled either the ACR or Systemic Lupus International Collaborating Clinics criteria and 784 control subjects. The EULAR/ACR SLE criteria had a sensitivity of 98% (95% CI 97-98), a specificity of 99% (95% CI 98-100), a +LR of 95.5 (95% CI 48.0-190), and a -LR 0.03 (95% CI 0.02-0.03). The criteria operated well in those with early disease, in women, in men, and in White, Black, Chinese, and Filipino people. A score of 10 maximized the accurate classification of patients with early disease (+LR 174.4, 95% CI 43.8-694.6; -LR 0.03, 95% CI 0.02-0.04). An increase in the threshold score from 10 to 11 resulted in significant worsening in the -LR (threshold score 10: -LR 0.03, 95% CI 0.02-0.03 vs threshold score 11: -LR 0.05, 95% CI 0.04-0.06). The EULAR/ACR SLE classification criteria threshold score of 10 performs well, particularly among those with early disease and across sexes and ethnicities.

Association of the Systemic Lupus International Collaborating Clinics Frailty Index and Damage Accrual in Longstanding Systemic Lupus Erythematosus.

To externally validate the Systemic Lupus International Collaborating Clinics Frailty Index (SLICC-FI) in a prevalent systemic lupus erythematosus (SLE) cohort and to assess the ability of the SLICC-FI to predict organ damage accrual among individuals with longstanding SLE. This was a secondary analysis of data from the Study of Lupus Vascular and Bone Long-Term Endpoints (SOLVABLE) cohort, which consists of adult women from the Chicago Lupus Database who met the 1997 revised American College of Rheumatology (ACR) classification criteria for SLE. There were 185 patients with SLE enrolled, of whom 149 patients were included in a 5-year follow-up analysis. The SLICC-FI and SLICC/ACR Damage Index (SDI) scores were calculated at baseline and 5-year follow-up. Unadjusted and adjusted logistic regression models estimated the association of baseline SLICC-FI scores (per 0.05 increase) with damage accrual at 5-year follow-up. At enrollment the mean ± SD age of the 149 patients was 43.30 ± 10.15 years, the mean ± SD disease duration was 11.93 ± 8.46 years, and the mean ± SD SDI score was 1.64 ± 1.83. At baseline, the mean ± SD SLICC-FI score was 0.18 ± 0.08, and 36% of participants were categorized as frail (SLICC-FI score >0.21). In a model adjusted for age, race, and disease duration, each 0.05-unit increase in the baseline SLICC-FI score was associated with 28% higher odds of subsequent damage accrual (odds ratio 1.28, 95% confidence interval 1.01-1.63). In a prevalent cohort of women with established SLE, higher baseline SLICC-FI scores were associated with a higher risk of subsequent damage accrual at 5-year follow-up.

Systemic Lupus Erythematosus with Initial Manifestation as Enlargement in Cervical, Axillary and Inguinal Lymphnodes: A Case Report

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that may affect the joints, skin, kidneys, lungs, nervous system, and serous membranes and/or other organs. Lymphadenopathy is characterized by changes in the characteristics and size of the lymph nodes. It results from reticuloendothelial proliferation secondary to inflammation, infection, or malignancies. Lymphadenopathy is common in SLE. It has been reported that lymph node enlargement is observed in 25-67% of SLE patients. We reported this thirty-three-year patient with presented with lymph node enlargement in cervical, axillary, and inguinal, joint pain, renal involvement and respiratory involvement diagnosed as Systemic lupus erythematosus according to ACR/EULAR criteria immunological and clinical domain SLICC (systemic lupus international collaborating clinics.&#x0D; In conclusion, lymphadenopathy is a manifestation in SLE. As illustrated by the case presented here, it can precede the diagnosis of SLE by many years; It is possible that the factors that induce lymph node proliferation are also responsible for the development of autoantibodies.