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A home-based exercise program during COVID-19 pandemic: Perceptions and acceptability of juvenile systemic lupus erythematosus and juvenile idiopathic arthritis adolescents.
Sieczkowska, SM, Astley, C, Marques, IG, Iraha, AY, Franco, TC, Ihara, BP, Martins Lavorato, SS, Lindoso, L, Demitrol Setoue, DN, Tanigava, NY, et al
Lupus. 2022;(4):443-456
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Abstract
OBJECTIVES To investigate the perceptions and acceptability of a home-based exercise intervention in systemic lupus erythematosus (JSLE) and juvenile idiopathic arthritis (JIA) adolescent patients during the COVID-19 pandemic, and to explore the effects of the intervention on health-related quality of life (HRQoL), sleep quality, and mental health conditions parameters. METHODS This was a randomized controlled trial of a 12-week, home-based exercise training program conducted between October and December 2020. During this period, social distancing measures were in place in Brazil to contain the spread of COVID-19. Adolescent patients diagnosed with JSLE and JIA participated in the study. Health-related qualitative and quantitative data were collected before and after the follow-up. RESULTS 21 JSLE patients and 30 JIA patients were analyzed. Six themes emerged from patients' feedback: 1) Suitability of the home-based format; 2) Appropriate trainer supervision, 3) Motivators and facilitators for the program; 4) Barriers to the program; 5) Health benefits; 6) Patients' suggestions to improve the program. Overall, data indicated that the intervention showed good acceptability and elicited improvements in the perceived HRQoL and fatigue in JIA and JSLE patients during the pandemic. However, further quantitative analyses with validated HRQoL, sleep quality, and mental health conditions instruments did not capture these benefits (p>0.05). CONCLUSION Our main findings based on in-depth qualitative assessments suggest that a home-based exercise training program was suitable and well-accepted by adolescents with JSLE and JIA during the COVID-19 pandemic. Nonetheless, adherence was not high, particularly among JIA patients, suggesting that facilitators and barriers identified in the current study should be explored to improve the quality of new home-based exercise programs implementation, particularly in a future emerging crisis.
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NETs decorated with bioactive IL-33 infiltrate inflamed tissues and induce IFN-α production in patients with SLE.
Georgakis, S, Gkirtzimanaki, K, Papadaki, G, Gakiopoulou, H, Drakos, E, Eloranta, ML, Makridakis, M, Kontostathi, G, Zoidakis, J, Baira, E, et al
JCI insight. 2021;(21)
Abstract
IL-33, a nuclear alarmin released during cell death, exerts context-specific effects on adaptive and innate immune cells, eliciting potent inflammatory responses. We screened blood, skin, and kidney tissues from patients with systemic lupus erythematosus (SLE), a systemic autoimmune disease driven by unabated type I IFN production, and found increased amounts of extracellular IL-33 complexed with neutrophil extracellular traps (NETs), correlating with severe, active disease. Using a combination of molecular, imaging, and proteomic approaches, we show that SLE neutrophils, activated by disease immunocomplexes, release IL-33-decorated NETs that stimulate robust IFN-α synthesis by plasmacytoid DCs in a manner dependent on the IL-33 receptor ST2L. IL33-silenced neutrophil-like cells cultured under lupus-inducing conditions generated NETs with diminished interferogenic effect. Importantly, NETs derived from patients with SLE are enriched in mature bioactive isoforms of IL-33 processed by the neutrophil proteases elastase and cathepsin G. Pharmacological inhibition of these proteases neutralized IL-33-dependent IFN-α production elicited by NETs. We believe these data demonstrate a novel role for cleaved IL-33 alarmin decorating NETs in human SLE, linking neutrophil activation, type I IFN production, and end-organ inflammation, with skin pathology mirroring that observed in the kidneys.
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Pure red cell aplasia in systemic lupus erythematosus, a nationwide retrospective cohort and review of the literature.
Lobbes, H, Mahévas, M, Alviset, S, Galicier, L, Costedoat-Chalumeau, N, Amoura, Z, Alric, L, Hot, A, Durupt, S, Michel, M, et al
Rheumatology (Oxford, England). 2021;(1):355-366
Abstract
OBJECTIVES To characterize the clinical and biological course, management and response to treatment in SLE-associated pure red cell aplasia (PRCA). METHODS This was a nationwide, multicentre, retrospective cohort study. From 2006 to 2018, we included adults with a diagnosis of PRCA supported by bone marrow examination and SLE or biologic manifestations of SLE after ruling out parvovirus B19 infection. RESULTS We enrolled 24 patients (20 women). SLE was diagnosed before PRCA for 14 patients (median delay 81 months). At PRCA diagnosis, mean age, haemoglobin level, and reticulocyte and differential erythroblast count were 39.2 (13.2) years, 62 ( 20) g/l, 9.1 (7.6) × 109/l and 2.8 ( 2.5)%, respectively. Eleven (45%) patients experienced multiple PRCA flares (median 6, range 2-11). CS therapy resulted in only three complete sustained responses, and 19 (79%) patients required immunosuppressive agents with highly variable regimens. After a median follow-up of 76 months (range 13-173), 17 (71%) patients showed complete response for PRCA, 5 (21%) partial response and 2 (8%) treatment failure. In total, 21 (87%) patients required red blood cell transfusion; 5 had a diagnosis of transfusion-related iron overload. Eighteen (75%) patients experienced severe infectious events requiring hospitalization. CONCLUSION SLE-associated PRCA is a severe condition. Repeated red blood cell transfusions and several lines of immunosuppressant therapy are mostly required, with high risk of severe infectious events and iron overload. Despite sustained response for PRCA and SLE obtained in most patients, the best therapeutic strategy remains to be determined.
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Prevalence of hydroxychloroquine retinopathy with long-term use in a cohort of Indian patients with rheumatic diseases.
Manoj, M, Sahoo, RR, Singh, A, Hazarika, K, Bafna, P, Kaur, A, Wakhlu, A
Rheumatology international. 2021;(5):929-937
Abstract
The study aims to estimate the prevalence of hydroxychloroquine (HCQ) retinopathy in a cohort of Indian patients and analyse the associated factors. Adult patients with rheumatological disorders aged ≥ 18 years using HCQ for more than 5 years and/or having received a cumulative dose > 400 g were included. Demographic and clinical data were collected and all underwent ophthalmological tests which included Humphrey automated visual fields (AVF) and spectral domain optical coherence tomography (SD-OCT). The various clinical characteristics of the patients were compared. The study included 110 patients with a mean age of 43.5 ± 10.1 years and predominantly females. Eleven patients (10%) were diagnosed with definite HCQ retinopathy. The mean daily dose of HCQ (mg/kg of real body weight) was significantly different in the groups with and without retinopathy (5.7 ± 0.9 vs 5.1 ± 0.8, p = 0.04). Patients with retinopathy had significantly more colour vision abnormalities (odds of 16.9; confidence interval 4.1-69.1, p = 0.0001) and higher prevalence of both parafoveal and perifoveal thinning (p < 0.0001). Age, gender, duration of HCQ use, cumulative HCQ dose and body mass index were not found to be associated with retinopathy. Four out of 11 patients had abnormalities only on 30-2 protocol for AVF testing, two had abnormalities only on 10-2 protocol, whereas five patients had abnormalities on both protocols. SD-OCT abnormalities were present in all patients with retinopathy. Hydroxychloroquine retinopathy was prevalent in the study cohort and significantly associated with a higher daily dose of HCQ (mg/kg real body weight).
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The Association between Interleukin-6 Gene Polymorphisms and Risk of Systemic Lupus Erythematosus: A Meta-analysis with Trial Sequential Analysis.
Liu, J, Liao, MQ, Cao, DF, Yang, Y, Yang, Y, Liu, YH, Zeng, FF, Chen, XH
Immunological investigations. 2021;(2-3):259-272
Abstract
BACKGROUND Molecular epidemiological studies have sought associations between interleukin-6 (IL-6) polymorphisms and the risk of systemic lupus erythematosus (SLE); however, the results are controversial. Therefore, we conducted a meta-analysis with trial sequential analysis to evaluate a more accurate estimation of the associations. METHODS Published literatures reporting the relationships of two IL-6 polymorphisms (G-174C and G-572C) and SLE risk were retrieved from electronic databases such as PubMed and EMBASE. The most appropriate genetic model was chosen for each polymorphism. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Trial sequential analysis (TSA) was introduced to assess the information size and the positive results. RESULTS With 17 studies (2780 cases and 3100 controls) included, a dominant association (CC+GC vs. GG) was suggested for G-174C polymorphism, and compared with the GG genotype, the CC+GC genotype of G-174C was associated with a decreased SLE risk (OR = 0.71; 95% CI = 0.56-0.88, P =.02). No association was found for G-572C under all genetic models (e.g. OR and 95%CI for CC+GC vs. GG: 0.89, 0.73-1.08, P =.22). Subgroup analyses indicated that SLE risk decreased in G-174C polymorphism by subgroups of Caucasian population, publications after 2010, studies with high quality, and studies complied with Hardy-Weinberg equilibrium (HWE). TSA suggested that the sample sizes used for G-572C were insufficient. CONCLUSION We found that the minor allele C of IL6G-174C polymorphism is a protective factor in SLE. Further studies with a larger sample size are needed to confirm the null association for G-572C.
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Telitacicept: First Approval.
Dhillon, S
Drugs. 2021;(14):1671-1675
Abstract
Telitacicept (Tai'ai®) is fusion protein comprising a recombinant transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) receptor fused to the fragment crystallizable (Fc) domain of human immunoglobulin G (IgG). Telitacicept is being developed by Yantai Rongchang Pharmaceutical through its subsidiary RemeGen for the treatment of B cell-mediated autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and multiple sclerosis (MS). Telitacicept binds to and neutralizes the activity of two cell-signalling molecules, B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), thereby suppressing the development and survival of plasma cells and mature B cells. In March 2021, telitacicept received its first approval in China for the treatment of patients with active SLE. Clinical studies of telitacicept in several other indications, including IgA nephropathy, MS, myasthenia gravis, neuromyelitis optica spectrum disorders, RA and Sjögren's syndrome are underway in China. This article summarizes the milestones in the development of telitacicept leading to this first approval for SLE.
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Scleroderma-associated thrombotic microangiopathy in overlap syndrome of systemic sclerosis and systemic lupus erythematosus: A case report and literature review.
Xie, X, Wang, G, Cheng, H, Sun, L, Dong, H
Medicine. 2020;(41):e22582
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Abstract
RATIONALE Systemic sclerosis (SSc) is a serious multisystem connective tissue disease. When SSc is accompanied by systemic lupus erythematosus (SLE), called SSc-SLE overlap syndrome. SSc associated thrombotic microangiopathy (SSc-TMA) can lead to scleroderma renal crisis, it mainly manifests hypertension or even malignant hypertension, acute kidney injury, and higher mortality. The case of SSc-SLE overlap syndrome combined with SSc-TMA has rarely been reported. PATIENT CONCERNS We report the case of an elderly male with SSc-SLE overlap syndrome combined with scleroderma renal crisis and SSc-TMA. DIAGNOSES The patient has typical of SSc on the face and hands, combined with pulmonary artery hypertension, interstitial lung disease, heart failure and malignant hypertension, as well as SLE, lupus nephritis class V, and TMA, which were definitively diagnosed by clinical laboratory examination and renal histopathology. INTERVENTIONS The patient was treated with prednisone, cyclophosphamid, renin-angiotensin system inhibitors, diuretics, and acetylcysteine. OUTCOMES The patient died suddenly of heart failure on the 35th day after discharge. LESSONS The occurrence of TMA leads to the deterioration of the prognosis of SSC-SLE overlap syndrome. The diagnosis of SSC-TMA in SSc-SLE overlap syndrome depends on clinical laboratory examination and renal histopathology.
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Primary breast diffuse large B-cell lymphoma in a patient with systemic lupus erythematosus: A case report and review of the literature.
Shen, F, Li, G, Jiang, H, Zhao, S, Qi, F
Medicine. 2020;(33):e21736
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Abstract
RATIONALE Pilot studies have reported that patients with systemic lupus erythematosus (SLE) appear more likely to develop into neoplasia, especially lymphatic hyperplasia diseases. To our knowledge, this is the first case report of the concomitant onset of SLE and primary breast diffuse large B-cell lymphoma (PB-DLBCL). PATIENT CONCERNS We reported an unusual case of the occurrence of primary breast diffuse large B-cell lymphoma in a 25-year-old female patient who had been diagnosed with SLE and treated with immunosuppressive drugs for about 4 years. She presented a 7-week history of a painless mass above the left breast and no history suggestive of any nipple discharge, fever, and weight loss. DIAGNOSIS Ultrasonography of the breast showed that there was 1 mass in the left breast. After breast mass surgical resection, histopathological examinations were performed and revealed that it was primary breast diffuse large B-cell lymphoma. INTERVENTIONS Treatment strategy with vincristine and dexamethasone was used to improve symptoms. However, the patient's renal function deteriorated and the blood potassium rose continuously and she and their family members refused the follow-up treatments. OUTCOMES The patient died 8 months after she was discharged from the hospital. LESSONS PB-DLBCL is a rare occurrence in SLE patients. Therefore, a careful examination is very important in SLE cohort, as activity of the disease and malignancy may mimic each other. Meanwhile, when symptoms cannot be explained or insensitive to treatment, the occurrence of malignant tumors must be highly considered.
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A systematic review of pharmacological therapies and their effectiveness on health-related quality of life outcomes in patients with juvenile-onset systemic lupus erythematosus.
Cintrón, D, Alanis, JM, Álvarez-Villalobos, N, Rodríguez-Gutiérrez, R, Vilá, LM
Lupus. 2020;(3):303-310
Abstract
Juvenile-onset systemic lupus erythematosus (JSLE) presents with an aggressive course and high morbidity associated with disease and treatment. JSLE patients have a poorer health-related quality of life (HRQoL) when compared with age-matched patients with other rheumatologic disorders. We aim to summarize the impact of current pharmacological therapies on the HRQoL of JSLE patients. Search strategies were developed across seven databases. Randomized clinical trials (RCTs) and cohort studies comparing interventions to standard therapy, placebo or pre-post cohort comparisons for more than 4 weeks were included. The outcome included self-reported scales compared at baseline and a therapeutic time point. Risk of bias was evaluated by using the Cochrane risk of bias tool and the Newcastle-Ottawa quality assessment scale. A total of 2812 articles were narrowed down to 309 for full-text screening. Four RCTs and one prospective cohort study, with a total of 634 JSLE patients, met the inclusion criteria. Four of the studies had a controlled intervention plus standard therapy compared with standard therapy alone or placebo. Multiple indices were used to evaluate HRQoL. These included the Pediatric Quality of Life Inventory, Childhood Health Assessment Questionnaire, Simple Measure of Impact of Lupus Erythematosus in Youngsters tool, Kids Fatigue Severity Scale and Child Depression Inventory. A single study reported a significant improvement while remaining studies reported no difference or failed to report the statistical analysis. Although HRQoL is significantly impaired in JSLE, evidence regarding its improvement is limited due to the small number of eligible studies, heterogeneity in scales, and HRQoL domains. A universal HRQoL questionnaire for JSLE needs to be established and used in both the research and clinical setting. All studies should adhere to reporting guidelines.
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Associations of four common VDR polymorphisms with rheumatoid arthritis and systemic lupus erythematosus: evidence from a meta-analysis.
Zhang, WT, Jin, TF, Chen, L
Lupus. 2020;(4):364-370
Abstract
Associations of polymorphisms in vitamin D receptor (VDR) with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have already been explored by many studies. The aim of this meta-analysis was to better clarify associations between polymorphisms in VDR and RA/SLE by combing the results of all relevant studies. Eligible studies were searched from Pubmed, Embase, WOS and CNKI. We used Review Manager to combine the results of eligible studies. Thirty-seven studies were included in this meta-analysis. VDR rs1544410 (recessive comparison: odds ratio (OR) = 1.36, 95% confidence interval (CI) 1.06-1.76; over-dominant comparison: OR = 0.81, 95% CI 0.71-0.93) and rs731236 (over-dominant comparison: OR = 0.77, 95% CI 0.63-0.94) polymorphisms were found to be significantly associated with RA in overall combined analyses. Besides, VDR rs1544410 (dominant comparison: OR = 0.61, 95% CI 0.46-0.82; over-dominant comparison: OR = 1.45, 95% CI 1.16-1.81; allele comparison: OR = 0.75, 95% CI 0.62-0.92), rs2228570 (dominant comparison: OR = 0.58, 95% CI 0.50-0.67; recessive comparison: OR = 1.57, 95% CI 1.21-2.03; allele comparison: OR = 0.69, 95% CI 0.60-0.80) and rs731236 (dominant comparison: OR = 0.69, 95% CI 0.50-0.96; allele comparison: OR = 0.80, 95% CI 0.70-0.90) polymorphisms were also found to be significantly associated with SLE in overall combined analyses. Subgroup analyses revealed that significant associations for VDR polymorphisms and RA/SLE were mainly driven by Asians. Collectively, this meta-analysis proved that VDR rs7975232, rs1544410, rs2228570 and rs731236 polymorphisms may confer susceptibility to RA and SLE, especially for Asians.