Adult Systemic Lupus Erythematosus Research Articles

Risk factors for mortality in systemic lupus erythematosus patients: Analysis of adult and pediatric cohorts in Taiwan.

Overall survival of systemic lupus erythematosus (SLE) patients significantly increased in recent decades, however, the relative risk of mortality is still high. Long-term survival outcome of pediatric SLE remains unclear. This study aims to explore the long-term survival rate and its predictors in patients with systemic lupus erythematosus (SLE). A retrospective, hospital-based cohort study was performed between 2004 and 2018 in a tertiary referral medical center in Taiwan. Data on comorbidities, medications, and causes of admission were collected for risk factor analysis using time-dependent multivariate Cox proportional hazards models. A total of 2392 adults and 115 pediatric SLE patients were enrolled (female, n = 2157 and 95, respectively). The 10-year survival rates were 93.2%, 90.2%, 98.9%, and 100% in adult women, adult men, girls, and boys with SLE, respectively. The overall mortality rate was 2.09 case/100 patient-years (PY) for male SLE and 1.39 case/100 PY for female SLE patients. Male SLE patients did not have a statistically significantly higher mortality rate than female SLE patients in each age stratification. Infectious disease (n = 119), heart failure (n = 21), and cerebrovascular accident (n = 14) were the leading causes of death in adult SLE patients. Advanced age (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 1.03-1.05), treatment with mean dosage of systemic glucocorticoid equivalent to >10 mg/d of prednisolone (HR: 1.71, 95% CI: 1.14-2.57), comorbidities with malignancy (HR: 1.94, 95% CI: 1.22-3.09), chronic kidney disease (HR: 1.86, 95% CI: 1.25-2.77), hypertension (HR: 1.42, 95% CI: 1.01-1.98), and admission due to bacterial pneumonia (HR: 1.92, 95% CI: 1.12-3.31) and sepsis (HR: 2.78, 95% CI: 1.51-5.13) were independent risk factors for mortality in SLE patients. SLE patients with advanced age, malignancy, chronic kidney disease, hypertension, treated with a higher average dosage of glucocorticoids, and admission due to bacterial pneumonia and sepsis have an increased risk of mortality.

Diagnostic accuracy of the European League against rheumatism/American College of Rheumatology-2019 versus the Systemic Lupus International Collaborating Clinics-2012 versus the ACR-1997 classification criteria in adult systemic lupus erythematosus: A systematic review and meta-analysis.

AimTo evaluate the diagnostic performance of the American College of Rheumatology (ACR)-1997, the Systemic Lupus International Collaborating Clinics (SLICC)-2012, and the European League against Rheumatism (EULAR)/ACR-2019 classification criteria in adult patients with systemic lupus erythematosus (SLE).MethodsPubMed, Embase, Web of Science and Cochrane Library databases were searched for literature comparing the three classification criteria of ACR-1997, SLICC-2012 and EULAR/ACR-2019, which took clinical diagnosis as reference. Meta-analysis was used to evaluate and compare the sensitivity, specificity and diagnostic odds ratio of ACR-1997, SLICC-2012 and EULAR/ACR-2019. To assess the early diagnosis capability of the classification criteria, subgroups of patients with disease duration < 3 years and < 1 year were selected for comparison of sensitivity and specificity based on the inclusion of the original study. The sensitivity and specificity of each item in three sets of classification criteria were evaluated. In addition, the clinical and immunological characteristics of patients who did not meet the three classification criteria were compared.ResultsNine original studies were included in the analysis, including 6404 SLE patients and 3996 controls. Results showed that the diagnostic odds ratios (95% confidence interval) of the SLICC-2012 [136.35 (114.94, 161.75)] and EULAR/ACR-2019 [187.47 (158.00, 222.42)] were higher than those of the ACR-1997 [67.53 (58.75, 77.63)]. Compared with ACR-1997[(0.86 (0.82, 0.89)], SLICC-2012[(0.96 (0.93, 0.97)] and EULAR/ACR-2019[(0.95 (0.92, 0.97)] had higher sensitivity. The specificity of the three classification criteria was similar: ACR-1997, SLICC-2012, and EULAR/ACR-2019 were 0.93 (0.89, 0.95), 0.86 (0.79, 0.91), and 0.91 (0.85, 0.95), respectively. The sensitivity of SLICC-2012 and EULAR/ACR-2019 were higher than that of ACR-1997 in early-course subgroups. Patients who did not meet ACR-1997 had more hypocomplementemia, patients who did not meet SLICC-2012 had more cutaneous lupus and photosensitivity, and patients who did not meet EULAR/ACR-2019 had more cutaneous lupus and leucopenia.ConclusionsSLICC-2012 and EULAR/ACR-2019 have better diagnostic ability than the ACR-1997, and the sensitivity of the former two criteria is also higher than that of the latter; Moreover, the SLICC-2012 and EULAR/ACR-2019 for patients in the early stages of disease performed equally excellent.

P13 A case of Kikuchi-Fujimoto disease triggered by an episode of bacterial cellulitis, associated with features of SLE

P13 A case of Kikuchi-Fujimoto disease triggered by an episode of bacterial cellulitis, associated with features of SLE

Childhood-onset systemic lupus erythematosus, probably triggered by severe acute respiratory syndrome coronavirus 2 infection, presenting with autoimmune haemolytic anaemia

Systemic lupus erythematosus (SLE) is a multisystemic and chronic autoimmune disease with varying clinical manifestations. The role of various infectious agents in triggering the disease onset in genetically predisposed patients has been implicated in the pathogenesis of SLE. The severe acute respiratory syndrome coronavirus 2 has been reported to trigger various autoimmune diseases including SLE in few adults. Herein, we report the case of a previously well 12-year-old girl who presented with warm antibody Coombs-positive autoimmune haemolytic anaemia, 3 weeks after testing positive for COVID-19. COVID IgG antibody test was positive. During the hospital stay, she developed multisystem involvement in the form of neurological manifestations and arthritis. She was managed with steroids, intravenous (IV) immunoglobulins and supportive measures. Her anti-nuclear antibody and anti-dsDNA antibodies were positive and complement levels were low, confirming a diagnosis of SLE. Her clinical condition improved rapidly and remained neurologically normal, and serial haemoglobin showed an improving trend. IV steroids were changed to oral form, and hydroxychloroquine was also added. She remained well on 3-week follow-up.

Abstract 097: Seasonal Travel Stressors Modulates Hypertension In Adult Female Lupus Mice

Systemic lupus erythematosus (SLE) is an autoimmune disorder linked to chronic renal inflammation and prevalent hypertension. We use an established murine model of SLE (NZBWF1) to mechanistically link renal inflammation to the development of hypertension. SLE mice travel to our university pre-puberty (3-6 weeks), develop autoantibodies by 20 weeks, and are consistently hypertensive by 35 weeks. We observed that when mice travel in the summer, autoantibody production is higher as the mice age vs. those that travel in the winter. This association was heightened in a subset of SLE mice that traveled to our university as adults (18-19 weeks), suggesting a role of seasonal factors, travel stressors, and age in altering disease severity. It is unknown whether these seasonal and environmental stressors can also alter blood pressure and inflammatory processes. Thus, we hypothesized that travel-induced seasonal stressors exacerbate hypertension and renal inflammation in adult SLE-prone mice. Female SLE mice traveled to our university in summer or winter at 3-6 or 18-19 weeks and were implanted with carotid catheters once they reached 35 weeks to assess mean arterial pressure (MAP). Mice were then euthanized and tissues collected to monitor plasma and renal interleukin (IL)-6, a proinflammatory cytokine. No seasonal differences were found in MAP of mice that traveled pre-puberty in summer (n = 17) and winter (n = 39) (143.6 ± 3.5 vs. 140.2 ± 2.2 mmHg; p = 0.4096) nor in plasma IL-6 (26.06 ± 7.25 vs. 15.54 ± 8.622 pg/mL; p = 0.2370) or renal IL-6 (0.01156 ± 0.00603 vs. 0.01099 ± 0.00523 pg/μg; p = 0.9445). Conversely, adult SLE mice that traveled in summer had higher MAP than those that traveled in winter (136.12 ± 2.63 vs. 128.81 ± 1.55 mmHg; p = 0.0339; n = 5-7), as well as higher plasma IL-6 (723.28 ± 220.72 vs. 280.73 ± 67.99 pg/mL; p = 0.0339) and renal IL-6 (0.078956 ± 0.017192 vs. 0.023413 ± 0.003801 pg/μg; p &lt; 0.0001). Together, our data indicate that hypertension and renal inflammation in mice subjected to travel stress as adults is seasonally dependent. Since there were no seasonal differences in hypertension in SLE mice that traveled pre-puberty, there may be a factor related to age, seasonal environmental factors, and/or timing of the stressors that is causing the detrimental effect.

Exploring urine:serum fractional excretion ratios as potential biomarkers for lupus nephritis.

ObjectivesThe goal of this exploratory study is to determine if urine:serum fractional excretion ratios can outperform the corresponding urinary biomarker proteins in identifying active renal disease in systemic lupus erythematosus (SLE).MethodsThirty-six adult SLE patients and twelve healthy controls were examined for serum and urine levels of 8 protein markers, namely ALCAM, calpastatin, hemopexin, peroxiredoxin 6 (PRDX6), platelet factor 4 (PF4), properdin, TFPI and VCAM-1, by ELISA. Fractional excretion of analyzed biomarkers was calculated after normalizing both the urine and serum biomarker levels against creatinine. A further validation cohort of fifty SLE patients was included to validate the initial findings.ResultsThe FE ratios of all 8 proteins interrogated outperformed conventional disease activity markers such as anti-dsDNA, C3 and C4 in identifying renal disease activity. All but VCAM-1FE were superior to the corresponding urine biomarkers levels in differentiating LN activity, exhibiting positive correlation with renal SLEDAI. ALCAMFE, PF4FE and properdinFE ratios exhibited the highest accuracy (AUC>0.9) in distinguishing active LN from inactive SLE. Four of the FE ratios exhibited perfect sensitivity (calpastatin, PRDX6, PF4 and properdin), while ALCAMFE, PF4FE and properdinFE exhibited the highest specificity values for active LN. In addition, several of these novel biomarkers were associated with higher renal pathology activity indices. In the validation cohort ALCAMFE, PF4FE and properdinFE once again exhibited higher accuracy metrics, surpassing corresponding urine and serum biomarkers levels, with ALCAMFE exhibiting 95% accuracy in distinguishing active LN from inactive SLE.ConclusionsWith most of the tested proteins, urine:serum fractional excretion ratios outperformed corresponding urine and serum protein measurements in identifying active renal involvement in SLE. Hence, this novel class of biomarkers in SLE ought to be systemically evaluated in larger independent cohorts for their diagnostic utility in LN assessment.

Identify differential inflammatory cellular and serology pathways between children and adult patients in the lupus registry.

Background:Age variances in systemic lupus erythematosus (SLE) may reflect different patterns and consequences. Monocyte differentiation is critical, and cytokine and chemokine milieu may be associated with long term outcome and treatment responses. This study aims to evaluate the inflammatory cellular and serology pathways associated with age in our lupus registry.Methods:We included patients with SLE and divided them into 2 groups according to age, ≤18 or >18 years old. We performed flow cytometry analysis to define the peripheral blood monocyte differentiation pattern and phenotypes and used the multiplex method to detect cytokine and chemokine panels. The results were then compared between the 2 subgroups.Results:In total, 47 SLE patients were included in this study. Of those, 23 patients were 18 years old or younger, and 24 patients were over the age of 18 years old. An increased distribution of circulating Type 2b macrophage (M2b) subsets was found in patients over 18 years old (P < 0.01), and we found the Type 1 macrophage (M1) to demonstrate a marked increase in those patients ≤18 years old (P = .05). Eotaxin values were significantly higher in patients >18 years old (P = .03), and Macrophage Inflammatory Protein (MIP)-1alpha, MIP-1beta, Interleukine (IL)-1Ra, Interferon (IFN)-alpha2, IL-12, IL-13, IL-17A, IL-1beta, IL-2, IL-4, IL-5, IL-7, IL-9, Monocyte Chemoattractant Protein (MCP)-3, Transforming Growth Factor (TGF)-alpha, and Tumor necrosis factor (TNF)-beta were significantly higher in patients ≤18 years old (all P < .05).Conclusions:We found significant M2b polarization in adult SLE patients, and several cytokines and chemokines were significantly higher in SLE patients ≤ 18 years old. Peripheral blood mononuclear cell differentiation and cytokine milieu could represent composite harm from both Type 2 helper T cells (Th2) and Type 17 helper T cells (Th17) pathways and may thus be a potential therapeutic target in younger SLE patients.

Importance of temporality and context in relation to life habit restrictions among patients with systemic lupus erythematosus: A psychosocial qualitative study.

Life habits (LH) encompass an individual's engagement in daily activities such as nutrition, fitness, personal care, communication, housing, and mobility, along with his/her social role (responsibility, interpersonal relationships, community life, education, employment, and recreation). This qualitative study explores the nature and context of LH restrictions in systemic lupus erythematosus (SLE) individuals across their SLE journey. Narrative interviews were conducted with adult SLE patients. Interview transcripts were subjected to a thematic content analysis, using the Disability Creation Process model as a framework. Forty participants were interviewed. Three major themes were highlighted: (1) Temporality, capabilities, and environmental contexts: although all participants experienced LH restrictions at some point, the expression of these limitations depended on the individual's and SLE disease characteristics as well as on temporal (time of life and lupus course) and environmental (material, social, and societal) contexts. (2) Identity issues, illness stigma, and (fear of) discriminations: LH were discussed through the lens of participants' social roles and identities. While illness stigma can influence social relations, it is also expressed at a societal level. (3) Masking and minimizing strategies: due to illness stigma and fear of discrimination, participants developed strategies to manage their relationships, including masking and minimization. Their use was both advantageous and disadvantageous regarding LH. For individuals with SLE, LH restrictions must be considered as an ongoing process that takes place within specific contexts. Our findings provide many opportunities for interventions that can benefit patients and their families, as well as healthcare providers.

Immunogenicity and Safety of mRNA Anti-SARS-CoV-2 Vaccines in Patients with Systemic Lupus Erythematosus.

Vaccination is the most effective preventive measure to control the spread of COVID-19 and reduce associated complications. This study aims to evaluate the efficacy and safety of mRNA COVID-19 vaccines in patients with systemic lupus erythematosus (SLE). A total of 41 adult SLE patients receiving two doses of the SARS-CoV-2 mRNA Comirnaty-BioNTech/Pfizer vaccine were enrolled. The quantitative determination of anti-trimeric spike protein-specific IgG antibodies to SARS-CoV-2 was assessed before (T0), 21 days after the administration of the first dose of the vaccine (T1), and between 21 and 28 days after the second dose (T2). They were compared with the same determinations from a cohort of 29 patients with C1-esterase inhibitor deficiency hereditary angioedema (C1-INH-HAE) as controls. All the SLE patients and controls demonstrated a positive serological response after a single dose of the vaccine (T1), which significantly increased after the second dose (T2). No significant difference was found between SLE patients and controls at T1 [t(52.81) = −0.68; p = 0.49] and at T2 [t(67.74) = −0.22; p = 0.825]. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) analysis showed that the vaccine did not influence SLE activity or caused disease flare in our cohort. In conclusion, COVID-19 vaccines produced a satisfactory response in SLE patients without variation in the disease activity.

Development of a claims-based flare algorithm for systemic lupus erythematosus

Objective To develop a claims-based algorithm identifying systemic lupus erythematosus (SLE) flares using a linked claims-electronic medical record (EMR) dataset. Methods This study was a retrospective analysis of linked administrative claims and EMR data spanning 1 January 2003 to 31 March 2019. Included were adult SLE patients with at least 12 months of continuous enrollment in claims data, 12 months of clinical activity in EMR, and an absence of malignancies excluding basal and squamous cell carcinoma. Patient follow-up was divided into 30-day windows, and a proxy SLEDAI-2K score based on the EMR data was calculated for each 30-day period. A flare was defined as an increase of at least 4 from the baseline score. A series of potential flare predictor variables identified in claims were based on a combination of established variables from a previous algorithm, with the addition of other SLE-related indicators based on clinical input. Logistic regression models were built to predict monthly SLE flares. Results Inclusion criteria identified 2427 patients. Results from a logistic model with forward selection capping the number of variables at 10 performed well with a c-statistic of 0.76 and a Brier score of 0.07. The top five predictors were any inpatient admission (OR = 4.76), outpatient office visit (OR = 3.04), MRI (OR = 2.26), ER visit (OR = 2.25), and number of rheumatology visits (OR = 1.75); p < .01 for all. Conclusions The final algorithm shows promise in providing an alternative and more streamlined way for identifying likely flares in administrative claims data that will advance the study of SLE within the context of flares.

Persistence of Depression and Anxiety despite Short-Term Disease Activity Improvement in Patients with Systemic Lupus Erythematosus: A Single-Centre, Prospective Study.

Mental disorders such as anxiety and depression are prevalent in systemic lupus erythematosus (SLE) patients, yet their association with the underlying disease activity remains uncertain and has been mostly evaluated at a cross-sectional level. To examine longitudinal trends in anxiety, depression, and lupus activity, a prospective observational study was performed on 40 adult SLE outpatients with active disease (SLE Disease Activity Index [SLEDAI]-2K ≥ 3 [excluding serology]) who received standard-of-care. Anxiety and depression were determined at baseline and 6 months by the Hospital Anxiety and Depression Scale. Treatment adherence was assessed with the Morisky Medication Adherence Scale-4. Increased anxiety (median [interquartile range] HADS-A: 11.0 [7.8]) and depression (HADS-D: 8.0 [4.8]) were found at inclusion, which remained stable and non-improving during follow-up (difference: 0.0 [4.8] and −0.5 [4.0], respectively) despite reduced SLEDAI-2K by 2.0 (4.0) (p < 0.001). Among possible baseline predictors, paid employment—but not disease activity—correlated with reduced HADS-A and HADS-D with corresponding standardized beta-coefficients of −0.35 (p = 0.017) and −0.27 (p = 0.093). Higher anxiety and depression correlated with lower treatment adherence (p = 0.041 and p = 0.088, respectively). These results indicate a high-mental disease burden in active SLE that persists despite disease control and emphasize the need to consider socioeconomic factors as part of comprehensive patient assessment.

Cell activation, PD-1 expression and in vitro cytokine production in patients with juvenile systemic lupus erythematosus.

Juvenile systemic lupus erythematosus (jSLE) is known to be more severe and with a higher frequency of renal and central nervous system impairment when compared to systemic lupus erythematosus in adults. The study of immunological characteristics of jSLE patients might help to envisage better treatment strategies to reduce the burden of the disease. To characterize peripheral lymphocytes, assessing activation markers, and PD-1 expression on T cells; to evaluate in vitro cytokine expression upon stimulation in jSLE patients and age-matched controls. Eighteen jSLE patients on low disease activity and 25 matched healthy adolescents were evaluated for immune activation and PD-1 expression on peripheral blood lymphocytes by flow cytometry. Twenty-one cytokines were assessed by X-MAP technology after in vitro stimulation of peripheral blood with phytohemagglutinin. jSLE patients had lower numbers of CD4 T, CD8 T, B, and NK cells; higher central memory CD8 T cell percentages were noted in jSLE adolescents in comparison with controls (p = 0.014). B cells subsets showed a higher percentage of exhausted memory subset than controls (p = 0.014). The expression of PD-1 on CD4 T and CD8 T cells did not show relevant changes in jSLE adolescents. After stimulation of peripheral blood, cell supernatant of jSLE patients showed a trend to lower concentrations of IL-10 (p=0.080) and higher concentrations of IL-23 (p = 0.063) than controls. jSLE patients on low disease activity maintain lymphopenia of all subsets, with a B cell profile of exhaustion. Upon in vitro stimulation, peripheral blood cell supernatant showed a shift to IL-23, suggesting a role of inhibitors of this cytokine as another potential therapeutic target for those patients.

Predictors of improvement in disease activity in first hospitalized patients with systemic lupus erythematosus: a multicenter retrospective study of a Chinese cohort

ObjectivesTo analyze the relative factors of improvement in disease activity (IDA) after first hospitalized treatment based on the systemic lupus erythematosus disease activity index (SLEDAI).MethodsA total of 1069 adult systemic lupus erythematosus (SLE) patients who were hospitalized for the first time in 26 hospitals in Jiangsu Province from 1999 to 2009 were retrospectively analyzed. SLEDAI decrease ≥ 4 during hospitalization was identified as IDA. Relative factors of IDA were assessed by univariate and multivariate logistic regression.ResultsA total of 783 (73.2%) adult SLE patients showed IDA after the first hospitalization, while the remaining patients (n = 286) were in the non-IDA group. The IDA group had higher SLEDAI at admission; fewer patients had SLICC/ACR damage index (SDI) ≥ 1, comorbidities at admission, especially Sjögren’s syndrome, abnormal serum creatinine, and glomerular filtration rate. More patients had mucocutaneous and musculoskeletal involvements, leukopenia, increased C-reactive protein, anti-dsDNA antibody positive, and hypocomplementemia at admission and were treated with methotrexate and leflunomide during hospitalization. After multivariate logistic regression analysis, SDI ≥ 1 (P = 0.005) and combined with Sjögren’s syndrome (P < 0.001) at admission had negative association with IDA. Musculoskeletal involvement (P < 0.001), anti-dsDNA antibody positive (P = 0.012), hypocomplementemia (P = 0.001), and use of leflunomide (P = 0.030) were significantly related with IDA.ConclusionOrgan damage or comorbidities at admission were adverse to SLE improvement. Anti-dsDNA antibody positive, hypocomplementemia, musculoskeletal involvements, and leflunomide treatment had positive association with IDA of SLE.Key Points• Organ damage or comorbidities at admission were negatively correlated with SLE improvement.• Anti-dsDNA antibody positivity, hypocomplementemia, musculoskeletal involvements, and leflunomide treatment were positively associated with SLE improvement.

Intestinal pseudo-obstruction in systemic lupus erythematosus: an analysis of nationwide inpatient sample.

Intestinal pseudo-obstruction (IPO) is a rare gastrointestinal complication of systemic lupus erythematosus (SLE). We aimed to determine the prevalence and in-hospital outcomes of SLE-related intestinal pseudo-obstruction (SLE-IPO) using a large national database. This is a retrospective study using Nationwide Inpatient Sample (NIS) from 2016 to 2018. We included adult patients with SLE using International Classification of Diseases 10th Revision (ICD-10) code M32 in combination with codes for IPO, and we determined the in-hospital mortality, occurrence of sepsis, length of hospitalization, use of total parenteral nutrition (TPN), and frequency of surgical gastrointestinal procedures. The prevalence of IPO among hospitalized adult SLE patients was 1.7%, and the in-hospital mortality of SLE-IPO was 5.04%. Compared with SLE patients without IPO (group 2), SLE-IPO patients had higher in-hospital mortality (OR 2.07, 95%CI 1.60-2.64), higher risk of sepsis (OR 1.63, 95%CI 1.42-1.87), longer in-hospital stay (β 3.09, 95%CI 2.76-3.42), and higher frequency of TPN (OR 16.20, 95%CI 11.62-22.21) and gastrointestinal procedures (OR 5.47, 95%CI 4.62-6.43). SLE-IPO was associated with increased risk of sepsis (OR 1.29, 95%CI 1.12-1.49), compared with idiopathic IPO patients (group 3), and a possible increase in the frequency of gastrointestinal procedures (OR 1.14, 95%CI 0.96-1.34) compared with IPO secondary to diabetes mellitus (group 4), although not statistically significant. SLE-IPO patients were at twofold risk of in-hospital mortality compared with SLE patients without IPO. SLE-IPO was also associated with longer in-hospital stay and increased frequency of TPN and gastrointestinal procedures. Key Points • The prevalence of IPO in adult SLE patients was 1.7% in this US-based database. • In-hospital mortality rate of SLE-IPO was 4.95%. SLE-IPO patients were associated with twofold risk of in-hospital mortality compared with those without IPO. •SLE-IPO patientswere also at increasedrisk of sepsis, and they had higher rate of TPN and gastrointestinal procedures.

The Role of Belimumab in Systemic Lupus Erythematosis: A Systematic Review.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple systems with a range of clinical presentations caused by the production of antibodies, activation of complements, and deposition of immune complexes. The exact cause of SLE is still unknown. The effectiveness of traditional treatment methods for SLE is very little. Nowadays, resistance to conventional therapy, steroids, and immunosuppressants is common among SLE patients. Patients with refractory disease and nephritis generally have severe drug-induced toxicity which contributes to organ dysfunction, despite available therapies. Different biologic agents and therapeutic antibodies have become an alternative and have been under experiment in clinical trials, enrolling patients whose disease is inadequately controlled by conventional treatment. Belimumab is the only targeted therapy approved for SLE treatment. This systematic review discusses one such biological agent for treating systemic lupus erythematosus, namely, belimumab.The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies included randomized clinical trials (RCTs) from 2005 to 2021 on adult SLE. patients treated with monoclonal antibodies to assess the efficacy and safety. Methodological quality was assessed using PubMed, PMC, the Cochrane Risk of Bias tool, and the QUality In Prognosis Studies Tool (QUIPS) for RCTs. Two independent reviewers performed an electronic search on MEDLINE, Cochrane Library, SCIELO, Scopus, and ResearchGate.Based on a systematic review of articles we found that belimumab appears to be efficacious and generally well-tolerated in the treatment of SLE as compared to other drugs. The long-term use of belimumab combined with standard therapy showed a low incidence of organ damage. A lower incidence of organ damage was seen after initiating treatment in patients with a high risk for organ dysfunction. Patients who test for antinuclear antibody or anti-dsDNA-positive SLE, with moderate symptoms in the skin and musculoskeletal systems despite immunosuppressants, are treated with belimumab as an adjunct therapy. Patients with severe lupus nephritis or active CNS lupus cannot be treated with belimumab. Belimumab is effective in most races, as a clinical trial done in North-East Asia showed improvement in SLE symptoms and decreased dependence on prednisone. Belimumab also decreased disease activity and severe flares. Belimumab had greater efficacy in children.

Differential impact of disease activity and damage on health-related quality of life in patients with systemic lupus erythematosus.

To study the association between disease activity, disease-related organ damage and health-related quality of life (HRQoL) among Asian patients with systemic lupus erythematosus (SLE). We prospectively recruited adult SLE patients from a single tertiary center and followed them three-monthly. We recorded the SLE Disease Activity Index 2000 (SLEDAI-2K) at each visit. SLICC-ACR damage index (SDI) and HRQoL (Medical Outcomes Survey Short Form 36 (SF-36)) were recorded annually. We evaluated the association between SLEDAI-2K and SDI with SF-36 physical (PCS) and mental (MCS) component scores using linear mixed effect models. We studied 198 patients, comprising Chinese, Malays and Indians. The mean (SD) age at enrollment was 47.1 (12.5) years. The baseline median (IQR) SLEDAI-2k was 2 (0-4). While the mean PCS improved significantly in the second and third year, MCS was unchanged. In the multivariable mixed model analysis, SDI, but not SLEDAI-2k, was significantly associated with poorer PCS (estimate of coefficient (SE) -0.81 (0.29), p < .01). Conversely, SLEDAI-2k, but not SDI, was negatively associated with MCS (estimate of coefficient (SE) -0.36 (0.17), p = .04). In this cohort of multi-ethnic Asian SLE patients, disease activity is associated with poorer mental, but not physical, HRQoL; whereas disease-related damage is associated with poorer physical, but not mental HRQoL. Our findings suggest a need to differentially approach the impaired HRQoL in SLE patients at different phases of disease; possibly by treating disease activity in patients with impaired mental HRQoL and addressing disease-related damage in patients with impaired physical functioning.

An evaluation of sleep habits and childhood-onset systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, known for its heterogeneous clinical presentation. Although it is rarer in children, a more severe clinical course can be seen than in adults. It is known that sleep has physiological and developmental importance in children, and there are many studies on sleep quality in adult SLE patients. The aims of this study are to evaluate the sleep habits of children and adolescents with SLE and to compare them with their healthy peers. The study included 48 children and adolescents with SLE and 64 healthy peers as a control group. The Children's Sleep Habits Questionnaire was used to evaluate the sleep characteristics of children. The age and gender of the children were similar across groups. The bedtime resistance and night waking scores of SLE patients were significantly higher than those of the control group. Total sleep score was higher in patients with SLE than in the control group, but there was no significant difference (47.13±7.63 vs 44.61±8.17; p=0.051). Similarly, the rate of sleep disorders in the patient group (75%) was higher than that of the control group (61%), though the differences were not statistically significant (p = 0.156). There was no correlation between disease severity and sleep problems. This research demonstrated that sleep disorders tend to increase in children and adolescents with SLE. Therefore, clinicians should pay attention to sleep disorders during the follow-up sessions of children and adolescents with SLE. Key Points • Sleep disorders tend to increase in children and adolescents with SLE. • Disease severity is not associated with sleep problems.

Systemic Lupus Erythematosus in Filipino Children: A 10-year Retrospective Analysis of Mortality, Morbidity and Survival

Background. Systemic Lupus Erythematosus (SLE) in children has been estimated to account for 15 to 20% of all SLE cases worldwide. It was described to have more severe disease at presentation including renal, neuropsychiatric, and hematologic involvements; more disease activity over time, and a significantly higher risk of organ damage. Thus, considered a significant risk factor for mortality among adult SLE patients.&#x0D; Objective. This is a retrospective cohort study aimed to determine the clinical profile, outcome, and survival of SLE among Filipino children.&#x0D; Methods. All SLE patients, less than 19 years old, diagnosed in the pediatric department of a tertiary hospital from January 2008 to December 2017 were included in the study. Their medical charts were retrieved for data gathering. Demographics, and clinical disease characteristics were collected from admission and on subsequent follow ups. Lost to follow up patients were contacted for updates of their current clinical status.&#x0D; Results. A total of 261 pediatric SLE patients were gathered. Average age at diagnosis is 14.5 years old (±2.7), with female to male ratio of 16:1. Symptoms starts at 3 months prior to consult (±2.1). Upon diagnosis, most of the patients have fever, malar rash, alopecia, oral ulcers, and proteinuria. Most common systemic organ involvement through time were mucocutaneous, hematologic, and renal. Steroids were the mainstay management for all patients, in which 95% started on oral Prednisone, while 71% needed IV Methylprednisolone in at least once during the disease course. Two patients received biologic treatment. Overall mortality rate was 14.9%, identified to be secondary to sepsis and/or SLE activity. Myocarditis, pleural effusion, and seizures were identified as significant risk factors for mortality. Survival rate at 1 year and 10 years were 92% and 79%, respectively.&#x0D; Conclusion. SLE in Filipino children mostly presents with mucocutaneous symptoms. Presence of seizures, myocarditis, and pleural effusion at any time of the disease entails risk for mortality. SLE nephritis is a substantial cause of morbidity due to its chronicity. The survival rate of Filipino children with SLE is comparable with the data from other developing countries.

Association of Human Leucocyte Antigen Class II, with viral load and immune response to Epstein-Barr virus in adult and pediatric Systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, which is known to be associated with HLA-DRB1 and Epstein-Barr virus (EBV) infection. In the Indian subcontinent where there is high seroendemicity of EBV, we postulated that the association of this virus in adult SLE (aSLE) and pediatric SLE (pSLE) patients would be different and differentially associate with the HLA-DRB1 susceptibility and protective genes. A total of 109 aSLE, 52 pSLE, 215 adult healthy and 63 pediatric healthy controls were recruited. HLA-DRB1 genotyping by PCR-SSP, EBV load estimation by real-time PCR and antibody profiling (IgG & IgM) to EBV antigens by line blot assay were performed. DRB1*15 was found predominant in pSLE patients and DRB1*03 in aSLE patients. DRB1*15/X heterozygous was predominant in overall SLE patients, although disease severity, like hypocomplementemia, higher autoantibody levels and more organ involvement was observed in *15/*15 homozygous state. EBV strongly associated with pSLE patients showing higher percent of EA-D IgG (p < 0.0001) and p22 IgG (p = 0.035) along with higher viral load (p = 0.001) as compared to healthy controls. In addition, the higher EBV DNA load significantly associated with anti-EA-D IgG (p = 0.013) and DRB1*15/*15 (p = 0.007) in pSLE patients as compared to aSLE patients. This study therefore indicates that different HLA-DRB1 allotypes confer susceptibility to SLE in children and adults and disease may be triggered by increased EBV reactivation.

P233 Environmental and occupational exposures in the development of systemic lupus erythematosus in adults: a narrative review

Abstract Background/Aims Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, of an autoimmune nature, of unknown origin, characterized by loss of tolerance to nuclear antigens and the deposition of immunecomplexes in the tissues leading to inflammation that can affect various organs and systems of the body. This narrative review aims to demonstrate that occupational factors and environmental exposure contribute to the development of SLE in adults. Methods This is a narrative review of literature that seeks to analyse the scientific production on environmental and occupational exposure in the development of systemic lupus erythematosus in adults, published in health journals. A literature search was conducted in the period between November 2020 and July 2021, considering the object of study, initially the articles related to the theme addressed were searched in the PubMed database, in the US National Institutes of Health (NIH) and Scientific Electronic Library Online (SCIELO) portals. Results Exposure to respirable silica dust (i.e. the crystalline form of quartz) is an established risk factor for SLE and other systemic autoimmune diseases. Exposure to toxic components of cigarette smoke (e.g., tar, nicotine, carbon monoxide, polycyclic aromatic hydrocarbons, and free radicals) can induce oxidative stress and directly damage endogenous proteins and DNA, leading to genetic mutations and gene activation, which may be involved in the development of SLE. Smoking stimulates the expression of CD95 on B and CD4 on T-cell surfaces, potentially inducing autoimmunity, and also increases the production of pro- inflammatory cytokines. Exposure to ultraviolet (UV) radiation may exacerbate pre-existing SLE; it is not yet known whether UV exposure plays a role in the pathogenesis of SLE. Thus, UV may result in a redistribution of nuclear antigens to the cell surface or in the production of new forms of autoantigens, effects that may be relevant given the mechanisms believed to be involved in SLE etiology. Several hypotheses have been postulated that air pollution may contribute to autoimmune diseases via oxidative stress, nitrosative stress, and systemic inflammation. Traffic-related air pollutants may cause oxidative stress and and systemic inflammation. The combination of CO with hemoglobin (Hb) to form carboxyhemoglobin (COHb) reduces the oxygen-carrying capacity of the blood and causes tissue hypoxia. Conclusion The articles analysed identified risk factors for exposure to current smoking, silica, ultraviolet radiation, and environmental pollution from CO, NO2, and minute particles. These are caused by oxidative stress, apoptosis inducers, systemic inflammation, genetic mutations, and activation of genes that will lead to immunological changes with increased pro-inflammatory cytokines, activation of genes, and increased autoantigens, leading to predisposition of these exposures in the development of systemic lupus erythematosus. In contrast, alcohol has been shown to be a neutralizing factor in systemic inflammation, causing a decrease in cellular responses and suppressing the synthesis of pro-inflammatory cytokines, showing the association of alcohol with a lower risk of developing SLE. Disclosure B.G. Monteiro: Grants/research support; FUNADESP. C.B. Pizarro: Grants/research support; FUNADESP.