Systemic Lupus Erythematosus Disease Activity Research Articles

Belimumab in the treatment of systemic lupus erythematosus with juvenile onset: Results of a single-center retrospective study

The treatment of systemic lupus erythematosus with juvenile onset (jSLE) remains a difficult task, taking into account the more aggressive course of the disease, requiring the appointment of various therapy regimens, including mainly a combination of high doses of glucocorticoids (GC) with immunosuppressive drugs, which on the one hand improves control by the course of the disease, but on the other hand leads to an increase in serious adverse effects from therapy. Modern therapy capabilities have improved significantly with the advent of the belimumab – first and alone registered biologics for children with SLE.The aim of the study – based on an open single-center retrospective study, to analyze the efficacy and safety of belimumab in children with SLE.Material and methods. The study included all patients with jSLE who were observed in the pediatric department of V.A. Na sonova Research Institute of Rheumatology and received at least 1 infusion of belimumab. Diagnosis of SLE based on 2012 SLICC (Systemic Lupus Erythematosus International Collaborating Clinics) criteria. The efficacy of therapy was evaluated among patients who received belimumab for 6 months or more, and safety in all who received at least 1 infusion.Results. The study included 31 patients, 24 girls/7 boys. The median (Me) age at onset of the disease was 12.6 [10.18; 13.5] years, the Me duration of the disease at the time of initiation of belimumab therapy was 2.15 [0.9; 4.4] years. The Me activity on the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) at the time of diagnosis verification was 12 [9; 17.5], at the time of start of belimumab – 8 [6; 12], 35.5% patients had severe activity, 51.6% – moderate, 12.9% – mild activity. The dose of GC per os at start of belimumab was 15 [10; 21.25] mg/day, 32.26% of patients received a high dose of GC, 54.84% – moderate dose, 12.9% – low dose. 9 patients had SDI (Systemic Lupus International Collaborating Clinics Damage Index) ≥1, Me – 1 [1; 2]. After 6 months of therapy, the Me of disease activity according to SLEDAI was 4 [2; 6], the dose of GC per os was reduced to 10 [8.25; 17.5] mg/day. In 15 patients, a decrease in antiDNA was recorded (57.7% of those who initially had elevated values of antiDNA), in 9 the level of complement was normalized (50% of those who initially had hypocomplementemia). After 12 months of therapy, the Me of SLEDAI was 4 [2; 4] (p=0.034), the dose of GC per os was 5 [5; 8.125] mg/day (p=0.012). 5 patients completed therapy within 12 months or more: 1 patient – remission, 4 patients – secondary inefficiency. Belimumab treatment was well tolerated, with the exception of three cases of serious adverse reactions (9.7%): prolonged diarrheal syndrome (after the 1st infusion), Lyell’s syndrome (after the 2nd infusion), infusion reaction (during the 2nd infusion). During the therapy of belimumab, no new damage were recorded; in 2 patients there was a decrease in the SDI.Conclusion. Belimumab therapy in patients with jSLE demonstrated high efficacy with a decrease in the activity of the disease according to SLEDAI, normalization of antiDNA and complement, the possibility of a significant reduction the dose of GC, the absence of progression of the SDI with a good safety profile in the vast majority of patients.

Immunophenotypes of systemic lupus erythematosus – features of clinical and laboratory disorders

The aim – to evaluate subpopulations of B lymphocytes and features of interferon (IFN) status in patients with systemic lupus erythematosus (SLE), to clarify the relationship of immunological parameters with clinical manifestations of the diseaseMaterial and methods. 139 patients (123 (88%) women and 16 (12%) men) with a definite diagnosis of SLE were included in the analysis. The disease duration was 3.0 [0.3; 12.0] years, SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index 2000) – 7 [4; 11] points, SDI (Systemic Lupus International Collaborating Clinics Damage Index) – 0 [0; 1] points. Immunophenotyping of peripheral blood lymphocytes, including determination of B cells, the general population of memory B cells, non-switched and switched memory B cells, naive, transient B cells, and plasmablasts was carried out using multicolor flow cytometry. IFN status was assessed by the expression of IFN-stimulated genes (MX1, RSAD2, EPSTI1) using real-time polymerase chain reactionResults. Two immunological “patterns” were identified – the prevailing immunological mechanism of the pathogenesis of the disease – SLE – with predominant activation of type I IFN and with predominant activation of the B cell component of the immune system. The immunological phenotype with activation of type I IFN was associated with high immunological activity, predominant skin damage, leukopenia, and the phenotype with predominant activation of the B cell link was associated with damage to the kidneys and nervous system.Conclusion. The results of the work suggest a wide variety of immune mechanisms underlying the pathogenesis of SLE. It is possible to identify a number of leading molecular “patterns” of the pathogenesis of the disease, which must be taken into account to select an effective “targeted” drug.

Serum IFN-γ Predicts the Therapeutic Effect of Belimumab in Refractory Lupus Nephritis Patients.

To evaluate belimumabf's efficacy in refractory lupus nephritis (LN) patients and identify predictive serum biomarkers for treatment response. In this single-arm retrospective study,we assessed clinical responses in LN patients at baseline and six months after initiating belimumab. Serum cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were quantified using multiplex magnetic bead flow immunoassay before and after treatment. Fourteen patients with various subtypes of refractory LN participated in the study: seven with class III and V LN, three with type V alone, two with class III, and two with class IV+V and V LN. Post six months of belimumab therapy, all participants exhibited a reduction in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K scores from their respective baseline values. Notably, most patients showed a decrease in the dosage of prednisone, levels of 24-hour urinary protein, immunoglobulins, erythrocyte sedimentation rate (ESR), and anti-double-stranded DNA antibody IgM, along with serum levels of IL-4, IL-6, IL-10, and IFN-γ. Meanwhile, levels of C3, C4, IL-2, and TNF-α were observed to increase. Of the participants, nine (64.29%) achieved a complete renal response, one (7.14%) showed a partial response, and four (28.57%) exhibited no response. Significantly, higher baseline serum IFN-γ levels were found in patients who did not achieve complete renal response (CR) compared to those who did (p = 0.009). Receiver operating characteristic (ROC) curve analysis demonstrated that baseline IFN-γ levels had an area under curve (AUC) of 0.96 (0.70-1.00), with a sensitivity of 0.89 and a specificity of 1.00 (p < 0.001). Belimumab shows potential efficacy in treating refractory LN. Baseline serum IFN-γ levels may predict response to belimumab therapy, potentially enabling more targeted treatment approaches for this challenging condition.

Lupus flare and recurrent lupus nephritis following kidney transplantation in patients with lupus nephritis

AbstractBackgroundClinical manifestations and risk factors associated with systemic lupus erythematosus (SLE) flares, including recurrent lupus nephritis (LN), in patients with LN who undergo kidney transplantation have been unclear.MethodsKidney transplant recipients with LN from January 1995 to December 2021 were included in this study. A disease flare was defined as either an increase in the non‐renal SLE disease activity index score or the presence of biopsy‐proven recurrent LN.ResultsAmong a total of 93 patients with LN who underwent kidney transplantation, 11 patients (11.8%) experienced SLE flares during a median follow‐up period of 76.9 months (IQR, 43.0–122.4). The most common clinical manifestations of SLE flares were recurrent LN (4/11, 36.4%) and hematologic manifestations (4/11, 36.4%). Patients who had flares had significantly higher anti‐double‐stranded DNA (anti‐dsDNA) antibody titers both before and after transplantation. Furthermore, an increased anti‐dsDNA antibody level before transplantation was associated with a high risk of an SLE flare (HR, 1.030; p = .008). Conversely, preemptive transplantation was associated with a lower risk of a flare (HR, 0.617; p = .026). The rate of patient death‐censored graft survival was found to be considerably lower in patients with recurrent LN than in those without LN.ConclusionsApproximately 10% of patients with LN experienced an SLE flare after transplantation, with recurrent LN being the most frequent manifestation. Anti‐dsDNA antibody titers before transplantation were significantly related to the risk of an SLE flare. Notably, preemptive transplantation was associated with a reduced risk of flares following transplantation.

Genetic variations of interleukin 32(rs28372698) and interleukin 37 (rs3811047), and their serum levels in systemic lupus erythematosus patients

BackgroundSystemic lupus erythematosus (SLE) is a complex autoimmune disease. The underlying pathogenesis still needs to be elucidated. Aim of the workTo investigate interleukin-32 (IL-32) (rs28372698) and interleukin-37 (IL-37) (rs3811047) genetic variations, measure their serum levels in SLE patients, and evaluate their relation with disease parameters. Patients and methodsThis work included 46 SLE patients and 43 matched controls. The SLE disease activity index (SLEDAI) and SLE damage index (SDI) were recorded. Genetic variations were assessed by real-time polymerase chain reaction (RT-PCR), and serum levels of IL-32 and IL-37 were measured by enzyme-linked immune-sorbent assay (ELISA). ResultsThe mean age of the patients was 29.2 ± 6.1 years, and the female: male ratio was 45:1. IL-37 genetic variation (rs3811047) GG was significantly more frequent in SLE patients (24/46,52.2 %) (p = 0.024), those with lupus nephritis (LN)(18/27,66.7 %) (p = 0.038), and active disease (15/21,68.2 %) (p = 0.002). The IL-37 G allele was significantly more represented in lupus patients (68/92,73.9 %)(p = 0.008), with IL-37 serum levels significantly increased in SLE patients (855.7 ± 465.4) compared to the control (504.1 ± 553.8) (p = 0.002). Although serum IL-32 was significantly higher in patients who received cyclophosphamide (CYC),and significantly correlated with total cholesterol, on regression analysis neither CYC nor cholesterol were significant factor for serum IL-32. The area under the curve for IL-37 serum levels to distinguish SLE patients from controls was 0.71, (CI 0.601–0.827; p = 0.001). ConclusionThe IL-37 genetic variation (rs3811047) GG was significantly elevated in SLE, LN, and active patients. G allele was significantly more represented in lupus patients. IL-37 serum levels were significantly increased in SLE patients.

Prevalence and risk factors of depression in juvenile systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organ systems, including the central nervous system. Depression is one of the neuropsychiatric manifestations of juvenile SLE . Objective To estimate the prevalence of depressive disorders in juvenile SLE and identify its potential risk factors. Methods This cross-sectional study was conducted in juvenile SLE patients at Dr. Mohammad Hoesin General Hospital, Palembang. Sociodemographic data and medications were recorded. Disease activity of SLE was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Physical activity was measured using the Physical Activity Questionnaire for Children (PAQ-C) and the Physical Activity Questionnaire for Adolescents (PAQ-A). All subjects were screened for depression using the Childhood Depression Inventory (CDI) questionnaire. Multiple linear regression analyses were used to determine risk factors for depressive disorders. Results We included 72 patients, of whom 67 (93.1%) were female. Mean age of the patients was 12 years 4 months (SD 2 years 6 months); most (67; 93.1%) were 10-18 years of age. Depression was found in 24 patients (33.3%). SLEDAI scores of ?3 (flare) were found in 54 patients (75%) and low physical activity was found in 62 (86.1%) patients. The prevalence of depression based on the Children's Depression Inventory was 33.3%. A SLEDAI score of ?3 and low physical activity were significantly associated with depression (P=0.009 and P=0.025, respectively). On multiple linear regression analysis, only SLEDAI score of ?3 remained significantly associated with depression (P= 0.017; OR 12.6; 95%CI 1.6–101.7). Gender, age, family economic status, father's education, mother's education, family history of depression, and duration of illness were not associated with depression. Conclusion A SLEDAI score indicating flare (?3) and low physical activity are significantly associated with an increased risk of depression. A SLEDAI score is an independent risk factor for depression when all other significant risk factors are considered.

Improving lupus care index documentation in patients with childhood-onset systemic lupus erythematosus.

Childhood-onset systemic lupus erythematosus (c-SLE) presents unique challenges due to increased risk for severe morbidity and mortality compared to adult-onset SLE. Effective disease management relies on accurate disease assessment and documentation. Our project aimed to improve the documentation of the Lupus Care Index (LCI), a disease assessment bundle, by implementing a quality improvement (QI) initiative. A QI project was conducted at Nationwide Children's Hospital (NCH), targeting patients with c-SLE. The LCI, comprising the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2k) Physician Global Assessment (PGA) and patient-reported pain score, was introduced to capture comprehensive disease assessment. Interventions included provider education, standardization of documentation procedures, and electronic health record (EHR) modifications. Automated reports tracked documentation rates, and Pareto charts identified areas for targeted interventions. Baseline analysis revealed incomplete documentation of LCI components in only one-third of c-SLE patients. Following interventions, documentation rates improved from 38% to 90%, with sustained improvement over at least a year. Enhancing documentation of LCI in patients with c-SLE is crucial for optimizing disease management. Our quality improvement initiative demonstrated the feasibility of improving documentation practices through targeted interventions and system modifications. Future research should explore the impact of comprehensive documentation on clinical outcomes in pediatric lupus patients. Improving documentation of LCI in patients with c-SLE is essential for optimizing care delivery and clinical outcomes; our QI initiative highlights the effectiveness of systemic interventions in enhancing documentation practices and underscores the importance of continued efforts to improve pediatric lupus care.

Mental health problems among children with lupus nephritis

Aim of the workTo assess and compare depression, anxiety, and cognitive impairments in juvenile systemic erythematous lupus (JSLE) children with lupus nephritis (LN) during the induction and maintenance phases of treatment and to investigate the association with disease activity, damage and immunosuppressive medications. Patients and methodsThis study included 33 patients diagnosed as JSLE with LN. Attention and working memory were assessed by the working memory index Wechsler Intelligence Scale (WISC). Depression and anxiety were assessed by the Children Depression Inventory (CDI) and the Spence Children Anxiety Scale respectively. The SLE disease activity index 2000 (SLEDAI-2 K) was recorded. ResultsThe mean age of the children was 11.6 ± 2.2 years, 88 % were females and 12 % males with disease duration of 16.9 ± 9.2 months and age at onset of 10.2 ± 2.3 years. Mean anxiety scores were higher among patients during the induction phase than those during maintenance phase (62.1 ± 7.2 and 40.2 ± 8.8 respectively; p < 0.001). The depression score was higher in the induction (19 ± 5.5) than in the maintenance group (12.4 ± 5.6) (p = 0.002). Mean anxiety scores significantly correlated with SLEDAI-2 K and corticosteroids dose (r = 0.58 and r = 0.43, p = 0.0004 and p = 0.013 respectively) and a significant negative correlation with duration of corticosteroids and number of cyclophosphamide doses (r = 0.46 and r = 0.69, p = 0.008 and p = 0.0001 respectively). ConclusionDepression and anxiety levels were higher in children with LN during the induction phase of treatment than those in the maintenance phase. Mental health problems must be screened among children with LN and treating these problems can improve the medical and psychosocial outcomes.

Efficacy and safety of sequential therapy with subcutaneous belimumab and one cycle of rituximab in patients with systemic lupus erythematosus: the phase 3, randomised, placebo-controlled BLISS-BELIEVE study

ObjectivesDisease activity control in patients with systemic lupus erythematosus (SLE) with corticosteroid and immunosuppressant withdrawal is a treatment goal. We evaluated whether this could be attained with sequential subcutaneous belimumab...

Musculoskeletal manifestations in childhood-onset systemic lupus erythematosus: an in-depth exploration

BackgroundChildhood-onset systemic lupus erythematosus (c-SLE) is a multifaceted autoimmune disorder predominantly affecting the musculoskeletal (MSK) system. This investigation delineated the spectrum and sequelae of MSK involvement in c-SLE patients.MethodsThis retrospective analysis included SLE patients aged ≤ 18 years treated at a tertiary center between 2009 and 2019. Data were extracted from electronic health records.ResultsThe cohort comprised 321 SLE patients (mean age 13.2 ± 2.5 years, 91.3% female). MSK manifestations were observed in 134 (41.7%) individuals, with joint pain universally present, followed by joint swelling in 32.1% and morning stiffness in 9.7%. Arthritis was documented in 52 (38.8%) patients, whereas 82 (61.2%) had arthralgia. Symmetrical joint involvement was observed in 96 (71.7%) subjects. The knees, wrists, and fingers were most commonly affected, with incidences of 43.3%, 40.3%, and 33.6%, respectively. Neither erosive arthritis nor Jaccoud’s arthropathy was detected. MSK symptoms were significantly correlated with older age at diagnosis, the presence of non-scarring alopecia, neuropsychiatric manifestations, and elevated SLE disease activity index scores at diagnosis. Over a median follow-up of 53.6 months (IQR 26.1–84.6), five patients developed septic arthritis or osteomyelitis, and avascular necrosis was identified in 16 (4.9%) patients.ConclusionsNearly half of c-SLE patients demonstrated MSK manifestations, chiefly characterized by symmetrical involvement of both large and small joints without evidence of erosive arthritis or Jaccoud’s arthropathy. Avascular necrosis is a critical concern and warrants close monitoring.

Correlation of anti-C1q antibodies with active systemic lupus erythematosus and lupus nephritis in children

To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus (SLE) and lupus nephritis (LN) in children, as well as their diagnostic value for active SLE and LN. A retrospective selection of 90 hospitalized children with SLE at the Children's Medical Center of Second Xiangya Hospital, Central South University from January 2016 to March 2019 as the SLE group, all of whom were tested for anti-C1q antibodies. A control group was formed by collecting 70 hospitalized children with other autoimmune diseases (OAD) during the same period. The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed, and the diagnostic value of anti-C1q in SLE and LN was evaluated. The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group (P<0.05). The SLE disease activity index score was positively correlated with anti-C1q antibodies (rs=0.371, P<0.001) and positively correlated with anti-double-stranded DNA antibodies (rs=0.370, P<0.001). The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90% and 53.90%, respectively, with an area under the curve of 0.720 (P<0.05) and a critical value of 5.45 U/mL. The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50% and 85.00%, respectively, with an area under the curve of 0.675 (P<0.05) and a critical value of 22.05 U/mL. Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.

Dynamic analysis of the relationship between systemic lupus erythematosus disease activity and psychosocial support.

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease that significantly affects both the physical and mental health of patients. Psychosocial support systems play a crucial role in managing chronic diseases, yet their specific impact on the disease activity of SLE patients remains unclear. This study aims to explore the dynamic relationship between disease activity in SLE patients and various types of psychosocial support systems. We conducted a retrospective longitudinal observational study, including 150 SLE patients who received treatment at our hospital from January 2022 to January 2023. Emotional support, tangible support, social interaction support, and informational support were assessed using the revised Social Support Rating Scale. Disease activity was quantified using the European Consensus Lupus Activity Measurement. The relationship between psychosocial support and disease activity was analyzed using Spearman's rank correlation coefficient and multiple linear regression models, with Bootstrap resampling employed to test the robustness of the results. We found a significant negative correlation between psychosocial support and SLE disease activity, with emotional support, social interaction support, and informational support showing stronger negative correlations. Multiple regression analysis revealed that the inhibitory effects of emotional support, social interaction support, and informational support on disease activity increased over time. Although the impact of tangible support was not statistically significant, it gradually became more apparent over time. Our findings indicate a significant negative correlation between psychosocial support and SLE disease activity, particularly with emotional support, social interaction support, and informational support. Over time, the impact of tangible support also becomes evident. These findings provide important references for the comprehensive treatment and management of SLE patients. However, due to the observational nature of the study, the causality of this relationship requires further exploration.

Pregnancy outcome predictors in systemic lupus erythematosus: a systematic review and meta-analysis

To enhance patient-tailored preconception risk assessment for women with systemic lupus erythematosus (SLE), knowledge on risk factors associated with adverse pregnancy outcomes is required. Therefore, we did a systematic review and meta-analysis to identify and provide unambiguous effect sizes of preconception predictors of pregnancy outcomes in women with SLE. In this systematic review and meta-analysis, we searched PubMed and Embase for studies reporting preconception predictors of pregnancy outcomes in women with SLE, from database inception to Aug 22, 2023. Studies were included if they presented original, quantitative data on pregnant women with SLE and reported on preconception risk factors on at least one of the outcomes as defined in the protocol. Studies were excluded if they had a sample size of less than 20 patients, were restricted to multiple pregnancies, had unclear timing of prognostication, or exclusively reported a composite outcome. Literature screening, data extraction, and risk-of-bias assessment (quality in prognostic studies tool) were done by two reviewers independently, in a blinded, standardised manner. The reported outcomes included livebirth, pre-eclampsia, small for gestational age, preterm birth, pregnancy loss before and after 20 weeks of gestation, and SLE flares. We computed pooled univariate odds ratios (ORs) and 95% CIs using a random effects model. We assessed heterogeneity using the I2 statistic and prediction intervals. This study is registered with PROSPERO, CRD42022344732. Of the 6705 unique articles identified, 72 (1·1%) were included in the meta-analysis, comprising 10 355 pregnancies in 8065 women with SLE. One potentially eligible study was retracted and therefore removed from our analysis. Previous lupus nephritis was associated with decreased livebirth probability (OR 0·62 [95% CI 0·47-0·81]; I2=0%), increased risk of preterm birth (2·00 [1·55-2·57]; I2=17%), and increased risk of pre-eclampsia (3·11 [2·35-4·12]; I2=0%). Chronic hypertension was associated with increased risk of disease flare (2·50 [1·74-3·58]; I2=0%), preterm birth (2·65 [1·87-3·77]; I2=0%), and pre-eclampsia (5·86 [3·41-10·06]; I2=33%). SLE disease activity at conception or preconception was associated with increased risk of preterm birth (2·91 [1·96-4·33]; I2=21%) and pre-eclampsia (2·32 [1·40-3·83]; I2=0%). Secondary antiphospholipid syndrome was associated with decreased livebirth probability (0·40 [0·27-0·58]; I2=0%), increased risk of pregnancy loss after 20 weeks of gestation (2·77 [1·44-5·31]; I2=0%), and increased risk of preterm birth (1·65 [1·29-2·11]; I2=0%). Across studies, risk-of-bias assessment suggested considerable bias in study attrition and confounding. We identified previous lupus nephritis, chronic hypertension, SLE disease activity before and at conception, and secondary antiphospholipid syndrome as predictors of adverse pregnancy outcomes in women with SLE. These findings contribute to an optimal patient-tailored risk assessment in preconception counselling. None.

Infection versus disease activity in systemic lupus erythematosus patients with fever

Backgroundto detect the role of procalcitonin, erythrocyte sedimentation rate to c-reactive protein (ESR/CRP) ratio, neutrophils-to-lymphocyte ratio (NLR), and platelets-to-lymphocyte ratio (PLR) in the diagnosis of infection in systemic lupus erythematosus (SLE) patients with fever, their diagnostic value to differentiate between infection and disease activity, and their correlation with disease activity.MethodsForty SLE patients and forty healthy control cases were included in the study. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K), and quality of life was assessed by Lupus QoL. A bacterial infection was detected by clinical symptoms and positive culture results. Laboratory tests were done for all patients and controls: complete blood count (CBC), ESR, CRP, and procalcitonin (PCT). NLR, PLR, and ESR/CRP ratios were calculated.ResultsThere was a statistically significant difference between infected SLE patients and non-infected SLE patients regarding PCT (p < 0.001), ESR (p = 0.002), CRP (p = 0.005), ESR/CRP ratio (0.002), and NLR (p = 0.023). PCT, ESR, CRP, and NLR were positively correlated with the presence of infection in SLE patients, while the ESR/CRP ratio was negatively correlated. There was no significant correlation with the SLEDAI-2 K score. Logistic regression analysis revealed that PCT was the best significant predictor of infection (OR 224.37, 95% CI 8.94–5631.35). PCT was a good predictor of infection, with a cut-off value of 0.90 ng/ml, which gave the best combination of sensitivity (84.62%) and specificity (85.71%).ConclusionPCT, ESR/CRP ratio, and NLR provide good diagnostic markers for the diagnosis of infection and can distinguish between infection and disease flare in SLE patients with fever.

Analysis of the association between the Slit2 biomarker and systemic lupus erythematosus

BackgroundTo assess the association between various systemic lupus erythematosus (SLE) disease manifestations, SLE disease activity index 2000 (SLEDAI-2K), systemic lupus international collaborating clinics/American College of Rheumatology Damage Index (SLICC/ACR- SDI) and serum levels of Slit2 in SLE patients.ResultsThe mean age of SLE patients was 31.12 ± 8.68 years while the age at onset was 26.05 ± 7.60 years. Female: male was 9 vs 1. The mean serum levels of Slit2 in SLE patients were significantly higher than the controls (0.55 ± 0.25 vs 0.42 ± 0.15) (P = 0.013). There was no significant difference in Slit2 levels between patients with active vs inactive SLE (P = 0.353) or between patients with and without lupus nephritis (P = 0.900). An insignificant difference in Slit2 levels was found among SLE patients using SDI (P = 0.982). No significant correlations were observed between the serum Slit2 and SLE patients’ demographics, laboratory data, SLEDAI-2K, and SDI except for a positive correlation with platelets and a negative correlation with serum albumin. ROC curve analysis showed that at a cutoff value of 0.44, the area under the curve was 0.677 (95% CI 0.538–0.816, P = 0.013) with a sensitivity of 74%, specificity of 56%, and accuracy of 68%.ConclusionWhile we observed elevated serum Slit2 levels in SLE patients, there was no significant correlation observed between serum Slit2 levels and SLE clinical manifestations, disease activity, or damage index.Trial registrationNCT05105217. Registered 3 November 2021

Rituximab Therapy for Adult Refractory Systemic Lupus Erythematosus with Neurological and/or Psychiatric Presentations: A PRISMACompliant Meta-Analysis

Rituximab (RTX) is used off-label for refractory cases of systemic lupus erythematosus (SLE) with extrarenal activity, including neurological and/or psychiatric (N/P) presentations. However, evidence from randomized controlled trials is limited. This study aimed to conduct a pooled analysis of the effectiveness and safety of RTX therapy for adult refractory SLE with N/P manifestations. Electronic searches in PubMed, Epistemonikos, and ICTRP databases and statistical analysis were conducted in May 2023. Electronic searches identified 20 studies (25 reports). A total of 59 patients (53 females; 90%) were included, with a mean age of 33.5±10.6 years and a median disease duration of 3.5 years (range, 0.08 to 25.0) who were followed up post-RTX therapy for a median time of 12 months (range, 3.0 to 46.2). The rate of clinical response (partial or major) was 90% (95% CI, 83 to 96) (n = 57 patients). A third of responders relapsed after a median time of 9.5 months (range, 3.0 to 33.0). Pooled pre-RTX/post-RTX scores for Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (n = 13) were 19±15/7±5 and for neurological British Isles Lupus Assessment Group (BILAG) (n = 29) were A/D (13), A/C (5), B/D (7), B/C (2), and A/A (2). Patients without mood disorder had a higher chance of clinical response {relative risk (RR) 1.4 (1.03 to 1.48)}. Patients who benefited the most from RTX therapy were those with psychosis (a higher chance of major clinical response; RR 1.9 (1.02 to 2.34)), without acute confusional state (a lower chance of relapse; RR 0.08 (0.006 to 0.791)), and with disease duration <3 years (a lower chance of relapse; RR 0.18 (0.014 to 0.992)). Infection rate during treatment was 33% (7/21). RTX therapy had good effectiveness. The pooled evidence for safety outcomes was limited and of low certainty.

Tofacitinib versus thalidomide for mucocutaneous lesions of systemic lupus erythematosus: A real-world CSTAR cohort study XXVII.

Thalidomide is an effective medication for refractory mucocutaneous lesions of systemic lupus erythematosus (SLE) and can treat arthritis in some autoimmune diseases, but it has some adverse reactions. Recently, the effectiveness of tofacitinib in treating mucocutaneous lesions of SLE has been reported. We aimed to compare the efficacy and safety of tofacitinib with thalidomide in treating mucocutaneous and musculoskeletal lesions in patients with SLE. This study was a real-world cohort study based on the Chinese SLE Treatment and Research group (CSTAR) registry. SLE patients who manifested mucocutaneous and/or musculoskeletal symptoms and were prescribed tofacitinib or thalidomide were included. We retrospectively conducted comparisons between the tofacitinib and thalidomide groups regarding clinical improvements, SLE disease activity, serological indicators, glucocorticoid doses, and adverse events at the 1, 3, and 6-months time points. At 3 and 6months, the tofacitinib group exhibited a higher proportion of patients with improvement in mucocutaneous and musculoskeletal issues. Additionally, a greater percentage of patients in the tofacitinib group achieved remission or a low disease activity state (LLDAS) at these time points. No significant serological improvements were observed in either the tofacitinib or thalidomide groups. Fewer adverse events were observed in the tofacitinib group than in the thalidomide group. Tofacitinib might be superior to thalidomide in the improvement of mucocutaneous and musculoskeletal lesions in SLE, and had a good safety profile.

PM2.5 constituents associated with mortality and kidney failure in childhood-onset lupus nephritis: A 19-year cohort study

BackgroundChildhood-onset lupus nephritis (cLN) is a severe form of systemic lupus erythematosus (SLE) with high morbidity and mortality. The impact of long-term exposure to fine particulate matter (PM2.5) on adverse outcomes in cLN remains unclear. MethodsWe combined a 19-years cLN cohort from seven provinces in China with high-resolution PM2.5 dataset from 2001 to 2020, investigating the association between long-term exposure to PM2.5 and its constituents (sulfate, nitrate, organic matter, black carbon, ammonium) with the risk of death and kidney failure, analyzed with multiple variables Cox models. We also evaluated the association between 3-year average PM2.5 exposure before study entry and baseline SLE disease activity index (SLEDAI) scores using linear regression models. ResultsEach 10 μg/m3 increase in annual average PM2.5 exposure was associated with an increased risk of death and kidney failure (HR = 1.58, 95 % CI: 1.24–2.02). Black carbon showed the strongest association (HR = 2.14, 95 % CI: 1.47–3.12). Higher 3-year average exposures to PM2.5 and its constituents were significantly associated with higher baseline SLEDAI scores. ConclusionsThese findings highlight the significant role of environmental pollutants in cLN progression and emphasize the need for strategies to mitigate exposure to harmful PM2.5 constituents, particularly in vulnerable pediatric populations.

Anifrolumab for systemic lupus erythematosus with multi-refractory skin disease: A case series of 18 patients.

Skin involvement is common in systemic lupus erythematosus (SLE), but may be resistant to conventional treatment. We sought to evaluate the efficacy of anifrolumab (ANI) in refractory cutaneous manifestations of SLE. Case series of patients with refractory cutaneous SLE from three Rheumatology Departments in Greece. Outcome measures were improvement in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), physician global assessment (PGA) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Clinically relevant improvement in skin was defined as decrease ≥50% (CLASI50) from baseline values. Eighteen patients received ANI; all had active skin involvement at baseline. Mean (SD) SLEDAI and PGA at ANI initiation were 7.4 (2.7) and 1.4 (0.5), respectively, with a mean prednisone dose 4.9 (4.5) mg/day. Mean CLASI (Activity/Damage) at baseline was 13.9 (9.7)/2.9 (4.6). Patients were refractory to a mean 6.3 (1.5) immunomodulatory agents (including hydroxychloroquine and glucocorticoids) before the initiation of ANI. After a mean 8.5 (4.6) months, 89% (n = 16/18) of patients demonstrated significant improvement in general lupus and cutaneous disease activity, and glucocorticoid tapering. Mean SLEDAI and mean CLASI at last visit were 3.4 (1.9) and 2.1 (2.4)/1.4 (2.2), respectively, and mean daily prednisone dose decreased to 2.4 (2.2). Of note, in this group of highly refractory patients CLASI50 was achieved in 16/18 (89%) patients. One patient discontinued ANI after 4 infusions due to a varicella-zoster virus infection and one patient, who initially responded to treatment with ANI, experienced a skin flare due to temporary discontinuation due to Covid 19 infection. DORIS remission and LLDAS were attained in two (11.1%) and eleven (61.1%) patients, respectively. Anifrolumab is highly effective in various skin manifestations of SLE, even after prior failure to multiple treatments.

Treatment selection in the clinical practice of systemic lupus erythematosus: results from the Kyushu Collagen Disease Network for Systemic Lupus Erythematosus (KCDN-SLE) registry.

This study aimed to describe the treatment selection for systemic lupus erythematosus (SLE) using data from the Kyushu Collagen Disease Network for SLE (KCDN-SLE) registry, a multicenter prospective registry in Japan. This study used data from patients registered between August 2022 and November 2023. Clinical characteristics, purpose of agent initiation, other candidate agents, and short-term efficacy and safety were evaluated. We analyzed 69 previously treated patients with SLE (mean age 43.7 years; 62 females, 7 males). Hydroxychloroquine, biological agents, and immunosuppressive agents were initiated during the maintenance phase in 12, 41, and 16 patients, respectively. In patients with active organ involvement, hydroxychloroquine and biological agents were widely used for initiation. In those who already achieved treatment goals, biological agents alone were predominantly selected. The SLE Disease Activity Index 2000 score and prednisolone dose declined significantly over a 6-month follow-up period. Among 48 patients with active disease, 22 achieved a lupus low disease activity state, but this had no evident association with the initiation of a biological agent. In total, 14 adverse events, predominantly infections, were observed. Biological agents were used preferentially, and the therapeutic agents were appropriately effective and mostly achieved the purpose of agent initiation.