Systemic Lupus Erythematosus Cohort Research Articles

Comparison of cell type and disease subset chromatin modifications in SLE.

Systemic lupus erythematosus (SLE) is an autoimmune disease with protean manifestations. There is little understanding of why some organs are specifically impacted in patients and the mechanisms of disease persistence remain unclear. While much work has been done characterizing the DNA methylation status in SLE, there is less information on histone modifications, a more dynamic epigenetic feature. This study identifies two histone marks of activation and the binding of p300 genome-wide in three cell types and three clinical subsets to better understand cell-specific effects and differences across clinical subsets. We examined 20 patients with SLE and 8 controls and found that individual chromatin marks varied considerably across T cells, B cells, and monocytes. When pathways were examined, there was far more concordance with conservation of TNF, IL-2/STAT5, and KRAS pathways across multiple cell types and ChIP data sets. Patients with cutaneous lupus and lupus nephritis generally had less dramatically altered chromatin than the general SLE group. Signals also demonstrated significant overlap with GWAS signals in a manner that did not implicate one cell type more than the others. The pathways identified by altered histone modifications and p300 binding are pathways known to be important from RNA expression studies and recognized pathogenic mechanisms of disease. NFκB and classical inflammatory pathways were strongly associated with increased peak heights across all cell types but were the highest-ranking pathway for all three antibodies in monocytes according to fgsea analysis. IL-6 Jak/STAT3 signaling was the most significant pathway association in T cells marked by H3K27ac change. Therefore, each cell type experiences the disease process distinctly although in all cases there was a strong theme of classical inflammatory pathways. Importantly, this NFκB pathway, so strongly implicated in the patients with generalized SLE, was much less impacted in monocytes when cutaneous lupus was compared to the general SLE cohort and also less impacted in lupus nephritis compared to general SLE. These studies define important cell type differences and emphasize the breadth of the inflammatory effects in SLE.

Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE.

Severe acute respiratory syndrome coronavirus 2 mRNA vaccination has reduced effectiveness in certain immunocompromised individuals. However, the cellular mechanisms underlying these defects, as well as the contribution of disease-induced cellular abnormalities, remain largely unexplored. In this study, we conducted a comprehensive serological and cellular analysis of patients with autoimmune systemic lupus erythematosus (SLE) who received the Wuhan-Hu-1 monovalent mRNA coronavirus disease 2019 vaccine. Our findings revealed that patients with SLE exhibited reduced avidity of anti-receptor-binding domain antibodies, leading to decreased neutralization potency and breadth. We also observed a sustained anti-spike response in IgD-CD27- 'double-negative (DN)' DN2/DN3 B cell populations persisting during memory responses and with greater representation in the SLE cohort. Additionally, patients with SLE displayed compromised anti-spike T cell immunity. Notably, low vaccine efficacy strongly correlated with higher values of a newly developed extrafollicular B and T cell score, supporting the importance of distinct B cell endotypes. Finally, we found that anti-BAFF blockade through belimumab treatment was associated with poor vaccine immunogenicity due to inhibition of naive B cell priming and an unexpected impact on circulating T follicular helper cells.

Fibromyalgia, mood disorders and chronic damage are the main determinants of worse quality of life in systemic lupus erythematosus patients: Results from a cross-sectional analysis.

As suggested by the EULAR recommendations, a comprehensive management of Systemic Lupus Erythematosus (SLE) should include the evaluation of disease activity, chronic damage, and quality of life (QoL). QoL is significantly impaired in SLE patients, even in those achieving a state of remission, suggesting the possible contribution of other factors. Thus, in the present study we aimed at analyzing QoL in a large SLE cohort by using LupusQoL, and at identifying the main determinant of poorer QoL. We conducted a cross-sectional study by including consecutive SLE patients diagnosed according to the 2019 ACR/EULAR criteria. Clinical, laboratory and therapeutical data were collected. Disease activity was assessed by SLEDAI-2k, while chronic damage by the SLICC Damage Index (SDI). The diagnosis of fibromyalgia was made in accordance with the ACR criteria (2016). At the time of the enrollment, all patients completed the following questionnaires: LupusQoL to assess quality of life and hospital anxiety and depression scale (HADS) for anxiety and depression. Our analysis included 237 SLE patients [92.4% female, median age 46years (IQR 19.5), median disease duration 156.8months (IQR 180.6)]. At the time of enrollment, we found a mean SLEDAI-2k of 1.7 (DS 2.4); 104 patients (43.9%) had chronic damage, with a mean SDI value of 0.8 (DS 1.3). Patients diagnosed with fibromyalgia were 69 (29.1%); moreover, HADS questionnaire identified a condition of anxiety and depression in 112 (47.3%) and 94 (39.7%) patients, respectively. The most compromised domain in the LupusQoL resulted "fatigue", followed by "burden to others". Patients with SDI ≥ 1 showed lower quality of life than patients without chronic damage, as demonstrated by significantly lower values in all items of the LupusQoL (p < .01). Furthermore, significantly lower values in all the LupusQoL domains were observed in patients with fibromyalgia, anxiety and depression, in comparison to those patients without these manifestations (p < .0001). No association was demonstrated between QoL and disease activity. Finally, the linear regression analysis confirmed mood disorders, in particular depression, and fibromyalgia as the main determinants of worse quality of life in our cohort. The present study demonstrated the influence of different factors in the quality of life of SLE patients. In particular, the presence of mood disorders, fibromyalgia and chronic damage resulted the main determinants of poorer QoL. This evidence reinforces the need for a comprehensive patient care.

Health seeking behaviour and diagnostic delays in SLE: A multi-ethnic Malaysian cohort study.

Heterogeneity of the clinical manifestations of systemic lupus erythematosus (SLE) may lead to diagnostic delays. This study is aimed at determining the health-seeking behaviour patterns and factors associated with diagnostic delays in a multi-ethnic SLE cohort in Malaysia. This was a cross-sectional study involving SLE patients who visited our institute between January 2020 and June 2021. A review of the medical records and face-to-face interviews were conducted to obtain sociodemographics, SLE disease characteristics and the intervals from the first symptoms to the diagnosis. Health-seeking behaviours were assessed by asking about the patients' first action during the initial symptoms and were divided into: (i) seeking professional health personnel; (ii) self-treatment; and (iii) the use of the internet as a primary source of information. Diagnostic delays were defined as the interval between initial symptoms and SLE diagnosis of more than 6months. Low-level disease activity state (LLDAS) at 12months was assessed from the medical records. Univariate and multivariate logistic regression analysis was subsequently conducted to determine factors associated with diagnostic delays. Among the 154 patients included in the study, 24% (n = 37) had delayed diagnosis. The delay was significantly higher among the Indian versus Malay versus Chinese (42.9% vs 28% vs 10.8%, p = 0.037). Patients with rash tend to have delayed diagnosis (37.8% vs 22.2%, p = 0.08) while fewer patients with frothy urine had delayed diagnosis (8.1% vs 21.4%, p = 0.09). No significant association was found between health-seeking behaviours and diagnostic delays. The rate of LLDAS at 12months was significantly lower among patients with delayed diagnosis (43.2% vs 70.0%, p = 0.006). Chinese ethnicity remained the only significant factor associated with lesser diagnostic delays in the multivariate analysis, with OR 0.30 (CI 0.09-0.93), p = 0.037. There were ethnic disparities in the early diagnosis of SLE in Malaysia, with Indian patients having a longer interval between the first symptom and diagnosis while the Chinese were associated with lower diagnostic delays. Early diagnosis predicted early attainment of LLDAS, suggesting that prompt recognition of the initial SLE symptoms is important.

Are Tattoos Safe in Patients With Systemic Lupus Erythematosus? Results From a Single-Center Study

Introduction: Systemic Lupus Erythematosus is a pleiotropic autoimmune disease with common skin involvement. To date, only one study has investigated tattoos safety in SLE patients. Objective: We performed a single-center study to evaluate the development of local and systemic complications after tattooing in a cohort of systemic lupus erythematosus (SLE) patients. Furthermore, we tried to identify SLE patients who had expressed the will to get a tattoo and why they decided not to. Methods: Consecutive SLE patients were asked to complete a questionnaire about tattoos, including their number, features, and side effects. Open questions were proposed to non-tattooed patients to describe why they did not have tattoos. Results: One hundred ninety-two SLE patients were enrolled [M/F 21/171; median age 41 years (IQR 18)]. Almost 50% of them had at least one tattoo. Seven patients (7.4%) referred adverse reactions to tattoos; interestingly, only one patient experienced a systemic reaction, specifically the occurrence of self-limiting lymphadenopathy. The main reason for not getting a tattoo was the diagnosis of SLE. Conclusions: Our results suggest the safety of tattoos in SLE patients, as demonstrated by a low prevalence of mild adverse events.

Extrafollicular CD19lowCXCR5−CD11c− double negative 3 (DN3) B cells are significantly associated with disease activity in females with systemic lupus erythematosus

ObjectiveB cells play a major role in the development and maintenance of systemic lupus erythematosus (SLE). Double negative (DN) B cells defined by the lack of surface expression of IgD and CD27 have attracted recent interest for their sensitivity to Toll-like receptor 7 (TLR7) ligands and their potential role in the production of autoantibodies. Here we aimed at investigating the possible association of DN B cells and their subsets with SLE disease activity specifically in female patients, in which TLR7 gene has been reported to escape X chromosome inactivation. MethodsPeripheral blood mononuclear cells were purified from woman participating to the clinically well-characterized Swiss SLE Cohort Study (SSCS). PBMC from age-matched healthy females were used as controls. PBMC were stained for cell surface markers, intracellular Tbet and analyzed by multicolor cytofluorimetry. Single nucleotide TLR7 polymorphisms were assessed by polymerase chain reaction. ResultsThe median SLE disease activity index of the 86 females was 2, IQR [0–6], all but 8 were under chronic SLE treatment. B cells co-expressing CD11c and Tbet were increased, the mean fluorescence intensity (MFI) of CD19 was considerably reduced and we observed a large increase in CD11c + CXCR5-and CD11c-CXCR5-concomitantly with a reduction of CD11c-CXCR5+ B cells in SLE compared to 40 healthy donors (HD). When focusing on the DN B cell subset, we found a reduction of DN1 (CD11c-CXCR5+) and an increase of DN2 (CD11c + CXCR5-) and most impressively of DN3 (CD11c-CXCR5-) cells. The DN subset, particularly DN3, showed the lowest level of CD19 expression. Both DN1 and DN3 percentages as well as the CD19 MFI of DN cells were associated with SLE disease activity. The use of glucocorticoids, immunosuppressants, and antimalarials impacted differentially on the frequencies of DN B cell subsets. CD19 MFI in B cells and the percentage of DN3 were the strongest biomarkers of disease activity. The TLR7 snp3858384 G allele was associated with increased percentages of B cells and CD19+CD11c-CXCR5+ and decreased CD19+CD11c-CXCR5-. ConclusionsDN3 B cells are strongly associated with SLE clinical activity pointing to their potential involvement in disease pathogenesis, and CD19 expression level performs accurately as disease activity biomarker.

Incidence and risk of arterial and venous thrombotic events in Systemic Lupus Erythematosus patients: a population-based study.

Current data on arterial and venous thrombotic events (ATE & VTE) and cardiovascular (CV) risk management in European systemic lupus erythematosus (SLE) population are limited. This study aimed to investigate the incidence and risk of thrombotic events and all-cause death in an Italian SLE cohort over the past decade, along with its pharmacotherapy. Incident SLE cases between 2010 and 2019 were identified using administrative health databases of the Lombardy Region. The association between SLE and outcomes, compared with age- and sex-matched controls, was reported as incidence rate per 1000 person-years and as adjusted hazard ratios with 95% confidence intervals. Overall, 2133 SLE patients and 21 283 no-SLE individuals were included. A higher incidence rate of ATE (4.22 vs 2.26 1000 PY), VTE (1.85 vs 0.67 1000 PY,) and all-cause death (15.18 vs 6.22 1000 PY) was reported in SLE patients than in those without (p< 0.0001) as well as an increased risk of ATE (HR, 1.65; 95% CI, 1.20-2.26), VTE (HR, 2.25; 95% CI, 1.35-3.74), and all-cause death (HR, 1.81; 95% CI, 1.52-2.15). After SLE diagnoses, hydroxychloroquine and glucocorticoids were prescribed for at least 60% of patients. Additionally, a higher exposure to cardiovascular medications was also seen in SLE patients. Our findings confirmed higher risks of ATE, VTE and all-cause death in SLE patients. While increased CV medications use after SLE diagnoses suggests heightened awareness to CV risk profile, more attention is required to balance SLE disease activity with minimizing exposure to drugs associated with exacerbating CV risk.

Prognostic impact of right atrial strain in systemic lupus erythematosus with pulmonary arterial hypertension.

The aim of this study was to assess right atrial (RA) function, including RA phase strain, via speckle-tracking echocardiography (STE) in a cohort of systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH) and in particular to explore the relationship between RA phase strain and the occurrence of cardiovascular events. STE analyses of RA function were evaluated in patients with SLE-PAH and in 33 healthy control subjects. Clinical associations, serum biomarkers, echocardiographic data, survival times, and adverse cardiovascular events were evaluated. A total of 66 patients with SLE-PAH were enrolled; they were divided into two groups based on the occurrence of adverse clinical events. RA phase strain was significantly reduced in patients with events than in patients without events. The endpoint was defined as the combined outcome of all-cause mortality, right heart failure, and rehospitalization due to disease progression. During a mean follow-up of 17.2±9.9 months, 23 patients (35%) reached the endpoint. Compared with patients with RA reservoir strain (RASr) ≥33.45%, patients with RASr<33.45% had more adverse long-term outcomes (log rank p<.0001). RASr was independently associated with adverse clinical outcomes according to multivariate analysis (p=.010). Our data suggest that RA function has prognostic value for SLE-PAH patients, and strain analysis revealed that the worse the RA function is, the worse the prognosis.

Panel miRNAs are potential diagnostic markers for chronic kidney diseases: a systematic review and meta-analysis

BackgroundAccurate detection of kidney damage is key to preventing renal failure, and identifying biomarkers is essential for this purpose. We aimed to assess the accuracy of miRNAs as diagnostic tools for chronic kidney disease (CKD).MethodsWe thoroughly searched five databases (MEDLINE, Web of Science, Embase, Scopus, and CENTRAL) and performed a meta-analysis using R software. We assessed the overall diagnostic potential using the pooled area under the curve (pAUC), sensitivity (SEN), and specificity (SPE) values and the risk of bias by using the QUADAS-2 tool. The study protocol was registered on PROSPERO (CRD42021282785).ResultsWe analyzed data from 8351 CKD patients, 2989 healthy individuals, and 4331 people with chronic diseases. Among the single miRNAs, the pooled SEN was 0.82, and the SPE was 0.81 for diabetic nephropathy (DN) vs. diabetes mellitus (DM). The SEN and SPE were 0.91 and 0.89 for DN and healthy controls, respectively. miR-192 was the most frequently reported miRNA in DN patients, with a pAUC of 0.91 and SEN and SPE of 0.89 and 0.89, respectively, compared to those in healthy controls. The panel of miRNAs outperformed the single miRNAs (pAUC of 0.86 vs. 0.79, p < 0.05). The SEN and SPE of the panel miRNAs were 0.89 and 0.73, respectively, for DN vs. DM. In the lupus nephritis (LN) vs. systemic lupus erythematosus (SLE) cohorts, the SEN and SPE were 0.84 and 0.81, respectively. Urinary miRNAs tended to be more effective than blood miRNAs (p = 0.06).ConclusionMiRNAs show promise as effective diagnostic markers for CKD. The detection of miRNAs in urine and the use of a panel of miRNAs allows more accurate diagnosis.

Retrospective cohort study identifying pulmonary complications in a cohort of patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multi organ involvement. One of the most common manifestations is pulmonary disease with a reported prevalence between 5%-90%. Given this wide range of prevalence, there is a need to more closely define types of pulmonary disease in SLE and associated risk factors. We sought to characterize the presentation of pulmonary manifestations in an established SLE cohort using electronic health record data. All patients were >18 years of age and had confirmed SLE by a rheumatologist using SLICC or 2019 ACR/EULAR classification criteria. 220 patients with imaging were included in this study; average age was 42.5 years, 86.7% identified as female, 60.5% identified as white, 37.3% as Black, and 1.82% as Asian. Generalized estimating equations were utilized to analyze the data, accounting for its repeated measured nature. We found an association between smoking (present/prior smoker) and radiologist reported disease on computerized tomography (CT) scan, as well as an association between smoking (present/prior smoker), older age, and male sex with having pulmonary disease identified on chest X-ray. The most common findings on CT and X-ray were increased lung density (24%, 12%) and atelectasis (18%, 10%). The most common disease found on CT was pleural effusion (24%) and mediastinal/axillary lymphadenopathy (16%). While our study is limited by the retrospective nature, our results show that certain factors, namely smoking, older age, or male sex should prompt clinicians to have a higher suspicion for lung disease in SLE patients.

Damage in a large systemic lupus erythematosus cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER) with emphasis on the cardiovascular system: a longitudinal analysis

ObjectiveTo assess organ damage, with emphasis on the cardiovascular system, over the different stages of the disease in a large SLE cohort.MethodsMulticentre, longitudinal study of a cohort of 4219 patients...

Hydroxychloroquine and Cardiovascular Events in Patients With Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) predisposes individuals to early cardiovascular (CV) events. While hydroxychloroquine is thought to mitigate CV risk factors, its protective role against CV events, particularly arterial ones, remains to be confirmed. To evaluate the association between hydroxychloroquine and the risk of myocardial infarction (MI), stroke, and other thromboembolic events (OTEs) in patients with SLE. This cohort study using a nested case-control design was conducted within the National French Healthcare Database (SNDS), which represents 99% of the French population, from 2010 to 2020. Participants were the cohort of all patients with SLE recorded in the SNDS. Patients with SLE experiencing CV events during the study period were the case group; those without CV events were controls. The analysis period was from February 2022 to September 2023. Hydroxychloroquine use within 365 days prior to the index date, defined as current (within 90 days), remote (91-365 days), or no exposure within the previous 365 days. Outcomes of interest were MI, stroke, and OTE, analyzed individually and as a composite outcome (primary analysis). Controls were matched to patients with CV events by age, sex, time since SLE onset and entry into the SNDS database, index date, prior antithrombotic and CV medication, chronic kidney disease, and hospitalization. Multivariable conditional logistic regression was performed using hydroxychloroquine exposure as the main independent variable. The SLE cohort included 52 883 patients (mean [SD] age, 44.23 [16.09] years; 45 255 [86.6%] female; mean [SD] follow-up, 9.01 [2.51] years), including 1981 patients with eligible CV events and 16 892 matched control patients. There were 669 MI events, 916 stroke events, and 696 OTEs in the individual outcome studies. For current exposure to hydroxychloroquine, the adjusted odds were lower for composite CV events (odds ratio [OR], 0.63; 95% CI, 0.57-0.69) as well as for MI (OR, 0.72; 95% CI, 0.60-0.85), stroke (OR, 0.69; 95% CI, 0.60-0.81), and OTEs (OR, 0.58; 95% CI, 0.49-0.69) individually compared with no hydroxychloroquine exposure within 365 days. In this nationwide cohort study of patients with SLE, a protective association was found between the current use of hydroxychloroquine and the occurrence of CV events, but not between remote use of hydroxychloroquine and CV outcomes, highlighting the value of continuous hydroxychloroquine treatment in patients with SLE.

Effects of systemic lupus erythematosus on the brain: a systematic review of structural MRI findings and their relationships with cognitive dysfunction

BackgroundCognitive dysfunction (CD) is highly prevalent in systemic lupus erythematosus (SLE), yet the underlying mechanisms are poorly understood. Neuroimaging utilising advanced MRI metrics may yield mechanistic insights. We conducted a...

Sensitivity of classification criteria from time of diagnosis in an incident systemic lupus erythematosus cohort: a population-based study from Norway

ObjectivesTo compare the sensitivity of 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) classification criteria against 1997 ACR criteria for systemic lupus erythematosus (SLE), for incident SLE...

Hydroxychloroquine Improves Low Complement Levels.

Having a low complement level is associated with clinical systemic lupus erythematosus (SLE) disease activity and future organ damage. We studied the association of hydroxychloroquine (HCQ) whole blood levels with changes in complement level. We performed two analyses on data prospectively collected from an SLE cohort. In the first (a "new starts on HCQ" analysis), we compared changes in complement level between those starting HCQ and those not starting it.The second analysis evaluated the association between HCQ whole blood levels and low complement level in all cohort visits using conditional logistic regression. In the "new starts on HCQ" analysis, a higher percentage of patients starting HCQ (as reflected in HCQ blood levels >50) experienced a normalization of C4 level compared to those not starting HCQ (23 of 57 [40%] vs. 9 of 56 [13%]; P = 0.011), as well as a significantly greater increase in both C3 and C4 level (P = 0.048 and P = 0.017, respectively). In the "all cohort visits" analysis, there was a statistically significant higher probability of having normal C4 levels in visits with higher HCQ whole blood levels (odds ratio 1.8-2.6 depending on the levels). This relationship was most pronounced for whole blood HCQ levels of 200 ng/mL or more. We observed significant improvement in complement levels when HCQ was started and among those with higher whole blood levels of HCQ, particularly with respect to C4. Modulating the pathogenic mechanisms that lead to complement consumption may be one mode by which HCQ prevents poor outcomes in SLE.

Coronary Artery Calcification Progression in Patients With Systemic Lupus Erythematosus.

To evaluate the progression of coronary artery calcification (CAC) and associated risk factors in a systemic lupus erythematosus (SLE) cohort. We reassessed the presence of CAC in patients with SLE who were screened 9 years before, using multidetector computed tomography. Clinical variables (cumulated disease activity and damage accrual), antiphospholipid syndrome and SLE serology, and cardiovascular (CV) risk factors (hypertension, BMI [kg/m2], modified Framingham risk score, lipid profile, menopausal status) were assessed longitudinally. We included 104 patients from the parent study. Most of them were women (94.2%), with a mean age of 41.0 (SD 8.3) years and mean disease duration of 14.8 (SD 2.9) years. We documented CAC in 17 patients (16.3%). Seven cases were from the parent study and 10 were incident cases. The cumulative incidence of CAC was 9% and the incidence density was 1 per 100 person-years. CAC occurred more frequently in the age groups 30-39 years and 40-44 years. All patients with previous CAC had worsening of their calcium indexes, and none developed clinical CV events. When comparing prevalent CAC cases (n = 17) vs patients without calcification (n = 87), both groups were similar in traditional CV risk factors, disease duration, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) area under the curve (AUC), and Systemic Lupus International Collaborating Clinics (SLICC) score, but were more likely to be postmenopausal and have higher apolipoprotein B (apoB) levels. Patients with previous CAC had higher apoB levels, SLEDAI-2K AUC scores, and anticardiolipin IgG antibodies than incident cases. CAC in patients with SLE progressed over time but was not associated with adverse CV events during the first 9 years of follow-up. ApoB levels and postmenopausal status might be associated with this progression.

Intercurrent infection as a risk factor for disease flares in patients with systemic lupus erythematosus

ObjectiveTo determine whether intercurrent infections are a risk factor for subsequent disease flares in systemic lupus erythematosus (SLE).MethodsDemographic and clinical characteristics of 203 patients with SLE participating in the Amsterdam...

Fungal Infections in Hospitalized Patients of Systemic Lupus Erythematosus: A United States Nationwide Cohort Analysis.

Introduction/objective Immunosuppressive therapy is the cornerstone of management in patients with systemic lupus erythematosus (SLE). Patients on immunosuppressive therapy are at increased risk of developing opportunistic fungal infections. We conducted this analysis to describe the epidemiology, including incidence, risk factors, and outcomes, of fungal infections in hospitalized patients with SLE in the United States. Method A retrospective cohort study was performed by analyzing the National Inpatient Sample (NIS) 2016-2020 for all patients with a discharge diagnosis of SLE and fungal infections, including histoplasmosis, pneumocystosis, cryptococcosis, aspergillosis, and blastomycosis, as a primary or secondary diagnosis via ICD-10 (International Classification of Diseases 10th Revision) codes. Frequencies, demographics, and trends were determined and compared between hospitalized patients with SLE and those without SLE. STATA version 17 was used for data analysis. A p-value of ≤0.05 was considered statistically significant. Results In hospitalized SLE patients, there were lower odds of developing fungal infections in females (odds ratio (OR): 0.63 (95% confidence interval (CI): 0.49-0.80)) and higher odds in Hispanic (OR: 1.52 (95% CI: 1.16-1.98) and Asian (OR: 1.78 (95% CI: 1.15-2.75) populations. Steroid use (OR: 1.96 (95% CI: 1.58-2.42)), concomitant HIV infection(OR: 22.39 (95% CI: 16.06-31.22)), and the presence of leukemias (OR: 3.56 (95% CI: 1.67-7.59)) and lymphomas (OR: 3.29 (95% CI: 1.78-6.09)) in hospitalized SLE patients were significant predictors of fungal infection (p < 0.01). There were differences in the incidence of fungal infections based on geographical areas in the US, with blastomycosis being more common in the Midwest. From 2016 to 2020, there was a decline in the incidence rate of hospitalization per 100,000 for non-SLE patientswith fungal infections (10.7 per 100,000 hospitalizations in 2016 versus 9.6 per 100,000 hospitalizations in 2020), whereas this rate remained steady for the SLE cohort (0.1 per 100,000 hospitalizations in 2016 versus 0.2 per 100,000 hospitalizations in 2020). Conclusions Hospitalized patients with SLE are at an increased risk of developing fungal infections, and this risk is increased further in patients who are males, are on steroid therapy, and have HIV or leukemia and lymphomas. Further studies can be done to explain the increased risk of fungal infections associated with these patient characteristics.

Unfavorable Outcomes Associated With Glucocorticoid Use in Current Standard-of-Care Management of Systemic Lupus Erythematosus in Canada.

Our objective was to describe the administration of glucocorticoids (GCs) and characterize its association with organ damage in a longitudinal systemic lupus erythematosus (SLE) cohort over a time period spanning the introduction of biologics in Canada. A retrospective observational study was conducted using data from a large SLE cohort in Canada, including adults without lupus nephritis or central nervous system lupus. Patients were observed from time of entry into the cohort to the last available clinic visit (up to December 31, 2020), with a minimum of 24 months of follow-up. Demographic and clinical characteristics, including average disease activity, treatment administration, and prevalence of organ damage, were examined. Organ damage was stratified by GC administration. A total of 1,255 patients were included. The mean follow-up duration was 10.5 (SD 8.6) years. One hundred eighty-two (15%) patients had organ damage at baseline. More than 80% of patients were prescribed GCs over the follow-up period, almost all patients had long-term GC treatment, and only 5% of patients took any biologics. Organ damage was more frequent in patients with a higher average GC dose and greater years of GC exposure. In this large cohort of patients with SLE, the majority of patients continue to rely on GC for SLE symptom management, with limited administration of biologics. GC administration was correlated with increased irreversible organ damage. Access to novel GC-sparing treatment options is critical to improve long-term outcomes for patients with SLE, especially given the continued reliance on GC despite the introduction of biologics.

Prevalence and target attainment of traditional cardiovascular risk factors in patients with systemic lupus erythematosus: a cross-sectional study including 3401 individuals from 24 countries

Systemic lupus erythematosus (SLE) is characterised by increased cardiovascular morbidity and mortality risk. We aimed to examine the prevalence of traditional cardiovascular risk factors and their control in an international survey of patients with systemic lupus erythematosus. In this multicentre, cross-sectional study, cardiovascular risk factor data from medical files of adult patients (aged ≥18) with SLE followed between Jan 1, 2015, and Jan 1, 2020, were collected from 24 countries, across five continents. We assessed the prevalence and target attainment of cardiovascular risk factors and examined potential differences by country income level and antiphospholipid syndrome coexistence. We used the Systemic Coronary Risk Evaluation algorithm for cardiovascular risk estimation, and the European Society of Cardiology guidelines for assessing cardiovascular risk factor target attainment. People with lived experience were not involved in the research or writing process. 3401 patients with SLE were included in the study. The median age was 43·0 years (IQR 33-54), 3047 (89·7%) of 3396 patients were women, 349 (10.3%) were men, and 1629 (48·1%) of 3390 were White. 556 (20·7%) of 2681 patients had concomitant antiphospholipid syndrome. We found a high cardiovascular risk factor prevalence (hypertension 1210 [35·6%] of 3398 patients, obesity 751 [23·7%] of 3169 patients, and hyperlipidaemia 650 [19·8%] of 3279 patients), and suboptimal control of modifiable cardiovascular risk factors (blood pressure [target of <130/80 mm Hg], BMI, and lipids) in the entire SLE group. Higher prevalence of cardiovascular risk factors but a better blood pressure (target of <130/80 mm Hg; 54·9% [1170 of 2132 patients] vs 46·8% [519 of 1109 patients]; p<0·0001), and lipid control (75·0% [895 of 1194 patients] vs 51·4% [386 of 751 patients], p<0·0001 for high-density lipoprotein [HDL]; 66·4% [769 of 1158 patients] vs 60·8% [453 of 745 patients], p=0·013 for non-HDL; 80·9% [1017 of 1257 patients] vs 61·4% [486 of 792 patients], p<0·0001 for triglycerides]) was observed in patients from high-income versus those from middle-income countries. Patients with SLE with antiphospholipid syndrome had a higher prevalence of modifiable cardiovascular risk factors, and significantly lower attainment of BMI and lipid targets (for low-density lipoprotein and non-HDL) than patients with SLE without antiphospholipid syndrome. High prevalence and inadequate cardiovascular risk factor control were observed in a large multicentre and multiethnic SLE cohort, especially among patients from middle-income compared with high-income countries and among those with coexistent antiphospholipid syndrome. Increased awareness of cardiovascular disease risk in SLE, especially in the above subgroups, is urgently warranted. None.