Mortality In Systemic Lupus Erythematosus Research Articles

Systemic Lupus Erythematosus-related Lung Disease.

Systemic Lupus Erythematosus (SLE) is a multifaceted, multisystem autoimmune disorder with diverse clinical expressions. While prevalence reports vary widely, pulmonary involvement accounts for significant morbidity and mortality in SLE. This comprehensive review explores the spectrum of pulmonary disease in SLE, including upper airway manifestations (e.g., laryngeal affection), lower airway conditions (e.g., bronchitis, bronchiolitis, bronchiectasis), parenchymal diseases (e.g., interstitial lung disease, acute lupus pneumonitis, diffuse alveolar hemorrhage), pleural diseases (e.g., serositis, shrinking lung syndrome), and vascular diseases (e.g., pulmonary arterial hypertension, pulmonary embolism, acute reversible hypoxemia syndrome). We discuss diagnostic modalities, treatment strategies, and prognosis for each pulmonary manifestation. With diagnostics remaining a challenge and with the absence of standardized treatment guidelines, we emphasize the need for evidence-based guidelines to optimize patient care and improve outcomes in this complex disease.

Role of F-18 FDG PET-CT in neuropsychiatric systemic lupus erythematosus

BackgroundNeuropsychiatric systemic lupus erythematosus (NPSLE) is a major contributor to morbidity and mortality in systemic lupus erythematosus (SLE) patients. To date no single clinical, laboratory or imaging test has proven accurate for NPSLE diagnosis which is a testament to the intricate and multifactorial pathophysiological mechanisms suspected to exist. Functional imaging with FDG PET-CT has shown promise in NPSLE diagnosis, detecting abnormalities prior to changes evident on anatomical imaging. Research indicates that NPSLE may be more aggressive in people of African descent with higher mortality rates, making rapid and correct diagnosis even more important in the African context. MethodsIn this narrative review, we provide a thorough appraisal of the current literature on the role of FDG PET-CT in NPSLE. Large, well-known databases were searched using appropriate search terms. Manual searches of references of retrieved literature were also included. FindingsA total of 73 article abstracts were assessed, yielding 26 papers that were directly relevant to the topic of FDG PET-CT in NPSLE. Results suggest that FDG PET-CT is a sensitive imaging test for NPSLE diagnosis and may play a role in assessing treatment response. It is complementary to routine anatomical imaging, particularly in diffuse manifestations of the disease. Newer quantitative analyses are commonly used for interpretation and can detect even subtle abnormalities, missed on visual inspection. Findings of group-wise analyses of FDG PET-CT scans in NPSLE patients are important in furthering our understanding of the complicated pathophysiological mechanisms involved. Limitations of FDG PET-CT include its lack of specificity, high cost and poor access. ConclusionFDG PET-CT is a sensitive test for NPSLE diagnosis but is hampered by lack of specificity. It is a valuable tool for clinicians managing SLE patients, particularly when anatomical imaging is negative. Its exact application will depend on the local context and clinical scenario.

Lupus nephritis – modern aspects of diagnosis and therapy. Part I

Lupus nephritis (LN) is considered to be one of the most frequent severe manifestations of systemic lupus erythematosus (SLE), its various colonic manifestations occur in at least 50% of SLE patients, both at the onset and at various stages of the disease, and develop LN is considered one of the most important predictors of mortality in SLE. The structure of nephritis is dominated by diffuse proliferative LN with clinical and morphological signs of progression and the rapid development of terminal renal failure. SLE is diagnosed based on the 2019 EULAR/ACR (European Alliance of Associations for Rheumatology/American College of Rheumatology) diagnostic classification criteria. To confirm the diagnosis, evaluate the prognosis, and choose the tactics of treating the dis-ease, all patients in the absence of contraindications require a kidney biopsy. In addition to LN, the spectrum of SLE-associated renal lesions includes vascular pathology represented by thrombotic microangiopathy, lupus vasculopathy or vasculitis, tubulointerstitial injury, and lupus podocytopathy.

Transcription Factors in the Pathogenesis of Lupus Nephritis and Their Targeted Therapy.

Systemic lupus erythematosus (SLE) is a prototype inflammatory autoimmune disease, characterized by breakdown of immunotolerance to self-antigens. Renal involvement, known as lupus nephritis (LN), is one of the leading causes of morbidity and a significant contributor to mortality in SLE. Despite current pathophysiological advances, further studies are needed to fully understand complex mechanisms underlying the development and progression of LN. Transcription factors (TFs) are proteins that regulate the expression of genes and play a crucial role in the development and progression of LN. The mechanisms of TF promoting or inhibiting gene expression are complex, and studies have just begun to reveal the pathological roles of TFs in LN. Understanding TFs in the pathogenesis of LN can provide valuable insights into this disease's mechanisms and potentially lead to the development of targeted therapies for its management. This review will focus on recent findings on TFs in the pathogenesis of LN and newly developed TF-targeted therapy in renal inflammation.

Choosing to End African American Health Disparities in SLE.

Systemic Lupus erythematosus (SLE) is 3 times more common and its' manifestations more severe in African American (AA) women compared to women of other races. It is not clear whether this is due to genetic differences or factors related to the physical or social environments, differences in health care or a combination of these factors. Health disparities in SLE between AAs and persons of other races have been reported since the 1960's and are correlated with measures of lower socioeconomic status. Risk factors for these disparities have been demonstrated but whether their mitigation improves outcomes for AA patients has not been tested except in self-efficacy. In 2002, Sacks conducted the first true U.S. population-based study of SLE with death certificate records and demonstrated a wide disparity between the number of AA women and white women dying from SLE. Five years ago, Yen showed that SLE mortality in the U.S. had improved, but that the AA mortality disparity persisted. Between 2014 and 2021 Lim and others demonstrated racism's deleterious effects in SLE. Racism may have been the unmeasured confounder, the proverbial "elephant in the room" - unnamed and unstudied. The etymology of "risk factor" has evolved from environmental risk factors to social determinants to now include structural injustice/structural racism. Racism in the U.S. has centuries long existence and is deeply ingrained and intertwined making its detection and resolution difficult. However, its being man-made means mankind can choose to change the situation. Health disparities in SLE should be addressed by viewing healthcare as a basic human right. We offer a conceptual framework and goals for both individual and national actions.

The Link Between Dysregulated Immunometabolism and Vascular Damage: Implications for the Development of Atherosclerosis in Systemic Lupus Erythematosus and Other Rheumatic Diseases.

A bimodal pattern of mortality in systemic lupus erythematosus (SLE) exists. Early-stage deaths are predominantly caused by infection, whereas later-stage deaths are mainly caused by atherosclerotic disease. Further, although SLE-related mortality has reduced considerably in recent years, cardiovascular (CV) events remain one of the leading causes of death in people with SLE. Accelerated atherosclerosis in SLE is attributed to both an increase in traditional CV risk factors and the inflammatory effects of SLE itself. Many of these changes occur within the microenvironment of the vascular-immune interface, the site of atherosclerotic plaque development. Here, an intimate interaction between endothelial cells, vascular smooth muscle cells, and immune cells dictates physiological vs pathological responses to a chronic type 1 interferon environment. Low-density neutrophils (LDNs) have also been implicated in eliciting vasculature-damaging effects at such lesion sites. These changes are thought to be governed by dysfunctional metabolism of immune cells in this niche due at least in part to the chronic induction of type 1 interferons. Understanding these novel pathophysiological mechanisms and metabolic pathways may unveil potential innovative pharmacological targets and therapeutic opportunities for atherosclerosis, as well as shed light on the development of premature atherosclerosis in patients with SLE who develop CV events.

Lupus nephritis and socioeconomic status: Findings from the Southern California lupus registry.

Lupus nephritis (LN) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Despite multiple studies addressing healthcare disparities, disparate outcomes in LN persist. We investigate herein the association between socioeconomic status (SES) and LN as well as the association between SES, SLE disease activity index (SLEDAI), and treatment response. Patients were selected from the Southern California Lupus Registry (SCOLR), a registry enrolling all-comers with SLE. Analysis was completed on individuals with public vs. private insurance. Insurance and ethnicity were used as surrogate variables for SES, and we tested differences in means. After adjusting for age and sex, public insurance was independently associated with the prevalence of LN. Analysis of 35 patients revealed greater proteinuria and mean SLEDAI in patients with public insurance at baseline and 6 months. Baseline, 6-, and 12-month SLEDAI means were significantly lower in Asian/Pacific Islanders (PI) compared to others. While non-Hispanic Whites demonstrated mean SLEDAI improvement over 6 months, Asians/PI, Blacks, and Hispanics demonstrated worsened disease activity on average. Low SES, when defined by insurance, is associated with greater adverse outcomes in SLE. This is the first regional study that compares differences in treatment response in LN patients with low SES as well as association of SES with long-term outcomes in SLE and LN in southern California.

Metabolic Modulators in Cardiovascular Complications of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a multifactorial disorder with contributions from hormones, genetics, and the environment, predominantly affecting young women. Cardiovascular disease is the primary cause of mortality in SLE, and hypertension is more prevalent among SLE patients. The dysregulation of both innate and adaptive immune cells in SLE, along with their infiltration into kidney and vascular tissues, is a pivotal factor contributing to the cardiovascular complications associated with SLE. The activation, proliferation, and differentiation of CD4+ T cells are intricately governed by cellular metabolism. Numerous metabolic inhibitors have been identified to target critical nodes in T cell metabolism. This review explores the existing evidence and knowledge gaps concerning whether the beneficial effects of metabolic modulators on autoimmunity, hypertension, endothelial dysfunction, and renal injury in lupus result from the restoration of a balanced immune system. The inhibition of glycolysis, mitochondrial metabolism, or mTORC1 has been found to improve endothelial dysfunction and prevent the development of hypertension in mouse models of SLE. Nevertheless, limited information is available regarding the potential vasculo-protective effects of drugs that act on immunometabolism in SLE patients.

Persisting mortality gap in systemic lupus erythematosus; a population-based study on juvenile- and adult-onset SLE in Norway 1999-2022.

To estimate mortality and survival rates of systemic lupus erythematosus (SLE) in a contemporary, population-based setting and assess potential influences by time, sex, ethnicity, classification criteria and age at diagnosis. We assessed mortality and survival in the Nor-SLE cohort, which includes all chart-review confirmed SLE cases resident in Southeast Norway (population 2.9 million) 1999-2017. Study end was at death, emigration, or 1 October 2022. We defined juvenile SLE by age <16 years at diagnosis. For standardized mortality rate (SMR) estimates, we applied 15 population controls per case, all matched for age, sex, residency, and ethnicity. We analyzed survival by Kaplan-Meier and risk factors by cox regression. The Nor-SLE cohort included 1558 SLE cases, of whom 749 were incident and met the 2019 European Alliance of Associations for Rheumatology and American College of Rheumatology (2019-EA) classification criteria. SMR was increased to 1.8 (95% CI 1.6-2.2) in incident adult-onset SLE but did not differ between females and males. Survival rates at 5-, 10-, 15 and 20-years were lower in incident adult-onset SLE than in matched controls. In multivariable analysis, lupus nephritis associated with decreased survival, while sex did not. Separate, long-term mortality analyses in the total Nor-SLE cohort showed that SMR peaked at 7.2 (95% CI 3.3-14) in juvenile-onset SLE (n = 93) and fell gradually by increasing age at SLE diagnosis. This study shows persistence of a mortality gap between adult-onset SLE and controls at population level and provides indications of worryingly high mortality in juvenile-onset SLE.

Impaired metabolism predicts coronary artery calcification in women with systemic lupus erythematosus

Patients with systemic lupus erythematosus (SLE) exhibit a high risk for cardiovascular diseases (CVD) which is not fully explained by the classical Framingham risk factors. SLE is characterized by major metabolic alterations which can contribute to the elevated prevalence of CVD. A comprehensive analysis of the circulating metabolome and lipidome was conducted in a large cohort of 211 women with SLE who underwent a multi-detector computed tomography scan for quantification of coronary artery calcium (CAC), a robust predictor of coronary heart disease (CHD). Beyond traditional risk factors, including age and hypertension, disease activity and duration were independent risk factors for developing CAC in women with SLE. The presence of coronary calcium was associated with major alterations of circulating lipidome dominated by an elevated abundance of ceramides with very long chain fatty acids. Alterations in multiple metabolic pathways, including purine, arginine and proline metabolism, and microbiota-derived metabolites, were also associated with CAC in women with SLE. Logistic regression with bootstrapping of lipidomic and metabolomic variables were used to develop prognostic scores. Strikingly, combining metabolic and lipidomic variables with clinical and biological parameters markedly improved the prediction (area under the curve: 0.887, p<0.001) of the presence of coronary calcium in women with SLE. The present study uncovers the contribution of disturbed metabolism to the presence of coronary artery calcium and the associated risk of CHD in SLE. Identification of novel lipid and metabolite biomarkers may help stratifying patients for reducing CVD morbidity and mortality in SLE. INSERM and Sorbonne Université.

Clustering of systemic lupus erythematosus mortality in southwestern Spain.

To analyse time trends in systemic lupus erythematosus (SLE) mortality and explore possible provincial clustering of SLE mortality in Spain (2001-2020). We conducted an ecological study using deaths registered in SLE at the Spanish National Institute of Statistics between 2001 and 2020. Jointpoint regression models have been used to evaluate temporal trends. To analyse the spatial pattern of SLE mortality in men and women in Spain, crude rates, age-standardised mortality rates (ASMRs), smooth relative risk (RR) and posterior probabilities (PP) for RR greater than one for the period 2001-2020 were calculated. The Global Moran I index was used to assess the existence of global spatial autocorrelation. Local indicators of spatial association (LISA) and Kulldorff's spatial scan statistic were used to identify clusters. Over the 20 years analyzed in this study, the SLE average ASMR for the period was 2.7 for women and 0.7 for men, with a sex ratio (female/male) of 3.8. In men, no province showed a RR>1. Conversely, in women, eight provinces showed values of RR> 1 with a PP greater than 0.8 (Seville, Cadiz, Huelva and Murcia in the south, Barcelona, Zaragoza, Huesca and Leon in the north). In men, neither of the two methods detected a clustering of provinces. However, in women, both methods identified a cluster of provinces located in the southwest of the country (Huelva, Cádiz, Seville and Malaga) as a cluster with significant excess mortality. In the second cluster (centred on the province of Huelva) obtained with the Kulldorff method, two more provinces were added (Badajoz and Cordoba, also located in the southwest). We detected a cluster of provinces with an excess risk of female SLE mortality in the southwest of Spain.

Mortality and causes of death in systemic lupus erythematosus in New Zealand: A population-based study.

This study aims to assess the mortality of systemic lupus erythematosus (SLE) patients and examine whether there are variations by subgroup. SLE patients from 2005-2021 were identified from the national administrative datasets. The underlying causes of death were examined. Standardised mortality ratio (SMR) was estimated to compare the relative rate of observed deaths in SLE patients to expected deaths in the general population. The hazard ratios (HR) and 95% confidence intervals (CI) of all-cause mortality and SLE specific mortality by ethnicity were estimated after adjustment for age using a Cox proportional hazards model. Of the 2,802 patients included for analysis, 699 (24.9%) died with 209 (29.9%) SLE deaths. The age-standardised mortality rate of SLE was 0.29 per 100 000 for women and 0.05 for men. The mean age at death was 65.3 ± 17.1 years. Younger patients were more likely to have SLE as the underlying cause of death, from 78.9% for those under 20 years old to 18.7% for those aged 70-79 years. Compared with the general population, SLE patients were four times more likely to die (SMR: 4.0; 95% CI: 3.7-4.3). Young patients had higher SMRs than older patients. Māori had worse all-cause mortality (HR: 1.72; 95% CI: 1.10-2.67) and SLE specific mortality (HR: 2.60; 95% CI: 1.29-5.24) than others. The outcomes of SLE in New Zealand were still very poor compared with the general population. Māori with SLE had worse survival than others. Further research is needed to identify the reasons to this disparity.

#3858 ASSESSING THE EFFECTIVENESS OF LONG-TERM BELIMUMAB THERAPY IN LUPUS NEPHRITIS: A SINGLE-CENTRE OBSERVATIONAL STUDY

Abstract Background and Aims Lupus nephritis (LN) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Belimumab, a monoclonal antibody that inhibits B-cell activating factor, has demonstrated efficacy in decreasing proteinuria, prevention of flares and achieving renal response after two years. However, data on its long-term efficacy is limited. The aim of this observational study is to assess the efficacy of belimumab in biopsy-proven LN patients over the medium and long term. Method In this retrospective observational study at our centre, patients with documented history of biopsy-proven LN who received belimumab were selected for analysis. Data on renal function, proteinuria (24 hours) and haematuria were collected. Immunologic activity (Anti-double-stranded-DNA, C3 and C4) was assessed. Data were retrieved at three moments: belimumab initiation, 12 months after the start of therapy and when treatment was discontinued. When treatment had not been discontinued, last available data was used. Renal flares were identified. The observational period was adjusted to be consistent between pre- and post-belimumab treatments. Clinically relevant outcomes such as possible adverse effects or major pathologic events were actively searched in patient records. Finally, the initiation of any additional antiproteinuric treatment was reported. Data analysis was performed using IBM SPSS Statistics 21®. When sample distributions were found to be normal, a parametric T-test was performed. An analysis of outcomes for patients receiving belimumab for more than 24 months was also performed. Results Seventeen patients diagnosed of LN between 1991 and 2021 began belimumab from 2014 to 2022, ten of whom received belimumab for more than 24 months. Mean treatment duration was 41,8 months. Patient characteristics are presented in Table 1, while analytic results are summarized in Table 2. A statistically significant decrease in proteinuria stands out 12 months after starting treatment with belimumab and a decrease in anti-dsDNA antibodies. As regards the subgroup of extended follow-up, results did not differ in hypothesis contrast tests. Overall, 17 renal flares were identified prior to belimumab initiation, while 9 flares were identified following its initiation (Fisher's Exact Test: P = 0,092). A patient was diagnosed with acute bacterial meningitis, although the relationship to the drug is unclear since the patient was also receiving other immunosuppressive medications. This event did not lead to drug withdrawal. Only one patient started an angiotensin converting enzyme inhibitor (ACEI), immediately after initiating belimumab. Conclusion Currently, the optimal treatment duration with belimumab in LN is not known. Despite a decline in median GFR, results from this cohort of patients suggest a tendency to controlling proteinuria, haematuria and immunologic activity, over the middle and long term. A remarkable yet not significant decline in renal flares was observed. Finally, no relevant changes in immunosuppressive or antiproteinuric medication were made, allowing to avoid biases for this reason.

#6843 CITATION CLASSICS IN LUPUS NEPHRITIS: A BIBLIOMETRIC ANALYSIS

Abstract Background and Aims Lupus nephritis is an important risk factor for morbidity and mortality in systemic lupus erythematosus. During the past three decades, extensive research has been done to address this important complication and devise better management strategies. In this article we aimed to perform a thorough assessment of the research productivity in lupus nephritis by identifying the 100 most-cited articles in lupus nephritis. Methods The top 100 most-cited English language articles on lupus nephritis from 1990 were examined by bibliometric analysis from the Google Scholar database of ‘Harzing's Publish or Perish’ software. These articles were subsequently analysed in detail and the chief characteristics are presented here. Results From 1990-2022, there were 111358 citations with 3480 cites/year and an average of 111 cites/paper. Thirty articles had greater than 400 citations, with 9 having more than1000 citations. Majority of the publications were from the United States of America (46%) with maximum publications from the National Institute of Health (NIH), Bethesda. Among these 100 most-cited articles, there were a median of 7 (5-12) authors per article with a mean of 9.6 authors. Twenty-six percent of the top-100 most-cited articles were randomized controlled trials while cohort and in-vivo studies addressing pathophysiology and biopsy related data accounted for one-fourth each. Among rheumatology journals, ‘Arthritis Rheum’, ‘Ann Rheum Dis’ and ‘Lupus’ were the most preferred journals for researchers working on lupus nephritis. Conclusion This article gives an overview of the research productivity, landmark publications and emerging trends in lupus nephritis. Increased emphasis on high-quality data from randomized controlled trials is revolutionising the management of lupus nephritis.

Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is Associated with Disease Activity and Risk of Incident Cardiovascular Disease in Patients with Systemic Lupus Erythematosus.

To study the relationship of serum PCSK9 and disease activity and major adverse cardiovascular events (MACEs) in systemic lupus erythematosus (SLE). Consecutive patients who fulfilled ≥ 4 ACR criteria for SLE and consented for a biomarker study in 2009-2013 were included. Stored serum samples were assayed for PCSK9. PCSK9 levels were correlated with SLE disease activity scores. Patients were divided into two groups according to the median PCSK9 level and new MACEs over time were evaluated. The effect of PCSK9 level on MACEs and mortality was studied by Cox regression, adjusted for confounders. A total of539 SLE patients were studied (93% women, age 41.9 ± 14.0 years). The median PCSK9 level at baseline was 220 ng/ml. Patients with higher PCSK9 (≥ 220 ng/ml; n = 269) had significantly higher SLE disease activity index (SLEDAI) than those with lower PCSK9 (< 220 ng/ml; n = 270). PCSK9 levels were significantly higher in patients with active renal than active non-renal SLE, which in turn were significantly higher than those with inactive SLE or healthy controls. PCSK9 level correlated with SLEDAI in the overall population (ρ = 0.30; p < 0.001). Over 91.3 ± 18.6 months, 29 patients developed 31 MACEs and 40 patients succumbed (25% for vascular events). The cumulative incidence of MACEs at 5 years was 4.8% in the higher PCSK9 and 1.1% in the lower PCSK9 group (HR2.51[1.11-5.70]; p = 0.03). Cox regression revealed higher PCSK9 was significantly associated with MACEs (HR1.003[1.000-1.005] per ng/ml; p = 0.02) independent of age, sex, renal function, baseline disease activity score, traditional atherosclerotic risk factors, antiphospholipid antibody and the use of aspirin/warfarin, statins and immunosuppressive drugs. PCSK9 level was also independently associated with all-cause (HR1.002[1.000-1.004] per ng/ml; p = 0.03) and vascular mortality (HR1.004[1.000-1.007]; p = 0.04). We concluded that serum PCSK9 level correlates with SLEdisease activity. Higher serum PCSK9 levels are associated with increased risk of cardiovascular events and mortality in SLE.

Renal Pathology Images Segmentation Based on Improved Cuckoo Search with Diffusion Mechanism and Adaptive Beta-Hill Climbing.

Lupus Nephritis (LN) is a significant risk factor for morbidity and mortality in systemic lupus erythematosus, and nephropathology is still the gold standard for diagnosing LN. To assist pathologists in evaluating histopathological images of LN, a 2D Rényi entropy multi-threshold image segmentation method is proposed in this research to apply to LN images. This method is based on an improved Cuckoo Search (CS) algorithm that introduces a Diffusion Mechanism (DM) and an Adaptive β-Hill Climbing (AβHC) strategy called the DMCS algorithm. The DMCS algorithm is tested on 30 benchmark functions of the IEEE CEC2017 dataset. In addition, the DMCS-based multi-threshold image segmentation method is also used to segment renal pathological images. Experimental results show that adding these two strategies improves the DMCS algorithm's ability to find the optimal solution. According to the three image quality evaluation metrics: PSNR, FSIM, and SSIM, the proposed image segmentation method performs well in image segmentation experiments. Our research shows that the DMCS algorithm is a helpful image segmentation method for renal pathological images.

Tuberculosis remains a leading contributor to morbidity due to serious infections in Indian patients of SLE.

Infections are a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). We assessed the incidence and risk factors for major infections in SLE in India. A retrospective review of a cohort of 1354 patients of adult SLE (ACR 1997 criteria) seen between 2000 and 2021 at a single center was conducted. Serious infections (need for hospitalisation, prolonged intravenous antibiotics, disability, or death) were recorded. Cox regression was used to determine factors associated with serious infection and the effects of serious infection on survival and damage. Among the 1354 patients (1258 females, mean age of 30.3years, follow-up of 7127.89 person-years), there were 439 serious infections in 339 patients (61.6 per 1000 person-years follow-up). Bacterial infections (N = 226) were the most common infection followed by mycobacterial infections (n = 81), viral (n = 35), and then invasive fungal infections (N = 13). Mycobacterium tuberculosis was the single most common microbiologically confirmed organism with incidence of 1136.4/100,000 person-years with 72.8% of them being extrapulmonary. Infection free survival at 1year and 5years was 82.9% and 73.8%. There were 119 deaths with infection attributable mortality in 65 (54.6%). On multivariable Cox regression analysis, higher baseline activity (HR 1.02, 1.01-1.05), gastrointestinal involvement (HR 2.75, 1.65-4.69), current steroid dose (HR 1.65, 1.55-1.76), and average cumulative steroid dose per year (HR 1.007, 1.005-1.009) were associated with serious infection and higher albumin (HR 0.65, 0.56-0.76) was protective. Serious infections led to greater damage accrual (median SLICC damage index of 1 vs. 0) and mortality (HR was 18.2, 32.7 and 81.6 for the first, second, and third infections). Serious infections remain a major cause of mortality and damage accrual in SLE and higher disease activity, gastrointestinal involvement, hypoalbuminemia, current steroid dose, and cumulative steroid dose are the risk factors for it.

Mortality and causes of death in systemic lupus erythematosus over the last decade: Data from a large population-based study

ObjectiveTo assess mortality rates (MRs), standardized mortality ratios, and causes of death in systemic lupus erythematosus (SLE) in a population-based study. MethodsWe analyzed linked administrative health databases of the Veneto Region (Italy, 4,900,000 residents). SLE was defined by any hospital diagnosis or healthcare copayment exemption for SLE. We analyzed mortality from January 1st, 2012, until December 31st, 2021. MRs per 1000 were stratified by year, sex, and age group. Standardized mortality ratios were derived by comparing MRs of the general regional population. Causes of death were coded using the ICD-10 coding system and they were grouped in: SLE, infectious diseases, cardiovascular diseases (CVD), cancer, or others. ResultsAmong 4283 SLE prevalent cases, 603 deaths occurred, corresponding to an average annual standardized MR of 18.6 per 1000 person/year (95% CI 17.0-20.2). Out of 1092 incident SLE patients, 90 died with a peak in the first year after diagnosis (MR 26.5 per 10,000 person/month). Standardized mortality ratio was 2.65 (95% CI 2.13-3.26) overall, and highest among younger patients (<45 years: 5.59, 95% CI 2.05-12.4). Five- and 8-year survival were 91% and 89%, respectively. About half of the deaths had CVD or cancer as underlying cause, whereas infections were less frequently reported. ConclusionsAlthough the medium-term survival since diagnosis is good, SLE mortality is still higher than that of the general population, especially in youngest patients. Nowadays, CVD seems to be the major cause of deaths in SLE, whereas infections account for a low proportion of deaths, at least in Western countries.

Refractory Systemic Lupus Erythematosus: Identification and Pharmacological Management.

Systemic lupus erythematosus (SLE) is characterized by an aberrant immune response, leading to an extremely heterogeneous clinical presentation, potentially affecting different systems and organs. Despite the fact that SLE mortality has greatly decreased since the introduction of steroids, some forms of refractory/severe SLE still have the potential to result in permanent organ damage as well as increased mortality and morbidity. Furthermore, SLE patients with multiple comorbidities may face a clinical conundrum and have a bad prognosis. An improved prognosis for severe refractory SLE depends on prompt and appropriate treatment. Due to the scarcity of solid data from a well-characterized group of patients with refractory/severe SLE coming from randomized controlled studies, this review aims to shed light on this with real-world evidence from clinical research performed at our Unit, the University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID) (Turin, Italy). In order to determine the key clinical and prognostic features, and therapeutic approaches for severe and/or refractory SLE, our experience will be described together with existing literature, primarily focused on dermatological, neuropsychiatric, and renal symptoms.

The association of systemic lupus erythematosus with short-term mortality in sepsis: a population-level analysis.

Systemic lupus erythematosus (SLE) is associated with higher risks of sepsis and sepsis-related mortality compared to the general population. However, the prognostic impact of SLE in sepsis is uncertain. We used statewide data to identify hospitalizations aged ≥18 years in Texas with sepsis, with and without SLE during 2014-2017. Multilevel logistic regression with propensity adjustment (primary model), propensity score matching, and multivariable logistic regression without propensity adjustment were used to estimate the association of SLE with short-term mortality (defined as in-hospital mortality or discharge to hospice) among sepsis hospitalizations. Among 283,025 sepsis hospitalizations, 2933 (1.0%) had SLE. Compared to sepsis hospitalizations without SLE, those with SLE were younger (aged ≥65 years, 25.0% vs 57.0%) and had higher burden of comorbidities (mean Deyo comorbidity index 3.0 vs 2.6). Short-term mortality of sepsis hospitalizations with and without SLE was 22.9% vs 31.3%. SLE remained associated with lower short-term mortality on the secondary models, but not on the primary one (adjusted odds ratio: 0.905; 95% confidence interval: 0.817-1.001). When in-hospital mortality was used as secondary outcome, SLE was associated with mortality only on propensity score matching. The increased sepsis-related mortality in SLE is driven by higher risk of sepsis, but not by higher case fatality among septic patients. SLE may be associated with lower risk of mortality among septic patients, but further studies are needed due to heterogeneity of the prognostic associations across models.