Severe and life-threatening onset of systemic lupus erythematosus / Una presentación grave y potencialmente fatal de lupus eritematoso sistémico

Macrophage activation syndrome (MAS) is a potentially life-threatening complication of rheumatic diseases. We report a unique case of a previously healthy 20-year-old female presenting with MAS as first presentation of systemic lupus erythematosus. Remission was achieved with hydroxychloroquine, intravenous methylprednisolone pulse followed by oral prednisolone and cyclosporine. However, the management of MAS is still challenging, and the mortality rate remains high.(AU)

El síndrome de activación macrofágica (SAM) es una complicación potencialmente letal de algunas enfermedades reumáticas. Presentamos un caso único de una mujer de 20 años previamente sana que se presentó con SAM como primera manifestación de lupus eritematoso sistémico. Se logró una remisión completa con hidroxicloroquina, pulsos intravenosos de metilprednisolona seguido de prednisolona oral y ciclosporina. Sin embargo, el manejo del SAM sigue siendo un desafío y la tasa de mortalidad sigue siendo alta.(AU)

Comparison of mortality and its causes in patients with complicated systemic lupus erythematosus on hemodialysis versus peritoneal dialysis: A meta-analysis.

BACKGROUND: Lupus nephritis is one of the most serious complications of systemic lupus erythematosus (SLE). Ten percent to 20% of patients with SLE progress to end-stage renal disease and would require renal replacement therapy or renal transplantation. In this analysis, we aimed to systematically compare mortality and the causes of mortality in patients with complicated SLE who were treated on hemodialysis (HD) versus peritoneal dialysis (PD). METHODS: Cochrane Central, Medical Literature Analysis and Retrieval System Online, Google Scholar, Web of Science, Excerpta Medica dataBASE, and http://www.ClinicalTrials.gov were searched for studies that compared HD versus PD in patients with SLE. The RevMan software version 5.4 (RevMan software, Cochrane Collaborations, United Kingdom) was used to analyze data. Heterogeneity was assessed using the Q and the I2 statistical tests. In this analysis, a random effects model was used during data assessment. Risk ratios (RRs) with 95% confidence intervals (CIs) were used to represent the results following analysis. RESULTS: A total number of 3405 SLE participants were included in this analysis, whereby 2841 were assigned to HD and 564 participants were assigned to PD. In patients with SLE who were on dialysis, our analysis showed that the risk of mortality was similar with HD and PD (RR, 0.69; 95% CI, 0.45-1.07; P = .10). When the cause of mortality was analyzed, cardiovascular death (RR, 0.63; 95% CI, 0.31-1.31; P = .22), death due to infection (RR, 0.74; 95% CI, 0.47-1.17; P = .20), death due to a respiratory cause (RR, 1.06; 95% CI, 0.18-6.21; P = .95), cause of death due to SLE flare up (RR, 2.54; 95% CI, 0.39-16.37; P = .33), and other causes of death (RR, 0.79; 95% CI, 0.35-1.77; P = .57) were not significantly different with HD and PD. CONCLUSION: This current analysis showed that in SLE patients who required dialysis, the risk of mortality between HD and PD was similar, and the causes of death including cardiovascular, infective, respiratory, SLE flare up, and other causes were not significantly different. Therefore, both dialysis methods were tolerable in these patients with SLE. Further studies with larger data would be required to confirm this hypothesis.

Systemic Lupus Erythematosus: Targeted Literature Review of the Epidemiology, Current Treatment, and Disease Burden in the Asia Pacific Region.

OBJECTIVE: To understand the epidemiology, current treatment, and disease burden of systemic lupus erythematosus (SLE) in the Asia Pacific (APAC) region. METHODS: A targeted literature review of published evidence on SLE in the APAC region was conducted, using the Medline database (2008-2018), conference proceedings, and other supplementary sources. RESULTS: The current review identified 70 studies conducted in China (n = 15), Japan (n = 13), Taiwan (n = 12), Korea (n = 9), Australia (n = 7), Hong Kong (n = 6), Singapore (n = 4), and multiple places within the APAC region (n = 4). Incidence rates (per 100,000 persons per year) ranged from 0.9-8.4, while prevalence rates ranged from 3.7-127 (per 100,000 persons); however, recent data were limited. Asian patients with SLE were reported to have higher disease severity, disease activity (higher SLE disease activity index scores), and organ damage accrual, along with increased morbidity, mortality, and susceptibility to renal involvement compared with other ethnicities in the APAC region. The risk of developing SLE is higher in the Asian population. Routinely used SLE therapies included belimumab, hydroxychloroquine, cyclophosphamide, tacrolimus, azathioprine, mycophenolate mofetil, and glucocorticoids; however, prescribing patterns varied across the region. Increased disease activity was associated with high economic burden and poor quality of life for SLE patients in the APAC region. CONCLUSION: SLE remains a disease with a significant unmet medical need for an innovative therapy that is well-tolerated and effective for patients in the APAC region. Further evidence is required to better characterize the disease and fully capture the burden and impact of SLE in the APAC region. This review has highlighted where there is a paucity of data from patients across the APAC region.

Survival after COVID-19-associated organ failure among inpatients with systemic lupus erythematosus in France: a nationwide study.

OBJECTIVE: We analysed the incidence of, the specific outcomes and factors associated with COVID-19-associated organ failure (AOF) in patients with systemic lupus erythematosus (SLE) in France. METHODS: We performed a cohort study using the French national medical/administrative hospital database for the January 2011-November 2020 period. Each patient with SLE diagnosed in a French hospital with a COVID-19-AOF until November 2020 was randomly matched with five non-SLE patients with COVID-19-AOF. We performed an exact matching procedure taking age ±2 years, gender and comorbidities as matching variables. COVID-19-AOF was defined as the combination of at least one code of COVID-19 diagnosis with one code referring to an organ failure diagnosis. RESULTS: From March to November 2020, 127 380 hospital stays in France matched the definition of COVID-19-AOF, out of which 196 corresponded with patients diagnosed with SLE. Based on the presence of comorbidities, we matched 908 non-SLE patients with COVID-19-AOF with 190 SLE patients with COVID-19-AOF. On day 30, 43 in-hospital deaths (22.6%) occurred in SLE patients with COVID-19-AOF vs 198 (21.8%) in matched non-SLE patients with COVID-19-AOF: HR 0.98 (0.71-1.34). Seventy-five patients in the SLE COVID-19-AOF group and 299 in the matched control group were followed up from day 30 to day 90. During this period, 19 in-hospital deaths occurred in the SLE group (25.3%) vs 46 (15.4%) in the matched control group; the HR associated with death occurring after COVID-19-AOF among patients with SLE was 1.83 (1.05-3.20). CONCLUSIONS: COVID-19-AOF is associated with a poor late-onset prognosis among patients with SLE.

Differences in the Clinical Manifestations and Mortality of Systemic Lupus Erythematosus Onset in Children and Adults: A Systematic Review and Meta-Analysis.

INTRODUCTION: The aim of this study was to assess the differences between childhood-onset and adult-onset systemic lupus erythematosus (cSLE and aSLE) for clinical manifestations and mortality using a meta-analytic approach. METHODS: The PubMed, EMBASE, and the Cochrane library were searched for eligible studies published between January 1982 and March 2021. The odds ratio (OR) with 95% confidence interval was used to calculate the pooled effect estimates using the random-effects model. RESULTS: Thirty-four studies involving 21,946 SLE patients were included. cSLE was associated with an increased risk of malar rash (OR: 1.64; p < 0.001), ulcers/mucocutaneous involvement (OR: 1.22; p = 0.039), general neurological involvement (OR: 1.52; p < 0.001), seizures (OR: 1.92; p < 0.001), general renal involvement (OR: 2.08; p < 0.001), proteinuria (OR: 1.35; p = 0.015), urinary cellular casts (OR: 1.67; p = 0.047), fever (OR: 2.31; p < 0.001), anemia (OR: 1.91; p < 0.001), thrombocytopenia (OR: 1.41; p < 0.001), leucopenia (OR: 1.57; p = 0.017), lymphadenopathy (OR: 2.40; p < 0.001), and cutaneous vasculitis (OR: 1.72; p = 0.001) as compared with aSLE. Moreover, cSLE versus aSLE was associated with a reduced risk of articular manifestations (OR: 0.63; p = 0.001), pulmonary involvement (OR: 0.54; p = 0.001), and pleuritis (OR: 0.61; p < 0.001). There were no significant differences between cSLE and aSLE for mortality risk (OR: 1.20; p = 0.203). CONCLUSION: We found that certain clinical manifestations of SLE are different in cSLE and aSLE. Moreover, the mortality risk of cSLE and aSLE was not significantly different.

Renal function deterioration is an independent mortality determinant in Koreans diagnosed with lupus nephritis.

OBJECTIVE: To evaluate the predictors of mortality, mortality rate, and causes of death in patients with lupus nephritis (LN) depending on final renal function. METHODS: The cohort included 401 Korean patients diagnosed with LN between 1985 and 2019. We retrospectively analyzed the clinical and laboratory indices, treatment response, and the final renal function. The final renal function was defined by the last stable level of eGFR measured in an out-patient department more than 3 times before death occurred and was categorized into five groups depending on CKD stage. RESULTS: The median follow-up time after the diagnosis of LN was 131 months. No difference in baseline demographic characteristics and laboratory findings was found except for the proportion of Hb less than 10 mg/dl and baseline eGFR (p = 0.011 and 0.037). We found no significant differences in therapeutic parameters, but all the response parameters including treatment response at 6 months (p = 0.004) and 12 months (p = 0.004), time to remission (p < 0.001), final renal response (p < 0.001), and the final renal function (p < 0.001) differed significantly between the two groups. In multivariate Cox proportional hazards analysis, the final renal function was an independent risk factor predicting mortality. The main causes of death were infection and SLE flare. Contrary to existing knowledge, SLE flare also triggered mortality in a few patients with LN progressed to end-stage renal disease (ESRD). Only two cases of mortality occurred in the kidney transplantation (KT) group (n = 25) with a median follow-up period of 224 months. The overall mortality rates calculated using the Kaplan-Meier method were 6.8%, 10.3%, 19.7%, and 28.0% at 5, 10, 20, and 30 years, respectively. CONCLUSION: Renal function deterioration was an independent determinant of mortality in Korean patients with LN. SLE flare also caused mortality in patients with LN who required maintenance dialysis, suggesting the benefit of KT on lupus activity and survival.

Global epidemiology of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with protean manifestations that predominantly affects young women. Certain ethnic groups are more vulnerable than others to developing SLE and experience increased morbidity and mortality. Reports of the global incidence and prevalence of SLE vary widely, owing to inherent variation in population demographics, environmental exposures and socioeconomic factors. Differences in study design and case definitions also contribute to inconsistent reporting. Very little is known about the incidence of SLE in Africa and Australasia. Identifying and remediating such gaps in epidemiology is critical to understanding the global burden of SLE and improving patient outcomes. Mortality from SLE is still two to three times higher than that of the general population. Internationally, the frequent causes of death for patients with SLE include infection and cardiovascular disease. Even without new therapies, mortality can potentially be mitigated with enhanced quality of care. This Review focuses primarily on the past 5 years of global epidemiological studies and discusses the regional incidence and prevalence of SLE and top causes of mortality.

A multicenter longitudinal study of the prevalence and mortality rate of systemic lupus erythematosus patients in Oman: Oman Lupus Study.

AIM: This study is a longitudinal multicenter study which aims to find the prevalence, the demographic data, survival and mortality rates of patients with systemic lupus erythematosus (SLE) in Oman. METHOD: All Omani patients, pediatrics and adults diagnosed with SLE, who fulfill either the 1997 American College of Rheumatology or Systemic Lupus International Collaborating Clinics classifications criteria for SLE were included from January 2006 till February 2020. RESULTS: In total 1160 patients were included in this cohort. Data analysis showed that patient's ages ranged from 2-82 years with female predominance and female-to-male ratio of 7:1 (87.7% female,12.3% male). The mean prevalence of SLE among different age groups was 38.8 (range 5-63 per 100 000 inhabitants). The mortality rate was found to be 5%. Male patients had significantly higher mortality rate than females (7.6% vs 5.4%, P value = .04). Sepsis was the commonest cause of mortality (34%). The coexistence of systemic sclerosis correlates significantly with death (P = .002). Survival analysis in our data showed 5, 10, 20, 40-year survival rates of 100%, 100%, 99% and 90% respectively for antinuclear antibody (ANA) positive patients and lower survival rate for ANA negative patients with 5,10, 20, 40-year survival rates of 100, 99%, 99% and 75%, respectively. CONCLUSION: This study showed that the mean prevalence of SLE in Oman to be 38.8 (range 5-63) per 100 000 inhabitants. The 40-year survival rate among patients with positive ANA was found to be 90%, while patients with negative ANA had worse survival outcomes.

All-cause and cause-specific mortality in systemic lupus erythematosus: a population-based study.

OBJECTIVE: To investigate all-cause and cause-specific mortality in SLE patients between two time periods, 1997-2005 and 2006-14. METHODS: We used an administrative health database from the province of British Columbia, Canada to match all incident SLE patients to 10 non-SLE individuals on sex, age and index date. Cohorts were divided into two subgroups, according to diagnosis year: early cohort 1997-2005 and late cohort 2006-14. The outcome was death [all-cause, renal disease, cancer, infection, cardiovascular disease (CVD) and other]. Hazard ratios (HR) and 95% CIs were estimated using univariate and multivariable Cox models. RESULTS: Among 6092 SLE patients and 60 920 non-SLE individuals, there were 451 and 1910 deaths, respectively. The fully adjusted all-cause mortality HR (95% CI) in the overall SLE cohort was 1.85 (1.66, 2.06), with no statistically significant improvement between early and late cohorts [1.95 (1.69, 2.26) vs 1.74 (1.49, 2.04)]. There was excess mortality from renal disease [3.04 (2.29, 4.05)], infections [2.74 (2.19, 3.43)] and CVD [2.05 (1.77, 2.38)], but not cancer [1.18 (0.96, 1.46)], in the overall SLE cohort. There was no statistically significant improvement in cause-specific mortality between early and late cohorts for renal disease [3.57 (2.37, 5.36) vs 2.65 (1.78, 3.93)], infection [2.94 (2.17, 3.98) vs 2.54 (1.84, 3.51)] and CVD [1.95 (1.60, 2.38) vs 2.18 (1.76, 2.71)]. There was no increase in cancer-related mortality in either cohort [1.27 (0.96, 1.69) vs 1.10 (0.82, 1.48)]. CONCLUSION: This population-based study demonstrates a persisting mortality gap in all-cause and cause-specific deaths in SLE patients, compared with the general population.

Increased risk of severe infections and mortality in patients with newly diagnosed systemic lupus erythematosus: a population-based study.

OBJECTIVE: To evaluate the risk of severe infection and infection-related mortality among patients with newly diagnosed SLE. METHODS: We conducted an age- and gender-matched cohort study of all patients with incident SLE between 1 January 1997 and 31 March 2015 using administrative health data from British Columbia, Canada. Primary outcome was the first severe infection after SLE onset necessitating hospitalization or occurring during hospitalization. Secondary outcomes were total number of severe infections and infection-related mortality. RESULTS: We identified 5169 SLE patients and matched them with 25 845 non-SLE individuals from the general population, yielding 955 and 1986 first severe infections during 48 367 and 260 712 person-years follow-up, respectively. The crude incidence rate ratios for first severe infection and infection-related mortality were 2.59 (95% CI: 2.39, 2.80) and 2.20 (95% CI: 1.76, 2.73), respectively. The corresponding adjusted hazard ratios were 1.82 (95% CI: 1.66, 1.99) and 1.61 (95% CI: 1.24, 2.08). SLE patients had an increased risk of a greater total number of severe infections with crude rate ratio of 3.24 (95% CI: 3.06, 3.43) and adjusted rate ratio of 2.07 (95% CI: 1.82, 2.36). CONCLUSION: SLE is associated with increased risks of first severe infection (1.8-fold), a greater total number of severe infections (2.1-fold) and infection-related mortality (1.6-fold).

Belimumab for systemic lupus erythematosus.

BACKGROUND: Belimumab, the first biologic approved for the treatment of systemic lupus erythematosus (SLE), has been shown to reduce autoantibody levels in people with SLE and help control disease activity. OBJECTIVES: To assess the benefits and harms of belimumab (alone or in combination) in systematic lupus erythematosus. SEARCH METHODS: An Information Specialist carried out the searches of CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, the World Health Organization (WHO) International Clinical Trials Registry Platform, and clinicaltrials.gov from inception to 25 September 2019. There were no language or date restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs) or controlled clinical trials (CCTs) of belimumab (alone or in combination) compared to placebo/control treatment (immunosuppressive drugs, such as azathioprine, cyclosporine, mycophenolate mofetil or another biologic), in adults with SLE. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. MAIN RESULTS: Six RCTs (2917 participants) qualified for quantitative analyses. All included studies were multicenter, international or US-based. The age range of the included participants was 22 to 80 years; most were women; and study duration ranged from 84 days to 76 weeks. The risk of bias was generally low except for attrition bias, which was high in 67% of studies. Compared to placebo, more participants on belimumab 10 mg/kg (Food and Drug Administration (FDA)-approved dose) showed at least a 4-point improvement (reduction) in Safety of Estrogen in Lupus National Assessment (SELENA) - Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, a validated SLE disease activity index: (risk ratio (RR) 1.33, 95% confidence interval (CI) 1.22 to 1.45; 829/1589 in belimumab group and 424/1077 in placebo; I2= 0%; 4 RCTs; high-certainty evidence). Change in health-related quality of life (HRQOL), assessed by Short Form-36 Physical Component Summary score improvement (range 0 to 100), showed there was probably little or no difference between groups (mean difference 1.6 points, 95% CI 0.30 to 2.90; 401 in belimumab group and 400 in placebo; I2= 0%; 2 RCTs; moderate-certainty evidence). The belimumab 10 mg/kg group showed greater improvement in glucocorticoid dose, with a higher proportion of participants reducing their dose by at least 50% compared to placebo (RR 1.59, 95% CI 1.17 to 2.15; 81/269 in belimumab group and 52/268 in placebo; I2= 0%; 2 RCTs; high-certainty evidence). The proportion of participants experiencing harm may not differ meaningfully between the belimumab 10 mg/kg and placebo groups: one or more serious adverse event (RR 0.87, 95% CI: 0.68 to 1.11; 238/1700 in belimumab group and 199/1190 in placebo; I2= 48%; 5 RCTs; low-certainty evidence; ); one or more serious infection (RR 1.01, 95% CI: 0.66 to 1.54; 44/1230 in belimumab group and 40/955 in placebo; I2= 0%; 4 RCTs; moderate-certainty evidence); and withdrawals due to adverse events (RR 0.82, 95% CI: 0.63 to 1.07; 113/1700 in belimumab group and 94/1190 in placebo; I2= 0%; 5 RCTs; moderate-certainty evidence). Mortality was rare, and may not differ between belimumab 10 mg/kg and placebo (Peto odds ratio 1.15, 95% CI 0.41 to 3.25; 9/1714 in belimumab group and 6/1203 in placebo; I2= 4%; 6 RCTs; low-certainty evidence). AUTHORS' CONCLUSIONS: The six studies that provided evidence for benefits and harms of belimumab were well-designed, high-quality RCTs. At the FDA-approved dose of 10 mg/kg, based on moderate to high-certainty data, belimumab was probably associated with a clinically meaningful efficacy benefit compared to placebo in participants with SLE at 52 weeks. Evidence related to harms is inconclusive and mostly of moderate to low-certainty evidence. More data are needed for the longer-term efficacy of belimumab.

Age differences in secular trends in black-white disparities in mortality from systemic lupus erythematosus among women in the United States from 1988 to 2017.

OBJECTIVE: To examine the age differences in secular trends in black-white disparities in mortality from systemic lupus erythematosus (SLE) among women in the United States from 1988 to 2017. METHODS: We used mortality data to calculate age-specific SLE and all-causes (as reference) mortality rates and black/white mortality rates ratios among women from 1988 to 2017. Annual percent change was estimated using joinpoint regression analysis. RESULTS: We identified 10,793 and 4,165,613 black women and 19,455 and 31,129,528 white women who died between 1988 and 2017 from SLE and all-causes, respectively. The black/white SLE mortality rate ratio according joinpoint regression model was 6.6, 7.2, 4.4, and 1.4 for decedents aged 0-24, 25-44, 45-64, and 65+ years in 1988 and was 7.2, 5.9, 4.1, and 1.9, respectively in 2017. No significant decline trend was noted and the annual percent change was 0.3%, -0.7%, -0.2%, and 1.0%, respectively. On the contrast, the black/white all-causes mortality rate ratio was 2.0, 2.5, 1.8, and 1.0, respectively in 1988 and was 1.7, 1.3, 1.5, and 0.9, respectively in 2017, a significant decline trend was noted in each age group. CONCLUSIONS: Black adults, youths and adolescents had four to seven times higher SLE mortality rates than their white counterparts and the black-white disparities persisted during the past three decades. On the contrast, black women had less than two times higher all-causes mortality rates than their white counterparts and black-white disparities significantly diminish during the past three decades.

Outcome of clinical and subclinical myocardial injury in systemic lupus erythematosus - A prospective cohort study.

OBJECTIVES: To determine the outcome of subclinical lupus myocarditis (LM) over twelve months with regards to: mortality; incidence of clinical LM and change in imaging parameters (echocardiography and cardiac magnetic resonance [CMR]). To evaluate the impact of immunosuppression on CMR evidence of myocardial tissue injury. METHODS: SLE patients with and without CMR evidence of myocardial injury (as per 2009 Lake Louise criteria [LLC]) were included. Analysis at baseline and follow-up included: clinical evaluation, laboratory and imaging analyses (echocardiography and CMR). Clinical LM was defined as clinical features of LM supported by echocardiographic and/or biochemical evidence of myocardial dysfunction. Subclinical LM was defined as CMR myocardial injury without clinical LM. RESULTS: Forty-nine SLE patients were included with follow-up analyses (after 12 months) available in 36 patients. Twenty-five patients (51%) received intensified immunosuppressive therapy during follow-up for indications related to SLE. Disease activity (SLEDAI-2K) improved (p < 0.001) from 13 (median;IQR:9-20) to 7 (3-11). One patient without initial CMR evidence of myocardial injury developed clinical LM. Mortality (n = 10) and SLE clinical features were similar between patients with and without initial CMR myocardial injury. Echocardiographic left ventricular ejection fraction (LVEF) (p = 0.014), right ventricular function (p = 0.001) and wall motion abnormalities (p = 0.056) improved significantly but not strain analyses nor the left LV internal diameter index. CMR mass index (p = 0.011) and LVEF (p < 0.001) improved with follow-up but not parameters identifying myocardial tissue injury (LLC). A trend towards a reduction in the presence of CMR criteria was counterbalanced by persistence (n = 7) /development of new criteria (n = 11) in patients. Change in CMR mass index correlated with change in T2-weighted signal (myocardial oedema) (r = 386;p = 0.024). Intensified immunosuppressive therapy had no significant effect on CMR parameters. CONCLUSION: CMR evidence of subclinical LM persisted despite improved SLEDAI-2K, serological markers, cardiac function and CMR mass index. Subclinical LM did not progress to clinical LM and had no significant prognostic implications over 12 months. Immunosuppressive therapy did not have any significant effect on the presence of CMR evidence of myocardial tissue injury. Improvement in CMR mass index correlated with reduction in myocardial oedema and may be used to monitor SLE myocardial injury.

Mortality Among Minority Populations with Systemic Lupus Erythematosus, Including Asian and Hispanic/Latino Persons - California, 2007-2017.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with manifestations that vary widely in severity. Although minority populations are at higher risk for SLE and have more severe outcomes (1), population-based estimates of mortality by race and ethnicity are often lacking, particularly for Asian and Hispanic/Latino persons. Among 812 patients in the California Lupus Surveillance Project (CLSP) during 2007-2009 (2,3), who were matched to the 2007-2017 National Death Index (NDI), 16.6% had died by 2017. This proportion included persons of White (14.4%), Black (25%), Asian (15.3%), and Hispanic/Latino (15.5%) race/ethnicity. Standardized mortality ratios (SMRs) of observed-to-expected deaths among persons with SLE within each racial/ethnic group were 2.3, 2.0, 3.8, and 3.9, respectively. These findings provide the first population-based estimates of mortality among Asian and Hispanic/Latino persons with SLE. Coordination of robust care models between primary care providers and rheumatologists could ensure that persons with SLE receive a timely diagnosis and appropriate treatments that might help address SLE-associated mortality.

The peptide symporter SLC15a4 is essential for the development of systemic lupus erythematosus in murine models.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease representing a serious unmet medical need. The disease is associated with the loss of self-tolerance and exaggerated B cell activation, resulting in autoantibody production and the formation of immune complexes that accumulate in the kidney, causing glomerulonephritis. TLR7, an important mediator of the innate immune response, drives the expression of type-1 interferon (IFN), which leads to expression of type-1 IFN induced genes and aggravates lupus pathology. Because the lysosomal peptide symporter slc15a4 is critically required for type-1 interferon production by pDC, and for certain B cell functions in response to TLR7 and TLR9 signals, we considered it as a potential target for pharmacological intervention in SLE. We deleted the slc15a4 gene in C57BL/6, NZB, and NZW mice and found that pristane-challenged slc15a4-/- mice in the C57BL/6 background and lupus prone slc15a4-/- NZB/W F1 mice were both completely protected from lupus like disease. In the NZB/W F1 model, protection persisted even when disease development was accelerated with an adenovirus encoding IFNα, emphasizing a broad role of slc15a4 in disease initiation. Our results establish a non-redundant function of slc15a4 in regulating both innate and adaptive components of the immune response in SLE pathobiology and suggest that it may be an attractive drug target.

The effect of smoking on cumulative damage in systemic lupus erythematosus: An incident cohort study.

OBJECTIVES: To investigate the relationship between smoking history and pack-year exposure on the rate of end-organ damage in systemic lupus erythematosus (SLE). METHODS: The SLE incident cohort included patients who met American College of Rheumatology (ACR) 1997 or SLE International Collaborating Clinics (SLICC) 2012 SLE criteria and had rheumatology encounters at a US academic institution (2008-16). The primary outcome was median time to SLICC/ACR damage index (SLICC/ACR-DI) increase or death. Main explanatory variables were smoking status and pack-years. Covariates included age, sex, race, ethnicity, receipt of Medicaid, neighborhood area deprivation index, and baseline SLE damage. Damage increase-free survival was evaluated by smoking status and pack-years using Kaplan-Meier and Cox proportional hazards methods. RESULTS: Patients of Black race and Medicaid recipients were more commonly current smokers (p's < 0.05). Former smokers were older and more likely to have late-onset SLE (54% versus 33% of never and 29% of current smokers, p = 0.001). Median time to SLICC/ACR-DI increase or death was earlier in current or former compared to never smokers (4.5 and 3.4 versus 9.0 yrs; p = 0.002). In multivariable models, the rate of damage accumulation was twice as fast in current smokers (HR 2.18; 1.33, 3.57) and smokers with a >10 pack-year history (HR 2.35; 1.15, 3.64) versus never smokers. CONCLUSIONS: In this incident SLE cohort, past or current smoking predicted new SLE damage 4-5 years earlier. After adjustment, current smokers and patients with a pack-year history of >10 years accumulated damage at twice the rate of never smokers.

Hospitalization in patients with systemic lupus erythematosus at Tawam Hospital, United Arab Emirates (UAE): Rates, causes, and factors associated with length of stay.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a relapsing and remitting multiorgan disease associated with significant morbidity and mortality. The survival rate of patients with SLE has recently improved, which was associated with increased morbidity and hospitalization rates. Therefore, this study aimed to examine the rate and causes of hospitalization in patients with SLE and explore factors associated with increased length of stay (LOS). METHODS: Patients who visited rheumatology clinics (Tawam hospital, United Arab Emirates (UAE)) and fulfilled the American College of Rheumatology (ACR) SLE criteria were identified. Retrospective charts were reviewed to determine previous admissions. Demographic data, reason for hospitalization, duration of hospitalization, intensive care unit (ICU) admission, number of specialist consultations, medications used, and SLE characteristics at time of admission were collected. The hospitalization rate was calculated as the number of hospitalized patients divided by the total number of patients with the disease. We performed multivariable regression analysis for factors associated with increased LOS. RESULTS: A total of 91 patients with SLE (88 women and 3 men) met the inclusion criteria with a mean disease duration of 10.2 years (SD 5.5). A total of 222 admissions were identified, and 66 of 91 patients were admitted at least once. The mean crude hospitalization rate calculated was 29.8%. The primary reason for admission was pregnancy (29%), SLE activity (24%), and infection (20%). When combining primary and secondary reasons, the proportion of admissions due to SLE activity increased to 32%. The mean LOS was 5.9 (SD 6.0) days. About 7% of admitted patients required ICU admission. In multivariable analysis, patients with lupus nephritis, complications during hospitalization, and increased number of specialists consultations and who were admitted to ICU and started new medication were all associated with increased LOS. CONCLUSION: A significant proportion of patients with SLE were hospitalized during their disease course. The hospitalization rate in this study appears to be higher than those reported elsewhere. Disease flare is the leading cause of admission in patients with SLE in this relatively young cohort. Lupus nephritis has been found to be significantly related to longer LOS. Measurements taken to reduce the incidence and severity of flares would likely decrease hospitalization rate and LOS in patients with SLE.

Analysis of trends and causes of death in SLE patients over a 40-years period in a cohort of patients in the United Kingdom.

BACKGROUND: Systemic Lupus Erythematosus (SLE) an autoimmune rheumatic disease with a complex pathogenesis, remains potentially life-threatening. SLE patients have increased morbidity and premature mortality compared to non-SLE patients. The five-year survival rate has improved from <50% in the 1950s to >90% in the 1980s. Lupus patients still have a mortality risk three times that of the general population. OBJECTIVES: To provide a detailed analysis of the causes of death, main characteristics and trends in the management of the deceased SLE patients from the lupus clinic at the University College London Hospital (UCLH); during the past four decades. METHODS: This was a non-interventional, retrospective study based on historical real-world data from paper and electronic records of patients followed up at UCLH. The analysis focused on data collected between 1st January 1978 and 31th December 2018. We collected the: causes of death, duration of disease, key laboratory and clinical parameters and the treatment received. We compared the results from the four decades to ascertain trends in the causes of mortality. All statistical analyses were performed using the Statistical Package for Social Sciences (SPSS), version 22.0. The 95% confidence intervals for the means of data were calculated. RESULTS: 111 SLE patients (15%), died during follow-up. Their median age was 51 years (interquartile range (IQR) = 38-63 years) and the median duration of disease, 15 years (IQR = 8.5-24 years). The main causes of death in the past 40 years were infection (31.7%), cancer (26.7%) and cardiovascular disease (CVD) (21.8%). 93.6% of these patients were immunosupressed. During the 40-year period, there were several therapeutic developments notably the introduction of mycophenolate mofetil (MMF) and rituximab; the latter initially only given to patients when more conventional inmunosupressants had failed, but more recently offered to patients at diagnosis. There was a statistically significant increase in the use of hydroxycloroquine (HCQ), MMF and rituximab. In contrast, the use of Azathioprine (AZA) and steroids, hardly changed over time. CONCLUSIONS: This retrospective review shows how epidemiological factors, causes of death and treatment of SLE patients have changed during the last 40 years in the UCLH cohort.

Mortality in SLE patients compared with population controls in Finland in years 2000-2015.

OBJECTIVE: To estimate the risk of mortality in the Finnish incident SLE cohort in a 16-year period compared with the general population. METHODS: Adults with new-onset SLE between 1 January 2000 and 31 December 2014 identified from the national drug reimbursement register and their individually matched controls from the Population Register Centre were followed up until death or 31 December 2015. Data on deaths were retrieved from the national causes of death register. Comorbidities and education were obtained by linkage to the other national registries. RESULTS: A total of 1006 patients with incident SLE and 3005 population controls were found (mean follow-up 8.6 years). Of these, 98 SLE patients subsequently died. Their 5 -, 10-, and 15-year survival rates were 95.0% (95% CI: 93.3, 96.2), 88.8% (86.2, 91.0), and 82.1% (77.6, 85.8), respectively. Crude hazard ratio (HR) was 1.61 (95% CI: 1.26, 2.06), adjusted for education level was almost the same 1.61 (95% CI: 1.26, 2.05). After adjustment for comorbidities and education at baseline, the difference in mortality disappeared: HR 1.14 (95% CI: 0.88, 1.48). The leading causes of death were cardiovascular diseases (CVDs) (33%), malignancies (27%) and neurological diseases (10%). Subhazard ratio for CVD deaths was 1.28 (95% CI: 0.85, 1.93), adjusted for comorbidities and education 0.88 (95% CI: 0.56, 1.39). CONCLUSIONS: These results suggest that the increased mortality in SLE patients is highly associated with comorbidities present at diagnosis. This underlines the importance to screen and treat comorbidities and disease actively without delays.

Mortality, causes of death and influence of medication use in patients with systemic lupus erythematosus vs matched controls.

OBJECTIVES: We wanted to estimate the magnitude of the risk from all-cause, cause-specific and sex-specific mortality in patients with SLE and relative risks compared with matched controls and to evaluate the influence of exposure to medication on risk of mortality in SLE. METHODS: We conducted a population-based cohort study using the Clinical Practice Research Datalink, Hospital Episode Statistics and national death certificates (from 1987 to 2012). Each SLE patient (n = 4343) was matched with up to six controls (n = 21 780) by age and sex. Cox proportional hazards models were used to estimate overall and cause-specific mortality rate ratios. RESULTS: Patients with SLE had a 1.8-fold increased mortality rate for all-cause mortality compared with age- and sex-matched subjects [adjusted hazard ratio (HR) = 1.80, 95% CI: 1.57, 2.08]. The HR was highest in patients aged 18-39 years (adjusted HR = 4.87, 95% CI: 1.93, 12.3). Mortality rates were not significantly different between male and female patients. Cumulative glucocorticoid use raised the mortality rate, whereas the HR was reduced by 45% with cumulative low-dose HCQ use. Patients with SLE had increased cause-specific mortality rates for cardiovascular disease, infections, non-infectious respiratory disease and for death attributable to accidents or suicide, whereas the mortality rate for cancer was reduced in comparison to controls. CONCLUSION: British patients with SLE had a 1.8-fold increased mortality rate compared with the general population. Glucocorticoid use and being diagnosed at a younger age were associated with an increased risk of mortality. HCQ use significantly reduced the mortality rate, but this association was found only in the lowest cumulative dosage exposure group.