Childhood-onset systemic lupus erythematosus in China, 2016-21: a nationwide study.

BACKGROUND: Childhood-onset systemic lupus erythematosus (SLE) is a complex autoimmune disorder that can lead to serious organ damage. Despite the prevalence of SLE among children in Asian countries, treatment guidelines, prognosis, and clinical decision making for children with SLE are limited by gaps in region-specific epidemiological data. The aim of this study was to analyse epidemiological characteristics of childhood-onset SLE and associated organ involvement and in-hospital mortality in China. METHODS: In this nationwide study, we searched standardised hospital discharge records submitted to the Hospital Quality Monitoring System (HQMS) between Jan 1, 2016, and Dec 31, 2021, for patients with a diagnosis of childhood-onset SLE based on the 2019 American College of Rheumatology or 2012 Systemic Lupus International Collaborating Clinics classification criteria. We selected records for patients aged 18 years and younger containing relevant ICD 10th revision diagnostic codes (specifically M32) among discharge diagnostic codes. We excluded records for patients younger than 5 years, whose SLE diagnosis was presumed to be monogenic lupus, and for patients with overlap syndromes or unidentified sex. Date of diagnosis (equal to the first hospital discharge date), age, organ involvement, intensive care unit (ICU) treatment, and in-hospital mortality were extracted from the records. Incidence rates for 2017, 2018, 2019, 2020, and 2021 were identified with five washout periods ranging from 12 months (Jan 1-Dec 31, 2016) to 60 months (Jan 1, 2016-Dec 31, 2020). Data were stratified by sex, age relative to puberty onset, organ involvement and concurrent infection at time of diagnosis, human development index of region of residence, hospital level, and hospital type. Incidence trends by sex, age relative to puberty onset, and year were derived by joinpoint regression analysis, with 95% CIs calculated by the Poisson exact method. Major organ involvement was assessed according to definitions in the British Isles Lupus Assessment Group 2004 disease activity index. Outcomes of ICU admission after first diagnosis and in-hospital death after ICU admission were analysed in Cox proportional hazards models, with p values and 95% CIs calculated with the parametric method. FINDINGS: Between Jan 1, 2016, and Dec 31, 2021, the HQMS received 134 956 hospital discharge records containing the M32 discharge diagnostic code for patients aged 18 years or younger. 6286 records were excluded, leaving 128 670 records representing 54 338 patients aged 5-18 years; of these, 43 756 patients (36 153 girls and 7603 boys) received their childhood-onset SLE diagnosis on or after Jan 1, 2017. Between Jan 1, 2017, and Dec 31, 2021, the SLE incidence rate was 3·97 (95% CI 3·93-4·01) per 100 000 person-years, with a declining trend during the 5-year period. Joinpoint analysis showed sex-dependent and age-dependent incidence patterns. After a relatively stable incidence rate among prepubertal children aged 5-7 years, the incidence rate increased among peripubertal children aged 8-12 years by 0·92 cases per 100 000 person-years with each 1-year increase in age (p<0·0001). Among peripubertal children aged 8-12 years, girls showed the largest change in incidence rate, with an increase of 1·64 per 100 000 person-years with each 1-year increase in age (p<0·0001), compared with 0·40 per 100 000 person-years with each 1-year increase in age among boys (p=0·013). The organ systems most affected in patients with childhood-onset SLE were the kidneys (56·8%) and the haematological system (27·8%). Among the 2471 patients admitted to the ICU, 213 (9%) of whom died in ICU, the three organ-related risk factors at initial diagnosis that showed greatest association with progression to critical illness were cardiovascular involvement (adjusted hazard ratio 2·50 [95% CI 2·18-2·87]; p<0·0001), neuropsychiatric SLE (2·10 [1·87-2·37]; p<0·0001), and serositis (2·03 [1·78-2·30]; p<0·0001). Other prominent risk factors for progression to critical illness were concurrent infections with Epstein-Barr virus (1·52 [1·16-1·98]; p=0·0020) or fungi (1·49 [1·22-1·83]; p=0·0001). In total, 396 (0·7%) of 54 338 patients with childhood-onset SLE died in hospital; the most common causes of death were pneumonia (146 [37%]), multi-organ dysfunction syndrome (99 [25%]), and renal failure (75 [19%]). Risk of in-hospital mortality was highest among pubertal children (hazard ratio 2·16 [95% 1·14-4·09]) compared with prepubertal children, and risk of ICU admission was highest among prepubertal children (2·95 [2·16-4·03]) compared with postpubertal children. INTERPRETATION: These nationwide data on the epidemiology of childhood-onset SLE in the Chinese paediatric population show for the first time a declining trend in incidence rates, rapid rise in puberty-onset rates, and the distinct involvement of vital organs from disease onset to mortality in China. They underscore the complexity of childhood-onset SLE pathogenesis and emphasise the imperative for stratified precision treatment, informed interventions, and health-care planning for childhood-onset SLE. FUNDING: National Key Research & Development Program of China.

The influence of autoantibody profile, disease manifestations and demographic features on survival in systemic lupus erythematosus: a comparative study.

OBJECTIVE: This study aims to investigate the influence of various clinical and immunological factors, including disease manifestations, autoantibody profile, age, gender, disease duration, and family history of systemic lupus erythematosus (SLE), on patient survival outcomes. METHODS: A comparative analysis was conducted between survivors and non-survivors of SLE. Stepwise logistic regression analysis was employed to evaluate the impact of each variable on mortality, allowing for a nuanced understanding of their respective contributions. RESULTS: A total of 229 patients were included in the study (187 survivors and 42 non-survivors). The median age at disease onset for survivors and non-survivors was 29 and 27.5 years respectively. A higher proportion of men was observed among non-survivors compared to survivors. Subgroup analysis revealed a significant difference in mortality rates between individuals under 22 years and those 22 years or older, with 23.5% and 7.8% mortality rates, respectively (P = 0.042). Moreover, specific clinical factors were found to be associated with increased mortality, including pulmonary arterial hypertension (PAH), anemia, thrombocytopenia, pulmonary disease, and renal disease. Conversely, certain manifestations such as arthritis and alopecia were associated with a reduced risk of mortality. Of particular importance, PAH emerged as the strongest predictor of mortality (OR 37.9, P < 0.012). CONCLUSION: The findings of this study underscore the complex interplay between clinical and immunological factors in influencing survival outcomes in SLE patients. Specifically, the identification of PAH as a key predictor of mortality highlights the importance of comprehensive monitoring, early detection, and timely intervention strategies in the management of SLE patients to improve long-term prognosis.

Prognostic analysis of concurrent Pneumocystis jirovecii pneumonia in patients with systemic lupus erythematosus: a retrospective study.

BACKGROUND: Systemic lupus erythematosus (SLE) has been less deadly since the advent of corticosteroid-sparing medications. SLE patients still have a higher mortality rate than the general population. Infectious disease is reported as one of the major causes of death in patients with SLE. Although bacteria are the most often isolated pathogens from patients with SLE, Pneumocystis jirovecii pneumonia (PJP) is more deadly than bacterial infection. METHODS: We retrospectively enrolled consecutive patients with SLE concurrent with PJP (SLE-PJP) in our center between January 2014 and December 2022. The participants were classified into two groups: survivors and non-survivors. Cox regression models and Kaplan‒Meier survival analyses were conducted to explore prognostic factors for survival. RESULTS: There were 57 patients with SLE (42.0 ± 15.8 years old, 78.9% female) complicated with PJP, 22 (38.6%) of whom died. Compared with the survival group, the non-survival group had more patients with hyperglycemia or diabetes mellitus, invasive ventilation (p < 0.01), respiratory failure, intensive care unit admission, non-invasive ventilation, and hospital-acquired pneumonia (p < 0.05). The non-survival group showed a higher neutrophil percentage, lactate dehydrogenase, D-dimer (p < 0.001), urea, high-sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), and ferritin (p < 0.05). It also had lower minimal albumin, hemoglobin (p < 0.001), immunoglobulin G, complement 3, peripheral lymphocyte count, platelet, NK cell count, and CD4+ T-cell count (p < 0.05). Multivariate analysis indicated that hyperglycemia or diabetes mellitus (HR = 4.25, p < 0.01, 95% CI: 1.51-11.97), thrombocytopenia (HR = 4.22, p < 0.01, 95% CI: 1.63-10.91) and lower complement 3 (C3) (HR = 4.06, p < 0.01, 95% CI: 1.60-10.33) were independent risk factors for the survival of SLE-PJP patients. CONCLUSIONS: The mortality rate of patients with SLE-PJP is still high. Hyperglycemia, decreased C3, and thrombocytopenia are independent survival risk factors.

Trends and disparities in cardiovascular deaths in systemic lupus erythematosus: A population-based retrospective study in the United States from 1999 to 2020.

PURPOSE: This study aimed to analyze two decades of consecutive mortality data to investigate cardiovascular deaths in Systemic Lupus Erythematosus (SLE) across the United States (US), identifying patterns and disparities in mortality rates. METHODS: A retrospective analysis was conducted using mortality data from the CDC WONDER database spanning 1999-2020. ICD-10 codes for diseases of circulatory system (I00-I99) and for SLE (M32) were used to identify cardiovascular-related deaths in SLE among adults aged 25 years and older at the time of death. Age-adjusted mortality rates (AAMRs) per 1,000,000 persons were calculated, and trends were assessed using Average Annual Percentage Change (AAPC) and Annual Percent Change (APC) using Joinpoint. Data were stratified by year, sex, race/ethnicity, and geographical regions. RESULTS: Between 1999 and 2020, cardiovascular-related deaths in SLE accounted for 6,548 deaths among adults aged 25 and older in the US. The overall AAMR for cardiovascular-related deaths in SLE decreased from 1.81 in 1999 to 1.53 in 2020, with an AAPC of -1.00 (95% CI: -1.91 to -0.24, p=0.025). A significant decline occurred from 1999 to 2014 with an APC of -3.20 (95% CI: -5.56 to -2.18; p=0.02), followed by a notable increase of 4.73 (95% CI: 0.41 to 18.29, p=0.23) from 2014 to 2020. Women exhibited higher AAMRs compared to men (women: 2.12, men: 0.53). The AAMR decreased for both men and women, with a steeper decline for men from 1999 to 2014 (APC: -4.85 95% CI: -15.58 to -2.62; p<0.02) compared to women in the same period (APC: -2.81 95% CI: -5.78 to -1.73; p<0.03). The Black cohort had a higher AAMR (3.54 95% CI: 3.37 to 3.70), compared to the White cohort (1.12 95% CI: 1.09 to 1.16). The highest mortality was in the Western region (AAMR: 1.60 95% CI: 1.52 to 1.68). Geographically, AAMRs ranged from 0.62 in Massachusetts to 3.11 in Oklahoma. Metropolitan areas had higher AAMRs than Non-metropolitan areas [(1.41 95% CI: 1.37 to 1.45) vs (1.29 95% CI: 1.21 to 1.37)], with a significant mortality reduction in Metropolitan area from 1999-2020 (AAPC: -1.04 95% CI: -1.95 to -0.28, p=0.0064) compared to Non-metropolitan areas in the same time frame (AAPC: -0.86, 95% CI: -2.43 to 0.33 p=0.152). CONCLUSIONS: This analysis highlights notable differences in mortality rates related to cardiovascular deaths in SLE. The target population was adult patients aged 25 and older in the United States. These results are based on demographic and geographic factors. Initially, there was a considerable decrease, but recently the mortality rates have started to rise. This highlights the importance of patient focused interventions to address disparities and improve health outcomes.

Monoclonal gammopathy in systemic lupus erythematosus is associated with distinctive clinical course, malignancy and mortality rate: a single-centre retrospective cohort study.

OBJECTIVES: Rheumatic diseases were previously associated with increased incidence of monoclonal gammopathy (MG) and its malignant transformation. The present study aimed to investigate the prevalence, malignant transformation risk, clinical correlates and prognostic impact of MG in SLE. METHODS: A retrospective cohort study based on the medical records of n=1039 patients with SLE fulfilling the 1997 American College of Rheumatology (ACR), the 2019 European Alliance of Associations for Rheumatology (EULAR)/ACR and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria managed at two tertiary care departments of the University Hospital (Krakow, Poland) from January 2012 until November 2019. RESULTS: SLE+MG cases were older at SLE diagnosis compared with non-MG SLE controls (53±15 years vs 37±15 years, respectively, p<0.01), had higher rates of lymphopenia, anaemia, haemolysis, serous effusions and interstitial lung disease (all p<0.05), and were more frequently treated with cyclophosphamide (57% vs 28%, p<0.01) or rituximab (13% vs 3%, p<0.01). Most MG cases were detected within a year after SLE diagnosis (Q25, Q75: 0, 12 years). With the median follow-up of 11 years (Q25, Q75: 6, 19 years), 34.8% (8 cases) of the SLE+MG cohort were diagnosed with malignancy, compared with 8.1% (82 cases) among the SLE controls (p<0.001). MG was associated with the relative hazard of death of HR 2.99 (95% CI 1.26 to 7.06, p<0.05) and a median survival time from SLE diagnosis to death of 5 years (Q25, Q75: 1, 14; range 0-41) for SLE+MG cases, as compared with 12 years (Q25, Q75: 6, 19; range 0-62) for the controls. The effect was non-independent on antimalarial medication use. CONCLUSIONS: Our study emphasises heightened malignancy and mortality rates in SLE+MG cases. The association between immunosuppression, MG incidence and progression warrants further research.

Modelling long-term outcomes for patients with systemic lupus erythematosus.

BACKGROUND: New treatments for systemic lupus erythematosus (SLE) aim to improve tolerability and disease activity control over standard of care (SoC) treatment. SoC typically includes daily glucocorticoid (GC) which carries a risk of organ damage over time. This study sought to develop natural history models to identify predictors of long-term outcomes with current SoC SLE treatment. METHODS: Generalized linear and parametric accelerated failure time survival models (GLM) and parametric accelerated failure time (AFT) survival models were designed to identify predictors of disease activity, flare rate, GC use, organ damage, and mortality beyond the first year of treatment in patients with SLE. Models were run using a longitudinal retrospective analysis of prospectively collected Toronto Lupus Cohort (TLC) study data, collected between 1997 and 2020. Covariates of clinical and statistical significance were selected by bivariate- then multi-variate regression to find the model of best fit. FINDINGS: Of the 1255 subjects included, 89 % were female 89 % and 65 % Caucasian. Mean follow-up was 10·5 years. At first visit, 51 % of patients had moderate-to-severe disease activity (SLEDAI-2 K score ≥ 6). Mean organ damage scores gradually increased over the years following diagnosis. Median survival of the cohort was ∼35 years from study entry. In the GLM models, SLEDAI-2 K yearly average, and average GC dose were key for predicting change in SLEDAI-2 K, GC use/ dose, and flare (any/rate). Together, adjusted mean SLEDAI-2 K and GC dose were shown to be predictors of mortality and damage in at least 9 of 12 organ systems considered. INTERPRETATION: These comprehensive, longitudinal, predictive models show that disease activity and GC use are significant predictors of organ damage and mortality in a patient population with predominantly moderate to severe SLE. This deepens understanding of SLE natural history and underscores the need for new treatment approaches that reduce disease activity and GC use with an aim to improve long-term SLE outcomes. FUNDING: This study was funded by AstraZeneca.

Hydroxychloroquine and Chloroquine-Induced Cardiac Arrhythmias and Sudden Cardiac Death in Patients With Systemic Autoimmune Rheumatic Diseases: A Systematic Review and Meta-Analysis.

ABSTRACT: Hydroxychloroquine (HCQ) and chloroquine (CQ) are foundational treatments for several systemic autoimmune rheumatic diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Concerns regarding the risk of cardiac arrhythmia and death have been raised, yet the burden of HCQ and CQ-related cardiac toxicities remains unclear. A systematic literature search was conducted in the MEDLINE and Embase databases for articles published between the earliest date and April 2023 reporting cardiac conduction abnormalities in patients with systemic autoimmune rheumatic diseases taking HCQ or CQ. Meta-analysis was performed to calculate the difference in mean corrected QT (QTc) interval and odds ratio of prolonged QTc interval in those taking HCQ or CQ versus not. Of 2673 unique records, 34 met the inclusion criteria, including 70,609 subjects. Thirty-three studies reported outcomes in HCQ and 9 in CQ. Five studies reported outcomes in RA, 11 in SLE, and 18 in populations with mixed rheumatic diseases. Eleven studies reported mean QTc and OR for prolonged QTc for meta-analysis, all reporting outcomes in HCQ. There was a significant increase in mean QTc (10.29 ms,  P  = 0.458) among HCQ users compared to non-HCQ users in patients with RA. There was no difference in mean QTc between HCQ and non-HCQ users in other systemic autoimmune rheumatic diseases. When rheumatic diseases were pooled, HCQ users were more likely to have prolonged QTc compared to non-HCQ users (odds ratio 1.57, 95% CI, 1.19, 2.08). The results of this study suggest that clinicians should be aware of potential adverse cardiac events of HCQ and consider QTc monitoring for patients on HCQ for the treatment of systemic autoimmune rheumatic diseases.

Mortality in patients with systemic lupus erythematosus: A meta-analysis of overall and cause-specific effects.

OBJECTIVES: Our objective was to assess the overall and cause-specific standardized mortality ratios (SMRs) among patients diagnosed with systemic lupus erythematosus (SLE). METHODS: An exhaustive systematic review was undertaken, encompassing studies that scrutinized SMRs, both overall and for specific causes, in patients diagnosed with SLE compared to the general populace. The databases of PUBMED, EMBASE, and Cochrane were meticulously searched to collate relevant literature. Following this comprehensive search, a meta-analysis was executed to methodically assess all-cause, sex-specific, ethnicity-specific, and cause-specific SMRs in individuals with SLE. RESULTS: The inclusion criteria were met by 29 studies encompassing 72,342 patients with SLE and documenting 7352 deaths. The meta-analysis disclosed a pronounced 2.87-fold elevation in the SMR for all-cause mortality in SLE patients relative to the general population (SMR, 2.866; 95% confidence interval [CI], 2.490-3.242; p < .001). Region-specific assessments showed variable all-cause SMRs, with Europe reporting 2.607 (95% CI, 1.939-3.275; p < .001), Asia revealing 3.043 (95% CI, 2.082-4.004; p < .001), and particularly high SMRs noted in North America and Oceania. Gender-focused analyses presented a pooled SMR of 3.261 (95% CI, 2.674-3.848; p < .001) for females, and 2.747 (95% CI, 2.190-3.304; p < .001) for males. Evaluations specific to cause of death illustrated notably elevated SMRs for renal disease (SMR, 4.486; 95% CI, 3.024-5.948; p < .001), infections (SMR, 4.946; 95% CI, 4.253-5.639; p < .001), cardiovascular diseases (CVD) (SMR, 2.931; 95% CI, 1.802-4.061; p < .001), cerebrovascular accidents (CVA) (SMR, 1.588; 95% CI, 0.647-2.528; p = .001), and cancer (SMR, 1.698; 95% CI, 0.871-2.525; p < .001). CONCLUSIONS: This meta-analysis underscores a significant 2.87-fold elevation in the SMR among patients with SLE compared to the general population, transcending differences in sex or geographical regions. Moreover, an appreciable increase in mortality due to specific causes, including renal disease, infection, CVD, CVA, malignancy, and neuropsychiatric SLE, accentuates the imperative for targeted interventions to mitigate these elevated risks in SLE patients.

Hospitalization and Mortality Due to Infection Among Children and Adolescents With Systemic Lupus Erythematosus in the United States.

OBJECTIVE: We aimed to determine the frequency and types of infections in hospitalized children with childhood-onset systemic lupus erythematosus (cSLE), and to identify risk factors for intensive care unit (ICU) admission and mortality. METHODS: We conducted a retrospective study of youth aged 2 to 21 years using International Classification of Diseases (ICD) codes for SLE assigned during admission to a hospital participating in the Pediatric Health Information System, a database of United States children's hospitals, from 2009 to 2021. Generalized linear mixed effects models were used to identify risk factors for ICU admission and mortality among children hospitalized with infection. RESULTS: We identified 8588 children with cSLE and ≥ 1 hospitalization. Among this cohort, there were 26,269 hospitalizations, of which 13% had codes for infections, a proportion that increased over time (P = 0.04). Bacterial pneumonia was the most common hospitalized infection. In-hospital mortality occurred in 0.4% (n = 103) of cSLE hospitalizations for any indication and 2% of hospitalizations for infection (n = 60). The highest mortality rates occurred with Pneumocystis jirovecii pneumonia (21%) and other fungal infections (21%). Lupus nephritis (LN) and endstage renal disease (ESRD) were associated with increased odds of ICU admission (odds ratio [OR] 1.47 [95% CI 1.2-1.8] and OR 2.40 [95% CI 1.7-3.4]) among children admitted for serious infection. ESRD was associated with higher mortality (OR 2.34 [95% CI 1.1-4.9]). CONCLUSION: Hospitalizations with ICD codes for infection comprised a small proportion of cSLE admissions but accounted for the majority of mortality. The proportion of hospitalizations for infection increased over time. LN and ESRD were risk factors for poor outcomes.

Temporal trends in mortality in patients with systemic lupus erythematosus: a Danish population-based matched cohort study.

OBJECTIVE: Excess mortality has been demonstrated in patients with SLE compared with the general population. We aimed to investigate the 5-year and 10-year all-cause mortality in patients with SLE compared with the general population in recent decades. METHODS: This was a Danish nationwide population-based exposure-matched cohort study. Incident cases of SLE diagnosed between 1996 and 2015 were identified using administrative health registries and followed until 2020, allowing for 5 and 10 years of follow-up. Patients with SLE were matched 1:5 on age and sex with individuals from the Danish general population. Time-to-event analyses were performed using the pseudo-observation approach. RESULTS: In total, 1351 incident cases of SLE and 6755 matched controls were identified. The crude risk difference (RD) for 5-year mortality decreased over the study period, from 10.3% (95% CI 6.5-14.1%) to 4.6% (95% CI 1.4-7.8%) for patients with SLE compared with controls. The relative risk (RR) for 5-year mortality decreased similarly in the same period. Adjustment for comorbidities revealed lower RD and RR for mortality in patients with SLE compared with controls, but the decreasing trend remained. The crude and adjusted RD and RR for 10-year mortality did not change over the calendar period. The 10-year RR was highest in young patients with SLE (<50 years of age). CONCLUSION: The 5-year mortality risk decreased over time for both patients with SLE and matched controls. However, excess 5-year mortality for patients with SLE in the most recent calendar period and excess mortality late in their disease course remained. Continued focus on preventing disease progression and comorbidity is required.

The impact of Libman-sacks endocarditis on inpatient outcomes with systemic lupus erythematosus: A retrospective study.

INTRODUCTION: The existing literature offers limited insights into the influence of Libman-Sacks Endocarditis (LSE) on inpatient outcomes in individuals with Systemic Lupus Erythematosus (SLE). This study aimed to explore the characteristics and prognosis of SLE patients with LSE and the impact of LSE in patients with SLE on inpatient outcomes including inpatient mortality, length of stay, acute heart failure, atrial fibrillation, and cerebrovascular accidents (CVA). METHODS: This study included adult patients who were hospitalized with SLE between the years 2019 and 2020, using the National Inpatient Sample (NIS) database. The total number of patients with a diagnosis of SLE in the years 2019 and 2020 in the NIS database was 150,411. Of those, 349 had a diagnosis of LSE. The study population was divided into two groups: one group with SLE and LSE, and another group with SLE but without LSE. RESULTS: Caucasians made up 54.9% of the patients with a diagnosis of SLE in our patient population, while African Americans made up 26.9% and the Hispanics accounted for 12.2%. Of patients with LSE, Caucasians and African Americans represented 42.9% each. Patients with a diagnosis of LSE had a higher inpatient mortality than those with SLE without LSE (aOR: 9.74 CI 1.12-84.79, p 0.04). Patients with SLE with LSE were more likely to have acute heart failure than those without LSE, although this was not statistically significant (aOR 1.18 CI 0.13-11.07, p 0.88). Similarly, patients with SLE with LSE were more likely to have atrial fibrillation than those without LSE (aOR 4.45 CI: 0.77-25.57, p 0.10). CVAs were significantly higher in SLE patients with LSE than those without LSE (aOR 141.43 CI 16.59-1205.52, p < .01). DISCUSSION: Patients who develop LSE were found to have significantly higher risks of inpatient mortality and cerebrovascular accidents. Early and precise detection of LSE in such patients may ensure timely intervention and prevention of the associated adverse outcomes. Further studies may attempt to develop screening methods for detection of LSE to effectively reduce morbidity and mortality associated with SLE.

In-hospital outcomes and trends of patients with autoimmune diseases undergoing percutaneous coronary intervention: A nationwide analysis.

BACKGROUND: The risk of coronary artery disease is exaggerated in patients with autoimmune diseases (AID). A higher risk of complications has been reported during and after percutaneous coronary intervention (PCI) in these patients. We aimed to analyze the in-hospital outcomes and trends of patients with AID, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD) undergoing PCI. METHOD: We identified all PCI procedures using the National In-patient Sample database from 2016 to 2020. Stratified them into cohorts with RA, SLE and IBD and compared them to cohorts without AID. The Chi-square test and multivariate logistic regression were used for analysis. A p-value <0.005 was considered statistically significant. RESULT: We identified 2,367,475 patients who underwent PCI. Of these, 1.6 %, 0.5 %, and 0.4 % had RA, IBD and SLE respectively. The odds of mortality were lower among patients with IBD (aOR: 0.56; CI 0.38-0.81, p = 0.002) but patients with RA had higher odds of having composite major complications [(MC) including cerebrovascular accident (CVA), cardiac arrest, acute heart failure (AHF), ventricular arrhythmia (VA), major bleeding, and acute kidney injury (AKI)] (aOR: 0.90; CI 0.83-0.98, p = 0.013). Our SLE cohort had higher rates of CVA (p = 0.017) and AKI (p = 0.002). Our cohort with IBD had lower rates of cardiac arrest but had longer hospital length of stay (4.9 days vs 3.9 days) and they incurred higher hospital charges compared to cohort without IBD. CONCLUSION: This study depicts the immediate adverse outcomes observed in patients with AID undergoing PCI. In contrast to those without AID, our cohorts with RA exhibited worse outcomes, as indicated by the higher odds of major complications. IBD is associated with lower risks of in-hospital adverse outcomes but with higher resource utilization.

A large cohort comparison of very late-onset systemic lupus erythematosus with younger-onset patients.

OBJECTIVES: Age has a significant impact on systemic lupus erythematosus (SLE). However, data on very late-onset SLE (vlSLE) are scarce. We have compared the clinical and serological features of vlSLE patients with younger-onset patients. METHODS: We assessed the clinical and laboratory data of all patients fulfilling SLE classification criteria evaluated at a university hospital from 1978 to 2023. Patients were divided into 4 groups according to age at diagnosis: juvenile SLE (jSLE <8 years); adult SLE (aSLE 18-49 years); late SLE (lSLE 50-59 years); vlSLE (≥60 years). RESULTS: 845 patients were enrolled. The jSLE, aSLE, lSLE, and vlSLE groups included 153, 630, 47, and 15 patients, respectively. The vlSLE group tended to have a lower female-to-male ratio (4:1; p=0.282), was mainly Caucasian (93.3%; p<0.001), and had the lowest survival time (20.3 years; p<0.001). vlSLE patients had the lowest prevalence of positive anti-dsDNA antibodies (26.7%; p=0.010) and low C3 levels (13.3%; p<0.001). Although arthritis was less common among vlSLE patients (73.3%; p=0.043), they more commonly developed Sjögren's syndrome (SS 33.3%; p<0.001) and rheumatoid arthritis (RA 13.3%; p<0.001). Infections and malignancy were the main causes of death. CONCLUSIONS: Compared with younger patients, in vlSLE, female predominance is less pronounced. Arthritis, anti-dsDNA antibodies and low C3 levels are less frequent. SS and RA are more common. Despite lower disease activity, vlSLE patients have the lowest survival rate. While uncommon, SLE should not be excluded as a possible diagnosis in the elderly.

The Diagnostic profile and clinical course of patients with rheumatic diseases in the medical intensive care unit.

Background/aim: Immunosuppressive and immunomodulatory treatments developed in recent years as a result of a better understanding of the pathophysiology of systemic rheumatic diseases (SRDs) improve the prognosis. Despite medical advances, individuals with SRDs at any stage may require intensive care and have a high mortality rate. The aim of this study was to investigate the demographic and clinical characteristics of patients with rheumatic diseases admitted to the intensive care unit (ICU), and the factors associated with the risk of mortality. Materials and methods: This was a retrospective, cross-sectional study that included patients with rheumatic diseases in the medical ICU. Factors of ICU 28-day mortality were identified by multiple-variable logistic analysis. Results: A total of 127 patients with SRDs admitted to the medical ICU were enrolled. Systemic lupus erythematosus (SLE) (32.3%) was the most common diagnosis of SRDs in patients admitted to the ICU. The reasons for admission to the ICU were combined infection and primary SRD flare-up (35.4%), primary SRD flare-up (22%), SRD-unrelated reasons (22%), infection (17.3%), drug side effects (3.9%), and SRD-related complications (0.8%). The most common organ dysfunctions before (49.6%) and during (77.2%) admission to ICU were in the respiratory system. The 28-day mortality was 78 (61.4%). While the maximum procalcitonin, serum lactate, and blood urea nitrogen (BUN) levels were higher in the nonsurvivor group, the platelet and serum albumin levels were statistically significantly lower than those in the survivor group (p < 0.05). Acute respiratory failure (ARF), the presence of septic shock, the need for invasive mechanical ventilation (IMV), BUN level, and low platelet-lymphocyte ratio (PLR) were significant in the final multiple-variable model. Conclusion: Significant predictors of mortality in patients with rheumatic diseases may include ARF, septic shock, the need for IMV, and high BUN and low PLR levels.

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.

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.

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.

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.