Mortality In Systemic Lupus Erythematosus Research Articles

Association of antimalarial drugs with decreased overall and cause specific mortality in systemic lupus erythematosus.

To evaluate the association and dose-response pattern between antimalarial drugs and overall and cause specific mortality in SLE patients. Medical records including information on HCQ/chloroquine (CQ) prescription were extracted from Jiangsu Lupus database. The database was designed to collect data from SLE patients that first-hospitalized during 1999-2009 in Jiangsu province, China, and a follow-up for survival status was performed in 2010 and 2015. Cox and restricted cubic spline models were used to estimate the hazard ratio and 95% CI. We identified 221 deaths among 2446 SLE patients in total. Compared with non-users, decreased overall mortality was associated with either HCQ or CQ users, with adjusted hazard ratio (95% CI) of 0.49 (0.35, 0.67) and 0.49 (0.27, 0.87), respectively. The association between HCQ/CQ and overall mortality was similar across subgroups, such as patients with comorbidities and organ involvements. Interestingly, both the time and the daily dosage of HCQ/CQ use were related to decreased mortality of SLE in a linear dose-response relationship. In cause specific analyses, HCQ/CQ was inversely associated with death from renal insufficiency and other organ (cardiopulmonary, gastrointestinal and haematological) involvements, with adjusted hazard ratio (95% CI) of 0.23 (0.09, 0.55) and 0.25 (0.10, 0.62), respectively, yet it was not significantly associated with mortality from infection and neuropsychiatric involvements. Antimalarial drugs were associated with lower risk of SLE mortality, especially renal insufficiency- and other organ involvement-related death. The protective effects for survival might be augmented by adherence and full dosage of these drugs.

Persistent Bacteriuria and Antibodies Recognizing Curli/eDNA Complexes From Escherichia coli Are Linked to Flares in Systemic Lupus Erythematosus.

Infections contribute to morbidity and mortality in systemic lupus erythematosus (SLE). Uropathogenic Escherichia coli (UPEC) are known to trigger urinary tract infections (UTIs) and form biofilms, which are multicellular communities of bacteria that are strengthened by amyloids such as curli. We previously reported that curli naturally form complexes with bacterial extracellular DNA (eDNA), and these curli/eDNA complexes induce hallmark features of lupus in mouse models. The present study was undertaken to investigate whether anti-curli/eDNA complex antibodies play a role in the pathogenesis of SLE or development of flares in SLE. In total, 96 SLE patients who met at least 4 Systemic Lupus International Collaborating Clinics disease criteria were investigated. Anti-curli/eDNA complex antibodies in the plasma were tested for both IgG and IgA subclasses. Results were compared to that in 54 age-, sex-, and race/ethnicity-matched healthy controls. Correlations of the levels of anti-curli/eDNA antibodies with clinical parameters, lupus disease status, and frequency of bacteriuria were assessed. Anti-curli/eDNA antibodies were detected in the plasma of SLE patients and healthy controls, and their levels correlated with the presence of asymptomatic persistent bacteriuria and occurrence of disease flares in lupus patients. Persistent bacteriuria contained curli-producing UPEC, and this was associated with an inflammatory phenotype. Finally, curli/eDNA complexes cross-reacted with lupus autoantigens, such as double-stranded DNA, in binding autoantibodies. These results suggest that UTIs and persistent bacteriuria are environmental triggers of lupus and its flares. Antibodies against curli/eDNA could serve as a sign of systemic exposure to bacterial products in SLE.

EP16 Challenges in treating new onset systemic lupus erythematosus with lupus nephritis and COVID-19 infection overlap

Case report - IntroductionCOVID-19 infection caused by a novel coronavirus SARS-coV-2 has made the diagnosis and the treatment of inflammatory diseases incredibly challenging. On the one hand, because of its pro-inflammatory state, that may aggravate or trigger flares in autoimmune diseases such as systemic lupus erythematosus (SLE). On the other hand, the risk of an immunosuppressive therapy during the active phase SARS-coV-2 infection that may lead to catastrophic outcomes. We report a case of a 24-year-old female newly diagnosed with SLE during COVID-19 pandemic who developed COVID-19 infection during her induction treatment for lupus nephritis.Case report - Case descriptionA 24-year-old Nepali female, with no past medical history of note, presented to her regional hospital with a history of flu-like symptoms few days ago, peripheral oedema, acute kidney injury with proteinuria and hypertension. Further investigations showed a high titre of double-stranded DNA antibodies, anti-cardiolipin IgM and B2 microglobulin positive and low C3. She also developed a haemolytic anaemia and thrombocytopenia during her admission. She received pulsed steroid therapy and was started on mycophenolate mofetil (MMF) for a probable lupus nephritis awaiting the results of biopsy, which showed later a lupus nephritis Class IV-G with active lesions. She then developed symptoms of COVID-19 infection and had a positive PCR leading to an interruption of her induction therapy. She was recruited to the RECOVERY trial on the lopinavir-ritonavir arm and made a good recovery.Case report - DiscussionIt is well known that viruses can trigger or aggravate auto-immune response in patients predisposed genetically. However, the role of SARS-coV-2 is not elucidated yet. The EULAR COVID-19 registry showed that rheumatoid arthritis and SLE were the most prevalent rheumatic diseases, and there was an increased risk in those who are on moderate to high dose corticosteroids. In patients with SLE and COVID-19 infection, it is agreed by all the national and international rheumatology societies to interrupt their immunosuppressive therapy until the symptoms resolve, especially those with renal involvement or an active disease. Which is the case in our patient. Luckily, she resumed her MMF a month later after a negative PCR and her renal function has continued to improve.Case report - Key learning pointsLupus nephritis is a major risk factor for overall morbidity and mortality in SLE. It requires an early immunosuppressive treatment to induce remission.Randomized clinical trials showed that MMF is at least equally effective as cyclophosphamide in inducing remission and that it has been associated with a reduced risk of infection and amenorrhea. It seems to be a suitable alternative in women of childbearing age. In patients with concomitant COVID-19 disease, immunosuppressive therapy should be paused until the symptoms improve.

Trends in mortality from lupus in Spain from 1980 to 2018.

Recent studies suggest that Systemic lupus erythematosus (SLE) mortality rates in Spain are decreasing. However, SLE mortality in Spain has been poorly studied. The purpose of study is to assess the temporal trends of mortality rates in the Spanish population with SLE from 1980 to 2018. Death records and mid-year population data were collected from the National Statistics Institute. Age-standardized mortality rates were calculated for overall population and for each sex and age group. Significant changes in mortality trends were identified by Joinpoint regressions. Also, an Age-period-cohort (APC) and Potential Years of Life Lost (PYLL) analysis was carried out to know the burden of SLE disease. The overall SLE mortality rates in Spain has experimented an increased through the last 39 years. Mortality rates from the period 1980-1984 was 0.83 per 1.000.000 inhabitants, reaching the value to 1.77 cases per 1.000.000 from the period 2014-2018. A decreasing trend has been observed since 1999. SLE mortality rate has increased in Spain between 1980 and 1999, with a sustained decrease up to our days.

Laboratory-confirmed bloodstream infection in systemic lupus erythematosus: Risk profiling and short-term mortality.

To delineate laboratory-confirmed bloodstream infection (LCBI), analyze risk factors for its occurrence and predictors for its short-term mortality in systemic lupus erythematosus (SLE) patients.Methods A single center, retrospective, case-controlled study was performed in 159 SLE patients (2013-2019) to identify risk factors of LCBI by comparing patients with LCBI (n = 39) to those without infection (n = 120). The predictors associated with 30-day mortality in LCBI patients were also analyzed. Altogether 40 bacteria strains were isolated in 39 LCBI patients with a predominance of the gram-negative bacilli (24 strains, 60.0%). Escherichia coli and Staphylococcus aureus were the leading Gram-negative and Gram-positive microorganisms, respectively. Occurrence of LCBI was independently predicted by: SLE disease duration >4 years, SLEDAI score >4 points, glucocorticoids dose >7.5 mg/d and the previous or concomitant occurrence of autoimmune hemolytic anemia (AIHA) or thrombotic microangiopathy (TMA). Based on the identified risk factors, we developed a matrix model for the risk of future LCBI. The 30-day mortality (39 cases) was 23.1% and healthcare-associated LCBI was a predictor for 30-day mortality in SLE patients compared with community-acquired LCBI. Longer duration, higher disease activity and glucocorticoids dose, and occurrence of AIHA or TMA were risk factors of LCBI in SLE and its poor short-term prognosis may attribute to healthcare-associated LCBI.

Bronchoalveolar lavage fluid analysis and mortality risk in systemic lupus erythematosus patients with pneumonia and respiratory failure.

Our aim was to characterize etiologic diagnoses obtained from bronchoalveolar lavage fluid (BALF) and blood specimens, and to identify risk factors for mortality in systemic lupus erythematosus (SLE) patients with pneumonia and respiratory failure. We conducted a retrospective analysis of SLE patients with pneumonia and respiratory failure. Clinical characteristics, laboratory profiles, and microbiology in BALF and blood samples were evaluated. We performed univariable analyses to identify mortality risk factors. All 24 patients (F:M=21:3, median age 46.5 years; disease duration 11 years) received mechanical ventilation (median duration: 11 days). Pathogens identified in BALF included Pneumocystis jiroveci (12 patients [50%]), cytomegalovirus (CMV, 7 patients [29.2%]), and bacteria (11 patients [45.8%]). Thirteen patients (54.2%) yielded pathogens in blood (CMV in 8 patients [33.3%] and Escherichia coli in 5 patients [20.8%]). Eight developed septic shock, and 9 died within 30 days. Univariable analysis identified thrombocytopenia (odds ratio [OR]: 8.0, 95% confidence interval [CI]: 1.23-52.25), bacteremia within 30 days before or after endotracheal intubation (OR: 8.0, 95% CI: 1.23-52.5), and P. jiroveci pneumonia (PJP, OR: 7.0, 95% CI: 1.04-46.95) as risk factors for 30-day mortality. Kaplan-Meier analysis confirmed an increased risk of 30-day mortality with thrombocytopenia and bacteremia. There are high prevalence rates of PJP and CMV infections as evidenced by BALF analyses in SLE patients with pneumonia and respiratory failure. BALF analysis can facilitate rescue therapy per pathogen. Thrombocytopenia, bacteremia, and PJP in SLE patients can increase their 30-day mortality, so warrant early and aggressive treatments.

Five-Year Follow-Up of Coronary Microvascular Dysfunction and Coronary Artery Disease in Systemic Lupus Erythematosus: Results From a Community-Based Lupus Cohort.

The present study was undertaken to investigate prospective change in the prevalence of coronary microvascular dysfunction (CMD) and obstructive coronary artery disease (CAD) in a cohort of subjects with systemic lupus erythematosus (SLE) initially evaluated for anginal chest pain (CP). Prior work documented a relatively high prevalence of CMD in the absence of obstructive CAD in subjects with SLE. Twenty female SLE subjects with CP who underwent stress cardiac magnetic resonance imaging (CMRI) and coronary computed tomography angiography at baseline were reevaluated at 5 years. Seventeen subjects (85%) were available and reenrolled, of which 11 (65%) had persistent CP at follow-up. Fourteen subjects had complete follow-up CMRI, of which 36% (n = 5) demonstrated CMD at follow-up. Further, 25% (1 of 4) of the originally abnormal myocardial perfusion reserve index (MPRI) findings at baseline were lower at follow-up, while 2 additional abnormal MPRI findings at follow-up were noted in previously normal MPRI results. The prevalence of CMD and nonobstructive/obstructive CAD both was unchanged between baseline and follow-up, respectively (both P values not significant). During follow-up, 33% of subjects (5 of 15) had adverse cardiac outcomes, including pericarditis, unstable angina, or intracranial aneurysm clipping procedure. At the 5-year follow-up of SLE subjects with CP who were evaluated at baseline and follow-up, a majority had persistent CP, and nearly one-half had similar or worse myocardial perfusion consistent with CMD without obstructive CAD. These findings propose an alternative explanation for CP in SLE subjects compared to the more common SLE-related accelerated obstructive CAD accounting for CP and adverse outcomes. These findings support further studies of CMD as an etiology for cardiac morbidity and mortality in SLE.

AB1332-HPR ASSESSING THE PATIENT EXPERIENCE OF LUPUS NEPHRITIS: DEVELOPMENT OF A CONCEPTUAL MODEL AND REVIEW OF EXISTING PATIENT-REPORTED OUTCOME (PRO) MEASURES

Background:Lupus nephritis (LN) is an autoimmune disease characterized by inflammation of the kidneys as a result of systemic lupus erythematosus (SLE). Approximately 50% of SLE patients will develop LN, which is considered to be one of the most severe manifestations of SLE and the leading cause of morbidity and mortality in SLE. While there is ample existing evidence on disease experience and PROs used in extra-renal SLE, little research has been done in LN. Qualitative interviews with patients can help identify concepts that are both important and relevant to the patient. In order to effectively evaluate treatment benefit, it is critical that PRO measures used to assess such concepts and define clinical trial endpoints are fit for purpose and have strong evidence of content validity in the specific context of use.Objectives:The objective of this study was to understand the patient experience of LN and to identify and characterize the signs and symptoms of LN and their impact on health-related quality of life (HRQoL) through the development of a disease-specific conceptual model. This model was then used to evaluate the content validity of existing PRO measures available for use in LN.Methods:A structured literature search was conducted in Medline, Embase and PsycINFO to identify qualitative research articles documenting the patient experience of LN. PRO measures developed or commonly used to assess patient experiences of LN were also identified. Semi-structured concept elicitation interviews were conducted with 15 adult patients in the US with a clinician-confirmed diagnosis of LN (defined in accordance with established clinical guidelines). Supplementary qualitative data were also collected from a review of publicly available online blogs/forums. Findings were used to inform the development of a conceptual model detailing the impact of LN signs, symptoms and HRQoL and evaluate the validity of existing measures used within LN.Results:Searches revealed a paucity of qualitative research conducted with LN patients, supporting the need for prospective research in LN. Consistent with existing literature in SLE, the core signs and symptoms identified from the qualitative literature review, interviews and blog/forum review included joint pain, fatigue, joint stiffness, swelling (particularly in the extremities) and skin rashes. LN patients also reported urinary frequency, urgency, foamy urine and blood in their urine. Disease impact on physical functioning, activities of daily living, emotions, social life, work/finances and sleep were reported. PRO measures commonly used to evaluate patient experiences in LN included the SF-36, LupusQOL, LupusPRO, SLE Symptom Checklist, KDQoL and KSQ. Conceptual mapping of instruments against the newly developed conceptual model (Figure 1) highlighted that no single measure provides a comprehensive assessment of all symptoms/impact important to LN patients. Furthermore, items are largely focused on impact of symptoms with few items on symptom severity.Figure 1.Conceptual model of lupus nephritis symptoms and associated impactsConclusion:The presentation of signs and symptoms in LN patients appears similar to those reported in extra-renal SLE populations, with the addition of swelling and urinary symptoms. Qualitative research with LN patients guided the development of a comprehensive LN conceptual model outlining the disease experience from the patients’ perspective. These insights can be useful to inform PRO measurement strategies for clinical trials in LN.Acknowledgments:With thanks to Dr. Betty Diamond and Dr. David Wofsy for their collaboration and helpful insightsDisclosure of Interests:Pamela Berry Employee of: Janssen, Kate Burrows Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract, Rebecca Hall Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract., Adam Gater Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract, Helena Bradley Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract, Amy Ward Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract, Chloe Tolley Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract, Patricia Delong Employee of: Janssen, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC

SAT0221 FACTORS AFFECTING MORTALITY OF SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS IN SPAIN IN THE 21ST CENTURY: DATA FROM THE RELESSER REGISTRY

Background:The mortality in Systemic Lupus Erythematosus (SLE) varies largely across different countries most probably due to social, healthcare and ethnic differences.Objectives:To analyze the causes and identify predictive factors of mortality of SLE in Spain in the present century.Methods:We performed a cross-sectional and retrospective study analyzing data from the RELESSER cohort (Spanish Registry of Systemic Lupus Erythematosus of the Spanish Society of Rheumatology). We included all patients diagnosed with SLE since the year 2000 and recorded sociodemographic, clinical and serological variables, comorbidities and treatments, as well as indicators of disease activity, damage and severity. The characteristics of the deceased patients were compared with those of the survivors, and variables with clinical significance or statistical significance were grouped into multivariate models to determine which ones were independently associated with the outcome of the disease.Results:A total of 2004 patients were included, 88.6% female, the mean age at diagnosis was 38.3 (± 15.3) years, with a mean delay in diagnosis of 28.9 (± 52.6) months. Up to 2.84% of the individuals had died. The leading cause of death was SLE activity (n=16), followed by infections (n=14), vascular events (n=7) and cancer (n=6). The mean age of death was 54.68 (± 20.13) years, and neither age, sex nor delay in diagnosis was independently associated with mortality. The presence of nephritis, depression, severe infections, organ damage (SLICC/ACR DI) or disease activity (SLEDAI), as well as the use of cyclophosphamide, rituximab or high doses of corticosteroids, were predictors of mortality in our cohort. Antimalarial treatment and skin manifestations were linked to improved survival.Conclusion:In the RELESSER cohort, clinical factors, co-morbidities, as well as therapeutic attitudes were associated with a significant increase in mortality in SLE. Interestingly, depression was independently associated to mortality. The activity of the disease and infections continue to be the main causes of death at the beginning of the 21st century amongst our patients.Disclosure of Interests:Clara Moriano: None declared, Jaime Calvo Grant/research support from: Lilly, UCB, Consultant of: Abbvie, Jansen, Celgene, Iñigo Rua-Figueroa: None declared, Elvira Diez Alvarez: None declared, Cristina Bermúdez: None declared, Francisco J López-Longo Grant/research support from: AbbVie and GSK, Speakers bureau: AbbVie, Actelion, Bristol Myers Squibb, GSK, MSD, Pfizer, Roche, and UCB Pharma, María Galindo-Izquierdo: None declared, Alejandro Olive: None declared, Eva Tomero Muriel: None declared, Antonio Fernandez-Nebro: None declared, Mercedes Freire González: None declared, Olaia Fernández- Berrizbeitia: None declared, Ana Pérez Gómez: None declared, Esther Uriarte Isacelaya: None declared, Carlos Marras Fernandez Cid: None declared, Carlos A. Montilla-Morales: None declared, Gregorio Santos Soler: None declared, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD, M. Rodíguez-Gómez: None declared, Paloma Vela-Casasempere: None declared, Alina Boteanu: None declared, J. Narváez: None declared, Victor Martinez Taboada: None declared, Blanca Hernández-Cruz Speakers bureau: Abbvie, Lilly, Sanofi, BMS, STADA, José Luis Andreu: None declared, José A Hernandez Beriain: None declared, Lorena Expósito: None declared, Raúl Menor-Almagro: None declared, Mónica Ibañez Barceló: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, Carles Galisteo: None declared, Enrique Raya: None declared, Víctor Quevedo Vila: None declared, Tomas Vazquez Rodriguez: None declared, Jesus Ibañez: None declared, Jose M Pego-Reigosa: None declared

MO007A PHASE 1B MULTIPLE ASCENDING-DOSE STUDY OF A CD6 TARGETED THERAPY, ITOLIZUMAB, IN SUBJECTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS WITH OR WITHOUT ACTIVE PROLIFERATIVE LUPUS NEPHRITIS

Abstract Background and Aims Lupus nephritis (LN) is a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. T cells are believed to play a central role in the pathogenesis of both SLE and LN. CD6 is a co-stimulatory receptor, predominantly expressed on T cells, that binds to activated leukocyte cell adhesion molecule (ALCAM), a ligand expressed on antigen presenting cells and various epithelial and endothelial tissues. The CD6-ALCAM pathway plays an integral role in modulating T cell activation, proliferation, differentiation and trafficking, and is central to immune mediated inflammation. Itolizumab (EQ001) is a humanized IgG1 monoclonal antibody that binds CD6, blocks the interaction between CD6 and ALCAM, and inhibits both the activation and trafficking of T cells. Inhibiting the CD6-ALCAM pathway with itolizumab potentially represents a promising therapeutic approach for the treatment of LN. The aim of this study is to assess the safety and tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of subcutaneously administered itolizumab in patients with SLE with and without active proliferative lupus nephritis (apLN). Method This cohort-based dose escalation study includes two types of patients: The Type A cohort will enroll ∼24 patients with SLE without apLN (all treated with itolizumab) and the Type B cohort will randomize in a blinded manner ∼36 patients (3:1, itolizumab:placebo) with biopsy-proven ISN/RPS class III or IV (+ V) apLN who have had inadequate response to induction and/or post-induction maintenance treatment, exhibiting urine protein to creatinine ratio [UPCR] ≥1 g/g and active serology. Within both the Type A and Type B cohorts, up to 4 dose groups will be tested (Figure). Background treatments for SLE or LN are allowed. Following 4 weeks of treatment in a new higher dose Type A cohort and recommendation by an independent safety data review committee (DRC), the dose studied in the Type A cohort may then be studied in a Type B Cohort for a 12-week treatment duration (Figure). The primary endpoint is the safety and tolerability of itolizumab. Efficacy endpoints (in the Type B cohorts) include UPCR, estimated glomerular filtration rate, prednisone dose requirements, renal response, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), FACIT Fatigue Scale, serologic markers, and other patient reported outcomes. In Type A cohort patients, clinical responses and pharmacologic activity will be assessed based on changes in serologic markers, SLEDAI-2K, FACIT Fatigue Scale. Pharmacodynamic markers, including markers that may allow future risk stratification, urinary ALCAM and CD6, will be examined in both cohort types. Results The study is ongoing. Six patients have been enrolled in Type A Cohort 1 (0.4 mg/kg dose) and completed both treatment and 4 weeks of post-treatment follow-up. The mean age was 59.5 (12.9) years, 100% were female; 67% were Hispanic/Latino; and 50% were White, and 50% were Black. Duration of SLE ranged from 3 years to 31 years. Concomitant medications for lupus included prednisone (83%, dose range 2.5 mg – 10 mg), methotrexate (33%), and anti-malarials (33%). Baseline SLEDAI-2K (mean 7.5 [2.2]) was based on findings of alopecia (83%); arthritis (67%); mucosal ulcers and rash (50% each); fever, increased dsDNA, and low complement (17% each). There were no adverse events. Additional data from this ongoing study will be presented. Conclusion Itolizumab, a monoclonal antibody blocking the CD6-ALCAM pathway, is a novel experimental treatment for LN. This is the first trial of itolizumab in patients with SLE and apLN. Data from the first cohort of patients suggest that the drug is safe and well-tolerated at a dose of 0.4 mg/kg over a 4-week treatment period. Additional cohorts of patients with SLE and apLN are currently being enrolled.

Assessment of vascular stiffness using different modalities in patients with systemic lupus erythematosus: a case control study

BackgroundCardiovascular disease is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. Accurate risk stratification would require a simple, non-invasive index integrating all traditional and emerging risk factors. Vascular stiffness fulfills these requirements and has better predictive value for cardiovascular events than traditional risk factors in hypertensives and patients with coronary artery disease. Our aim was to determine whether arterial stiffness is increased in SLE patients compared to healthy controls and to correlate the arterial stiffness in SLE patients with cardiovascular risk factors, namely, hypertension and diabetes mellitus.ResultsThis study included 50 SLE patients and 50 age- and gender-matched healthy individuals. SLE patients had higher median aortic stiffness index (SI) and lower strain and distensibility, compared to controls (p value for all < 0.001). SLE patients had significantly impaired flow-mediated dilation (FMD) compared to controls: the median (range) in SLE patients was 8.82 (2.5–21.87), compared to 19 (12–37.5) in controls (z = − 7.695, p ˂ 0.001). Regarding quality arterial stiffness (QAS) parameters, SLE patients had significantly lower median carotid distension, distensibility coefficient, and compliance coefficient, with higher median carotid SI, carotid pulse wave velocity (PWV), and augmentation index (AI), compared to controls (p value for all ≤ 0.001). SLE patients had a higher median cf-PWV 6.5 m/s (4.8–11.8), compared to a median of 4.6 m/s (3.8–6.9) in controls (z = − 8.193, p ˂ 0.001). Linear regression analysis to adjust for hypertension and diabetes mellitus yielded a statistically significant difference between both groups for all of the above parameters (p = 0.014 for maximum carotid intima media thickness (IMT) and < 0.001 for remaining parameters), with the exception of the maximum carotid augmentation index (p = 0.184).ConclusionSLE patients have significantly increased arterial stiffness and impaired FMD compared to healthy controls. This is true even after adjusting for hypertension and diabetes mellitus, highlighting the fact that SLE could be an independent cardiovascular risk factor. These findings emphasize the need for early management of SLE together with aggressive risk factor modification.

Association between organ damage and mortality in systemic lupus erythematosus: a systematic review and meta-analysis

ObjectiveAt least half of patients with systemic lupus erythematosus (SLE) develop organ damage as a consequence of autoimmune disease or long-term therapeutic steroid use. This study synthesised evidence on the...

The association between adipokines and stigmata of atherosclerosis in patients with systemic lupus erythematosus

Aim of the workEarly cardiovascular disease is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE). The study was designed to assess the relationship between the serum levels of adipokines and atherosclerotic risk factors in SLE patients. Patients and methods56 patients and 31 control were included. Serum levels of leptin, adiponectin, traditional and new risk factors for atherosclerosis including plasma glucose levels, lipid profile, high-sensitivity C-reactive protein (hs-CRP), vascular cell adhesion molecule-1 (VCAM-1) and homocysteine were measured. The intima-media thickness (IMT) of the carotid was measured by ultrasonography. The SLE disease activity index (SLEDAI-2k) was assessed. ResultsThe patients mean age was 30.8 ± 9.9 years, disease duration was 55.7 ± 59.3 months and were 54 (91.5%) females and 5 (8.5%) males. Serum adiponectin levels were significantly lower in patients (3.58 ± 0.4 ng/ml) compared to control (3.9 ± 0.26 ng/ml) (p < 0.001) while leptin levels were comparable. Serum adiponectin levels correlated with triglyceride (r = 0.3, p = 0.003) and high-density lipoprotein (HDL) (r = 0.2, p = 0.04). Serum leptin significantly correlated with the BMI and total cholesterol (r = 0.43, p = 0.002 and r = 0.3, p = 0.04 respectively) as well as with the anti-double stranded deoxyribonucleic acid (anti-dsDNA) (r = 0.28, p = 0.04). There was lack of a meaningful relationship between serum adiponectin and leptin levels and disease duration or risk factors such as hsCRP, VCAM, homocysteine and IMT as well as with the SLEDAI-2k or complement. ConclusionsSerum adiponectin levels inversely correlate with HDL. A significant correlation of leptin with BMI and total cholesterol was found in SLE. None of the two adipokines were associated with atherosclerosis as assessed with the carotid IMT or with the disease activity.

In-hospital mortality in patients with systemic lupus erythematosus: a study from Jordan 2002-2017.

We aimed to study the mortality among hospitalized patients with systemic lupus erythematosus (SLE). We performed a retrospective cross-sectional study and identified patientswithSLEwho were hospitalized at Jordan University Hospital (JUH) between 2002 and 2017.There were 990 admissions among which 283 were SLE patients. The mean age at disease onset was 34 ± 12.5years and the female to male ratio was 8.4:1. Forty patients died during the 15-year period. In-hospital case fatality was 14% over 15years. For the deceased patients, the female to male ratio was 3.4:1, mean age at disease onset was 27.8 ± 11.5years, mean age at death was 35.1 ± 12years, and mean disease duration was 7.5 ± 6.9years. Twenty patients had disease duration ≤ 5years. Infection and SLE-related complication contributed equally to mortality in hospitalized SLE patients (42.5% [CI 27.5%-59%] and 40% [95% CI 25%-56.5%], respectively). Infection related mortality compared to SLE-related mortality was associated with younger age and shorter disease duration (29.5years versus 38.3years and 6.4 versus 8.7years, respectively). CRP was higher in infection related mortality compared to SLE-related mortality (131.4mg/dl versus 87.6mg/dl, respectively). Most SLE-related deaths were secondary to pulmonary disease. Renal disease did not contribute directly to mortality. No fatalities were attributed to cardiovascular disease (CVD) or cancer. Infection and active SLE accounted for the majority of deaths at a young age. Significant pulmonary related deaths may indicate a change in trends in SLE mortality, as renal related mortality is expected to decline due to proper management.

Septicaemia is associated with increased disease activity and mortality in systemic lupus erythematosus: a retrospective analysis from Taiwan.

This study aimed to investigate how septicaemia, non-septicaemia infection and the disease itself are associated with disease activity and mortality in inpatients with systemic lupus erythematosus (SLE) in Taiwan. We retrospectively reviewed 1115 patients and enrolled 427 with SLE admitted for lupus flare-ups and co-morbidities. Disease activity and infection type/site were recorded and categorized according to the causes of admission and mortality into three categories, of which two were specified as follows: (a) septicaemia admissions, non-septicaemia admissions; and (b) septicaemia mortality, non-septicaemia infection mortality and non-infection mortality. The relationships between lupus flare-ups and mortality in different groups were analysed using an unpaired t-test, Mann-Whitney U-test and logistic regression. Septicaemia was the major cause of mortality in SLE inpatients. There were 98 (22.95%) mortality patients among all 427 SLE patients. The septicaemia admissions had higher disease activity (SLE Disease Activity Index 2000 = 13.00 ± 7.98) than the non-septicaemia admissions (9.77 ± 5.72; p < 0.01). The mean current SLEDAI score of the septicaemia mortality group (14.91 ± 8.01) was higher than that of the non-septicaemia infection mortality group (10.05 ± 5.75; p = 0.02), in spite of the similar mean earlier SLEDAI score. The risk of mortality in the septicaemia mortality group due to previous septicaemia admissions was 13.2 times (odds ratio) higher than in the non-septicaemia infection mortality group and 15.6 times higher than in the non-infection mortality group. Septicaemia relates to increased lupus disease activity and is associated with a greater risk of mortality in the SLE patients than other causes of admission. Fewer previous septicaemia admissions decrease the risk of septicaemia mortality.

Frequency of Cardiovascular Risk Factors in Systemic Lupus Erythematosus: A Case-Control Study in a Department of Internal Medicine in Sub-Saharan Africa

Background: The morbidity and mortality of systemic lupus erythematosus are largely due to accelerated atherosclerosis. This is partly related to the high prevalence of traditional cardiovascular risk factors. The aim of our study was to determine the frequency of these factors in lupus patients compared to a control population in a department of internal medicine. Methods: We realized a case-control study in patients with systemic lupus erythematosus according to ACR criteria in 1997. Patients were matched by age and gender with controls subjects without autoimmune disease. We studied the frequency of traditional cardiovascular risk factors in both populations. The study was done in the department of internal medicine of Aristide Le Dantec teaching Hospital, in Senegal, during the period from August 2017 to December 2018. The statistical analysis was performed with SPSS 23.0 software and the level of significance was retained for a p-value < 0.05. Results: We recruited 100 subjects including 50 patients and 50 controls. The mean age was 33.5 ± 11.3 years in cases and 33.3 ± 11.3 years in controls. Dyslipidemia was significantly associated with systemic lupus erythematosus (p = 0.009). Levels of triglycerides (p < 0.001) and uricemia (p < 0.001) were significantly higher in patients. The level of HDL cholesterol (p = 0.028) was lower in cases. Thus, low HDL cholesterolemia (p = 0.001), hypertriglyceridemia (p < 0.001), and hyperuricemia (p = 0.043) were more common in the cases. Renal failure was associated with systemic lupus erythematosus (p < 0.001). Difference in LDL-cholesterol (p = 0.103), hypertension (p = 1) and metabolic syndrome (p = 1) between cases and controls was not significant. Obesity and overweight were predominant in controls (p = 0.028). Conclusion: Traditional cardiovascular risk factors including dyslipidemia and hyperuricemia were more common in patients. Similarly, renal failure was associated with lupus.

Predictors of cardiac involvement in systemic lupus erythematosus patients

Cardiac involvement is the first cause of mortality in systemic lupus erythematosus (SLE). Echocardiography can be used as a non-invasive tool for the assessment of this involvement. To investigate the cardiac involvement in patients diagnosed with SLE assessed by echocardiography and to study relationship between several factors and cardiac manifestation. An echocardiographic study of 76 patients with diagnosis of SLE between 2005 and 2017. We also collected epidemiological characteristic of population, data related to lupus disease. Patients were assigned into cardiac abnormalities group (40 patients) and non-cardiac abnormalities group (30 patients) and compared to study relations between several factors and cardiac manifestation. Cardiac involvement was found in echocardiography in 52% of patients (40 patients). Echocardiographic findings showed 12 cases (38%) of pericardial effusion. Valvular abnormalities were observed in 19 cases (48%), Myocardium was involved in 5 cases (12.5%). High arterial pulmonary hypertension was reported in 4 cases (10%). Men were more vulnerable to cardiac involvement in lupus, there was significant relationship between disease duration and cardiac abnormalities ( P : 0.04), age was not associated significantly to echocardiographic abnormalities, positive antiphospholipid antibodies (aPL+) was observed in higher frequency in cardiac involvement group with P < 0.01 and especially in valvular anomalies. Echocardiography can be helpful tool for early detection of the cardiac involvement in SLE. Men gender, longer disease duration and a PL+ are to be associated to these cardiac abnormalities.

Korelasi antara kadar serum trigliserida dan nilai carotid intima media thickness pada pasien dengan lupus eritematosus sistemik

Background: Early atherosclerosis and its complications are currently the main problems causing morbidity and mortality in systemic lupus erythematosus (SLE). Early detection and diagnosis of atherosclerosis is performed using ultrasound (USG) B-mode by measuring the mean carotid intima media thickness (CIMT). One of the risk factors of atherogenesis that are still controversy and have not been studied are triglycerides.&#x0D; Objective: This study aimed to determine the correlation between serum triglyceride levels and CIMT mean values in patients with SLE at Sanglah Hospital.&#x0D; Method: Design of the study was an analytic cross sectional study. The inclusion criteria in this study were 12-year-old or better male and female SLE patients, willing to participate in the study by signing informed consent. The exclusion criteria in this study were patients with other autoimmune diseases, diabetes, obesity, end-stage chronic kidney disease, hypertension, malignancy, smokers. Serum triglyceride levels were tested from blood samples and CIMT mean values were measured with B-mode ultrasound.&#x0D; Results: From 54 samples, data characteristics were all females, median of age 31.5 (15-57) years, disease duration 44.5 ± 5.408 months, body mass index 20.48 ± 0.541 kg / m2, serum triglyceride 168.46 ± 17.49 mg / dL and mean CIMT 0,475 (0.28-0.84) mm. Those data were analyzed with Spearman correlation, between serum triglyceride level and mean value of CIMT were r= 0,391 and p= 0,003.&#x0D; Conclusion: Conclusion of this study was that there was a moderate mean correlation between serum triglyceride levels and CIMT mean values ??in patients with SLE in Sanglah Hospital.

Differences in clinical manifestations and increased severity of systemic lupus erythematosus between two groups of Hispanics: European Caucasians versus Latin American mestizos (data from the RELESSER registry).

Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038-2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30-1.66)). SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.

Infectious complications as predictors of adverse outcome in a patient with systemic lupus erythematosus (clinical case)

Systemic lupus erythematosus is a systemic autoimmune disease. Over the past decades, great success has been achieved in its treatment. However, mortality in systemic lupus erythematosus is still high. An adverse outcome may occur because of kidney damage, damage of the nervous system, severe hematological disorders, etc. The factor of unfavorable prognosis is infectious complications. The article presents a prospective clinical observation of a faytal case of severe course of systemic lupus erythematosus. The patient was treated in the rheumatology department of the State Regional Clinical Hospital in Saratov from 2007 to 2014. The presence of high disease activity, multiple system disorders — polyarthritis, lupus nephritis, hepatitis, leukopenia, and recurrent necrotizing cutaneous vasculitis required the administration of high doses of immunosuppressive drugs. The progressive course of the disease, resistance to hormonal therapy, the rapid development of infectious complications made the prognosis for the patient’s life extremely unfavorable. Persistent autoimmune leukopenia was the background condition for the development of complications. We used combined therapy — the oral administration of high doses of glucocorticoids together with intravenous injections (pulse therapy), broad-spectrum antibacterial drugs, intravenous immunoglobulin, drugs that improve tissue trophy and microcirculation. It was possible to decrease the disease activity, and also to restore the functional activity of the patient, to maintain low disease activity for 3 years, to prolong the life of a young patient by 8 years. The adverse combination of high activity of systemic lupus erythematosus with recurrent soft tissue infections caused difficulties for the therapy. Administration of adequate doses of cytostatic and biological agents were impossible due to leukopenia and secondary infection, which led to the death of the patient.