scholarly journals The Main Challenges in Systemic Lupus Erythematosus: Where Do We Stand?

2021 ◽  
Vol 10 (2) ◽  
pp. 243
Author(s):  
Matteo Piga ◽  
Laurent Arnaud
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Systemic Disease ◽  
Unmet Need ◽  
Clinical Manifestations ◽  
New Drugs ◽  
Systemic Lupus ◽  
Major Step ◽  
Damage Accrual

Systemic lupus erythematosus (SLE) is an immune-mediated multi-systemic disease characterized by a wide variability of clinical manifestations and a course frequently subject to unpredictable flares. Despite significant advances in the understanding of the pathophysiology and optimization of medical care, patients with SLE still have significant mortality and carry a risk of progressive organ damage accrual and reduced health-related quality of life. New tools allow earlier classification of SLE, whereas tailored early intervention and treatment strategies targeted to clinical remission or low disease activity could offer the opportunity to reduce damage, thus improving long-term outcomes. Nevertheless, the early diagnosis of SLE is still an unmet need for many patients. Further disentangling the SLE susceptibility and complex pathogenesis will allow to identify more accurate biomarkers and implement new ways to measure disease activity. This could represent a major step forward to find new trials modalities for developing new drugs, optimizing the use of currently available therapeutics and minimizing glucocorticoids. Preventing and treating comorbidities in SLE, improving the management of hard-to-treat manifestations including management of SLE during pregnancy are among the remaining major unmet needs. This review provides insights and a research agenda for the main challenges in SLE.

Factors predictive of serious infections over time in systemic lupus erythematosus patients: data from a multi-ethnic, multi-national, Latin American lupus cohort

Lupus ◽  
2019 ◽  
Vol 28 (9) ◽  
pp. 1101-1110 ◽  
Author(s):  
V R Pimentel-Quiroz ◽  
M F Ugarte-Gil ◽  
GB Harvey ◽  
D Wojdyla ◽  
G J Pons-Estel ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Latin American ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Hazard Ratio ◽  
Systemic Lupus ◽  
Serious Infections ◽  
Damage Accrual ◽  
Over Time

Aim The aim of this study was to identify factors predictive of serious infections over time in patients with systemic lupus erythematosus (SLE). Methods A multi-ethnic, multi-national Latin American SLE cohort was studied. Serious infection was defined as one that required hospitalization, occurred during a hospitalization or led to death. Potential predictors included were sociodemographic factors, clinical manifestations (per organ involved, lymphopenia and leukopenia, independently) and previous infections at baseline. Disease activity (SLEDAI), damage (SLICC/ACR Damage Index), non-serious infections, glucocorticoids, antimalarials (users and non-users), and immunosuppressive drugs use; the last six variables were examined as time-dependent covariates. Cox regression models were used to evaluate the predictors of serious infections using a backward elimination procedure. Univariable and multivariable analyses were performed. Results Of the 1243 patients included, 1116 (89.8%) were female. The median (interquartile range) age at diagnosis and follow-up time were 27 (20–37) years and 47.8 (17.9–68.6) months, respectively. The incidence rate of serious infections was 3.8 cases per 100 person-years. Antimalarial use (hazard ratio: 0.69; 95% confidence interval (CI): 0.48–0.99; p = 0.0440) was protective, while doses of prednisone >15 and ≤60 mg/day (hazard ratio: 4.18; 95 %CI: 1.69–10.31; p = 0.0019) and >60 mg/day (hazard ratio: 4.71; 95% CI: 1.35–16.49; p = 0.0153), use of methylprednisolone pulses (hazard ratio: 1.53; 95% CI: 1.10–2.13; p = 0.0124), increase in disease activity (hazard ratio: 1.03; 95% CI: 1.01–1.04; p = 0.0016) and damage accrual (hazard ratio: 1.22; 95% CI: 1.11–1.34; p < 0.0001) were predictive factors of serious infections. Conclusions Over time, prednisone doses higher than 15 mg/day, use of methylprednisolone pulses, increase in disease activity and damage accrual were predictive of infections, whereas antimalarial use was protective against them in SLE patients.

Association of serum MIP-1α, MIP-1β, and RANTES with clinical manifestations, disease activity, and damage accrual in systemic lupus erythematosus

2006 ◽  
Vol 26 (5) ◽  
pp. 718-722 ◽  
Author(s):  
Luis M. Vilá ◽  
María J. Molina ◽  
Angel M. Mayor ◽  
José J. Cruz ◽  
Eddy Ríos-Olivares ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Systemic Lupus ◽  
Damage Accrual

Vitamin D Levels are Associated with Disease Activity and Damage Accrual in Systemic Lupus Erythematosus Patients

2020 ◽  
pp. 109980042098359
Author(s):  
María Correa-Rodríguez ◽  
Gabriela Pocovi-Gerardino ◽  
José-Luis Callejas-Rubio ◽  
Raquel Ríos-Fernández ◽  
María Martín-Amada ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Vitamin D ◽  
Disease Activity ◽  
Vitamin D Deficiency ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Systemic Lupus ◽  
Vitamin D Levels ◽  
Damage Accrual ◽  
The Impact

Vitamin D has immunosuppressive properties and is considered a therapeutic option, although there is controversy about the role of this vitamin in the pathogenesis of systemic lupus erythematosus (SLE). We aimed to determine the prevalence of vitamin D insufficiency and deficiency and their potential association with disease activity, damage accrual, SLE-related clinical manifestations, and cardiovascular risk factors in SLE patients. A cross-sectional study of 264 patients was conducted (89.4% females; mean age 46.7 ± 12.9 years). The SLE Disease Activity Index (SLEDAI-2 K) and the SDI Damage Index were used to assess disease activity and disease-related damage, respectively. The mean 25(OH)D value was 25.1 ± 13.0 ng/ml. Eleven patients (4.2%) had 25(OH)D <10 (deficiency) and 178 patients (70.6%) had 25(OH)D <30 (insufficiency). In the 25(OH)D deficiency group, SLEDAI was significantly higher than the insufficiency ( p = 0.001) and normal groups ( p < 0.001). Also, patients with vitamin D deficiency presented significantly higher SDI scores than patients with 25(OH)D insufficiency ( p = 0.033) and 25(OH)D normal levels ( p = 0.029). There is a high prevalence of both vitamin D deficiency and insufficiency in Caucasian SLE patients and this status was associated with higher SLEDAI and SDI scores, supporting the impact of vitamin D levels on disease activity and damage accrual in SLE patients. Longitudinal studies on the relationship between vitamin D status and disease activity and progression are therefore required.

scholarly journals AB0983 LIPID METABOLISM AND DISEASE ACTIVITY IN JSLE PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1785.1-1785
Author(s):  
S. Ganhão ◽  
A. Mendes ◽  
F. Aguiar ◽  
M. Rodrigues ◽  
I. Brito
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lipid Metabolism ◽  
Disease Activity ◽  
Lipid Profile ◽  
Lupus Erythematosus ◽  
Systemic Disease ◽  
Density Lipoprotein ◽  
Systemic Lupus ◽  
Parametric Test ◽  
Bivariate Correlation

Background:Systemic lupus erythematosus (SLE) is an autoimmune systemic disease associated with premature atherosclerosis. Risk factors include dyslipoproteinemia, inflammation, oxidized low-density lipoprotein (LDL), hyperhomocysteinemia and antiphospholipid antibodies. Hyperlipidemic condition is being reported to promote the production of proinflammatory cytokines such as IL-1β, IL-6, and IL-27 and lowering blood lipid levels improves the disease. Oxidative stress is elevated, mainly due to mitochondrial dysfunction, further disrupting lipid metabolism. Some drugs also have an impact on lipid profile, such as chronic steroid use, which worsens LDL, HDL, and TG levels.Objectives:To assess the relationship between lipid profile and disease activity in juvenile SLE (jSLE) patients.Methods:Retrospective study of jSLE patients, fulfilling both 2012 and 2019 EULAR/ACR classification criteria for SLE. Juvenile-onset was defined as age at diagnosis <18 years. Demographics and clinical characteristics were collected. To evaluate the activity of jSLE, the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was used. Statistical analysis was performed with SPSS®. Spearman’s rank non-parametric test or Pearson’s parametric test were used to assess the bivariate correlation for inflammatory and metabolic variables. P value <0.05 was considered significant for all the statistical tests.Results:35 patients were included, with current median (min-max) age of 22 (16-35) years, mean (SD) age of diagnosis of 15.8 (2.4) years; 91.4%female. Median ESR was 19 (2-75) mm/h, CRP 1.65 (0.1-9.6) mg/L, albumin 41.6 (16.7-46.3) g/L, proteinuria 0.2 (0-3) g/dL, leukocyturia 0 (0-1362.7)/uL, erythrocyturia 0 (0-501.9)/uL and anti-double stranded DNA 89.3 (10-800) U/mL. Mean C3 was 102.1 (21.6), C4 17.1 (7.4) mg/dL and creatinine 0.63 (0.1) mg/dL. Median SLEDAI was 2 (0-12). All were ANA positive, 40 % positive for antinucleossome antibodies, 25.7% anti-ribossomal P protein antibody, 11.4% anti-Sm, 8.6% autoantibodies againstβ2-glycoproteinI, 8.6% anti-cardiolipin, 14.3% lupus anticoagulant, 37.1% anti-SSA and 8.6% anti-SSB. Articular manifestations were present in 48.6%, mucocutaneous in 77.1%, haematological in 45.7%, lupus nephritis in 42.9%, serositis in 8.6% and pulmonary interstitial disease in 2.9%. Mean (SD) total cholesterol values (TC) was 165.5 (44.7) mg/dL and LDL 94.5 (29.9) mg/dL. Median high-density lipoprotein was 52 (28-92) and triglycerides (TG) 81.5 (41-253) mg/dL. Median daily prednisolone dose was 5 (0-40) mg. 88.6% were treated with hydroxychloroquine, 31.4% with mychophenolate mophetil and 14.3% with azathioprine. TC was negatively correlated with serum albumin (p=0.043, rho=-378) and positively with SLEDAI (p=0.032; rho= 0.392), proteinuria (p=0.009; rho= 0.469) and leukocyturia (p=0.031; rho= 0.394). A positive correlation was found between LDL and proteinuria (p=0.043; rho= 0.385) and between TG and CRP (p=0.001; rho= 0.575). TG were also positively correlated with prednisolone daily dose (p=0.035; rho= 0.394). Mean LDL was higher in anti-Sm positive patients (p=0.022). No differences were found regarding anti-phospholipids antibodies. Nephritic lupus patients had worse lipid metabolism, but this did not reach statistical significance.Conclusion:In out cohort, increased expression of TC, LDL and TGs is associated with disease activity in SLE. As expected, higher doses of prednisolone also correlated with lipid metabolism.References:[1]Machado D et al. Lipid profile among girls with systemic lupus erythematosus. Rheumatol Int. 2017 Jan;37(1):43-48Disclosure of Interests:None declared

Elevated levels of IL-24 in systemic lupus erythematosus patients

Lupus ◽  
2019 ◽  
Vol 28 (6) ◽  
pp. 748-754 ◽  
Author(s):  
R C Li ◽  
J Guo ◽  
L C Su ◽  
A F Huang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Inflammatory Cytokine ◽  
Activity Index ◽  
Clinical Manifestations ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Good Ability

Objective This study aimed to assess IL-24 levels and their association with clinical manifestations in patients with systemic lupus erythematosus (SLE). Methods There were 75 patients with SLE and 58 healthy controls recruited in this study. Serum levels of IL-24 were measured by enzyme-linked immunosorbent assays, and mRNA levels of IL-24 were tested by quantitative real-time polymerase chain reaction . The area under the curve of the receiver operating characteristic (ROC) curve was used for diagnostic ability of the inflammatory cytokine. Results Serum IL-24 levels were significantly higher in SLE patients than that in healthy controls. SLE patients with nephritis had higher IL-24 levels than those without nephritis. Active SLE patients showed higher expression of IL-24 as compared to less active disease patients. The mRNA levels of IL-24 were much higher in SLE patients. Correlation analysis showed significant correlation between serum IL-24 levels and SLE disease activity index. In addition, ROC analysis may suggest good ability of serum IL-24 in differentiating SLE. Conclusion The inflammatory cytokine correlated with SLE disease activity, and may be involved in this disease pathogenesis.

Disease Damage Accrual and Low Bone Mineral Density in Female Patients with Systemic Lupus Erythematosus

2021 ◽  
pp. 109980042110055
Author(s):  
María Correa-Rodríguez ◽  
Gabriela Pocovi-Gerardino ◽  
José-Luis Callejas-Rubio ◽  
Raquel Ríos-Fernández ◽  
Blanca Rueda-Medina ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Systemic Lupus Erythematosus ◽  
Lumbar Spine ◽  
Bone Mass ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Mineral Density ◽  
Systemic Lupus ◽  
Damage Accrual ◽  
Disease Damage

Osteoporosis is a common comorbidity in patients with systemic lupus erythematosus (SLE), but the potential contribution of disease-associated factors to bone status in SLE is not well known because the reported risk factors from different studies differ greatly. We aimed to examine frequency of reduced bone mass in women with SLE, and determine their potential associations with disease activity, damage accrual and SLE-related clinical markers. A cross-sectional study including 121 Caucasian pre-menopausal and postmenopausal women was conducted (mean age 49.2 ± 12.4 years). The SLE Disease Activity Index (SLEDAI-2 K) and the SDI Damage Index were used to assess disease activity and disease-related damage, respectively. Bone mineral density (BMD) of the left femoral neck and lumbar spine (L2–L4) were measured by dual-energy X-ray absorptiometry. Ten patients (8.3%) had osteoporosis, 63 (52.1%) patients had osteopenia and 6.8% of women had history of previous fracture. Patients with low bone mass had a significantly higher mean SDI (1.3 ± 1.2 versus 0.7 ± 1.0 p = 0.003). T-score at lumbar spine was inversely correlated with SDI score (r = -0.222, p = 0.014) and complement C3 level ( r = −0.206, p = .024). SDI scores were significantly different between patients with osteoporosis, osteopenia, and normal BMD after adjusting for covariates ( p = .004). There is a high prevalence of low BMD in Caucasian women with SLE, and this status was associated with higher damage accrual scores, supporting that disease damage may itself be a major contributor to the low BMD. Women with SLE with organ damage require regular bone status monitoring to prevent further musculoskeletal damage.

Longterm Outcomes and Damage Accrual in Patients with Childhood Systemic Lupus Erythematosus with Psychosis and Severe Cognitive Dysfunction

2013 ◽  
Vol 40 (4) ◽  
pp. 513-519 ◽  
Author(s):  
Lily Siok Hoon Lim ◽  
Arlette Lefebvre ◽  
Susanne Benseler ◽  
Earl D. Silverman
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Cognitive Dysfunction ◽  
Lupus Erythematosus ◽  
Clinical Course ◽  
Immunosuppressive Treatment ◽  
Damage Index ◽  
Response To Treatment ◽  
Systemic Lupus ◽  
Damage Accrual

Objective.(1) To describe the clinical course and response to treatment; and (2) to evaluate and compare damage accrual of distinct phenotypic subgroups of patients with clinically important psychiatric illness of pediatric systemic lupus erythematosus (pSLE).Methods.A single-center cohort study of patients with pSLE followed at a pediatric lupus clinic from 1985 to July 2009. Clinical course and response to treatment were studied. Remission was defined by absence of psychiatric/cognitive symptoms while receiving minimal doses of prednisone. Disease activity and damage were measured using SLE Disease Activity Index and SLE Damage Index.Results.Fifty-three children were included: 40 with psychosis and cognitive dysfunction (PSYC group) and 13 with isolated cognitive dysfunction (COG group). All received immunosuppressive treatment. Eighteen of 32 treated with azathioprine required a change to cyclophosphamide for poor response but none on cyclophosphamide required a change. The median times to remission were 72 weeks (PSYC) and 70 weeks (COG). Eight patients (7 PSYC, 1 COG) experienced flare following response/remission. New damage was noted in 50% of children at a median of 11 months: 57% of PSYC group, 31% of COG group. Persistent cognitive dysfunction was seen in 16% of PSYC patients and 15% of COG patients.Conclusion.Most patients responded to immunosuppressive treatment, although median time to remission was > 1 year. Roughly half the patients acquired a new damage item, most of which did not interfere with functional abilities. Fewer than 20% of patients developed neuropsychiatric damage. Both phenotypes of psychiatric pSLE responded equally well to current treatment.

scholarly journals Epidemiology of disease-activity related ophthalmological manifestations in Systemic Lupus Erythematosus: A systematic review

Lupus ◽  
2021 ◽  
pp. 096120332110503
Author(s):  
Nitish Jawahar ◽  
Jessica K Walker ◽  
Philip I Murray ◽  
Caroline Gordon ◽  
John A Reynolds
Keyword(s):  
Systematic Review ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Systemic Disease ◽  
Retinal Vasculitis ◽  
Small Sample ◽  
Systemic Lupus ◽  
Ocular Manifestations ◽  
Ophthalmic Manifestations

Objective Ophthalmic complications in Systemic Lupus Erythematosus (SLE) are broad and can occur in up to a third of patients. The British Isles Lupus Assessment Group (BILAG) 2004 Index identifies 13 ocular manifestations of active SLE, as opposed to those related to previous disease activity and/or the consequences of therapy. We conducted a systematic review of published literature to determine the frequency of ophthalmic manifestations of active SLE. Methods A systematic literature search of Ovid MEDLINE and EMBASE from their respective inceptions to July 2020 was conducted to identify cohort, case–control and cross-sectional studies. Results 22 studies meeting eligibility criteria were included. Most studies featured small sample sizes and were judged to have a high risk of methodological bias. The number and quality of studies did not allow us to confidently estimate the incidence of the conditions. No studies reported epidemiological data for orbital inflammation/myositis/proptosis. The prevalence of each of the other ocular manifestations, with the exception of retinal vaso-occlusive disease, was consistently less than 5%. Retinal vasculitis, uveitis and isolated cotton wool spots tended to be associated with more active SLE disease. Conclusion The prevalence of eye disease due to SLE activity is uncommon, but clinicians should be aware that some conditions tend to be associated with more active systemic disease. Further studies to determine the incidence and risk factors for these ophthalmic manifestations are needed.

scholarly journals Polymorphisms of MFGE8 are associated with susceptibility and clinical manifestations through gene expression modulation in Koreans with systemic lupus erythematosus

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Wook-Young Baek ◽  
Ji-Min Woo ◽  
Hyoun-Ah Kim ◽  
Ju-Yang Jung ◽  
Chang-Hee Suh
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Milk Fat ◽  
Clinical Manifestations ◽  
Αvβ3 Integrin ◽  
Apoptotic Cells ◽  
Systemic Lupus ◽  
Dsdna Antibody

AbstractSystemic lupus erythematosus (SLE) is characterized by impaired clearance of apoptotic cells. Milk fat globule epidermal growth factor 8 (MFGE8) is a protein that connects αvβ3 integrin on phagocytic macrophages with phosphatidylserine on apoptotic cells. We investigated whether genetic variation of the MFGE8 gene and serum MFGE8 concentration are associated with SLE. Single nucleotide polymorphisms (SNPs) were genotyped and serum concentrations were analyzed. The rs2271715 C allele and rs3743388 G allele showed higher frequency in SLE than in healthy subjects (HSs). Three haplotypes were found among 4 SNPs (rs4945, rs1878327, rs2271715, and rs3743388): AACG, CGCG, and CGTC. CGCG haplotype was significantly more common in SLE than in HSs. rs4945 was associated with the erythrocyte sedimentation rate and rs1878327 was associated with alopecia, C-reactive protein, complement 3, anti-dsDNA antibody, and high disease activity. rs2271715 and rs3743388 were associated with renal disease, cumulative glucocorticoid dose, and cyclophosphamide and mycophenolate mofetil use. Serum MFGE8 concentrations were significantly higher in SLE than in HSs. Furthermore, the levels of MFGE8 were significantly higher in SLE than HSs of the rs2271715 CC genotype. In conclusion, MFGE8 genetic polymorphisms are associated not only with susceptibility to SLE but also with disease activity through modulation of gene expression.

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