scholarly journals Association of Childhood Abuse with Incident Systemic Lupus Erythematosus in Adulthood in a Longitudinal Cohort of Women

2019 ◽  
Vol 46 (12) ◽  
pp. 1589-1596 ◽  
Author(s):  
Candace H. Feldman ◽  
Susan Malspeis ◽  
Cianna Leatherwood ◽  
Laura Kubzansky ◽  
Karen H. Costenbader ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Sexual Abuse ◽  
Childhood Abuse ◽  
Lupus Erythematosus ◽  
Emotional Abuse ◽  
Parental Education ◽  
Cox Regression ◽  
Health Study ◽  
Systemic Lupus ◽  
Increased Risk

Objective.Exposure to severe stressors may alter immune function and augment inflammation and cytokine release, increasing risk of autoimmune disease. We examined whether childhood abuse was associated with a heightened risk of incident systemic lupus erythematosus (SLE).Methods.Data were drawn from the Nurses’ Health Study II, a cohort of US female nurses enrolled in 1989, followed with biennial questionnaires. We measured childhood physical and emotional abuse with the Physical and Emotional Abuse Subscale of the Childhood Trauma Questionnaire and sexual abuse with the Sexual Maltreatment Scale of the Parent-Child Conflict Tactics Scale, both administered in 2001. We identified incident SLE (≥ 4 American College of Rheumatology 1997 classification criteria) through 2015. We used multivariable Cox regression models to evaluate the association between childhood abuse and SLE, accounting for potential confounders (e.g., parental education, occupation, home ownership) and mediators [e.g., depression, posttraumatic stress disorder (PTSD)].Results.Among 67,516 women, there were 94 cases of incident SLE. In adjusted models, exposure to the highest versus lowest physical and emotional abuse was associated with 2.57 times greater risk of SLE (95% CI 1.30–5.12). We found that 17% (p < 0.0001) of SLE risk associated with abuse could be explained by depression and 23% (p < 0.0001) by PTSD. We did not observe a statistically significant association with sexual abuse (HR 0.84, 95% CI 0.40–1.77, highest vs lowest exposure).Conclusion.We observed significantly increased risk of SLE among women who had experienced childhood physical and emotional abuse compared with women who had not. Exposure to childhood adversity may contribute to development of SLE.

scholarly journals Increased Risk of Systemic Lupus Erythematosus in 29,000 Patients with Biopsy-verified Celiac Disease

2012 ◽  
Vol 39 (10) ◽  
pp. 1964-1970 ◽  
Author(s):  
JONAS F. LUDVIGSSON ◽  
ALBERTO RUBIO-TAPIA ◽  
VAIDEHI CHOWDHARY ◽  
JOSEPH A. MURRAY ◽  
JULIA F. SIMARD
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Celiac Disease ◽  
General Population ◽  
Lupus Erythematosus ◽  
Cox Regression ◽  
Villous Atrophy ◽  
Case Series ◽  
Excess Risk ◽  
Systemic Lupus ◽  
Increased Risk

Objective.To investigate a possible association between celiac disease (CD) and systemic lupus erythematosus (SLE). Case series have indicated a possible association, but population-based studies are lacking.Methods.We compared the risk of SLE in 29,048 individuals with biopsy-verified CD (villous atrophy, Marsh 3) from Sweden’s 28 pathology departments with that in 144,352 matched individuals from the general population identified through the Swedish Total Population Register. SLE was defined as having at least 2 records of SLE in the Swedish Patient Register. We used Cox regression to estimate hazard ratios (HR) for SLE.Results.During followup, 54 individuals with CD had an incident SLE. This corresponded to an HR of 3.49 (95% CI 2.48−4.90), with an absolute risk of 17/100,000 person-years and an excess risk of 12/100,000. Beyond 5 years of followup, the HR for SLE was 2.54 (95% CI 1.57−4.10). While SLE was predominantly female, we found similar risk estimates in men and women. When we restricted our outcome to individuals who also had a dispensation for a medication used in SLE, the HR was 2.43 (95% CI 1.22−4.87). The HR for having 2 records of SLE diagnoses, out of which at least 1 had occurred in a department of rheumatology, nephrology/dialysis, internal medicine, or pediatrics, was 2.87 (95% CI 1.97−4.17).Conclusion.Individuals with CD were at a 3-fold increased risk of SLE compared to the general population. Although this excess risk remained more than 5 years after CD diagnosis, absolute risks were low.

scholarly journals Dietary patterns and risk of systemic lupus erythematosus in women

Lupus ◽  
2019 ◽  
Vol 29 (1) ◽  
pp. 67-73
Author(s):  
S K Tedeschi ◽  
M Barbhaiya ◽  
J A Sparks ◽  
E W Karlson ◽  
L D Kubzansky ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dietary Patterns ◽  
Lupus Erythematosus ◽  
Dietary Pattern ◽  
Intestinal Microbiome ◽  
Health Study ◽  
Systemic Lupus ◽  
Western Dietary Pattern ◽  
Increased Risk ◽  
Time Varying Covariates

Objective Dietary intake is a complex exposure and a potential risk factor for systemic lupus erythematosus (SLE) due to its impact on lipid and glucose metabolism, oxidative stress, and the intestinal microbiome. We aimed to test whether a prudent dietary pattern is associated with a lower risk of SLE, and whether a Western dietary pattern is associated with a higher risk of SLE. Methods We prospectively investigated two dietary patterns and SLE risk among women in the Nurses' Health Study (NHS, 1984–2014) and Nurses' Health Study II (NHSII, 1991–2015). Food frequency questionnaires were completed every four years. Congruent with prior work in NHS and NHSII, we derived two separate dietary patterns (prudent and Western) using principal component analysis within each cohort. Incident SLE was confirmed by the American College of Rheumatology's 1997 criteria. We estimated hazard ratios (HR) and 95% confidence intervals ( CI) for SLE by dietary pattern quartiles using Cox models adjusted for time-varying covariates. Models were performed separately in each cohort and results were meta-analyzed. Stratified analyses tested the association of dietary patterns with anti-dsDNA positive SLE and anti-dsDNA negative SLE. Results We confirmed 82 NHS incident SLE cases and 98 NHSII SLE cases during 3,833,054 person-years of follow-up. A higher (healthier) prudent dietary pattern score was not associated with SLE risk (meta-analyzed HRQ4 versus Q1 0.84 [95% CI 0.51, 1.38]). Women with higher (less healthy) Western dietary pattern scores did not have a significantly increased risk for SLE (meta-analyzed HRQ4 versus Q1 1.35 [95% CI 0.77, 2.35]). Results were similar after further adjustment for body mass index. Incident anti-dsDNA positive SLE and anti-dsDNA negative SLE were not associated with either dietary pattern. Conclusion We did not observe a relationship between prudent or Western dietary pattern score and risk of SLE.

scholarly journals Incidence of COVID-19 Hospitalisation in Patients with Systemic Lupus Erythematosus: A Nationwide Cohort Study from Denmark

2021 ◽  
Vol 10 (17) ◽  
pp. 3842
Author(s):  
René Cordtz ◽  
Salome Kristensen ◽  
Louise Plank Holm Dalgaard ◽  
Rasmus Westermann ◽  
Kirsten Duch ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cohort Study ◽  
General Population ◽  
Lupus Erythematosus ◽  
Cox Regression ◽  
Hazard Ratio ◽  
Systemic Lupus ◽  
Increased Risk ◽  
Study Results ◽  
The Impact

Background: Patients with systemic lupus erythematosus (SLE) have an increased risk of infections due to impaired immune functions, disease activity, and treatment. This study investigated the impact of having SLE on the incidence of hospitalisation with COVID-19 infection. Methods: This was a nationwide cohort study from Denmark between 1 March 2020 to 2 February 2021, based on the linkage of several nationwide registers. The adjusted incidence of COVID-19 hospitalisation was estimated for patients with SLE compared with the general population in Cox-regression models. Among SLE patients, the hazard ratio (HR) for hospitalisation was analysed as nested case-control study. Results: Sixteen of the 2533 SLE patients were hospitalised with COVID-19 infection. The age-sex adjusted rate per 1000 person years was 6.16 (95% CI 3.76–10.08) in SLE patients, and the corresponding hazard ratio was 2.54 (95% CI 1.55–4.16) compared with the matched general population group after adjustment for comorbidities. Among SLE patients, hydroxychloroquine treatment was associated with a HR for hospitalisation of 0.61 (95% CI 0.19–1.88), and 1.06 (95% CI 0.3–3.72) for glucocorticoid treatment. Conclusion: Patients with SLE were at increased risk of hospitalisation with COVID-19.

scholarly journals Systemic Lupus Erythematosus Features in Rheumatoid Arthritis and Their Effect on Overall Mortality

2009 ◽  
Vol 36 (1) ◽  
pp. 50-57 ◽  
Author(s):  
MURAT ICEN ◽  
PAULO J. NICOLA ◽  
HILAL MARADIT-KREMERS ◽  
CYNTHIA S. CROWSON ◽  
TERRY M. THERNEAU ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Mortality Risk ◽  
Lupus Erythematosus ◽  
Cox Regression ◽  
Systemic Lupus ◽  
Risk Of Death ◽  
Acr Criteria ◽  
Increased Risk ◽  
Overall Mortality

ObjectiveFeatures of systemic lupus erythematosus (SLE) are commonly observed in patients with rheumatoid arthritis (RA). However, their frequency and clinical significance are uncertain. We examined the frequency of SLE features in RA and their effect on overall mortality.MethodsWe assembled a population-based incidence cohort of subjects aged ≥ 18 years first diagnosed with RA [1987 American College of Rheumatology (ACR) criteria] between 1955 and 1995. Information regarding disease characteristics, therapy, comorbidities, and SLE features (1982 ACR criteria) were collected from the complete inpatient and outpatient medical records. Cox regression models were used to estimate the mortality risk associated with lupus features.ResultsThe study population comprised 603 subjects with incident RA (mean age 58 yrs, 73% women) with a mean followup time of 15 years. By 25 years after RA incidence, ≥ 4 SLE features were observed in 15.5% of the subjects with RA. After adjustment for age and sex, occurrence of ≥ 4 SLE features was associated with increased overall mortality [hazard ratio (HR) 5.54, 95% confidence interval (CI) 3.59–8.53].With further adjustment for RA characteristics, therapy, and comorbidities, the association weakened but remained statistically significant (HR 2.56, 95% CI 1.60–4.08). After adjustment for age, sex, RA characteristics, therapy, and comorbidities, thrombocytopenia (2.0, 95% CI 1.2, 3.1) and proteinuria (1.8, 95% CI 1.3, 2.6) were significantly associated with mortality.ConclusionSLE features were common in RA, given sufficient observation time. Subjects with RA who developed ≥ 4 SLE features had an increased risk of death. Proteinuria and thrombocytopenia were individually associated with an increased mortality risk.

scholarly journals Cigarette smoking and the risk of systemic lupus erythematosus, overall and by anti-double stranded DNA antibody subtype, in the Nurses’ Health Study cohorts

2017 ◽  
Vol 77 (2) ◽  
pp. 196-202 ◽  
Author(s):  
Medha Barbhaiya ◽  
Sara K Tedeschi ◽  
Bing Lu ◽  
Susan Malspeis ◽  
David Kreps ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cigarette Smoking ◽  
Lupus Erythematosus ◽  
Cox Regression ◽  
Smoking Status ◽  
Clinical Manifestations ◽  
Health Study ◽  
Systemic Lupus ◽  
Double Stranded Dna ◽  
Never Smokers

ObjectivesSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease, subtyped according to clinical manifestations and autoantibodies. Evidence concerning cigarette smoking and SLE risk has been conflicting. We investigated smoking and SLE risk, overall and by anti-double stranded DNA (dsDNA) presence, in two prospective cohort studies.MethodsThe Nurses’ Health Study (NHS) enrolled 121 701 US female nurses in 1976; Nurses’ Health Study II (NHSII) enrolled 116 430 in 1989. Lifestyle, environmental and medical data were collected through biennial questionnaires. Incident SLE was confirmed by medical record review. Cox regression models estimated HRs of SLE, overall and by dsDNA subtype, in association with time-varying smoking status and cumulative smoking pack-years through the 2-year cycle prior to diagnosis, controlling for potential confounders.ResultsAmong 286 SLE cases identified (159 in NHS (1978–2012) and 127 in NHSII (1991–2013)), mean age was 49.2 (10.3) years and 42% were dsDNA+ at SLE diagnosis. At baseline, 45% of women had ever smoked, 51% of whom currently smoked. Compared with never smokers, current smokers had increased dsDNA+ SLE risk (HR 1.86 (1.14–3.04)), whereas past smokers did not (HR 1.31 (0.85–2.00)). Women who smoked >10 pack-years (vs never) had an elevated dsDNA+ SLE risk (HR 1.60(95% CI 1.04 to 2.45)) compared with never smokers. No associations were observed between smoking status or pack-years and overall SLE or dsDNA− SLE.ConclusionStrong and specific associations of current smoking and >10 pack-years of smoking with dsDNA+ SLE were observed. This novel finding suggests smoking is involved in dsDNA+ SLE pathogenesis.

scholarly journals Predictors of renal damage in systemic lupus erythematous patients: data from a multiethnic, multinational Latin American lupus cohort (GLADEL)

RMD Open ◽  
2020 ◽  
Vol 6 (3) ◽  
pp. e001299
Author(s):  
Cristina Reátegui-Sokolova ◽  
Manuel F Ugarte-Gil ◽  
Guillermina B Harvey ◽  
Daniel Wojdyla ◽  
Guillermo J Pons-Estel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Latin American ◽  
Lupus Erythematosus ◽  
Renal Damage ◽  
Cox Regression ◽  
Damage Index ◽  
Early Response ◽  
Male Gender ◽  
Systemic Lupus

AimA decrease in proteinuria has been considered protective from renal damage in lupus nephritis (LN), but a cut-off point has yet to be established. The aim of this study was to identify the predictors of renal damage in patients with LN and to determine the best cut-off point for a decrease in proteinuria.MethodsWe included patients with LN defined clinically or histologically. Possible predictors of renal damage at the time of LN diagnosis were examined: proteinuria, low complement, anti-double-stranded DNA antibodies, red cell casts, creatinine level, hypertension, renal activity (assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)), prednisone dose, immunosuppressive drugs and antimalarial use. Sociodemographic variables were included at baseline. Proteinuria was assessed at baseline and at 12 months, to determine if early response (proteinuria <0.8 g/day within 12 months since LN diagnosis) is protective of renal damage occurrence. Renal damage was defined as an increase of one or more points in the renal domain of The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). Cox regression models using a backward selection method were performed.ResultsFive hundred and two patients with systemic lupus erythematosus patients were included; 120 patients (23.9%) accrued renal damage during their follow-up. Early response to treatment (HR=0.58), antimalarial use (HR=0.54) and a high SES (HR=0.25) were protective of renal damage occurrence, whereas male gender (HR=1.83), hypertension (HR=1.86) and the renal component of the SLEDAI (HR=2.02) were risk factors for its occurrence.ConclusionsEarly response, antimalarial use and high SES were protective of renal damage, while male gender, hypertension and higher renal activity were risk factors for its occurrence in patients with LN.

scholarly journals Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sarfaraz A. Hasni ◽  
Sarthak Gupta ◽  
Michael Davis ◽  
Elaine Poncio ◽  
Yenealem Temesgen-Oyelakin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Kinase Inhibitor ◽  
Janus Kinase ◽  
Controlled Clinical Trial ◽  
Type I ◽  
Systemic Lupus ◽  
Double Blind ◽  
Premature Cardiovascular Disease ◽  
Increased Risk

AbstractIncreased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In lupus animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We conducted a randomized, double-blind, placebo-controlled clinical trial of tofacitinib in SLE subjects (ClinicalTrials.gov NCT02535689). In this study, 30 subjects are randomized to tofacitinib (5 mg twice daily) or placebo in 2:1 block. The primary outcome of this study is safety and tolerability of tofacitinib. The secondary outcomes include clinical response and mechanistic studies. The tofacitinib is found to be safe in SLE meeting study’s primary endpoint. We also show that tofacitinib improves cardiometabolic and immunologic parameters associated with the premature atherosclerosis in SLE. Tofacitinib improves high-density lipoprotein cholesterol levels (p = 0.0006, CI 95%: 4.12, 13.32) and particle number (p = 0.0008, CI 95%: 1.58, 5.33); lecithin: cholesterol acyltransferase concentration (p = 0.024, CI 95%: 1.1, −26.5), cholesterol efflux capacity (p = 0.08, CI 95%: −0.01, 0.24), improvements in arterial stiffness and endothelium-dependent vasorelaxation and decrease in type I IFN gene signature, low-density granulocytes and circulating NETs. Some of these improvements are more robust in subjects with STAT4 risk allele.

FRI0516 FACTORS ASSOCIATED WITH DECREASED CERVICAL CANCER SCREENING IN WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 857.1-857
Author(s):  
S. Bruera ◽  
R. Zogala ◽  
X. Lei ◽  
X. Pundole ◽  
H. Zhao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cervical Cancer ◽  
Cancer Screening ◽  
Autoimmune Disease ◽  
Cervical Cancer Screening ◽  
Lupus Erythematosus ◽  
Screening Rate ◽  
Systemic Lupus ◽  
Comorbidity Score ◽  
Increased Risk

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that carries an increased risk for both viral illnesses and malignancies, including a greater risk for both human papilloma virus (HPV) infection and cervical cancer. Due to this increased risk, the American Society of Colposcopy and Cervical Pathology guidelines for SLE patients recommend more frequent cervical cancer screening. Few studies have examined patient characteristics associated with decreased cervical cancer screening in patients with autoimmune disease, specifically SLE.Objectives:To estimate cervical cancer screening rates in women with recently diagnosed SLE, and to identify characteristics associated with decreased screening.Methods:We identified women with an initial diagnosis of SLE in the United States MarketScan Commercial Claims and Encounter (CCAE, age 18-64) administrative claims database. We included patients with at least three claims with a lupus diagnosis (first and last at least >90 days apart), no lupus claims within the year before initial claim, and who had been on antimalarial drugs for at least 90 days. We excluded all patients with a previous claim for hysterectomy.Cervical cancer screening was ascertained using diagnosis and procedure codes within 1 year before and 2 years after the first SLE claim. Our covariates included the year of first SLE claim (2001-2014), age at first SLE claim, comorbidity score, insurance type, geographical region, and prescriptions for multiple types of corticosteroids. Control patients included age-matched females without autoimmune disease. Univariate comparison and multivariate logistic regression models were built to evaluate determinants of screening.Results:We included 4,316 SLE patients (median age 45) and 86,544 control patients. The screening rate in SLE patients was 73.4% vs 58.5% in the controls (P < 0.001). The screening rate was 71% in 2001, increased to 75% in 2004, then decreased to 70% in 2014 (trend P =0.005). In the multivariate model the following factors were associated with decreased cervical cancer screening: year of first SLE claim 2012-2014 versus 2001-2005 (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.53 – 0.84, P < 0.001); older age 61-64 versus 21-30 (OR 0.27, 95% CI 0.19 – 0.39, P < 0.001); comorbidity score of ≥2 versus <2 (OR 0.71, 95% CI 0.6 – 0.83, P < 0.001); and use of corticosteroids for ≥ 90 days versus <90 days (OR 0.73, 95% CI 0.59 – 0.9, P = 0.003). Insurance type and geographical region were not associated with cervical cancer screening.Conclusion:About three quarters of women with SLE underwent cervical cancer screening within 3 years of their first lupus claim, at higher rates than controls. However, there was a concerning downward trend in screening rates in recent years. In addition, higher risk populations for cervical cancer (older age, increased comorbidities, and longer duration of corticosteroids) had lower screening rates. These findings highlight the need to enhance education for healthcare providers to improve utilization of screening in women with SLE at high risk of cervical cancer.Disclosure of Interests:Sebastian Bruera: None declared, Richard Zogala: None declared, Xiudong Lei: None declared, Xerxes Pundole: None declared, Hui Zhao: None declared, Sharon Giordano: None declared, Jessica Hwang Grant/research support from: MERCK grant funding unrelated to SLE., Maria Suarez-Almazor: None declared

scholarly journals An Analytic Approach Using Candidate Gene Selection and Logic Forest to Identify Gene by Environment Interactions (G × E) for Systemic Lupus Erythematosus in African Americans

Genes ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 496 ◽  
Author(s):  
Bethany Wolf ◽  
Paula Ramos ◽  
J. Hyer ◽  
Viswanathan Ramakrishnan ◽  
Gary Gilkeson ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Secondhand Smoke ◽  
Gene Selection ◽  
Search Space ◽  
Higher Order ◽  
Candidate Snps ◽  
Systemic Lupus ◽  
Increased Risk ◽  
Main Effects

Development and progression of many human diseases, such as systemic lupus erythematosus (SLE), are hypothesized to result from interactions between genetic and environmental factors. Current approaches to identify and evaluate interactions are limited, most often focusing on main effects and two-way interactions. While higher order interactions associated with disease are documented, they are difficult to detect since expanding the search space to all possible interactions of p predictors means evaluating 2p − 1 terms. For example, data with 150 candidate predictors requires considering over 1045 main effects and interactions. In this study, we present an analytical approach involving selection of candidate single nucleotide polymorphisms (SNPs) and environmental and/or clinical factors and use of Logic Forest to identify predictors of disease, including higher order interactions, followed by confirmation of the association between those predictors and interactions identified with disease outcome using logistic regression. We applied this approach to a study investigating whether smoking and/or secondhand smoke exposure interacts with candidate SNPs resulting in elevated risk of SLE. The approach identified both genetic and environmental risk factors, with evidence suggesting potential interactions between exposure to secondhand smoke as a child and genetic variation in the ITGAM gene associated with increased risk of SLE.

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