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Objective: To assess the prevalence of systemic lupus erythematosus (SLE) in a psoriatic arthritis (PsA) cohort and to compare it to the general population using the database of a large healthcare provider., Methods: We analyzed the database of a PsA cohort (2002-2017), matched for age and sex, with randomly selected controls for demographics, clinical and laboratory manifestations, and dispensed medications. Statistical analysis used t test and chi-square test as appropriate. In the PsA group, incidence density sampling was performed matching PsA patients without SLE as controls to each case of PsA with SLE by age and follow-up time. Univariable and multivariable conditional logistic regression analyses were used to assess factors affecting SLE development., Results: The PsA and control groups consisted of 4836 and 24,180 subjects, respectively, with a median age of 56 ± 15 years, and of whom 53.8% were female. Eighteen patients (0.37%) in the PsA group and 36 patients (0.15%) in the control group were diagnosed with SLE ( P = 0.001). SLE patients without PsA had higher anti-dsDNA and anticardiolipin antibodies. The usage of drugs with known potential to induce SLE was higher in the PsA than in the control group. Older age at PsA diagnosis, shorter PsA duration, and statin treatment were associated with SLE in PsA patients., Conclusion: A 2.3-fold increase in the prevalence of SLE in PsA relative to the control group was found. Risk factors for SLE development included older age at PsA diagnosis, shorter PsA duration, and statin treatment. The association between PsA and SLE may affect treatment choices and medication development., (Copyright © 2021 by the Journal of Rheumatology.)

The coexistence of alopecia areata (AA) and systemic lupus erythematosus (SLE) has been described, but the association between these conditions is yet to be firmly established. We aimed to evaluate the association between AA and SLE using a large-scale real-life computerized database. A cross-sectional study was conducted comparing the prevalence of SLE among patients with AA and among age-, sex-, and ethnicity-matched control subjects. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study was performed utilizing the computerized database of Clalit Health Services ensuring 4.4 million subjects. A total of 51,561 patients with AA and 51,410 controls were included in the study. The prevalence of SLE was increased in patients with AA as compared to the control group (0.3% vs. 0.1%, respectively; OR, 2.1; 95% CI, 1.6-2.9; P < 0.001). The association increased consistently with age and was stronger among female and Jewish patients. In a multivariate analysis adjusting for sex, age, ethnicity, and other comorbidities, AA was still associated with SLE (OR, 2.1; 95% CI, 1.6-2.9; P < 0.001). To conclude, a significant positive association was observed between AA and SLE. Further longitudinal observational studies are necessary to establish these findings in other study populations. Physicians treating patients with AA may be aware of this possible association and may consider screening for SLE in patients with relevant symptoms.

The coexistence of pemphigus and systemic lupus erythematosus (SLE) had been reported anecdotally. Anti-desmoglein (Dsg)1 and anti-Dsg3 antibodies were detected concomitantly with antinuclear autoantibodies among blood donors. The aim of the current study was to study the association between pemphigus and SLE in Israeli patients and to synthesize existing data on this association in the current literature. The current study included two sections. Initially, a cross-sectional study was performed to compare pemphigus patients with age-, sex-, and ethnicity-matched control subjects regarding the prevalence of SLE using a real-life large-scale computerized database. Next, a systematic review and meta-analysis of similar observational studies in Medline, Embase, and Web of Science (1823-2017) was conducted. As for the cross-sectional study, a total of 1985 patients with pemphigus and 9874 controls were included in the study. The prevalence of SLE was slightly higher among patients with pemphigus as compared to controls (OR, 1.85; 95% CI, 0.89-3.82). In a sensitivity analysis that included patients who received pemphigus-related treatments, the association between pemphigus and SLE had been substantiated and was statistically significant (OR, 2.10; 95% CI, 1.00-4.48). In the meta-analysis section, three eligible studies, comprising 10,389 pemphigus patients met the eligibility criteria. The overall pooled multivariate OR was 2.50 (95% CI 1.54-4.07, I 2  = 44.19%, P = 0.167) across all studies. In conclusion, the meta-analysis provides epidemiologic evidence that these B cell-driven diseases are significantly associated. Further research is required to elucidate the molecular mechanism underlying this association.

Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting a wide range of systems including the peripheral and central nervous system. Cognitive impairment leading to dementia is one of the harmful central nervous system afflictions of SLE. The aim of this study was to investigate the association of SLE with dementia., Methods: A cross-sectional study was conducted using Clalit Health Care database, the largest health maintenance organization in Israel with more than 4.4 million enrollees. Systemic lupus erythematosus patients were compared in a 1:5 ratio to age- and sex-matched controls. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis., Results: The study included 4886 SLE patients and 24 430 age-frequency- and sex-frequency-matched controls without SLE. The proportion of dementia was higher among SLE patients compared to controls (1.56% and 0.51%, respectively; P < .001). This finding was consistent across all age groups by univariate analysis. In a multivariate logistic regression analysis, SLE was significantly associated with dementia (odds ratio = 1.51, 95% confidence interval, 1.11-2.04)., Conclusion: Systemic lupus erythematosus is significantly associated with dementia. This finding should give rise to search for SLE in patients with an ambiguous cause for dementia, especially those with an early onset cognitive decline., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objective: Epilepsy is characterized by a relevant epidemiological and clinical burden. In the extant literature, an increased risk of seizures has been described in several inflammatory/autoimmune disorders, including systemic lupus erythematosus (SLE). However, so far, relatively few and small size-based studies have been conducted. We aimed to investigate the link between seizure and SLE utilizing a large sample of subjects and extensive data analysis., Methods: Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of epilepsy in a cross-sectional study. Chi-square and t tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services., Results: The study included 5,018 patients with SLE and 25,090 age- and gender-frequency-matched controls. The proportion of epilepsy was found significantly higher among SLE patients (4.03 vs. 0.87%, p < 0.001). Using logistic regression, adjusting for multiple confounding factors, older age (≥70 years) resulted as negative predictor (OR 0.42 [95% CI 0.27-0.62], p <0.001), whereas the presence of SLE was a positive predictor of epilepsy (OR 4.70 [95% CI 3.94-5.82], p < 0.001). Interaction between SLE and elderly age resulted in high OR of 5.47 for epilepsy (95% CI 2.53-11.9)., Conclusion: Our study confirms the higher prevalence of epilepsy in SLE patients. Physicians should be aware of such findings and have a lower threshold for suspecting epileptic seizures in these patients. Further studies are needed to better elucidate the mechanisms by which SLE favors the insurgence of seizures., (© 2017 S. Karger AG, Basel.)

Aims: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease involving multiple organs, including the central nervous system. Evidence of immune dysfunction exists also in schizophrenia, a psychiatric illness involving chronic or recurrent psychosis. The aim of our study was to investigate if there is an epidemiological association between SLE and schizophrenia., Method: A cross-sectional study was conducted comparing patients with SLE with age and gender-matched controls regarding the proportion of patients with comorbid schizophrenia. χ 2- and t-tests were used for univariate analysis, and interaction of schizophrenia with SLE across strata of covariates was checked. A logistic regression model was used for multivariate analysis. The study was performed utilising the medical database of Clalit Health Services in Israel., Results: The study included 5018 patients with SLE and 25 090 controls. SLE patients had a female predominance, and a higher proportion of smoking compared with age and sex-matched controls. In multivariate analysis, SLE was found to be independently associated with schizophrenia while controlling for age, gender, socioeconomic status (SES) and smoking (OR 1.33, p = 0.042)., Conclusions: We found a positive association between SLE and schizophrenia across patients of different age, gender and SES. This association can contribute to understanding the pathophysiology of the two disorders and may also have clinical implications for earlier as well as better diagnosis and treatment.

Background: Both smoking and obesity have been demonstrated as risk factors in several autoimmune diseases. Little is known about the relationship between systemic lupus erythematosus (SLE) and both smoking and obesity., Objectives: To investigate the association between SLE, tobacco consumption and body mass index (BMI)., Materials and Methods: Using data from the largest Health Maintenance Organization (HMO) in Israel, the Clalit Health Services, we searched for an association between SLE, smoking and obesity. Chi-square and t-test were used for univariate analysis, and a logistic regression model was used for multivariate analysis. Data available from Clalit Health Services database included age, sex, BMI, smoking status, socioeconomic status (SES) and diagnoses of chronic diseases., Results: The study included 5018 patients with SLE and 25 090 age- and sex-matched controls. In multivariate analysis, we found a significant association between smoking and SLE (OR = 1·91). Conversely, there was no association between BMI and SLE., Conclusion: In this study, we have shown that smoking is independently associated with SLE, whereas BMI scores were not., (© 2017 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease that has a wide variety of physical manifestations, including neuropsychiatric features. Bipolar disorder (BD) is a chronic, episodic illness, that may present as depression or as mania. The objective of this study was to investigate the association between SLE and BD using big data analysis methods., Methods: Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of BD in a cross-sectional study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis, adjusting for confounders. The study was performed utilizing the chronic disease registry of Clalit Health Services medical database., Results: The study included 5018 SLE patients and 25,090 matched controls. BD was found in a higher prevalence among SLE patients compared to controls (0.62% vs. 0.26%, respectively, P<0.001). BD patients had a greater prevalence of smokers compared to non-BD patients (62.5% vs 23.5%, respectively, P<0.001). In a multivariate analysis, smoking and SLE were both found to be significantly associated with BD., Conclusions: SLE was found to be independently associated with BD. These findings may imply that an autoimmune process affecting the central nervous system among SLE patients facilitates the expression of concomitant BD., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Association between antiphospholipid syndrome in systemic lupus erythematosus (SLE) and valvular heart disease (VHD) is well reported, but relatively few studies have been carried out to establish the linkage between VHD and SLE itself. We aimed to investigate link between VHD and SLE and to evaluate the association of diverse factors with VHD among these patients in a large-scale population-based study., Materials and Methods: We used the databases of the largest state-mandated health service organization in Israel. All SLE patients were included (n = 5018) as well as their age and sex-matched controls (n = 25 090), creating a cross-sectional population-based study. Medical records of all subjects were analysed for documented VHD and the presence of antiphospholipid antibodies (aPLs). A logistic regression model was carried out to evaluate the diverse factors including SLE and aPLs as independent risk factors for VHD., Results: Valvular heart disease were found to be more frequent among SLE group when compared to controls (aortic stenosis, 1·08% vs. 0·35% respectively, P < 0·001; aortic insufficiency, 1·32% vs. 0·29% respectively, P < 0·001; mitral stenosis, 0·74% vs. 0·21% respectively, P < 0·001; mitral insufficiency, 1·91% vs. 0·39% respectively, P < 0·001). Male sex, hypertension, aPLs and SLE were found to be significant independent risk factors for VHD., Conclusion: All VHD are more prevalent among SLE patients when compared to controls. SLE and aPLs are independent risk factor for VHD (OR of 2·46 and 1·7, respectively). Physicians must be aware of such significant association, and routine echocardiography should be considered in SLE patients regardless of their aPL status., (© 2017 Stichting European Society for Clinical Investigation Journal Foundation.)

The association between viral infection and autoimmune diseases is an established phenomenon in medicine. Hepatitis C viral infection is known to have such an association; however, its association with systemic lupus erythematosus has not been studied in a real life study driven from a large national database. The objective of this study was to investigate the association between SLE and chronic hepatitis C viral infection. Patients with SLE were compared with age- and sex-matched controls regarding the proportion chronic HCV infection. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services in Israel. There was a significant higher proportion of hepatitis C viral infection in SLE patients as compared to controls (1.06 and 0.39%, respectively; p < 0.001). A significant association was also observed among patients of higher socioeconomic status. In a multivariate logistic regression analysis, SLE was significantly associated with hepatitis C viral infection (OR = 2.07, 95% CI = 1.46-2.90). To conclude, Patients with SLE have a greater proportion of chronic HCV infection than matched controls.

Autoimmune conditions reflect dysregulation of the immune system; this may be of clinical significance in the development of several malignancies. Previous studies show an association between systemic lupus erythematosus (SLE) and the development of malignancies; however, their investigations into the development of specific malignancies are inconsistent, and their external validity may be questionable. The main objective of this study is to investigate the association between the presence of SLE and various malignancies, in a large-scale population-based study. Data for this study was collected from Clalit Health Services, the largest state-mandated health service organization in Israel. All adult members diagnosed with SLE were included (n = 5018) and their age and sex-matched controls (n = 25,090), creating a cross-sectional population-based study. Medical records of all subjects were analyzed for documentation of malignancies. Logistic regression models were built separately for each malignant condition, controlling for age, gender, BMI, smoking, and socioeconomic status. Diagnosis of malignancy (of any type) was more prevalent in the SLE population (odds ratio [OR] 3.35, 95% confidence interval [CI] 3.02-3.72). SLE diagnosis was also found to be independently associated with higher proportions of non-Hodgkin lymphoma (OR 3.02, 95% CI 2.72-3.33), Hodgkin lymphoma (OR 2.43, 95% CI 1.88-2.99), multiple myeloma (OR 2.57, 95% CI 1.85-3.28), cervix uteri malignancies (OR 1.65, 95% CI 1.10-2.20), and genital organ malignancies (OR 2.32, 95% CI 1.42-3.22), after adjustment for confounding variables. The presence of an SLE diagnosis was found to be independently associated with higher proportions of malignancies, particularly hematologic malignancies. These findings should be considered while treating SLE patients, and possibly supplement their screening routine.

Ischemic heart disease (IHD) is a well identified cause of mortality in systemic lupus erythematosus (SLE) patients due to an accelerated premature atherosclerosis. We investigated the proportion of comorbid IHD among SLE patients derived from a large, national real-life database. Using data from the largest HMO in Israel, the Clalit Health Services, we selected for patients with SLE. These patients were compared with age and sex matched controls with regards to the proportion of IHD in a case-control study. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study included 5018 patients with SLE and 25090 age and sex-frequency matched controls. The prevalence of IHD in patients with SLE was increased in comparison to controls (11.3 and 3.1%, P < 0.001). In a multivariate analysis, SLE was associated with IHD (OR 3.77, 95% confidence interval 3.34-4.26). We have confirmed that SLE patients suffer a high prevalence of IHD. Our data supports that SLE is an independent risk factor for IHD. When evaluating by gender, the risk seems even more substantial in females. No significant difference was found in the risk of IHD in SLE among the difference socioeconomic strata.

The association between hepatitis B and autoimmune disorders has been intriguing for decades. Many reports have speculated on the possible linkage between these two conditions, yet never before data driven from a large national database was utilized in order to investigate this issue. The objective of this study was to investigate the association between SLE and hepatitis B carrier state. Patients with SLE were compared with age- and sex-matched controls regarding the proportion of hepatitis B carrier state in a case-control study. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. The study included 5018 lupus patients over the age of 20 years and 25,090 age- and sex-frequency-matched controls without SLE. The proportion of hepatitis B carriers was higher in SLE patients as compared to controls (0.9 and 0.56 %, respectively; p < 0.001). A significant association was also observed among patients in lower socioeconomic status. In a multivariate logistic regression analysis, SLE was significantly associated with hepatitis B (OR = 1.828, 95 % CI = 1.291-2.590). Patients with SLE have a greater proportion of hepatitis B carrier state than matched controls.

Objectives: Several reports have indicated an association between systemic lupus erythematosus (SLE) and low levels of vitamin D. We examined several blood work parameters in SLE patients and controls and performed an extensive data analysis in order to investigate the links between blood levels of calcium, vitamin D, and SLE disease., Methods: 4,278 SLE patients and 16,443 age and sex-matched controls were selected from a national health insurer database in Israel. Patients with no blood work results or having renal disease were excluded. Retrospective data from five consecutive years of routine blood work results were then analysed for mean serum calcium, albumin, albumin-corrected calcium, vitamin D levels, and the presence of a hypocalcaemic episode (Corrected Ca <8.5 mg/dL)., Results: The mean levels of corrected serum calcium levels were slightly higher among SLE patients than controls (9.23±0.34 vs. 9.19±0.36 mg/dL p≤.001 respectively). In contrast to results of published studies, SLE patients had slightly higher levels of 25(OH)-vitamin D (SLE patients: 22.2±9.06 ng/ml, controls: 20.0±8.76 ng/ml, p≤.001). The most impressive finding entailing SLE patients was that they were twice as likely to experience episodes of hypocalcaemia in comparison to controls (SLE patients: 13.8%, controls: 6.4%, OR 2.34; 95% CI 2.33-2.83)., Conclusions: Calcium levels may play a significant role in the SLE disease process, more than originally thought, since SLE patients are at a higher risk for hypocalcaemic events. Specific changes in vitamin D and calcium homeostasis in SLE patients may be responsible for the severity of symptoms. Further research is required to determine the role of calcium supplementation.

Background: The data regarding the association between inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE) is mostly composed of case reports and case series indicating an infrequent association., Objectives: To investigate the association between IBD and SLE., Methods: Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of ulcerative colitis (UC) and Crohn's disease (CD) in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services., Results: The study included 5018 patients with SLE and 25,090 age- and sex-matched controls. The prevalence of UC was significantly higher in patients with SLE than in controls in a univariate analysis (0.4% and 0.2%, respectively; p<0.017). However, in a multivariate logistic regression model SLE was not associated with UC (OR 1.67, 95% CI 0.99-2.815, p<0.052). The prevalence of CD was higher in patients with SLE than in controls in a univariate analysis (0.7% and 0.3%, respectively; p<0.001). A multivariate logistic regression model confirmed this finding and corroborated that SLE was associated with comorbid CD (OR 2.23, 95% CI 1.46-3.4, p<0.001)., Conclusions: Patients with SLE have a greater prevalence of CD than matched controls. The distinction of IBD from SLE gastrointestinal involvement can be challenging as clinical manifestations, laboratory tests, and radiographic findings may appear similar between the two diseases. Therefore, physicians treating patients with rather IBD or SLE should consider this potential association., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: Aortic aneurysm is a life threatening cardiovascular complication in patients with systemic lupus erythematosus (SLE).The purpose of this study was to investigate the association between SLE and occurrence of aortic aneurysms., Methods: Patients with SLE were compared with age- and sex-matched controls regarding the proportion of aortic aneurysm in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services., Results: The study included 5018 patients with SLE and 25,090 age- and sex-matched controls. The proportion of aortic aneurysm in patients with SLE was increased compared with the proportion in controls (0.6% and 0.1%, respectively, p < 0.001). In a multivariate analysis SLE was associated with the coexistence of aortic aneurysms (odds ratio 2.06, 95% confidence interval 1.21-3.51)., Conclusions: Patients with SLE have a higher proportion of aortic aneurysms as compared with matched controls. Therefore, physicians treating patients with SLE should be aware of this life threatening association., (© The Author(s) 2016.)

Background: Case reports and case series have indicated a possible association between celiac disease (CD) and systemic lupus erythematosus (SLE), but additional population-based studies are required. The true prevalence of CD in SLE patients is still unknown, but is indeed an important factor when considering the clinical implications, notably the necessity of screening strategies in SLE patients. Our objective was to investigate the association between CD and SLE using a community-based approach in a real-life population database., Methods: Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of CD in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services., Results: The study included 5018 patients with SLE and 25,090 age- and sex-matched controls. The prevalence of CD was significantly higher in patients with SLE than in controls in univariate analysis (0.8% and 0.2%, respectively, p<0.001). Also, SLE was associated with CD (OR 3.92, 95% CI 2.55-6.03, p<0.001) in a multivariate logistic regression model., Conclusions: Patients with SLE had a greater prevalence of CD than matched controls in a large case-control study. A complex combination of genetic, immunological and novel environmental factors may explain this positive association. Physicians should keep in mind that CD can be a tricky diagnosis in SLE patients, yet a treatable condition, probably more common in this population than we used to think., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The prevalence of hypothyroidism in SLE patients varies considerably and early reports were mainly based on small cohorts., Objectives: To investigate the association between SLE and hypothyroidism., Methods: Patients with SLE were compared with age and sex-matched controls regarding the proportion of hypothyroidism in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services., Results: The study included 5018 patients with SLE and 25,090 age and sex-matched controls. The proportion of hypothyroidism in patients with SLE was increased compared with the prevalence in controls (15.58% and 5.75%, respectively, P<0.001). In a multivariate analysis, SLE was associated with hypothyroidism (odds ratio 2.644, 95% confidence interval 2.405-2.908)., Conclusions: Patients with SLE have a greater proportion of hypothyroidism than matched controls. Therefore, physicians treating patients with SLE should be aware of the possibility of thyroid dysfunction., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Despite the frequently encountered association between thyroid disease and systemic lupus erythematosus (SLE) is well known, it is of surprise that only several reports compromised of small population size support this observation., Objectives: To investigate the association of comorbid SLE and hyperthyroidism., Methods: Using the database of the largest health maintenance organization (HMO) in Israel, the Clalit Health Services, we searched for the co-existence of SLE and hyperthyroidism. Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of hyperthyroidism in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis., Results: The study included 5018 patients with SLE and 25,090 age- and sex- matched controls. The prevalence of hyperthyroidism in patients with SLE was increased compared with the prevalence in controls (2.59% and 0.91%, respectively, p < 0.001). In a multivariate analysis, SLE was associated with hyperthyroidism (odds ratio 2.52, 95% confidence interval 2.028-3.137)., Conclusions: Patients with SLE have a greater prevalence of hyperthyroidism than matched controls. Therefore, physicians treating patients with SLE should be aware of this possibility of this thyroid dysfunction.