Depression and anxiety in systemic lupus erythematosus: A case-control study on prevalence and associated factors in a single-center cohort.

OBJECTIVES: To evaluate the prevalence of self-perceived depression and anxiety in patients with systemic lupus erythematosus (SLE) and to explore associated factors. METHODS: Cross-sectional study of unselected patients with SLE (ACR-97 criteria) and controls with chronic inflammatory rheumatic diseases. Both completed the Hospital Anxiety and Depression Scale (HADS). Demographic and clinical characteristics, comorbidity, and treatments were collected, and a multivariate analysis was performed to explore factors associated with depression and anxiety in SLE. RESULTS: The study population comprised 172 patients and 215 controls. Women accounted for 93% of the patients with SLE. Fibromyalgia was recorded in 12.8% and a history of depression in 17%. According to HADS, 37.2% fulfilled the diagnostic criteria for depression and 58.7% those for anxiety; prevalence was similar in the controls (32.6% and 55.1%, respectively). Up to a third of patients with self-perceived depression were not receiving antidepressants. There was no concordance between a previous history of depression and current depression. In the multivariate model, current depression was associated with single marital status (OR 2.69; 95% CI: 1.17-6.42; p = .022), fibromyalgia (7.69; 2.35-30.72; p = .001), smoking (3.12; 1.24-8.07; p = .016), severity of SLE (0.76; 0.6-0.94; p = .016), and organ damage (1.27; 1.01-1.61; p = .042). Current anxiety was only associated with fibromyalgia (3.97; 1.21-17.98; p = .036). CONCLUSIONS: Depression and anxiety are most likely underdiagnosed in SLE. Prevalence appears to be similar to that of other chronic inflammatory rheumatic diseases. Anxiety is associated with fibromyalgia, while depression is also associated with single marital status, smoking, organ damage, and severity of SLE.

Role of targeted therapies in rheumatic patients on COVID-19 outcomes: results from the COVIDSER study.

OBJECTIVES: To analyse the effect of targeted therapies, either biological (b) disease-modifying antirheumatic drugs (DMARDs), targeted synthetic (ts) DMARDs and other factors (demographics, comorbidities or COVID-19 symptoms) on the risk of COVID-19 related hospitalisation in patients with inflammatory rheumatic diseases. METHODS: The COVIDSER study is an observational cohort including 7782 patients with inflammatory rheumatic diseases. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Antirheumatic medication taken immediately prior to infection, demographic characteristics, rheumatic disease diagnosis, comorbidities and COVID-19 symptoms were analysed. RESULTS: A total of 426 cases of symptomatic COVID-19 from 1 March 2020 to 13 April 2021 were included in the analyses: 106 (24.9%) were hospitalised and 19 (4.4%) died. In multivariate-adjusted models, bDMARDs and tsDMARDs in combination were not associated with hospitalisation compared with conventional synthetic DMARDs (OR 0.55, 95% CI 0.24 to 1.25 of b/tsDMARDs, p=0.15). Tumour necrosis factor inhibitors (TNF-i) were associated with a reduced likelihood of hospitalisation (OR 0.32, 95% CI 0.12 to 0.82, p=0.018), whereas rituximab showed a tendency to an increased risk of hospitalisation (OR 4.85, 95% CI 0.86 to 27.2). Glucocorticoid use was not associated with hospitalisation (OR 1.69, 95% CI 0.81 to 3.55). A mix of sociodemographic factors, comorbidities and COVID-19 symptoms contribute to patients' hospitalisation. CONCLUSIONS: The use of targeted therapies as a group is not associated with COVID-19 severity, except for rituximab, which shows a trend towards an increased risk of hospitalisation, while TNF-i was associated with decreased odds of hospitalisation in patients with rheumatic disease. Other factors like age, male gender, comorbidities and COVID-19 symptoms do play a role.

Tobacco smoking is an independent factor associated with retinal damage in systemic lupus erythematosus: a cross-sectional and retrospective study.

To analyze the influence of tobacco smoking on systemic lupus erythematosus (SLE) clinical features and damage. Cross-sectional and retrospective, case-control study comparing SLE patients with and without tobacco exposure. Cumulative clinical data and comorbidities were collected, and severity (Katz index) and damage (SLICC/ACR damage index) (SDI) indices were calculated. Pack-years (PY) was used to estimate lifetime tobacco exposure. A logistic regression was carried out to explore the impact of tobacco use on retinal damage. 216 patients were included. The mean age was 49 years (± 12.7), 93% were females, and median disease duration was 17 years [interquartile range (IQR):9-25]. Fifty-three percent of patients were smokers at some point. The median PY was 13 (IQR: 6-20.5). Only 54.8% of active smokers recalled having been informed of the negative effects of smoking, versus 83.3% of never smokers (< 0.001). In a bivariant analysis, an association between tobacco use at any time and discoid lupus [OR: 3.5(95%CI 1.5-8.9); p = 0.002] photosensitivity [OR: 2.06(95%CI 1.16-3.7); p = 0.01] and peripheral arteriopathy (p = 0.007) was found. Considering SDI item by item, a significant association with retinal damage, adjusted for age [OR: 1.03(95%CI 1-1.07); p = 0.04], was found. Using PYs, an association was found with discoid lupus (p = 0.01), photosensitivity (p = 0.03) and peripheral arteriopathy (p = 0.01), global SDI > 0 (p = 0.002) and retinal damage (p = 0.02). In a multivariate analysis exploring factors associated with retinal damage, any previous smoking history and SDI remained associated with retinal damage. Tobacco smoking is associated with cutaneous manifestations and damage and is an independent predictor of retinal damage in SLE patients.

Incidence, associated factors and clinical impact of severe infections in a large, multicentric cohort of patients with systemic lupus erythematosus.

OBJECTIVES: To estimate the incidence of severe infection and investigate the associated factors and clinical impact in a large systemic lupus erythematosus (SLE) retrospective cohort. METHODS: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ≥4 ACR-97 SLE criteria were retrospectively investigated for severe infections. Patients with and without infections were compared in terms of SLE severity, damage, comorbidities, and demographic characteristics. A multivariable Cox regression model was built to calculate hazard ratios (HRs) for the first infection. RESULTS: A total of 3658 SLE patients were included: 90% female, median age 32.9 years (DQ 9.7), and mean follow-up (months) 120.2 (±87.6). A total of 705 (19.3%) patients suffered ≥1 severe infection. Total severe infections recorded in these patients numbered 1227. The incidence rate was 29.2 (95% CI: 27.6-30.9) infections per 1000 patient years. Time from first infection to second infection was significantly shorter than time from diagnosis to first infection (p < 0.000). Although respiratory infections were the most common (35.5%), bloodstream infections were the most frequent cause of mortality by infection (42.0%). In the Cox regression analysis, the following were all associated with infection: age at diagnosis (HR = 1.016, 95% CI: 1.009-1.023), Latin-American (Amerindian-Mestizo) ethnicity (HR = 2.151, 95% CI: 1.539-3.005), corticosteroids (≥10mg/day) (HR = 1.271, 95% CI: 1.034-1.561), immunosuppressors (HR = 1.348, 95% CI: 1.079-1.684), hospitalization by SLE (HR = 2.567, 95% CI: 1.905-3.459), Katz severity index (HR = 1.160, 95% CI: 1.105-1.217), SLICC/ACR damage index (HR = 1.069, 95% CI: 1.031-1.108), and smoking (HR = 1.332, 95% CI: 1.121-1.583). Duration of antimalarial use (months) proved protective (HR = 0.998, 95% CI: 0.997-0.999). CONCLUSIONS: Severe infection constitutes a predictor of poor prognosis in SLE patients, is more common in Latin-Americans and is associated with age, previous infection, and smoking. Antimalarials exerted a protective effect.

Comorbidities in Patients With Primary Sjögren's Syndrome and Systemic Lupus Erythematosus: A Comparative Registries-Based Study.

OBJECTIVE: To compare the prevalence of the main comorbidities in 2 large cohorts of patients with primary Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE), with a focus on cardiovascular (CV) diseases. METHODS: This was a cross-sectional multicenter study where the prevalence of more relevant comorbidities in 2 cohorts was compared. Patients under followup from SJOGRENSER (Spanish Rheumatology Society Registry of Primary SS) and RELESSER (Spanish Rheumatology Society Registry of SLE), and who fulfilled the 2002 American-European Consensus Group and 1997 American College of Rheumatology classification criteria, respectively, were included. A binomial logistic regression analysis was carried out to explore potential differences, making general adjustments for age, sex, and disease duration and specific adjustments for each variable, including CV risk factors and treatments, when appropriate. RESULTS: A total of 437 primary SS patients (95% female) and 2,926 SLE patients (89% female) were included. The mean age was 58.6 years (interquartile range [IQR] 50.0-69.9 years) for primary SS patients and 45.1 years (IQR 36.4-56.3 years) for SLE patients (P < 0.001), and disease duration was 10.4 years (IQR 6.0-16.7 years) and 13.0 years (IQR 7.45-19.76 years), respectively (P < 0.001). Smoking, dyslipidemia, and arterial hypertension were associated less frequently with primary SS (odds ratio [OR] 0.36 [95% confidence interval (95% CI) 0.28-0.48], 0.74 [95% CI 0.58-0.94], and 0.50 [95% CI 0.38-0.66], respectively) as were life-threatening CV events (i.e., stroke or myocardial infarction; OR 0.57 [95% CI 0.35-0.92]). Conversely, lymphoma was associated more frequently with primary SS (OR 4.41 [95% CI 1.35-14.43]). The prevalence of severe infection was lower in primary SS than in SLE (10.1% versus 16.9%; OR 0.54 [95% CI 0.39-0.76]; P < 0.001). CONCLUSION: Primary SS patients have a consistently less serious CV comorbidity burden and a lower prevalence of severe infection than those with SLE. In contrast, their risk of lymphoma is greater.

Results of a specific smoking cessation program for patients with arthritis in a rheumatology clinic.

The purpose of this study is to evaluate an intervention program in smoker patients. We selected consecutive active smoker patients with rheumatoid arthritis, spondyloarthritis, or connective tissue diseases. The intervention consisted of the following: (1) a baseline visit, which included verbal and written advice by the rheumatologist, emphasizing the practical benefits of smoking cessation. Patients completed a questionnaire that included smoking dependence tests and previous attempts to quit. (2) A follow-up visit to the nurse in the 3rd month for reinforcement and the receiving of pharmacological treatment to help patients quit smoking. The primary outcome was total abstinence in the last 7 days of a phone interview at 3, 6, and 12 months. The secondary outcome was a reduction in cigarette consumption by at least 50%. A total of 945 patients were screened. About 185 (19.5%) were current smokers, and 152 were included for intervention. In the previous 5 years, the mean annual withdrawal rate was 4.6%. The smoking cessation rate was 11.8, 14.4, and 15.7% at 3, 6, and 12 months (OR compared with previous cessation rate 3.8 (CI 95% 1.8-8.1)). Twenty-nine patients (19%) reduced ≥50% of the cigarette consumption at 12 months. The linear regression analysis showed that a score of less dependence (p = 0.03) and previous attempts to quit smoking (p = 0.04) were significantly associated with definitive smoking cessation at 12 months. One out of six patients quit smoking with the aid of an educational program which included verbal and written advice by the rheumatologist and the nurse. As far as we know, this is the first interventional study in smoker patients with arthritis.

Association of the microsatellite in the 3' untranslated region of the CD154 gene with rheumatoid arthritis in females from a Spanish cohort: a case-control study.

CD40-CD154 interaction is an important mediator of inflammation and has been implicated in T helper type 1-mediated autoimmune diseases including rheumatoid arthritis (RA). Linkage studies have shown association of markers in the proximity of the CD154 gene. In the present work we investigated whether specific allele variants of the microsatellite in the 3' UTR of the CD154 gene might modulate the risk of RA. The study, in a case-control setting, included 189 patients and 150 healthy controls from the Canary Islands, Spain. The 24CAs allele was less represented in female patients than in controls (0.444 in controls versus 0.307 in patients, P = 0.006, odds ratio (OR) 0.556, 95% confidence interval (CI) 0.372 to 0.831) but not in males (0.414 versus 0.408), and only when homozygous (P = 0.012; OR 0.35, 95% CI 0.16 to 0.77). We also verified that CD154 association with RA was independent of human leukocyte antigen (HLA) phenotype. A further functional study showed that after stimulation anti-CD3, CD154 mRNA was more stable in CD4+ T lymphocytes from patients with RA bearing the 24CAs allele (mRNA half-life 208 minutes) than in patients without the 24CAs allele (109 minutes, P = 0.009). However, a lower percentage of CD154+CD4+ T lymphocytes was seen in freshly isolated peripheral blood mononuclear cells from patients carrying 24CAs alleles (mean 4.28 versus 8.12; P = 0.033), and also in CD4+ T lymphocytes stimulated with anti-CD3 (median 29.40 versus 47.60; P = 0.025). These results were concordant with the smaller amounts of CD154 mRNA isolated from stimulated T lymphocytes with 24CAs alleles. The CD154 microsatellite therefore seems to affect the expression of the gene in a complex manner that implies not only mRNA stability. These data suggest that the CD154 microsatellite contributes to the regulation of mRNA and protein expression, although further studies will be necessary to elucidate its role in disease predisposition.