Cardiovascular disease in patients with systemic autoimmune diseases: The relationship between self-perceived risk and actual risk.

INTRODUCTION: Autoimmune diseases are known to be associated with an elevated risk of cardiovascular diseases; however, there exists a lack of awareness regarding this increased risk among patients. OBJECTIVE: This study aimed to assess the prevalence of cardiovascular risk factors and events in various systemic autoimmune diseases, including Systemic Sclerosis (SSc), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Sjögren's syndrome (SS), matched by age, sex, and disease duration. Additionally, the study aimed to evaluate the perceived and actual risks of cardiovascular disease among patients. METHODS: A cross-sectional self-reported survey on the patient's perspective of cardiovascular risk was conducted between January and June 2023. Sociodemographic and clinical data, including disease activity, were collected through medical records and questionnaires. Traditional cardiovascular risk factors and events were assessed, alongside the perceived cardiovascular risk. The SCORE calculation and Charlson Comorbidity Index (CCI) were employed for cardiovascular risk assessment. RESULTS: Survey responses from 180 patients (45 patients each with SSc, SLE, RA, and SS) with systemic autoimmune diseases revealed that 20% perceived a low risk, 23% perceived neither lower nor higher, and 56% perceived a higher risk of developing cardiovascular diseases in the next ten years. Only 45% agreed that their autoimmune disease could increase the risk of a heart attack, even in the absence of other risk factors, and 46.7% were unaware that NSAIDs pose a cardiovascular risk. An association between cardiovascular risk measured by SCORE, comorbidities, and risk perception was observed in RA, SSc, and SS patients, with no association found in SLE patients (p=0.27). Except for SS patients (p=0.02), no association between CCI and disease activity level was found. Regarding the influence of age, working status, and education in CVD risk perception, an association between CVD risk perception and age was observed (p=0.01), with patients over 40 years exhibiting a higher perception of CVD risk. No differences were found regarding working status (p=0.19) nor education level (p=0.06). CONCLUSIONS: Patients with SS, RA, and SSc displayed a heightened perception of cardiovascular risk, correlating with their actual risk and preexisting comorbidities. However, patients exhibited unawareness of certain cardiovascular risk behaviors. This underscores the need for tailored education programs on cardiovascular risk for autoimmune disease patients, to be implemented at the time of diagnosis and during follow-up in outpatient clinics.

The diagnosis and management of systemic autoimmune rheumatic disease-related interstitial lung disease: British Society for Rheumatology guideline scope.

Interstitial lung disease (ILD) is a significant complication of many systemic autoimmune rheumatic diseases (SARDs), although the clinical presentation, severity and outlook may vary widely between individuals. Despite the prevalence, there are no specific guidelines addressing the issue of screening, diagnosis and management of ILD across this diverse group. Guidelines from the ACR and EULAR are expected, but there is a need for UK-specific guidelines that consider the framework of the UK National Health Service, local licensing and funding strategies. This article outlines the intended scope for the British Society for Rheumatology guideline on the diagnosis and management of SARD-ILD developed by the guideline working group. It specifically identifies the SARDs for consideration, alongside the overarching principles for which systematic review will be conducted. Expert consensus will be produced based on the most up-to-date available evidence for inclusion within the final guideline. Key issues to be addressed include recommendations for screening of ILD, identifying the methodology and frequency of monitoring and pharmacological and non-pharmacological management. The guideline will be developed according to methods and processes outlined in Creating Clinical Guidelines: British Society for Rheumatology Protocol version 5.1.

Coalition for Health and Gender Equity (CHANGE)-a protocol for a global cross-sectional survey of health and gender equity in rheumatology.

Objectives: The primary aim of the CHANGE survey is to determine the current state of gender equity within rheumatology, and secondarily, to review the physician perspective on bullying, harassment and equipoise of opportunities within rheumatology. Methods: The CHANGE e-survey is a cross-sectional self-reported questionnaire adapted from EULAR's gender equity in academic rheumatology task force. The survey was launched in January 2023; it is available in six languages and distributed widely via rheumatology organizations and social media. Eligible participants include rheumatologist physicians and rheumatology health-care professionals. Survey responses will undergo descriptive analysis and inter-group comparison aiming to explore gender-based discrimination using logistic regression, with subgroup analyses for country/continent variations. Conclusion: This e-survey represents a comprehensive global initiative led by an international consortium, aimed at exploring and investigating the gender-related disparities and obstacles encountered by rheumatologists and rheumatology health-care professionals across diverse communities and health-care environments. By pursuing this initiative, we aim to take the broader rheumatology community a step closer to understanding the underlying origins of inequities and their determinants. Such insights are pivotal in identifying viable interventions and strategies to foster gender equity within the field. Ultimately, our collective objective is to ensure equitable access to opportunities for every individual, irrespective of gender, thereby promoting inclusivity and fairness across the entire spectrum of professional practice and career development.

KL6 and IL-18 levels are negatively correlated with respiratory function tests and ILD extent assessed on HRCT in patients with systemic sclerosis-related interstitial lung disease (SSc-ILD).

BACKGROUND: Interstitial lung disease (ILD) is one of the leading causes of mortality in patients with systemic sclerosis (SSc). Serum biomarkers have been suggested as indicators for pulmonary damage with clinical value in the diagnosis and prognosis of SSc-ILD. OBJECTIVES: To investigate the role of serum biomarkers (Krebs von den Lungen-6 KL-6, IL-18 and IL-18BP) as a potential biomarker reflecting the severity of SSc-ILD as assessed through high-resolution computed tomography (HRCT) and pulmonary function tests (PFT), including forced vital capacity (%FVC) and diffusing capacity of the lung for carbon monoxide (%DLCO). METHODS: A cross-sectional study including patients with SSc fulfilling the 2013 ACR/EULAR criteria was performed. Patients were classified according to disease duration and pulmonary involvement (presence of ILD). All SSc patients underwent chest HRCT scans and pulmonary function test at baseline. Serum concentration of KL-6, IL8 and IL18BP were determined using the quantitative ELISA technique, sandwich type (solid phase sandwich Enzyme Linked-Immuno-Sorbent Assay), with kits from MyBiosource for KL-6 and from Invitrogen for IL18 and IL18BP. A semiquantitative grade of ILD extent was evaluated through HRCT scan (grade 1, 0-20%; grade 2, >20%). Extensive disease was defined as >20% lung involvement on HRCT, and FVC <70% predicted and limited lung involvement as ≤20% ILD involvement on HRCT, and an FVC ≥70% predicted. RESULTS: 74 patients were included, 27% were male. The mean age at diagnosis was 57.5±15 years and the mean time since diagnosis was 7.67±8 years. 28 patients had ILD (38%). 64% of patients had <20% ILD extent classified through HRCT scan. SSc-ILD patients had elevated serum KL-6 and IL-18 levels compared to patients without ILD (p=0.003 and p=0.04), and those findings were preserved after adjusting for age and sex. Negative correlation between KL-6 levels and%FVC (ß=-0.25, p 0.037) and% DLCO (ß=-0.28, p 0.02) and between IL-18 levels and%FVC (ß=-0.38, p 0.001) and%DLCO (ß=-0.27, p 0.03) were found. Serum KL-6 and IL-18 levels successfully differentiated grades 1 and 2 of the semiquantitative grades of ILD extent (p = 0.028 and p = 0.022). Semiquantitative grades of ILD on the HRCT scan were significantly proportional to the KL-6 (p = 0.01) and IL-18 (p = 0.03). A positive correlation between extensive lung disease and KL-6 (ß=0.42, p = 0.007) but not with IL-18 was found. CONCLUSIONS: Serum KL-6 levels and IL-18 were increased in patients with SSc-ILD and showed a positive correlation with ILD severity as measured using a semiquantitative CT grading scale and negative correlation with PFT parameters. Serum KL-6 and IL-18 could be a clinically useful biomarker in screening and evaluating SSc-ILD.

Factors Associated With Adverse Outcomes in Uveitis Related to Spondyloarthritis: Development of an Outcome Score (SpA-U).

BACKGROUND: Evaluating the efficacy and refractoriness to treatment and determining factors associated with adverse outcomes in uveitis associated with spondylarthritis (SpA) are complicated by the lack of validated outcome measures. OBJECTIVES: The aims of this study were to develop an outcome score SpA-U in patients with uveitis associated with SpA and to determine factors associated with adverse outcomes in patients with uveitis under systemic treatment. METHODS: The outcome score SpA-U was defined by best-corrected visual acuity, anterior chamber inflammation, macular edema and inflammation of posterior chamber, global assessment, and refractoriness to treatment. Factors associated with adverse outcomes in uveitis were studied using linear regression. For categorical factors, marginal averages and their SEs are displayed together with linear regression coefficients with 95% confidence intervals. For continuous factors, averages and SDs are reported in addition to linear regression coefficients with 95% confidence interval. Two regression coefficients are reported for each variable: unadjusted and adjusted for age at diagnosis and sex. RESULTS: One hundred ninety-seven uveitis outbreaks were included. Sixty-two uveitis outbreaks (31%) were classified as severe, 42 as moderate (21%), and 93 as mild (47%) based on the definition and construction of outcome score. The results of the linear regression model revealed that the uveitis activity was more severe in patients with smoking history ( ß = 0.34), axial and peripheral involvement ( ß = 0.43), Ankylosing Spondylitis Disease Activity Score >2.1 ( ß = 0.45), positive HLA-B27 ( ß = 0.29), female sex ( ß = 0.19), patients with C-reactive protein elevation ( ß = 0.002), and bilateral ocular involvement ( ß = 0.32). At the same time, shorter disease evolution ( ß = -0.02) was associated with less severe uveitis activity. CONCLUSION: We have determined factors associated with adverse outcomes in patients with uveitis associated with SpA by developing an outcome score SpA-U that integrates ocular inflammatory activity, visual acuity, global assessment, and refractoriness to treatment.

Polyautoimmunity in systemic lupus erythematosus: secondary Sjogren syndrome.

BACKGROUND: Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands. It can be associated with other connective tissue diseases, including systemic lupus erythematosus (SLE). OBJECTIVE: This study aimed to determine the incidence of secondary SS (sSS) in patients diagnosed with SLE (SLE-SS) and compare the clinical and serological features of SLE-SS to SLE only. METHODS: A retrospective observational study including patients diagnosed with SLE (SLICC criteria) seen at the Rheumatology Department between 1990 and 2020 was performed. A total of 453 SLE patients were assessed for fulfilment of the criteria for SS using the European questionnaire and Schirmer test, fluorescein staining/non-stimulated whole-salivary flow, anti-Ro/La antibodies, and lip biopsy. Anti-Ro/SSA and anti-La/SSB antibodies and rheumatoid factor (RF) were measured at entry and at SS assessment. SLE-SS was defined according to the American-European Consensus Criteria (AECC). SLE-SS was defined as a case that initially only fulfilled SLE classification criteria but which exhibited disease progression during follow-up and then met classification criteria for sSS. RESULTS: SLE-SS occurred in 11% of the SLE patients. In comparison to SLE-only patients, the SLE-SS group was older at inclusion and onset, and had a longer disease course. Sicca syndrome, oral ulcers, pulmonary involvement, and peripheral neuropathy were more frequent. Anti-SSA, anti-SSB, RF, and total IgG were higher in the SLE-SS group. CONCLUSION: SLE-SS appears to be a subgroup of patients with distinct clinical and serologic features. The frequency of SLE-SS increases with age. Patients with SLE-SS have a higher frequency of oral ulcers, anti-Ro and anti-La antibodies, and a lower frequency of renal disease, anti-dsDNA antibodies, anti-SM, and lower C3 and C4 hypocomplementemia.

Factors associated with adverse pregnancy outcomes in patients with systemic lupus erythematosus.

BACKGROUND: Pregnancies in Systemic lupus erythematosus (SLE) are considered high risk and associated with maternal and obstetric complications. OBJECTIVES: To determine the most important predictors for each of the main adverse pregnancy outcomes in SLE patients. METHODS: Patients with SLE were retrospectively analysed from 1990 to 2020. Maternal and fetal complications in pregnant women with SLE were retrieved. We compared clinical and analytical characteristics of SLE patients with adverse pregnancy outcomes to controls with SLE diagnosis without adverse pregnancy outcomes. Qualitative data were analysed by Chi-square test and Fisher's exact test. Continuous variables were analysed by using Student's t test. Multiple logistic regression was performed to determine the predictive factors for adverse pregnancy outcomes with adjustment of confounding factors. RESULTS: 135 multiparous women were included (42% with adverse pregnancy outcomes). A total of 57 pregnancies (42%) were linked to adverse outcomes. The occurrence of abortion was correlated with anti-DNAds (ß = 0.71, p = 0.04), renal involvement (ß = 0.28, p 0.03), antiphospholipid antibodies (APA) (ß = 0.29, p 0.03), erythrocyte sedimentation rate (ESR) elevation (ß = 0.81, p = 0.02) and C-reactive protein (CPR) elevation (ß = 0.91, p = 0.01). Stillbirth was also correlated with renal involvement (ß = 0.26, p = 0.04), APA (ß = 0.22, p = 0.03) and ESR elevation (ß = 0.53, p = 0.02). Preeclampsia was correlated with direct Coombs positivity (ß = 0.42, p = 0.01), serositis (ß = 0.31, p = 0.02), ESR elevation (ß = 0.52, p = 0.03) and CPR elevation (ß = 0.32, p = 0.04). Neonatal Lupus was correlated with anti-RNP (ß = 0.16, p = 0.03) and anti-Ro/SSA (ß = 0.16, p 0.02). CONCLUSIONS: The most unfavourable pregnancy outcome in women with SLE was spontaneous abortion. Renal involvement, anti-DNAds positivity, antiphospholipid antibody positivity, anti-Ro/SSA, elevated ESR and a younger age at disease onset increased the risk of pregnancy complications.

Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory rheumatic diseases.

BACKGROUND: Patients with immune-mediated rheumatic diseases (IMRDs) are commonly treated with immunosuppressors and prone to infections. Recently introduced mRNA SARS-CoV-2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-CoV-2 mRNA vaccines. AIMS: To fully characterise B-cell and T-cell immune responses elicited by mRNA SARS-CoV-2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccine's immunogenicity. METHODS: Humoral, CD4 and CD8 immune responses were investigated in 100 naïve patients with SARS-CoV-2 with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-CoV-2 mRNA vaccine. Responses were compared with age, gender and disease-matched patients with IMRD not receiving immunosuppressors and with healthy controls. RESULTS: Patients with IMRD showed decreased seroconversion rates (80% vs 100%, p=0.03) and cellular immune responses (75% vs 100%, p=0.02). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept decreased humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed impaired humoral responses, but cellular responses were often preserved. Antibody titres were reduced with mycophenolate and azathioprine but preserved with leflunomide and anticytokines. CONCLUSIONS: Patients with IMRD exhibit impaired SARS-CoV-2 vaccine immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine's immunogenicity.

Anti-TNF-α-induced lupus syndrome : Two case reports and review of current literature.

Anti-tumor necrosis factor­α (TNF-α)-induced lupus (ATIL) represents a diagnostic and treatment challenge. Most cases are caused by infliximab and in some cases by etanercept and adalimumab. Symptoms can range from cutaneous manifestations to more rare and serious conditions. Diagnosis requires a temporal relationship between symptoms and positive autoantibody determination. Arthritis and cutaneous symptoms are the most common manifestations accompanied by positive antinuclear antibody (ANA) and anti-double strand DNA (dsDNA) determinations. The etiology of ATILS remains to be definitively established. Several mechanisms have been proposed for anti-TNF-α-induced lupus, including apoptosis, immunosuppression and humoral autoimmunity. Treatment includes discontinuation of anti-TNF­α agents and in some cases corticosteroids and immunosuppressors. Questions to be answered: (1) Are soluble TNF receptor fusion proteins such as etanercept and anti-TNF chimeric antibodies equally likely to cause ATIL? (2) Can patients with ATIL switch from one anti-TNF­α antagonist to another? (3) Can the concurrent use of a conventional synthetic disease-modifying antirheumatic drug (csDMARD) like methotrexate or hydroxychloroquine reduce the probability of ATIL?