Diversity of NF-κB signalling and inflammatory heterogeneity in Rheumatic Autoimmune Disease.

Systemic Autoimmune Rheumatic Diseases, including Rheumatoid Arthritis, Systemic Lupus Erythematosus and Sjogren's syndrome, are characterised by a loss of immune tolerance and chronic inflammation. There is marked heterogeneity in clinical and molecular phenotypes in each condition, and the aetiology of these is unclear. NF-κB is an inducible transcription factor that is critical in the physiological inflammatory response, and which has been implicated in chronic inflammation. Genome-wide association studies have linked risk alleles related to the NF-κB pathway to the pathogenesis of multiple Systemic Autoimmune Rheumatic Diseases. This review describes how cell- and pathway-specific NF-κB activation contribute to the spectrum of clinical phenotypes and molecular pathotypes in rheumatic disease. Potential clinical applications are explored, including therapeutic interventions and utilisation of NF-κB as a biomarker of disease subtypes and treatment response.

Paxlovid use is associated with lower risk of cardiovascular diseases in COVID-19 patients with autoimmune rheumatic diseases: a retrospective cohort study.

BACKGROUND: Paxlovid has been shown to be effective in reducing mortality and hospitalization rates in patients with coronavirus disease 2019 (COVID-19). It is not known whether Paxlovid can reduce the risk of cardiovascular diseases (CVD) in COVID-19-surviving patients with autoimmune rheumatic diseases (AIRDs). METHODS: TriNetX data from the US Collaborative Network were used in this study. A total of 5,671,395 patients with AIRDs were enrolled between January 1, 2010, and December 31, 2021. People diagnosed with COVID-19 were included in the cohort (n = 238,142) from January 1, 2022, to December 31, 2022. The Study population was divided into two groups based on Paxlovid use. Propensity score matching was used to generate groups with matched baseline characteristics. The hazard ratios (HRs) and 95% confidence intervals of cardiovascular outcomes, admission rate, mortality rate, and intensive care unit (ICU) admission rate were calculated between Paxlovid and non-Paxlovid groups. Subgroup analyses on sex, age, race, autoimmune diseases group, and sensitivity analyses for Paxlovid use within the first day or within 2-5 days of COVID-19 diagnosis were performed. RESULTS: Paxlovid use was associated with lower risks of cerebrovascular complications (HR = 0.65 [0.47-0.88]), arrhythmia outcomes (HR = 0.81 [0.68-0.94]), ischemic heart disease, other cardiac disorders (HR = 0.51 [0.35-0.74]) naming heart failure (HR = 0.41 [0.26-0.63]) and deep vein thrombosis (HR = 0.46 [0.24-0.87]) belonging to thrombotic disorders in AIRD patients with COVID-19. Compared with the Non-Paxlovid group, risks of major adverse cardiac events (HR = 0.56 [0.44-0.70]) and any cardiovascular outcome mentioned above (HR = 0.76 [0.66-0.86]) were lower in the Paxlovid group. Moreover, the mortality (HR = 0.21 [0.11-0.40]), admission (HR = 0.68 [0.60-0.76]), and ICU admission rates (HR = 0.52 [0.33-0.80]) were significantly lower in the Paxlovid group than in the non-Paxlovid group. Paxlovid appears to be more effective in male, older, and Black patients with AIRD. The risks of cardiovascular outcomes and severe conditions were reduced significantly with Paxlovid prescribed within the first day of COVID-19 diagnosis. CONCLUSIONS: Paxlovid use is associated with a lower risk of CVDs and severe conditions in COVID-19-surviving patients with AIRD.

Short- and Long-Term Mortality of Hospitalized Patients With Autoimmune Rheumatic Diseases and Serious Infections: A National Cohort Study.

OBJECTIVE: Infectious conditions are a significant cause of mortality in autoimmune rheumatic diseases (ARD). Among patients hospitalized with an infection, we compared in-hospital and long-term (3-year) mortality between those with and without ARD. METHODS: This retrospective analysis included members of the largest health maintenance organization in Israel, aged > 18 years at the first episode of infection, who required hospitalization during 2003-2019. We compared in-hospital mortality and the results of a 3-year landmark analysis of those who survived the index hospitalization between patients with ARD, according to disease subgroups, and patients without ARD. Additionally, we compared mortality outcomes among patients with ARD, according to subgroup diagnosis, matched in a 1:3 ratio by age, sex, and ethnicity to patients without ARD. RESULTS: Included were 365,247 patients who were admitted for the first time with the diagnosis of a serious infection. Of these, we identified 9755 with rheumatoid arthritis (RA), 1351 with systemic lupus erythematosus, 2120 with spondyloarthritis (SpA), 584 with systemic sclerosis, and 3214 with vasculitis. In a matched multivariate analysis, the risk for in-hospital mortality was lower among patients with RA (odds ratio [OR] 0.89, 95% CI 0.81-0.97) and SpA (OR 0.77, 95% CI 0.63-0.94). In a similar analysis, the risk of 3-year mortality was lower among patients with RA (hazard ratio [HR] 0.82, 95% CI 0.78-0.86) and vasculitis (HR 0.86, 95% CI 0.80-0.93). CONCLUSION: Among patients hospitalized for an infection, the risk of in-hospital and 3-year mortality was not increased among those with ARD compared to those without ARD.

Chimeric antigen receptor T-Cell therapy: a new emerging landscape in autoimmune rheumatic diseases.

Chimeric antigen receptor T cell (CAR-T) therapy, an innovative immune cell therapy, has revolutionised the treatment landscape of haematological malignancies. The past two years have witnessed the successful application of CD19-targeting CAR constructs in refractory cases of autoimmune rheumatic diseases, including systemic lupus erythematosus, systemic sclerosis, and anti-synthetase syndrome. In comparison to existing B cell depletion therapies, targeting CD19 has demonstrated a more rapid and profound therapeutic effect, enabling drug-free remission with manageable adverse events. These promising results necessitate validation through long-term, large-sample, randomized controlled studies. Corroborating the role of CAR-T therapy in refractory rheumatological disorders and affirming safety, efficacy and durability of responses are the aims of future clinical studies. Optimising the engineering strategies and better patient selection are also critical to further refining the successful clinical implementation of CAR-T therapy.

Humoral and cellular immunity in patients with rare autoimmune rheumatic diseases following SARS-CoV-2 vaccination.

OBJECTIVES: Coronavirus 2019 vaccine responses in rare autoimmune rheumatic diseases (RAIRDs) remain poorly understood; in particular there is little known about whether people develop effective T cell responses. We conducted an observational study to evaluate the short-term humoral and cell-mediated T cell response after the second severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in RAIRD patients compared with healthy controls (HCs). METHODS: Blood samples were collected after the second dose and anti-spike, anti-nucleocapsid antibody levels and SARS-CoV-2-specific T cell responses were measured and compared with those of HCs. Activation-induced marker and deep phenotyping assays were used to identify differences in T cells between high and no/low antibody groups, followed by multidimensional clustering. RESULTS: A total of 50 patients with RAIRDs were included (31 with AAV, 4 with other systemic vasculitis, 9 with SLE and 6 with myositis). The median anti-spike levels were significantly lower in RAIRD patients compared with HCs (P < 0.0001). Fifteen (33%) patients had undetectable levels and 26 (57%) had levels lower than the lowest HC. Rituximab in the last 12 months (P = 0.003) was associated with reduced immunogenicity compared with a longer pre-vaccination period. There was a significant difference in B cell percentages (P = 0.03) and spike-specific CD4+ T cells (P = 0.02) between no/low antibody vs high antibody groups. Patients in the no/low antibody group had a higher percentage of terminally differentiated (exhausted) T cells. CONCLUSIONS: Following two doses, most RAIRD patients have lower antibody levels than the lowest HC and lower anti-spike T cells. RAIRD patients with no/low antibodies have diminished numbers and poor quality of memory T cells that lack proliferative and functional capacities.

COVID-19 infection, admission and death and the impact of corticosteroids among people with rare autoimmune rheumatic disease during the second wave of COVID-19 in England: results from the RECORDER Project.

OBJECTIVES: To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the second wave of the COVID-19 pandemic in England, and describe the impact of corticosteroids on outcomes. METHODS: Hospital Episode Statistics data were used to identify people alive on 1 August 2020 with ICD-10 codes for RAIRD from the whole population of England. Linked national health records were used to calculate rates and rate ratios of COVID-19 infection and death up to 30 April 2021. Primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. NHS Digital and Office for National Statistics general population data were used for comparison. The association between 30-day corticosteroid usage and COVID-19-related death, COVID-19-related hospital admissions and all-cause deaths was also described. RESULTS: Of 168 330 people with RAIRD, 9961 (5.92%) had a positive COVID-19 PCR test. The age-standardized infection rate ratio between RAIRD and the general population was 0.99 (95% CI: 0.97, 1.00). 1342 (0.80%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.76 (95% CI: 2.63, 2.89) times higher than in the general population. There was a dose-dependent relationship between 30-day corticosteroid usage and COVID-19-related death. There was no increase in deaths due to other causes. CONCLUSIONS: During the second wave of COVID-19 in England, people with RAIRD had the same risk of COVID-19 infection but a 2.76-fold increased risk of COVID-19-related death compared with the general population, with corticosteroids associated with increased risk.

Prevalence and identification of neuropsychiatric symptoms in systemic autoimmune rheumatic diseases: an international mixed methods study.

OBJECTIVE: A limited range of neuropsychiatric symptoms have been reported in systemic autoimmune rheumatic diseases (SARDs), with varied symptom prevalence. This study aimed to investigate a wider range of potential symptoms than previous studies, compare patient self-reports with clinician estimates, and explore barriers to symptom identification. METHODS: Mixed methods were used. Data from SARDs patients (n = 1853) were compared with controls (n = 463) and clinicians (n = 289). In-depth interviews (n = 113) were analysed thematically. Statistical tests compared means of survey items between: patients and controls, 8 different SARD groups, and clinician specialities. RESULTS: Self-reported lifetime prevalences of all 30 neuropsychiatric symptoms investigated (including cognitive, sensorimotor and psychiatric) were significantly higher in SARDs than controls. Validated instruments assessed 55% of SARDs patients as currently having depression and 57% anxiety. Barriers to identifying neuropsychiatric symptoms included: 1) limits to knowledge, guidelines, objective tests, and inter-specialty cooperation; 2) subjectivity, invisibility and believability of symptoms; and 3) under-eliciting, under-reporting and under-documenting. A lower proportion of clinicians (4%) reported never/rarely asking patients about mental health symptoms than the 74% of patients who reported never/rarely being asked in clinic (p< 0.001). Over 50% of SARDs patients had never/rarely reported their mental health symptoms to clinicians; a proportion under-estimated at < 10% by clinicians (p< 0.001). CONCLUSION: Neuropsychiatric symptom self-reported prevalences are significantly higher in SARDs than controls, and greatly underestimated by most clinicians. Research relying on medical records and current guidelines is unlikely to accurately reflect patients' experiences of neuropsychiatric symptoms. Improved inter-specialty communication and greater patient involvement is needed in SARD care and research.

Fourth dose of BNT162b2 vaccine for patients with autoimmune rheumatic diseases in a nationwide setting.

OBJECTIVE: The effectiveness of COVID-19 vaccinations wanes due to immune evasion by the B.1.1.529 (Omicron) variant and diminished antibody titres over time. We aimed to evaluate the benefit of a fourth vaccination dose in patients with autoimmune rheumatic diseases (ARDs). METHODS: This retrospective analysis included ARD patients aged 18 years or older and members of Clalit Health Services in Israel (which at the time of the study insured 52% of the entire population), and covered the period from 16 January 2022 to 31 March 2022, when the predominant SARS-CoV-2 variant was Omicron. We compared patients without previous COVID-19 infection who had received three doses of the BNT162b2 vaccine (the control group) with those who had received the fourth dose. The primary outcome was COVID-19 infection, which was analysed using multivariate Cox regression in the entire cohort and within ARD subgroups. Secondary outcomes were COVID-19-related hospitalizations and COVID-19-related death. RESULTS: We included 43 748 ARD patients, of whom 27 766 and 15 982 were in the control and fourth vaccination groups, respectively. COVID-19 infection occurred in 6942 (25.0%) of the control group and 1754 (11.0%) of the fourth dose group (P < 0.001). Patients vaccinated with the fourth dose had a lower risk of COVID-19 infection than the entire cohort [Hazard Ratio (HR) 0.54, 95% CI 0.52, 0.58] and throughout every subgroup regardless of the baseline characteristic or medical treatment, except for rituximab. A similar association was observed for risk of COVID-19-related hospitalization (HR 0.36, 95% CI 0.22, 0.61) and of COVID-19-related death (HR 0.41, 95% CI 0.24, 0.71). CONCLUSION: A fourth BNT162b2 vaccination of ARD patients was associated with favourable outcomes compared with three doses among patients with no history of COVID-19 infection.

Risk factors associated with COVID-19 in systemic lupus erythematosus: Results from a longitudinal prospective cohort.

INTRODUCTION: Patients with SLE (systemic lupus erythematosus) have a higher risk of infection due to dysregulated immune system as well as long-term use of immunosuppressants (IS). This could influence the risk of COVID-19 and its outcome. METHODS: We conducted a longitudinal prospective study across 15 rheumatology centres during the first wave of the pandemic to understand the risk factors contributing to COVID-19 in SLE patients. During the 6 months follow-up, those who tested positive for COVID-19, their clinical course and outcome information were recorded. RESULTS: Through the study period (April-December 2020), 36/1379 lupus patients (2.9%) developed COVID-19. On analysing the COVID-19 positive versus negative cohort during the study period, male gender (adjusted RR 3.72, 95% C.I. 1.85,7.51) and diabetes (adjusted RR 2.94, 95% C.I. 1.28, 6.79) emerged as the strongest risk factors for COVID-19, in the adjusted analysis. There was no significant influence of organ involvement, hydroxychloroquine, glucocorticoid dosage (prednisolone< 7.5 mg or ≥ 7.5 mg/day) or IS on the risk of COVID-19. There was only one death (1/36) among the lupus patients due to COVID-19. CONCLUSION: Traditional risk factors rather than lupus disease process or IS influenced the risk of COVID-19 in our cohort.

Advances of autoimmune rheumatic diseases related to malignant tumors.

BACKGROUND: Malignant neoplasms are a well-recognized global public health concern, with significant impacts on human health and quality of life. The interplay between tumors and autoimmune rheumatic diseases is complex, and the resulting tumor-associated rheumatic diseases represent a rare and intricate group of conditions that occur in the context of malignant tumors. In addition, various rheumatic diseases can arise as a consequence of oncology treatment. These diseases present with intricate clinical manifestations and pathological features, often rendering them challenging to diagnose and impacting patients' quality of life. Despite this, they have yet to be fully recognized. METHODS: This article presents a literature review of published original articles and review articles concerning paraneoplastic rheumatic syndromes and rheumatic diseases associated with cancer treatment. We conducted a comprehensive literature search in PubMed, Web of Science and Google Scholar databases, excluding duplicated and irrelevant studies. In cases of duplicated research, we selected articles with higher impact factors for the review. RESULTS: This review focuses on the clinical features, diagnosis, and treatment of paraneoplastic rheumatic diseases, as well as the pathogenesis of these diseases. Additionally, we summarize the autoimmune rheumatic diseases associated with cancer treatment. Ultimately, the goal of this review is to enhance recognition and improve the management of autoimmune rheumatic diseases related to tumors.

Evaluation and correlation analysis of ocular surface disorders and quality of life in autoimmune rheumatic diseases: a cross-sectional study.

OBJECTIVE: This cross-sectional study aimed to reveal the association between ocular surface disorders and psychological, physiological situations among autoimmune rheumatic patients. METHODS: Ninety autoimmune rheumatic patients (180 eyes) hospitalized in the Department of Rheumatology, The Second Xiangya Hospital, Central South University and 30 controls (60 eyes) were enrolled in the study. All participants were assessed for ocular surface disorders including dry eye disease (DED) by the Ocular Surface Disease Index (OSDI) for symptoms evaluation, and slim lamp examinations for tear break-up time (TBUT), meibomian gland secretion, symblepharon and corneal clarity, Schirmer I test, corneal fluorescein staining (CFS), lid-parallel conjunctival folds (LIPCOF). Systematic conditions were evaluated using the Short Form 36-Health Survey (SF-36) for health-related quality of life, Hospital Anxiety and Depression Scale (HADS) for anxiety and depression, Health Assessment Questionnaire-Disability Index (HAQ-DI) for difficulties in activities of daily living, and Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Pearson and spearman's analysis were conducted to examine the relationship between systematic conditions and ocular surface conditions. RESULTS: The analyses were controlled for age and sex. 52.22% of eyes (94 in 180) of autoimmune rheumatic patients and 21.67% of eyes (13 in 60) of controls were diagnosed with DED. The autoimmune rheumatic patients showed significant higher OSDI score, fewer basal tear secretion, more severe CFS and conjunctivochalasis than controls. There were no statistically significant differences in TBUT, meibomian gland secretion, symblepharon, and corneal clarity between the two groups. For systematic conditions, autoimmune rheumatic patients had significantly lower SF-36 scores, higher anxiety scores, and HAQ-DI scores than controls. No statistically significant differences were detected in depression scores and PSQI between the two groups. Among autoimmune rheumatic patients, OSDI scores were moderately correlated with quality of life, anxiety, depression and sleep quality. CONCLUSION: Factors including quality of life, anxiety, depression, and sleep quality are associated with ocular surface conditions, especially DED symptoms. Management of systemic conditions and psychotherapy should also be considered as part of the treatment among autoimmune rheumatic patients.

Trends in mortality in patients with systemic autoimmune rheumatic diseases (SARD) during the COVID-19 pandemic in Mexico.

The study aimed to analyze the influence of the COVID-19 pandemic on mortality rates in patients with systemic autoimmune rheumatic diseases (SARD) in Mexico. We selected SARD-related deaths using National Open Data and Information from the Ministry of Health, Mexico, and ICD-10 codes. We assessed the observed compared to the predicted mortality values for 2020 and 2021, employing trends from 2010 to 2019 with joinpoint and prediction modelling analyses. Among 12,742 deaths due to SARD between 2010 and 2021, the age-standardized mortality rate (ASMR) increased significantly between 2010 and 2019 (pre-pandemic) (annual percentage change [APC] 1.1%; 95% CI 0.2-2.1), followed by a non-significant decrease during the pandemic period (APC 13.9%; 95% CI 13.9-5.3). In addition, the observed ASMR of 1.19 for 2020 for SARD and of 1.14 for 2021 were lower than the predicted values of 1.25 (95% CI 1.22-1.28) for 2020 and 1.25 (95% CI 1.20-1.30) for 2021. Similar findings were identified for specific SARD, mainly systemic lupus erythematosus (SLE), or by sex or age group. Interestingly, the observed mortality rates for SLE in the Southern region of 1.00 in 2020 and 1.01 in 2021 were both significantly greater than the predicted values of 0.71 (95% CI 0.65-0.77) in 2020 and 0.71 (95% CI 0.63-0.79). In Mexico, the observed SARD mortality rates were not higher than the expected values during the pandemic, except for SLE in the Southern region. No differences by sex or age group were identified.

Assessment of cardiopulmonary manifestations and its correlation with semi-quantitative scoring of high-resolution computed tomography in patients with autoimmune rheumatic diseases.

PURPOSE: Autoimmune rheumatic diseases (ARD) are groups of diseases that are commonly associated with cardiac and pulmonary manifestations and may affect the morbidity and mortality of the patients. The study aimed to the assessment of cardiopulmonary manifestations and their correlation with the semi-quantitative scoring of high-resolution computed tomography (HRCT) in ARD patients. METHODS AND PATIENTS: 30 patients with ARD were included in the study (mean age 42.2 ± 9.76 years) [10 patients were scleroderma (SSc), 10 patients were rheumatoid arthritis (RA), and 10 patients were systemic lupus erythematosus (SLE)]. They all met the diagnostic criteria of the American College of Rheumatology and underwent spirometry, echocardiography, and chest HRCT. The HRCT was assessed by a semi-quantitative score for parenchymal abnormalities. Correlation between HRCT lung scores and: inflammatory markers, lung volumes in spirometry, and echocardiographic indices has been performed. RESULTS: The total lung score (TLS) by HRCT was 14.8 ± 8.78 (mean ± SD), ground glass opacity score (GGO) was 7.20 ± 5.79 (mean ± SD) and fibrosis lung score (F) was 7.63 ± 6.05 (mean ± SD). TLS correlated significantly with ESR (r 0.528, p 0.003), CRP (r 0.439, p 0.015), PaO2 (r -0.395, P 0.031) FVC% (r -0.687, p 0.001), and echocardiographic Tricuspid E (r -0.370, p 0.044), Tricuspid E/è (r -0.397,p 0.03), ESPAP (r 0.459,p 0.011), TAPSE (r -0.405, p 0.027), MPI-TDI (r -0.428, p 0.018) and RV Global strain(r -0.567, p 0.001). GGO score correlated significantly with ESR (r 0.597, p 0.001), CRP (r 0.473, p 0.008), FVC% (r -0.558, p 0.001), and RV Global strain(r -0.496, p 0.005). F score correlated significantly with FVC% (r -0.397, p 0.030), Tricuspid E/è (r -0.445, p 0.014), ESPAP (r 0.402, p 0.028), and MPI-TDI (r -0.448, p 0.013). CONCLUSION: The total lung score and GGO score in ARD were found to be consistently significantly correlated with FVC% predicted, PaO2, inflammatory markers, and RV functions. Fibrotic score correlated with ESPAP. Therefore, in a clinical setting, most clinicians who monitor patients suffering from ARD should concern with the applicability of semiquantitative HRCT scoring in clinical practice.

The Use of Superb Microvascular Imaging in Evaluating Rheumatic Diseases: A Systematic Review.

Background and Objectives: Superb microvascular imaging is an advanced Doppler algorithm that seems to be useful in detecting low-velocity blood flow without using a contrast agent. Increasing evidence suggests that SMI is a more sensitive tool than conventional Doppler techniques for evaluating rheumatic diseases, especially inflammatory arthritis. We aimed to assess the use of SMI in evaluating joints and extraarticular structures. Materials and Methods: Two reviewers independently reviewed the literature to provide a global overview of the possibilities of SMI in rheumatology. Original English-language articles published between February 2014 and November 2022 were identified through database (PubMed, Medline, Ebsco, the Cochrane Library, and ScienceDirect) searching, and analysed to summarise existing evidence according to PRISMA methodology. Inclusion criteria covered original research articles reporting applications of SMI on rheumatic diseases and musculoskeletal disorders secondary to rheumatic conditions. Qualitative data synthesis was performed. Results: A total of 18 articles were included. No systematic reviews fulfilled our inclusion criteria. Most studies focused on characterising the synovial vascularity of rheumatoid arthritis. There have been several attempts to demonstrate SMI's value for evaluating extra-articular soft tissues (fat pads or salivary glands) and large-diameter vessels. The quantitative importance of SMI vascular indices could become a useful non-invasive diagnostic marker. Studies on therapeutic applications are still scarce, and the majority of studies have gaps in reporting the methodology (ultrasound performance technique and settings) of the research. Conclusions: SMI has proved to be useful in characterising low-flow vascularity, and growing evidence indicates that SMI is a non-invasive and lower-cost tool for prognostic assessment, especially in inflammatory arthritis. Preliminary findings also suggest potential interest in evaluating the effect of treatment.

[Autoimmunity in rheumatology: A review].

Autoimmunity and autoinflammation, co-potentiating pathological processes, are considered within the "immune-inflammatory" continuum (continuity with a variety of elements), reflecting the close relationship between the innate and acquired immune responses. Autoimmunity is the leading pathogenetic mechanism for a specific type of human chronic inflammatory disorders - autoimmune diseases, affecting more than 10% of people in the general population. Advances in molecular biology, pharmacogenetics, and bioinformatics provided the background for individualizing therapy for systemic autoimmune rheumatic diseases within personalized medicine. Studying the immunopathogenesis mechanisms, improving diagnostics, interpreting the molecular taxonomy, and developing approaches to the prevention and personalized therapy of systemic autoimmune rheumatic diseases are the priority issues of modern medicine.

[Current view on the pathogenesis of immune-mediated inflammatory diseases associated with ocular manifestations]. / Sovremennyi vzglyad na patogenez immunovospalitel'nykh zabolevanii, assotsiirovannykh s glaznymi proyavleniyami.

This literature review discusses the new concept of pathogenesis of systemic immune-mediated inflammatory diseases (IMIDs), presents their classification and analyzes their association with ocular manifestations.

COVID-19 infection, admission and death among people with rare autoimmune rheumatic disease in England: results from the RECORDER project.

OBJECTIVES: To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the first wave of the COVID-19 pandemic in England compared with the general population. METHODS: We used Hospital Episode Statistics to identify all people alive on 1 March 2020 with ICD-10 codes for RAIRD from the whole population of England. We used linked national health records (demographic, death certificate, admissions and PCR testing data) to calculate rates of COVID-19 infection and death up to 31 July 2020. Our primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. General population data from Public Health England and the Office for National Statistics were used for comparison. We also describe COVID-19-related hospital admissions and all-cause deaths. RESULTS: We identified a cohort of 168 680 people with RAIRD, of whom 1874 (1.11%) had a positive COVID-19 PCR test. The age-standardized infection rate was 1.54 (95% CI: 1.50, 1.59) times higher than in the general population. A total of 713 (0.42%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.41 (2.30-2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population. CONCLUSIONS: During the first wave of COVID-19 in England, people with RAIRD had a 54% increased risk of COVID-19 infection and more than twice the risk of COVID-19-related death compared with the general population. These increases were seen despite shielding policies.

Telemedicine in rheumatology: a mixed methods study exploring acceptability, preferences and experiences among patients and clinicians.

OBJECTIVES: The Covid-19 pandemic necessitated a rapid global transition towards telemedicine; yet much remains unknown about telemedicine's acceptability and safety in rheumatology. To help address this gap and inform practice, this study investigated rheumatology patient and clinician experiences and views of telemedicine. METHODS: Sequential mixed methodology combined analysis of surveys and in-depth interviews. Between and within-group differences in views of telemedicine were examined for patients and clinicians using t-tests. RESULTS: Surveys (patients n = 1340, clinicians n = 111) and interviews (patients n = 31, clinicians n = 29) were completed between April 2021 and July 2021. The majority of patients were from the UK (96%) and had inflammatory arthritis (32%) or lupus (32%). Patients and clinicians rated telemedicine as worse than face-to-face consultations in almost all categories, although >60% found it more convenient. Building trusting medical relationships and assessment accuracy were great concerns (93% of clinicians and 86% of patients rated telemedicine as worse than face-to-face for assessment accuracy). Telemedicine was perceived to have increased misdiagnoses, inequalities and barriers to accessing care. Participants reported highly disparate telemedicine delivery and responsiveness from primary and secondary care. Although rheumatology clinicians highlighted the importance of a quick response to flaring patients, only 55% of patients were confident that their rheumatology department would respond within 48 hours. CONCLUSION: Findings indicate a preference for face-to-face consultations. Some negative experiences may be due to the pandemic rather than telemedicine specifically, although the risk of greater diagnostic inaccuracies using telemedicine is unlikely to be fully resolved. Training, choice, careful patient selection, and further consultation with clinicians and patients is required to increase telemedicine's acceptability and safety. TRIAL REGISTRATION: This telemedicine study is part of a pre-registered longitudinal multi-stage trial, the LISTEN study (ISRCTN-14966097), with later Covid-related additions registered in March 2021, including a pre-registered statistical analysis plan.

Coronary microvascular disease: The "Meeting Point" of Cardiology, Rheumatology and Endocrinology.

BACKGROUND: Exertional chest pain/dyspnea or chest pain at rest are the main symptoms of coronary artery disease (CAD), which are traditionally attributed to insufficiency of the epicardial coronary arteries. However, 2/3 of women and 1/3 of men with angina and 10% of patients with acute myocardial infarction have no evidence of epicardial coronary artery stenosis in X-ray coronary angiography. In these cases, coronary microvascular disease (CMD) is the main causative factor. AIMS: To present the pathophysiology of CMD in Cardiology, Rheumatology and Endocrinology. MATERIALS-METHODS: The pathophysiology of CMD in Cardiology, Rheumatology and Endocrinology was evaluated. It includes impaired microvascular vasodilatation, which leads to inability of the organism to deal with myocardial oxygen needs and, hence, development of ischemic pain. CMD, observed in inflammatory autoimmune rheumatic and endocrine/metabolic disorders, brings together Cardiology, Rheumatology and Endocrinology. Causative factors include persistent systemic inflammation and endocrine/metabolic abnormalities influencing directly the coronary microvasculature. In the past, the evaluation of microcirculation was feasible only with the use of invasive techniques, such as coronary flow reserve assessment. Currently, the application of advanced imaging modalities, such as cardiovascular magnetic resonance (CMR), can evaluate CMD non-invasively and without ionizing radiation. RESULTS: CMD may present with a variety of symptoms with 1/3 to 2/3 of them expressed as typical chest pain in effort, more commonly found in women during menopause than in men. Atypical presentation includes chest pain at rest or exertional dyspnea,but post exercise symptoms are not uncommon. The treatment with nitrates is less effective in CMD, because their vasodilator action in coronary micro-circulation is less pronounced than in the epicardial coronary arteries. DISCUSSION: Although both classic and new medications have been used in the treatment of CMD, there are still many questions regarding both the pathophysiology and the treatment of this disorder. The potential effects of anti-rheumatic and endocrine medications on the evolution of CMD need further evaluation. CONCLUSION: CMD is a multifactorial disease leading to myocardial ischemia/fibrosis alone or in combination with epicardial coronary artery disease. Endothelial dysfunction/vasospasm, systemic inflammation, and/or neuroendocrine activation may act as causative factors and bring Cardiology, Rheumatology and Endocrinology together. Currently, the application of advanced imaging modalities, and specifically CMR, allows reliable assessment of the extent and severity of CMD. These measurements should not be limited to "pure cardiac patients", as it is known that CMD affects the majority of patients with autoimmune rheumatic and endocrine/metabolic disorders.

Use of gonadotropin-releasing hormone agonists for ovarian preservation in patients receiving cyclophosphamide for systemic lupus erythematosus: A meta-analysis.

BACKGROUND: Cyclophosphamide (CYC) has known cytotoxic effects on ovarian reserve and has been linked to premature ovarian failure (POF) in systemic lupus erythematosus (SLE). The concurrent use of gonadotropin-releasing hormone agonists (GnRHas) is postulated to preserve ovarian function by reducing the number of follicles exposed to CYC, but there is paucity of data to establish its efficacy. We conducted a meta-analysis to summarize the effect of concurrent GnRHa use in persevering ovarian function and pregnancy. METHODS: English language databases of PubMed, Embase, and Cochrane were searched to include studies published between 2000 and 2021. Studies in females with rheumatic diseases receiving concurrent GnRHa and CYC therapy to evaluate ovarian preservation as defined by amenorrhea, follicle stimulating hormone (FSH), anti-mullerian hormone (AMH), or estradiol levels or successful pregnancy were included. We used a fixed effect, exact, Mantel-Haenszel approach to estimate the overall odds ratio (OR) and associated 95% confidence intervals (95% CIs). RESULTS: Seven studies with 218 female patients were included. The ovarian function was preserved in 125/132 (94.6%) of women who received GnRHa concurrently with CYC compared to 50/86 (58%) of women who did not receive GnRHa (OR = 10.3, CI = 4.83-36.29). The OR for pregnancy with GnRHa use = 2.94 (CI = 1.04-9.89). CONCLUSION: Our results based on limited published studies suggest that concurrent GnRHa use preserves ovarian function and increase odds of pregnancy. It can be considered for premenopausal SLE females receiving CYC. Long-term follow-up studies are needed to establish the efficacy and safety of GnRHa use for ovarian preservation.