Autoimmune Rheumatic Diseases Research Articles

Risk of mycobacterial infections in a cohort of silicosis patients with autoimmune rheumatic diseases

Objective: To evaluate the incidence rates of mycobacterial infections in silicosis patients with systemic autoimmune rheumatic disease (ARD). Methods: This was a retrospective cohort of silicosis patients between January of 1999 and December of 2023. We compared the incidence of tuberculosis and nontuberculous mycobacterial disease (NTM) in patients with silicosis with and without ARD. We also compared the tuberculosis incidence in the overall cohort with general Brazilian population estimates. Results: The study comprised 369 silicosis patients, of whom 35 (9.5%) had ARD. Having ARD did not affect the cumulative incidence of mycobacterial diseases. The risk of tuberculosis was higher in the cohort when compared with that in the adult Brazilian male population (age-adjusted incidence rate ratio = 20.46; 95% CI 14.89-28.13). Conclusions: In this cohort of patients with silicosis, ARD was not associated with the incidence of mycobacterial diseases.

Serum levels of free light chains and syndecan-1 in patients with rheumatoid arthritis and systemic lupus erythematosus.

Systemic autoimmune rheumatic diseases (SARDs) are characterized by chronic inflammation. Reliable biomarkers are crucial for diagnosis, monitoring disease progression and therapeutic responses. This study explores serum Syndecan-1 (SDC-1) as a biomarker for these conditions and its relationship with free light chain (FLC) levels. A retrospective analysis was performed on sera from 60 patients with rheumatoid arthritis (RA) and from 60 with systemic lupus erythematosus (SLE), alongside 50 healthy donors (HD). Κ- and λ- FLCs were determined by turbidimetric assay, while SDC-1 levels by ELISA. Kruskal-Wallis test, Wilcoxon-Mann-Whitney U test, multivariable linear regression and Spearman's correlation were employed to compare biomarker levels across groups and to explore correlations. SDC-1, κ-FLC, and λ-FLC were significantly increased in RA and SLE patients compared with HD (p< 0.001), while no significant differences in the κ/λ ratio were observed among the groups (p= 0.4). A significant difference in subject age was also identified. However, multivariate regression analysis indicated that RA and SLE are significantly associated with the levels of these markers, with minimal confounding by age. A significant correlation was observed separately in all groups between the FLC markers. Conversely, no correlation was detected between SDC-1 and FLCs, nor between these markers and age or disease activity indices. Elevated serum levels of FLCs and SDC-1 in RA and SLE patients compared with HD underscore their potential as biomarkers for SARDs. The findings also suggest sustained plasma cell activation, supporting the multifaceted role of SDC-1 in the pathogenesis of SARDs.

Comparison of group versus individual patient education for promoting safety skills of patients with autoimmune rheumatic diseases treated with biologics: a multicentre randomised controlled trial.

To evaluate the effectiveness of a nurse-led intervention combining face-to-face and group education sessions for the acquisition of safety skills by patients with autoimmune rheumatic diseases treated with biologics. This multicentre randomised controlled trial compared two individual patient education sessions against a combination of an individual session at baseline and a group session 3months later. The primary outcome was a validated questionnaire (BioSecure) scored at 6 and 12 months that assessed competencies and problem-solving abilities to deal with fever, infection, vaccination, and daily situations. Secondary outcomes were fear of disease, anxiety, depression, and arthritis helplessness. A total of 120 patients with rheumatoid arthritis and spondyloarthritis were included (60 in each arm) from 7 French rheumatology departments; 99 patients completed the study at 6months and 83 at 12months. The BioSecure score improved at 6months in both arms (delta from baseline 14.9 ± 16.3 in face-to-face education and 16.0 ± 17.9 in combined education) and was maintained for 12months but no significant difference was found between arms at 6 and 12months (p = 0.35 and p = 0.13, respectively). Fear of disease, arthritis helplessness, and anxiety were improved at 6 and 12months with no difference between arms. Educating patients using individual nurse-led sessions or a combination of individual and group sessions increased their safety skills on biologics, with no superiority shown for the combined format. Given the time and resources required to educate patients, these results could lead to potential cost savings. Clinical Trials: NCT03838939. Key Points • Face-to-face patient education has been shown effective in promoting safety skills of patients treated with biologics compared to information provided by the rheumatologist in usual care. • This randomised controlled trial showed that a patient education format combining one individual and one group session was not superior to two individual sessions regarding safety skills assessed at 6 and 12months • Safety skills, fear of disease, arthritis helplessness, and anxiety were improved in both arms. • As the most common barriers to the implementation of patient education are constraints in time and resources, these results could lead to potential cost savings.

The Impact of Anti-inflammatory Therapy on Parkinson's Disease Incidence: A Retrospective Cohort Study

BackgroundPrevious research suggests shared pathophysiology between Parkinson's Disease (PD) and autoimmune disorders, with inflammation reduction as a potential PD intervention. The impact of anti-tumor necrosis factor (anti-TNF) and anti-interleukin (IL)-17 drugs on PD development has yielded conflicting results. ObjectivesThe study investigated the association between PD incidence and immunosuppressive anti-inflammatory drugs in patients with autoimmune diseases (rheumatoid arthritis, ulcerative colitis, Crohn’s disease, ankylosing spondylitis, psoriasis/psoriatic arthritis). MethodsA retrospective study was conducted using data from 2014-2022 from the US Komodo Health claims database. Two cohorts of patients diagnosed with autoimmune diseases were designed: 1) exposed to biologic disease-modifying antirheumatic drugs (bDMARDS e.g., anti-TNF/anti-IL-17 drugs) and 2) absent such exposure. Person-time incidence rates of PD per 100 person-years (PY) and incidence rate ratios (IRRs) were calculated and covariate adjusted via Poisson regressions. ResultsAmong 2,105,677 identified patients with autoimmune disease, 114,082 were treated with anti-TNF/anti-IL-17 and 1,991,595 were not. Unadjusted analyses indicated lower PD incidence in those treated with bDMARDscompared to the not treated (0.661 vs 0.949 per 100-PY; IRR 0.696 [95% CI: 0.669-0.724]). Multivariate Poisson models comparing cohorts exposed to bDMARDs vs those lacking exposure resulted in significantly lower risk of PD (adjusted IRR 0.77 [95% CI 0.74-0.80], p-value <.0001). For patients exposed to anti-TNF or anti-IL-17 therapies, the IRRs were 0.77 (95% CI 0.74-0.81) and 0.64 (95% CI 0.52-0.80), respectively (p-values<0.001). ConclusionsThe results suggest that reduced systemic inflammation via anti-TNF or anti-IL-17 treatment may decrease PD risk in patients with autoimmune diseases.

Rheumatic manifestations and sequela of acute parvovirus B19 infection in hospitalized adult population.

Parvovirus B19 infection has been associated with various clinical entities including musculoskeletal manifestations and the development of different autoimmune diseases. The aim of our study is to examine the musculoskeletal manifestations associated with acute parvovirus B19 infection and the possible development of chronic autoimmune rheumatic diseases. Retrospective cohort study that included adult hospitalized patients diagnosed with an acute parvovirus B19 infection between 1 January 2021 and 1 February 2024. Subjects were followed-up for 6-12 months after hospitalization aiming to identify patients who developed chronic autoimmune rheumatic diseases. The study included 23 patients diagnosed with acute parvovirus B19 infection. Patients were predominantly females (16, 69.6%) with mean age at diagnosis of 39.3 ± 13.11 years. Most patients were Jewish (15, 65.2%). The two most common acute symptoms were fever (82.6%) and myalgia (56.5%). Polyarthritis was present only in three patients (13%) and all of them had wrists involvement. Anti-nuclear antibodies and rheumatoid factor were the most common autoantibodies present with equal prevalence each (13%). Five patients were treated with prednisone during the acute phase (21%), two (8.7%) of them needed drug escalation and were subsequently treated with hydroxychloroquine and methotrexate. One patient developed systemic lupus erythematosus during the first 6 months of follow-up. Musculoskeletal manifestations developing during acute parvovirus B19 are usually self-limited with only a small minority of patients developing chronic autoimmune diseases. It is crucial to differentiate self-limited manifestations related to acute parvovirus B19 from idiopathic autoimmune diseases aiming to avoid unnecessary immunosuppressive therapy.

P35 Pyrexia of unknown origin in a patient with long standing rheumatoid arthritis

Abstract Introduction Pyrexia of unknown origin (PUO) can be challenging in treated rheumatic auto-immune disease. Many conditions may have fever as part of the symptom complex, treatment may mask signs and symptoms and can also make opportunistic infection more likely. Unusual or fastidious infections can be particularly difficult to diagnose. We describe a case of ureaplasma infection that evaded detection for a prolonged period in a female with long standing rheumatoid arthritis (RA). Case description 47 year old female presented January 2023 with fevers, weight loss and persistently high CRP. RA diagnosed in 1998. Erosive wrist and MTP disease, initial RF 32, CCP 8. Treatment- 5-10 mg prednisolone since 1998, adalimumab 2010, rituximab 2013-2022. Normal Ig levels, IgG lamda paraprotein since 2016 (too low to quantify). Frequency and dysuria March 2022. Cystoscopy- small bladder; biopsies in May 2022 and August 2023 showed acute on chronic inflammatory infiltrate with granulation tissue. Interstitial cystitis diagnosed. She had recurrent episodes of pyuria and was given several courses of antibiotics, including meropenem, temocillin, fluconazole, gentamicin. Despite the recurrent pyuria no organisms were cultured. CT CAP February 2023 -ground glass opacity right lower lobe. Later CXR clear. Quantiferon negative, also negative 2016, 2019. Other normal / negative tests- TTG, HIV, Hep ABCE, TFTs, EBV viral load. EBV, CMV IgG +ve. CMV titres 696 c/ml June 2023. CD 19 undetectable. IgG4 0.02 g/L. MPO, PR3 negative. BK virus was detected in urine. There was no sustained response to iv methylprednisolone and a course of filgotinib given for possible systemic RA symptoms. She developed a dry cough and shortness of breath. PET-CT July 2023 - bilateral FDG avid large confluent areas of consolidation. Urine + bronchial washings were negative for TB growth at 42 days. However, in view of deterioration empirical TB treatment was started July 2023. CT urogram in September 2023 showed likely bilateral renal abcesses, as well as bilateral hydronephrosis. Left renal cyst aspirate was performed and empirical doxycycline started at 100 mg bd. Ureaplasma detected from the aspirate on PCR. 3 weeks doxycyline given with rapid resolution of fevers and CRP. February 2024- cystectomy and ileal conduit in for refractory interstitial cystitis with a poorly compliant, small capacity, thick walled fibrotic bladder which had caused bilateral ureteric obstruction. She has made a good recovery. TB treatment course was completed. Discussion This case shows the difficulties in diagnosing infection from a little known and difficult to detect organism, ureaplasma. Discovered in the 1950s, it has no cell wall and very small genome and is therefore an obligate parasite /saprophyte. Together with mycoplasma it belongs to the bacterial class of Mollicutes. It cannot be routinely cultured nor gram stained. PCR or specialist culture is required. It may be present as a commensal but has been implicated in symptomatic genitourinary infections. It has also been implicated in native and non-native joint infections, and in infants can cause a pneumonic illness. Empirical treatment may be indicated due to long turn around times for diagnosis. There is some evidence that reduced humoral immunity may be a contributory factor to infection. We have found a previous case described of ureaplasma renal abcesses in a patient with MS and neurogenic bladder treated with rituximab. Our patient had normal immunoglobulin levels though still had profound CD19 suppression. Further immune suppression resulted from methylprednisolone and course of filgotinib, which may have accelerated the course of infection. Ureaplasma and mycoplasma do not have a cell wall, thus making beta-lactam antibiotics and vancomycin ineffective. Cyclines, josamycin and fluroquinolones are effective, though there is increasing resistance developing. We gave a relatively long course of doxycycline as our patient was very unwell and had apparent extensive urinary tract involvement. BK virus seropositivity is present in 90% of the normal population and asymptomatic viruria in up to 20%. However, it is a cause of renal tract inflammation in the immunosuppressed – in particular post-transplant. We felt it was unlikely to be significant in our patient in view of the clinical picture, lack of BK viraemia and negative viral findings on bladder biopsy. Key learning points • Ureaplasma should be on the list of organisms to consider in cases of PUO when the more common infective causes have been ruled out, particularly in immune suppressed patients. Patience and close collaboration with colleagues is essential. This patient had multiple MDT meetings involving infectious disease, respiratory, secondary and tertiary care urology and rheumatology specialists. The collaboration was invaluable. A course of doxycycline may be considered as a relatively low risk approach while awaiting microbiological confirmation in such cases.

Information and communication technology-based patient education for autoimmune inflammatory rheumatic diseases: A scoping review

ObjectiveThis review aimed to map the existing the information and communication technology (ICT)-based patient education for autoimmune inflammatory rheumatic diseases and identify key effectiveness factors and guidelines for professionals. MethodsA scoping review systematically reviewed PubMed, Cochrane library, EMBASE and Web of Science. We designed search strategies to identify ICT-based patient education for autoimmune inflammatory rheumatic diseases focused on rheumatoid arthritis, ankylosing spondylitis, and systemic lupus erythematosus, published between January 2011 and October 2023. Data extraction was independently screened by two reviewers according to the eligibility criteria. ResultsOf 13,861 records, 18 met the eligibility criteria. Most studies were randomized controlled trials, primarily conducted in the USA, focusing on rheumatoid arthritis. ICT-based interventions included web-based platforms, aiming to improve self-management, medication adherence, with most interventions showing significant improvements. Digital tools such as websites, chatbots were common. Five groups representing the ICT functions were identified: digital self-management tools, multimedia learning materials, personalized educational sessions, behavior change and empathy games, and interactive online communities and peer support. Most studies lacked theoretical frameworks, or guidelines for developing patient education. ConclusionICT-based patient education has significant potential for enhancing self-management and behavior changes in patients with autoimmune inflammatory rheumatic diseases.

Exercise for improving bone health in patients with AIRDs: Understanding underlying biology and physiology.

Exercise has numerous health benefits in patients with autoimmune inflammatory rheumatic diseases (AIRDs). Regular physical activity can help maintain/improve bone health. The aim of the present article was to review current knowledge on the effects of exercise on bone health in patients with AIRDs, particularly in those experiencing a high corticosteroid burden. The article also aimed to discuss potential mechanisms underlying the benefits of physical activity/exercise on bone tissue. Potential explanations regarding the role of exercise on bone health in AIRDs include anti-inflammatory effects, mechanical loading, improvement in muscle strength, hormonal changes, improvement in balance, and effects on telomere erosion, deoxyribonucleic acid methylation, and gene expression. Current evidence regarding the outcomes of exercise on bone health in patients with AIRDs is predominantly derived from studies focused on rheumatoid arthritis. Expanding research to include other rheumatic conditions would enhance the overall understanding of this topic.

Clinical Characteristics of Anti-Synthetase Syndrome: Analysis from the CLASS project.

Anti-synthetase syndrome (ASSD) is a rare systemic autoimmune rheumatic disease (SARD) with significant heterogeneity and no shared classification criteria. We aimed to identify clinical and serological features associated with ASSD that may be suitable for inclusion in the data-driven classification criteria for ASSD. We utilized a large, international, multi-center "Classification Criteria for Anti-synthetase Syndrome" (CLASS) project database, which includes both ASSD patients and controls with mimicking conditions, namely SARDs and/or interstitial lung disease (ILD). The local diagnoses of ASSD and controls were confirmed by project team members. We employed univariable logistic regression and multivariable Ridge regression to evaluate clinical and serological features associated with an ASSD diagnosis in a randomly selected subset of the cohort. Our analysis included 948 ASSD cases and 1077 controls. Joint, muscle, lung, skin, and cardiac involvement were more prevalent in ASSD than in controls. Specific variables associated with ASSD included arthritis, diffuse myalgia, muscle weakness, muscle enzyme elevation, ILD, mechanic's hands, secondary pulmonary hypertension due to ILD, Raynaud phenomenon, and unexplained fever. In terms of serological variables, Jo-1 and non-Jo-1 anti-synthetase autoantibodies, antinuclear antibodies with cytoplasmic pattern, and anti-Ro52 autoantibodies were associated with ASSD. In contrast, isolated arthralgia, dysphagia, electromyography/MRI/muscle biopsy findings suggestive of myopathy, inflammatory rashes, myocarditis, and pulmonary arterial hypertension did not differentiate between ASSD and controls or were inversely associated with ASSD. We identified key clinical and serological variables associated with ASSD, which will help clinicians and offer insights into the development of data-driven classification criteria for ASSD.

Cost-Related Medication Behaviors for Patients With and Without Systemic Autoimmune Rheumatic Diseases.

Medication nonadherence challenges the management of systemic autoimmune rheumatic diseases (SARDs). We investigated cost-related medication behaviors among patients with SARDs, and compared them to those of patients without SARDs, in a large diverse cohort across the United States. As part of the All of Us (version 7), a nationwide diverse adult cohort with linked electronic health records begun in 2017, participants completed questionnaires concerning cost-related medication behaviors. Chi-square tests compared responses between patients with SARDs, by disease and medication type, and to those without SARDs. Logistic regression analyses were used to calculate odds ratios (95% confidence intervals [CIs]). We analyzed data from 3,997 patients with SARDs and 73,990 participants without SARDs. After adjustment, patients with versus without SARDs had 1.56 times increased odds of reporting unaffordability of prescription medicines (95% CI 1.43-1.70), 1.43 times increased odds of cost-related medication nonadherence (95% CI 1.31-1.56), and 1.23 times increased odds of using cost-reducing strategies (95% CI 1.14-1.32). Patients with SARDs who reported unaffordability were 16.5% less likely to receive a disease-modifying drug (95% CI 0.70-0.99) but 18.1% more likely to receive glucocorticoids (95% CI 0.99-1.42). In addition, unaffordability of prescription medicines was likely to have 1.27 times increased odds of one to two emergency room visits per year (95% CI 1.03-1.57) and 1.38-fold increased odds of three or more emergency room visits per year (95% CI 0.96-1.99). In this large diverse cohort, patients with versus without SARDs had more self-reported cost-related medication behaviors, and those who reported medication unaffordability received fewer disease-modifying drugs and had more emergency room visits.

Features of proinflammatory activation of macrophages in patients with rheumatoid arthritis and systemic lupus erythematosus

Autoimmune rheumatic diseases (ARDs) are chronic pathological conditions that arise from an abnormal immune response and are accompanied by systemic inflammation. The most common ARDs include rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). The exact pathogenesis of ARDs remains unclear, but the complex influence of genetic, immunological and external environmental factors leads to the occurrence and further progression of ARDs. It has been shown that the cause of chronic inflammation may be proinflammatory activation of macrophages, in which an increase in the secretion of cytokines is observed. The aim of this study was to evaluate the inflammatory response of macrophages in patients with RA, SLE and SSc. Materials and methods. The study included 143 participants: 47 patients with RA, 45 patients with SLE, 34 patients with SSc, and 17 people without ARDs and other chronic diseases. Isolation of a primary culture of monocytes was carried out by centrifugation in a ficoll gradient using magnetic separation from the whole blood of study participants. Lipopolysaccharide (LPS) was added to stimulate cells along the proinflammatory pathway. Cell cultivation was carried out for 24 hours. Determination of basal and LPS-stimulated secretion of IL-8 by macrophages was carried out in the culture fluid using an enzyme-linked immunosorbent assay (ELISA). Proinflammatory activation of macrophages was calculated as the ratio of LPS-stimulated and basal IL-8 secretion. Research results. Basal secretion of IL-8 by macrophages was statistically significantly higher in the groups of patients with RA and SSc compared with the SLE and control groups. LPS-stimulated secretion of IL-8 by macrophages in the SSc group had statistically higher values compared to the RA and SLE groups. Proinflammatory activation of macrophages was reduced in the group of patients with RA compared to patients with SLE and the control group, and was also statistically significantly lower in patients with SSc compared to the control group.

Increased risk of adverse events among patients with vs. without systemic autoimmune rheumatic disease prescribed sodium-glucose cotransporter 2 inhibitors: a retrospective cohort study.

Systemic autoimmune rheumatic disease (SARD) patients have been excluded from sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials given putative risks, but this risk magnitude is unknown. We aimed to quantify SGLT2i adverse event risks among patients with vs. without SARD. METHODS: In a retrospective cohort study, patients with SARD at Mass General Brigham, a multihospital system in Boston, Massachusetts, prescribed SGLT2i were age-, self-reported race-, and sex-matched to patients prescribed the same SGLT2i between 1/1/2016 and 12/10/2021. Cumulative incidence and Cox models, overall and sex-stratified, estimated patient-reported adverse event risks from prescription date, censoring for discontinuation, death, or study end (12/12/2022). Four hundred sixty-eight SARD and 420 matched non-SARD patients were compared: mean age 64years (SD 11.3), 61% female, and 70% White. SARD patients had shorter SGLT2i use duration (8.4 vs. 12.7months; p < 0.0001) and time to adverse event (0.59 vs. 0.85years; p 0.04). Yeast infections (9.8% vs. 6.2%; p 0.047) and muscular symptoms (3.4% vs. 1.0%, p 0.01) were more prevalent among those with SARD. Adjusting for baseline demographics, adverse event risk was higher (MV HR 1.68;95% CI 1.28, 2.21), in patients with vs. without SARD. Risk was higher in women than men overall and in women with SARD vs. without (adjusted HR 1.86; 95% CI 1.36, 2.54). Patients with vs. without SARD had 68% higher adverse event risk with SGLT2i use. Women with vs. without SARD had > 85% higher adverse event risks, although most were not serious. Trials of safety and efficacy of SGLT2i among SARD patients are warranted. Key Points •To our knowledge, this is the first study to compare adverse events associated with SGLT2i utilization in patients with vs. without SARD, despite RCT exclusion and documented SGLT2i use in the population. •In our comparison of 468 patients with SARD and 420 patients without, we identified a greater than 65% increase in risk of adverse event outcomes among patients with SARD. •Furthermore, we found that this risk disproportionately affected female patients, with a 4.4-fold increased risk among women with SARD compared to men without.

Artificial intelligence for predicting treatment responses in autoimmune rheumatic diseases: advancements, challenges, and future perspectives.

Autoimmune rheumatic diseases (ARD) present a significant global health challenge characterized by a rising prevalence. These highly heterogeneous diseases involve complex pathophysiological mechanisms, leading to variable treatment efficacies across individuals. This variability underscores the need for personalized and precise treatment strategies. Traditionally, clinical practices have depended on empirical treatment selection, which often results in delays in effective disease management and can cause irreversible damage to multiple organs. Such delays significantly affect patient quality of life and prognosis. Artificial intelligence (AI) has recently emerged as a transformative tool in rheumatology, offering new insights and methodologies. Current research explores AI's capabilities in diagnosing diseases, stratifying risks, assessing prognoses, and predicting treatment responses in ARD. These developments in AI offer the potential for more precise and targeted treatment strategies, fostering optimism for enhanced patient outcomes. This paper critically reviews the latest AI advancements for predicting treatment responses in ARD, highlights the current state of the art, identifies ongoing challenges, and proposes directions for future research. By capitalizing on AI's capabilities, researchers and clinicians are poised to develop more personalized and effective interventions, improving care and outcomes for patients with ARD.

MIP-C: A new autoimmune rheumatic disease concomitant with the COVID-19 pandemic.

MIP-C: A new autoimmune rheumatic disease concomitant with the COVID-19 pandemic.

ANA-positive versus ANA-negative Antiphospholipid Antibody-positive Patients: Results from the APS ACTION Clinical Database and Repository.

This study focused on the prevalence and impact of antinuclear antibodies (ANA) in antiphospholipid antibody (aPL)-positive patients without concomitant systemic autoimmune rheumatic diseases (SARDs). Data from aPL-positive patients with or without Revised Sapporo APS classification criteria were retrieved from the APS ACTION Registry. Patients with concomitant SARDs were excluded. 430 aPL-positive patients were included in the analysis, 56% ANA-positive and 44% negative. ANA positivity was significantly associated with history of hematologic manifestations (persistent autoimmune hemolytic anaemia, thrombocytopenia, leukopenia and/or lymphopenia) (16% of ANA-positive vs 7% of ANA-negative, p= 0.006). Triple aPL-positivity was more frequent in the ANA-positive subgroup (p= 0.02), along with low baseline C3 and C4 levels (p= 0.05 and p= 0.009, respectively), and higher frequency for extractable nuclear antigens (ENA). Among aPL-positive patients with no APS classification, ANA-positive patients showed a higher rate of arthritis (p= 0.006). Among female patients who have experienced at least one pregnancy, 113 were ANA-positive and 96 were ANA-negative; ANA-negative patients had a higher number of pregnancies (p= 0.018), and number of live births (p= 0.014). A wider proportion of ANA-positive patients were treated with hydroxychloroquine (HCQ) (p< 0.001). When we analysed aPL-positive patients with no other SARDs, ANA status was not associated with thrombosis or pregnancy morbidity. Interestingly, ANA-positive patients showed higher rates of systemic autoimmune features, including hematologic manifestations, multiple aPL positivity, lower complement levels, ENA positivity, and joint involvement, and were more often treated with HCQ. Finally, aPL-positive subjects who were ANA-negative had a higher rate of pregnancies and live births.

Efficacy Evaluation of COVID-19 Vaccines in Patients with Autoimmune Rheumatic Diseases in Mashhad, Iran

vaccination. However, since the majority of studies in the related literature are focused on the efficacy of messenger RNA in rheumatic patients, the present study aimed to assess the efficiency of the inactivated whole virus vaccines and viral vector COVID-19 vaccines in rheumatic diseases in Mashhad, Iran. Methods: This prospective cross-sectional study was conducted on ARDs patients who were referred to private clinics and rheumatologic clinics of Ghaem and Imam Reza Hospitals, Mashhad, Iran, during 2021-22. Anti-neutralizing antibodies have been considered to check antibodies of Sinopharm and Barkat vaccines, and an anti-spike antibody was considered to check Sputnik V and AstraZeneca vaccine antibodies. Humoral immunity was investigated using the anti-spike Enzyme-linked immunosorbent assay and anti-neutralizing antibodies. Results: The obtained results showed that humoral immunity after COVID-19 vaccination was observed in 73.9% of the patients with ARDs. However, humoral immunity was lower in ARDs patients who took tacrolimus and higher in patients with a history of COVID-19 infection (χ2=5.84, p=0.01). The infection after the second COVID-19 vaccination was lower in patients with humoral immunity (χ2=5.69, p=0.01). Conclusion: This study demonstrated that a homologous second dose of an inactivated whole viral vector SARS-CoV-2 vaccine was safe and provided a remarkable antibody response in ARDs patients.

Development and validation of an image-based questionnaire ARTROVIS to identify risk factors for the articular syndrome and related conditions

Background: The importance of timely diagnosis of rheumatic diseases is beyond any doubt. However, in the real practice the time from manifestation of the first symptoms to the assessment by a rheumatologist and treatment administration often exceeds the window of opportunity for disease control. At the moment, there has been no Russian-language questionnaire that would allow a primary care physician to suspect a rheumatic disease manifesting with an articular syndrome. Aim: To develop, validate and test a questionnaire to identify risk factors for joint disorders and related conditions. Methods: From November 2022 to April 2024, we performed the study on the image-based questionnaire on identification of the risk factors for joint syndromes and associated conditions (ARTROVIS), which we have developed for early detection of both joint syndromes, as well as comorbid conditions associated with elevated serum uric acid levels (hyperuricemia). The initial test version of the questionnaire was tested in a focus group of respondents (n = 20) who came for regular medical examination. Based on the results of this face validity assessment, we corrected the wording of 10 questionnaire items. At the second study step, we assessed the primary validity and reliability of the questionnaire in a group of 41 rheumatology patients. The third study step involved 828 respondents (408 men and 420 women, median age 19 [18,0; 20,0] years; 21% with joint syndromes), who came for routine medical examination. The reliability of the questionnaire, its face and discriminant validity, as well as sensitivity and specificity (the ROC analysis) were assessed from 827 questionnaires included in the final processing (one was excluded due to questionnaire completion defects). Results: The self-report questionnaire for patients (ARTROVIS) has 24 items aimed at collecting social and demographic data, identifying risk factors for non-communicable diseases, assessing genetic aspects, identifying complaints from various organ systems, providing information on medical treatments taken by the patient (non-steroid anti-inflammatory agents, diuretics, antihypertensives, glucocorticosteroids, chemotherapy and radiation therapy), as well as an additional question for women on current pregnancy pathology. The questionnaire contains visual aids (colored photos) that facilitate the detection of clinical signs of autoimmune (psoriatic arthritis, Reynolds’s syndrome) and inflammatory rheumatic disease (gout), as well as the differential diagnosis of the joint syndrome. The assessment of face validity of the questionnaire showed the total number of missed answers of 3.42%; 62.85% of the respondents gave their full answers to all items. Good discriminant validity was demonstrated. The ROC analysis showed high correlation between the questionnaire score and the presence of a joint syndrome: the area under the curve was 0.884. The Cronbach’s alfa was 0.798, which is sufficient for a medical questionnaire. Conclusion: We have performed the approbation and standardization of the questionnaire to identify risk factors for the joint syndrome and related comorbidities by assessing its validity and reliability. The ARTROVIS as a self-report questionnaire can be used in primary care as a tool enabling general practitioners and internists to decide on further patient routing to corresponding specialists.

Epstein-Barr virus as a potentiator of autoimmune diseases.

The Epstein-Barr virus (EBV) is epidemiologically associated with development of autoimmune diseases, including systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis and multiple sclerosis. Although there is well-established evidence for this association, the underlying mechanistic basis remains incompletely defined. In this Review, we discuss the role of EBV infection as a potentiator of autoimmune rheumatic diseases. We review the EBV life cycle, viral transcription programmes, serological profiles and lytic reactivation. We discuss the epidemiological and mechanistic associations of EBV with systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis and multiple sclerosis. We describe the potential mechanisms by which EBV might promote autoimmunity, including EBV nuclear antigen 1-mediated molecular mimicry of human autoantigens; EBV-mediated B cell reprogramming, including EBV nuclear antigen 2-mediated dysregulation of autoimmune susceptibility genes; EBV and host genetic factors, including the potential for autoimmunity-promoting strains of EBV; EBV immune evasion and insufficient host responses to control infection; lytic reactivation; and other mechanisms. Finally, we discuss the therapeutic implications and potential therapeutic approaches to targeting EBV for the treatment of autoimmune disease.

Increased prevalence of inflammatory arthritis, systemic lupus erythematosus and systemic sclerosis, during 2020-2023 versus 2016-2019 in a Nation-Wide Cohort Study.

Although several studies have explored the geoepidemiology of autoimmune rheumatic diseases (ARD), trends of their frequency overtime are under-investigated. Herein, in a nation-wide study, we examine trends in the prevalence of various ARD over-time, taking also into account the Covid-19 pandemic. In this retrospective study in the entire Greek adult population (approximately 10.000.000 people), we searched the electronic prescription database of the e-Government Centre for Social Security Services using prespecified ICD-10 codes to capture all adult patients with Psoriatic Arthritis (PsA), Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc) and Polymyalgia Rheumatica or Giant Cell Arteritis (PMR/GCA). Two sequential 4-year periods, namely 2016-2019 and 2020-2023 were compared. Prevalence of RA, PsA, AxSpA, SLE and SSc increased significantly during 2020-2023 compared to 2016-2019. This applies to both genders and to all age groups for RA, PsA and AxSpA, to female patients in SLE and SSc and to patients 18-39years in SLE and ≥ 60years in SSc. Overall, there was 47% increase in prevalence for AxSpA (0.100% in 2016-19 vs 0.147% in 2020-23), 36.5% for PsA (0.148% vs 0.202%), 20.6% for RA (0.467% vs 0.563%), 19% for SLE (0.137% vs 0.163%) and 13% for SSc (0.023% vs 0.026%). A 16.3% decrease was evident in GCA/PMR, limited to those ≥ 40years old. In a nation-wide study we confirm that ARD prevalence increases over-time, whereas a contribution of Covid-19 pandemic to our results during 2020-2023, cannot be excluded. Additional human, medical and financial resources will be needed to cover the increased needs of ARD patients.

Prevalence of Adhesive Capsulitis in Patients With Type 2 Diabetes Mellitus: A Single-Center Cross-Sectional Study From Pakistan.

Background An inflammatory condition leading to stiffness and pain in the shoulder joint, adhesive capsulitis is associated with conditions such as diabetes mellitus, cervical spondylosis, thyroid dysfunction, autoimmune rheumatic diseases, and shoulder injury due to trauma, fracture, rotator cuff tear, surgery, or immobilization. Adhesive capsulitis may affect a notable proportion of the diabetic population. There are numerous studies that show that patients with type 2 diabetes mellitus are not only at higher risk of developing adhesive capsulitis but also suffer poor outcomes despite treatment, especially in patients with long-standing diabetes mellitus. Furthermore, there is significant variation in data regarding the prevalence of adhesive capsulitis in Pakistani patients with type 2 diabetes mellitus. Objective To determine the prevalence of adhesive capsulitis among patients with type 2 diabetes mellitus presenting to a tertiary care hospital in Bahawalpur, Pakistan. Methods The present observational cross-sectional study was carried out at the Department of Medicine, Bahawal Victoria Hospital, Quaid-e-Azam Medical College, Bahawalpur, Pakistan, from February 2024 to August 2024. Type 2 diabetes mellitus was labeled by HbA1c of more than 7.0%, or two random blood glucose levels of 200 mg/dL or more, or an existing diagnosis of diabetes mellitus, and/or use of anti-hyperglycemic therapy. Adhesive capsulitis was diagnosed clinically on the basis of history (gradual onset shoulder pain with limitation of movements) and examination (reduction in active and passive range of motion (ROM) of the shoulder, especially abduction, internal rotation, and external rotation) in the absence of significant abnormalities on shoulder X-ray. After ethical approval and obtaining informed consent, 430 patients with type 2 diabetes mellitus were included in the study using a non-probability consecutive sampling technique. Demographic information, diabetes control, and HbA1c levels were noted, and the patients were assessed for adhesive capsulitis. All the data was recorded and entered into IBM SPSS Statistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, NY, USA), for analysis. Results Having a female preponderance (266, or 61.9%), the mean age of the participants was 54.0 ± 13.1 years. With regard to occupational status, 126 (29.3%) had a sedentary occupation, 45 (10.5%) were unemployed, and 259 (60.2%) had a non-sedentary occupation. The mean diabetes duration was 6.4 ± 5.3 years, and the majority of patients had poor diabetes control (322, or 74.9%). Adhesive capsulitis was present in 61 (14.2%) patients with type 2 diabetes mellitus. On stratification, no significant statistical association of adhesive capsulitis was seen with gender (p-value: 0.075), age (p-value: 0.465), occupation (p-value: 0.056), diabetes duration (p-value: 0.118), or diabetes control (p-value: 0.090). Conclusion Adhesive capsulitis was not an uncommon finding in our study, reported in almost one-fifth of the 430 patients enrolled. We recommend that treating physicians screen diabetic patients for adhesive capsulitis so that proper pain relief, physiotherapy, and rehabilitation may be provided timely and efficiently, thereby reducing morbidity and improving the quality of life for such patients.