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Background and Objectives: The coronavirus disease of 2019 (COVID-19) pandemic has posed a serious threat to humanity and is considered a global health emergency. Antimalarial drugs (ADs) have been used in the treatment of immuno-inflammatory arthritis (IIA) and coronavirus infection (COVID-19). The aim of this review is to analyze the current knowledge about the immunomodulatory and antiviral mechanisms of action, characteristics of use, and side effects of antimalarial drugs. Material and Methods: A literature search was carried out using PubMed, MEDLINE, SCOPUS, and Google Scholar databases. The inclusion criteria were the results of randomized and cohort studies, meta-analyses, systematic reviews, and original full-text manuscripts in the English language containing statistically confirmed conclusions. The exclusion criteria were summary reports, newspaper articles, and personal messages. Qualitative methods were used for theoretical knowledge on antimalarial drug usage in AIRDs and SARS-CoV-2 such as a summarization of the literature and a comparison of the treatment methods. Results: The ADs were considered a "candidate" for the therapy of a new coronavirus infection due to mechanisms of antiviral activity, such as interactions with endocytic pathways, the prevention of glycosylation of the ACE2 receptors, blocking sialic acid receptors, and reducing the manifestations of cytokine storms. The majority of clinical trials suggest no role of antimalarial drugs in COVID-19 treatment or prevention. These circumstances do not allow for their use in the treatment and prevention of COVID-19. Conclusions: The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for COVID-19. Furthermore, the need for high doses in the treatment of viral infections increases the likelihood of gastrointestinal side effects, the prolongation of QT, and retinopathy. Large randomized clinical trials (RCTs) have refuted the fact that there is a positive effect on the course and results of COVID-19. [ABSTRACT FROM AUTHOR]

The identification of novel, robust biomarkers for the diagnosis of rheumatic diseases (RDs) and the presence of active disease might facilitate early treatment and the achievement of favourable long-term outcomes. We conducted a systematic review and meta-analysis of studies investigating the acute phase reactant, serum amyloid A (SAA), in RD patients and healthy controls to appraise its potential as diagnostic biomarker. We searched PubMed, Scopus, and Web of Science from inception to 10 April 2024 for relevant studies. We evaluated the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively (PROSPERO registration number: CRD42024537418). In 32 studies selected for analysis, SAA concentrations were significantly higher in RD patients compared to controls (SMD = 1.61, 95% CI 1.24–1.98, p < 0.001) and in RD patients with active disease compared to those in remission (SMD = 2.17, 95% CI 1.21–3.13, p < 0.001). Summary receiving characteristics curve analysis showed a good diagnostic accuracy of SAA for the presence of RDs (area under the curve = 0.81, 95% CI 0.78–0.84). The effect size of the differences in SAA concentrations between RD patients and controls was significantly associated with sex, body mass index, type of RD, and study country. Pending the conduct of prospective studies in different types of RDs, the results of this systematic review and meta-analysis suggest that SAA is a promising biomarker for the diagnosis of RDs and active disease. [ABSTRACT FROM AUTHOR]

The identification of novel, yet easily measurable biomarkers of inflammation and oxidative stress might assist in the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a systematic review and meta-analysis of studies investigating the circulating concentrations of bilirubin, the end product of heme metabolism and a potent endogenous antioxidant with anti-inflammatory properties, in patients with RDs and healthy controls. The electronic databases PubMed, Scopus, and Web of Science were searched from inception to 31 December 2023 for relevant articles. We evaluated the risk of bias and the certainty of evidence using the Joanna Briggs Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation Working Group system, respectively. In 17 eligible studies, all with low risk of bias, compared to controls, patients with RDs had significantly lower concentrations of total bilirubin (standard mean difference, SMD=-0.68, 95% CI -0.91 to -0.44, p<0.001; I² = 92.5%, p<0.001; low certainty of evidence), direct (conjugated) bilirubin (SMD=-0.67, 95% CI -0.92 to -0.41, p<0.001; I² = 81.7%, p<0.001; very low certainty of evidence), and the active antioxidant and anti-inflammatory indirect (unconjugated) form of bilirubin (SMD=-0.71, 95% CI -1.18 to -0.24, p=0.003; I² = 95.1%, p<0.001; very low certainty of evidence). The results of the meta-analysis were stable in sensitivity analysis. In meta-regression, there were no significant associations between the SMD of total bilirubin and several clinical and demographic characteristics, including age, male to female ratio, number of participants, liver enzymes and erythrocyte sedimentation rate. In subgroup analysis, the SMD of total bilirubin was significant across a range of RDs, including rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren syndrome, and myositis. Therefore, the results of our systematic review and metaanalysis suggests that the reductions in bilirubin concentrations observed in patients with RDs reflect a state of impaired antioxidant and anti-inflammatory defence due to bilirubin consumption and highlight the promising role of this endogenous product as a biomarker of RDs. [ABSTRACT FROM AUTHOR]

Background: Eponyms do not describe any pathogenesis of a disease. So, there is no other way than to memorize the disease or anatomical area. Over the years, new nomenclatures have been suggested for some diseases due to a better understanding of the pathogenesis. In this article, the changes in the use of Churg–Strauss syndrome were investigated. Methods: In the study, a computerized search was performed using the PubMed database. Books and documents, clinical trials, editorials, meta-analyses, reviews, and case reports were included in the study. Data were obtained from the title of the database, and the variations or distribution by year for the nomenclature of the most related studies were evaluated. Results: Overall, 68.3% of the articles included CSS, 25.7% included eosinophilic granulomatous polyangiitis (EGPA), and 6.0% included both nomenclatures. When evaluated in terms of the distribution according to years, it was determined that there was a statistically significant increase in use in terms of EGPA. When evaluated among specific section journals, the highest rate was in Rheumatology (29.4%). The highest rate of using CSS was in the Rheumatology (25.1%) journals, followed by Pulmonary/Respiratory (17%), Cardiovascular (12%), and Allergy/Immunology/Biology (9.8%). The use of EGPA combined with CSS decreased in all the specific journals from 2012 to the present. Conclusions: The findings of the study revealed that the number of articles with the eponym of EGPA showed an increased frequency in contrast to a decreasing frequency for those with CSS during recent years. Today, with the elaboration of the disease pathogenesis and the increase in knowledge, the trend has shifted in this direction. [ABSTRACT FROM AUTHOR]

Objectives Inflammatory arthritis (IA) is considered the last stage of a disease continuum, where features of systemic autoimmunity can appear years before clinical synovitis. Time to progression to IA varies considerably between at-risk individuals, therefore the identification of biomarkers predictive of progression is of major importance. We previously reported on the value of three CD4+T cell subsets as biomarkers of progression. Here, we aim to establish the value of 18 lymphocyte subsets (LS) for predicting progression to IA. Methods Participants were recruited based on a new musculoskeletal complaint and being positive for anti-citrullinated-peptide antibody. Progression (over 10 years) was defined as the development of clinical synovitis. LS analysis was performed for lymphocyte lineages, naive/memory subsets, inflammation-related cells (IRC) and regulatory cells (Treg/B-reg). Modelling used logistic/Cox regressions. Results Of 210 patients included, 93 (44%) progressed to IA, 41/93 (44%) within 12 months (rapid progressors). A total of 5/18 LS were associated with progression [Treg/CD4-naïve/IRC (adjusted P  < 0.0001), CD8 (P  = 0.021), B-reg (P  = 0.015)] and three trends (NK-cells/memory-B-cells/plasmablasts). Unsupervised hierarchical clustering using these eight subsets segregated three clusters of patients, one cluster being enriched [63/109(58%)] and one poor [10/45(22%)] in progressors. Combining all clinical and LS variables, forward logistic regression predicted progression with accuracy = 85.7% and AUC = 0.911, selecting smoking/rheumatoid-factor/HLA-shared-epitope/tender-joint-count-78 and Treg/CD4-naive/CD8/NK-cells/B-reg/plasmablasts. To predict rapid progression, a Cox regression was performed resulting in a model combining smoking/rheumatoid factor and IRC/CD4-naive/Treg/NK-cells/CD8+T cells (AUC = 0.794). Conclusion Overall, progression was predicted by specific LS, suggesting potential triggers for events leading to the development of IA, while rapid progression was associated with a different set of subsets. [ABSTRACT FROM AUTHOR]

Background: The burden of musculoskeletal (MSK) pain and disabilities is high in health facilities but remains unknown in the community due to a lack of community‐level studies. The community‐oriented program for control of rheumatic diseases (COPCORD) is focused on determining MSK pain and disabilities through epidemiological surveys. This study adopted the COPCORD stage I protocol to determine the prevalence of rheumatic MSK pain and disability and its associated factors in the Pyuthan district of Nepal. Methodology: A cross‐sectional community‐based study using the quantitative method was conducted in Pyuthan municipality as per COPCORD stage I protocol. COPCORD stage I (phase I and phase II) questionnaires were used to collect data through the interview technique. Populations aged 18 years and above were included in the study. A multistage sampling technique was used, and the total sample size was 2145. The collected data from phase I and phase II were entered in Epidata version 3.1. Descriptive and analytical analysis was done in SPSS. The Chi‐square test was used to find the association between dependent and independent variables. Findings: The overall prevalence (past and current MSK pain/swelling) was 26.81% (95% CI 24.9–28.7). Current MSK pain/swelling was found in 19.53% of the participants, and past MSK pain/swelling was found in 25.87%. Among self‐reported chronic diseases, joint pain was reported by the majority of the participants (17.86%). Age, sex, education, nature of work, current smoking, tobacco use, and alcohol use were found to be associated with past and current MSK pain/swelling. Conclusions: More than one‐fourth of the participants had MSK pain/swelling. The prevalence of MSK pain/swelling was higher in elderly participants, females, illiterates, heavy workers, smokers, tobacco users, and alcohol users. Similar studies should be conducted in other regions of the country, and this study should also be expanded to COPCORD Stages II and III to identify the risk factors and to improve the management of MSK pain and disorders. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the clinical outcomes and risk factors for severe coronavirus disease 2019 (COVID-19) in patients with inflammatory rheumatic disease (IRD) of a national cohort. Patients and methods: The multicenter cross-sectional study was carried out between July 15, 2020, and February 28, 2021. Data collection was provided from a national network database system, and 3,532 IRD patients (2,359 males, 1,173 females; mean age: 48.7±13.9 years; range; 18 to 90 years) were analyzed. Demographics, clinics about rheumatic disease, comorbidities, smoking status, being infected with COVID-19, and the course of the infection were questioned by rheumatology specialists. Results: One hundred seventeen patients were infected with COVID-19, the hospitalization rate due to COVID-19 was 58.9%, and the mortality rate was 1.7%. There was no difference between the COVID-19 positive and negative groups in terms of rheumatic disease activities and receiving drugs. It was observed that patients with COVID-19 had worse compliance with isolation rules, and bacillus Calmette-Guérin (BCG) vaccination was less common. The mean age and the rate of smoking of hospitalized COVID-19 patients were higher than those without hospitalization. Conclusion: In this cohort, in which real-life data were analyzed, COVID-19 rates in IRD patients were similar to the general population for the same period. Compliance with the isolation rules and BCG vaccination attracted attention as components that reduce the risk of COVID-19 infection. The risk factors for hospitalization were older age and smoking. [ABSTRACT FROM AUTHOR]

Introduction: The identification of novel, easily measurable disease biomarkers might enhance the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a systematic review and meta‐analysis of ischemia‐modified albumin (IMA), a marker of oxidative stress, acidosis, and ischemia, in RD patients and healthy controls. Methods: We searched PubMed, Web of Science, and Scopus from inception to January 15, 2024. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively. Results: In 20 studies investigating a total of 1188 RD patients (mean age 45 years, 64% females) and 981 healthy controls (mean age 44 years, 66% females), RD patients had significantly higher IMA concentrations when compared to controls (standard mean difference, SMD = 0.50, 95% CI: 0.18−0.83, p =.003; I2 = 92.4%, p <.001; low certainty of evidence). In subgroup analysis, the pooled SMD was significantly different in studies investigating ankylosing spondylitis (p <.001), Behçet's disease (p <.001), and rheumatoid arthritis (p =.033), but not familial Mediterranean fever (p =.48). Further associations were observed between the pooled SMD and the broad classification of autoimmune and/or autoinflammatory diseases, the study country, and the method used to measure IMA. Conclusion: Our study suggests that IMA is a promising biomarker of oxidative stress, acidosis, and ischemia, as it can effectively discriminate between patients with different types of RDs and healthy controls. Our results warrant confirmation in longitudinal studies of patients with different types of RDs and different ethnicities (PROSPERO registration number: CRD42024509126). [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to reveal the relationship between the health literacy (HL) levels of children with juvenile idiopathic arthritis (JIA) and their parents, and the general health status and physical performance of the children. Methods: This study included 79 children aged 9–18 years with a diagnosis of JIA and one of their parents. HL levels were evaluated with the Turkish version of the Health Literacy for School‐Aged Children and Turkish Health Literacy‐32 (THL‐32) for children and Adult Health Literacy Scale (AHLS) for their parents. The Childhood Health Assessment Questionnaire (CHAQ), 6‐minute walk test (6‐MWT), 10‐meter walking test (10‐MWT) and 10‐stair climbing test (10‐SCT) was used to evaluate the children. Juvenile Arthritis Biopsychosocial Questionnaire (JAB‐Q) was used to assess the children's and parents' psychosocial status and perception of health. Results: HL levels of patients with JIA were 16.5% low HL, %55.7 moderate HL and 27.8% high HL. According to THL‐32 scale score, HL level of parents were as follows: inadequate, 3.8%; problematic, 22.8%; sufficient, 34.2%; and excellent, 39.2%. Children's HL levels increase positively as they get older, and no significant relationship was found with other parameters. The AHLS, CHAQ and JAB‐Q scores were better in the group with higher education levels of the parents. No statistically significant association was found between the HL of the children and that of the parents. Conclusion: In our study, it was found that the high education levels of the parents positively affected the quality of life and physical condition of their children and parental HL levels. In addition, it was shown that the HL levels of children with JIA were not statistically related to other parameters. Patient or Public Contribution: Children diagnosed with JIA and one of their parents actively participated in the study. Feedback from children and families provided important information about obtaining and using HL information before and during the study. The importance of therapy programs and information focusing on the patient and their family, as well as the inter‐multidisciplinary approach, in combating a chronic disease at an early age was reinforced by the feedback received from patients and their families. [ABSTRACT FROM AUTHOR]

Aim: The use of tumor necrosis factor-alpha (TNF-α) inhibitors is associated with potential side effects such as infusion reactions, anaphylaxis, development of infection, and cutaneous and paradoxical side effects. We evaluated the side effects observed with the use of these agents in patients with rheumatic diseases followed by TNF-α inhibitors in our clinic. Material and Methods: Patients admitted to our clinic in the last 5 years with a diagnosis of inflammatory rheumatic disease and treated with TNF-α inhibitors were included in the study. Demographic data, diagnoses, treatment, and side effects were recorded. Statistical analysis was performed using SPSS version 21.0. Results: Forty-two patients with rheumatic disease receiving TNF-α inhibitors were analyzed. Infliximab had cutaneous side effects in 26 patients, including one infusion reaction and two cases of anaphylaxis. These side effects included allergic rash, psoriasis, bullous pemphigoid, dermatitis herpetiformis, erythema AB Igne, dermatitis, and small vessel vasculitis. Golimumab caused neutropenia in two patients. The other adverse events were cervical intraepithelial lesions and Kaposi's sarcoma in one patient with psoriatic arthritis. Infections were the most common adverse events and were reported in four patients. Conclusion: TNF-α inhibitors are widely used in the treatment of inflammatory rheumatic diseases. These agents have side effects, and it is important to be aware of and cautious about potential side effects. [ABSTRACT FROM AUTHOR]

BackgroundThere was less research about cytokines in lung involvement of childhood-onset rheumatic diseases (RD) patients.ObjectiveIn this investigation, blood levels of 12 cytokines were tested in order to explore their associations with lung involvement in newly diagnosed childhood-onset RD patients.MethodsHigh-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) were performed on 53 newly diagnosed RD patients without any treatment in our department between July 2021 and December 2023. Patients were separated into groups based on whether their lungs were involved or not according to abnormalities found on HRCT or PFTs. We examined the serum cytokines with 41 healthy, age and gender-matched controls.ResultsThe majority of serum cytokine levels were statistically different between the RD group with lung involvement and the control group. The RD group with lung involvement had considerably higher serum IL-6 and IFN-γ levels than the RD group without lung involvement or control group. The median serum IL-6 levels were 19 pg/ml [interquartile range (IQR) 6.9, 27.6], 4.4 pg/ml (IQR 2.0, 10.5), and 2.0 pg/ml (IQR 2.0, 2.0) in RD group with lung involvement, RD group without lung involvement, and control group, respectively. Similarly, the median serum IFN-γ levels were 6.0 pg/ml (IQR 5.0, 15), 5.0 pg/ml (IQR 5.0, 5.0), and 5.0 pg/ml (IQR 5.0, 5.0) in RD group with lung involvement, RD group without lung involvement, and control group, respectively. The receiver operating characteristic (ROC) curve study showed that IL-6 and IFN-γ had area under the curve (AUC) values of 0.782 and 0.742, respectively, indicating their significant diagnostic potential for lung involvement in RD patients.ConclusionOur findings imply that IL-6 and IFN-γ may be associated with the development of lung illnesses and may be involved in the pathophysiology of RD. Thus, in individuals with RD, elevated levels of IFN-γ over 5.42 pg/ml or IL-6 above 6.25 pg/ml may warrant suspicion of lung involvement.

Abstract Introduction Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrosis, vascular damage, and immune dysregulation. Fractalkine or chemokine (C‐X3‐C motif) ligand 1 (CX3CL1), a chemokine and adhesion molecule, along with its receptor CX3CR1, have been implicated in the inflammatory processes of SSc. CX3CL1 functions as both a chemoattractant and an adhesion molecule, guiding immune cell trafficking. This systematic review examines the role of CX3CL1 and its receptor CX3CR1 in the pathogenesis of SSc, with a focus on pulmonary and vascular complications. Methods A systematic literature search was conducted across databases including PubMed, Scopus, and Web of Science from inception to November 2020. The search focused on studies investigating the CX3CL1/CX3CR1 axis in the context of SSc. Results The review identified elevated CX3CL1 expression in SSc patients, particularly in the skin and lungs, where CX3CR1 is expressed on infiltrating immune cells. Higher levels of CX3CL1 were correlated with the severity of interstitial lung disease in SSc patients, indicating a potential predictive marker for disease progression. CX3CR1‐positive monocytes and NK cells were recruited to inflamed tissues, contributing to fibrosis and tissue damage. Animal studies showed that inhibition of the CX3CL1/CX3CR1 axis reduced fibrosis and improved vascular function. Conclusion The CX3CL1/CX3CR1 axis plays a key role in immune cell recruitment and fibrosis in SSc. Elevated CX3CL1 levels are associated with lung and vascular complications, making it a potential biomarker for disease progression and a promising therapeutic target.

BackgroundObservational studies have suggested a link between rheumatic diseases and arrhythmias. However, these studies have been limited by confounding factors and reverse causality, leaving the causal relationship between rheumatic diseases and arrhythmias uncertain. This study addresses this inquiry using genetic evidence.MethodsSelected single nucleotide polymorphisms (SNPs) from genome-wide association study (GWAS) data were employed as instrumental variables. Inverse variance weighting (IVW), MR-Egger regression, and the weighted median method were utilized in the two-sample Mendelian randomization analysis. Horizontal pleiotropy was identified and rectified through the MR-PRESSO test and MR-Egger regression. The stability and reliability of the Mendelian randomization results were appraised using the remain-one method, Cochran Q-test, and funnel plot. Odds ratios (OR) were utilized to assess the causal relationship between six rheumatic diseases and five types of arrhythmias.ResultsThe Inverse Variance Weighted (IVW) method indicated a significant association between rheumatoid arthritis (RA) and an elevated risk of right bundle branch block (RBBB) (OR: 1.10, 95% CI: 1.02–1.18, p = 0.009). Additionally, gout was significantly correlated with an augmented risk of RBBB (OR: 1.28, 95% CI: 1.09–1.51, p = 0.003). Conversely, dermatomyositis (DM) exhibited a negative association with the risk of atrioventricular block (AVB) (OR: 0.94, 95% CI: 0.90–0.99, p = 0.020). No significant associations were observed between other rheumatic diseases and arrhythmias.ConclusionA two-sample Mendelian Randomization (MR) study provides data indicating that in European populations, a genetically predicted gout or rheumatoid arthritis (RA) may increase the incidence of right bundle branch block (RBBB). To clarify and investigate the processes behind these causal links, more research is necessary. Because racial genetic variability exists, care should be used when interpreting our findings.

Background: Studies reported an association between rheumatoid arthritis and Diabetes mellitus. We sought to assess the causal association between rheumatoid arthritis and Diabetes mellitus risk using a two-way two-sample Mendelian randomization (MR) analysis. Methods: Data on Diabetes mellitus and rheumatoid arthritis were obtained from the GWAS genome-wide database, and the MR method was used to explore the bidirectional causal association, the inverse variance weighted (IVW) method was used as the primary analysis method, and sensitivity analysis was performed. Results: IVW results and MR-Egger method indicate that there is a significant correlation between Diabetes mellitus and rheumatoid arthritis (IVW: P = 0.002, OR = 1.057, 95%CI: 1.02–1.096, MR-Egger: P = 0.037, OR = 1.096, 95%CI: 1.006–1.194), MR-Egger intercept analysis shows that the P-value is 0.362 (>0.05), IVW results showed a significant association between rheumatoid arthritis and Diabetes mellitus (IVW: P = 2.65 × 10–9, OR = 1.797, 95%CI: 1.481–2.180), MR-Egger intercept analysis shows that the P-value is 0.221 (>0.05). Conclusion: The results confirm that Diabetes mellitus and rheumatoid arthritis have a two-way causal chain, and it is necessary to strengthen bidirectional surveillance.

OBJECTIVE: To describe obstetric outcomes based on COVID-19 vaccination status, in women with rheumatic and musculoskeletal diseases (RMDs) who developed COVID-19 during pregnancy. METHODS: Data regarding pregnant women entered into the COVID-19 Global Rheumatology Alliance registry from 24 March 2020-25 February 2022 were analysed. Obstetric outcomes were stratified by number of COVID-19 vaccine doses received prior to COVID-19 infection in pregnancy. Descriptive differences between groups were tested using the chi-squared or Fishers exact test. RESULTS: There were 73 pregnancies in 73 women with RMD and COVID-19. Overall, 24.7% (18) of pregnancies were ongoing, while of the 55 completed pregnancies, 90.9% (50) of pregnancies resulted in livebirths. At the time of COVID-19 diagnosis, 60.3% (n = 44) of women were unvaccinated, 4.1% (n = 3) had received one vaccine dose while 35.6% (n = 26) had two or more doses. Although 83.6% (n = 61) of women required no treatment for COVID-19, 20.5% (n = 15) required hospital admission. COVID-19 resulted in delivery in 6.8% (n = 3) of unvaccinated women and 3.8% (n = 1) of fully vaccinated women. There was a greater number of preterm births (PTB) in unvaccinated women compared with fully vaccinated 29.5% (n = 13) vs 18.2% (n = 2). CONCLUSIONS: In this descriptive study, unvaccinated pregnant women with RMD and COVID-19 had a greater number of PTB compared with those fully vaccinated against COVID-19. Additionally, the need for COVID-19 pharmacological treatment was uncommon in pregnant women with RMD regardless of vaccination status. These results support active promotion of COVID-19 vaccination in women with RMD who are pregnant or planning a pregnancy.

ObjectiveTo provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs).MethodsThis guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation.ResultsThis guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence.ConclusionApplication of these recommendations should consider patients' individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.

Background/objectiveThis study describes the impact of immunomodulatory and/or immunosuppressive (IM/IS) drugs in the outcomes of COVID-19 infection in a cohort of patients with immune-mediated inflammatory diseases (IMIDs).MethodsAdult patients with IMIDs with a confirmed SARS-CoV-2 infection were included. Data were reported by the treating physician between August 13, 2020 and July 31, 2021. Sociodemographic data, comorbidities, and DMARDs, as well as clinical characteristics, complications, and treatment of the SARS-CoV-2 infection, were recorded. Descriptive analysis and multivariable logistic regression models were carried out.ResultsA total of 1672 patients with IMIDs were included, of whom 1402 were treated with IM/IS drugs. The most frequent diseases were rheumatoid arthritis (47.7%) and systemic lupus erythematosus (18.4%). COVID-19 symptoms were present in 95.2% of the patients. A total of 461 (27.6%) patients were hospitalized, 8.2% were admitted to the intensive care unit, and 4.4% died due to COVID-19.Patients without IM/IS treatment used glucocorticoids less frequently but at higher doses, had higher levels of disease activity, were significantly older, were more frequently hospitalized, admitted to the intensive care unit, and died due to COVID-19. After adjusting for these factors, treatment with IM/IS drugs was not associated with a worse COVID-19 outcome (World Health Organization-Ordinal Scale ≥5) (odds ratio, 1.24; 95% confidence interval, 0.73-2.06).ConclusionsSAR-COVID is the first multicenter Argentine registry collecting data from patients with rheumatic diseases and SARS-CoV-2 infection. After adjusting for relevant covariates, treatment with IM/IS drugs was not associated with severe COVID-19 in patients with IMIDs.Study registrationThis study has been registered in ClinicalTrials.gov under the number NCT04568421.

Abstract Background Macrophage activation syndrome (MAS), an example of secondary hemophagocytic lymphohistiocytosis, is a potentially fatal complication of rheumatic diseases. We aimed to study the clinical and laboratory characteristics, treatment schemes, and outcomes of different rheumatic disorders associated with MAS in children. Early warning indicators of MAS have also been investigated to enable clinicians to make a prompt and accurate diagnosis. Methods Fifty-five patients with rheumatic diseases complicated by MAS were enrolled between January 2017 and December 2022. Clinical and laboratory data were collected before disease onset, at diagnosis, and after treatment with MAS, and data were compared between patients with systemic juvenile idiopathic arthritis (sJIA), Kawasaki disease (KD), and systemic lupus erythematosus (SLE). A random forest model was established to show the importance score of each variable with a significant difference. Results Most (81.8%) instances of MAS occurred during the initial diagnosis of the underlying disease. Compared to the active stage of sJIA, the platelet count, erythrocyte sedimentation rate, and fibrinogen level in sJIA-MAS were significantly decreased, whereas ferritin, ferritin/erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and D-dimer levels were significantly increased. Ferritin level, ferritin/erythrocyte sedimentation rate, and platelet count had the greatest predictive value for sJIA-MAS. The level of IL-18 in the sJIA-MAS group was significantly higher than in the active sJIA group, whereas IL-6 levels were significantly lower. Most patients with MAS were treated with methylprednisolone pulse combined with cyclosporine, and no deaths occurred. Conclusions Thrombocytopenia, ferritin levels, the ferritin/erythrocyte sedimentation rate, and elevated aspartate aminotransferase levels can predict the occurrence of MAS in patients with sJIA. Additionally, our analysis indicates that IL-18 plays an important role in the pathogenesis of MAS in sJIA-MAS.

Abstract Background Patients with rheumatoid arthritis (RA) are at risk of developing interstitial lung disease (ILD), which is associated with high mortality. Screening tools based on risk factors are needed to decide which patients with RA should be screened for ILD using high-resolution computed tomography (HRCT). The ANCHOR-RA study is a multi-national cross-sectional study that will develop a multivariable model for prediction of RA-ILD, which can be used to inform screening for RA-ILD in clinical practice. Methods Investigators will enrol consecutive patients with RA who have ≥ 2 of the following risk factors for RA-ILD: male; current or previous smoker; age ≥ 60 years at RA diagnosis; high-positive rheumatoid factor and/or anti-cyclic citrullinated peptide (titre > 3 x upper limit of normal); presence or history of certain extra-articular manifestations of RA (vasculitis, Felty’s syndrome, secondary Sjögren’s syndrome, cutaneous rheumatoid nodules, serositis, and/or scleritis/uveitis); high RA disease activity in the prior 12 months. Patients previously identified as having ILD, or who have had a CT scan in the prior 2 years, will not be eligible. Participants will undergo an HRCT scan at their local site, which will be assessed centrally by two expert radiologists. Data will be collected prospectively on demographic and RA-related characteristics, patient-reported outcomes, comorbidities and pulmonary function. The primary outcomes will be the development of a probability score for RA-ILD, based on a multivariable model incorporating potential risk factors commonly assessed in clinical practice, and an estimate of the prevalence of RA-ILD in the study population. It is planned that 1200 participants will be enrolled at approximately 30 sites in the USA, UK, Germany, France, Italy, Spain. Discussion Data from the ANCHOR-RA study will add to the body of evidence to support recommendations for screening for RA-ILD to improve detection of this important complication of RA and enable early intervention. Trial registration clinicaltrials.gov NCT05855109 (submission date: 3 May 2023).

This study aimed to evaluate the impact of Complementary and Alternative Medicine (CAM) use on functional status and pain relief in patients with Chronic Rheumatic Diseases (CRDs) using the Visual Analogue Pain Scale (VAS) and Health Assessment Questionnaire (HAQ). This cross-sectional multicentre study involved patients from rheumatology outpatient clinics who met the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) criteria for rheumatic disease diagnosis. The exclusion criteria included acute flares or comorbid conditions that could interfere with the outcomes. Data collection included demographic and clinical data, pharmacotherapy, CAM usage, and its impact on the VAS and HAQ scales. The study included 126 patients. A significant proportion (57%) reported CAM use, with a preference for one (67%) or multiple (33%) modalities. CAM users exhibited significantly lower VAS scores, indicating reduced pain perception, and lower HAQ scores, suggesting better functional status than non-users. Correlation analyses highlighted strong positive associations between patient age, disease duration, and CAM use preference, as well as between educational level and specific CAM therapies. CAM use among patients with CRDs is associated with significant improvements in pain perception and functional capacity, as evidenced by lower VAS and HAQ scores. These findings suggest the potential of CAM to complement conventional rheumatology treatments, highlighting its value in patient-centered care and indicating its role in improving patient outcomes. However, the study's cross-sectional design and reliance on self-reported data necessitate further research for causal inferences and robust establishment of CAM efficacy. [Med-Science 2024; 13(3.000): 557-63]

Background The ongoing conflict in Syria has significantly affected the health care system, particularly in the realm of rheumatology. The purpose of this study is to assess the current state of rheumatic diseases in the northwestern region of Syria, where the health care infrastructure has been severely impacted.

Abstract Objective To investigate the psychosocial burden in children and adolescents with juvenile rheumatic diseases during the COVID-19 pandemic. Methods As part of the multicentre observational KICK-COVID study linked to the National Pediatric Rheumatology Database, adolescents

Proinflammatory extracellular and intracellular DAMPs are the dominant etiological factors of sterile inflammation in immuno-inflammatory rheumatic diseases. They are generated by systemic progressive disorganization of loose fibrous unformed connective tissue, programmed cell death and cell necrosis. Sterile inflammation is a multi-stage process which is induced by a sequence of reactions mediated by leukocytes and resident cells of the macrophage-monocyte series, aimed at cleansing the focus of inflammation from cellular and tissue detritus, followed by restoration of homeostasis of damaged tissue. An important role in this process belongs to the transendothelial migration of leukocytes to the focus of sterile inflammation and formation of cellular inflammatory infiltrate. The key feature of these events is the reactivity of PRR receptors followed by a cascade of PRR-DAMPs interactions with subsequent launch of molecular and cellular processes causing the local and/or systemic manifestations of sterile inflammation. Activation of innate immunity is the result of PRR-DAMPs interactions which launches the molecular and cellular reactions. Hence, it is possible to attribute the immunoinflammatory rheumatic diseases to the category of systemic sterile autoinflammatory processes. Generalization of the pathophysiological effects of pro-inflammatory DAMPs and, accordingly, the systemic and multi-organ nature of tissue and internal organ damage in immunoinflammatory rheumatic diseases is due to the wide occurrence of receptors for “danger signals”. The most important place in the development of DAMP-mediated sterile inflammation is occupied by the phenomenon of cross-presentation and autophagy. The cross-presentation causes exposition of extracellular DAMPs from internalized proteins with MHC class I molecules to autoreactive CD8+ cytotoxic T lymphocytes. Autophagy provides processsing of intracellular peptide DAMPs, their loading onto MHC class II molecules with subsequent induction of adaptive immune response in CD4+T cell populations. The innate lymphoid cells (ILC) make an important contribution to these processes. The model of functional coupling and complementarity between ILCs and Th-CD4+T cells has expanded our understanding of immune regulation by extending the activity of innate and adaptive immunity to the level of maintaining tissue homeostasis, morphogenesis, repair, regeneration and inflammation. Progression of systemic sterile inflammation may be a result of PRR-DAMP interactions of tissue ILCs followed by switching of ILC/Th-CD4+T cell partners. The data presented in this review define the promising molecular and cellular targets aiming for regulation and/or inhibition of sterile inflammation in immunoinflammatory rheumatic diseases.

The aim – to study risk factors for severe COVID-19 in patients with rheumatic diseases (RD).Patients and methods. The study included medical histories of 464 patients with RD who were admitted at the V.A. Nasonova Research Institute of Rheumatology from September 27, 2021 to April 26, 2023Results. Age over 60 years, hypertension, obesity, lung disease, chronic kidney disease, coronary heart disease, diabetes mellitus, acute cerebrovascular accident or a history of pulmonary tuberculosis increase the risk of hospitalization in patients with RD with COVID-19 by 3–5 times. In addition, with an increase in the number of concomitant diseases, an increase in the risk of hospitalization was noted by 2–6 times. Taking glucocorticoids, including at a dose of ≥10 mg per day for prednisolone, mycophenolate mofetil and rituximab, leads to an increase risk of hospitalization by 1.5–4.5 times, while patients taking hydroxychloroquine or tumor necrosis factor α inhibitors was more often required outpatient treatment.Conclusions. It has been established that older age, the presence of comorbid pathology and the use of glucocorticoids, including at a dose of ≥10 mg per day for prednisolone, mycophenolate mofetil and rituximab, are risk factors for severe COVID-19.