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Chronic pain in inflammatory arthritis (IA) reflects a complex interplay between active disease in a peripheral joint and central pronociceptive mechanisms. Because intra-articular lidocaine may be used to abolish joint-specific peripheral input to the central nervous system, we aimed to validate its use as a clinical tool to identify those patients with IA whose pain likely incorporates centrally mediated mechanisms. We began by investigating whether there was a placebo response of intra-articular injection in patients with IA 1:1 randomised to receive intra-articular lidocaine or control (0.9% saline). After, in a larger patient cohort not randomized to placebo vs lidocaine groups, we tested whether patients with IA could be stratified into 2 cohorts based on their response to intraarticular lidocaine according to markers of centrally mediated pain. To this end, we evaluated postlidocaine pain numerical rating scale (NRS) scores alongside baseline painDETECT, fibromyalgia criteria fulfillment, and quantitative sensory testing outcomes. Numerical rating scale scores were collected at baseline and 3-, 5-, and 10-minutes postinjection. Firstly, the placebo effect of intraarticular injection was low: compared to baseline, the mean pain NRS score 5-minutes postinjection was reduced by 3.5 points in the lidocaine group vs 1.2 points in the control group. Secondly, postlidocaine NRS scores were significantly higher in those with a high (.18) baseline painDETECT score, fibromyalgia, and low-pressure pain threshold at the trapezius (P 5 0.002, P 5 0.001, P 5 0.005, respectively). Persistent high pain after intra-articular lidocaine injection could be used as an indicator of pronociceptive mechanisms that are centrally mediated, informing centrally targeted analgesic strategies. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of iguratimod (IGU) in the treatment of inflammatory arthritis and degenerative arthritis. Methods: Initially, randomized controlled trials (RCTs) on using IGU in treating inflammatory arthritis and degenerative arthritis were systematically gathered from various databases up to February 2024. Subsequently, two researchers independently screened the literature, extracted data, assessed the risk of bias in included studies, and conducted a meta-analysis using RevMan 5.4 software. Results: Fifty-four RCTs involving three inflammatory arthritis were included, including ankylosing spondylitis (AS), osteoarthritis (OA), and rheumatoid arthritis (RA). For AS, the meta-analysis results showed that IGU may decrease BASDAI (SMD −1.68 [−2.32, −1.03], P < 0.00001) and BASFI (WMD −1.29 [−1.47, −1.11], P < 0.00001); IGU may also decrease inflammatory factor [ESR: (WMD −10.33 [−14.96, −5.70], P < 0.0001); CRP: (WMD −10.11 [−14.55, −5.66], P < 0.00001); TNF-α: (WMD −6.22 [−7.97, −4.47], P < 0.00001)]. For OA, the metaanalysis results showed that IGU may decrease VAS (WMD −2.20 [−2.38, −2.01], P < 0.00001) and WOMAC (WMD −7.27 [−12.31, −2.24], P = 0.005); IGU may also decrease IL-6 (WMD −8.72 [−10.00, −7.45], P < 0.00001). For RA, the meta-analysis results showed that IGU may improve RA remission rate [ACR20: (RR 1.18 [1.02, 1.35], P = 0.02); ACR50: (RR 1.32 [1.05, 1.64], P = 0.02); ACR70: (RR 1.44 [1.02, 2.04], P = 0.04)] and decrease DAS28 (WMD −0.92 [−1.20, −0.63], P < 0.00001); IGU may also decrease inflammatory factors [CRP: (SMD −1.36 [−1.75, −0.96], P < 0.00001); ESR: (WMD −9.09 [−11.80, −6.38], P < 0.00001); RF: (SMD −1.21 [−1.69, −0.73], P < 0.00001)]. Regarding safety, adding IGU will not increase the incidence of adverse events. Conclusion: IGU might emerge as a promising and secure therapeutic modality for addressing AS, OA, and RA. [ABSTRACT FROM AUTHOR]

Background/Objectives: Rheumatoid arthritis is a chronic, systemic, inflammatory disease of an autoimmune nature that causes pain and disability in affected patients. Foot pain has become a challenge due to its negative impact on physical function. The objective of this updated systematic review is to describe the effect of foot orthoses and/or footwear in patients with rheumatoid arthritis and foot problems. Methods: Scopus, PubMed, CINALH, WOS, and Dialnet were searched for all articles published from January 2013 to September 2024. Inclusion criteria included randomised clinical trials and crossover trials (level of evidence I), published within the last 10 years, involving adults with a diagnosis of rheumatoid arthritis, with no restrictions on gender, race, or ethnicity. All studies that addressed the use of foot orthoses and/or shoe therapy in any type of comparison between these interventions were considered relevant. Review Manager was used to carry out the bias analysis of the selected studies. The reporting was based on the new PRISMA guidelines. Results: A total of 9 relevant articles were selected from an initial sample of 438. These articles analyse and compare the effectiveness of various types of foot orthoses in reducing pain, functional limitation, and disability, as well as improving balance and kinetic and kinematic parameters affected by rheumatoid arthritis. Conclusions: Foot orthoses reduce pain and disability in rheumatoid arthritis, improving balance and kinematic parameters. However, no significant improvements in the patients' functionality and walking ability have been demonstrated. Customised ones with good arch control, heel reinforcement, and metatarsal pad are more effective. No results on the impact of footwear on patients with rheumatoid arthritis have been found in the last 10 years. This systematic review was registered in PROSPERO (CRD42023405645). [ABSTRACT FROM AUTHOR]

Intracellular oligonucleotide delivery possesses unparalleled potential for precise regulation of pathogenic gene expression and alteration of cell destiny. However, limited by its feeble resistance against humoral environment, hindered intracellular transportation, and lysosomal phagocytosis, oligonucleotide therapy remains a formidable challenge. The discovery of cationic peptides has provided innovative insights for the effective delivery of oligonucleotides, yet the stable, efficient, and convenient assembly of peptides and oligonucleotides remains an elusive goal, referred to as the "Holy Grail" challenge in the field. Addressing this challenge, it has pioneered the development of a straightforward and highly efficient engineering carrier‐free covalent peptide‐oligonucleotide nano‐conjugates (PONs) through a mild click reaction. Notably, this PONs can realize self‐assemble into nanoparticles under amphiphilic electrostatic interactions, which exhibits significant RNase resistance and surprisingly effective intracellular oligonucleotide delivery as well as lysosomal escape. Based on this strategy, a PONs named CPP‐(DOPA)6‐miRNA‐223 is synthesized, which demonstrates rapid and effective cellular uptake, swift lysosomal escape in macrophage, remarkable accumulation in inflammatory regions and excellent therapeutic effect in an inflammatory arthritis model. Therefore, this work may provide a breakthrough for the clinical application of all oligonucleotide delivery therapies and expanding the applications in gene therapy. [ABSTRACT FROM AUTHOR]

Hidradenitis Suppurativa (HS) is a chronic, debilitating, auto‐inflammatory condition often associated with inflammatory arthritis, significantly impacting patients' quality of life. Early diagnosis of both conditions is crucial for optimal management. The objective of this study was to determine the prevalence and factors associated with the development of inflammatory arthritis among HS patients. A cross‐sectional study was conducted between November 2021 and February 2023 at an academic dermatology centre in Canada. Adult patients with HS were consecutively sampled, and 52 patients consented to participate and completed assessments. Variables examined included age, sex, HS severity, treatment, ethnicity, family history, lifestyle factors and comorbidities. The main outcomes were rheumatologist‐confirmed inflammatory arthritis diagnosis and associated risk factors. Among 52 patients (24 males, 28 females; mean age: 37.4 years), 12 had inflammatory arthritis. Multivariate analysis revealed that Blacks (OR = 0.10, p < 0.001, CI: 0.026–0.343) and Asians (OR = 0.02, p < 0.001, CI: 0.005–0.109) had lower inflammatory arthritis odds compared to Whites. Every 1‐year increase in age at HS onset correlated with a 1.17‐fold increase in the odds of developing inflammatory arthritis (OR: 1.17, p < 0.001, CI: 1.12–1.24). Smoking (OR = 0.01, p < 0.001, CI: 0.002–0.49), hypertension (OR: 0.23, p = 0.04, CI: 0.057–0.930) and depression (OR: 0.12, p < 0.001, CI: 0.041–0.330) reduced inflammatory arthritis odds. White ethnicity and older age at HS onset were positively associated with inflammatory arthritis, while smoking, hypertension and depression were negatively associated. These findings suggest a distinct subset of HS patients with inflammatory arthritis that warrant further prospective studies. This study contributes to the understanding of inflammatory arthritis in HS patients and emphasises the importance of rheumatology referral during dermatologic clinic visits. [ABSTRACT FROM AUTHOR]

Objectives This mixed-methods systematic review aimed to identify and synthesize knowledge of the characteristics, content, and preferred format of information to support people with inflammatory arthritis (IA) to take MTX. Methods A literature search using MEDLINE, The Cochrane Library, EMBASE, CINAHL, PsychInfo, GreyEU, Web of Science and Open Dissertation was conducted to identify all studies published from 2000 to December 2022. Included studies detailed factors related to MTX information needs of people aged ≥18 years with IA published in English. The Joanna Briggs Institute Guidelines (JBI) for convergent integrated mixed-methods systematic reviews were followed using validated tools for data extraction and quality. The data was analysed using reflexive thematic analysis. Results Thirteen studies (seven quantitative, two mixed-methods and four qualitative) were included, involving 3425 adults, mainly female n  = 2434 (71%), age 20–84 years. An overarching theme of a requirement for person-centred care was developed, with three interlinking themes: (1) accepting the need for treatment with MTX, (2) concerns about taking MTX, and (3) a need for tailored information and support. Limitations of the evidence included the use of heterogeneous outcome measures and instruments for measuring information needs. Conclusion People with IA have individual, multifaceted information and support needs about MTX that are often unresolved when a one-size-fits-all approach is used. The findings of this review can inform rheumatology training to support a person-centred approach to identifying and addressing the specific needs and concerns and development of consistent easy-to-understand accessible MTX information. [ABSTRACT FROM AUTHOR]

Connective tissue, rheumatological and dermatological conditions affect a large proportion of the pregnant population and have important implications for women and their babies. Some conditions are chronic but may occur de novo in pregnancy whereas some are seen only during pregnancy. Multidisciplinary care is essential to maximise fetal and maternal outcomes, since many of these women require immunosuppressive treatment and close monitoring of their pregnancies. The development of biological therapies has revolutionised treatment of many connective tissue and arthritic diseases, allowing both more targeted treatments and an increase in treatment options. Their impact on fertility is minimal compared to older treatments and hence more women are able to conceive. With new treatments there will always be concerns about safety in pregnancy but concerns around neonatal immunosuppression have largely been unfounded and the benefits of continuing medication are significant. This article uses four cases to illustrate the challenges of management. [ABSTRACT FROM AUTHOR]

[Display omitted] • Inflammatory arthritis can cause peripheral nerve sensitization. • GBP can intervene in peripheral nerve sensitization caused by inflammatory arthritis. • NR2B may be the cause of peripheral sensitization in inflammatory arthritis. • GBP may alleviate pain through the downregulation of NR2B. • This study provides a theoretical basis for the inflammatory arthritis. Inflammatory arthritis leads to peripheral nerve sensitization, but the therapeutic effect is often unsatisfactory. Our preliminary studies have found that in mice with inflammatory arthritis, the use of ionotropic glutamate receptor antagonists can produce a good analgesic effect without altering foot swelling, suggesting that pain relief may be related to the improvement of neuropathic pain. However, the underlying mechanisms remain unclear. To further investigate the effects of neuropathic pain medications on inflammatory arthritis and the impact of the ionotropic glutamate receptor NR2B subunit (NR2B) on inflammatory arthritis, this study employed gabapentin (GBP) treatment on the inflammatory arthritis mouse model (the adjuvant induced arthritis, AIA), and we found a significant reduction in pain. Further studies revealed that in AIA, the expression levels of NR2B, TRPV1, pain-related molecules (substance P, PGE 2), inflammatory cytokines (IL-1, IL-6, TNF-α, and GM-CSF) and Ca2+ were elevated in the foot and dorsal root ganglia (DRG). GBP treatment was able to influence the downregulation of the expression levels of NR2B, TRPV1, pain-related molecules, inflammatory cytokines and Ca2+. Mechanistic studies have shown that GBP treatment affects the downregulation of NR2B, and the downregulation of NR2B expression leads to the downregulation of TRPV1, pain-related molecules and inflammatory cytokines, thereby alleviating pain. These results suggest that in peripheral sensitization caused by AIA, GBP can play a role in improving pain, and NR2B may be a key target of peripheral nerve sensitization induced by inflammatory arthritis. GBP provides a theoretical basis for the clinical treatment of inflammatory arthritis. [ABSTRACT FROM AUTHOR]

Inflammatory arthritis are common chronic inflammatory autoimmune diseases characterised by progressive, destructive inflammation of the joints leading to a loss of function and significant comorbidities; importantly, there are no cures and only 20% of patients achieve drug-free remission for over 2 years. Macrophages play a vital role in maintaining homeostasis, however, under the wrong environmental cues, become drivers of chronic synovial inflammation. Based on the current "dogma", M1 macrophages secrete pro-inflammatory cytokines and chemokines, promoting tissue degradation and joint and bone erosion which over time lead to accelerated disease progression. On the other hand, M2 macrophages secrete anti-inflammatory mediators associated with wound healing, tissue remodelling and the resolution of inflammation. Currently, four subtypes of M2 macrophages have been identified, namely M2a, M2b, M2c and M2d. However, more subtypes may exist due to macrophage plasticity and the ability for repolarisation. Macrophages are highly plastic, and polarisation exists as a continuum with diverse intermediate phenotypes. This plasticity is achieved by a highly amenable epigenome in response to environmental stimuli and shifts in metabolism. Initiating treatment during the early stages of disease is important for improved prognosis and patient outcomes. Currently, no treatment targeting macrophages specifically is available. Such therapeutics are being investigated in ongoing clinical trials. The repolarisation of pro-inflammatory macrophages towards the anti-inflammatory phenotype has been proposed as an effective approach in targeting the M1/M2 imbalance, and in turn is a potential therapeutic strategy for IA diseases. Therefore, elucidating the mechanisms that govern macrophage plasticity is fundamental for the success of novel macrophage targeting therapeutics. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is a complex multi-system immune-mediated condition, characterised by a high comorbidity burden, one of the most prevalent of which is cardiovascular disease (CVD), affecting up to 80% of patients. This narrative review explores the current understanding of cardiovascular comorbidities in PsA, focusing on mechanistic pathways, risk assessment, and the impact of treatment choices on cardiovascular health. Here, we outline the role of inflammatory cytokines, immune system dysregulation, and genetic predispositions in PsA, not only as drivers of musculoskeletal manifestations but also atherosclerosis and endothelial dysfunction, giving rise to cardiovascular pathology. Given these insights, accurately assessing and predicting cardiovascular risk in PsA patients is a critical challenge. This review evaluates traditional risk calculators as well as innovative biomarkers and imaging techniques, emphasising their utility and limitations in capturing the true cardiovascular risk profile of PsA patients. There are multiple complexities surrounding the treatment of PsA in the context of concurrent CVD, and therapeutic choices must carefully balance efficacy in managing PsA symptoms with the potential cardiovascular implications. A multidisciplinary approach, integrating dermatological, rheumatological, and cardiological perspectives, amongst others, to optimise patient outcomes, is key. Overall, a heightened clinical awareness and research focus on cardiovascular comorbidities in PsA is warranted, aiming to refine risk assessment strategies and therapeutic interventions that holistically address the multifaceted needs of patients with PsA. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the effects of different ω-3 polyunsaturated fatty acid (PUFA) enriched diets, including a novel renewable plant source of ω-3 fatty acids (Buglossoides arvensis), on the development and progression of rheumatoid arthritis (RA). Methods: RA was induced in mice consuming experimental diets using the K/BxN model. The experimental diets consisted of either a western control diet (control), diets containing B. arvensis oil or fish oil. The effects of the diets on platelets, platelet microvesicles (PMVs), and inflammatory markers such as clinical index, ankle thickness and cytokine/chemokine release were measured. Results: While ω-3 PUFA-enriched diets did not prevent the development of arthritis in the K/BxN model, a significant decrease in ankle swelling was observed compared to the control group. Platelets isolated from mice consuming either low content of B. arvensis oil or fish oil diets exhibited significantly decreased PMVs production compared to mice consuming the control diet. Conclusion: Our study provides insight into the contribution of ω-3 PUFA supplementation in modulating the pro-inflammatory phenotype of platelets in RA pathology. Furthermore, our study suggests that low concentrations of dietary B. arvensis oil may have similar anti-inflammatory potential seen with dietary fish oil supplementation. [ABSTRACT FROM AUTHOR]

Abstract Ankylosing spondylitis (AS) is a chronic inflammatory arthritis affecting the spine, presenting a considerable morbidity risk. Although evidence consistently indicates an elevated risk of ischemic heart disease among AS patients, debates persist regarding the likelihood of these patients developing left ventricular dysfunction (LVD). Our investigation aimed to determine whether individuals with AS face a greater risk of LVD compared to the general population. To accomplish this, we identified studies exploring LVD in AS patients across five major databases and Google Scholar. Initially, 431 studies were identified, of which 30 met the inclusion criteria, collectively involving 2933 participants. Results show that AS patients had: (1) poorer Ejection Fraction (EF) [mean difference (MD): −0.92% (95% CI: −1.25 to −0.59)], (2) impaired Early (E) and Late (atrial—A) ventricular filling velocity (E/A) ratio [MD: −0.10 m/s (95% CI: −0.13 to −0.08)], (3) prolonged deceleration time (DT) [MD: 12.30 ms (95% CI: 9.23–15.36)] and, (4) a longer mean isovolumetric relaxation time (IVRT) [MD: 8.14 ms (95% CI: 6.58–9.70)] compared to controls. Though AS patients show increased risks of both systolic and diastolic LVD, we found no significant differences were observed in systolic blood pressure [MD: 0.32 mmHg (95% Confidence Interval (CI): −2.09 to 2.73)] or diastolic blood pressure [MD: 0.30 mmHg (95% CI: −0.40 to 1.01)] compared to the general population. This study reinforces AS patients' susceptibility to LVD without a notable difference in HTN risk.

This document summarizes a study on the cardiovascular risks of Janus kinase inhibitors (JAKi) in patients with rheumatic diseases. The study found that the impact of JAKi on cardiovascular risk is complex and may vary depending on factors such as baseline risk factors, disease activity, and type of rheumatic disease. Some studies suggest an increased cardiovascular risk with JAKi, especially in older patients with risk factors, while others found no significant difference compared to other treatments. More research is needed to fully understand the relationship between JAKi and cardiovascular risk. [Extracted from the article]

Inflammatory arthritis may be the principal feature or one component of an inflammatory rheumatological disease. It is a clinical diagnosis, principally made based on the patient’s history and examination. Specific investigations, such as rheumatoid factor and human leucocyte antigen B27 gene, may support the diagnosis in the context of a suggestive clinical presentation, but a diagnosis cannot be made based on these tests alone because positive results may also be seen in healthy individuals. To reduce the likelihood of false positive results, laboratory and radiological investigations should be tailored to the suspected diagnosis based on pretest probability. While musculoskeletal symptoms are a common presentation in general practice, specific features that increase suspicion of an inflammatory arthritis include prolonged morning stiffness (more than 1 hour) that is improved by exercise or movement. A broad ‘rheumatological panel’ increases the likelihood of false positive results and should be avoided to prevent unnecessary further investigations and treatment, and unwarranted anxiety in both the patient and the doctor. [ABSTRACT FROM AUTHOR]

Background: Systemic sclerosis is a type of autoimmune connective tissue disease. It is more prevalent in the Northern and Northeastern regions of Thailand compared to other regions, with diffuse cutaneous systemic sclerosis (dcSSc) being the most common subtype. Musculoskeletal involvement, including arthritis, is a major cause of disability and reduced quality of life in patients with systemic sclerosis. Objective: To investigate the prevalence of arthritis in patients with systemic sclerosis and define the clinical association with arthritis. Materials and Methods: The present research was an observational analytical study conducted at Sunpasitthiprasong Hospital, Ubon Ratchathani Province, Thailand, between January 2022 and January 2023. One hundred ninety-seven patients with systemic sclerosis were included in the study, and logistic regression analysis was used for investigating the clinical association with arthritis. Results: One hundred ninety-seven patients were included and comprised of 138 (70.1%) with arthritis. The majority of patients with arthritis were female, at 71.1%, and dcSSc, at 91.4%, with the mean age of 51.6±11.8 years. Multivariable logistic regression analysis after controlling for other variables revealed that periarticular osteopenia was significantly associated with arthritis in patients with systemic sclerosis (95% confidence interval: 8.34 to 67.36). Conclusion: Arthritis was a common clinical feature in systemic sclerosis for 70.1%. The presence of periarticular osteopenia was independently associated with arthritis. This clinical factor could be utilized to aid in the diagnosis of arthritis in systemic sclerosis patients and improve treatment outcomes. [ABSTRACT FROM AUTHOR]

The advent of immune checkpoint inhibitors (ICIs) in cancer treatment has marked a transformative era, albeit tempered by immune-related adverse events (irAEs), including those impacting the musculoskeletal system. The lack of precise epidemiologic data on rheumatic irAEs is attributed to factors such as potential underrecognition, underreporting in clinical trials, and the tendency to overlook manifestations without immediate life-threatening implications, further complicating the determination of accurate incidence rates, while the complete understanding of the mechanisms driving rheumatic irAEs remains elusive. This literature review comprehensively examines rheumatic irAEs in cancer patients undergoing ICI therapy, encompassing epidemiology, risk factors, mechanisms, clinical manifestations, and current management guidance for prevalent conditions such as inflammatory arthritis, polymyalgia rheumatica, and myositis. Less frequent rheumatic and musculoskeletal irAEs are also explored, alongside insights into ongoing clinical trials testing therapeutic and preventive strategies for irAEs. A thorough literature search on Medline and the National Cancer Institute Clinical Trials Database was conducted up to October 2023 to compile relevant information. In light of the evolving landscape of cancer immunotherapy, there is a compelling need for prospective longitudinal studies to enhance understanding and inform clinical management strategies for rheumatic irAEs. [ABSTRACT FROM AUTHOR]

Objective: To compare the risk of infection in inflammatory arthritis patients treated with tumor necrosis factor (TNF) inhibitors. Methods: PubMed, Embase, and the Cochrane Library were systematically searched from inception to 28 December 2023 for randomized controlled trials (RCTs) assessing TNF inhibitors and reporting infections. Subsequently, pairwise and network meta-analyses were conducted to determine odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Results: A total of 61 RCTs involving 20,458 patients were included. Pairwise meta-analysis revealed that certolizumab pegol was significantly associated with an increased risk of serious infection compared to placebo (OR:2.28, 95% CI: 1.13–4.62). Both adalimumab and certolizumab pegol were also significantly associated with an increased risk of any infection compared to placebo (OR:1.18, 95% CI: 1.06 to 1.30 and OR:1.40, 95% CI: 1.11 to 1.76, respectively). Moreover, a network meta-analysis indicated that certolizumab pegol and infliximab were associated with a higher risk of serious infection compared to other TNF inhibitors. In the cumulative ranking of any infection risk, certolizumab pegol had the highest risk compared with others. TNF inhibitors increased the risk of tuberculosis but not that of herpes zoster. Conclusion: Available evidence indicates etanercept and golimumab are likely associated with a lower risk of infection compared to other TNF inhibitors in inflammatory arthritis. For patients at a heightened risk of infection, prioritizing the use of etanercept and golimumab may be advisable to minimize patient risk. [ABSTRACT FROM AUTHOR]

Objectives Inflammatory arthritis causes significant work disability. Studies regarding this frequently fail to report important contextual information such as employment type. Our objective was to explore work participation, by gender and occupation type, in early inflammatory arthritis. Methods Data are from the National Early Inflammatory Arthritis Audit for 2018–2020. At diagnosis, clinicians collected information on demographics, inflammatory arthritis disease activity, and working status. Participants completed patient-reported outcomes at baseline, 3 months and 12 months, including occupation and Work Productivity and Activity Impairment (WPAI). Descriptive analyses of work participation and WPAI scores by occupational class at all time points were performed. Regression models were used to examine associations between WPAI score and occupation. Results In all, 12 473 people received a diagnosis of inflammatory arthritis and reported employment status, among whom 5999 (47%) were in paid work for at least 20 hours/week. At diagnosis, the working cohort had statistically significant lower measures of disease activity (P  < 0.001). Occupational data were available for 3694 individuals. At diagnosis, 2793 completed a WPAI; 200 (7.2%) had stopped work and 344 (12.3%) changed jobs because of inflammatory arthritis symptoms. There was a high burden of absenteeism (30%) and presenteeism (40%). Compared with managerial or professional workers, the burden of work disability was greater among those in routine (manual) occupations. During follow-up, 9.4% of WPAI completers stopped work and 14.6% changed roles. Work drop-out occurred almost entirely among people doing routine jobs. Conclusion It is easier to retain work in certain employment sectors. Participation in routine jobs is more affected, which may widen health inequalities. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis affecting the spine, presenting a considerable morbidity risk. Although evidence consistently indicates an elevated risk of ischemic heart disease among AS patients, debates persist regarding the likelihood of these patients developing left ventricular dysfunction (LVD). Our investigation aimed to determine whether individuals with AS face a greater risk of LVD compared to the general population. To accomplish this, we identified studies exploring LVD in AS patients across five major databases and Google Scholar. Initially, 431 studies were identified, of which 30 met the inclusion criteria, collectively involving 2933 participants. Results show that AS patients had: (1) poorer Ejection Fraction (EF) [mean difference (MD): −0.92% (95% CI: −1.25 to −0.59)], (2) impaired Early (E) and Late (atrial—A) ventricular filling velocity (E/A) ratio [MD: −0.10 m/s (95% CI: −0.13 to −0.08)], (3) prolonged deceleration time (DT) [MD: 12.30 ms (95% CI: 9.23–15.36)] and, (4) a longer mean isovolumetric relaxation time (IVRT) [MD: 8.14 ms (95% CI: 6.58–9.70)] compared to controls. Though AS patients show increased risks of both systolic and diastolic LVD, we found no significant differences were observed in systolic blood pressure [MD: 0.32 mmHg (95% Confidence Interval (CI): −2.09 to 2.73)] or diastolic blood pressure [MD: 0.30 mmHg (95% CI: −0.40 to 1.01)] compared to the general population. This study reinforces AS patients' susceptibility to LVD without a notable difference in HTN risk. [ABSTRACT FROM AUTHOR]

Pyoderma gangrenosum is a rare inflammatory skin disease. It is a type of neutrophilic dermatosis characterised by painful, rapidly enlarging ulcerations. Its frequent co-occurrence with diseases such as inflammatory bowel disease or rheumatic disorders, including psoriatic arthritis, is noteworthy. Using the patient's case and the available literature, we show that the diagnosis and treatment of pyoderma gangrenosum are complex and require a multi-specialist approach due to its rarity and systemic comorbidities. New diagnostic criteria and developed treatment algorithms may facilitate diagnosis and shorten the time to introduce effective treatment, including biological therapy, and current research on PG appears promising. [ABSTRACT FROM AUTHOR]

Objectives The objective of this study was to determine baseline risk factors for requiring immunosuppression and having persistent arthritis in patients with immune checkpoint inhibitor–induced inflammatory arthritis (ICI–inflammatory arthritis). Methods Participants were adults with rheumatologist diagnosed ICI–inflammatory arthritis. The primary outcome was requirement of conventional synthetic (cs) or biologic (b) DMARDs; other outcomes were persistence of inflammatory arthritis >6 months after ICI cessation and requirement of CSs. Logistic regression models evaluated associations between clinical features and primary and secondary outcomes, with adjustment for potential confounders, as appropriate. Results One hundred and twenty-six patients with ICI–inflammatory arthritis were included; 53 patients (42%) required a csDMARD/bDMARD. In the univariate logistic regression analysis, higher clinical disease activity index (CDAI), tenosynovitis, longer symptom duration before first rheumatology visit and longer ICI duration were significantly associated with a higher likelihood of requiring DMARDs; in addition, there was a trend towards those treated with prior chemotherapy being less likely to need DMARDs. After adjustment, tenosynovitis, longer symptom duration and higher CDAI remained associated with requiring DMARDs, while those with prior chemotherapy were significantly less likely to require DMARDs. Combination anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein-4)/PD-1 (Programmed cell death protein-1) therapy and CS use at baseline were associated with a higher risk of persistent inflammatory arthritis. Conclusion Higher levels of disease activity, tenosynovitis and longer symptom duration prior to rheumatology referral were associated with requiring DMARDs for ICI–inflammatory arthritis, while those treated previously with chemotherapy were less likely to require additional immunosuppression. The presence of risk factors for severe disease at baseline may indicate a role for higher initial CS dose, earlier rheumatology referral, and adoption of immunosuppression beyond CSs to improve outcomes. [ABSTRACT FROM AUTHOR]

Aim: To compare the effects of Yoga with traditional exercise on the mobility and functional capacity of individuals with ankylosing spondylitis (AS). Methods: The participants of the study were recruited at the rheumatology department, adhering to the study's inclusion and exclusion criteria. Participants were randomized into two groups (Group A – Yoga, and Group B – exercise).The candidates participated in an 8‐week intervention consisting of 3 weekly sessions of either Yoga or Exercise intervention. Outcomes were collected at pre‐treatment, at 8 weeks, and at 12 weeks. Results: The within‐group comparison showed an improvement in all outcome measures with p <.05 between post‐treatment and the follow‐up. In the yoga group, there was an improvement in the measures of BASMI (p =.001), BASFI (p =.005), PSQI (p =.021), CE (p =.053) and NPRS (p =.001). Similarly, in the exercise group, there was an improvement in BASMI (p =.002), BASFI (p =.003), PSQI (p =.010), CE (p =.004) and NPRS (p =.001). In the between group comparison at post‐treatment, there were no statistically significant differences in BASMI (yoga = 3.0 ± 1.50, exercise = 2.3 ± 1.38), PSQI (yoga = 5.3 ± 1.50, exercise = 4.9 ± 1.17) and NPRS (yoga = 1.3 ± 2.22, exercise = 0.4 ± 0.50) CE (yoga = 4.0 ± 1.18, exercise = 3.4 ± 0.96), BASFI (yoga = 1.8 ± 2.14, exercise = 2.1 ± 1.87). Conclusion: The results demonstrated a statistically significant improvement in within‐group scores of mobility, functional capacity, sleep quality and pain in AS patients of both intervention programs but there were no significant differences between the groups. [ABSTRACT FROM AUTHOR]

Purpose of Review: In the clinical evaluation of inflammatory arthritis and the research into its pathogenesis, there is a growing role for the direct analysis of synovial tissue. Over the years, various biopsy techniques have been used to obtain human synovial tissue samples, and there have been progressive improvements in the safety, tolerability, and utility of the procedure. Recent Findings: The latest advancement in synovial tissue biopsy techniques is the use of ultrasound imaging to guide the biopsy device, along with evolution in the characteristics of the device itself. While ultrasound guided synovial biopsy (UGSB) has taken a strong foothold in Europe, the procedure is still relatively new to the United States of America (USA). Summary: In this paper, we describe the expansion of UGSB in the USA, elucidate the challenges faced by rheumatologists developing UGSB programs in the USA, and describe several strategies for overcoming these challenges. [ABSTRACT FROM AUTHOR]

Interleukin 27 has both pro-inflammatory and anti-inflammatory properties in autoimmunity. The anti-inflammatory effects of IL-27 are linked with inhibition of Th17 differentiation but the IL-27 effect on myeloid cells is less studied. Herein we demonstrate that IL-27 inhibits IL-23-induced inflammation associated not only with Th17 cells but also with myeloid cell infiltration in the joints and splenic myeloid populations of CD11b+ GR1+ and CD3-CD11b+CD11c-GR1- cells. The IL-27 anti-inflammatory response was associated with reduced levels of myeloid cells in the spleen and bone marrow. Overall, our data demonstrate that IL-27 has an immunosuppressive role that affects IL-23-dependent myelopoiesis in the bone marrow and its progression to inflammatory arthritis and plays a crucial role in controlling IL-23 driven joint inflammation by negatively regulating the expansion of myeloid cell subsets.

IntroductionCoronavirus disease 2019 (COVID-19) vaccines aroused concerns about the risk of flares and adverse events in inflammatory arthritis (IA) since the vaccine clinical trials did not specifically investigate this subset of patients.MethodsA systematic literature review and meta-analysis to summarize the data on joint disease flare and adverse events following immunization (AEFI). Two researchers independently evaluated the literature on Pubmed, Scopus, and EMBASE databases from 22nd March 2020 to 30th September 2023. A random-effects model was used to pool odds ratios (OR) (with 95% CI) for the risk of joint disease flares and adverse events. Subgroup analyses were performed to evaluate the risk of disease flare between different IA and adverse events. Heterogeneity was assessed by I2 statistic.ResultsA total of 9874 IA patients were included in the study: 6579 (66.6%) patients affected by RA and 3295 (33.4%) spondyloarthritis (SpA). The overall rate of flares was higher in RA vs. SpA (9.1% vs. 5.3%). However, the pooled estimated analysis showed no increased risk of joint disease flare following COVID-19 vaccination in patients affected by RA vs. SpA [OR 0.88, 95% CI: 0.77-1.00]. Furthermore, a subgroup analysis showed an increased risk of joint flares in psoriatic arthritis (PsA) patients vs. RA [OR 0.79, 95% CI: 0.68-0.93, p=0.004]. The pooled estimated analysis revealed no increased risk of AEFI in patients with RA vs. SpA [1.02, 95% CI: 0.63-1.65].ConclusionsOur meta-analysis summarized the current evidence on joint disease flares and COVID-19 vaccine-associated AEFI in IA patients. Pooled analysis showed an increased risk of disease flares in PsA vs. RA patients.

Background: People with inflammatory rheumatological conditions (IRCs) are at high risk of developing other conditions including cardiovascular disease (CVD) and mood disorders. Aim: To explore perspectives of people with IRCs and healthcare practitioners (HCPs) on the content and delivery of a review consultation aimed at identification and management of multiple long-term conditions (mLTCs). Design & setting: Semi-structured interviews and focus groups with people with IRCs and HCPs in primary and secondary care. Method: People with IRCs participated in individual semi-structured interviews by telephone or online platform. HCPs (including primary and secondary care clinicians) participated in online focus groups. Data were transcribed verbatim and analysed using inductive thematic analysis. Results: Fifteen people with IRCs were interviewed; three focus groups with HCPs were conducted. The following two main themes were identified: reflecting on the value of review consultations; and what would a new review look like? Overall, people with IRCs and HCPs reflected that access to reviews is inequitable, leading to duplication of reviews and fragmentation in care. People with IRCs, at times, had difficulty conceptualising reviews, especially when discussing their future risk of conditions. People suggested that preparation before the healthcare review could align patient and HCP agendas as part of a flexible and person-centred discussion. Conclusion: Any review introduced for people with IRCs must move beyond a ‘tick-box’ exercise. To gain maximum value from a review, preparation from both patient and HCP may be required alongside a person-centred approach while ensuring they are targeted at people most likely to benefit.

Background: Systemic juvenile idiopathic arthritis (sJIA)is a cause of persisting arthralgia which is often missed. Diagnosing sJIA can be challenging, especially when overt arthritis is absent at presentation, highlighting the need for a diagnostic biomarker. Few recent studies have assessed potential biomarkers for sJIA, however, there is no consensus in detecting early. We conducted a study evaluating serum IL-1, IL-6, IL-18, S100A8, and S100A9 as potential diagnostic markers to distinguish sJIA from other conditions presenting as joint pain in children. Methods: A prospective study was conducted in our institute from May-2019 to October-2020 in children under 16 years, who had persisting arthralgia. Serum concentrations of IL-1, IL-6, IL-18, S100A9, and S100A8 were determined using ELISA kits. Receiver operating curve (ROC) analysis was used to determine the cut-off values for IL-1, IL-6, IL-18, S100A8, and S100A9 for differentiating sJIA from other causes of joint pain and fever. Results- Out of 47 children who presented with joint pain and fever 19 of them were eventually diagnosed with sJIA. In the other 28 children, arthralgia and fever was attributed to conditions other than sJIA (non-sJIA). The non-sJIA group comprised children with acute lymphoblastic leukemia, hemophagocytic histiocytosis, systemic lupus erythematosus, Kawasaki disease, Kikuchi disease, and inflammatory bowel disease. Serum levels of IL-18, S100A8, and S100A9 were significantly higher in patients with sJIA compared to the non-sJIA group (p 2030.45 pg/ml was useful for differentiating between sJIA and other diseases with a sensitivity of 66.67% and specificity of 75.86% for the diagnosis of sJIA. Conclusion- Serum IL-18, S100A8, and S100A9 can be useful in differentiating sJIA early from other causes of persisting arthralgia in children provided with appropriate identification of symptomatology and suspicion.

Aims: The aims of this study were to identify and evaluate the current literature examining the prognostic factors which are associated with failure of total elbow arthroplasty (TEA). Methods: Electronic literature searches were conducted using MEDLINE, Embase, PubMed, and Cochrane. All studies reporting prognostic estimates for factors associated with the revision of a primary TEA were included. The risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool, and the quality of evidence was assessed using the modified Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. Due to low quality of the evidence and the heterogeneous nature of the studies, a narrative synthesis was used. Results: A total of 19 studies met the inclusion criteria, investigating 28 possible prognostic factors. Most QUIPS domains (84%) were rated as moderate to high risk of bias. The quality of the evidence was low or very low for all prognostic factors. In low-quality evidence, prognostic factors with consistent associations with failure of TEA in more than one study were: the sequelae of trauma leading to TEA, either independently or combined with acute trauma, and male sex. Several other studies investigating sex reported no association. The evidence for other factors was of very low quality and mostly involved exploratory studies. Conclusion: The current evidence investigating the prognostic factors associated with failure of TEA is of low or very low quality, and studies generally have a moderate to high risk of bias. Prognostic factors are subject to uncertainty, should be interpreted with caution, and are of little clinical value. Higher-quality evidence is required to determine robust prognostic factors for failure of TEA. Cite this article: Bone Joint Res 2024;13(5):201–213.

Abstract Background Immune checkpoint inhibitors (ICIs) have expanded the arsenal of cancer therapeutics over the last decade but are associated with a spectrum of immune-related adverse events (irAEs), including inflammatory arthritis. While these complications are increasingly recognized in the adult population, no cases of inflammatory arthritis irAEs have been reported in the pediatric literature. Case Presentation A 14-year-old female with metastatic epithelioid mesothelioma was referred to the pediatric rheumatology clinic after developing progressive inflammatory joint pain in her bilateral shoulders, hips, and small joints of hands following the second cycle of Nivolumab and Ipilimumab. Initial examinations showed bilateral shoulder joint line tenderness, positive FABERs test bilaterally, tenderness over bilateral greater trochanters, and bilateral second PIP effusions. Her serological profile was notable for positive HLA-B27, positive anti-CCP, negative Rheumatoid Factor, and negative ANA. PET-CT scan performed for disease response following immunotherapy showed symmetric increased metabolic activity primarily involving the supraspinatus, gluteus medius and minimus, and semimembranosus tendon insertions. Her presentation was consistent with a grade 1 irAE that worsened to a grade 2 irAE despite NSAID therapy, prompting a short course of oral prednisolone. She achieved clinical remission of her mesothelioma following six cycles of Nivolumab and Ipilimumab and her inflammatory arthritis was controlled on Celebrex monotherapy. Conclusions To our knowledge, this is the first pediatric case of ICI-induced inflammatory arthritis and enthesitis. This case highlights the importance of increasing awareness of diagnosis and management of irAEs in children.

Abstract Background Exercise and physical activity (EPA) are recommended for people with chronic musculoskeletal disease; however, lower levels of engagement with EPA has been consistently reported in people from the South Asian community across a range of diseases. As language can pose a significant barrier in healthcare, this study aimed to understand the enablers and barriers to the acceptance of EPA among non-English speaking South Asian people who attended rheumatology clinics. Methods 12 non-English speaking individuals from the South Asian community who had chronic musculoskeletal disease with significant pain scores were interviewed via telephone or face-to-face in their spoken languages. The audio recordings of the interviews were translated into English and transcribed verbatim. Data was analysed using thematic analysis implemented in the NVivo 12 Pro software program. Results The mean age was 52 years (9 women and 2 men). One main theme was identified: ‘Enablers and barriers to exercise and physical activity’. Enablers to EPA were having knowledge about the benefits of EPA, being given resources in a language that they understood, and supportive environments such as having access to community facilities for those who could not undertake EPA in their houses. Barriers included physical health such as pain and fatigue, lack of time, difficulties with transportation to exercise venues, dislike of group exercises and lack of understanding of what and how to do exercise and be physically active. Participants’ beliefs about EPA and whether they impacted their physical health seemed to influence whether they were undertaken or not. There was a perception that their culture shaped their compatriots’ beliefs about EPA, and it was not normal practice for people from their country of birth to engage in it. Conclusions This is the first qualitative study to explore the barriers and enablers to engagement in EPA in non-English speaking South Asian people with chronic musculoskeletal disease. Modifiable factors such as addressing the level of knowledge on the benefits of EPA in the management of chronic joint and muscle pain; aiding the development of the skills required to exercise safely and confidently despite chronic pain and providing information and services in the native language could promote the EPA engagement of non-English speaking South Asian individuals with chronic musculoskeletal disease. The findings may inform improvements within clinical services to promote the benefits, impact and self-efficacy of engagement with EPA as part of chronic musculoskeletal disease management. Ethics approval The West Midlands-Edgbaston Research Ethics Committee (reference:20/WM/0305).

Inflammatory arthritis (IA) represents a less common indication for anatomic and reverse total shoulder arthroplasty (TSA) than osteoarthritis (OA). The safety and efficacy of anatomic and reverse TSA in this population has not been as well studied compared to OA. We analyzed the differences in outcomes between IA and OA patients undergoing TSA. Patients who underwent primary anatomic total shoulder arthroplasty (aTSA) and reverse total shoulder arthroplasty (rTSA) from 2016-2020 were identified in the Premier Healthcare Database. Inflammatory arthritis (IA) patients were identified using International Classification of Diseases, Tenth Revision , diagnosis codes and compared to osteoarthritis controls. Patients were matched in a 1:8 fashion by age (±3 years), sex, race, and presence of pertinent comorbidities. Patient demographics, hospital factors, and patient comorbidities were compared. Multivariate regression was performed following matching to account for any residual confounding and 90-day complications were compared between the 2 cohorts. Descriptive statistics and regression analysis were employed with significance set at P <.05. Prior to matching, 5685 IA cases and 93,539 OA controls were identified. Patients with IA were more likely to be female, have prolonged length of stay and increased total costs (P <.0001). After matching and multivariate analysis, 4082 IA cases and 32,656 controls remained. IA patients were at increased risk of deep wound infection (OR 3.14, 95% CI 1.38-7.16, P =.006), implant loosening (OR 4.11, 95% CI 1.17-14.40, P =.027), and mechanical complications (OR 6.34, 95% CI 1.05-38.20, P =.044), as well as a decreased risk of postoperative stiffness (OR 0.36, 95% CI 0.16-0.83, P =.002). Medically, IA patients were at increased risk of PE (OR 2.97, 95% CI 1.52-5.77, P =.001) and acute blood loss anemia (OR 1.27, 95% CI 1.12-1.44, P <.0001). Inflammatory arthritis represents a distinctly morbid risk profile compared to osteoarthritis patients with multiple increased surgical and postoperative medical complications in patients undergoing aTSA and rTSA. Surgeons should consider these potential complications and employ a multidisciplinary approach in preoperative risk stratification of IA undergoing shoulder replacement. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have expanded the arsenal of cancer therapeutics over the last decade but are associated with a spectrum of immune-related adverse events (irAEs), including inflammatory arthritis. While these complications are increasingly recognized in the adult population, no cases of inflammatory arthritis irAEs have been reported in the pediatric literature. Case Presentation: A 14-year-old female with metastatic epithelioid mesothelioma was referred to the pediatric rheumatology clinic after developing progressive inflammatory joint pain in her bilateral shoulders, hips, and small joints of hands following the second cycle of Nivolumab and Ipilimumab. Initial examinations showed bilateral shoulder joint line tenderness, positive FABERs test bilaterally, tenderness over bilateral greater trochanters, and bilateral second PIP effusions. Her serological profile was notable for positive HLA-B27, positive anti-CCP, negative Rheumatoid Factor, and negative ANA. PET-CT scan performed for disease response following immunotherapy showed symmetric increased metabolic activity primarily involving the supraspinatus, gluteus medius and minimus, and semimembranosus tendon insertions. Her presentation was consistent with a grade 1 irAE that worsened to a grade 2 irAE despite NSAID therapy, prompting a short course of oral prednisolone. She achieved clinical remission of her mesothelioma following six cycles of Nivolumab and Ipilimumab and her inflammatory arthritis was controlled on Celebrex monotherapy. Conclusions: To our knowledge, this is the first pediatric case of ICI-induced inflammatory arthritis and enthesitis. This case highlights the importance of increasing awareness of diagnosis and management of irAEs in children. [ABSTRACT FROM AUTHOR]

There are about 14,000 pseudogenes that are mutated or truncated sequences resembling functional parent genes. About two-thirds of pseudogenes are processed, while others are duplicated. Although initially thought dead, emerging studies indicate they have functional and regulatory roles. We study 14-3-3ζ, an adaptor protein that regulates cytokine signaling and inflammatory diseases, including rheumatoid arthritis, cancer, and neurological disorders. To understand how 14-3-3ζ (gene symbol YWHAZ) performs diverse functions, we examined the human genome and identified nine YWHAZ pseudogenes spread across many chromosomes. Unlike the 32 kb exon-to-exon sequence in YWHAZ, all pseudogenes are much shorter and lack introns. Out of six, four YWHAZ exons are highly conserved, but the untranslated region (UTR) shows significant diversity. The putative amino acid sequence of pseudogenes is 78–97% homologous, resulting in striking structural similarities with the parent protein. The OMIM and Decipher database searches revealed chromosomal loci containing pseudogenes are associated with human diseases that overlap with the parent gene. To the best of our knowledge, this is the first report on pseudogenes of the 14-3-3 family protein and their implications for human health. This bioinformatics-based study introduces a new insight into the complexity of 14-3-3ζ's functions in biology. [ABSTRACT FROM AUTHOR]

Background: A pro-inflammatory cytokine called interleukin 6 (IL-6) is important for both autoimmune and chronic inflammation. Objective: This study aimed to evaluate the ability to use serum level of IL-6 in differentiating between inflammatory and non-inflammatory arthritis and to correlate its level with clinical manifestations, disease activity, laboratory parameters, radiological grading and disease severity. Methods: This comparative cross-sectional study was carried out on 60 patients diagnosed as rheumatoid arthritis (RA) (Group I), osteoarthritis (Group II) and psoriatic arthritis (PsA) (Group III) together with 20 apparently healthy volunteers selected as control (Group IV), all were age- and sex-matched. The disease activity score 28 (DAS-28) and disease activity index in PsA were developed to quantify disease activity among RA and PsA patients, respectively. Radiographic changes were evaluated by Larsen score among RA patients and by modified Steinbrocker score among PsA patients. Routine lab work was done and serum IL-6 was measured by ELIZA. Results: Highly statistically significant differences were reported between the studied groups regarding serum IL-6 level (P < 0.05) being higher among patients with inflammatory arthritis than others. Significant positive correlations were found between IL-6 with disease activity and severity parameters among RA and PsA patients. Regarding univariate analysis, among RA patients, it was found that DAS-28 score, disease severity, morning stiffness, number of tender and swollen joints, ESR and radiographic changes (Larsen score) were significantly associated with IL-6. Conclusions: IL-6 is a strong predictor of disease activity and severity in RA and PsA patients but not in OA patients because it plays an important role in mediating inflammation and joint degradation, therefore monitoring the blood level of this cytokine may be beneficial in determining clinical status. [ABSTRACT FROM AUTHOR]

This narrative review discusses the importance of rehabilitation in rheumatic and musculoskeletal diseases (RMDs), ultimately aiming to reduce their impact on individuals and society. It specifically emphasizes the need for rehabilitation in inflammatory arthritis (IA), particularly in cases where medical management is insufficient. It acknowledges that the complexity of rehabilitation demands a flexible approach. Thereby, it touches on the various models of rehabilitation, which may include multidisciplinary team care, extended practice models, shared care, remote care, and work rehabilitation. It discusses the challenges in research, practice, and policy implementation. In research, the need for innovative research designs is highlighted, whereas regarding clinical practice the importance of early detection of disability and patient engagement is underlined, as well as the role of telehealth and AI in reshaping the rehabilitation landscape. Financial barriers and work force shortages are identified as challenges that hinder the effective delivery of rehabilitative care. On the policy level, this paper suggests that the allocation of healthcare resources often prioritizes acute conditions over chronic diseases, leading to disparities in care. This paper concludes by emphasizing the critical role of evidence-based rehabilitation in improving the quality of life for people with RMDs, in particular for those with IA, and promoting their healthy aging. It also calls for tailored rehabilitation models and the early identification of persons with rehabilitation needs as future challenges in this field. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is a major comorbidity of psoriasis and may lead to irreversible joint damage and disability. This study aims to describe the clinical profile, treatment and quality of life (QoL) of patients with PsA in Malaysia. This is a multicentre retrospective cross‐sectional study of psoriasis patients who were notified to the Malaysian Psoriasis Registry (MPR) from January 2007 to December 2018. Of 21 735 psoriasis patients, 2756 (12.7%) had PsA. The male to female ratio was 1:1. The mean age of psoriasis onset for PsA patients was 34.73 ± 14.44 years. They had a higher rate of family history of psoriasis (26% vs. 22.4%, p < 0.001), scalp (82.7% vs. 81.0%, p = 0.04) and nail involvement (73.3% vs. 53.3%, p < 0.001), obesity (62.6% vs. 54.4%, p < 0.001), dyslipidaemia (23.8% vs. 15.4%, p < 0.001), hypertension (31.1% vs. 22.7%, p < 0.001) and diabetes mellitus (20.9% vs. 15.2%, p < 0.001) compared to non‐PsA patients. More than half (54.3%) had severe psoriasis [(body surface area >10% and/or Dermatology Life Quality Index (DLQI) >10)]. Most had oligo‐/monoarthropathy (40.3%), followed by distal interphalangeal arthropathy (31.3%), symmetrical polyarthropathy (28.3%), spondylitis/sacroiliitis (8.2%) and arthritis mutilans (3.2%). Nearly 40% of PsA patients received systemic treatment, but only 1.6% received biologic agents. QoL was more significantly affected in PsA than in non‐PsA patients (mean DLQI 10.12 ± 7.16 vs. 9.52 ± 6.67, p < 0.001). One in eight patients with psoriasis in Malaysia had PsA. They had a higher incidence of comorbidities, severe disease, impaired QoL and were more likely to receive systemic and biological treatment compared to non PsA patients. [ABSTRACT FROM AUTHOR]

BackgroundThe causal associations between dietary intake and the risk and severity of Inflammatory Arthritis (IA) are currently unknown.ObjectiveIn this study, we aimed to investigate the causal relationship between nine dietary categories (30 types of diet) and IA using Mendelian randomization (MR).MethodsWe analyzed data from 30 diets and IA in a genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) that could influence the results of MR analyses were screened out through the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. SNPs were analyzed through two-sample bidirectional MR using inverse variance weighting, MR-Egger regression, and weighted median method. The multiplicity and heterogeneity of SNPs were assessed using MR-Egger intercept term tests and Cochran’s Q tests. FDR correction was used to correct the p-values.ResultsIVW results showed that Beef intake [Odds ratio (OR) = 2.862; 95% confidence interval (CI), 1.360–6.021, p = 0.006, p_fdr 0.05) was positively associated with psoriatic arthritis (PsA); Cheese intake (OR = 0.579; 95% CI, 0.367–0.914, p = 0.019, p_fdr > 0.05) was negatively associated with PsA; both were suggestive evidence. Processed meat intake (OR = 0.238; 95% CI, 0.100–0.565, p = 0.001, p_fdr 0.05) and no directional pleiotropy was detected. Leave-one-out analyses demonstrated the robustness of the causal relationship in the positive results.ConclusionOur study presents genetic evidence supporting a causal relationship between diet and an increased risk of IA. It also identifies a causal relationship between various dietary modalities and different types of IA. These findings have significant implications for the prevention and management of IA through dietary modifications.

Abstract Background PD-1 is an immune checkpoint on T cells, and interventions to block this receptor result in T cell activation and enhanced immune response to tumors and pathogens. Reciprocally, despite a decade of research, approaches to treat autoimmunity with PD-1 agonists have only had limited successful. To resolve this, new methods must be developed to augment PD-1 function beyond engaging the receptor. Methods We conducted a flow cytometry analysis of T cells isolated from the peripheral blood and synovial fluid of patients with rheumatoid arthritis. In addition, we performed a genome-wide CRISPR/Cas9 screen to identify genes associated with PD-1 signaling. We further analyzed genes involved in PD-1 signaling using publicly available bulk and single-cell RNA sequencing datasets. Results Our screen confirmed known regulators in proximal PD-1 signaling and, importantly, identified an additional 1112 unique genes related to PD-1 ability to inhibit T cell functions. These genes were strongly associated with the response of cancer patients to PD-1 blockades and with high tumor immune dysfunction and exclusion scores, confirming their role downstream of PD-1. Functional annotation revealed that the most significant genes uncovered were those associated with known immune regulation processes. Remarkably, these genes were considerably downregulated in T cells isolated from patients with inflammatory arthritis, supporting their overall inhibitory functions. A study of rheumatoid arthritis single-cell RNA sequencing data demonstrated that five genes, KLRG1, CRTAM, SLAMF7, PTPN2, and KLRD1, were downregulated in activated and effector T cells isolated from synovial fluids. Backgating these genes to canonical cytotoxic T cell signatures revealed PD-1+ HLA-DRHIGH KLRG1LOW T cells as a novel inflammatory subset of T cells. Conclusions We concluded that PD-1+ HLA-DRHIGH KLRG1LOW T cells are a potential target for future PD-1 agonists to treat inflammatory diseases. Our study uncovers new genes associated with PD-1 downstream functions and, therefore, provides a comprehensive resource for additional studies that are much needed to characterize the role of PD-1 in the synovial subset of T cells.

Abstract Background Janus kinase inhibitors (JAKi) are new targeted synthetic disease-modifying antirheumatic drugs (DMARDs) licenced in the UK to treat rheumatoid and psoriatic arthritides. Unlike currently often prescribed biological DMARDs, they target a different part of the inflammatory pathway and are taken orally. The aim of this study was to explore what UK-based rheumatology clinicians and inflammatory arthritis (IA) patients think about the awareness, prescription and use of JAKi; how they compare with biologics; and how the COVID-19 pandemic has affected how JAKi are viewed and prescribed. Methods Rheumatology clinicians and IA patients completed online surveys and participated in interviews/focus groups between September 2021 and January 2022. Survey data were analysed descriptively, and interview/focus group data underwent an inductive thematic analysis. Results 66.6% of patients had at least some awareness of JAKi, 73.0% from their rheumatology team. Problems getting earlier access to these drugs were raised by some patients, with many being prescribed JAKi after multiple other therapies had failed. 91.5% of clinicians prescribed JAKi in keeping with their local guidelines, with 72.3% prescribing them frequently as a monotherapy. Some clinicians had lingering safety concerns over JAKi use. Despite experiencing side effects and knowing of possible long-term risks, patients felt overall the benefits of JAKi outweighed the risks. 39.3% of patients were ‘very satisfied’ on JAKi, compared with 25.0% on biologics. Patients on JAKi appreciated their short half-life when it comes to infections, and their convenience as an oral therapy. When JAKi were discontinued in patients, it was predominantly due to inefficacy and non-cardiovascular adverse events. The COVID-19 pandemic resulted in increased prescription of JAKi as an alternative to injections and infusions, primarily to avoid potentially exposing patients to the coronavirus. Some patients believed their JAKi may confer some protection against developing severe COVID-19. Conclusion JAKi are an effective treatment option for IA and are liked by patients. The COVID-19 pandemic appears to have impacted their prescription favourably. However, clinicians have safety concerns over JAKi use. Any decision to go on a JAKi should be informed and take into account individual patient risk factors, circumstances and preferences.

Inflammatory arthritis are common chronic inflammatory autoimmune diseases characterised by progressive, destructive inflammation of the joints leading to a loss of function and significant comorbidities; importantly, there are no cures and only 20% of patients achieve drug-free remission for over 2 years. Macrophages play a vital role in maintaining homeostasis, however, under the wrong environmental cues, become drivers of chronic synovial inflammation. Based on the current “dogma”, M1 macrophages secrete pro-inflammatory cytokines and chemokines, promoting tissue degradation and joint and bone erosion which over time lead to accelerated disease progression. On the other hand, M2 macrophages secrete anti-inflammatory mediators associated with wound healing, tissue remodelling and the resolution of inflammation. Currently, four subtypes of M2 macrophages have been identified, namely M2a, M2b, M2c and M2d. However, more subtypes may exist due to macrophage plasticity and the ability for repolarisation. Macrophages are highly plastic, and polarisation exists as a continuum with diverse intermediate phenotypes. This plasticity is achieved by a highly amenable epigenome in response to environmental stimuli and shifts in metabolism. Initiating treatment during the early stages of disease is important for improved prognosis and patient outcomes. Currently, no treatment targeting macrophages specifically is available. Such therapeutics are being investigated in ongoing clinical trials. The repolarisation of pro-inflammatory macrophages towards the anti-inflammatory phenotype has been proposed as an effective approach in targeting the M1/M2 imbalance, and in turn is a potential therapeutic strategy for IA diseases. Therefore, elucidating the mechanisms that govern macrophage plasticity is fundamental for the success of novel macrophage targeting therapeutics.

Objectives To improve the definitions of inflammatory arthritis within the musculoskeletal (MSK) domain of the BILAG-2004 index by incorporating imaging findings and clinical features predictive of response to treatment. Methods The BILAG MSK Subcommittee proposed revisions to the BILAG-2004 index definitions of inflammatory arthritis, based on review of evidence in two recent studies. Data from these studies were pooled and analysed to determine the impact of the proposed changes on the severity grading of inflammatory arthritis. Results The revised definition for severe inflammatory arthritis includes definition of 'basic activities of daily living'. For moderate inflammatory arthritis, it now includes synovitis, defined by either observed joint swelling or MSK US evidence of inflammation in joints and surrounding structures. For mild inflammatory arthritis, the definition now includes reference to symmetrical distribution of affected joints and guidance on how US may help re-classify patients as moderate or no inflammatory arthritis. Data from two recent SLE trials were analysed (219 patients). A total of 119 (54.3%) were graded as having mild inflammatory arthritis (BILAG-2004 Grade C). Of these, 53 (44.5%) had evidence of joint inflammation (synovitis or tenosynovitis) on US. Applying the new definition increased the number of patients classified as moderate inflammatory arthritis from 72 (32.9%) to 125 (57.1%), while patients with normal US (n  = 66/119) could be recategorized as BILAG-2004 Grade D (inactive disease). Conclusions Proposed changes to the definitions of inflammatory arthritis in the BILAG-2004 index will result in more accurate classification of patients who are more or less likely to respond to treatment. [ABSTRACT FROM AUTHOR]

Objectives Autoantibody responses increase years before the onset of inflammatory arthritis (IA) and are stable during transitioning from clinically suspect arthralgia (CSA) to IA. Cytokine and chemokine levels also increase years before IA onset. However, the course in the at-risk stage of CSA during progression to disease or non-progression is unknown. To increase the understanding of processes mediating disease development, we studied the course of cytokine, chemokine and related receptors gene expression in CSA patients during progression to IA and in CSA patients who ultimately did not develop IA. Methods Whole-blood RNA expression of 37 inflammatory cytokines, chemokines and related receptors was determined by dual-colour reverse transcription multiplex ligation-dependent probe amplification in paired samples of CSA patients at CSA onset and either at IA development or after 24 months without IA development. ACPA-positive and ACPA-negative CSA patients developing IA were compared at CSA onset and during progression to IA. Generalised estimating equations tested changes over time. A false discovery rate approach was applied. Results None of the cytokine/chemokine genes significantly changed in expression between CSA onset and IA development. In CSA patients without IA development, G-CSF expression decreased (P  = 0.001), whereas CCR6 and TNIP1 expression increased (P  < 0.001 and P  = 0.002, respectively) over a 2 year period. Expression levels in ACPA-positive and ACPA-negative CSA patients who developed IA were similar. Conclusion Whole-blood gene expression of assessed cytokines, chemokines and related receptors did not change significantly from CSA to IA development. This suggests that changes in expression of these molecules may not be related to the final process of developing chronicity and may have occurred preceding CSA onset. Changes in gene expression in CSA patients without IA development may provide clues for processes related to resolution. [ABSTRACT FROM AUTHOR]

In this pictorial review, an introductory paragraph emphasizes the significance of some anatomical aspects for optimal imaging of the temporomandibular joint (TMJ). The most frequent pathologies: internal derangement (ID) and osteoarthritis (OA) are comprehensively discussed and illustrated. Less common conditions: ID and OA-like changes in children and adolescents, idiopathic condylar resorption, inflammatory arthritis, and juvenile idiopathic arthritis are briefly discussed. A short paragraph on differential diagnostics in young patients is included followed by a brief comment on expansile lesions that occasionally may occur in the TMJ. [ABSTRACT FROM AUTHOR]

Many patients with inflammatory arthritis (IA) were instructed to shield during the COVID-19 pandemic. Despite the ending of lockdowns and vaccination, large proportions of IA patients were continuing to shield when it is no longer needed. Given the detrimental effects of shielding on mental and physical health, understanding the rates and reasons for shielding is needed to help clinicians advise patients accordingly. This study was a 12-month prospective study following participants with IA during the COVID-19 pandemic. The proportions of IA patients shielding at each time point were calculated. Additionally, regressions and odds ratios for shielding were determined to assess medication type, mental health, and risk perception. While the extent of shielding fluctuated over the year of lockdowns, nearly all IA patients (93.5%) were still engaging in some shielding in 2021, with nearly half (43%) still shielding most or all of the time. Medications that were previously considered higher risk were not significantly associated with higher rates of shielding (OR = 1.60, p = 0.29), but greater symptoms of depression in June 2020 (OR = 1.07, p = 0.03) was both associated with increased the odds of shielding in June 2021. The high rates of IA patients continuing to shield in 2021 put more strain on patients and professionals as social isolation is linked with worsening mental and physical health, as well as greater difficulty with self-management. It is important for clinicians to be aware of this trend to ease the stress on patients. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to explore the experiences of people with RA of participating in an exercise intervention to improve their sleep. Methods Using a qualitative descriptive design, semi-structured face-to-face interviews were conducted with 12 people with RA who had completed an 8-week walking-based exercise intervention to improve their total sleep time, sleep quality and sleep disturbance. Data were analysed using thematic analysis. Results Four themes were generated: positive impact of exercise on participants' sleep ('I really didn't think any type of exercise would help me sleep better, if I'm honest'); positive experiences of the exercise intervention ('I learnt so much regarding walking that I didn't even think about'); clear mental health benefits ('If you don't sleep well then it will have a knock-on effect to your mental health'); and achieving empowerment and ownership when exercising ('I feel empowered now and confident that I'm not doing harm to myself'). Conclusion The findings demonstrated that participants had not expected exercise to improve their sleep. Although there is a growing consensus that exercise will benefit sleep and mitigate some disease symptoms, research is severely lacking in people with RA. [ABSTRACT FROM AUTHOR]

Objective Patients with inflammatory arthritis were especially vulnerable to the psychosocial and health impacts of coronavirus disease 2019 (COVID-19) and the lockdowns. This study investigated the impact of these changes on mental health, physical health and quality of life for inflammatory arthritis patients over 1 year following the initial lockdown in the UK. Methods Three hundred and thirty-eight participants with inflammatory arthritis completed an ambidirectional study consisting of online questionnaires at four time points for 1 year. The questionnaires assessed demographic information, inflammatory arthritis condition, mental health, physical symptoms, self-management behaviours, COVID-19 status and impacts. Means, linear regressions and structural equation modelling for mediations were conducted over 12 months. Results Physical health concerns peaked during June 2020, then declined, but did not return to baseline. Depression was associated with worse quality of life at baseline, as shown by the beta coefficient, (β= 0.94, P  < 0.01), September (β = 0.92, P  < 0.01), November (β= 0.77, P  < 0.01) and 1 year (β = 0.77, P  < 0.01). Likewise, anxiety was associated with worse quality of life at baseline (β = 1.92, P  < 0.01), September (β = 2.06, P  < 0.01), November (β = 1.66, P  = 0.03) and 1 year (β = 1.51, P  = 0.02). The association between depression and quality of life was mediated by physical activity (β= 0.13, P  < 0.01) at baseline. The association between anxiety and quality of life was also mediated by physical activity (β = 0.25, P  = 0.04) at baseline. Conclusion Physical health continued to be worse 1 year later compared with before the COVID-19 lockdowns in patients with inflammatory arthritis. Mental health showed long-term effects on quality of life, with an impact for ≥12 months. Lastly, physical activity mediated between mental health and quality of life in the short term. [ABSTRACT FROM AUTHOR]