Chronic Inflammatory Joint Disease Research Articles

Cardiovascular Risk Management In Patients With Rheumatoid Arthritis: A Systematic Review.

Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory joint disease associated with pain, swelling, and morning stiffness. It not only affects the joints but also exhibits many extra-articular manifestations. It is recognized as an independent risk factor for cardiovascular (CV) abnormalities. The possibility of cardiovascular disease (CVD) risk in patients with RA is about twofold higher compared to non-RA individuals. Therefore, early risk assessment and management of risk factors are crucial to reduce the CV morbidity and mortality associated with RA. This systematic literature review summarizes the data available on the management of CVD risk factors in RA. A total of 61 articles from the most reputable journals published between 2013 and 2023 were reviewed, of which seven papers were selected for in-depth analysis. We tried to eliminate bias using various bias-eliminating tools. This analysis considers the proposed solution for CV risk prevention and management in RA patients. Optimal control of disease activity and persistent monitoring of other factors responsible for increased CV events in RA patients is the ultimate management of CV abnormalities. This study summarizes the recommendations for the management of CV risk factors in patients with RA.

Is Active Synovitis of Metacarpophalangeal Joints a Neuropathic Condition in Rheumatoid Arthritis Patients? Results from an Ultrasound Study of Palmar Digital Nerves.

(1) Background: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, primarily characterized by pain. A significant proportion of patients report symptoms suggestive of neuropathic pain. The objectives of this study were to investigate the presence of an increased cross-sectional area (CSA) of the palmar digital nerves by ultrasound in patients with active synovitis of the metacarpophalangeal joints and to identify potential predictors of such an increase. (2) Methods: An ultrasound examination of the clinically most affected hand (from the second to the fifth metacarpophalangeal joint) was performed. The presence of synovitis was scored using a 0-3 semiquantitative method for each joint. The CSA of each pair of palmar digital nerves was measured. (3) Results: A significant correlation was found between the sum of the CSAs of the nerves and the Clinical Disease Activity Index (CDAI) (r = 0.387), as well as with the ultrasonographic grading of synovitis (r = 0.381) both at the patient and the joint level. These two variables, aimed at measuring disease activity, along with male gender, are the only predictors of the CSA of the palmar digital nerves. (4) Conclusions: Synovial inflammation of the metacarpophalangeal joints is, therefore, a condition that can influence the CSA of the palmar digital nerves and may partially explain neuropathic pain in patients with RA.

Tetramethylpyrazine alleviates hypoxia-induced proliferation, migration, and inflammatory response of fibroblast-like synoviocytes via inhibiting the HIF-1α- circCDC42BPB pathway

ObjectivesRheumatoid arthritis (RA) is a chronic inflammatory joint disease, which might trigger cartilage, bone damage, and disability. Recent studies have suggested that Tetramethylpyrazine (TMP), an alkaloid monomer isolated from the rhizome of the traditional herbal medicine Ligusticum wallichii Franch, exerts a broad spectrum of pharmacological properties, containing anti-inflammatory. This study aimed to analyze the role and underlying mechanism of TMP in RA.MethodsUnder Hypoxia condition, RA-Fibroblast-like synoviocyte (FLS) were treated with TMP at different doses. Cell viability, proliferation, cell cycle progression, and migration were detected using Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2’-deoxyuridine (EdU) assay, flow cytometry assay, wound healing assay, and transwell assay. Cyclin D1, Proliferating cell nuclear antigen (PCNA), Matrix metalloproteinase-2 (MMP2), MMP9, and hypoxia-inducible factor-1α (HIF-1α) protein levels were measured using western blot assay. Interleukin-6 (IL-6) and IL-8 were evaluated using ELISA. Circular RNA (circRNA) hsa_circ_0005178 (circCDC42BPB), CDC42BPB, and HIF-1α expression were determined using real-time quantitative polymerase chain reaction (RT-qPCR). Binding between HIF-1α and CDC42BPB promoter was predicted by JASPAR and verified using dual-luciferase reporter and Chromatin immunoprecipitation (ChIP) assays.ResultsTMP might hinder FLS proliferation, cycle progression, migration, and inflammatory response under hypoxic conditions. CircCDC42BPB expression was increased in RA patients and RA-FLSs treated with hypoxia, while its level was obviously reduced in RA-FLSs treated with hypoxia and TMP. TMP might abolish hypoxia-induced circCDC42BPB expression. Upregulation of circCDC42BPB might partially overturn the repression of TMP on hypoxia-caused RA-FLS damage. TMP might regulate circCDC42BPB level via HIF-1α in RA-FLSs under hypoxic conditions.ConclusionTMP might block RA-FLS injury partly via regulating the HIF-1α- circCDC42BPB pathway, providing a promising therapeutic target for RA.

Impact of treatment of rheumatoid arthritis on periodontal disease: A review.

Numerous studies support a bidirectional association between rheumatoid arthritis (RA), a chronic autoimmune degenerative inflammatory joint disease, and periodontitis, a chronic inflammatory disease caused by the immune reaction to bacteria organized in biofilms. RA and periodontitis are both multifactorial chronic inflammatory diseases that share common modifiable and non-modifiable risk factors. There is no cure for RA; treatment is based on lifestyle modifications and a variety of medications: nonsteroidal anti-inflammatory drugs (NSAID), glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs, e.g., conventional synthetic DMARDs [csDMARDs]; biological DMARDs [bDMARD] and targeted synthetic DMARDs). There are molecular pathways of inflammation that are common to both RA and periodontitis. Thus, there is a potential effect of RA treatments on periodontitis. This systematic review aims to assess the impact of antirheumatic agents on periodontal conditions of patients suffering from both RA and periodontitis. PubMed/MEDLINE, Cochrane Library, and Embase online databases were systematically explored, and a manual search was performed to identify relevant studies published until January 2023. This review is registered in the PROSPERO database (CRD42023409006). A total of 2827 articles were identified, and 35 fulfilled the inclusion criteria. The included studies generally show a consensus that, at normal dosage, NSAID and corticosteroids have negligible impact on periodontium. Similarly, csDMARD alone or in combination with other csDMARD demonstrated no adverse effect on periodontium. Monotherapy with bDMARD had a positive effect on periodontal pocket depths and gingival inflammation in the longitudinal studies up to 6 months but showed negligible effect on the periodontium in interventional studies with a longer follow-up (9 months and 15.1 months). However, the combination of tumor necrosis factor (TNF)-α inhibitors+methotrexate (MTX) was associated with a rise in gingival inflammation. Due to the considerable heterogeneity of the study designs, a meta-analysis could not reasonably be performed. Within the limitations of the available studies, there is evidence to suggest that bDMARD monotherapy may improve the periodontal condition of RA patients with periodontal disease to a certain extent; the concomitant medication of TNF inhibitor+MTX could worsen gingival inflammation. More data are required to understand the impact of RA therapies on periodontal health.

Mechanism of lysine oxidase-like 1 promoting synovial inflammation mediating rheumatoid arthritis development.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that causes great distress to patients and society. Early diagnosis is the key to the successful treatment of RA. The basement membrane, one of the oldest tissue structures, is localized under the epithelium. Its complex composition and rich biological functions have made it a focus of research in recent years, while basement membrane-associated genetic variants are involved in most human disease processes. The aim of this study is to find new diagnostic biomarkers for RA and explore their role and possible mechanism in rheumatoid arthritis. The GSE12021, GSE55235 and GSE55457 datasets were downloaded from the GEO database. Their fraction associated with basement membrane genes was analyzed and differentially expressed genes between the disease and normal groups were explored. We identified two basement membrane-associated genes, lysine oxidase-like 1 (LOXL1) and discoid peptide receptor 2 (DDR2). Focusing on the more interesting LOXL1, we found that LOXL1 expression was significantly elevated in the synovium of patients with rheumatoid arthritis, and LOXL1 mRNA and protein levels were elevated in tumor necrosis factor α-stimulated human synovial sarcoma cells (SW982). And LOXL1 knockdown inhibited tumor necrosis factor α-induced inhibition in SW982 cells expression of inducible nitric oxide synthase (INOS), cyclooxygenase-2 (COX2), and interleukin-6 (IL-6). Interestingly, knockdown of LOXL1 inhibited the phosphorylation of PI3K and AKT. In summary, LOXL1 may become a novel diagnostic gene for RA, and knockdown of LoxL1 may inhibit synovial inflammation by affecting PI3K/AKT pathway.

Clinical and imaging findings in enteropathic spondyloarthritis with special emphasize in diagnostic delay: a cross-sectional study.

Enteropathic spondyloarthritides (eSpAs) are chronic inflammatory joint diseases associated with inflammatory bowel disease (IBD). Limited data are available on the prevalence since arthritis in IBD patients may be underestimated because medications may hide disease activity with a possible diagnostic delay. We aimed to evaluate diagnostic delay in eSpA and explore associated demographic, clinical, and radiographic characteristics. Single-centre cross-sectional study conducted on consecutive out-patients referred to the combined Gi-Rhe clinic (November 2018-October 2019). We analysed eSpA patients for diagnostic delay, disease activity, inflammatory markers, conventional radiography (CR) and magnetic resonance images (MRI) of sacroiliac joints/spine. A total of 190 eSpA patients [118 peripheral SpA, 72 axial (Ax) SpA including 44 non-radiographic (nr)-axSpA] were enrolled. axSpA patients had a higher prevalence of men sex, HLA-B27 positivity, uveitis and pancolitis compared with peripheral eSpA. Median diagnostic delay in eSpA was 48 months (IQR 6-77) with no difference between axial and peripheral patients. Radiographic-axial SpA (r-axSpA) patients displayed a higher diagnostic delay compared with nr-axSpA (median/IQR 36/17-129 versus 31/10-57 months, p = 0.03) and were older, with longer disease duration, low education status and high rate of employment than patients with nr-axSpA. r-axSpA patients with sclerosis, syndesmophytes and bridge at CR had higher diagnostic delay than those without lesions. Men showed higher prevalence of spine damage lesions than women as sclerosis, squaring, syndesmophytes and bridges. Longer disease duration was detected in patients with radiographic damage as bridge and sacroiliitis grade 3. On MRI, sacroiliac bone oedema was associated with reduced diagnostic delay, whereas bone erosions were associated with higher diagnostic delay compared with that in patients without these lesions. Patients with psoriasis displayed a higher diagnostic delay compared to those without skin involvement. Diagnostic delay was higher in r-axSpA compared with nr-axSpA despite the same treatment. Demographic, clinical features and radiological lesions were associated with diagnostic delay.

Follow-Up of Patients With Axial Spondyloarthritis in Specialist Health Care With Remote Monitoring and Self-Monitoring Compared With Regular Face-to-Face Follow-Up Visits (the ReMonit Study): Protocol for a Randomized, Controlled Open-Label Noninferiority Trial.

Patients with chronic inflammatory joint diseases such as axial spondyloarthritis have traditionally received regular follow-up in specialist health care to maintain low disease activity. The follow-up has been organized as prescheduled face-to-face visits, which are time-consuming for both patients and health care professionals. Technology has enabled the remote monitoring of disease activity, allowing patients to self-monitor their disease and contact health care professionals when needed. Remote monitoring or self-monitoring may provide a more personalized follow-up, but there is limited research on how these follow-up strategies perform in maintaining low disease activity, patient satisfaction, safety, and cost-effectiveness. The Remote Monitoring in Axial Spondyloarthritis (ReMonit) study aimed to assess the effectiveness of digital remote monitoring and self-monitoring in maintaining low disease activity in patients with axial spondyloarthritis. The ReMonit study is a 3-armed, single-site, randomized, controlled, open-label noninferiority trial including patients with axial spondyloarthritis with low disease activity (Ankylosing Spondylitis Disease Activity Score <2.1) and on stable treatment with a tumor necrosis factor inhibitor. Participants were randomized 1:1:1 to arm A (usual care, face-to-face visits every sixth month), arm B (remote monitoring, monthly digital registration of patient-reported outcomes), or arm C (patient-initiated care, self-monitoring, no planned visits during the study period). The primary end point was disease activity measured with the Ankylosing Spondylitis Disease Activity Score, evaluated at 6, 12, and 18 months. We aimed to include 240 patients, 80 in each arm. Secondary end points included other measures of disease activity, patient satisfaction, safety, and cost-effectiveness. The project is funded by the South-Eastern Norway Regional Health Authority and Centre for the treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Norway. Enrollment started in September 2021 and was completed with 242 patients by June 2022. The data collection will be completed in December 2023. To our knowledge, this trial will be among the first to evaluate the effectiveness, safety, and cost-effectiveness of remote digital monitoring and self-monitoring of patients with axial spondyloarthritis compared with usual care. Hence, the ReMonit study will contribute important knowledge to personalized follow-up strategies for patients with axial spondyloarthritis. These results may also be relevant for other patient groups with inflammatory joint diseases. ClinicalTrials.gov NCT05031767; hpps://www.clinicaltrials.gov/study/NCT05031767. DERR1-10.2196/52872.

Snake and arthropod venoms: Search for inflammatory activity in human cells involved in joint diseases

Most anti-inflammatory drugs currently adopted to treat chronic inflammatory joint diseases can alleviate symptoms but they do not lead to remission. Therefore, new and more efficient drugs are needed to block the course of joint inflammatory diseases. Animal venoms, rich in bioactive compounds, can contribute as valuable tools in this field of research. In this study, we first demonstrate the direct action of venoms on cells that constitute the articular joints. We established a platform consisting of cell-based assays to evaluate the release of cytokines (IL-6, IL-8, TNFα, IL-1β, and IL-10) by human chondrocytes, synoviocytes and THP1 macrophages, as well as the release of neuropeptides (substance-P and β-endorphin) by differentiated sensory neuron-like cells, 24 h after stimulation of cells with 21 animal venoms from snake and arthropod species, sourced from different taxonomic families and geographic origins.Results demonstrated that at non-cytotoxic concentrations, the venoms activate at varying degrees the secretion of inflammatory mediators involved in the pathology of articular diseases, such as IL-6, IL-8, and TNF-α by chondrocytes, synoviocytes, and macrophages and of substance P by neuron-like cells. Venoms of the Viperidae snake family were more inflammatory than those of the Elapidae family, while venoms of Arthropods were less inflammatory than snake venoms. Notably, some venoms also induced the release of the anti-inflammatory IL-10 by macrophages. However, the scorpion Buthus occitanus venom induced the release of IL-10 without increasing the release of inflammatory cytokines by macrophages. Since the cell types used in the experiments are crucial elements in joint inflammatory processes, the results of this work may guide future research on the activation of receptors and inflammatory signaling pathways by selected venoms in these particular cells, aiming at discovering new targets for therapeutic intervention.

Bisdemethoxycurcumin, a curcumin derivative, ameliorates adjuvant-induced arthritis by suppressing inflammatory reactions and macrophage migration

Rheumatoid arthritis (RA) is a highly prevalent and chronic inflammatory synovial joint disease manifested by hyperplasia and continuous inflammation. Curcumin (Cur) has been studied for alleviating RA. However, poor stability and oral bioavailability restrict its therapeutic value. Bisdemethoxycurcumin (BDMC), a curcumin (Cur) derivative, exerts better stability and oral bioavailability than Cur. However, the efficacy of BDMC on RA has not been fully clarified. The aim of the study was to investigate the therapeutic effects and underlying mechanisms of BDMC on RA. The in-vivo anti-arthritic activity of BDMC was determined via adjuvant-induced arthritis (AIA) rat model. Paw swelling, body weight, arthritic index, and histopathological assessments were performed. RAW264.7 cell was stimulated by lipopolysaccharides (LPS) in vitro. The cell viability were determined by CCK8 assay, while the migration ability was determined using cell wound healing and transwell assays. Furthermore, in-vivo and in-vitro levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) were assayed by ELISA, and that of IκBα, p-NF-κB, NF-κB, and COX-2 were assessed via Western blot or immunofluorescence. In AIA rat model, it suggested a higher anti-arthritic activity of BDMC than Cur, including amelioration of swelling in hind paws, reduced arthritic index, and alleviated histopathological injury in rats. Furthermore, BDMC also substantially decreased the levels of the aforementioned pro-inflammatory cytokines in both in-vivo and in-vitro, inhibited the IκBα degradation, down-regulated the COX-2 levels and p-NF-κB/NF-κB ratio in AIA rats and LPS-stimulated RAW264.7 cells. Additionally, BDMC showed an inhibitory effect on the migration of LPS-stimulated RAW264.7 cells. BDMC could effectively ameliorate RA by suppressing inflammatory reactions and inhibiting macrophage migration, more potentially than Cur.

The role of ultrasound diagnostics in the management of patients with juvenile psoriatic arthritis

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the peripheral joints, entheses, and spine joints, affecting 10–25% of patients with psoriasis. Early diagnosis of the disease is challenging due to the possible delayed skin and joint symptoms and signs. Before the advent of ultrasound examination, the diagnosis of joint diseases was limited only to the radiological method. The ultrasound diagnosis of joint diseases in children is not established and needs a more comprehensive study.&#x0D; Materials and methods. The study included 50 PsA patients aged 3 to 17 years. We performed an ultrasound examination of 178 various joints. Knee joints were involved in 46 children, hip joints in 24, ankle joints in 34, and interphalangeal joints in 10. The mean age at onset was 7.8 years (range 1.5 to 14 years). The mean duration of the disease was 4.7 years.&#x0D; Results. Homogeneous joint effusion was the most common finding in patients with juvenile PsA (JPsA) – 83%. The effusion heterogeneity (17%) was due to hyperechoic inclusions (fibrin) in anechoic content. Diffuse synovium thickening was found in 91% of the joints. In 12.3% of joints, cartilage thinning was observed (in patients with a disease duration of 5 years or more), with fuzzy contours in some cases and normal echostructure in others.&#x0D; Conclusion. Periarticular structures, most often ligaments and tendons, are also involved in JPsA. The inflammation progresses steadily, with the rate depending on disease activity. Joint ultrasound is a reliable and highly informative method of JPsA diagnosing. It can identify a wide range of joint abnormalities; moreover, the severity of ultrasound abnormalities correlates with the disease severity, enabling using this method for monitoring disease-modifying therapy and as a screening tool for detecting the early signs of arthritis in patients with psoriasis. Joint ultrasound helps to detect early abnormalities.

Drug in Therapeutic Polymer: Sinomenine-Loaded Oxidation-Responsive Polymeric Nanoparticles for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that frequently involves cartilage damage and the destruction of the bone structure, ultimately resulting in disability and long-term pain. It is clear that overexpression of reactive oxygen species (ROS) and the complex inflammatory microenvironment are the main causes of RA pathogenesis; thereby, the efficacy of any single-drug treatment is limited. Herein, we formulated a therapeutic hyaluronic acid derivative (PAM-HA) with adsorption capacity to the subchondral bone, a long retention time within inflamed joints, and ROS-scavenging capacity, which was used as a drug carrier for realizing the controlled release of sinomenine (Sin) within arthritic joints. This "drug in therapeutic polymer" design strategy was aimed at realizing antioxidant and anti-inflammatory combination therapy for RA. In vivo experiments suggest that PAM-HA@Sin NPs can be retained in the inflamed joints of rats for a long time compared with commercially available free Sin injections. As expected, therapeutic PAM-HA polymeric carriers can increase joint lubrication and reduce oxidative stress, while the released Sin induces downregulation of proinflammatory factors (TNF-α and IL-1β) and upregulation of anti-inflammatory factors (Arg-1 and IL-10) via the NF-κB pathway. In summary, a ROS-scavenging hyaluronic acid (HA) derivative was developed as the nanocarrier for Sin delivery to simultaneously remodel the oxidative/inflammatory microenvironment in RA, which opens up new horizons for the development of therapeutic polymers and the combined therapeutic strategies.

Real-world data show high efficacy of IL23 inhibitors guselkumab and risankizumab in psoriatic arthritis and difficult-to-treat areas.

Psoriasis and psoriatic arthritis are chronic inflammatory skin and joint diseases requiring effective therapies. Although clinical studies have shown the efficacy of IL-23 inhibitors, real-world data are limited. We conducted a single-center retrospective Greek study enrolling patients with psoriatic arthritis and moderate-to-severe plaque psoriasis being treated at our multidisciplinary psoriasis outpatient clinic. Our aim was to investigate the efficacy and safety of IL-23 inhibitors guselkumab and risankizumab. Additionally, we sought to determine the clinical characteristics affecting treatment response. Primary endpoints were the evaluation of absolute Psoriasis Area and Severity Index (aPASI) and Disease Activity Index for Psoriatic Arthritis (DAPSA) at week 24. Fifty-nine patients (55.9% male, 69.5% early onset) with a mean age of 51.7 years were included. Twenty-four patients (40.7%) had a concomitant psoriatic arthritis. Obesity was the main comorbidity (49.2%) with a mean body mass index (BMI) of 31.3 kg/m2 . Additional comorbidities were hypertension (44.1%), dyslipidemia (32.2%), and diabetes (18.6%). Only eight patients (13.6%) were naïve to previous systemic treatments, whereas 40 patients (67.8%) were bio-experienced. A statistically significant improvement of aPASI and DAPSA was demonstrated after 4, 16, and 24 weeks of treatment (P < 0.05). IL23 blockers were also efficacious in difficult-to-treat areas. Clinical outcome was affected from previous treatment with biologics. Treatment response was the same between guselkumab and risankizumab (P > 0.05). This real-world study confirms the efficacy and safety of guselkumab and risankizumab in psoriatic arthritis and psoriasis reported from clinical trials.

Peripheral CD4+ /CD8+ T cell composition distinct from healthy individuals is shared by ankylosing spondylitis and rheumatoid arthritis.

Ankylosing spondylitis (AS) and rheumatoid arthritis (RA) are chronic inflammatory joint diseases, linking to the alterations of immune cells. We attempted to assess whether the alterations in the composition of CD4+ /CD8+ T cells are different between AS and RA and identify the characteristic cells between male and female patients. The proportions of CD3+ or double positive T cells, 6 CD4+ T subsets and 9 CD8+ T cell subsets were detected by flow cytometry and compared in 30 healthy individuals, 42 AS patients and 45 RA patients. The differentially altered cells were individually analyzed for associations with disease activity parameters. In addition, their proportions were compared between different genders in the 3 groups. The proportions of CD4+ T cells, naive CD4+ T cells and central memory CD4+ T cells were lower in AS patients (P = 0.001, P = 0.002 and P = 0.007, respectively) and RA patients (P = 0.032, P < 0.001 and P = 0.016, respectively), but the proportion of effector memory ones was higher when compared with healthy populations (both P < 0.001), as were the decrease of naive/central memory CD8+ T cells in AS (P = 0.003 and P = 0.016, respectively) and RA (P < 0.001 and P = 0.006, respectively), and the increased tendency of terminally differentiated CD8+ T cells. However, these above-mentioned cells, regulatory T (Treg) cells and CD8+ T cells with different CD127 expressions between AS and RA were similar in proportion. Furthermore, naive CD4+ T cells were positively associated with C-reactive protein (CRP) in AS, whereas CD4+ T cells and terminally differentiated CD8+ T of RA patients were associated with CRP in RA. The gender-related alterations predominantly displayed the overexpressions of Treg cells and naive CD8+ T cells in female patients with AS and RA, respectively. AS patients and RA patients have some similar peripheral CD4+ /CD8+ T cell subsets but are distinct from healthy individuals, which may contribute to disease severity. Females are respectively characterized by the up-regulation of Treg cells and naive CD8+ T cells in AS patients and RA patients. The study offers an in-depth understanding of the role of T cell subsets in the similarities of the disorders and helps us to monitor disease changes and may offer a theoretical basis of developing novel therapies against common targets.

Protective effects of ginseng and ginsenosides in the development of osteoarthritis (Review).

Osteoarthritis (OA) is a chronic inflammatory joint disease. Traditional chinese medicine provides a resource for drug screening for OA treatment. Ginseng and the associated bioactive compound, ginsenosides, may reduce inflammation, which is considered a risk factor for the development of OA. Specifically, ginsenosides may exhibit anti-inflammatory and anti-oxidative stress activities, and inhibit extracellular matrix degradation by suppressing the NF-κB and MAPK signaling pathways. Notably, specific ginsenosides, such as compound K and Rk1, may physically interact with IκB kinase and inhibit the associated phosphorylation. Thus, ginsenosides exhibit potential as therapeutic candidates in the management of OA. However, the low water solubility limits the clinical applications of ginsenosides. Numerous effective strategies have been explored to improve bioavailability; however, further investigations are still required.

E59 Deforming juvenile idiopathic arthritis: a case report in Bouake (Cote D’ivoire)

Abstract Introduction Juvenile Idiopathic Arthritis (JIA) is a group of conditions characterized by chronic inflammatory joint disease of unknown aetiology before the age of 16. This joint damage is complicated by joint deformities, amplitude limitations, muscle imbalances causing a reduction in the functional capacities of the child. The delayed diagnosis, the inaccessibility of biotherapies give rise to deformations which hinder the development of the physical capacities and the social, educational and then professional integration of the child. Objective Sensitize practitioners about early diagnosis and multidisciplinary management of JIA, in order to avoid severe deformities. Observation A 17-year-old girl, out of school, was admitted to a rheumatology unit for the evolution of chronic polyarthralgia with transient skin eruption evolving by inflammatory attack with partial remission since the age of 8 years. There was no notable story. On physical examination, the affected joints were painful. Deformities were observed such as valgus of the knees and forefeet, ulnar deviation of the wrists and nonspecific of the fingers (Figs. 1 and 2). The biological inflammatory syndrome was present with (CRP 90 mg/l, VS 48 mm/h) and a blood count (Hb 12.5 g/dl, Plq 205 000/μL, GB 14. 109/l). Serum ferritin was elevated at 197.7 μg/ml. The other assessments in particular (blood cultures, FAN, FR, blood smears) came back negative. The diagnosis of AJI in systemic form was retained. The X-ray showed osteoarticular destruction with fixed exostoses, Larsen's stage 4 (Figs. 3 and 4) and Steinbrocker's stage 3 with minimal functional capacity. The treatment included an NSAID (ibuprofen at 40 mg/kg/day), followed by corticosteroid therapy (Prednisolone at a dose of 1 mg/kg/day) and as background treatment methotrexate (10 mg/week). evolution at 3 months was favorable on the pain. The management of the deformities was the subject of a multidisciplinary consultation meeting (physiotherapists, rheumatologists, orthopedic surgeons and paediatricians) very expensive for the parents. Thus it benefited a physical treatment made up of joint maintenance physiotherapy and equipment for joints that are still mobile. Discussion In Africa, osteoarticular pathology in children most often evokes diagnoses of sickle cell disease and acute articular rheumatism. From the first symptoms, children are referred to traditional healers, especially in rural areas where there is no specialist, then to pediatrics [1]. These reasons could explain the long delay in diagnosis as in the patient whose delay was 9 years. The diagnostic age of our patient was 17 years, higher than elsewhere [2] but consistent with the results of Diomandé in Abidjan with an average delay of 10 years [3]. Most studies find a female predominance with an age of onset between 4 and 8 years [4, 5]. In our patient, the involvement was polyarticular from the outset and the FRs were negative, as in most studies [1, 3]. The presence of these deformities was a source of significant handicap in our patient, which led to her dropping out of school, as stipulated in the literature. In first intention, we used NSAIDs, however unsatisfactory. Faced with the persistence of pain, she received prednisolone at 1 mg/kg/d favorable. As basic treatment she received methotrexate, biotherapies being inaccessible in our context because of their high cost. The management of deformities was the subject of a multidisciplinary consultation meeting (physiotherapists, rheumatologists, orthopedic surgeons and paediatricians) whose costs were beyond the reach of indigent parents. Conclusion The diagnosis and the multidisciplinary treatment must be early and continuous of the disease in order to avoid the deformations, which once installed are irreversible.

E18 What is the relationship between body mass index and juvenile idiopathic arthritis characteristics?

Abstract Introduction Juvenile idiopathic arthritis (JIA) is a group of pediatric chronic inflammatory joint diseases. The various forms of JIA may be associated with delayed growth or local growth disturbances. Objectives We conducted this study to evaluate the relationship between the different clinical and biological characteristics of JIA and the anthropometric parameters of patients. Methods Retrospective study including adults with long-standing JIA according to International League of Associations of Rheumatology (ILAR) criteria over a period from 1994 to 2022. Clinical and biological parameters were collected. Body mass index (BMI) was interpreted according to World Health Organization cut-offs as follows: underweight &amp;lt;18.5, normal [18.5–24.9], overweight [25–29.9], and obese ≥30 kg/m2. Results Seventeen women and 12 men were included. The mean age was 35.69 ± 11.72 [18–61] years. The mean age of disease onset was 11.10 ± 4.25 [2–16] years. The average diagnostic delay was 52.96 ± 95.97 [0–336] months. The average disease duration was 24.48 ± 12.76 [1–47] years. The polyarticular form was the most frequent (55.2%). Rheumatoid factor, ACPA and antinuclear antibodies were present in 41.4%, 24.1% and 17.2% of cases respectively. At least one extra-articular manifestation was noted in 16 patients: ophthalmologic (n = 6), skin (n = 4), cardiac (n = 4), pulmonary (n = 3) and renal (n = 2) involvement. Osteoporosis was noted in 7 cases. Mean C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were 42.74 ± 63.37 [2–218] mg/l and 69.67 ± 36.23 [36–108] mm. An elevation of inflammation markers was noted in 19 cases. The mean haemoglobin value was 11.31 ± 2.10 [6.5–15] g/dl Anaemia was noted in 20 cases. The mean body mass index was 21.20 ± 4.88 [14.17–27.55] kg/m2, 36.4% of patients were underweight, 27.2% had a normal BMI, and 36.4 were overweight. No patient was obese. Growth delay was noted in 3 cases. Our statistical study found a correlation of BMI with ESR (r = 0.998; P &amp;lt; 0.001), rheumatoid factor positivity (r = -1.000; P &amp;lt; 0.001), and osteoporosis (r = 0.803; P = 0.030). No other correlation of BMI with clinical and biological characteristics of the study population was identified. Conclusion BMI should be well considered in the JIA evaluation and treatment. BMI correlated with ESR, rheumatoid factor positivity, and osteoporosis in our study.

Carbon Quantum Dots Derived from Herbal Medicine as Therapeutic Nanoagents for Rheumatoid Arthritis with Ultrahigh Lubrication and Anti-inflammation.

As a typical chronic inflammatory joint disease with swelling and pain syndromes, rheumatoid arthritis (RA) is closely related to articular lubrication deficiency and excessive proinflammatory cytokines in its progression and pathogenesis. Herein, inspired by the dual effects of joint lubrication improvement and anti-inflammation to treat RA, two novel potential therapeutic nanoagents have been developed rationally by employing herbal medicine-derived carbon quantum dots (CQDs), i.e., safflower (Carthamus tinctorius L.) CQDs and Angelica sinensis CQDs, yielding ultrahigh lubrication and anti-inflammation bioefficacy. In vitro experimental results show that the two nanoagents display excellent friction reduction due to their good water solubility and spherical structure. Using RA rat models, it is indicated that the nanoagents significantly relieved swelling symptoms and inhibited the expression of related inflammatory cytokines, including IL-1, IL-6, and TNF-α, indicating their extraordinary anti-inflammation bioefficacy. Thus, combining the lubricating and anti-inflammation bioefficacy of CQDs derived from herbal medicine is an attractive strategy to develop new nanoagents for RA treatment.

Evaluation of a machine learning tool for the early identification of patients with undiagnosed psoriatic arthritis – A retrospective population-based study

BackgroundPsoriatic arthritis (PsA), an immune-mediated chronic inflammatory skin and joint disease, affects approximately 0.27% of the adult population, and 20% of patients with psoriasis. Up to 10% of psoriasis patients are estimated for having undiagnosed PsA. Early diagnosis and treatment can prevent irreversible joint damage, disability and deformity. Questionnaires for screening to identify undiagnosed PsA patients require patient and physician involvement. ObjectiveTo evaluate a proprietary machine learning tool (PredictAI™) developed for identification of undiagnosed PsA patients 1–4 years prior to the first time that they were suspected of having PsA (reference event). MethodsThis retrospective study analyzed data of the adult population from Maccabi Healthcare Service between 2008 and 2020. We created 2 cohorts: The general adult population (“GP Cohort”) including patients with and without psoriasis and the Psoriasis cohort (“PsO Cohort”) including psoriasis patients only. Each cohort was divided into two non-overlapping train and test sets. The PredictAI™ model was trained and evaluated with 3 years of data predating the reference event by at least one year. Receiver operating characteristic (ROC) analysis was used to investigate the performance of the model, built using gradient boosted trees, at different specificity levels. ResultsOverall, 2096 patients met the criteria for PsA. Undiagnosed PsA patients in the PsO cohort were identified with a specificity of 90% one and four years before the reference event, with a sensitivity of 51% and 38%, and a PPV of 36.1% and 29.6%, respectively. In the GP cohort and with a specificity of 99% and for the same time windows, the model achieved a sensitivity of 43% and 32% and a PPV of 10.6% and 8.1%, respectively. ConclusionsThe presented machine learning tool may aid in the early identification of undiagnosed PsA patients, and thereby promote earlier intervention and improve patient outcomes.

Resveratrol alleviates MSU-induced gouty arthritis in rats through inhibition of HIF-1α- and NLRP3-derived IL-1β secretion in macrophages.

Gouty arthritis is an acute and chronic joint inflammatory joint disease characterized by the deposition of monosodium urate (MSU) crystals in joints and periarticular tissues. Resveratrol (3, 5, 4-trihydroxy-trans-stilbene, RV), a natural polyphenolic compound, has anti-inflammatory and antioxidant properties. The purpose of this study was to investigate the effect of resveratrol on rats with gouty arthritis and its molecular mechanism. THP-1-derived macrophages were induced by lipopolysaccharide (LPS) and MSU to create an in vitro gout cell inflammation model, and rats were injected with MSU crystals into the right ankle joint for an in vivo acute gouty arthritis model. We investigated the anti-inflammatory properties of resveratrol using these in vitro and in vitro models. Our findings suggested that resveratrol effectively reduced ankle swelling and synovial inflammation in a dose-dependent manner in rats with acute gouty arthritis, with almost the same effect as colchicine treatment. In MSU-treated THP-1-derived macrophages, resveratrol inhibited NLRP3 inflammasome activation and IL-1β secretion. Furthermore, resveratrol and the HIF-1α inhibitor PX478 both inhibited the expression of the NLRP3 inflammasome, IL-1β, and HIF-1α. This study demonstrated that resveratrol significantly improved the symptoms of acute gouty arthritis and its potential mechanism may be IL-1β reduction via HIF-1α modulation and inhibition of NLRP3 inflammasome activation. Our study might offer a novel sight for the treatment of gouty arthritis.

Apoptotic cell clearance components in inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints that affects ~1% of the human population. Joint swelling and bone erosion, hallmarks of RA, contribute to disability and, sometimes, loss of life. Mechanistically, disease is driven by immune dysregulation characterized by circulating autoantibodies, inflammatory mediators, tissue degradative enzymes, and metabolic dysfunction of resident stromal and recruited immune cells. Cell death by apoptosis has been therapeutically explored in animal models of RA due to the comparisons drawn between synovial hyperplasia and paucity of apoptosis in RA with the malignant transformation of cancer cells. Several efforts to induce cell death have shown benefits in reducing the development and/or severity of the disease. Apoptotic cells are cleared by phagocytes in a process known as efferocytosis, which differs from microbial phagocytosis in its "immuno-silent," or anti-inflammatory, nature. Failures in efferocytosis have been linked to autoimmune disease, whereas administration of apoptotic cells in RA models effectively inhibits inflammatory indices, likely though efferocytosis-mediated resolution-promoting mechanisms. However, the nature of signaling pathways elicited and the molecular identity of clearance mediators in RA are understudied. Furthermore, canonical efferocytosis machinery elements also play important non-canonical functions in homeostasis and pathology. Here, we discuss the roles of efferocytosis machinery components in models of RA and discuss their potential involvement in disease pathophysiology.