Common Extra-articular Manifestation Research Articles

The malic acid inhibiting inflammation in ankylosing spondylitis by interfering M1 macrophage polarization

Ankylosing spondylitis (AS) is a motor system immune disease with significant genetic characteristics, resulting in joint fusion, deformity, rigidity, seriously affecting the quality of life of patients. Inflammatory bowel disease (IBD), characterized by intestinal mucosal damage and inflammatory changes, the most common extra-articular manifestation of AS. Due to the limitations of the application of therapeutic drugs, it is urgent to look for new mechanisms and strategies to effectively inhibit AS inflammation is. The content of malic acid (MA) was significantly decreased in peripheral blood of AS patients, and it was significantly negatively correlated with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). MA dramatically alleviated spinal damage and intestinal inflammation in mouse models of AS induced by β-1, 3-glucan solution. Mechanically, MA suppressed the NF-κB pathway by inhibiting polarization of M1-type macrophages, thereby alleviating spinal and intestinal inflammation. From the perspective of material metabolism, this study explored the mechanism by which MA, an intermediate product of glucose metabolism, reducing M1 polarization of macrophages to inhibit AS inflammation, providing a reliable basis for the pathogenesis research and precise targeted treatment of AS in the later stage.

Clinical case of a patient with rheumatoid arthritis and pulmonary rheumatoid nodules treated with Tocilizumab

Rheumatoid arthritis is the most common disorder of the spectrum of inflammatory arthropaties worldwide. It is a chronic autoimmune disease with clinical manifestation of symmetrical erosive polyarthritis of small and large joints in the upper and lower extremities. In some forms of the disease, involvement of other organs and systems is observed. The case report we present is of a young polymorbid patient who we diagnosed with seropositive rheumatoid arthritis. In the course of treatment with Methotrexate, a rare manifestation of the disease with lung involvement was found , where multiple rheumatoid nodules were seen using several imaging methods. A biopsy of a nodule was done and histologically verified. Although rheumatoid nodules are the most common extra-articular manifestation of the disease (25%), pulmonary localization is very rare, varying between 1-5% according to different sources. The patient’s comorbidities significantly limit the possibilities of treatment and makes it a therapeutic problem. Biologic therapy with an anti-IL-6 monoclonal antibody was initiated. On follow-up radiography 5 months later, the rheumatoid nodules had regressed.

Comprehensive single-cell profiling of monocytes in HLA-B27-positive ankylosing spondylitis with acute anterior uveitis.

Acute anterior uveitis (AAU) is a common extra-articular manifestation of ankylosing spondylitis (AS), particularly in patients positive for the human leucocyte antigen (HLA)-B27 genetic marker. To explore the underlying mechanisms of HLA-B27+ AS-associated AAU, we employed single-cell RNA sequencing to profile the transcriptomes of peripheral blood mononuclear cells in three HLA-B27+ AS-associated AAU patients and three healthy controls (HCs). We identified 11 distinct immune cell clusters, with a particular focus on monocytes, revealing six subsets, including three previously unidentified subsets, namely, GTPase immune-associated proteins, Th17-related, and lncRNA monocytes, with unique gene expression patterns. Significant differences in monocyte composition, activation states, and gene expression were observed between patients and HCs, particularly within HLA monocyte subpopulations. Notably, enhanced expression of X-inactive specific transcript and myeloid cell nuclear differentiation antigen genes was validated across monocyte subclusters in patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted significant enrichment in antigen processing and presentation pathways, shedding light on the disease's molecular mechanisms. These findings provide novel insights into the molecular mechanisms of HLA-B27+ AS-associated AAU and may contribute to the development of targeted diagnostic and therapeutic strategies. Further clinical validation is essential.

Multikingdom characterization of gut microbiota in patients with rheumatoid arthritis and rheumatoid arthritis-associated interstitial lung disease.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a serious and common extra-articular disease manifestation. Patients with RA-ILD experience reduced bacterial diversity and gut bacteriome alterations. However, the gut mycobiome and virome in these patients have been largely neglected. In this study, we performed whole-metagenome shotgun sequencing on fecal samples from 30 patients with RA-ILD, and 30 with RA-non-ILD, and 40 matched healthy controls. The gut bacteriome and mycobiome were explored using a reference-based approach, while the gut virome was profiled based on a nonredundant viral operational taxonomic unit (vOTU) catalog. The results revealed significant alterations in the gut microbiomes of both RA-ILD and RA-non-ILD groups compared with healthy controls. These alterations encompassed changes in the relative abundances of 351 bacterial species, 65 fungal species, and 4,367 vOTUs. Bacteria such as Bifidobacterium longum, Dorea formicigenerans, and Collinsella aerofaciens were enriched in both patient groups. Ruminococcus gnavus (RA-ILD), Gemmiger formicilis, and Ruminococcus bromii (RA-non-ILD) were uniquely enriched. Conversely, Faecalibacterium prausnitzii, Bacteroides spp., and Roseburia inulinivorans showed depletion in both patient groups. Mycobiome analysis revealed depletion of certain fungi, including Saccharomyces cerevisiae and Candida albicans, in patients with RA compared with healthy subjects. Notably, gut virome alterations were characterized by an increase in Siphoviridae and a decrease in Myoviridae, Microviridae, and Autographiviridae in both patient groups. Hence, multikingdom gut microbial signatures showed promise as diagnostic indicators for both RA-ILD and RA-non-ILD. Overall, this study provides comprehensive insights into the fecal virome, bacteriome, and mycobiome landscapes of RA-ILD and RA-non-ILD gut microbiota, thereby offering potential biomarkers for further mechanistic and clinical research.

P166 Assessing the effectiveness of a musculoskeletal rheumatology back pain questionnaire in early referral and diagnosis of ankylosing spondylitis in uveitis patients

Abstract Background/Aims Spondyloarthritis represents a chronic inflammatory condition primarily targeting the joints of the spine. Uveitis stands as the most common initial extra-articular manifestation of axial spondyloarthritis (SpA), occurring in up to a third of patients. There is a diagnostic delay in axial SpA, with studies showing that the time from symptom onset to diagnosis is 5-7 years. The delay of diagnosis can be attributed to the non-specific presentation of chronic back pain as well as late ophthalmology referrals to rheumatology. A previous audit in our department showed that 25% of uveitis patients who were clinically indicated to have been referred to rheumatology were not. One main objective was to implement the use of the MSK Rheumatology Inflammatory Back Pain Questionnaire as a referral tool, to find out whether the relevant history and questions were asked to all uveitis patients, to mitigate diagnostic delays and enable early management. Methods Patients presenting to the uveitis clinic at NGH were reviewed prospectively from May 2023-July 2023. Medi-viewer/Symphony were used to see patient details, whether the patients were already under rheumatology, any previous episodes and family history. The MSK Rheumatology Inflammatory Back Pain questionnaire was completed by all attending patients. It included 12 questions; a score ⩾4 signified a need for referral. Results A total of 40 patients (M:F ratio 2:3, mean age 52) presented to the uveitis clinic and were reviewed. All patients with uveitis were investigated with the relevant blood tests to rule out any inflammatory conditions. 16 patients were HLA B27 positive. All patients were asked to complete MSK Rheumatology Inflammatory Back Pain questionnaires to rule out inflammatory disease. 60% had back pain history before the age of 45, 21 were of inflammatory type of pain, 15 had disturbed second half of sleep. 25% of patients had other positive inflammatory markers. 40% of patients had a strong family history of HLA-B27. 67% scored ⩾4 on our questionnaire. 23% were already under rheumatology care, 20% were referred to rheumatology and 23 were not referred, of which 13/23 scored ⩽4. The remaining 10 were not referred due to awaiting blood results, further follow up, or lack of systemic features resulting in discharge. Conclusion Uveitis ranks among the most frequent occurrences in the field of ophthalmology, with a significant proportion being associated with HLA-B27. A considerable 40% of uveitis patients have undiagnosed spondyloarthritis due to inadequate referrals. A comprehensive questionnaire and utilising pain scoring can serve as effective tools for directing patients toward proper evaluation for inflammatory diseases. Our study shows that only appropriate cases were referred and had relevant investigations before referral, underscoring the importance of a partnership between ophthalmology and rheumatology to optimise the management of inflammatory spondyloarthritis. Disclosure F. Bangash: None. N. Kalla: None. A. Bangash: None. A. Rahim: None. M. Kamal: None. I. Mahmood: None.

P010 To establish compliance with British Society for paediatric and adolescent rheumatology (BSPAR) and the Royal College of Ophthalmology (RCOphth) guidelines for screening for uveitis in juvenile idiopathic arthritis (JIA) at a District General Hospital: a retrospective audit

Abstract Background/Aims JIA associated Uveitis (JIA-U) is most common extra-articular manifestation of JIA. The prevalence of uveitis in JIA is approximately 8-30%, but may be as high as 45-57% in young patients with oligoarticular disease. Uveitis is predominantly asymptomatic and requires slit-lamp examination for diagnosis. Up to 67% of JIA-U cases develop ocular complications such as cataracts (20%), glaucoma (19%), band keratopathy (16%), macular oedema and irreversible permanent visual impairment. The primary objective of our audit was to establish compliance of our service with BSPAR/RCOphth 2006 uveitis screening guidelines and therefore reduce the risk of visual complications in children with JIA. Methods A retrospective review of clinical records of children with rheumatological conditions attending our clinic was performed over five-year period. A total of 42 patients with JIA were identified. Data was collated using excel sheet audit tool. Results Results were analysed in accordance with the four major guideline domains as below. 1. Initial Screening exam within 6 weeks of referral: 40 out of 42 children screened within six weeks with 95% compliance rate. 2. Symptomatic patients seen within one week of referral: 4 out of 13 children seen in time with 30% compliance. 70% non-compliance was due to non-availability of ophthalmology appointment. 3. Uveitis may flare on stopping Methotrexate/DMARD’s. Patients should get screened two monthly for six months: 9 out of 13 children were screened with 70% compliance. 15% non-compliance was due to non-availability of ophthalmology appointment. 4. Ongoing screening at two-monthly intervals from onset of arthritis for six months, then 3-4 monthly: 15 out of 20 children screened with 75% compliance. 20% non-compliance was due to non-availability of ophthalmology appointment. Conclusion Practice at our centre as judged against the BSPAR/RCOphth guidelines was suboptimal. The main cause of non-compliance was due to staffing issue, rather than lack of healthcare professional training, delay in onward referral or non-attendance of patients. Non-availability of regular ophthalmology cover with cross-site commitment stretched the uveitis screening service at our centre. We presented this audit in our trust paediatric governance meeting. As a result of this audit, the frequency of paediatric ophthalmology clinics was increased to one a week. The paediatric nurse specialist facilitated liaison with the ophthalmology department and improved compliance with attendance. Patient database on shared drive was regularly updated with separate column for ophthalmology follow-up. The ophthalmologists were granted access to this database detailing clinic attendance and diagnosis. Parent education, reinforced with appropriate literature and a child friendly clinic environment improved awareness and reduces non-attendance. Combined clinics with ophthalmology are being explored. We plan to re-audit the service in near future to assess the impact after above remedial measures. A similar multi-site nation-wide audit may help identify and address local and national concerns. Disclosure K.K. Garg: None. T. Walton: None. A. Holliday: None.

Incidence of Uveitis in Patients With Axial Spondylarthritis Treated With Biologics or Targeted Synthetics: A Systematic Review and Network Meta-Analysis.

Anterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease-modifying drugs in AxSpA. We conducted a systematic review and meta-analysis to identify phase II/III double-blinded randomized controlled trials of anti-tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti-interleukin-17 (anti-IL-17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient-exposure years (PEY) were calculated using the per-protocol approach. Incidence rate (IR) of AU/100 person-years were calculated by treatment group using the random effects approach. Network meta-analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias-2 tool. Forty-four trials were included: 17 anti-TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti-IL-17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti-TNF mAb: 4.1, 95% confidence interval (CI) 0-8.5; etanercept: 5.4, 95% CI 0-16.0; anti-IL-17: 2.8, 95% CI 1.6-4.1; JAKi: 1.5, 95% CI 0.0-3.0; and placebo: 10.8, 95% CI 7.4-14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti-TNF mAb: 0.32, 95% CI 0.10-1.04; etanercept 0.42, 95% CI 0.08-2.38; anti-IL-17: 0.43, 95% CI 0.19-0.98; and JAKi: 0.32, 95% CI 0.06-1.67. Comparisons between anti-TNF mAb, anti-IL-17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti-TNF mAbs were associated with the lowest risk followed by JAKi, anti-IL-17, and etanercept. All treatments were ranked superior to placebo. Anti-TNF mAbs, JAKi, and anti-IL-17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments.

Bilateral Sacroiliitis in a Patient with Rheumatoid Arthritis: Unraveling the Rope: A Case Report

Rheumatoid arthritis (RA) and spondyloarthritis(SpA) are chronic inflammatory disorders with unique symptoms and pathologies. Misclassification of these two entities is prevalent due to overlapping clinical features and the presence of typical symptoms for both disorders. Rheumatoid nodules are one of the most common extra articular manifestations in rheumatoid arthritis, usually associated with severe disease activity. Herein, we describe a case of rheumatoid arthritis with bilateral sacroiliitis, an uncommon joint involvement of rheumatoid arthritis, and accelerated subcutaneous nodulosis after treatment with adalimumab. Introduction RA is a chronic, autoimmune disorder that primarily affects peripheral synovial joints [1]. The axial skeleton is usually spared other than the cervical spine, particularly C1 to C2 [1]. Though sacroiliitis is a paramount sign of SpA, it can be rarely observed in RA [2]. The commonest extra-articular manifestation of RA is subcutaneous nodules, which can be accelerated with RA treatments [3]. Herein, we describe a patient presented with bilateral sacroiliitis, along with the diagnostic and therapeutic challenges we surmounted. Case presentation A-45-years-old female presented with a one-year history of inflammatory arthritis of bilateral metacarpophalangeal, wrist, and ankle joints. She also had inflammatory-type back pain with buttock pain and plantar fasciitis. The Left-sided Faber test was positive. The laboratory investigations revealed elevated inflammatory markers, negative RF and HLA-B27. MRI-SI joints revealed bilateral active sacroiliitis. She was treated as SpA with NSAIDS at first, followed by subcutaneous adalimumab due to inadequate response. Though arthritis improved following adalimumab, multiple firm subcutaneous nodules occurred in the extensor surface of the elbow and hands after six-doses of adalimumab. Biopsy was compatible with rheumatoid nodule and anti-cyclic citrullinated peptide was positive. Based on the presence of rheumatoid nodules and positive anti-CCP antibodies, the patient was diagnosed with seropositive RA and bilateral sacroiliitis, an unusual joint involvement in RA. Discussion Sacroiliitis is the paramount clinical sign in SpA [2]. However, it can be seen in a wide range of disease conditions [4]. Misclassification between SpA and RA can occur due to overlapping clinical manifestations [4]. The Rheumatoid nodule is the most common cutaneous manifestation of RA and often seen in seropositive RA and more severe disease [3]. There have been case reports of accelerated subcutaneous nodulosis in patient with RA, treated with MTX, leflunomide, azathioprine, TNF alfa inhibitors and tocilizumab [3]. Though Inflammatory back pain, active sacroiliitis, and plantar fasciitis mislead the diagnosis, rheumatoid nodules and positive anti-CCP antibodies aid the classification of RA.

Antifibrotic Agents in Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Systematic Review and Meta-Analysis.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a common extra-articular clinical manifestation of rheumatoid arthritis (RA) that has negative impacts on morbidity and mortality. In addition, there has been no proven treatment for RA-ILD to date. Thus, we planned a meta-analysis of a literature search to confirm the clinical effects of antifibrotic agents in RA-ILD patients. We conducted the literature search in Ovid MEDLIVE® databases, Cochrane Library databases, EMBASE, and KoreaMed and identified references elucidating the role of nintedanib or pirfenidone in adult patients with RA-ILD. Among the identified studies, those with comparative interventions, complete results of clinical trials, and available full text were included in the analysis. The primary outcome was the effect of the antifibrotic agent on disease progression in RA-ILD patients assessed with a mean difference in the change of forced vital capacity (FVC) and the proportion of patients with an increase in percent predicted FVC of 10% or more over 52 weeks. Analysis for heterogeneity was assessed through I2 statistics. Meta-analysis with a fixed effect model was performed on changes in FVC. A total of 153 articles were identified through database searches, of which 28 were excluded because of duplication. After additional screening, 109 studies were selected with full text and two articles qualified for analysis according to the set inclusion and exclusion criteria. As a result, two randomized controlled studies were selected, comparing nintedanib and pirfenidone to placebo, respectively. The meta-analysis revealed that antifibrotic agents showed a significant reduction in FVC decline compared to placebo in patients with RA-ILD (mean difference, 88.30; 95% CI, 37.10-139.50). Additionally, there were significantly fewer patients experienced an increase in percent predicted FVC of 10% or more in the antifibrotic agent group compared to the placebo group (Odds ratio 0.42; 95% CI 0.19-0.95, p = 0.04). There was no significant heterogeneity between the two included studies (χ2 = 0.35, p = 0.0007, I2 = 0%). The meta-analysis suggests that nintedanib and pirfenidone may have clinical utility in reducing disease progression in patients with RA-ILD. Further research is needed to confirm the clinical benefits of antifibrotic agents in RA-ILD.

Symposium 4

Interstitial lung disease (ILD) is a fibrotic disease of the lung parenchyma. It can occur in different connective tissue diseases, including rheumatoid arthritis (RA). Smoking, male gender and longstanding RA are possible risk factors for developing ILD 1 . Being a common extra-articular manifestation of RA, it can contribute to decreased quality of life, chronic disability, high utilization of healthcare resources, and may also lead to substantial morbidity and mortality for affected patients1. Hence, early identification and management is of paramount importance to improve patient outcomes. Clinical presentation, chest X-ray, pulmonary function testing and high-resolution computed tomography are common tools for investigation and they also allows assessment of subtype and disease extent 2 . The histopathologic and radiographic features of RA-ILD are heterogeneous. The most frequent patterns of RA-ILD are usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). Distinguishing the patterns is useful in predicting prognosis and would also affect subsequent management approach 2 . Traditionally treatment initiated for RA-ILD was generally empirical. Corticosteroids were often used as first-line agents and immunosuppressants maybe added2. However, these treatments are not specific and mainly target inflammation instead of fibrosis. With the advance in medicine, antifibrotic is now indicated for treating fibrosing ILD with progressive phenotype. FVC decline can be slowed in patients with connective tissue disease associated progressive ILD 3 . In this lecture, Prof. Vanessa Smith will share the current knowledge and evidence in RA-ILD. The approach on identifying and screening ILD in RA patients would be presented. The management strategy and options would also be reviewed.

Targeted Therapy in Rheumatoid-Arthritis-Related Interstitial Lung Disease.

Rheumatoid arthritis (RA) is a chronic autoimmune multisystem inflammatory disease in which lung involvement is the most common extra-articular manifestation. Parenchymal lung involvement or interstitial lung disease (ILD) is a significant cause of morbidity and mortality and there is a paucity of evidence-based guidance on how to best treat RA-ILD. This review article aims to evaluate the evidence from cohort studies and best real word data from registries. Extensive discussion of the relative merits and drawbacks of glucocorticoids, various biologics, small molecules and anti-fibrotics is presented. The limited available guidelines in RA-ILD are also discussed and a rational treatment algorithm is offered.

Comparison of clinical characteristics between patients with axial spondyloarthritis with and without acute anterior uveitis: a multicentre study of the Chinese Spondyloarthritis Registry.

This study explores the clinical characteristics associated with the occurrence of acute anterior uveitis (AAU) in patients with axial spondyloarthritis (axSpA) within a large, multicentre database. This observational, cross-sectional study of patients with axSpA used data from the Chinese Spondyloarthritis Registry between August 1, 2018, and March 31, 2020. The demographic and clinical features of patients with and without AAU were compared. Univariate and multivariate analyses were performed to determine the association between variables and uveitis. A total of 4304 patients were included in this study. The prevalence of AAU in patients with axSpA was 10.59%. Multivariate logistic regression analysis revealed a positive correlation between AAU and age at diagnosis (odds ratio [OR], 1.026; p<0.001), disease duration (OR, 2.117; p<0.001), current or past Achilles tendinitis (OR, 1.692; p<0.001), current or past dactylitis (OR, 1.687; p=0.002), current or past psoriasis (OR, 3.932; p<0.001), presence of human leukocyte antigen-B27 (HLA-B27) (OR, 2.787; p<0.001), and a good response to non-steroidal anti-inflammatory drugs (NSAIDs) (OR, 1.343; p=0.027). AAU was the most common extra-articular manifestation in the Chinese Spondyloarthritis Registry. In Chinese patients with axSpA, older age at diagnosis, longer disease duration, presence of HLA-B27, current or past Achilles tendinitis, current or past dactylitis, current or past psoriasis, and a good response to NSAIDs were positively associated with AAU.

E26 Macrophage activation syndrome in systemic juvenile idiopathic arthritis, one centre experience

Abstract Background Macrophage Activation Syndrome (MAS) in Systemic Juvenile Idiopathic Arthritis (SoJIA) is a potentially life-threatening condition. The prevalence of MAS in SoJIA population is estimated to be 10%. However, reports suggested that the number of SoJIA patients with subclinical MAS may be as high as 40%. Early recognition of MAS is crucial because timely treatment is important for survival. Objective To describe the clinical and laboratory features of patients with MAS associated with SoJIA Methods Data from cohort of 38 SoJIA patients with and without MAS from January 2006 to January 2020 were included and retrospectively reviewed. Data were collected on demography, clinical/laboratory features and treatment. Results There were 38 patients with SoJIA diagnosed according to the International League Against Rheumatism (ILAR) criteria. 47.4% of them were males and 52.6% were females. They were followed up for a period of 6.3 ± 4.4 years. The mean period from appearance of symptoms to first follow up in rheumatology clinic was 5 ± 6 months. The disease course was monocyclic in 39.5%, polycyclic in 28.9% and persistent in 31.6% of the patients. Of the total cohort, 10% of the patients were classified as having MAS, half of them presented with MAS at diagnosis and the rest developed MAS during the disease course. Only One patient experienced recurrent MAS (3 times). Male to female ratio is 3:1. The mean age at diagnosis was 8 ± 6 years. Skin rash was the most presenting feature in the two groups. Hepatosplenomegaly and serositis were most common in sJIA with MAS patients. In comparison to SoJIA patients without MAS, all patients have thrombocytopenia, leukopenias, with mean ferritin level of 1668 in MAS patient and 947 in non-MAS group. The obligate criteria for the diagnosis of MAS according to the 2016 MAS classification criteria are increased ferritin &amp;gt;684 μg/l, elevated lactate dehydrogenase (LDH) and Glutamic Oxaloacetic Transaminase (GOT). All patients have a declining ESR and high CRP and all patients were anaemic. Bone marrow biopsy was done in 50% of the patients. In SoJIA without MAS, ESR mean level was 94 (±38.5) mm/h, CRP mean level of 62 (± 65.8) mg/dl and platelets count mean level of 561 (±215) × 109/l. Treatment all MAS-SoJIA patients were treated with IV methylprednisolone and IVIG compared with 50% of non-MAS-SoJIA patients. In the MAS group, dose of oral prednisolone was (1–2 mg/kg/day) while in non-MAS group was (0.5–1 mg/kg/day). A patient developed MAS twice while on the 7th dose of anakinra and the third MAS on the 6th dose of tocilizumab. Ciclosporin (3 mg per/kg/day) was the treatment of choice for him. Conclusions In our series, prevalence of MAS was 10% which mainly affect the male which is the same as the estimated prevalence of MAS worldwide. Arthritis occurred less frequent in MAS group cases in comparison to hepatosplenomegaly which was more common among MAS group. Rash and serositis were the most common extra-articular manifestations. The main treatment modality was steroid in all of the patients. All the MAS patients were successfully treated with high dose of IVIG, methylprednisolone and ciclosporin, including the patients who developed MAS while on biologics. Ethics Our study was approved by local ethical committee of pediatric department at Tripoli children hospital.

Integrating bioinformatic resources to identify characteristics of rheumatoid arthritis-related usual interstitial pneumonia

BackgroundRheumatoid arthritis (RA) is often accompanied by a common extra-articular manifestation known as RA-related usual interstitial pneumonia (RA-UIP), which is associated with a poor prognosis. However, the mechanism remains unclear. To identify potential mechanisms, we conducted bioinformatics analysis based on high-throughput sequencing of the Gene Expression Omnibus (GEO) database.ResultsWeighted gene co-expression network analysis (WGCNA) analysis identified 2 RA-positive related modules and 4 idiopathic pulmonary fibrosis (IPF)-positive related modules. A total of 553 overlapped differentially expressed genes (DEG) were obtained, of which 144 in the above modules were further analyzed. The biological process of “oxidative phosphorylation” was found to be the most relevant with both RA and IPF. Additionally, 498 up-regulated genes in lung tissues of RA-UIP were screened out and enriched by 7 clusters, of which 3 were closely related to immune regulation. The analysis of immune infiltration showed a characteristic distribution of peripheral immune cells in RA-UIP, compared with IPF-UIP in lung tissues.ConclusionsThese results describe the complex molecular and functional landscape of RA-UIP, which will help illustrate the molecular pathological mechanism of RA-UIP and identify new biomarkers and therapeutic targets for RA-UIP in the future.

The other side of the coin: Uveitis in patients with juvenile idiopathic arthritis

Objective: Juvenile idiopathic arthritis (JIA) is a childhood rheumatic disease that causes joint inflammation and tissue damage. Non-infectious uveitis is the most common extra-articular manifestation of JIA.The aim of this study is to evaluate the risk factors that play a role in occurrence and recurrence of uveitis and, to determine the relationship between arthritis and uveitis activity in patients with JIA. Material and Methods: This retrospective, cross sectional study included JIA patients with/without uveitis from a referral center in Turkey. The Juvenile Arthritis Disease Activity Score was used to evaluate the disease activity and calculated for arthritis and uveitis separately. Results: Uveitis was seen in 26 (13.3%) of 195 JIA patients. Of 26 JIA associated uveitis (JIA-U) patients, 19 (73%) had an oligoarticular subtype. The median age at diagnosis of JIA with uveitis was younger than without uveitis (p=0.015). Oligoarticular JIA was found to be associated with recurrence of uveitis (p=0.021). The occurrence age of arthritis and uveitis was significantly younger in patients with recurrent uveitis (p=0.041, p=0.002, respectively). The median JADAS27 score at the onset of uveitis was lower in the recurrent group (p=0.038). Conclusion: Early age is a significant risk factor for occurrence and recurrence of uveitis. It is important to remember that, during the disease course, patients with low disease activity may also develop uveitis.

Overview on the Link Between the Complement System and Auto-Immune Articular and Pulmonary Disease.

Complement system (CS) dysregulation is a key factor in the pathogenesis of different autoimmune diseases playing a central role in many immune innate and adaptive processes. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by ta breach of self-tolerance leading to a synovitis and extra-articular manifestations. The CS is activated in RA and seems not only to mediate direct tissue damage but also play a role in the initiation of RA pathogenetic mechanisms through interactions with citrullinated proteins. Interstitial lung disease (ILD) represents the most common extra-articular manifestation that can lead to progressive fibrosis. In this review, we focused on the evidence of CS dysregulation in RA and in ILD, and highlighted the role of the CS in both the innate and adaptive immune responses in the development of diseases, by using idiopathic pulmonary fibrosis as a model of lung disease. As a proof of concept, we dissected the evidence that several treatments used to treat RA and ILD such as glucocorticoids, pirfenidone, disease modifying antirheumatic drugs, targeted biologics such as tumor necrosis factor (TNF)-inhibitors, rituximab, tocilizumab, and nintedanib may act indirectly on the CS, suggesting that the CS might represent a potential therapeutic target in these complex diseases.

Patient Survey Exploring the Burden of Inflammatory Back Pain in Patients With Uveitis.

Background In the UK, diagnostic delays remaina challenge in axial spondyloarthritis (axSpA). Studies have shown that acute anterior uveitis is the most common extra-articular manifestation associated with axSpA. As part of a National Axial Spondyloarthritis Society (NASS) Aspiring to Excellence quality improvement project, this study aimed to ascertain the burden of inflammatory back pain (IBP) in patients attending a uveitis clinic and to establish the number of these patients who had not been referred to a rheumatologist, thereby contributing to the diagnostic delay. The secondary aims were to explore the factors contributing to the diagnostic delay. Methods A 22-question patient survey was created to identify the burden of back pain in patients attending a specialist uveitis clinic at a London NHS Trust. Participants were recruited when attending their clinic appointments. Survey content included patient demographics and whether they had experienced back pain for longer than three months. The Berlin Criteria was used to identify the presence of inflammatory back pain, and it was also ascertained whether participants had a previous diagnosis of axSpA. Participants were asked if they had seen any healthcare professionals regarding their back pain and the total number of consultations they had had with each profession. Results A cohort of 50 patients who attended the uveitis clinic at the Royal Free London NHS Trust completed the survey between February and July 2022. The mean age of the respondents was 52 years with a mean length of time with uveitis of 6.57 years. Of them, 64% were female and 36% were male. Forty per cent (40%) of participants (20 respondents) reported experiencing back pain for more than three months and 12% (six respondents) had a diagnosis of axSpA. Of those who reported back pain for more than three months, the mean age of onset of back pain was 28.6 years. Of the 14 participants (28%) who had back pain and were not diagnosed with axSpA, nine (18%) fulfilled the Berlin criteria for IBP. All participants had seen a GP or allied health professional specifically for their back pain. On average, respondents had seen two allied healthcare professionals, but only 40% (eight) of respondents with back pain had been seen by a rheumatologist. Conclusions In this study, thedata highlights that inflammatory back pain is common in patients with uveitis and themajority of patients with inflammatory back pain had not been referred to a rheumatology service and potentially haveundiagnosed axSpA. Contributing factors to this potential delay in diagnosis include a lack of awareness of axSpA and its presenting features and associated conditions and a lack of onward referral for a specialist rheumatology opinion. This highlights the need for public, patient and healthcare professional education and the development of timely referral pathways to reduce delays in diagnosis.

Rheumatoid nodules: a narrative review of histopathological progression and diagnostic consideration.

Rheumatoid nodules (RNs) are the most common extra-articular manifestation of rheumatoid arthritis and are also seen in patients with other autoimmune and inflammatory diseases. The development of RNs includes histopathological stages of acute unspecified inflammation, granulomatous inflammation with no or minimal necrosis, necrobiotic granulomas typically with central fibrinoid necrosis surrounded by palisading epithelioid macrophages and other cells, and likely an advanced stage of "ghost" lesions containing cystic or calcifying/calcified areas. In this article, we review RN pathogenesis, histopathological features in different stages, diagnostically related clinical manifestations, as well as diagnosis and differential diagnosis of RNs with an in-depth discussion about challenges in distinguishing RNs from their mimics. While the pathogenesis of RN formation remains elusive, it is hypothesized that some RNs with dystrophic calcification may be in transition and may be in coexistence or collision with another lesion in patients with RA or other soft tissue diseases and comorbidities. The diagnosis of typical or mature RNs in usual locations can be readily made by clinical findings often with classic RN histopathology, but in many cases, particularly with atypical or immature RNs and/or unusual locations, the clinical and histopathological diagnosis can be challenging requiring extensive examination of the lesional tissue with histological and immunohistochemical markers to identify unusual RNs in the clinical context or other lesions that may be coexisting with classic RNs. Proper diagnosis of RNs is critical for appropriate treatment of patients with RA or other autoimmune and inflammatory diseases.

Tocilizumab in Juvenile Idiopathic Arthritis Associated Uveitis, a Narrative Review

Juvenile idiopathic arthritis (JIA) associated uveitis (JIA-U) is the most common extra-articular manifestation of JIA, affecting 10-15% of patients, especially in oligoarticular JIA where its course may be faint. Therefore, JIA-U is one of the most challenging pediatric uveitis, associated with major ocular morbidity and possibly leading to irreversible structural ocular damage and to vision-threatening complications. Adequate management is crucial for avoiding visual impairment complications. Since the introduction of biologic disease modifying anti-rheumatic drugs (bDMARDS), the visual prognosis of JIA-U has dramatically improved over the decades. Tumor necrosis factor-α (TNF-α) blockers are the most used bDMARDs in treating JIA-U with large evidence of efficacy. However, inadequate response to these agents, either due to intolerance or inefficacy, may be observed, requiring a swap to other classes of immunosuppressive agents, including anti-IL-6, anti-CD20, and, more recently, JAK inhibitors. Tocilizumab is a humanized monoclonal antibody to the interelukin-6 receptor preventing IL-6 from binding to its soluble and membrane-bound receptors. A growing body of literature provides promising results about the efficacy of intravenous and subcutaneous tocilizumab in the treatment of JIA-U. A narrative review of the literature on this topic will improve our knowledge on the potential use of tocilizumab in JIA-U.

Clinical and Laboratory Profile of Patients with Newly Diagnosed Juvenile Idiopathic Arthritis: An Observational Study from a Tertiary Care Centre, Karnataka, India

Introduction: Juvenile Idiopathic Arthritis (JIA) is the most common rheumatic condition of childhood. It represents a heterogeneous group of childhood arthritis. Aim: To study the clinical profile and laboratory characteristics of all newly diagnosed JIA patients. Materials and Methods: This hospital-based prospective observational study was conducted in the Department of Paediatric Rheumatology in Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India between December 2017 to April 2019. All children who fulfilled International League of Associations for Rheumatology (ILAR) criteria for the diagnosis of JIA were enrolled in the study, and their clinical and laboratory parameters were evaluated. The analysis between matchedpairs data like the comparison between age of onset and age of presentation in males and females were done by paired t-test. Results: Fifty one children were included in the study with M:F of 1:1.12. Mean age at onset was 8.71±4.02 years and median duration of disease was 13 months (2-96 months). The most common subgroup was polyarticular JIA 18 (35.3%) followed by Systemic Onset Juvenile Idiopathic Arthritis (SOJIA) 14 (27.5%), enthesitis-related arthritis 13 (25.5%) and oligoarticular JIA 4 (7.8%). Knee (94%) was the most common joint involved followed by the ankle (70.5%). Fever was the most common extra-articular feature present in 73% of cases. Hepatomegaly, splenomegaly and lymphadenopathy was present in 33.3%, 9.8% and 21.6% children, respectively. Anaemia, leukocytosis, thrombocytosis and elevated Erythrocyte Sedimentation Rate (ESR) were more common in SOJIA. Macrophage Activation Syndrome (MAS) was diagnosed in 2 cases of SOJIA (14.3%) with no mortality. Conclusion: Polyarticular JIA was the common subtype in the study, followed by SOJIA. Most common joint involved was knee, followed by ankle and fever is the most common extraarticular manifestation.