Rheumatology Centers Research Articles

P156 Type I interferon is raised across connective tissue diseases and is associated with haematological abnormalities and specific autoantibody profiles

Abstract Background/Aims The overlapping clinical and serological features among connective tissue diseases (CTDs) suggest a shared molecular aetiology. A molecular taxonomy of CTDs offers new opportunities in clinical trial design, which can potentially be translated into targeted treatment. In a previous study of 164 patients, we identified a type I interferon (IFN) positive subgroup within an unselected CTD cohort associated with specific clinical and serological features. Here, we aim to investigate the relationship between type I IFN and the clinical and immunological phenotype in a larger CTD cohort and determine whether a distinct subpopulation of patients can be identified. Methods Adult patients with at least 1 CTD clinical feature and CTD-related autoantibody were recruited from five rheumatology centres in North West England into the Lupus Extended Autoimmune Phenotype (LEAP) cohort. A 24-gene interferon-stimulated gene (ISG) score was calculated using NanoString as described by Neasens et al. 2022. Results Most patients had lupus (36%). 160 of 344 (46.5%) patients had a positive ISG score across all CTDs with 64/125 (51%) of lupus patients (Fig.1). Patients with positive ISG score were younger and had longer disease duration (p < 0.005 for both). There were no differences in mucocutaneous or internal organ involvement between the ISG subgroups. The ISG-positive group had significantly increased frequency of specific autoantibodies (anti-Smith, anti-Chromatin, anti-RNP, anti-Ro) and Rheumatoid Factor, and haematological abnormalities (lower haemoglobin, and lower total white cell and neutrophil counts) in an adjusted model including the CTD subtype. Conclusion In CTD patients, IFN type I positivity was identified across a subset of patients of all CTDs and is associated with specific autoantibodies and haematological parameters; these results support the findings of our previous smaller study. The identification of an IFN I-positive subgroup within an unselected CTD regardless of clinical diagnosis supports a molecular-based approach to treatment. Disclosure A. Madenidou: Grants/research support; Janssen and UCB. G.I. Rice: None. S. Dyball: Grants/research support; UCB, Novartis,Eli Lilly. B. Parker: Honoraria; Fresenius-Kabi and AbbVie. Member of speakers’ bureau; Eli Lilly and Roche. Grants/research support; Genzyme/Sanofi and GlaxoSmithKline. T.A. Briggs: Grants/research support; Janssen. I.N. Bruce: Consultancies; AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck Serono and UCB. Member of speakers’ bureau; AstraZeneca, GlaxoSmithKline and UCB. Grants/research support; Genzyme/Sanofi, GlaxoSmithKline, Roche, Novartis, Janssen and UCB.

P147 M2 macrophage associated fibrosis in early stage systemic sclerosis: an update on plasma biomarkers

Abstract Background/Aims Systemic sclerosis is an autoimmune connective tissue disease characterised by vasculopathy and fibrosis. The CCN family of matricellular proteins have a regulatory role in inflammation and fibrosis. CD206, an M2 macrophage surface marker, is cleaved by metalloproteases to release soluble form of CD206; this acts as an active disease marker in systemic sclerosis. We investigated the profile of CCN2 and CCN3 in the presence of soluble CD206 (sCD206) in patients with early and late stage diffuse systemic sclerosis (dcSSc). Methods Patients with a diagnosis of dcSSc at the UCL Centre for Rheumatology and Connective Tissue Diseases were recruited. Informed consent was obtained from patients and healthy controls (HC). Blood samples were taken from which plasma was isolated and stored at -80 °C prior to assay. Expression of CCN2, CCN3, and sCD206 was measured in these plasma samples by ELISA. Study participants were categorised into healthy controls (n = 20), early stage dcSSc (n = 20) and late dcSSc (n = 20), with early stage defined as the blood sample taken within two years since diagnosis, and late stage defined as over five years since diagnosis. Results Plasma CCN2, CCN3 and sCD206 levels were significantly higher in early dcSSc patients, when compared to HC. CCN2 was raised in early dcSSc patients (early dcSSc mean 20,221pg/ml, SD 16,503, p < 0.05) with concentration in late disease matching that of HC (late dcSSc 12,893pg/ml, HC 11,289pg/ml). CCN3 was significantly higher in early and late disease when compared to HC (early mean 16,526pg/ml, late 12,838pg/ml, HC 4,201pg/ml, p < 0.05). sCD206 levels were higher in early dcSSc (mean 5356pg/ml, SD 3154, p < 0.05), with there being no significance between levels in late dcSSc (mean 4184pg/ml, SD 3900, p > 0.05) and HC (mean 3319pg/ml, SD 1925). CCN2 expression was higher compared to that of CCN3 in early disease, with CCN2:CCN3 ratio elevated in early dcSSc (mean 3.17, SD 8.26) compared to late dcSSc (mean 1.26, SD 0.99) and HC. Conclusion This investigation demonstrates that upregulation of CCN2 and CCN3 expression has a regulatory role in fibrosis in early stage dcSSc. These biomarkers of M2 macrophage associated fibrosis are to be correlated with their clinical phenotype and have potential for a role in targeted treatment of systemic sclerosis. Disclosure L.A. Leeves: None. Z. Kannan: None. Y. Ali: None. L. Pan: None. T. Malley: None. D. Abraham: None. A. Leask: None. B. Riser: None. B. Ahmed Abdi: None. R.J. Stratton: None.

P090 Real-world data on immuno-modulation therapies and body mass index in children and young people with juvenile idiopathic arthritis

Abstract Background/Aims There is some evidence that children and young people (CYP) with Juvenile Idiopathic Arthritis (JIA) who are overweight/obese have less favourable disease control and treatment outcomes. The aim of this study was to investigate any association between BMI and total number of immune modulation therapies used in CYP with JIA. Methods This was a retrospective observational study at a tertiary paediatric rheumatology centre. Cross-sectional data was captured in April 2022 from CYP receiving immunomodulation therapies for JIA. Data on diagnosis, treatments and weight/height at last routine follow-up was included. BMI was calculated for each patient and centile assigned using Royal College of Paediatrics and Child Health electronic BMI charts as follows: BMI ≥85th to 94th centile - overweight, ≥95th centile - obese, as per population monitoring British 1990 growth reference (UK90). Results 187 CYP were identified and 180 included (seven were excluded due to missing BMI data). Baseline demographic, disease and treatment data are summarised in Table A. 67% were female. Median (interquartile range (IQR)) age in years at diagnosis and follow-up was 4.3 (2.7, 8) and 11.9 (8.5, 14.4) respectively. At follow-up, 41.1% of CYP were either obese or overweight. The median (IQR) number of total immunomodulation therapies per patient according to BMI categories were: under/normal weight 2 (1, 3); overweight 3 (2, 3) and obese 3 (2, 5). The median (IQR) years of follow-up in under/normal weight, overweight and obese groups were 4.77 (2, 8.74); 5.27 (1.86, 7) and 5.5 (3, 9.1) respectively. Conclusion CYP that were overweight/obese received more therapies compared to under/normal weight. The high proportion (41%) of CYP in this study who were either overweight or obese is similar to prevalence (44.2%) for children in year six at school in this region. Corticosteroid use and limited physical activity is associated with inadequate control of joint inflammation and increased BMI but this data was not collected and is an important limitation, in addition to cross-sectional and retrospective study design. The overweight/obese group had longer follow-up and may have accumulated more therapies. Future research to evaluate optimal dosing of immunomodulation in CYP with high BMI is warranted. Disclosure K. Hartley: Grants/research support; NIHR BRC Internship. S. Jandial: None. F. McErlane: None. E. Sen: None. S. Sampath: None.

P095 Association between autism and chronic musculoskeletal pain; a single tertiary adolescent rheumatology centre experience

Abstract Background/Aims Autism is a common neurodevelopmental disorder and can present with atypical sensorimotor function and altered pain response. Evidence suggests that patients with autism have a different processing mechanism which can alter pain perception. Pain evaluation and management is often insufficient in patients with autism. Chronic musculoskeletal pain in adolescents is common and is frequently associated with other co-morbidities. The adolescent musculoskeletal pain service at University College London Hospital uses a multidisciplinary approach to provide treatment and ongoing support for young people with chronic musculoskeletal pain up to the age of 19 years, bridging significant and often stressful life events such as exams and moving away from home. Methods A retrospective review of patient records was conducted between October 2021 and October 2023. New patients attending the adolescent chronic musculoskeletal pain clinic at University College London Hospital were identified and the prevalence of autism was noted. The presence of other co-morbidities and symptoms was also recorded. Statistical analysis was undertaken using GraphPad Prism (Fisher’s exact test) to determine any differences between patients with and without a diagnosis of autism. Results Retrospective data was obtained on 82 new patients aged between 13 and 18 years seen in the adolescent chronic musculoskeletal pain clinic. 28 patients (34%) had a diagnosis of autism. A higher proportion of autistic patients with chronic musculoskeletal pain were male compared to those without autism (36% vs 11%, p = 0.016). More patients with autism reported co-existing mental health difficulties, especially anxiety and depression (68% vs 37%, p = 0.011). Conversely, patients without autism reported a higher incidence of postural orthostatic tachycardia symptoms (POTS) or symptoms of postural dizziness (57% vs 25%, p = 0.009). Other co-morbidities and symptoms were found to be similar between patients with and without autism (headaches 18% vs 39%, abdominal pain 36% vs 54%, fatigue 61% vs 46%, sleep difficulties 68% vs 54%, attention deficit hyperactivity disorder 18% vs 9%). Conclusion This small retrospective study demonstrates that over a third of new patients seen in the adolescent chronic musculoskeletal pain service are autistic. This suggests a possible link between autism and chronic pain but more research is needed to evaluate this and larger studies are required. Patients with chronic musculoskeletal pain and autism were more likely to be male and have mental health difficulties compared to those without autism. The high incidence of mental health difficulties highlights the need for multidisciplinary team working, in particular psychological support. The results of this study have important implications for training and suggest that novel treatment strategies are needed to help advance therapies for chronic musculoskeletal pain in young people with autism. Disclosure E. Williams: None. S. Mavrommatis: None. J. Glanville: None. M. Leandro: None. D. Sen: None. C. Fisher: None.

E073 The use of magnetic resonance imaging to assess disease activity in axial spondyloarthritis- data from a tertiary rheumatology centre

Abstract Background/Aims The role of MRI of the spine and sacroiliac joints to aid the diagnosis of axial spondyloarthritis (axSpA) is now well established. However, its utility in disease monitoring, in particular assessment of treatment non-response is unclear with limited and conflicting data on the relationship between inflammatory changes suggestive of disease activity on MRI and outcome measures such as ASDAS-CRP and BASDAI. Although the most recent ASAS/EULAR guidelines recommend against routine use of MRI in the assessment of treatment response in axSpA, this is a pragmatic approach often undertaken in NHS clinics with substantial cost implications. We aimed to explore the current use of MRI to assess disease activity in axSpA in a large tertiary centre, in particular its utility in exploring treatment non-response and its impact on treatment switching decision. Methods As part of a service evaluation audit, MRIs performed under the “inflammatory back pain protocol” at Leeds Teaching Hospitals Trust between December 2021 and May 2023 were identified from radiology request data. Patients with axial spondyloarthritis (nr-axSpA, r-axSpA or axial psoriatic spondyloarthritis [axPsA]), were identified. Demographic data, baseline MRI findings, current medications, repeat MRI findings for ongoing axial symptoms, outcome measures and inflammatory markers were extracted from the clinical notes. Data on MRI findings consistent with inflammatory or structural changes related to axSpA or alternative findings, were extracted from the radiologist’s report. Results Overall, 111 patients had an MRI to assess disease activity, 93 had axSpA (49 r-axSpA, 44 nr-axSpA) and 18 axPsA. Patients were predominantly male (58.5%) and HLA-B27 positive (65.8%), 25.2% and 27.9% current smokers and ex-smokers respectively. A history of psoriasis was documented in 25.2% and peripheral arthritis in 42.3%. Baseline MRI was available on 76 patients (68.9%), of which 61 (80.3%) had spinal or sacroiliac inflammation as per the radiologist report. In total, 79 patients were on bDMARD therapy, with TNFi the commonest class (n = 59, 52.7%). Repeat MRI demonstrated active inflammation in the spine or sacroiliac joints in 58.6% (n = 65) as per the radiologist report. Patients with active inflammation in the repeat scan were more likely to have their bDMARD switched or treatment escalated (54% vs 36%). Other important findings included spinal stenosis (n = 4), disc disease (n = 15), vertebral fractures (n = 2) and potential malignancy (n = 1). Conclusion In our practice, MRI is of utility in the monitoring and assessment of non-response in axSpA in two-thirds of cases, aiding treatment decision making by leading to a switch of bDMARD in half of patients and excluding alternative pathologies, such as vertebral fractures and disc disease which may also affect components of disease activity scores. Further research exploring association of MR findings with clinical outcomes, including economic evaluation of routine MRI to assess disease activity in axSpA is warranted. Disclosure J. Weddell: None. R. Shah: None. P. Robinson: None. A. Barr: None. C. Vandevelde: None. J. Freeston: None. D. McGonagle: None. H. Marzo-Ortega: None.

P033 Online educational resources in paediatric and adolescent rheumatology- what’s new?

Abstract Background/Aims Paediatric and adolescent rheumatology (PAR) is a small sub-specialty, and due to the rarity of some conditions, UK trainees find it difficult to access relevant educational materials. Furthermore, due to the wide geographical distribution of paediatric rheumatology centres, regional educational opportunities are limited. A 2022 survey of the UK PAR trainee group confirmed that the creation of more PAR specific online educational materials and signposting of current guidelines/ resources was needed. Survey participants were supportive of a range of delivery methods, including webinars, e-learning, case studies and podcasts. Methods A PAR trainee education team was formed in 2022, with the aim of promoting learning opportunities, by developing and collating educational resources. The PAR trainee education team has been working both independently and in conjunction with the British Society of Rheumatology (BSR) education team and Digital Learning Board (DLB) to achieve this aim. Activities have included the following: a) Creation of a BSR hosted Teams channel to store PAR specific educational information; b) PAR trainee inclusion on the BSR DLB, which creates digital education resources including podcasts and the monthly blended learning Spotlight topic series; c) Creation of PAR focused podcasts within the BSR Talking Rheumatology podcast series; d) Organisation of webinars on PAR relevant topics; e) Creation of a PAR podcast playlist on the Spotify platform; f) Production of a resource list and education newsletter to signpost relevant existing/upcoming learning opportunities and events. Results A 2023 follow up survey of the PAR trainee group (n = 16 respondents), showed the most used resources were podcasts (69%), the newsletter (63%) and resource list (43%). Webinars (38%), the Teams channel (38%) and the BSR Spotlight series (31%) had been accessed less. BSR podcast download data illustrated that PAR relevant podcasts from the Talking Rheumatology/ Talking Rheumatology Spotlight series have a UK and international audience. There have been over 2500 downloads from six PAR relevant podcasts covering myositis guidelines, biologics in PAR, HLH, antiphospholipid syndrome and ultrasound in PAR. Feedback from those who have used the various educational resources has been extremely positive, although comments have indicated a barrier in terms of awareness of the materials and how to access them. Conclusion Good progress has been made, however maximising means and opportunities to disseminate available resources within the PAR community is vital. Work to develop, collate and signpost more PAR educational content is ongoing. A project is in progress to create condition-specific lists of classification criteria, guidelines and key studies. The PAR trainee group are very grateful to all of those who have supported this work including the professionals who have shared their knowledge and expertise via podcasts and webinars, members of the BSR DLB and the education team at BSR. Disclosure J. Lemon: Other; Unpaid member of the BSR Digital Learning Board. R. Close: None. G. Dobson: None. K. Maxey: Other; Works for the BSR as Events and Education Officer. J. May: None. D. McLaughlin: None. I. Rajarathinam: None. S. Saadalla: None. L. Yeo: None. P.A. Watson: Other; Works for the BSR in a paid role (2PA per week ) as digital learning editor.

CINCA/NOMID is a rare autoinflammatory syndrome in rheumatological practice. Experience of diagnosis, management and therapy with interleukin-1 inhibitors

Objective: to present the experience of diagnosis, management and therapy with interleukin-1 inhibitors (iIL1) in patients with Chronic Infantile Onset Neurologic Cutaneous Articular/Neonatal Onset Multisystem Inflammatory Disease (CINCA/NOMID) according to the Russian Federal Rheumatological Center data.Material and methods. From 2007 to 2023, eight patients were included in the study (7 men) aged 10 months to 33 years, including 3 with a disease duration of more than 10 years (13, 17 and 33 years). Genetic testing was performed in all patients and mutations in the NLRP3 gene were identified in 6 cases.Results and discussion. The age of onset of the disease ranged from 0 to 6 months. The delay in diagnosis and prescription of therapy ranged from 10 months to 33 years. All patients had the classic manifestations of CINCA/NOMID, including fever, rash, central nervous system (CNS) involvement, elevated ESR and CRP levels, 6 patients had articular manifestations, 7 had ocular manifestations and 6 had sensorineural hearing loss. Amyloidosis was detected in 1 case. All patients were prescribed iIL1. Anakinra was used in 6 patients (in 5 as the first line, in 1 as the second line therapy) with a positive response; subsequently 2 of these patients were switched to canakinumab once every 4 weeks (1 patient deteriorated and was readministered anakinra). Five patients received canakinumab (3 as first-line therapy, 2 as second-line therapy), 1 patient was switched to anakinra due to insufficient CNS response. The response to iIL1 therapy was positive in all patients, but incomplete in some of them due to the severity of the manifestations and the presence of irreversible organ damage.Conclusion. Patients with CINCA/NOMID have a severe disease and a poor prognosis. In this context, early administration of iIL1 is necessary. In the case of CNS involvement, the use of anakinra is preferable, as it is characterized by better penetration of the blood-brain barrier and is therefore more effective. Later it is possible to switch the patient to canakinumab, however, to achieve a complete response, it is sometimes necessary to increase the dose of the drug and reduce the interval between doses.

Evaluation of autologous fat grafting in the treatment of juvenile localized scleroderma with facial involvement

Objectives: The objective of this study was to evaluate the effect of autologous fat grafting in patients with juvenile localized scleroderma with facial involvement. Methods: We retrospectively studied patients with juvenile localized scleroderma who were followed at the Hamburg Center for Pediatric and Adolescent Rheumatology at least 6 months post-operative follow-up and received at least one autologous fat transplantation for a facial lesion. Autologous fat grafting was conducted independent of disease-modifying treatment and/or disease activity. The effectiveness of the intervention was evaluated by assessing the immediate volume enhancement after injection of fat tissue compared with volume retained after 6 months. The volume enhancement was calculated from three-dimensional photo images analyzed in Mirror Medical Imaging Software, Canfield Scientific (New Jersey, USA). Results: Data of 22 juvenile patients were assessed from March 2006 to September 2021. In six patients, the photos could not be evaluated for the study. The median age of the remaining 16 patients at the beginning of the first fat graft was 8 years (range = 2.5–22 years). Patients underwent mean three interventions (range = 1–9). Evaluation of three-dimensional images showed that the volume retention at 6 months post autologous fat grafting is approximately 50%. The Modified Localized Scleroderma Skin Severity Index value did not correlate to volume changes at 6 months. In 4 of 16 patients, a decrease of the Localized Scleroderma Damage Index occurred. In all seven patients with cheek involvement, mean tragus-nose distance difference decreased (mean decrease 1.09 cm). We did not observe any significant clinical side effects. Conclusion: In this first bigger pediatric case series, the mean facial lesion volume increased around 50% after a mean of three interventions at 25 months of follow-up. No flares of the underlying disease were noted. Autologous fat grafting is a promising method to improve the cosmetic appearance of those patients.

An “On Demand” canakinumab regimen for treating children with Colchicine-Resistant familial Mediterranean fever – A multicentre study

ObjectivesCanakinumab, a human monoclonal antibody targeted at interleukin-1 beta, has demonstrated safety and efficacy in preventing familial Mediterranean fever (FMF) attacks among individuals with colchicine-resistant (crFMF). The manufacturer orders prescribe monthly subcutaneous injections. However, a subset of our patients is treated with an “canakinumab on demand ” (COD) strategy, with wider intervals between drug administrations. Therefore, we aimed to compare disease activity and drug safety between COD and “canakinumab fixed frequency” (CFF) policies. MethodsThis retrospective study collected data from three Israeli paediatric rheumatology centres, of children with crFMF who were treated with canakinumab. Epidemiological and clinical parameters, cumulative drug dosages, and adverse events were compared between children treated by both policies. ResultsTwenty-five (49 %) children were treated according to COD policy and 26 according to CFF policy. Demographic parameters and most of the disease features did not differ significantly between the groups. Both groups showed significant reduction in attacks after canakinumab introduction. The median number (interquartile range) of attacks per month did not differ significantly between the COD and CFF groups (0.33 (0.08, 0.58) and 0.13 (0, 0.5), respectively, p = 0.485 (even though, per definition, COD patients presumably had an attack before receiving the second canakinumab dose). The mean monthly dose was lower for the COD than the CFF group (1.13 ± 1.13 vs. 3.16 ± 1.46 mg/kg, p < 0.001). Adverse events were similar between the groups. ConclusionFor individuals with crFMF, COD compared to CFF policy can achieve similar efficacy and safety, with a lower accumulated canakinumab dose, rendering it less immunosuppressive and less expensive.

Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study

ObjectivesTo investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it.MethodsPregnant women with different ARD were enrolled for up to 20 gestational weeks...

Real-Life Experience of Safety Profile of a Rituximab Biosimilar (Reditux®) in Patients at a Rheumatology Center in India

Abstract Aim: The aim of this study was to study the safety profile of a rituximab (RTX) biosimilar Reditux® in patients of rheumatological disorders at a tertiary care hospital in North India. Methodology: An observational study was carried out to ascertain the safety of RTX in rheumatology patients. A total of 60 patients initiated on RTX were followed up for a mean duration of 14 months for adverse events. Results: A total of seven mild infusion reactions were recorded during the first infusion of RTX. Eighteen infective events were recorded including a case of extrapulmonary tuberculosis (TB), three cases of hepatitis B virus (HBV) reactivation, four cases of herpes zoster, and a fatal case of disseminated varicella infection. There were no cases of JC virus infection or malignancies in our study. Conclusion: This study highlights a much higher incidence of infections following the use of RTX in India as compared to international studies published so far. We also observed a higher rate of reactivation of HBV, varicella zoster virus, and TB in our cohort. This emphasizes the need for revising protocols for screening, vaccination, and chemoprophylaxis for chronic infections in countries with high burden of infections.

Self-Reported Symptoms of Depression, Anxiety, and Stress Among Patients with Rheumatic Diseases Reported at Rheumatology Centres: A Study of Prevalence and Correlation

Background: The intersection of rheumatic diseases with psychological factors such as stress, resilience, and social support plays a crucial role in shaping the quality of life for patients. Understanding these dynamics is essential for developing holistic care strategies that address both the physical and psychological aspects of arthritis. Objective: This study aims to explore the prevalence of stress, resilience, and social support among patients with arthritis and examine their correlation with life satisfaction. Methods: A total of 58 male and female arthritis patients aged 18 to 90 were selected from three hospitals in Faisalabad, Punjab, Pakistan, using a stratified random sampling technique. Descriptive statistics were used to analyse socio-demographic variables. The Perceived Stress Scale (PSS), Life Satisfaction Scale (LSS), Resilience Scale (RS), and the Multidimensional Scale of Perceived Social Support (MSPSS) assessed psychological factors. Pearson correlation, t-tests, and regression analyses were conducted using SPSS version 25 to explore relationships among variables and the mediation effect of resilience between stress, social support, and life satisfaction. Results: The mean scores for perceived stress (M = 23.31, SD = 5.67), life satisfaction (M = 43.60, SD = 8.28), resilience (M = 74.15, SD = 11.42), and social support (M = 46.32, SD = 18.69) were calculated. Gender differences were non-significant for stress and resilience. Correlation analysis revealed a significant negative relationship between perceived stress and life satisfaction (r = -.339, p &lt; .01), while resilience showed a strong positive correlation with social support (r = .621, p &lt; .01). Regression analysis highlighted that resilience did not significantly mediate the relationship between perceived stress and life satisfaction (ΔR² = .02), nor between social support and life satisfaction (ΔR² = .006). Conclusion: The study underscores the profound impact of psychological factors on the quality of life in arthritis patients. While stress negatively affects life satisfaction, resilience and social support emerge as crucial for enhancing well-being. These findings advocate for integrated psychological interventions in arthritis management to improve patient outcomes.

Investigation Few Biomarkers for Pantoea Infection with Systemic Lupus Erythematosus Patients

Background: Systemic lupus erythematosus (SLE) is a disease known as systemic lupus erythematosus. SLE is an autoimmune condition in which the immune system attacks the body’s own tissues, leading to extensive tissue damage and inflammation in other organs. One of the most frequent causes of death and morbidity in SLE patients is infection. Patients with SLE may contract a genus of gram-negative bacteria called Pantoea. This study aims to find biomarkers for Pantoea infection in SLE patients in Iraq’s Najaf Governorate. Methods: About 60 individuals with systemic lupus erythematosus from Al-Sader Medical City in Al-Najaf Province had blood samples taken at a specialized rheumatology and nephrology center between September 2022 and February 2023. Some bio-markers has been evaluated. Results: The results of microbiological analyses indicate that 26/60 samples contain bacteria. Pantoea was discovered in 3 (11.6%) of the 26 specimens. Despite SLE, increased autoantibody levels in patients. The results of this analysis indicate a significant decrease in Hb, WBC, and platelet levels. In contrast to the control group, the serum levels of CD69, IL-21, and IL-35 increased significantly. Conclusion: Pantoea produces elevated diagnostic and immunological parameters in SLE patients. Consequently, it is necessary to conduct assays to identify bacterial infections in patients, with a significant increase in CD69, IL-21, and IL-35 in the event that SLE patients are infected with bacteria.

Economic evaluation of a trial exploring the effects of a web-based support tool for parents of children with juvenile idiopathic arthritis.

To explore the cost-effectiveness of a web-based support tool for parents of children with Juvenile idiopathic arthritis. A multi-centred randomized controlled trial was conducted in paediatric rheumatology centres in England. The WebParC intervention consisted of online information about JIA and its treatment and a toolkit using cognitive-behavioural therapy principles to support parents manage their child's JIA. An economic evaluation was performed alongside the trial involving 220 parents. The primary outcome was the self-report Pediatric Inventory for Parents measure of illness-related parenting stress, with two dimensions: difficulty and frequency. These measures along with costs were assessed post intervention at 4 and 12 months. Costs were calculated for healthcare usage using a UK NHS economic perspective. Data was collected and analysed on the impact of caring costs on families. Uncertainty around cost-effectiveness was explored using bootstrapping and cost-effectiveness acceptability curves. The intervention arm showed improved average Pediatric Inventory for Parents scores for the dimensions of frequency and difficulty, of 1.5 and 3.6 respectively at 4 months and 0.35 and 0.39 at 12 months, representing improved PIP scores for the intervention arm. At both 4 and 12 month follow-up, the average total cost per case was higher in the control group when compared with the intervention arm with mean differences of £360 (95% CI £29.6 to £691) at 4 months and £203 (95% CI £16 to £390) at 12 months. The probability of the intervention being cost-effective ranged between 49% and 54%. The WebParC intervention led to reductions in primary and secondary healthcare resource use and costs at 4 and 12 months. The intervention demonstrated particular savings for rheumatology services at both follow-ups. Future economies of scale could be realised by health providers with increased opportunities for cost-effectiveness over time. ISRCTN, ISRCTN13159730.

Evaluation of diagnostic and therapeutic delay in patients with rheumatoid arthritis and psoriatic arthritis

Objective. A monocentric cross-sectional study recruiting rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients residing in the Lazio region, Italy, to assess factors related to diagnostic delay and treatment accessibility. Methods. Clinical/serological data, including the time between symptom onset, diagnosis, and the beginning of treatment, were collected. Residence, referral to a rheumatologic center, physician who made the diagnosis, and previous misdiagnosis were also evaluated. Results. A higher diagnostic delay (p=0.003), and time between symptom onset and the start of I-line therapy (p=0.006) were observed in PsA compared to RA. A delayed start of II-line therapy was observed in RA compared to PsA (p=0.0007). Higher diagnostic delay (p=0.02), and time between symptom onset and the start of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (p=0.02) were observed among residents of small-medium cities for both groups. Patients who have been diagnosed by another physician rather than a rheumatologist had a longer diagnostic delay (p=0.034) and a delayed start of I-line therapy (p=0.019). Patients who received a different previous diagnosis experienced greater diagnostic delay (p=0.03 and p=0.003) and time of start of csDMARDs (p=0.05 and p=0.01) compared with those receiving RA or PsA as the first diagnosis. PsA had a delay in starting targeted synthetic disease-modifying anti-rheumatic drugs (p=0.0004) compared to RA. Seronegative RA had delayed diagnosis (p=0.02) and beginning of therapies (p=0.03; p=0.04) compared to seropositive ones. Conclusions. According to our results, greater diagnostic delay was found in PsA compared to RA, in patients living in small-medium cities, in those who did not receive the diagnosis from a rheumatologist, in those who were previously misdiagnosed, and in seronegative RA.

The prevalence, epidemiological characteristics and mortality trends of inflammatory myopathies patients in Oman: the Prevision study.

This research aims to investigate the prevalence, epidemiological characteristics, mortality rates, survival rates and the rate of malignancy in patients diagnosed with inflammatory myopathies (IIM) in Oman. This is a longitudinal study, that covered a span of 16 years at eight rheumatology centres in Oman. The study included all adults and paediatric patients diagnosed with different types of idiopathic inflammatory myopathies (IIM) and who fulfil either the Bohan classification criteria or the 2017 EULAR/ACR classification criteria. The study included a total of 116 patient with an average age of 38.78 (±17.61 SD) years. The most prevalent form of myositis was found to be dermatomyositis (DM) 48 (41.38%), followed by polymyositis (PM) 36 (31.03%) and juvenile myositis (JDM) 18(15.52%). However, inclusion body myositis and necrotising myopathy were relatively rare conditions. The prevalence rates for DM, PM and JDM were determined as 2.2, 2.2, and 1.14 per 100,000 population respectively. Cardiac complications were observed in 14.66% of cases. Among the individuals studied, a history of malignancy was present in around 1.72% of cases. ANA antibodies were present in 71.55% of the cases, anti-Jo 1 and anti-RNP/SM antibodies were detected in 8.62%, and Anti-Ro antibodies in 24.14%. The overall mortality rate was found to be 6.90% with a rate of 11.1% among JDM cases. The five-year survival rates for PM, DM and JDM were found to be 94.4%, 91.7% and 89.0% respectively. These rates decline over a 10-year period to 67%, 69% and 83.3% respectively. The study highlights the prevalence, mortality, and survival rates of IIM in Oman. Patients with JDM had a higher mortality rate. This underscores the significance of using novel healthcare strategies to improve clinical outcomes and meet special requirements for this group of patients.

Clinical and Genetic Spectrum of Nine Cases of NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) and Identification of One Novel NLRP3 Mutation by Genetic Variation Analyses.

NLRP3-associated autoinflammatory disease (NLRP3-AID) is characterized by gain-of-function variants in the NLRP3 gene. Since there are little literature focusing on pediatric NLRP3-AID in China, we aimed to elucidate the phenotypic and genotypic profiles of Chinese patients with NLRP3-AID. Patients with NLRP3-AID at three rheumatology centers in China were genotyped through whole exome sequencing or gene panel sequencing. Sanger sequencing was performed on all patients and their parents. Clinical phenotype, treatment, and prognosis were analyzed. Nine patients with NLRP3-AID were enrolled between December 2014 and October 2022 with an average follow-up period exceeding 30 months. The median age of onset was 12 months, and 66.7% were younger than 3 years old. The diagnosis was significantly delayed and the median delay duration was 115 months. The patients most commonly presented with rash (100%), arthritis/arthralgia (88.9%), lymphadenopathy (88.9%), fever (77.8%), and growth retardation (44.4%). During acute attack, white blood cell, C-reactive protein, and/or erythrocyte sedimentation rate all increased in all cases, and inflammatory markers remained elevated beyond 7 days postfever resolution in 57.1% of patients (4/7). Two cases of chronic infantile neurological cutaneous articular syndrome (CINCA) had clubbed fingers, one with interstitial lung disease, a finding rarely reported. Treatment with glucocorticoids (77.8%) and biologic agents (33.3%) yielded 66% complete remission and 33% partial remission. Genetic analysis identified eight pathogenic NLRP3 missense mutations, including one novel mutation. Our study illuminated the distinct clinical and genetic features of Chinese NLRP3-AID patients, emphasizing the significance of early genetic screening. Despite delayed diagnosis, treatment primarily with glucocorticoids and biologic agents, led to favorable outcomes. Genetic heterogeneity, including a novel mutation, highlighted the complexity of NLRP3-AID in this population.

Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis on anti-interleukin-1 or -6 therapy.

The aim of this study is to investigate the effect of anti-interleukin (IL)-1/-6 biologics on systemic juvenile idiopathic arthritis (sJIA)-associated macrophage activation syndrome (MAS). Demographic, clinical, and laboratory data of patients followed up with a diagnosis of sJIA-associated MAS assessed from sixteen pediatric rheumatology centers across the country. The clinical and laboratory features of MAS developing while on biological drugs were compared with those without this treatment. One hundred and sixty-two patients were included in the study. 45 of the MAS events were detected under the effect of anti-IL-1/-6 biologics, while the patients experiencing the remaining 155 events have not received biological treatment in the last three months. Platelet count [128 (72-232) vs 199 (130-371) 109/l], ferritin level on admission [1107 (676-2050) vs 2863 (1193-9562) ng/ml], C-reactive protein level [15.4 (2.9-56) vs 90 (32-160) mg/l], erythrocyte sedimentation rate [13 (3-36) vs 43.5 (13-77) mm/h] and fever duration [5 (4-7.5) vs 10 (7-14.3) days] were found lower in the group under the impact of anti-IL-1/-6 biologics. Among patients treated with biologics, 26.6% did not meet the published 2016 MAS classification criteria at presentation. The rates of hepatomegaly and splenomegaly were relatively lower in the canakinumab-treated group when compared with those receiving other biologicals or to patients, not on biologicals. Anti-IL-1/-6 therapies can mask the clinical and laboratory features of MAS, and proposed guidelines for MAS classification criteria may not be met.

ROLE OF URIC ACID IN CLINICAL MANIFESTATIONS OF ANKYLOSING SPONDYLITIS

Prevalence of ankylosing spondylitis (AS) is about 0.2–0.8% and increasing during last decades in Russia. Coronary Heart Disease (CHD) plays an important role in mortality in patients with rheumatic diseases. AS mainly affects able-bodied age persons thus having a significant social and economic impact. There plenty of biomarkers of AS, including those for early diagnosis. Purpose. To study the level of uric acid (UA) in patients with AS and its role in development of AS. Materials and methods. A total of 72 medical charts of patients hospitalized at Smolensk Regional Rheumatological Center were evaluated, among them 73.6% were men and 26.4% – women. AS was diagnosed according to classification criteria. Lab tests were done in a central lab using standard methodology. All data collected for each patient was entered into an Excel spreadsheet and analyzed. Results. Average patients age was 49.6±12.4 years. BMI was 28.1±5.4 kg/m2. Arterial Hypertension (AH) and CHD was diagnosed in 44.4% of patients. Glomerular Filtration Rate (GFR) was 95.1±21.9 mL/min. UA concentration were equal to 301.3±94.3 mmol/L, total cholesterol (TC) – 5.0±1.0 mmol/L, CRP – 60.5±35.1 IU/L. A direct correlation between CRP and BMI was revealed (p&lt;0.005). UA concentration in patients with AS and CHD was 347.3±73.9 mmol/L, while in patients with AS without CHD it was significantly lower: 261.8±77.4 mmol/L (p&lt;0,001). UA concentration in patients with AS and HLA-B27(+) was 345.1±90.8 mmol/L, in patients with AS and HLA-B27(-) – 259.1±75.1 mmol/L (p&lt;0,001). BASDAI in patients with AS was equal to 5.7±2.1. UA concentration in patients with mild to moderate AS was 255.4±77.7 mmol/L; severe AS – 343.4±75.3 mmol/L (p&lt;0.001). Correlations between TC level and BASDAI (p&lt;0.05) as well as between UA level and BASDAI (p&lt;0.05) were revealed. Conclusion. In patients with AS increased level of UA supports inflammation activity, forces subjective symptoms of the disease (pain), correlates with disease activity and BASDAI. Hyperuricemia increases risk of CHD, worsens prognosis of AS. UA may be considered as a biomarker of disease activity and prognosis of AS, atherosclerosis and cardiovascular diseases

10-year experience of early arthritis clinic at a tertiary rheumatology center: achievements and challenges.

To characterize patients evaluated in our Early Arthritis Clinic (EAC) in the first ten years; to assess diagnostic delay and its underlying causes; and to evaluate the level of agreement between the referring physician and the rheumatologist regarding the presence of referral criteria. Cross-sectional study including patients attending EAC between 2012 and 2021. Demographic data, provenience, final diagnosis, referral criteria and time related to diagnosis delay were retrieved from clinical files and the Portuguese Registry of Rheumatic Patients (reuma.pt). Characteristics of the patients and the time variables were analysed with descriptive statistical analysis. The agreement between the referring physician and rheumatologist regarding the referral criteria was evaluated using Cohen's Kappa. A total of 440 patients (68.9% females, mean age of 54±16.7 years) were referred, mostly from primary care (71.6%). Inflammatory Rheumatic Disease was diagnosed in 65.7% of the patients, with 58.9% classified as early arthritis. The median time from onset of symptoms to referral for EAC was 76 days (IQR 33.5-144.0); the median time from referral to the first EAC was 34 (IQR 19.0-46.0) days, and the median time from onset of symptoms to first EAC was 114.5 (IQR 66.8-190.3) days (16.3 weeks). Only about 10% were observed by a Rheumatologist before six weeks after symptom onset. The level of agreement between the referring physician and the rheumatologist was slight to fair to clinical criteria and moderate to substantial to laboratory criteria. A significant delay still is observed in patients with early arthritis suspicion, being the time from onset of symptoms to referral is the most relevant. A low agreement between referral and Rheumatologists suggests that non-rheumatologists education/training is needed. Identifying the barriers that prevent the adequate referral of patients is necessary to define strategies to improve it.