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Objectives To describe the clinical features and treatment outcomes of children with juvenile psoriatic arthritis (JPsA) and compare the distinct patterns of the disease between early-onset and late-onset age groups. Methods Patients with JPsA followed regularly for at least 6 months between 2010 and 2020 in seven paediatric rheumatology centres in Turkey were included in the study. The demographic features, clinical manifestations, treatment strategies and outcomes of the patients were evaluated retrospectively. Results A total of 87 (46 male/41 female) patients were included in the study. The mean age at diagnosis was 11.9 years (s. d. 4.5). Fifty-seven (65.5%) patients had psoriasis at the time of diagnosis and arthritis preceded psoriasis in 10 (11.5%) patients. Thirty (34.5%) patients had dactylitis, 28 (32.2%) had nail pitting, 36 (41.4%) had involvement of the small joints and 20 (23%) had enthesitis. Sacroiliitis was detected in 11 (12.6%) patients by MRI. ANA was positive in 35 (40.2%) patients. Twelve children (13.8%) were in the early-onset (<5 years) group. Uveitis and ANA positivity were more common in the early-onset group. Active joint counts and activity scores of our patients showed significant improvement at month 6 and at the last control compared with baseline. Conclusion About one-third of patients with JPsA do not have psoriasis at the time of diagnosis. In some patients, no skin lesion is seen during the course of the disease. Children with PsA seem to display two different phenotypes. Younger children have a female predominance, ANA positivity and uveitis, while older children have more axial involvement. [ABSTRACT FROM AUTHOR]

Objective To develop a machine learning-based prediction model for identifying hyperuricemic participants at risk of developing gout. Methods A retrospective nationwide Israeli cohort study used the Clalit Health Insurance database of 473 124 individuals to identify adults 18 years or older with at least two serum urate measurements exceeding 6.8 mg/dl between January 2007 and December 2022. Patients with a prior gout diagnosis or on gout medications were excluded. Patients' demographic characteristics, community and hospital diagnoses, routine medication prescriptions and laboratory results were used to train a risk prediction model. A machine learning model, XGBoost, was developed to predict the risk of gout. Feature selection methods were used to identify relevant variables. The model's performance was evaluated using the receiver operating characteristic area under the curve (ROC AUC) and precision-recall AUC. The primary outcome was the diagnosis of gout among hyperuricemic patients. Results Among the 301 385 participants with hyperuricemia included in the analysis, 15 055 (5%) were diagnosed with gout. The XGBoost model had a ROC-AUC of 0.781 (95% CI 0.78–0.784) and precision-recall AUC of 0.208 (95% CI 0.195–0.22). The most significant variables associated with gout diagnosis were serum uric acid levels, age, hyperlipidemia, non-steroidal anti-inflammatory drugs and diuretic purchases. A compact model using only these five variables yielded a ROC-AUC of 0.714 (95% CI 0.706–0.723) and a negative predictive value (NPV) of 95%. Conclusions The findings of this cohort study suggest that a machine learning-based prediction model had relatively good performance and high NPV for identifying hyperuricemic participants at risk of developing gout. [ABSTRACT FROM AUTHOR]

Objective To evaluate the risk of end-stage kidney disease (ESKD) in LN patients using tubulointerstitial lesion scores. Methods Clinical profiles and histopathological presentations of 151 biopsy-proven LN patients were retrospectively examined. Risk factors of ESKD based on characteristics and scoring of their tubulointerstitial lesions [e.g. interstitial inflammation (II), tubular atrophy (TA) and interstitial fibrosis (IF)] were analysed. Results The mean age of 151 LN patients was 36 years old, and 136 (90.1%) were female. The LN cases examined included: class I/II (n  = 3, 2%), class III/IV (n  = 119, 78.8%), class V (n  = 23, 15.2%) and class VI (n  = 6, 4.0%). The mean serum creatinine level was 1.4 mg/dl. Tubulointerstitial lesions were recorded in 120 (79.5%) patients. Prior to receiving renal biopsy, nine (6.0%) patients developed ESKD. During the follow-up period (mean, 58 months), an additional 47 patients (31.1%) progressed to ESKD. Multivariate analyses identified serum creatinine [hazard ratio (HR): 1.7, 95% CI: 1.42–2.03, P   <  0.001] and IF (HR: 3.2, 95% CI: 1.58–6.49, P   =  0.001) as independent risk factors of ESKD. Kaplan–Meier analysis further confirmed a heightened risk of ESKD associated with IF. Conclusion Tubulointerstitial involvement is commonly observed in the histopathological presentation of LN. However, IF, rather than II or TA, was found to increase the risk of ESKD in our cohort. Therefore, to predict renal outcome in LN patients prior to adjusting immunosuppressive treatment, the degree of IF should be reviewed. [ABSTRACT FROM AUTHOR]

Objectives Systemic sclerosis (SSc) is characterized by multiple clinical manifestations. Vasculopathy is a main disease hallmark and ranges in severity from an exacerbated Raynaud phenomenon to pulmonary arterial hypertension (PAH). The potential involvement of the immune system in SSc-associated vascular abnormalities is not clear. Here, we set out to study SSc-related immune parameters and determine whether and which peripheral T cell subsets associate with vascular severity in SSc patients. Methods Peripheral blood and clinical data were collected from 30 SSc patients, 5 patients with idiopathic PAH and 15 age and sex-matched healthy donors (HD). In this cross-sectional cohort, SSc patients with PAH (n  = 15) were matched for their age, sex and medication with SSc patients with no signs of PAH (n  = 15). Lymphocyte subsets were quantified by multi-colour flow cytometry. Results SSc patients exhibited elevated percentages of T peripheral helper cells (Tph), CD4+GZMB+ T cells and decreased levels of Th1 cells compared with HD. Increased presence of both CD4+ and CD8+ exhausted-like (CD28−) T cells, characterized by raised cytokine and cytotoxic signature, was also observed in SSc compared with HD blood. Furthermore, IL-4 expressing CD4+CD8+ T cells were significantly increased in SSc peripheral blood. Interestingly, the presence of PAH in SSc was accompanied by a distinct T helper profile, characterized by raised percentages of Th17 and Tph cells. Conclusion SSc patients with severe vasculopathy (presence of PAH) exhibited a distinct T cell profile, suggesting a potential role of auto-immune inflammation in SSc vascular complications. [ABSTRACT FROM AUTHOR]

Objectives ACPA-positive and ACPA-negative RA differ in underlying risk factors but have a similar clinical presentation at RA diagnosis. It is unknown what the ACPA-associated differences or similarities are during the symptomatic at-risk stage of RA, i.e. clinically suspect arthralgia (CSA). To deepen insights into these differences/similarities, we compared the course of symptoms/impairments and subclinical joint inflammation in the CSA phase during progression to inflammatory arthritis (IA) or to CSA resolution. Methods A total of 845 CSA patients were followed for a median of 24 months; 136 patients developed IA and an additional 355/505 patients had resolution of CSA according to rheumatologists. Patient burden (pain, morning stiffness, fatigue, functional disabilities, presenteeism) was assessed at baseline and 4, 12 and 24 months and at IA development. Subclinical joint inflammation in the hands and feet was assessed over time with 1.5T MRI. Linear and Poisson mixed models were used. Results In both ACPA-positive and ACPA-negative patients, patient burden increased towards IA development and decreased towards CSA resolution. However, patient burden was lower in ACPA-positive vs ACPA-negative disease at all timepoints. Conversely, subclinical joint inflammation tended to increase more rapidly during development of ACPA-positive IA [incidence rate ratio (IRR) 1.52 (95% CI 0.94, 2.47), P  = 0.089] and remained higher over time in ACPA-positive CSA patients achieving resolution compared with ACPA-negative patients [IRR 1.52 (95% CI 1.07, 2.15), P  = 0.018]. Although correlation coefficients between changes in patient burden and subclinical joint inflammation during progression to IA were weak, they were consistently higher in ACPA-positive than ACPA-negative disease, e.g. ρ = 0.29 vs 0.12 for functional disabilities. Conclusion During RA development and CSA resolution, ACPA-positive CSA patients have lower patient burden but more subclinical joint inflammation than ACPA-negative CSA patients. These data strengthen the notion that the development of ACPA-positive and ACPA-negative RA is pathophysiologically different and encourage further research on these differences. [ABSTRACT FROM AUTHOR]

Objective Familial aggregation of systemic autoimmune diseases is frequently reported, but little is known about how fathers and mothers differentially contribute to the development of autoimmune diseases in their offspring. This study aimed to investigate the impact of maternal and paternal autoimmunity on the risk of offspring rheumatic diseases. Methods We constructed a nationwide population-based cohort using data from the Maternal and Child Health Database and the Taiwan National Health Insurance Research Data (NHIRD) from 2004 to 2019. The outcome was presence of an autoimmune disease in the offspring. Inverse probability of treatment–weighted Cox models were used to estimate adjusted hazard ratios (aHRs) and 95% CIs for autoimmune diseases. Results Babies born to a father or mother with an autoimmune disease had, respectively, 1.22 times and 1.38 times the risk of developing an autoimmune disease compared with their counterparts with no parental autoimmune diseases. Maternal autoimmunity substantially contributed to the risk of SLE (aHR = 5.46, 95% CI: 5.28–5.66), and paternal autoimmunity contributed to the risk of JIA (aHR = 1.76, 95% CI: 1.71–1.81) and of type 1 diabetes mellitus (aHR = 1.59, 95% CI: 1.39–1.81) in their offspring. The contributions of mothers to the risk of development of SLE (aHR = 8.55, 95% CI: 8.10–9.02) and inflammatory myopathy (aHR = 2.08, 95% CI: 1.72–2.51) in their offspring were exacerbated in boys. Babies of two parents with an autoimmune disease showed a 1.39-fold risk of developing an autoimmune disease. The maternal contribution effect was stronger for preterm births than for full-term births. Conclusion This study demonstrated broadly how autoimmune diseases pass from parents to infants of both genders and separately quantified the maternal and paternal contributions to disease. [ABSTRACT FROM AUTHOR]

Objectives To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations and malignancy, between adults with anti-synthetase syndrome (ASyS) and DM. Methods Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1γ/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron's papules/sign, violaceous rash, shawl sign, V-sign, erythroderma, and/or periorbital rash). Results In total 1054 patients were included (DM, n  = 405; ASyS, n  = 649). In the ASyS cohort, 31% (n  = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic's hands, Raynaud's phenomenon, arthritis, interstitial lung disease and cardiac involvement differentiated ASyS-DMskin from DM (all P  < 0.001), whereas higher frequency of any of four DM-type rashes—heliotrope rash (n  = 248, 61% vs n  = 90, 44%), violaceous rash (n  = 166, 41% vs n  = 57, 9%), V-sign (n  = 124, 31% vs n  = 28, 4%), and shawl sign (n  = 133, 33% vs n  = 18, 3%)—differentiated DM from ASyS-DMskin (all P  < 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n  = 67, 17%) compared with ASyS (n  = 21, 3%) and ASyS-DMskin (n  = 7, 3%) cohorts (both P  < 0.001). Conclusion DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management. [ABSTRACT FROM AUTHOR]

Objective Patients with secondary RP show a wide range of symptoms depending on the condition of vascular structures. If the symptoms are localized to specific fingers and angiography reveals a discrete segment of occlusion of a proper digital artery, we perform proper digital artery reconstruction with an interposition vein graft. The objective of this study was to evaluate the results of the surgery in patients with chronic hand ischaemia. Methods A retrospective chart review was performed on patients who underwent proper digital artery reconstruction. Each digit that underwent grafting was analysed separately. The results of surgical intervention and recurrence based on patient symptoms were evaluated. Cox proportional hazards regression models were used to identify independent risk factors associated with recurrence, and the Kaplan–Meier method was used to predict the 5-year recurrence-free rate. Results A total of 79 digits from 57 patients were included in this study. The majority of patients demonstrated resolution of ischaemic pain and ulceration (97.5% and 95.3%, respectively). Recurrence occurred in 16 (20.3%) patients during the follow-up period. In two cases (2.5%) surgery had no effect. In the multivariate Cox regression analysis, smoking and concomitant periarterial sympathectomy were significant factors associated with recurrence. In the Kaplan–Meier analysis, the 5-year recurrence-free rate in the total study population was 69.3%. Conclusions Digital artery reconstruction using an interposition vein graft is an effective procedure for improving ischaemic pain and ulceration in patients with RP. Smoking and concomitant periarterial sympathectomy were significantly associated with recurrence. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to assess the incidence and risk factors of major adverse cardiovascular events (MACEs) in patients with systemic sclerosis (SSc). Methods We conducted a nationwide, population-based, cohort study using Taiwan's National Health Insurance Research Database. We performed propensity score matching (PSM) using a 1:2 ratio, resulting in inclusion of 1379 patients with SSc and 2758 non-SSc individuals in the analysis. We assessed the association between SSc and MACEs, using the multivariable Cox proportional hazard regression model with adjustment of time-dependent covariates, and investigated risk factors for MACEs in patients with SSc, shown as adjusted hazard ratios (aHRs) with 95% CIs. Results SSc was not significantly associated with the risk of MACEs (aHR 1.04; 95% CI 0.77–1.42). Nevertheless, SSc was associated with increased risk of myocardial infarction [incidence rate ratio (IRR) 1.76; 95% CI 1.08–2.86] and peripheral arterial occlusion disease (IRR 3.67; 95% CI 2.84–4.74) but not of ischaemic stroke (IRR 0.89; 95% CI 0.61–1.29). Factors independently associated with MACEs in SSc patients included age (aHR 1.02), male gender (aHR 2.01), living in a suburban area (aHR 2.09), living in a rural area (aHR 3.00), valvular heart disease (aHR 4.26), RA (aHR 2.14), use of clopidogrel (aHR 26.65), and use of aspirin (aHR 5.31). Conclusions The risk of MACEs was not significantly increased in Taiwanese patients with SSc, and our investigation effectively identified the factors independently associated with MACEs in SSc patients. Additionally, patients with SSc exhibited higher risks of myocardial infarction and peripheral arterial occlusion disease but not of ischaemic stroke. [ABSTRACT FROM AUTHOR]

Objectives Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (MDA5+) dermatomyositis patients exhibit a variety of clinical features. We therefore investigated whether patterns of B-cell epitope recognition are linked to the clinical course of MDA5+ dermatomyositis. Methods Our cross-sectional study used ELISA-based methods to determine the relationship between antibody recognition of overlapping 155 amino acid MDA5 subfragments and clinical features of 24 MDA5+ myositis patients. Correlations between clinical features and standardized anti-MDA5 subfragment antibody titres were assessed via Spearman's rank correlation coefficients. Results Twenty-four MDA5+ patients submitted serum samples within a median of 0 (interquartile range, 0–74) days from the initial clinic visit. In addition to typical dermatomyositis rashes, these patients exhibited muscle symptoms (n  = 11), vascular dysfunction (n  = 9) and interstitial lung disease (ILD) (n  = 16). Female patients exhibited higher titres of antibodies recognizing fragment H (aa 905–1026) compared with male patients. Muscle involvement was associated with higher levels of anti-fragment F (aa 646–801) antibody. Conversely, patients with vascular abnormalities had higher anti-fragment B (aa 130–284) and E (aa 517–671) antibody titres than those without vascular dysfunction. Four patients died due to ILD progression and showed higher anti-fragment A (aa 1–155) antibody titres than the other 20 patients. Differences in the ratio of anti-fragment to anti-full-length MDA5 antibody titres were found for sex (H: anti-MDA5) and vascular dysfunction (anti-fragment B, E: anti-MDA5). Conclusions Various clinical features of MDA5+ dermatomyositis correlated with levels of antibodies targeting selected subfragments of this autoantigen, providing a link between fragment-specific immune responses and disease course. [ABSTRACT FROM AUTHOR]

Objective Patients with RA treated with Janus kinase inhibitors (JAKis) are at increased risk of herpes zoster (HZ). The objective of this study was to investigate the serological immunogenicity and safety of the HZ subunit (HZ/su) vaccine in RA patients treated with JAKi, for which little is known. Methods RA patients treated with JAKi (n  = 82) at the Department of Rheumatology, Skåne University Hospital, Lund and Malmö, Sweden, and healthy controls (n  = 51) received two doses of the HZ/su vaccine (Shingrix). Vaccine-specific antibody responses were analysed using indirect ELISA. Post-vaccination antibody levels were compared between patients and controls using analysis of covariance. Potential predictors for vaccine response were investigated using a multivariable linear regression analysis. Self-reported adverse events (AEs) and changes in RA disease activity were analysed. Results Following vaccination, vaccine-specific antibody levels increased significantly in both patients and controls (P  < 0.0001). A total of 80.5% of patients and 98.0% of controls achieved a ≥4-fold increase in antibody levels. Post-vaccination antibody levels were lower in patients than controls [ratio 0.44 (95% CI 0.31, 0.63)] and lower in patients receiving JAKi + methotrexate than JAKi monotherapy [ratio 0.43 (95% CI 0.24, 0.79)]. AEs, mostly mild/moderate, were common. One patient developed HZ and six patients (6.5%) had increased RA disease activity following vaccination. Conclusion The HZ/su vaccine was serologically immunogenic in most RA patients treated with JAKi. Moreover, the vaccine had an acceptable safety profile. These results support recommendations for use of the HZ/su vaccine in this vulnerable population. Trial registration ClinicalTrials.gov (https://clinicaltrials.gov), NCT03886038. [ABSTRACT FROM AUTHOR]

Objectives To quantify associations of serum alarmins with risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Methods Using serum collected at enrolment, three alarmins (IL-33, thymic stromal lymphopoietin [TSLP] and IL-25) were measured in a multicentre prospective RA cohort. ILD was classified using systematic medical record review. Cross-sectional associations of log-transformed (IL-33, TSLP) or quartile (IL-25) values with RA-ILD at enrolment (prevalent RA-ILD) were examined using logistic regression, while associations with incident RA-ILD developing after enrolment were examined using Cox proportional hazards. Covariates in multivariate models included age, sex, race, smoking status, RA disease activity score and anti-cyclic citrullinated antibody positivity. Results Of 2835 study participants, 115 participants (4.1%) had prevalent RA-ILD at baseline and an additional 146 (5.1%) developed incident ILD. There were no associations between serum alarmin concentrations and prevalent ILD in unadjusted or adjusted logistic regression models. In contrast, there was a significant inverse association between IL-33 concentration and the risk of developing incident RA-ILD in unadjusted (hazard ratio [HR] 0.73 per log-fold increase; 95% CI: 0.57, 0.95; P  = 0.018) and adjusted (HR 0.77; 95% CI: 0.59, 1.00; P  = 0.047) models. No significant associations of TSLP or IL-25 with incident ILD were observed. Conclusion In this study, we observed a significant inverse association between serum IL-33 concentration and the risk of developing incident RA-ILD, but no associations with prevalent ILD. Additional investigation is required to better understand the mechanisms driving this relationship and how serum alarmin IL-33 assessment might contribute to clinical risk stratification in patients with RA. [ABSTRACT FROM AUTHOR]

Objective To describe the frequency of progressive pulmonary fibrosis (PPF) in an incident cohort of systemic sclerosis (SSc)-related interstitial lung disease (ILD) and its impact on survival. Methods Incident ILD was defined as the new development of characteristic fibrotic changes on chest HRCT scan. PPF was defined as per the 2022 American Thoracic Society. Determinants of PPF were identified using generalised estimating equations. Impact on survival was analysed using accelerated failure time regression modelling. Results Of our incident SSc-ILD cases, 38.8% (n  = 180) experienced PPF within a 12-month period after ILD diagnosis. Determinants of PPF included older age (OR 1.02, 95%CI 1.00–1.03, P  = 0.011), dcSSc (OR 1.54, 95% CI 1.06–2.25, P  = 0.024) and SSc-specific antibodies (anticentomere antibody OR 0.51, 95%CI 0.29–0.91, P  = 0.021 and anti-Scl-70 antibody OR 1.46, 95%CI 1.01–2.09, P  = 0.043). Raised CRP was numerically associated with PPF but did not reach statistical significance (OR 1.29, 95%CI 0.99–1.68, P  = 0.064) nor did GORD or dysphagia (OR 1.18, 95%CI 0.57–2.42, P  = 0.658 and OR 1.17, 95%CI 0.57–2.40, P  = 0.664, respectively). The presence of PPF significantly impacted survival in SSc-ILD (hazard ratio 2.66, 95%CI 1.59–4.41, P  < 0.001). Conclusions PPF occurred in a third of our incident SSc-ILD cohort; however, its occurrence was significantly associated with mortality indicating an at-risk group who may be suitable for earlier introduction of immunosuppressive and/or antifibrotic therapy. [ABSTRACT FROM AUTHOR]

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

Lupus enteritis (LE) is a rare manifestation of systemic lupus erythematosus. The pathophysiology of LE has not been fully elucidated, although inflammatory and thrombotic processes are likely important factors. The underlying pathophysiological mechanisms may depend on which portion of the intestine is affected. Over half of the patients with LE also present with renal or haematological complications. The diagnosis of LE is based on clinical, histopathological and imaging findings; abdominal computed tomography (CT) is the gold standard in diagnosis. Abdominal CT can also identify factors that predict complications and could potentially guide pharmacological and nutritional management. Timely identification and prompt treatment initiation are paramount to avoid life and organ threatening complications. Glucocorticoids are often the first-line treatment. Additional therapy including immunosuppressive therapy is utilised on a case-by-case basis as there are no clinical trials to define the optimal therapeutic approach. Surgical intervention may be needed especially if there is bowel perforation or peritonitis. In general, the prognosis of LE is good. [ABSTRACT FROM AUTHOR]

Objectives Multimorbidity is burdensome for people with RA. We investigated differences in multimorbidity and comorbidities by sex and age in the RA population. Methods This cross-sectional analysis used national administrative claims (OptumLabs ® Data Warehouse) from people with RA and non-RA comparators (matched on age, sex, race, census region, index year and length of baseline insurance coverage) from 2010–2019. RA was determined using a validated algorithm. Multimorbidity was defined as ≥2 (MM2+) or ≥5 (MM5+) comorbidities from a validated set of 44 chronic conditions. We used logistic regression to assess associations between characteristics and multimorbidity. Results The sample included 154 391 RA patients and 154 391 non-RA comparators. For people aged 18–50 years, RA women (vs RA men) had 7.5 and 4.4 (vs 3.2 and 0.9 in non-RA women vs non-RA men) percentage point increases for MM2+ and MM5+, respectively. For people aged 51+ years, RA women (vs RA men) had 2.1 and 2.5 (vs 1.2 and 0.3 in non-RA women vs non-RA men) percentage point increases for MM2+ and MM5+, respectively. Interactions revealed that differences in multimorbidity between women and men were exacerbated by RA (vs non-RA) (P  < 0.05), with more pronounced effects in people aged 18–50. Men had more cardiovascular-related conditions, whereas RA women had more psychological, neurological and general musculoskeletal conditions. Other comorbidities varied by sex and age. Conclusion Multimorbidity disproportionately impacts women with RA. Research, clinical and policy agendas for rheumatic diseases should acknowledge and support the variation in care needs by sex and gender across the lifespan. [ABSTRACT FROM AUTHOR]

Objectives To investigate the hypothesis that a history of PMR is associated with a more severe and damaging disease course in newly diagnosed GCA patients. Methods This was a retrospective analysis of GCA patients diagnosed between December 2006 and May 2021. We compared vascular ultrasound findings (presence of vasculitis and vascular stenosis) in GCA patients with and without prior PMR. Results Forty-nine of 311 GCA patients (15.8%) had prior PMR in a median of 30.6 (IQR 7.1–67.3) months before GCA diagnosis. Patients with prior PMR more often had large vessel vasculitis (LVV) (51.0% vs 25.0%, P  < 0.001) and stenosis within the vasculitic segments (18.4% vs 3.1%, P  < 0.001) on ultrasound. In multivariable analysis, prior PMR remained significantly associated with LVV (odds ratio 7.65, 95% CI: 2.72, 23.97, P  < 0.001). Polymyalgic symptoms at GCA diagnosis in the patients without prior PMR were not associated with a higher prevalence of LVV (P  = 0.156). Conclusion Patients with a diagnosis of PMR before GCA diagnosis had two times more often large vessel involvement and significant more vasculitic stenoses on ultrasound examination than patients without prior PMR. Pre-existing PMR is an independent risk factor for more extensive and advanced ultrasound findings at GCA diagnosis. The contribution of subclinical vasculitis to disease associated damage should be further studied. [ABSTRACT FROM AUTHOR]

Objective To evaluate differences in nailfold videocapillaroscopy (NVC) findings between SSc patients with and without a diagnosis of pulmonary arterial hypertension (PAH). Methods One hundred and ten SSc patients were enrolled in this cross-sectional, case–control, multicentre study. Patients were divided into cases (SSc-PAH confirmed by right heart catheterization) and controls (SSc-nonPAH with low probability of PAH). NVC patterns (early, active and late) and morphological parameters (microvascular density, non-specific abnormalities, giant capillaries, micro-haemorrhages, avascular areas) were considered using a semiquantitative scoring system. Results SSc-PAH patients showed higher frequencies of late pattern (P  < 0.01), non-specific abnormalities (P  < 0.01), lower capillary density (P  < 0.01), higher avascular areas (P  < 0.01) and a higher mean NVC score (P  < 0.01). Contrarily, the early/active pattern (P  < 0.01) and a higher rate of micro-haemorrhages (P  = 0.04) were more frequent in non-PAH patients. By a multivariate analysis, SSc-PAH patients, compared with non-PAH, had more non-specific abnormalities [27/55, 49.1% vs 10/55, 18.2%; adjusted odd ratio (OR) 16.89; 95% CI: 3.06, 93.16], a lower capillary density (grade 3, 20/55, 36.4% vs 5/55, 9.1%; adjusted OR 38.33; 95% CI: 2.34, 367.80) and avascular areas (18/55, 32.7% vs 10/55, 18.2%; adjusted OR 16.90; 95% CI: 2.64, 44.35). A correlation was found between the mean pulmonary arterial pressure and avascular areas (P  < 0.01), capillary density (P  < 0.01) and non-specific abnormalities (P  < 0.01). A clinical model including the NVC variables may be able to predict a diagnosis of PAH. Conclusion Our results indicate that the distinctive peripheral microcirculatory injury of SSc, i.e. capillary loss and morphological abnormalities, appear more severe and pronounced in patients with SSc-PAH. [ABSTRACT FROM AUTHOR]

Objective This study aimed to establish prediction models for respiratory-related mortality in microscopic polyangiitis (MPA) complicated by interstitial lung disease (ILD) using clinical characteristics. Methods We enrolled patients with MPA with ILD between May 2005 and June 2021 in a multicentre cohort of Japanese patients with MPA (REVEAL cohort). We evaluated the demographic, clinical, laboratory, radiological findings, treatments and the presence of honeycombing 1 cm above the diaphragm using chest high-resolution CT (HRCT) on admission. We explored the risk factors predictive of respiratory-related mortality. Results Of 115 patients, 26 cases died of respiratory-related diseases during a median follow-up of 3.8 years. Eighteen patients (69%) died due to respiratory infection, three (12%) had diffuse alveolar haemorrhage, and five (19%) had exacerbation of ILD. In univariate analysis, older age, lower percent forced vital capacity (%FVC), lower percent diffusing capacity of carbon monoxide (%DLCO), and the presence of honeycombing in the right lower lobe were identified as risk factors. Additionally, in multivariate analysis adjusted for age and treatment, %FVC, %DLCO and the presence of honeycombing in the right lower lobe were independently associated with respiratory-related mortality. We created prediction models based on the values of %FVC, %DLCO and presence of honeycombing on chest HRCT (termed "MPF model"). The 5-year respiratory-related death-free rate was significantly different between patients with MPA with ILD stratified by the number of risk factors based on the MPF model. Conclusions Our study indicates that the MPF model may help predict respiratory-related death in patients with MPA with ILD. [ABSTRACT FROM AUTHOR]

Objectives APS-associated heart valve disease (HVD) is well described. Nonetheless, limited data exist on clinical parameters associated with the course of primary APS (pAPS) patients with HVD. The goal of this study was to assess clinical features and related outcomes in patients with APS-associated HVD. Methods In this multicentre retrospective study, we identified 33 pAPS patients with HVD (pAPS-HVD group) and compared their clinical course with 128 pAPS patients with normal heart valves on echocardiography (pAPS-control group). Results pAPS-HVD patients had more cerebrovascular events (56.3% vs 25%, P  = 0.005) and livedo reticularis (24.2% vs 7.8%, P  = 0.013) than pAPS-controls. Furthermore, catastrophic-APS (CAPS) (12.1% vs 2.4%, P  = 0.034), recurrent thrombosis (33.3% vs 4.7%, P  < 0.001) and need for advanced therapy (i.e. IVIG, plasmapheresis or rituximab) were more frequent in pAPS-HVD patients. Anti-β2-glycoprotein 1 IgG (84.8% vs 63.2%, P  = 0.034), anti-cardiolipin IgG (90.9% vs 64.8%, P  = 0.005) and triple positive aPL (75.8% vs 56.5%, P  = 0.047) were commoner in pAPS-HVD patients vs pAPS-controls. Ten of the 33 patients with pAPS-HVD underwent valve surgery, which was associated with male gender, smoking, arterial limb ischaemia and livedo reticularis. Conclusion pAPS-HVD patients had a more severe APS clinical course including CAPS and thrombotic events as well as a specific serology, namely IgG isotype aPL antibodies and triple positivity. Our data suggest that pAPS-HVD represents a high-risk subgroup of APS patients. [ABSTRACT FROM AUTHOR]

Objective To evaluate the prevalence of clinical and US (grey-scale and Doppler) abnormalities in joints, periarticular structures and nails of children affected by skin psoriasis (PsO). Methods We conducted a cross-sectional study including consecutive children affected by PsO. A systematic clinical and US evaluation of joints, entheses, tendons and nails were performed by independent examiners blinded to each other's assessment. Results A total of 57 children [26 girls (46%)] with a mean age of 9 years (s. d. 4) were divided into two groups, asymptomatic (Asy, 42 children) and symptomatic (Sy, 15 children), according to musculoskeletal pain. Differences were observed between the two groups in relation to age [9 years (s. d. 3) vs 11 years (s. d. 4), P  < 0.05], PsO duration [2.4 years (s. d. 2.4) vs 5.4 years (s. d. 3.9), P  < 0.001], systemic treatment [23 (54.8%) vs 2 [13.3%], P  < 0.01], tender joint count [0 vs 12 children (80%), P  < 0.001], swollen joint count [0 vs 3 children (20%), P  < 0.01] and entheseal pain [0 vs 10 (66.7%), P  < 0.001] in Asy and Sy children, respectively. US evaluation showed statistically significant differences between the Asy and Sy groups for the presence of US abnormalities [16/42 (38%) vs 12/15 (80%)], synovitis [1/42 (2%) vs 4/15 (25%)] and enthesitis [4/42 (9.5%) vs 5/15 (33%)]. Three children in the Sy group were classified with juvenile PsA (JPsA). Conclusions US abnormalities were higher in the Sy group, with synovitis and enthesitis as the most prevalent findings. Asy patients were more frequently under systemic treatment. US and a systematic clinical evaluation are useful tools for detecting subclinical JPsA in children with PsO and musculoskeletal symptoms. [ABSTRACT FROM AUTHOR]

Objectives Frailty is a risk factor for adverse health in SLE. The Fried phenotype (FP) and the SLICC Frailty Index (SLICC-FI) are common frailty metrics reflecting distinct approaches to frailty assessment. We aimed to (1) compare frailty prevalence according to both metrics in women with SLE and describe differences between frail and non-frail participants using each method and (2) evaluate for cross-sectional associations between each metric and self-reported disability. Methods Women aged 18–70 years with SLE were enrolled. FP and SLICC-FI were measured, and agreement calculated using a kappa statistic. Physician-reported disease activity and damage, Patient Reported Outcome Measurement Information System (PROMIS) computerized adaptive tests, and Valued Life Activities (VLA) self-reported disability were assessed. Differences between frail and non-frail participants were evaluated cross-sectionally, and the association of frailty with disability was determined for both metrics. Results Of 67 participants, 17.9% (FP) and 26.9% (SLICC-FI) were frail according to each metric (kappa = 0.41, P  < 0.01). Compared with non-frail women, frail women had greater disease damage, worse PROMIS scores, and greater disability (all P  < 0.01 for FP and SLICC-FI). After age adjustment, frailty remained associated with a greater odds of disability [FP: odds ratio (OR) 4.7, 95% CI 1.2, 18.8; SLICC-FI: OR 4.6, 95% CI 1.3, 15.8]. Conclusion Frailty is present in 17.9–26.9% of women with SLE. These metrics identified a similar, but non-identical group of women as frail. Further studies are needed to explore which metric is most informative in this population. [ABSTRACT FROM AUTHOR]

Objective We investigated the incidence of and risk factors for myelodysplastic syndrome (MDS) in patients with rheumatologic disease. Methods We conducted a retrospective cohort study of patients who were diagnosed with rheumatologic diseases at a tertiary care hospital between May 2009 and July 2022 and identified the patients who were subsequently diagnosed with MDS. Each patient with MDS was matched with five age- and sex-matched controls chosen from the cohort of patients with each specific rheumatologic disease. Results During a total follow-up of 55 841 person-years (PY), MDS occurred in 64 patients, yielding an incidence rate of 1.15/1000 PY {median age 57.0 years [interquartile range (IQR) 41.0–69.0], median duration to MDS diagnosis 6.5 years (IQR 3.0–9.0)]. In an age-matched analysis, SLE was a significant risk factor for MDS [adjusted hazard ratio 2.61 (CI 1.19, 36.06), P  = 0.01]. Refractory cytopenia with multilineage dysplasia was the most common phenotype of MDS (35.9%), and more than half of the patients had karyotypes with a favourable prognosis (54.7%). Compared with matched controls, RA, SLE and AS patients with MDS had lower levels of haemoglobin at the time of diagnosis of rheumatologic disease. Furthermore, the MDS patients with SLE and Behçet's disease had higher levels of glucocorticoid use in terms of frequency of use and mean dose than control patients. Conclusion SLE is a significant risk factor for MDS among patients with rheumatologic diseases. A lower haemoglobin level at the time of diagnosis of rheumatologic disease was associated with the future development of MDS. [ABSTRACT FROM AUTHOR]

Objective To examine whether patients with ANCA-associated vasculitis (AAV) have an increased risk of cardiovascular disease in the months prior to diagnosis of AAV. Methods Using a nested case–control framework, patients with granulomatosis with polyangiitis and microscopic polyangiitis were identified through the Danish Nationwide Registries from 1996 to 2021 and matched 1:3 with age- and sex-matched controls without AAV. Each control was assigned the same index date (date of AAV diagnosis) as their corresponding case. Conditional logistic regression was used to compute adjusted hazard ratios (HRs) for major adverse cardiovascular events (MACE), ischaemic heart disease, coronary angiogram, heart failure, venous thromboembolism, atrial fibrillation, ischaemic stroke, pericarditis and ventricular arrhythmias/implantable cardioverter defibrillator implantation/cardiac arrest (VA/ICD/CA) within 12 months, 6 months, 3 months, 2 months and 1 month before index date. Results A total of 2371 patients with AAV (median age 63 years, 53.7% male) were matched with 7113 controls. The prevalence of any cardiovascular outcome and MACE within 12 months preceding index date were 10.3% and 2.4% for AAV, compared with 3.8% [HR 3.05 (95% CI 2.48–3.75)] and 1.3% [HR 1.98 (95% CI 1.39–2.82)] of controls. The risk of cardiovascular outcomes was similarly increased in temporal proximity to the diagnosis, with the highest HR at 1 month prior to index date: any cardiovascular outcome [HR 10.73 (95% CI 7.05–16.32)] and MACE [HR 5.78 (95% CI 2.67–12.52)]. In individual analysis, a significantly higher rate was observed for all outcomes (excluding VA/ICD/CA). Conclusions AAV disease is associated with an increased risk of cardiovascular disease in the months preceding diagnosis, which underlines the importance of early clinical vigilance towards cardiovascular disease. [ABSTRACT FROM AUTHOR]

Objectives Assessment of construct validity and reliability of a novel patient-reported outcome (PRO) instrument for assessing the severity and impact of RP in SSc. Methods An international multicentre study validation study of the 27-item Assessment of Systemic Sclerosis-Associated Raynaud's Phenomenon (ASRAP) and 10-item short-form (ASRAP-SF) questionnaires. The relationship between ASRAP questionnaires and demographics, clinical phenotype and legacy instruments for assessing SSc-RP severity, disability and pain was assessed. Repeatability was evaluated at 1 week. Anchor-based statements of health status facilitated assessment of ASRAP thresholds of meaning. Results A total of 420 SSc subjects were enrolled. There was good correlation between ASRAP (and ASRAP-SF) with RP visual analogue scale (VAS) and Scleroderma Health Assessment Questionnaire RP VAS (rho range 0.648–0.727, P  < 0.001). Correlation with diary-based assessment of SSc-RP attack frequency and duration was lower (rho range 0.258–0.504, P  < 0.001). ASRAP questionnaires had good correlation with instruments for assessing disability, hand function, pain and global health assessment (rho range 0.427–0.575, P  < 0.001). Significantly higher ASRAP scores were identified in smokers, patients with active digital ulceration (DU), previous history of DU and calcinosis (P  < 0.05 for all comparisons). There was excellent repeatability at 1 week among patients with stable SSc-RP symptoms (intra-class coefficients of 0.891 and 0.848, P  < 0.001). Patient-acceptable symptom state thresholds for ASRAP and ASRAP-SF were 45.34 and 45.77, respectively. A preliminary Minimally Important Clinical Difference threshold of 4.17 (95% CI 0.53, 7.81, P  = 0.029) was estimated. Conclusion ASRAP and ASRAP-SF questionnaires are valid and reliable novel PRO instruments for assessing the severity and impact of SSc-RP. [ABSTRACT FROM AUTHOR]

Objectives Juvenile PsA (JPsA) has varied clinical features that are distinctive from other JIA categories. This study investigates whether such features impact patient-reported and clinical outcomes. Methods Children and young people (CYP) were selected if recruited to the Childhood Arthritis Prospective Study, a UK multicentre JIA inception cohort, between January 2001 and March 2018. At diagnosis, patient/parent-reported outcomes (as age-appropriate) included the parental global assessment (10 cm visual analogue scale), functional ability (Childhood Health Assessment Questionnaire (CHAQ)), pain (10 cm visual analogue scale), health-related quality of life (Child Health Questionnaire PF50 psychosocial score), mood/depressive symptoms (Moods and Feelings Questionnaire) and parent psychosocial health (General Health Questionnaire 30). Three-year outcome trajectories have previously been defined using active joint counts, physician and parent global assessments (PGA and PaGA, respectively). Patient-reported outcomes and outcome trajectories were compared in (i) CYP with JPsA vs other JIA categories and (ii) CYP within JPsA, with and without psoriasis via multivariable linear regression. Results There were no significant differences in patient-reported outcomes at diagnosis between CYP with JPsA and non-JPsA. Within JPsA, those with psoriasis had more depressive symptoms (coefficient = 9.8; 95% CI: 0.5, 19.0) than those without psoriasis at diagnosis. CYP with JPsA had 2.3 times the odds of persistent high PaGA than other ILAR categories, despite improving joint counts and PGA (95% CI: 1.2, 4.6). Conclusion CYP with psoriasis at JPsA diagnosis report worse mood, supporting a greater disease impact in those with both skin and joint involvement. Multidisciplinary care with added focus to support wellbeing in children with JPsA plus psoriasis may help improve these outcomes. [ABSTRACT FROM AUTHOR]

Objectives Pulmonary hypertension (PH) is a leading cause of death in patients with SSc. The purpose of this study was to determine the prognostic significance of pericardial effusion in patients with SSc-PH. Methods Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) is a prospective multicentre registry which enrolled patients with newly diagnosed SSc-PH from 2005 to 2016. The prognostic impact of pericardial effusion status, including those who ever or never had pericardial effusion, and those who had persistent or intermittent pericardial effusion, was analysed. Kaplan–Meier survival analyses, log-rank test, and multivariable Cox proportional hazards regression were performed. Results Of the 335 patients with SSc-PH diagnosed by right heart catheterization and documentation of pericardial effusion presence or absence on echocardiogram, 166 (50%) ever had pericardial effusion. Ever having pericardial effusion was not predictive of survival (log-rank test P  = 0.49). Of the 245 SSc-PH patients who had at least two echocardiograms, 44% had a change in pericardial effusion status over an average of 4.3 years of follow up. Having a persistent pericardial effusion was an independent predictor of survival [adjusted hazard ratio (aHR)=2.34, 95% CI 1.20, 4.64, P  = 0.002], while intermittent pericardial effusion was not a predictor of survival (aHR = 0.89, 95% CI 0.52, 1.56, P  = 0.68), in a multivariable-adjusted analysis. Conclusion Persistent pericardial effusion, but not ever having had pericardial effusion or intermittent pericardial effusion, was independently associated with poorer survival. Incorporating information from serial echocardiograms may help clinicians better prognosticate survival in their SSc-PH patients. [ABSTRACT FROM AUTHOR]

Background Lung ultrasound (LUS) is a promising tool for detecting SSc-associated interstitial lung disease (SSc-ILD). Currently, consensus on the best LUS findings and execution technique is lacking. Objectives To compare qualitative and quantitative assessment of B-lines and pleural line (PL) alterations in SSc-ILD with chest CT analysis. Methods During 2021–2022, consecutive SSc patients according to 2013 ACR/EULAR classification criteria underwent pulmonary functional tests (PFTs). On the same day, if a CT was performed over a ± 6 months period, LUS was performed by two certified blinded operators using a 14-scans method. The ≥10 B-lines cut-off proposed by Tardella and the Fairchild's PL criteria fulfilment were selected as qualitative findings. As quantitative assessment, total B-lines number and the quantitative PL score adapted from the semi-quantitative Pinal-Fernande z score were collected. CT scans were evaluated by two thoracic radiologists for ILD presence, with further processing by automated texture analysis software (QCT). Results Twenty-nine SSc patients were enrolled. Both qualitative LUS scores were significantly associated to ILD presence on CT, with Fairchild's PL criteria resulting in slightly more accuracy. Results were confirmed on multivariate analysis. All qualitative and quantitative LUS findings were found to be significantly associated with QCT ILD extension and radiological abnormalities. Mid and basal PL quantitative score correlated with mid and basal QCT ILD extents. Both B-lines and PL alterations differently correlated with PFTs and clinical variables. Conclusion This preliminary study suggests the utility of a comprehensive LUS assessment for SSc-ILD detection compared with CT and QCT. [ABSTRACT FROM AUTHOR]

Objectives In a cross-sectional study, we explored possible differences in sleep parameters between SLE patients and age- and gender-matched healthy controls through actigraphic and self-reported measures. Furthermore, we aimed to identify possible predictors of such disturbances in the patient cohort. Methods Participants' sociodemographic data and sleep parameters were collected. Sleep parameters were evaluated through the Pittsburgh Sleep Quality Index, the Insomnia Severity Index and 7-day actigraphic monitoring. The 10-item Perceived Stress Scale was used to investigate stress. Disease activity and daily glucocorticoid dose were assessed in SLE patients. Possible predictors of the SLE group were explored through two binomial logistic models. Within the SLE group, possible predictors of sleep parameters were tested estimating multiple linear regression models. Results A total of 40 SLE patients and 33 controls were included in the study. The SLE group showed worse sleep maintenance actigraphic parameters (i.e. sleep efficiency and wake after sleep onset), higher total sleep time and higher perceived stress. Within the SLE cohort, the daily glucocorticoids dose was associated with an impairment in sleep maintenance despite no reduction in sleep duration, typical of normal sleep duration insomnia, whereas perceived stress was associated with short sleep duration insomnia. Conclusion Compared with healthy controls, SLE patients showed worse sleep quality and greater perceived stress severity. As glucocorticoids and perceived stress are associated with different types of insomnia in these patients, a multidimensional approach to both sleep characterization and therapy might be preferred. [ABSTRACT FROM AUTHOR]

Objectives Fibrotic interstitial lung disease (ILD) is a progressive lung disease characterized by loss of lung volume, resulting in a leading cause of death in patients with RA. Crucially, acute exacerbation (AE) of ILD shows higher morbidity and mortality with rapid deterioration of the lungs. However, a quantitative assessment for physiological changes at AE has yet to be performed. This study hypothesized that quantitative assessments of lung volume (LV) accurately indicate disease severity and mortality risk in patients with AE-RA-ILD. Methods This multicentre cohorts study quantitatively assessed physiological changes of RA-ILD at diagnosis (n  = 54), at AE (discovery-cohorts; n  = 20, and validation-cohort; n  = 33), and controls (n  = 35) using 3D CT (3D-CT) images. LV was quantitatively measured using 3D-CT and standardized by predicted forced vital capacity. Results Patients with RA-ILD at diagnosis showed decreased LV, predominantly in lower lobes, compared with controls. Further substantial volume loss was found in upper- and lower lobes at AE compared with those at diagnosis. During AE, decreased standardized 3D-CT LV was associated with a worse prognosis in both cohorts. Subsequently, standardized 3D-CT LV was identified as a significant prognostic factor independent of age, sex and the presence of UIP pattern on CT by multivariate analyses. Notably, a composite model of age and standardized 3D-CT LV successfully classified mortality risk in patients with AE-RA-ILD. Conclusion Volume loss at AE in patients with RA-ILD was associated with increased mortality. Assessing physiological change using standardized 3D-CT might help evaluate disease severity and mortality risk in patients with AE-RA-ILD. [ABSTRACT FROM AUTHOR]

Objectives Patients with SLE have an increased risk of comorbidities and impaired survival. We aimed to assess whether various thresholds of oral CS (OCS) can predict development of infections, comorbidities, malignancies and survival in SLE using data from national health registries in Sweden. Methods All incident SLE cases, age >18 years, in Sweden (n  = 5309) between 2005 and 2020 and matched population controls (n  = 26 545) were included and followed until 2020, a total of 257 942 patient years. Data from national registers were retrieved including information from the National Prescribed Drug Register. Risk factors were analysed using time-dependent Cox regression models. Results Compared with no OCS, >0 to <5.0 mg/day, 5.0–7.5 mg/day as well as >7.5 mg/day OCS predicted development of infections (pneumonia, influenza, herpes zoster and urinary tract infection), osteoporosis, osteonecrosis, gastroduodenal ulcers, cataracts, hypertension and mortality (all P  < 0.05). OCS >0 to <5.0 mg/day was associated with lower hazard ratios for these comorbidities than higher doses of OCS. Fifteen years after diagnosis, 48% of patients were taking OCS at a median dose of 5.7 mg/day. A small reduction of OCS treatment 5 years after diagnosis in patients diagnosed with SLE 2006–10 compared with 2011–15 was observed, 49% vs 46% respectively (P  = 0.039). Conclusion Results highlight the potential harm associated with even low OCS dose treatment in SLE and the need to judiciously use OCS at the lowest possible dose to maximize efficacy and minimize harm. [ABSTRACT FROM AUTHOR]

Objective The rate of pleuroparenchymal involvement in patients with SpA varies widely, from 0% to 85%. The most common form is apical fibrobullous disease (AFLD). The aim of this study was to determine the incidence of AFLD and associated factors in SpA patients under and/or planned to start biologic DMARDs (bDMARDs) therapy. Methods The records of 3021 SPA patients registered with HUR-BIO who had indication of bDMARDs between 2010 and 2021 were scanned. The study included 2489 patients with at least one chest radiograph (X-ray). Patient demographics, comorbidities, laboratory data, bDMARDs used, baseline DASs, and purified protein derivative and/or QuantiFERON test results before initiation of bDMARDs were recorded. Results Of the 2489 patients, 36 (1.4%) were found to have AFLD by X-ray and/or CT. The mean disease duration was 11.7 (7.1) years. Patients with AFLD were more likely to be male [28 (77.8%) vs 1321 (53.9%), P  = 0.004], older [56.3 (10.5) years vs 44.8 (11.4) years, P  < 0.001], heavy smokers [27 (79.4%) vs 1468 (60.9%), P  = 0.028] and have had longer disease duration [17. 7 (9.7) years vs 11.6 (7) years, P  = 0.001]. QuantiFERON positivity was higher in the AFLD group [9 (36%) vs 309 (16.1%), P  = 0.013]. While treatment with adalimumab was less preferred in those with AFLD, treatment with etanercept was more frequently preferred. Conclusion As the radiological findings of AFLD can be confused with those of tuberculosis, special attention should be paid to differentiating between tuberculosis and the disease in males and in patients who have had long disease duration. [ABSTRACT FROM AUTHOR]

Objectives To investigate the association between periodontal disease and the development of inflammatory arthritides in the general population. Methods In total, 489 125 participants from the UK Biobank without a previous history of RA, AS and PsA were enrolled. The primary outcome was the incidence of inflammatory arthritides, which was a composite of RA, AS and PsA according to the presence of periodontal disease based on self-reported oral health indicators. Multivariate Cox proportional hazard regression analyses using four different models were performed to assess the association between periodontal disease and inflammatory arthritides development. Results In all, 86 905 and 402 220 individuals were categorized as with and without periodontal disease, respectively. Cox hazard analysis indicated that the presence of periodontal disease was an independent predictor of the occurrence of composite outcomes of inflammatory arthritides, which was also consistent for RA and AS. Significant associations were found to be consistent in the four Cox models and were replicated even when different criteria were used to define periodontal disease. Subgroup analyses indicated that periodontal disease was associated with an increased RA risk in those aged <60 years, and this risk was persistent for both male and female patients and for patients with seropositive/seronegative RA. Conclusion Self-reported periodontal disease is associated with inflammatory arthritides incidence in participants included in the UK Biobank, particularly for RA and AS. Higher clinical attention and optimal dental care in patients with signs of periodontal disease may be recommended for early disease detection and for reducing this risk. [ABSTRACT FROM AUTHOR]

Objective The presence of anti-U1 RNP antibodies (Abs) is critical for diagnosing MCTD. The aim of this study is to evaluate the clinical relevance of anti-survival motor neuron (SMN) complex Abs, which often coexist with anti-U1 RNP Abs. Methods A total of 158 newly diagnosed consecutive cases of SLE, SSc or MCTD with anti-U1 RNP Abs were enrolled in this multicentre observational study between April 2014 and August 2022. Serum anti-SMN complex Abs were screened by immunoprecipitation of 35S-methionine-labelled cell extracts, and associations between anti-SMN complex Abs positivity and clinical characteristics were analysed. Results Anti-SMN complex Abs were detected in 36% of MCTD patients, which was significantly higher than that in SLE (8%) or SSc (12%). Among MCTD patients classified based on the combination of the clinical features of SLE, SSc and idiopathic inflammatory myopathies, anti-SMN complex Abs showed the highest prevalence in a subset with clinical features of all three components. Anti-SMN complex Abs–positive MCTD had a higher prevalence of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), which are related to poor prognosis, than negative patients. Moreover, all three cases of death within 1 year of the treatment were positive for anti-SMN complex Abs. Conclusions Anti-SMN complex Abs is the first biomarker of a typical subset of MCTD which bears organ damages such as PAH and ILD. [ABSTRACT FROM AUTHOR]

Objective Interstitial lung disease (ILD) is the leading cause of mortality in SSc. Novel biomarkers are crucial to improve outcomes in SSc-ILD. We aimed to compare the performance of potential serum biomarkers of SSc-ILD that reflect different pathogenic processes: KL-6 and SP-D (epithelial injury), CCL18 (type 2 immune response), YKL-40 (endothelial injury and matrix remodelling) and MMP-7 (ECM remodelling). Methods Baseline and follow-up serum samples from 225 SSc patients were analysed by ELISA. Progressive ILD was defined according to the 2022-ATS/ERS/JRS/ALAT guidelines. Linear mixed models and random forest models were used for statistical analyses. Results Serum levels of KL-6 [MD 35.67 (95% CI 22.44–48.89, P  < 0.01)], SP-D [81.13 (28.46–133.79, P  < 0.01)], CCL18 [17.07 (6.36–27.77, P  < 0.01)], YKL-40 [22.81 (7.19–38.44, P  < 0.01)] and MMP-7 [2.84 (0.88–4.80, P  < 0.01)] were independently associated with the presence of SSc-ILD. A machine-learning model including all candidates classified patients with or without ILD with an accuracy of 85%. The combination of KL-6 and SP-D was associated with the presence [0.77 (0.53–1.00, P'  <0.01)] and previous progression of SSc-ILD [OR 1.28 (1.01–1.61, P'  =0.047)]. Higher baseline levels of KL-6 [OR 3.70 (1.52–9.03, P  < 0.01)] or SP-D [OR 2.00 (1.06–3.78, P  = 0.03)] increased the odds of future SSc-ILD progression, independent of other conventional risk factors, and the combination of KL-6 and SP-D [1.109 (0.665–1.554, P  < 0.01)] showed improved performance compared with KL-6 and SP-D alone. Conclusion All candidates performed well as diagnostic biomarkers for SSc-ILD. The combination of KL-6 and SP-D might serve as biomarker for the identification of SSc patients at risk of ILD progression. [ABSTRACT FROM AUTHOR]

Objectives We aimed to examine the impact of concomitant interstitial lung disease (ILD) on achieving clinical remission and the occurrence of unfavourable clinical events in patients with RA. Methods Among the participants in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort from 2011 to 2012, patients not achieving remission of 28-joint disease activity score (DAS28) at baseline and those with chest CT images were enrolled. Based on the chest CT images, the patients were divided into two groups: the ILD group and non-ILD group. The associations among the presence of ILD with time to achieving DAS28 remission and development of death, hospitalized infection, major adverse cardiac events (MACE), or malignancy within 5 years were evaluated using time-dependent Cox regression models. Results We enrolled 287 patients in the ILD group and 1235 in the non-ILD group. DAS28 remission was achieved at least once in 55.7% and 75.0% of the ILD and non-ILD groups within 5 years, respectively. Presence of ILD was significantly associated with failure to achieve DAS28 remission (adjusted hazard ratio [aHR]: 0.71; 95% CI: 0.58, 0.89). ILD was also a significant factor associated with death (aHR: 3.24; 95% CI: 2.08, 5.03), hospitalized infection (aHR 2.60; 95% CI: 1.77, 3.83), MACE (aHR: 3.40; 95% CI: 1.76, 6.58), and lung cancer (aHR: 16.0; 95% CI: 3.22, 79.2), but not with malignant lymphoma (aHR: 2.27; 95% CI: 0.59, 8.81). Conclusion Concomitant ILD was a significant factor associated with failure to achieve clinical remission and the occurrence of the unfavourable clinical events in patients with RA. [ABSTRACT FROM AUTHOR]

Objectives OA is characterized by cartilage degeneration and persistent pain. The majority of OA patients present with synovitis, which is associated with increased cartilage damage. Activated synovial macrophages are key contributors to joint destruction. Therefore, a marker that reflects the activation of these cells could be a valuable tool to characterize the destructive potential of synovitis and benefit monitoring of OA. Here, we aimed to investigate the use of CD64 (FcγRI) as a marker to characterize the damaging potential of synovitis in OA. Methods Synovial biopsies were obtained from end-stage OA patients that underwent joint replacement surgery. CD64 protein expression and localization was evaluated using immunohistochemistry and immunofluorescence and quantified using flow cytometry. qPCR was performed to measure the expression of FCGR1 and OA-related genes in synovial biopsies, and in primary chondrocytes and primary fibroblasts stimulated with OA conditioned medium (OAS-CM). Results Our data exposed a wide range of CD64 expression in OA synovium and showed positive correlations between FCGR1 and S100A8 , S100A9 , IL1B , IL6 and MMP1/2/3/9/13 expression. CD64 protein correlated with MMP1 , MMP3 , MMP9 , MMP13 and S100A9. Furthermore, we observed that synovial CD64 protein levels in source tissue for OAS-CM significantly associated with the OAS-CM-induced expression of MMP1 , MMP3 and especially ADAMTS4 in cultured fibroblasts, but not chondrocytes. Conclusion Together, these results indicate that synovial CD64 expression is associated with the expression of proteolytic enzymes and inflammatory markers related to structural damage in OA. CD64 therefore holds promise as marker to characterize the damaging potential of synovitis. [ABSTRACT FROM AUTHOR]

Objective Acute calcium pyrophosphate (CPP) crystal arthritis is a distinct manifestation of calcium pyrophosphate crystal deposition (CPPD). No studies have specifically examined whether acute CPP crystal arthritis is associated with progressive structural joint damage. The objective of this retrospective cohort study was to evaluate the relative rate of hip and knee joint arthroplasties as an estimate of structural joint damage accrual, in a population of patients with acute CPP crystal arthritis. Methods Data were collected from Waikato District Health Board (WDHB) to identify an acute CPP crystal arthritis cohort with clinical episodes highly characteristic of acute CPP crystal arthritis. Data on hip and knee joint arthroplasties were collected from the New Zealand Orthopaedic Association's Joint Registry. The rate of arthroplasties in the cohort was compared with the age–ethnicity-matched New Zealand population. Additional analysis was performed for age, obesity (BMI) and ethnicity. Results The acute CPP crystal arthritis cohort included 99 patients; 63 were male and the median age was 77 years (interquartile range, 71–82). The obesity rate was 36% with a median BMI of 28.4 kg/m2 (interquartile range, 25.8–32.2), comparable to the New Zealand population. The standardized surgical rate ratio in the cohort vs the age–ethnicity-matched New Zealand population was 2.54 (95% CI: 1.39, 4.27). Conclusion Our study identified a considerable increase in the rate of hip and knee joint arthroplasties in patients with episodes of acute CPP crystal arthritis. This suggests CPP crystal arthritis may be a chronic condition, leading to progressive joint damage. [ABSTRACT FROM AUTHOR]

Objective Myocardial fibrosis occurs in the early subclinical stage of cardiac involvement in idiopathic inflammatory myopathies (IIMs). Soluble suppression of tumorigenicity 2 (sST2) is known to have an immunomodulatory impact during autoimmune disease development. The current study investigated the diagnostic value of sST2 for myocardial fibrosis during early stage of cardiac involvement in IIM. Methods A total of 44 IIM patients with normal heart function and 32 age- and gender-matched healthy controls (HCs) were enrolled. Serum sST2 levels were measured by ELISA and cardiac magnetic resonance (CMR) parameters for myocardial fibrosis [native T1, extracellular volume (ECV), late-gadolinium enhancement (LGE)] and oedema (T2 values) were analysed. Results IIM patients had significantly higher sST2 levels than HCs [67.5 ng/ml (s. d. 30.4)] vs 14.4 (5.5), P  < 0.001] and levels correlated positively with diffuse myocardial fibrosis parameters, native T1 (r = 0.531, P  = 0.000), ECV (r = 0.371, P  = 0.013) and focal myocardial fibrosis index and LGE (r = 0.339, P  = 0.024) by Spearman's correlation analysis. sST2 was an independent predictive factor for diffuse and focal myocardial fibrosis after adjustment for age, gender, BMI and ESR. Risk increased ≈15.4% for diffuse [odds ratio (OR) 1.154 (95% CI 1.021, 1.305), P  = 0.022] and 3.8% for focal [OR 1.038 (95% CI 1.006, 1.072), P  = 0.020] myocardial fibrosis per unit increase of sST2. Cut-off values for diagnosing diffuse and focal myocardial fibrosis were sST2 ≥51.3 ng/ml [area under the curve (AUC) = 0.942, sensitivity = 85.7%, specificity = 98.9%, P  < 0.001] and 53.3 ng/ml (AUC = 0.753, sensitivity = 87.5%, specificity = 58.3%, P  < 0.01), respectively. Conclusion sST2 showed a marked elevation during the subclinical stage of cardiac involvement in IIM and has potential as a biomarker for predicting diffuse and focal myocardial fibrosis in IIM. [ABSTRACT FROM AUTHOR]

The article discusses a multi-center cohort study which investigated predictors of myositis in systemic sclerosis (SSc). Topics discussed include the demographic and clinical characteristics of SSc patients with and without myositis, the screening for myositis with heart and lung involvement, and independent predictors of myositis including male sex and oesophageal involvement.

The article discusses a study which investigated the risk for pulmonary hypertension (PH) in Behçet's disease patients with Budd-Chiari syndrome. Topics discussed include the clinical characteristics of Behçet's disease patients with BCS, the results of transthoracic echocardiogram, and possible causes of PH in Behçet's disease.

The article describes the case of a 32-year-old Japanese woman of inborn good health who experienced fever and EBV viremia. Topics discussed include findings on laboratory tests, the hospital admission of the patient at the age of 35 years becuase of dyspnea and pancytopenia, and her death 68 days after admission, despite intensive care.

The article describes the first case of microvascular colonic ischaemia suspected to represent systemic sclerosis (SSc)-associated microscopic vasculopathy of the gastrointestinal tract that responded to iloprost without any other identifiable secondary causes. Topics discussed include medical history of the patient, medical procedures done to investigate her symptoms, and role of therapies targeting the microvasculature.

The article explores studies on the safety of immunosuppression as a treatment for gastrointestinal (GI) diseases in patients with systemic sclerosis (SSc). Topics discussed include the challenges in treating GI complications of SSc, the importance of the timing and application of immune modulating/suppressive therapies in such patients, and the use of abatacept for the treatment of chronic intestinal pseudo-obstruction in SSc patients.

Local and systemic low-grade inflammation, mainly involving the innate immune system, plays an important role in the development of OA. A receptor playing a key role in initiation of this inflammation is the pattern-recognition receptor Toll-like receptor 4 (TLR4). In the joint, various ligands for TLR4, many of which are damage-associated molecular patterns (DAMPs), are present that can activate TLR4 signalling. This leads to the production of pro-inflammatory and catabolic mediators that cause joint damage. In this narrative review, we will first discuss the involvement of TLR4 ligands and signalling in OA. Furthermore, we will provide an overview of methods for inhibit, TLR4 signalling by RNA interference, neutralizing anti-TLR4 antibodies, small molecules and inhibitors targeting the TLR4 co-receptor MD2. Finally, we will focus on possible applications and challenges of these strategies in the dampening of inflammation in OA. [ABSTRACT FROM AUTHOR]

Objective Accumulating evidence from microbial studies have highlighted the modulatory roles of intestinal microbes in numerous human diseases, however, the shared microbial signatures across different diseases remain relatively unclear. Methods To consolidate existing knowledge across multiple studies, we performed meta-analyses of 17 disease types, covering 34 case–control datasets of 16S rRNA sequencing data, to identify shared alterations among different diseases. Furthermore, the impact of a microbial species, Lactobacillus salivarius , was established in a dextran sodium sulphate–induced colitis model and a collagen type II–induced arthritis mouse model. Results Microbial alterations among autoimmune diseases were substantially more consistent compared with that of other diseases (cancer, metabolic disease and nervous system disease), with microbial signatures exhibiting notable discriminative power for disease prediction. Autoimmune diseases were characterized by the enrichment of Enterococcus , Veillonella , Streptococcus and Lactobacillus and the depletion of Ruminococcus , Gemmiger , Oscillibacter , Faecalibacterium , Lachnospiracea incertae sedis , Anaerostipes , Coprococcus , Alistipes , Roseburia , Bilophila , Barnesiella , Dorea , Ruminococcus2 , Butyricicoccus , Phascolarctobacterium , Parabacteroides and Odoribacter , among others. Functional investigation of L. salivarius , whose genus was commonly enriched in numerous autoimmune diseases, demonstrated protective roles in two separate inflammatory mouse models. Conclusion Our study highlights a strong link between autoimmune diseases and the gut microbiota, with notably consistent microbial alterations compared with that of other diseases, indicating that therapeutic strategies that target the gut microbiome may be transferable across different autoimmune diseases. Functional validation of L. salivarius highlighted that bacterial genera associated with disease may not always be antagonistic, but may represent protective or adaptive responses to disease. [ABSTRACT FROM AUTHOR]

Objectives We aimed to evaluate cardiovascular (CV) risk in patients with idiopathic inflammatory myopathies (IIM) compared with healthy controls (HC) and to assess its association with disease-specific features. Methods Ninety IIM patients and 180 age-/sex-matched HC were included. Subjects with a history of CV disease (angina pectoris, myocardial infarction and cerebrovascular/peripheral arterial vascular events) were excluded. All participants were prospectively recruited and underwent examinations of carotid intima–media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition. The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE) and its modifications. Results Compared with HC, IIM patients had a significantly higher prevalence of traditional CV risk factors, carotid artery disease (CARD), abnormal ABI and PWV. After propensity score matching (using traditional CV risk factors), the prevalence of CARD and pathological PWV remained significantly higher in IIM than HC. No significant difference in SCORE was observed. The most unfavourable CV risk profile was observed in patients with necrotizing myopathy, especially in statin-induced anti-HMGCR+ patients. The calculated CV risk scores by SCORE, SCORE2 and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to CIMT and the presence of carotid plaques. SCORE was demonstrated to be most inaccurate in predicting CV risk in IIM. Age, disease activity, lipid profile, body composition parameters and blood pressure were the most significant predictors of CV risk in IIM patients. Conclusion Significantly higher prevalence of traditional risk factors and subclinical atherosclerosis was observed in IIM patients compared with HC. [ABSTRACT FROM AUTHOR]

Objective To validate the predictive value of the DAS28 γ-glutamyl transferase (DAS28-γGT) for the occurrence of major cardiovascular (CV) events (MACE) in the 'Etude et Suivi des Polyarthrites Indifférenciées Récentes' ESPOIR cohort. Methods Analysis of 13-year outcome from the ESPOIR cohort. RA patients with missing data for baseline γGT activity and those not followed-up to 1 year were excluded. Baseline DAS28-γGT was calculated using the following formula: 0.56*√TJ-28 + 0.28 * √SJ-28 + 2*ln(γGT) + 0.014 * GH. Our primary outcome was the merit of the DAS28-γGT in predicting the occurrence of MACE. Results Among the 696 patients [536 women, mean (s. d.) age of 49 (12) years], 34 MACE were recorded, with a mean time to event of 71 (44) months. Receiver operating characteristic curve analysis indicated that a DAS28-γGT >9.4 had the best sensitivity and specificity for the diagnosis of MACE during the observation period. DAS28-γGT >9.4 was predictive of the occurrence of MACE, with a hazard ratio (HR) of 3.11 (95% CI 1.41, 5.43). Multivariate Cox analyses confirmed higher DAS28-γGT (HR 2.44, 95% CI 1.05, 5.64) together with age (HR 1.04, 95% CI 1.01, 1.07) and diabetes mellitus (HR 4.12, 95% CI 1.55, 10.95) as independent predictors of MACE. There was a dose effect of the DAS28-γGT for MACE-risk prediction, which was in line with the application of the Framingham risk score. Conclusion The DAS28-γGT was identified in this large prospective cohort as an independent predictor of MACE in patients with RA. The DAS28-γGT is a simple and useful tool to evaluate CV risk in routine and warn the clinician about the CV risk burden in patients with RA. [ABSTRACT FROM AUTHOR]

Objectives Colchicine forms the mainstay of treatment in FMF. Approximately 5–10% of FMF patients are colchicine resistant and require anti-IL-1 drugs. We aimed to compare the characteristics of colchicine-resistant and colchicine-responsive patients and to develop a score for predicting colchicine resistance at the time of FMF diagnosis. Methods FMF patients (0–18 years) enrolled in the Turkish Paediatric Autoinflammatory Diseases (TURPAID) registry were included. The predictive score for colchicine resistance was developed by using univariate/multivariate regression and receiver operating characteristics analyses. Results A total of 3445 FMF patients [256 (7.4%) colchicine-resistant and 3189 colchicine-responsive) were included (female:male ratio 1.02; median age at diagnosis 67.4 months). Colchicine-resistant patients had longer, more frequent attacks and were younger at symptom onset and diagnosis (P  < 0.05). Fever, erysipelas-like erythema, arthralgia, arthritis, myalgia, abdominal pain, diarrhoea, chest pain, comorbidities, parental consanguinity and homozygosity/compound heterozygosity for exon 10 MEFV mutations were significantly more prevalent among colchicine-resistant than colchicine-responsive patients (P  < 0.05). Multivariate logistic regression analysis in the training cohort (n  = 2684) showed that age at symptom onset, attack frequency, arthritis, chest pain and having two exon 10 mutations were the strongest predictors of colchicine resistance. The score including these items had a sensitivity of 81.3% and a specificity of 49.1%. In the validation cohort (n  = 671), its sensitivity was 93.5% and specificity was 53.8%. Conclusion We developed a clinician-friendly and practical predictive score that could help us identify FMF patients with a greater risk of colchicine resistance and tailor disease management individually at the time of diagnosis. [ABSTRACT FROM AUTHOR]

In 2006, at a meeting in Sydney, Australia, consensus was reached by an international group of specialists to establish a number of serological criteria that identify patients with a history of thrombosis or pregnancy complications as having antiphospholipid syndrome (APS). These criteria were originally formulated for research purposes and to compare clinical trials in different centres. However, these same criteria are now generally used and accepted for the diagnosis and treatment of patients. The practice of using these criteria for direct patient care requires that these criteria are based on sound scientific evidence. Indeed, for all the autoantibodies that are officially included in the serological criteria, it has been shown that they induce thrombosis and fetal loss when infused into mice. There are also a number of additional autoantibodies that have been identified in these patients but for these antibodies there was not enough evidence to meet the official APS criteria in 2006. Seventeen years have now passed since the consensus meeting, therefore, this review examines whether additional studies performed with these 'non-criteria' autoantibodies have provided sufficient results to suggest the inclusion of these autoantibodies in the official serological criteria of APS. [ABSTRACT FROM AUTHOR]