ObjectiveThe synovial tissue pathotype may determine the treatment response in rheumatoid arthritis (RA); however, biopsies are not widely available. Synovial fluid is a promising tissue surrogate. Our purpose was to compare RA synovial fluid cell counts with histopathology and use synovial fluid to predict tissue inflammation.MethodsSynovial fluid and tissue were collected during knee arthroplasty. Patients were stratified based on their medication treatment history. Synovial lymphocytic inflammation (SLI) was graded from low to high. Synovial fluid white blood cell (WBC) count and differentials were performed in the clinical laboratory. Descriptive statistics, correlations, receiver operating characteristic curve analysis, and multivariable regression were performed to determine the associations with tissue SLI.ResultsSixty‐four patients with RA had paired synovial tissue and synovial fluid data available. The mean Clinical Disease Activity Index (CDAI) score was 17.9. High tissue SLI was observed in 29 patients, and low SLI was observed in 35 patients, with roughly equal distribution among treatment groups. The mean synovial fluid WBC count was 5,661 cells/μL and was not correlated with CDAI but correlated positively with SLI and percentage polymorphonuclear cells (PMN%). Synovial fluid WBC count ≥1,400 cells/μL was sensitive (0.86) and specific (0.91) for high SLI (area under the curve 0.91). In a multivariable regression, PMN% was associated with high SLI (odds ratio [OR] 1.46 [95% confidence interval (CI) 1.14–1.85]). Synovial fluid monocyte percentage was negatively associated with high SLI (OR 0.44 [95% CI 0.27–0.73]).ConclusionSynovial fluid WBC count is sensitive and specific for differentiating high and low lymphocytic synovial inflammation. Further analysis of the synovial fluid as it relates to the adjacent tissue in different cohorts is needed.

Severalstudies have highlighted the role of Type I interferons (IFN-I) in activating inflammatory pathways in lupus. However, no previous research focused on investigating the role of IFN-I gene expression in the ophthalmologic involvement of systemic lupus erythematosus (SLE). We aimed to assess the association between the IFN-I gene signature and ophthalmologic involvement in SLE. Cross-sectional study includes patients ≥18 years old, fulfilling the 2019 EULAR or American College of Rheumatology criteria for SLE. Ophthalmologic evaluation, the Systemic Lupus Erythematosus Disease Activity Index-2K index, and blood sample collection were performed at the time of study assessment. Peripheral blood mononuclear cells were isolated, RNA was extracted, and complementary DNA was synthesized. Gene expression of IFI27, IFI44L, IFIT1, ISG15, RSAD2, and SIGLEC1 was assessed by real-time polymerase chain reaction, using RPLP0 and EEF1A1 as reference genes for normalization. The median normalized relative quantity of the genes for each patient was used to calculate the fold change (FC) of the "Interferon Score." Group comparisons were conducted using the Mann-Whitney U test, and correlations between variables were assessed using Spearman's rank correlation coefficient. We included 32 patients with SLE. Ocular involvement occurred in 62.5%, either due to aqueous-deficient dry eye (46.88%) or lupus retinopathy. A higher expression of the IFN-I gene was found in patients with ocular involvement (FC = 2.52 ± 1.96; P = 0.0027) compared with those without ophthalmologic changes. The upregulation of the IFN-I gene expression was associated with ophthalmologic involvement in SLE, potentially playing a role in its pathogenesis.

Prompt referral to a rheumatologist is essential for the prevention of joint damage in people with inflammatory arthritis (IA). We investigated whether rheumatology referrals can improve triage if additional information from two self-assessment tools, namely the tender joint count (TJC) and the Early Inflammatory Arthritis Detection Tool (EIADT), was included with the referral letter. Newly referred patients with no history of IA were recruited from two rheumatology practices. All patients were randomly allocated within a 2 × 2 factorial design to one of the following four groups: (1) no self-assessment, (2) TJC + EIADT, (3) TJC, and (4) EIADT. Participants were blinded to group allocation. Primary outcome was urgency rating, which was either 0 to 4 weeks, 4 to 6 weeks, 6 to 12 weeks, or nonurgent (>12 weeks). For each patient, an urgency rating was assigned to each of the following: (1) referral letter, (2) referral letter plus self-assessment, and (3) clinical assessment. Two hundred two patients were recruited and allocated across the four groups. Compared to referral letter alone, adding self-assessment to the referral letter significantly increased the number of participants marked nonurgent in the EIADT group (P < 0.05, McNemar-Bowker test), but not in any of the other groups. Also, in the EIADT group, clinical assessment did not significantly increase the number of nonurgent ratings compared to referral letter plus self-assessment (P ≥ 0.05, McNemar-Bowker test). Including the EIADT with the referral letter may improve triage for new referrals.

ObjectiveMultisystem inflammatory syndrome in children (MIS‐C) is a rare hyperinflammatory syndrome that follows SARS‐CoV‐2 infection. Prior plasma proteomic analysis from a 2020 cohort of patients with MIS‐C at our center revealed a profile characterized by thrombotic microangiopathy (TMA), macrophage activation syndrome (MAS)‐associated proteins, and dysregulated interferon‐γ (IFNγ) responses. However, a limitation of that study was that samples were often acquired after treatment. The objective of this study was to identify plasma proteomic signatures that uniquely define MIS‐C versus other viral syndromes unconfounded by treatment effects in an independent cohort.MethodsPlasma proteomics was performed using the Olink Explore HT platform on plasma from patients enrolled at emergency department admission with suspected MIS‐C (final diagnoses N = 12 MIS‐C, N = 30 other viral syndromes). Plasma autoantibody analysis was performed using a custom microbead‐based protein array.ResultsConsistent with findings in the 2020 cohort, TMA‐ and MAS‐associated proteins were more highly expressed, and there was a higher CXCL9 response to IFNγ in MIS‐C compared to viral infection. In contrast to the 2020 cohort, patients with MIS‐C did not have lower expression of the IFNγ suppressive protein TRIM21. On reanalysis of the 2020 cohort, only patients who received intravenous Ig (IVIg) treatment before sampling had low TRIM21 (also known as Ro52/SSA). IVIg recipients also had anti‐Ro52 autoantibodies.ConclusionWe have validated several unique features of the plasma proteome of patients with MIS‐C first identified in 2020. Discrepant TRIM21 expression in these two cohorts is due to anti‐Ro52 autoantibodies in IVIg‐treated patients. These data support the use of plasma cytokine profiling to rapidly diagnose MIS‐C.

Interstitial lung disease (ILD) is common in idiopathic inflammatory myositis (IIM), particularly in antisynthetase syndrome (ASyS), antimelanoma differentiation-associated protein 5 (anti-MDA5) syndrome, and scleromyositis. ILD can progress despite resolution of extrapulmonary symptoms, termed postmyopathic progressive pulmonary fibrosis (PmPPF). We outlined ILD trajectories in these subgroups of IIM, focusing on PmPPF. A retrospective review of patients with IIM (ASyS, anti-MDA5+ dermatomyositis [DM], scleromyositis) from a British Columbia cohort (2019-2024) assessed demographics, auto-antibodies, treatments, and ILD progression. Among 111 patients with ASyS, anti-MDA5+ DM, and scleromyositis (median age 51 years, follow-up 35.5 months), ILD prevalence was highest in ASyS (87.5%), followed by anti-MDA5+ DM (84.6%), and scleromyositis (65.5%). PmPPF occurred in 13.5% of the cohort, predominantly in anti-MDA5+ DM (23.1%) and ASyS (16.1%) but not in scleromyositis. Patients with PmPPF had higher rates of active disease (46.7% vs 9.3%), rapidly progressive ILD (33.3% vs 5.3%), and lung transplantation (20% vs 1.3%). Anti-MDA5+ DM exhibited the highest remission rate (88.5%) but also the highest transplant requirement (11.5%). Organizing pneumonia (OP)/nonspecific interstitial pneumonia (NSIP) overlap on high-resolution computed tomography was more common in PmPPF (33.3% vs 9.3%). PmPPF showed a nonsignificant trend toward higher mortality compared to non-PmPPF (20% vs 4%). Rituximab use was greater in PmPPF (73.3% vs 37.3%). This study highlights distinct ILD patterns across three idiopathic inflammatory myopathy subtypes, with PmPPF occurring more frequently in ASyS and anti-MDA5+ DM but not in scleromyositis. The persistence of ILD progression independent of extrapulmonary disease activity underscores the importance of ongoing pulmonary monitoring and multidisciplinary management.

Psychological distress is common in individuals undergoing total joint arthroplasty (TJA). Understanding psychological phenotypes and their transitions from before to after surgery can inform risk stratification and targeted care. This study aimed to characterize psychological phenotypes, examine transitions, and compare patient outcomes across phenotypes. This retrospective study included 494 patients who underwent primary hip (43%) or knee (57%) arthroplasty at Duke University Health System (2018–2024). Latent transition analysis identified and examined transitions of psychological phenotypes preoperatively and postoperatively using the Optimal Screening for Prediction of Referral and Outcome Yellow Flag tool. Demographic characteristics, phenotype transitions, Patient‐Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI), PROMIS Physical Function (PF), pain intensity, and high‐impact chronic pain (HICP) were compared across phenotypes. The optimal model fit was a constrained model comprising five classes: class 1 (low self‐efficacy with poor pain coping), class 2 (low distress), class 3 (poor pain coping), class 4 (high distress), and class 5 (low self‐efficacy with acceptance). Most patients (n = 271, 55%) transitioned to a different phenotype. The probabilities for remaining in the same class ranged from 0.19 (poor pain coping) to 0.61 (low distress). The incidence of high distress was 6% within 12 months after TJA. High distress was associated with lower PROMIS‐PF and higher PROMIS‐PI scores, pain intensity, and prevalence of HICP (P < 0.001). Transitions were observed across all phenotypes, with some demonstrating greater stability and others showing more state‐like variability. Identifying phenotypes with distinct trajectories and outcomes may support targeted screening and preoperative risk stratification.