Persistence of power Doppler ultrasonography-detected synovitis over 1 year of follow-up predicts poor prognosis in rheumatoid arthritis in clinical remission: the SONORE prospective longitudinal study.

OBJECTIVES: (1) To assess the progression of ultrasonography-detected synovitis in a cohort of patients with rheumatoid arthritis (RA) in remission during 1 year of follow-up (2) to evaluate the ability of consecutive examinations of ultrasonography to predict relapse (R) or radiographic progression (RP) at 1 year. METHODS: Patients with RA (2010 American College of Rheumatology-European Alliance of Associations for Rheumatology criteria) in clinical remission (Disease Activity Score in 28 joints (DAS28)<2.6 without clinically active synovitis) were included. An independent investigator performed ultrasonography every 3 months for 1 year. Ultrasonography-detected synovitis was defined as power Doppler-positive ultrasonography synovitis (PDUS) grade ≥1 in at least one joint. PDUS at ≥2 consecutive visits during the follow-up defined persistent PDUS. An increase of ≥1 point in the modified total Sharp score defined RP. An increase in DAS28-C-reactive protein (CRP)>0.6 or DAS28-CRP>3.2 and any modification of disease-modifying anti-rheumatic drugs or glucocorticoids defined relapse. Univariate and multivariate Cox regression analyses were used to evaluate factors associated with R/RP at 1 year. RESULTS: PDUS was detected in 75 (65.2%), 66, 60, 46 and 29 of the 115 patients with RA at baseline and at months 3, 6, 9 and 12, respectively. 58 (50.4%) patients exhibited persistent PDUS. After 1 year, 22/85 (25.9%) experienced relapse and 12 (14.1%) showed RP. On multivariate analysis, factors predicting R/RP at 1 year were persistent PDUS (HR=2.98, p=0.014) and an increase in DAS28-CRP level at the visit before relapse (HR=4.36, p=0.004). CONCLUSION: Persistent PDUS during follow-up, rather than at baseline, predicted worse outcome at 1 year and requires careful monitoring.

The prevalence of Legg-Calvé-Perthes disease among paediatric patients with transient synovitis of the hip: a systematic review and meta-analysis.

BACKGROUND: Transient synovitis of the hip is the most common cause of limping in paediatric emergency departments. There is no consensus regarding routine follow-up after hip synovitis among children, and there are no standardized criteria for selecting cases that warrant follow-up due to persistent or recurring symptoms to rule out the possibility of Legg-Calvé-Perthes disease. Delayed treatment of Legg-Calvé-Perthes disease may increase the risk of developing early secondary coxarthrosis. Understanding the prevalence of Legg-Calvé-Perthes disease among paediatric patients with transient synovitis of the hip is of paramount importance and could empower both parents and paediatricians to make well-informed decisions when selecting follow-up care for children, thus ensuring that no cases of Legg-Calvé-Perthes disease are missed among diagnosis paediatric patients with transient synovitis of the hip. The aim of this review was to estimate the prevalence of Legg-Calvé-Perthes disease among paediatric patients with transient synovitis of the hip. METHODS: This study was conducted in strict accordance with the PRISMA guidelines and was registered with PROSPERO. The PubMed, Embase, and Cochrane Library databases were comprehensively searched up to July 2024 to identify relevant studies. The inclusion criteria were as follows: patients diagnosed with transient synovitis of the hip; patients aged up to 18 years; and studies with a minimum of 10 cases of paediatric transient synovitis of the hip. To pool the prevalence rates from individual studies, we utilized a random-effects meta-analysis. To assess the quality of the included studies in detail, we employed the Joanna Briggs Institute's quality assessment checklist. RESULTS: A total of 19 studies were ultimately included for the final analysis, with 2,617 paediatric cases of transient synovitis of the hip. The results of meta-analysis revealed that the pooled prevalence estimate of Legg-Calvé-Perthes disease among all paediatric patients with transient synovitis of the hip was 2.7% (95% CI 1.4-5.1). Significant heterogeneity was observed across the studies included in this analysis (I2 = 79.990%; P = 0.000). The pooled prevalence estimate of Legg-Calvé-Perthes disease among paediatric patients with recurrent or persistent transient synovitis of the hip was 36.3% (95% CI 21.6-54.2). Significant heterogeneity was also observed across the studies included in this analysis (I2 = 51.519%; P = 0.036). Furthermore, the follow-up period varied from 6 weeks to 24 months. The primary diagnostic imaging modality utilized for identifying Perthes disease was X-ray. CONCLUSION: Our study revealed that among paediatric patients with transient synovitis of the hip, routine X-ray follow-up of the hips after 6 weeks to rule out Legg-Calvé-Perthes disease is warranted only in patients who exhibit persistent or recurrent symptoms.

Treatment of Chronic Haemophilic Synovitis with PRP: Clinical and In Vitro Studies.

Intra-articular blood, iron and hemosiderin, hydroxyl radical cytokines, and neo-angiogenesis cause synovial inflammation, which leads to cartilage and joint damage. Platelet-rich plasma (PRP) inhibits most of the mediators that produce and maintain synovitis. We compile here our work showing the clinical effectiveness of intra-articular PRP injections and their potential role in stopping articular cartilage damage due to bleeding and its possible repair. A total of 116 joints, including knees (63%), elbows (19.8%), and ankles (17.2%), were treated with intra-articular injections of PRP. Moreover, we also show here the number of extracellular DNA traps (ETs) and the PRP effect in the synovial fluid of patients at the time of treatment and six months after. Clinically, it is demonstrated that PRP is effective in reducing bleeding episodes (p < 0.001) and pain (p < 0.0001) and improving the hemophilia joint health score (HJHS) (p < 0.001) at one year of follow-up. Furthermore, our results demonstrate that PRP inhibits ET formation in vitro and reconstitutes the immune system's cellular components in the synovial fluid of patients after treatment. We conclude that PRP can be considered an effective, safe, and easy treatment for hemophilic synovitis.

Blau syndrome-the skin as a warning sign.

Blau syndrome is an autosomal dominant chronic inflammatory disease, which may begin with skin manifestations in the first months of life, alerting physicians to the diagnosis. This case reports a patient diagnosed jointly by pediatric dermatology and rheumatology consultants at two years of age.

Transient/Toxic Synovitis.

Transient synovitis (TS) is a self-limiting inflammatory condition of the joints, predominantly affecting children and characterized by symptoms such as pain, swelling, warmth, and erythema. It is often triggered by an immune response to a viral infection, leading to acute inflammatory arthritis. Diagnosis involves a combination of patient history, physical examinations, imaging techniques, and laboratory tests, although there are no specific laboratory tests for TS. Treatment primarily consists of symptom management through rest, analgesics, and nonsteroidal anti-inflammatory drugs. The condition underscores the importance of distinguishing TS from more serious joint diseases to prevent unnecessary interventions and to ensure appropriate management.

Proteomic Profiling of Tears in Blau Syndrome Patients in Identification of Potential Disease Biomarkers.

Blau syndrome (BS) is a rare autoinflammatory granulomatosis characterized by granulomatous arthritis, uveitis, and dermatitis. Ocular complications are particularly severe in BS, significantly contributing to morbidity. This study aims to identify potential biomarkers for BS ocular degeneration through proteomic profiling of tear samples from affected patients. Seven subjects from the same family, including four carriers of the BS-associated NOD2 mutation (p.E383K), were recruited alongside healthy controls. Tear samples were collected using Schirmer strips and analyzed via mass spectrometry. A total of 387 proteins were identified, with significant differences in protein expression between BS patients, healthy familial subjects, and healthy controls. Key findings include the overexpression of alpha-2-macroglobulin (A2M) and immunoglobulin heavy constant gamma 4 (IGHG4) in BS patients. Bioinformatic analysis revealed that differentially expressed proteins are involved in acute-phase response, extracellular exosome formation, and protein binding. Notably, neutrophils' azurophilic granule components, as azurocidin (AZU1), myeloperoxidases (MPO), and defensins (DEFA3), were highly expressed in the most severely affected subject, suggesting a potential role of neutrophils in BS ocular severity. These proteins might be promising biomarkers for ocular involvement in BS, facilitating early detection and tailored treatment strategies.

Analysis of synovitis patterns in early RA supports the importance of joint-specific factors.

BACKGROUND: Rheumatoid arthritis (RA) is classically considered a systemic disorder, but the role of local factors in driving synovial inflammation is increasingly being recognized. These joint-specific factors may consequently modulate disease phenotype. OBJECTIVES: Our goal was to study the spatial distribution of swelling, tenderness and erosions in a large cohort of early RA (ERA) patients, to assess for patterns of simultaneously-involved joint clusters. We also aimed to investigate the link between arthritis localization and phenotypic features such as bone erosions and response to methotrexate therapy. METHODS: DMARD-naive patients from the ERA UCLouvain Brussels cohort were included. Forty-four joints were clinically assessed for swelling and tenderness before treatment, and 6 months later for methotrexate-treated patients. Clusters of joints were identified using Principal component analysis and Cramer's correlation coefficients. Frequency of bone erosions and joint-specific response to methotrexate were compared across different clusters. RESULTS: 452 ERA patients were included. Analysis of the spatial distribution of swelling and tenderness allowed for the identification of 3 joint clusters that showed significant simultaneous involvement: (i) MTP1-5 joints, (ii) hand joints (MCPs and PIPs), and (iii) larger joints. These clusters were associated with different susceptibility to bone erosions and distinct clinical features, but similar local response (joint swelling resolution) to methotrexate. CONCLUSION: This is the first study investigating the spatial distribution of arthritis in a large cohort of early RA using an unbiased approach. We identify clusters of simultaneously involved joints, supporting the importance of local factors in driving synovitis in RA.

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome.

Camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) is a rare autosomal recessive disease caused by mutation in proteoglycan 4 (PRG4) gene on chromosome 1q25-q31. We faced a dilemma and delay in diagnosis in two sisters. The elder sister had pericardial effusion with constrictive pericarditis, underwent pericardiectomy and received empirical treatment for suspected tuberculosis. After 2 years, she developed bilateral knee swelling with restriction of movement. At the same time, her younger sister also presented with bilateral knee swelling which aroused the suspicion of genetic disease. The whole-genome sequencing revealed homozygous PRG4 mutation suggestive of CACP syndrome.

Gallic acid ameliorates synovial inflammation and fibrosis by regulating the intestinal flora and its metabolites.

Gallic acid (GA) has been found by a large number of studies to have pharmacological effects such as antioxidant and anti-inflammatory properties. However, the underlying therapeutic mechanisms are not fully understood.. Studies have shown that altering the intestinal flora affects host metabolism and effectively mediates the development of synovitis. The aim of this study was to explore the pharmacological effects of GA in the treatment of synovial inflammation and anti-synovial fibrosis in knee osteoarthritis (KOA) and the underlying mechanisms by macrogenomics combined with off-target metabolomics. We established a synovitis model via in vivo and in vitro experiments to observe the effect of GA intervention on synovitis. Moreover, we collected serum and feces from rats and analyzed the changes in intestinal flora by macro-genome sequencing and the changes in metabolites in the serum by untargeted metabolomics. We found that GA reduced the levels of IL-1ß, IL-6, and TNF-α, and decreased the protein expression levels of α-SMA, TGF-ß, and Collagen I in synovial tissues and cells, and the composition and function of the intestinal flora were similarly altered. Combined with macrogenomic pathway enrichment analysis and metabolic pathway enrichment analysis, these findings revealed that GA impacts Bacteroidia and Muribaculaceae abundance, and via the following metabolic pathways: sphingolipid metabolism, glycerophospholipid metabolism, and arginine biology.to ameliorate synovial inflammation and fibrosis in KOA. The therapeutic effect of GA on KOA synovitis and fibrosis is partly attributed to the alleviation of metabolic disorder and the rebalancing of the intestinal flora. These results provides a rationale for the therapeutic application of GA in the treatment of synovitis.

How much different is the semi-quantification of synovitis according to the ultrasound system and the blood flow detection technology?

AIM: To compare synovial blood flow scoring between different technologies and ultrasound (US) systems in active and inactive rheumatoid arthritis (RA). MATERIAL AND METHODS: Fifty-nine RA patients underwent B-mode, power Doppler (PD), colour Doppler (CD), B-Flow and High-Resolution (High-Res) PDI assessments of 6 joints with two US systems at two European centres. Each joint was semi-quantitatively scored for all ultrasound parameters. PD, CD and High-Res PDI synovial signal was also quantitatively scored. RESULTS: Correlations between the total score of SH with system 1 and 2 were very high (≥ 0.90, p<0.0001). Baseline correlations between systems for PD and CD total scores were moderate to very high (0.44-0.96, p<0.05). At baseline, there were no significant differences between ultrasound systems for PD or CD semiquantitative-based total scores in active or inactive patients (p>0,05). B-Flow and High-Res total scores were significantly lower than PD or CD total scores (p<0.05). CONCLUSION: A high-end and an entry-level US system were interchangeable for scoring SH and showed similar sensitivity and responsiveness in scoring synovial blood flow by PD and CD but not interchangeability. B-Flow and High-Res PDI were responsive, but they showed different sensitivity to detect synovial blood flow compared to conventional Doppler.

Effectiveness of Genicular Artery Embolization for Reducing Synovitis as Assessed by Contrast-Enhanced MR Imaging in Knee Osteoarthritis: A Pilot Study.

PURPOSE: To investigate the impact of genicular artery embolization (GAE) on synovitis in knee osteoarthritis (OA) using contrast-enhanced magnetic resonance (MR) imaging and to assess its predictive role in pain response. MATERIALS AND METHODS: A single-center retrospective analysis was conducted using contrast-enhanced MR imaging on 33 patients treated with GAE for knee OA between December 2022 and March 2023. MR assessments before the procedure and at 3 months after embolization were utilized in a semiquantitative scoring system for synovitis severity and distribution analysis. Pain and function through Western Ontario and McMaster Universities Osteoarthritis Index and visual analog scale scores were also assessed. RESULTS: Significant synovitis reduction was noted after GAE, particularly in parapatellar and periligamentous areas. Synovial contrast enhancement scores significantly decreased from 5.1 (SD ± 2.0) to 2.9 (SD ± 2.0) at 3 months (P < .001), with a moderate negative correlation between synovial enhancement scores and pain levels (P = .005). CONCLUSIONS: GAE significantly reduced synovitis in knee OA, evidenced by contrast-enhanced MR imaging. The correlation between preprocedural synovial contrast enhancement scores and pain relief after the procedure, although promising, requires careful interpretation because of the complex factors affecting pain in knee OA.

Multicenter study investigating long-term survival after synovial lavage of contaminated and septic synovial structures in horses presented to 10 UK referral hospitals.

OBJECTIVE: To report the long-term survival of adult horses that were subjected to synovial lavage for treatment of contaminated and septic synovial structures. STUDY DESIGN: Multicenter, prospective observational trial. ANIMALS: Horses (n = 240) presented for synovial sepsis at 10 UK referral centers. METHODS: Data for horses presented for treatment of synovial sepsis were collected over a 15 month recruitment period. Owners were contacted a minimum of 365 days after surgery using a structured client interview to assess long term survival. Descriptive statistics, and univariable and Cox proportional hazards models for postoperative survival time were developed. RESULTS: Survival to discharge was 228/240 (95%) and overall long-term survival was 89.4% (185/207). Unknown cause of injury (p = .017), increasing duration of surgery (p = .003), increasing weight (p = .008), forelimb injuries (p = .027), and type of synovial structure (p = .008) were found to be associated with death using Cox proportional hazards models. CONCLUSION: This study provides information on risk factors associated with survival and death after treatment for synovial sepsis at referral hospitals in the UK. Survival to discharge and long-term survival was excellent. Heavier horses, injuries affecting the forelimbs, tendon sheaths and bursae were associated with poorer long term outcomes. Longer duration of surgery was also found to be associated with a worse prognosis. CLINICAL SIGNIFICANCE: These findings help to provide prognostic information for owners and veterinarians treating horses with synovial sepsis.

Thirteen Indians with camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome (MIM# 208250) is a rare monogenic disorder, characterized by early onset of camptodactyly, progressive coxa vara, bilateral arthropathy and constrictive pericarditis. The syndrome is caused by biallelic loss-of-function variants in PRG4 . Deficiency of PRG4 results in progressive worsening of joint deformity with age. Thirteen individuals with CACP syndrome from eight consanguineous Indian families were evaluated. We used exome sequencing to elucidate disease-causing variants in all the probands. These variants were further validated and segregated by Sanger sequencing, confirming the diagnosis of CACP syndrome in them. Seven females and six males aged 2-23 years were studied. Camptodactyly (13/13), coxa vara (11/13), short femoral neck (11/13) and arthritis in large joints (12/13) [wrists (11/13), ankle (11/13), elbow (10/13) and knee (10/13)] were observed commonly. Five novel disease-causing variants (c.3636G>T, c.1935del, c.1134dup, c.1699del and c.962T>A) and two previously reported variants (c.1910_1911del and c.2816_2817del) were identified in homozygous state in PRG4 . We describe the phenotype and mutations in one of the large cohorts of patients with CACP syndrome, from India.

Blau Syndrome: Challenging Molecular Genetic Diagnostics of Autoinflammatory Disease.

The aim of this study was to describe the clinical and molecular genetic findings in seven individuals from three unrelated families with Blau syndrome. A complex ophthalmic and general health examination including diagnostic imaging was performed. The NOD2 mutational hot spot located in exon 4 was Sanger sequenced in all three probands. Two individuals also underwent autoinflammatory disorder gene panel screening, and in one subject, exome sequencing was performed. Blau syndrome presenting as uveitis, skin rush or arthritis was diagnosed in four cases from three families. In two individuals from one family, only camptodactyly was noted, while another member had camptodactyly in combination with non-active uveitis and angioid streaks. One proband developed two attacks of meningoencephalitis attributed to presumed neurosarcoidosis, which is a rare finding in Blau syndrome. The probands from families 1 and 2 carried pathogenic variants in NOD2 (NM_022162.3): c.1001G>A p.(Arg334Gln) and c.1000C>T p.(Arg334Trp), respectively. In family 3, two variants of unknown significance in a heterozygous state were found: c.1412G>T p.(Arg471Leu) in NOD2 and c.928C>T p.(Arg310*) in NLRC4 (NM_001199139.1). In conclusion, Blau syndrome is a phenotypically highly variable, and there is a need to raise awareness about all clinical manifestations, including neurosarcoidosis. Variants of unknown significance pose a significant challenge regarding their contribution to etiopathogenesis of autoinflammatory diseases.

Disease-Modifying Effects of Lenvatinib, a Multiple Receptor Tyrosine Kinase Inhibitor, on Posttraumatic Osteoarthritis of the Knee.

Angiogenesis and vascular endothelial growth factor (VEGF) are involved in osteoarthritis (OA). We previously reported the inhibitory effect of bevacizumab in a rabbit model of OA. In the current study, we investigated the effects of lenvatinib, an angiogenesis inhibitor targeting the VEGF and fibroblast growth factor receptors, on synovitis, osteophyte formation, and cartilage degeneration in a rabbit OA model. Posttraumatic OA was induced by anterior cruciate ligament transection (ACLT) on one knee of each rabbit. Rabbits were placed into four groups according to the following lenvatinib doses: untreated control (n = 12), L0.3: 0.3 mg/kg/day (n = 15), L1.0: 1.0 mg/kg/day (n = 14), and L3.0: 3.0 mg/kg/day (n = 13) groups. We evaluated limb pain using the weight distribution ratio measured with an incapacitance tester, macroscopic osteophyte formation, and femoral condyle synovium and cartilage histology. For cartilage evaluation, the following distal sites of the femur were evaluated separately: femoral-tibial (FT), femoral-patellar (FP), and femoral corner (between FP and FT). The weight distribution ratio at 12 weeks after surgery was higher in the L0.3 and L1.0 groups than in the control group. Osteophyte formation and synovitis scores were significantly lower in the L0.3, L1.0, and L3.0 groups than in the control group. The Osteoarthritis Research Society International scores of the FT, corner, and FP sites in the L0.3 group were lower than in the control group. The cartilage thickness ratio at the FT and corner sites was significantly lower in the L0.3 group than in the control group. Krenn's grading system of cartilage synovitis showed that all lenvatinib-administered groups had significantly lower scores than the control group. MMP3 expression level in cartilage tissue was significantly lower in the L3.0 group compared with the other three groups. ADAMTS5 expression was lower in the L3.0 group compared with the control and L0.3 groups. Oral administration of lenvatinib inhibited synovitis, osteophyte formation, and cartilage degeneration and reduced pain in a rabbit ACLT model. Lenvatinib is an oral VEGF inhibitor that is easier to administer than other VEGF inhibitors and may have potential as a treatment of posttraumatic OA.

Deep learning-based classification of erosion, synovitis and osteitis in hand MRI of patients with inflammatory arthritis.

OBJECTIVES: To train, test and validate the performance of a convolutional neural network (CNN)-based approach for the automated assessment of bone erosions, osteitis and synovitis in hand MRI of patients with inflammatory arthritis. METHODS: Hand MRIs (coronal T1-weighted, T2-weighted fat-suppressed, T1-weighted fat-suppressed contrast-enhanced) of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients from the rheumatology department of the Erlangen University Hospital were assessed by two expert rheumatologists using the Outcome Measures in Rheumatology-validated RA MRI Scoring System and PsA MRI Scoring System scores and were used to train, validate and test CNNs to automatically score erosions, osteitis and synovitis. Scoring performance was compared with human annotations in terms of macro-area under the receiver operating characteristic curve (AUC) and balanced accuracy using fivefold cross-validation. Validation was performed on an independent dataset of MRIs from a second patient cohort. RESULTS: In total, 211 MRIs from 112 patients (14 906 region of interests (ROIs)) were included for training/internal validation using cross-validation and 220 MRIs from 75 patients (11 040 ROIs) for external validation of the networks. The networks achieved high mean (SD) macro-AUC of 92%±1% for erosions, 91%±2% for osteitis and 85%±2% for synovitis. Compared with human annotation, CNNs achieved a high mean Spearman correlation for erosions (90±2%), osteitis (78±8%) and synovitis (69±7%), which remained consistent in the validation dataset. CONCLUSIONS: We developed a CNN-based automated scoring system that allowed a rapid grading of erosions, osteitis and synovitis with good diagnostic accuracy and using less MRI sequences compared with conventional scoring. This CNN-based approach may help develop standardised cost-efficient and time-efficient assessments of hand MRIs for patients with arthritis.

Platelet-to-lymphocyte ratios as a haematological marker of synovitis in rheumatoid arthritis with normal acute phase reactant level.

BACKGROUND: Although normal acute phase reactants (APRs) play an important role in assessing disease activity of rheumatoid arthritis (RA), some studies pointed out the discordance between disease activity and APR level. Neutrophil-to-lymphocyte ratios (NLRs), platelet-to-lymphocyte ratios (PLRs) and lymphocyte-to-monocyte ratios (LMRs) have been reported to be sensitive measures of inflammatory reaction. This study aims to explore the value of these haematological makers in assessment of APR-negative RA patients. METHODS: Out of a cohort of 418 consecutive patients with RA, we enrolled 135 patients with normal APR for this study. We performed ultrasound assessments to evaluate synovitis and bone erosion in the affected joints. Synovitis was evaluated by ultrasound grey scale (GS) and power Doppler (PD) with semi-quantitative scoring (0-3). Demographic, clinical and laboratory data were collected from the patients. Disease Activity Score-28 joints (DAS28), NLR, MLR and PLR were calculated. RESULTS: In RA patients with normal APR, PLR exhibited a positive correlation with ultrasound-detected synovitis and bone erosion, whereas NLR, MLR showed no significant correlation with ultrasonography parameters. The area under the ROC curve (AUC) for identifying synovitis with a GS grade ≥2 based on a PLR cutoff value of ≥159.6 was 0.7868 (sensitivity: 80.95%, specificity: 74.24%). For synovitis with a PD grade ≥2, the AUC was 0.7690, using a PLR cutoff value of ≥166.1 (sensitivity: 68.0%, specificity: 83.87%). CONCLUSIONS: Our findings suggested that PLR might be a reliable and cost-effective marker for identifying moderate-to-severe synovitis in RA patients with normal APR.

Two Broad Categories Overlapping With Rheumatoid Arthritis Observed in Synovial Biopsies from Patients With Juvenile Idiopathic Arthritis.

OBJECTIVE: The objective is to characterize transcriptomic profiles and immune cell composition and distribution in juvenile idiopathic arthritis (JIA) synovial biopsies, assess for associations of these features with clinical parameters, and compare JIA and rheumatoid arthritis (RA) synovial features. METHODS: RNA sequencing (RNASeq) was performed on 24 samples, with pathway analysis and inference of relative abundance of immune cell subsets based on gene expression data. Two multiplex fluorescence immunohistochemistry (IHC) panels were performed on 28 samples (including 13 on which RNASeq was performed), staining for CD206- classical and CD206+ nonclassical macrophages, and CD8+ and CD4+ T and B lymphocytes. Data were compared to a published series of early RA synovial biopsies. RESULTS: Pathway analysis of the most variably expressed genes (n = 339) identified a B and plasma cell signature as the main driver of heterogeneity in JIA synovia, with strong overlap between JIA and RA synovitis. Multiplex IHC confirmed heterogeneity of immune cell infiltration. M1-like macrophage-rich synovial lining was associated with greater lining hypertrophy and higher (CD45+) pan-immune cell and CD8+ T cell infiltration. CONCLUSION: Our study indicates significant similarities between JIA and RA synovitis. Similar to RA, JIA synovia may be broadly categorized into two groups: (1) those with an inflammatory/adaptive immune transcriptomic signature, M1-like macrophage and CD8+ T cell infiltration, and thicker, M1-like macrophage-rich synovial lining, and (2) those with an M2-like macrophage transcriptomic signature, greater M2/M1-like macrophage ratios, and thinner, M2-like macrophage-rich synovial lining. Synovial features were not significantly associated with clinical parameters, likely because of group size and heterogeneity.

Safety and Efficacy of Radiosynoviorthesis: A Prospective Canadian Multicenter Study.

Radiosynoviorthesis is approved in several European countries and the United States to treat refractory synovitis in many inflammatory joint diseases, such as rheumatoid arthritis, spondyloarthropathies, and other arthritic joint diseases. No radiopharmaceuticals for radiosynoviorthesis are currently approved in Canada. The aim of this Health Canada-approved trial was to demonstrate the safety and efficacy of radiosynoviorthesis. Methods: Between July 2012 and November 2017, we conducted a multicenter, prospective, interventional Canadian trial. Patients (n = 360) with synovitis refractory to standard treatments after failing 2 intraarticular glucocorticoid injections were included. They were followed up at 3, 6, and 12 mo. Outcome measures included adverse events (AEs) and clinical signs of synovitis (pain, swelling, and joint effusion) measured with the Health Assessment Questionnaire Disability Index, the Disease Activity Score, and the Visual Analog Scale. Results: In total, 392 joints were treated, including those reinjected after 6 mo (n = 34). Of these, 83.4% (327/392) were injected with [90Y]Y-citrate for the knees and 9.9% (39/392) with [186Re]Re-sulfide for medium-sized joints. Of the joints treated, 82.7% (324/392) were knees. Fifty-five AEs, most of them of mild grade, occurred and resolved without sequelae and were not life-threatening. The incidence of radiosynoviorthesis-related AEs was 9.4% (34/360). The proportion of patients showing an improvement in synovitis symptoms after radiosynoviorthesis was significant at 3 mo and was maintained up to 12 mo (P < 0.001). Conclusion: This study confirmed the safety of radiosynoviorthesis in the treatment of patients with synovitis refractory to standard treatments. There is evidence of sustained clinical efficacy at 12 mo, suggesting that radiosynoviorthesis is an effective treatment for improving synovitis symptoms.