Joint Erosions Research Articles

Comparison of the inhibitory effect of tocilizumab and etanercept on the progression of joint erosion in rheumatoid arthritis treatment

We compared the efficacy of tocilizumab and etanercept in inhibiting radiographic progression of joint destruction in rheumatoid arthritis. Overall, 187 patients treated with etanercept or tocilizumab were selected. To adjust for baseline patient characteristics between the tocilizumab and etanercept treatment groups, a propensity score matching was performed. Radiographic progression of joint destruction was compared between patients treated with tocilizumab or etanercept. Clinical disease activity index (CDAI) and modified health assessment questionnaire (mHAQ) scores at the administration of biologic treatment and after 12 months of tocilizumab and etanercept therapy were measured and compared to radiographical parameters between the groups. Levels of C-reactive protein (CRP), matrix metalloproteinase-3 (MMP-3), CDAI, and mHAQ scores improved after 12 months of treatment in the two groups. Proportion of patients with no Sharp erosion score progression was significantly higher with tocilizumab treatment than with etanercept treatment (p = 0.032). Multivariate analysis demonstrated that Sharp erosion score was significantly associated with baseline CDAI (odds ratio, 1.05; 95% confidence interval, 1.003–1.099, p = 0.037). Tocilizumab treatment suppressed joint erosion progression compared to etanercept, and the progression correlated with baseline CDAI.

Etanercept is Effective and Halts Radiographic Progression in Rheumatoid Arthritis and Psoriatic Arthritis: Final Results from a German Non-interventional Study (PRERA).

Etanercept (ETN) has been shown to slow radiographic progression of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical trials. This real-world, non-interventional study assessed radiographic progression in patients with RA or PsA treated with ETN for ≤ 36months in outpatient care in Germany (NCT01623752). Patients with RA or PsA attended ≤ 10 visits across two study phases (phase 1: seven visits, baseline to month 18; phase 2: three visits until month 36). Radiographs were taken at baseline (Rx1), months 12-18 (Rx2), and/or months 30-36 (Rx3). Historic radiographs (Rx0) taken 12-48months pre-baseline were also evaluated (if available). The primary endpoint was the change in modified total Sharp score (mTSS). The erosion score (ES) and joint space narrowing score (JSN) were also evaluated. Overall, 1821 patients were enrolled (RA: n = 1378; PsA: n = 440). In patients with Rx1 and Rx2 (RA: n = 511; PsA: n = 167), the mean mTSS remained stable for both disease groups, and the annualized median change in mTSS was 0. In patients with Rx0, Rx1, and Rx2 (RA: n = 180; PsA: n = 47), annualized radiographic progression in mTSS, ES, and JSN was larger in the pre-ETN treatment phase than during ETN treatment in both disease groups. The percentage of patients with radiographic non-progression was higher during ETN treatment versus pre-ETN. Improvement in clinical disease activity and patient-reported outcomes was also observed. This was the first real-world, non-interventional study to report systematically collected radiographic data in a large cohort of patients with RA or PsA under treatment with a biologic. In patients with available radiographic data, mean radiographic progression was lower and the proportion of patients without progression was greater during ETN treatment than in the pre-ETN period.

Clinical Factors and the Outcome of Treatment with Methotrexate in Rheumatoid Arthritis: Role of Rheumatoid Factor, Erosive Disease and High Level of Erythrocyte Sedimentation Rate.

To identify the clinical factors predicting the outcome of treatment with methotrexate in rheumatoid arthritis, we examined 312 patients (253 females, 59 males) with rheumatoid arthritis diagnosed according to the criteria of the American College of Rheumatology. All patients included in this analysis began treatment with a regimen of oral MTX 7.5 mg weekly, with the dosage increasing to 15 mg weekly after 4 weeks, in combination with folic acid (1 mg daily). Good responders were defined as patients who had a DAS28 of ≤2.4 at 6 months (patients with remission of disease symptoms). Poor responders were defined as patients who had a DAS28 of >2.4. In this study, we analyzed the association between clinical parameters such as sex of patients, age of patients, age at disease onset, disease duration, rheumatoid factor, anti-CCP antibodies, ESR values, presence of joints erosions, presence of extra-articular manifestations and the response to MTX in RA patients. Multivariate logistic regression analysis showed four independent factors significantly associated with good response to MTX treatment: older age at disease onset, low ESR, no erosive disease and negative RF. The results of our study suggest that a younger age at disease onset, the presence of RF, erosive disease, as well as a high level of ESR are associated with worse response to MTX therapy.

Utilization of the Psoriasis Epidemiology Screening Tool (PEST): A Risk Stratification Strategy for Early Referral of Psoriatic Arthritis Patients to Minimize Irreversible Erosive Joint Damage.

Psoriatic arthritis (PsA) can affect a diverse range of anatomical sites and its heterogeneous presentation contributes to misdiagnosis and delayed treatment with conventional and biologic disease-modifying antirheumatic drugs (DMARDs). Up to 15% of psoriasis (PsO) patients affected by PsA remain undiagnosed. Early detection and referral to a rheumatologist are crucial to optimize care and minimize irreversible erosive joint damage. To improve the rheumatology referral process, the authors propose a risk stratification tool to identify and triage patients with possible psoriatic arthritis. With the aim of ultimately assisting in early treatment initiation, this risk stratification algorithm can be used in both dermatology and primary care clinics. It is based on the Psoriasis Epidemiology Screening Tool (PEST) combined with the ClASsification criteria for Psoriatic Arthritis (CASPAR). This article intends to provide a rationale for further prospective studies whose objective would be to validate this screening algorithm.

39 Pediatric monoarthritis of the elbow: atypical onset of a common disease

Abstract Background Oligoarticular type of juvenile idiopathic arthritis (oligoJIA) is considered the most common type of JIA. It usually affects one or < 4 joints. The knee is the most common affected joint followed by the ankle and wrist. Oligoarticular JIA presenting with erosive elbow monoarthritis as an initial sign of the disease is a rare condition which needs prompt diagnosis and management. Objective To recognize that isolated chronic elbow monoarthrits is an atypical presentation for oligoJIA. Case presentation: A 14-year-old volleyball player female child presented with chronic recurrent left elbow swelling of six months’ duration. No history of morning stiffness, constitutional symptoms, other joint swelling, uveitis, or skin manifestations were reported. On examination there was mild cubitus valgus with elbow effusion associated with limited last degree elbow extension with no other signs of inflammation or infection (redness, tenderness, hotness). Hypermobility was noted in both elbows and knees. Patient was advised to rest the elbow and symptomatic treatment was recommended. On follow up there was mild improvement of the swelling, so further investigations were ordered. Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), Rheumatoid factor (RF) and antinuclear antibody (ANA) showed average normal values. X-ray of the elbow showed degenerative changes. Musculoskeletal ultrasound showed mild elbow effusion and magnetic resonance imaging (MRI) was ordered revealing effusion and early joint erosion at the ulnar articular surface with no synovial hypertrophy. Arthroscopy was recommended to detect the underlying pathology and histopathology revealed chronic active synovitis suggesting JIA. Non-steroidal anti-inflammatory drugs (NSAIDs) were recommended but one month later knee arthritis was noted, so methotrexate was started and the condition started to improve. Results We report a 14-year-old female child who presented with atypical isolated chronic swelling of the elbow and was diagnosed by arthroscopy and histopathology. Non-steroidal anti-inflammatory drugs (NSAIDS) were tried as a first line treatment followed by methotrexate. Conclusion Chronic elbow monoarthritis is an atypical onset of oligoJIA and its diagnosis is important to prevent irreversible joint damage. Synovial biopsy can have a major role in the diagnosis of atypical monoarticular JIA and can help in early diagnosis and management improving the outcome. The implication to policy, practice, research, and advocacy: Monoarthritis of the elbow as initial sign of oligoJIA is an atypical onset of this disease and in the absence of systemic signs or other clinical indicators determining the exact cause of monoarthritis in children might be difficult. Synovial biopsy can have an important role in the diagnosis of monarticular arthritis in pediatric patients.

Synthetic MRI in the detection and quantitative evaluation of sacroiliac joint lesions in axial spondyloarthritis.

ObjectiveOur primary objective was to verify the hypothesis that synthetic magnetic resonance imaging (MRI) is similar to conventional MRI in detecting sacroiliac joint lesions in patients with axial spondyloarthritis (axSpA). A secondary objective was to assess the quantitative value of synthetic mapping in bone marrow edema (BME) and fat metaplasia.MethodsA total of 132 axSpA patients who underwent synthetic and conventional MRI from October 2019 to March 2021 were included in this prospective study. Two independent readers visually evaluated active inflammatory (BME, capsulitis, enthesitis, and inflammation at site of erosion) and structural lesions (erosion, sclerosis, ankylosis, and fat metaplasia) of the sacroiliac joints on conventional and synthetic magnetic resonance (MR) images. In addition, T1, T2, and proton density (PD) values, which were generated by synthetic mapping, were used to further quantitatively evaluate BME and fat metaplasia. A McNemar test was used to compare the differences between the two methods in the detection of sacroiliac joint lesions. Intraclass correlation coefficients (ICCs) were used to assess the inter-reader consistency of quantitative values. Mann–Whitney tests were performed, and receiver operating characteristic (ROC) curves were created for all quantitative analyses.ResultsThere were no statistical difference between synthetic and conventional MRI in the detection of sacroiliac joint lesions (all p-values > 0.05). A total of 103 images of BME and 111 images of fat metaplasia were quantitatively evaluated using T1, T2, and PD values. The consistency of quantitative values among readers was good (ICC 0.903–0.970). T1 and T2 values were consistently higher in BME than in normal marrow (p < 0.001), but PD values were not significantly different (p = 0.830). T2 and PD values were higher in fat metaplasia than in normal marrow, but T1 values were lower (p < 0.001). In the case of BME, T1 values had greater diagnostic efficiency [area under the curve (AUC) 0.99] than T2 values (AUC 0.78). There were no significant differences in the diagnostic efficiency of T1 (AUC 0.88), T2 (AUC 0.88), and PD (AUC 0.88) values in the case of fat metaplasia.ConclusionSynthetic MRI is as effective as conventional MRI in detecting sacroiliac joint lesions in patients with axSpA. Furthermore, synthetic mapping can accurately quantify BME and fat metaplasia.

The Role of Fibronectin and its Isoforms in the Pathogenesis and Progression of Rheumatoid Arthritis: A Review

Rheumatoid arthritis (RA) remains a desolating and devastating disease with a strong social impact on the world. Current drugs and therapies are showing poor responses toward RA due to its unknown progression. Evidence has shown that Extra Domain A fibronectin, recognized as a damage-associated molecular pattern (DAMPs), interacts with pathogen recognition receptors (PRR), which play a vital role in the erosion and degradation of joints. The post-translational modification and citrullination of fibronectin enhance the expression of EDA fibronectin (EDA+Fn). Fibronectin and its interacting receptors, such as TLR-4 may be a potential target for the treatment of RA. This review critically summarizes the recent discoveries and breakthroughs in the role of fibronectin and its isoforms in the pathogenesis and progression of RA.

Anti-Protein-Arginine Deiminase 4 IgG and IgA Delineate Severe Rheumatoid Arthritis.

There is a strong need for biomarkers of rheumatoid arthritis (RA) in all phases of the patient’s journey and to enable the implementation of precision medicine strategies to improve patient care. The objective of this study was to evaluate the presence of anti-protein-arginine deiminase (PAD) 4 IgG and IgA in the sera of RA patients and disease controls, and to investigate their association with joint erosion and biological treatment use. Sera from 104 RA and 155 controls were tested for the presence of anti-PAD4 IgG and IgA using a new particle-based multi-analyte technology (PMAT). Information on the erosive disease and biological treatment use was available for 54 of the RA patients, who were also tested for anti-citrullinated protein antibodies (ACPA). An association between the autoantibodies and these clinical features was investigated. Anti-PAD4 showed sensitivity and specificity values of 25.0% and 94.2% for IgG and of 21.2% and 94.8% for IgA for RA, respectively. The levels of these antibodies were also significantly higher in RA patients vs. controls, in erosive RA vs. non-erosive disease, and in patients under biologics vs. patients that were not on this treatment regimen. The anti-PAD4 IgG and IgA levels were correlated (rho = 0.60, p < 0.0001), but individuals that were positive for only one of the two isotypes were also observed. Anti-PAD4 IgG and IgA are associated with severe RA, and they represent valuable biomarkers for prognosis prediction and patient stratification.

Low-Frequency Magnetic Resonance Imaging Identifies Hand Joint Subclinical Inflammation in Systemic Sclerosis.

Objectives: The aim of this work was to determine hand joint inflammation in systemic sclerosis (SSc); patients with rheumatoid arthritis (RA) with hand joint involvement were used as controls. Our investigation also aimed at examining the relationship between these subclinical inflammatory changes in the hands, verified by low-frequency MRI, and clinical (especially cardiopulmonary) manifestations, disease activity, and functional capacity in patients with diffuse cutaneous (dcSSc) and limited cutaneous SSc (lcSSc). Methods: Out of 250 SSc patients, the selection included 82 patients with signs and symptoms of joint involvement, and 35 consecutive RA patients. These patients underwent clinical and laboratory investigations, and hand X-ray and MRI of the dominant hand. Synovitis/tenosynovitis, bone edema, and erosions were investigated, and the bone changes were quantified and scored using the RAMRIS method. HAQ index, modified Rodnan skin score, examination of internal organ involvement, and serological markers for SSc, as well as rheumatoid factor (RF) and cyclic citrullinated peptides antibodies (ACPA), were performed on all experimental group subjects. Results: MRI of the dominant hand showed a significantly higher number of cases with synovitis (78%) than the number of patients with clinically swollen joints (17.1%; p < 0.001); bone edema was found in 62 (75.6%) SSc patients. MRI also showed a higher number of erosions (52; 63.4%) compared to those (22; 27.5%) detected with X-ray (p < 0.001). The average values of the total MRI score of synovitis/edema and erosions in the wrist (p < 0.001) and MCP joints (p < 0.001) were statistically higher in RA than in SSc patients (p < 0.001). The probability of the MRI-detected inflammatory changes was considerably higher in SSc patients who had vascular complications (digital ulceration, OR = 4.68; 95% IP: 1.002–22.25; p < 0.05), in patients with more severe functional impairment (OR = 8.22; 95% IP: 1.74–38.89; p < 0.01), and in patients with active disease (OR = 3.132; 95% IP: 1.027–9.551; p < 0.05). In our investigation, patients with a limited form of the disease and with inflammatory changes on MR more often had higher functional impairment compared to the other group without MRI inflammation. Conclusions: Our data show that in SSc MRI can detect a significant subclinical joint inflammation. RAMRIS confirmed the high degree of joint inflammation in RA, but also revealed a great deal of joint inflammation in SSc. That inflammation is associated with systemic inflammation (disease activity), vascular complications, and more severe forms of the disease, as synovitis cannot be precisely diagnosed by the clinical examination of joints. These results suggest that a careful joint investigation is necessary in SSc, and that in symptomatic patients, MRI may identify joint inflammation. In clinical practice, this evidence might drive to an early targeted therapy, thus preventing joint erosions.

Blurring and Irregularity of the Subchondral Cortex in Pediatric Sacroiliac Joints on T1 Images: Incidence of Normal Findings That Can Mimic Erosions.

To determine prevalence of variations of subchondral bone appearance that may mimic erosions on T1-weighted magnetic resonance imaging (MRI) of pediatric sacroiliac (SI) joints according to age and sex. With ethics committee approval and informed consent, SI joint MRIs of 251 children (132 girls), mean age 12.4 years (range 6.1-18.0 years), were obtained in 2 cohorts: 127 children imaged for nonrheumatic reasons, and 124 children with low back pain but no features of sacroiliitis at initial clinical MRI review. MRIs were reviewed by 3 experienced radiologists, blinded from each other, for 3 features of the cortical black line representing the subchondral bone plate on T1-weighted MRI: visibility, blurring, and irregularity. Based on agreement from 2 or more readers, the cortical black line was partially absent in 88.4% of the children, blurred in 34.7%, and irregular in 41.4%. All these features were most common on the iliac side of SI joints and at the first sacral vertebra level. Clearly visualized, sharply delineated SI joints with none of these features were seen in only 8.0% of children, or in 35.1% if we conservatively required agreement of all 3 readers to consider a feature present. There was no significant difference between sexes or cohorts; findings were similar across pediatric age groups. Understanding the normal MRI appearance of the developing SI joint is necessary to distinguish physiologic findings from disease. At least two-thirds (65%) of normal pediatric SI joints showed at least 1 feature that is a component of the adult definition of SI joint erosions, risking overdiagnosis of sacroiliitis.

Awareness of temporomandibular joint involvement in rheumatoid arthritis patients by physicians dealing with rheumatology

The aim of this study is to evaluate the attitudes and awareness of physicians dealing with rheumatology about temporomandibular joint (TMJ) involvement while evaluating rheumatoid arthritis (RA) patients with the TMJ questionnaire we created. For this purpose, an online TMJ evaluation questionnaire consisting of 10 questions was prepared and completed by the physicians via the Google Forms application. Among those who participated in the survey; the percentage of correct answers to the question of whether the TMJ joint is a synovial joint was 95.5%. While the rate of those who correctly knew that more than half of the RA patients had TMJ involvement remained at 35.5%, the rate of those who correctly identified that RA rarely affected the first TMJ was 75.5%. The rate of those who knew that TMJ involvement is frequently bilateral in RA was 62.7%. The number of participants who answered the question of what the clinical findings are in TMJ involvement correctly was over 60%. When asked about radiological findings in TMJ involvement in RA, more than 75% of the participants expected joint space narrowing, erosion, and mandibular destruction. On the other hand, the number of physicians who expected radiological findings such as ostephitis and sclerosis as radiological findings was below 40%. While the number of physicians who performed TMJ inquiries and examinations in RA patients was only 15.5%, if there was a TMJ complaint, this rate increased to 80%. The number of participants using objective tests for the evaluation of TMJ was below 30%. Also, 85.5% of the participants ignored TMJ involvement in RA. In conclusion, our study showed that physicians dealing with rheumatology have low awareness of TMJ involvement in RA.

A Crowdsourcing Approach to Develop Machine Learning Models to Quantify Radiographic Joint Damage in Rheumatoid Arthritis

An automated, accurate method is needed for unbiased assessment quantifying accrual of joint space narrowing and erosions on radiographic images of the hands and wrists, and feet for clinical trials, monitoring of joint damage over time, assisting rheumatologists with treatment decisions. Such a method has the potential to be directly integrated into electronic health records. To design and implement an international crowdsourcing competition to catalyze the development of machine learning methods to quantify radiographic damage in rheumatoid arthritis (RA). This diagnostic/prognostic study describes the Rheumatoid Arthritis 2-Dialogue for Reverse Engineering Assessment and Methods (RA2-DREAM Challenge), which used existing radiographic images and expert-curated Sharp-van der Heijde (SvH) scores from 2 clinical studies (674 radiographic sets from 562 patients) for training (367 sets), leaderboard (119 sets), and final evaluation (188 sets). Challenge participants were tasked with developing methods to automatically quantify overall damage (subchallenge 1), joint space narrowing (subchallenge 2), and erosions (subchallenge 3). The challenge was finished on June 30, 2020. Scores derived from submitted algorithms were compared with the expert-curated SvH scores, and a baseline model was created for benchmark comparison. Performances were ranked using weighted root mean square error (RMSE). The performance and reproductivity of each algorithm was assessed using Bayes factor from bootstrapped data, and further evaluated with a postchallenge independent validation data set. The RA2-DREAM Challenge received a total of 173 submissions from 26 participants or teams in 7 countries for the leaderboard round, and 13 submissions were included in the final evaluation. The weighted RMSEs metric showed that the winning algorithms produced scores that were very close to the expert-curated SvH scores. Top teams included Team Shirin for subchallenge 1 (weighted RMSE, 0.44), HYL-YFG (Hongyang Li and Yuanfang Guan) subchallenge 2 (weighted RMSE, 0.38), and Gold Therapy for subchallenge 3 (weighted RMSE, 0.43). Bootstrapping/Bayes factor approach and the postchallenge independent validation confirmed the reproducibility and the estimation concordance indices between final evaluation and postchallenge independent validation data set were 0.71 for subchallenge 1, 0.78 for subchallenge 2, and 0.82 for subchallenge 3. The RA2-DREAM Challenge resulted in the development of algorithms that provide feasible, quick, and accurate methods to quantify joint damage in RA. Ultimately, these methods could help research studies on RA joint damage and may be integrated into electronic health records to help clinicians serve patients better by providing timely, reliable, and quantitative information for making treatment decisions to prevent further damage.

Systems biology approach delineates critical pathways associated with disease progression in rheumatoid arthritis

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease leading to inflammation, cartilage cell death, synoviocyte proliferation, and increased and impaired differentiation of osteoclasts and osteoblasts leading to joint erosions and deformities. Transcriptomics, proteomics, and metabolomics datasets were analyzed to identify the critical pathways that drive the RA pathophysiology. Single nucleotide polymorphisms (SNPs) associated with RA were analyzed for the functional implications, clinical outcomes, and blood parameters later validated by literature. SNPs associated with RA were grouped into pathways that drive the immune response and cytokine production. Further gene set enrichment analysis (GSEA) was performed on gene expression omnibus (GEO) data sets of peripheral blood mononuclear cells (PBMCs), synovial macrophages, and synovial biopsies from RA patients showed enrichment of Th1, Th2, Th17 differentiation, viral and bacterial infections, metabolic signalling and immunological pathways with potential implications for RA. The proteomics data analysis presented pathways with genes involved in immunological signaling and metabolic pathways, including vitamin B12 and folate metabolism. Metabolomics datasets analysis showed significant pathways like amino-acyl tRNA biosynthesis, metabolism of amino acids (arginine, alanine aspartate, glutamate, glutamine, phenylalanine, and tryptophan), and nucleotide metabolism. Furthermore, our commonality analysis of multi-omics datasets identified common pathways with potential implications for joint remodeling in RA. Disease-modifying anti-rheumatic drugs (DMARDs) and biologics treatments were found to modulate many of the pathways that were deregulated in RA. Overall, our analysis identified molecular signatures associated with the observed symptoms, joint erosions, potential biomarkers, and therapeutic targets in RA. Communicated by Ramaswamy H. Sarma

Supplementing clinical diagnostics of erosive joint diseases with bio-inspired ratiometric sensors

Inflammatory rheumatological disorders are often characterised by altered levels of matrix metalloproteinase levels in joint fluid and joint membranes. Therefore, monitoring of MMP activity in synovial fluid is essential to enable timely diagnosis, prognosis, and effective treatment. Here we report a novel fluorescence assay to measure protease activity in aspirated synovial fluid. Our fluorescent reporters contain cleavable linkers based on the peptide sequences of protease substrates, showing a ratiometric output upon cleavage. We have validated our reporters in patient-derived synovial fluid, and demonstrated their ability to characterise disease type.

Migration and homeostasis of regulatory T cells in rheumatoid arthritis.

Regulatory T (Treg) cells are garnering increased attention in research related to autoimmune diseases, including rheumatoid arthritis (RA). They play an essential role in the maintenance of immune homeostasis by restricting effector T cell activity. Reduced functions and frequencies of Treg cells contribute to the pathogenesis of RA, a common autoimmune disease which leads to systemic inflammation and erosive joint destruction. Treg cells from patients with RA are characterized by impaired functions and by an altered phenotype. They show increased plasticity towards Th17 cells and a reduced suppressive capacity. Besides the suppressive function of Treg cells, their effectiveness is determined by their ability to migrate into inflamed tissues. In the past years, new mechanisms involved in Treg cell migration have been identified. One example of such a mechanism is the phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Efficient migration of Treg cells requires the presence of VASP. IL-6, a cytokine which is abundantly present in the peripheral blood and in the synovial tissue of RA patients, induces posttranslational modifications of VASP. Recently, it has been shown in mice with collagen-induced arthritis (CIA) that this IL-6 mediated posttranslational modification leads to reduced Treg cell trafficking. Another protein which facilitates Treg cell migration is G-protein-signaling modulator 2 (GPSM2). It modulates G-protein coupled receptor functioning, thereby altering the cellular activity initiated by cell surface receptors in response to extracellular signals. The almost complete lack of GPSM2 in Treg cells from RA patients contributes to their reduced ability to migrate towards inflammatory sites. In this review article, we highlight the newly identified mechanisms of Treg cell migration and review the current knowledge about impaired Treg cell homeostasis in RA.

The effect of subchondral oedema in T2-weighted Dixon MRI sequence evaluation of sacroiliac joint erosion in axial spondyloarthropathy

To evaluate the effect of subchondral oedema in T2-weighted Dixon magnetic resonance imaging (MRI) sequence evaluation of sacroiliac joint erosion in patients with axial spondyloarthropathy. Twenty patients diagnosed with axial spondyloarthritis underwent MRI at a tertiary referral centre from December 2019 to March 2021 were included. In-phase, opposed-phase and fat-only images were scored by two musculoskeletal radiologists independently for the presence of erosions in eight sacroiliac joint quadrants. Sensitivity, specificity and areas under the curve (AUC) of the receiver operating characteristic curve were determined using T1W sequence as reference standard. Intra-observer and interobserver reliability were calculated using Cohen's kappa coefficient. The diagnostic performance of fat-only and in-phase images were similar (AUC 0.857-0.902 and 0.828-0.868) and better than opposed-phase images (AUC 0.613-0.658). The interobserver reliability of fat-only and in-phase images were substantial (k=0.747 and 0.712), and moderate for opposed-phase images (k=0.417). Intra-observer reliability was almost perfect for all the images. In the subgroup analysis, the specificity and AUC for oedema-positive group were lower than oedema-negative group in all image sets. Interobserver reliability was substantial for fat-only and in-phase images in both groups, but slight and moderate for the opposed-phase oedema-positive and negative groups, respectively. The presence of subchondral oedema in active sacroiliitis decreased the diagnostic accuracy of sacroiliac joint erosion detection on T2W Dixon MRI images.

Prevalence of Subclinical Activity by Ultrasound Examination in Mexican Children with Juvenile Idiopathic Arthritis in Remission

Background: Juvenile Idiopathic Arthritis (JIA) is a chronic disease that affects 0.6 - 1.9 /1,000 children. Persistent joint inflammation conditions cartilage damage and erosions. Recent studies have shown that clinical examination significantly underestimates joint inflammation, with ultrasound having a higher sensitivity. The aim of this study was determined the prevalence of subclinical synovitis by musculoskeletal ultrasound in Mexican children with JIA in remission. Methods: Cross-sectional study, patients with JIA in clinical remission based on the Wallace criteria were included, with and without pharmacological treatment, we also included a control group of healthy children. The evaluation was performed by a certified Rheumatologist in Pediatric Musculoskeletal Ultrasound by EULAR. Joints clinically examined were also evaluated following the standard guidelines. Results: A total of 37 JIA patients with clinical remission and 33 healthy children were evaluated (1260 joints scanned), subclinical activity was detected in 15/37 (40.5%) patients and none of healthy children; 14 patients were still on treatment (93.3%). The subclinical activity was detected by gray scale in 22/1260 (1.7%) or by power Doppler (PD) in 15/1260 (1.1%) joints, the knee was involved in 13/22 (59%) joints. The subtype mainly affected was the rheumatoid factor-positive (FR) polyarticular (33.3%), erosions were detected in three patients (8%). In the knee, we observed slight distention of the supra patellar recess, evidenced in 19/33 healthy children (57.5%), predominantly among children aged 4 to 8 years. When comparing the groups with or without subclinical synovitis, no statistically significant differences were found with regard to age, evolution time or acute phase reactants. Conclusions: Subclinical synovitis was detected in 40.5% of the patients in clinical remission using gray scale or by power Doppler, mainly on those who were still on treatment. The most affected subtype was the rheumatoid factor-positive polyarticular, the knees were the most frequent involved. In the healthy children, a slight distention of the supra patellar recess was observed in almost half of cases.

Prevalence of Subclinical Activity by Ultrasound Examination in Mexican Children with Juvenile Idiopathic Arthritis in Remission

Background: Juvenile Idiopathic Arthritis (JIA) is a chronic disease that affects 0.6 - 1.9 /1,000 children. Persistent joint inflammation conditions cartilage damage and erosions. Recent studies have shown that clinical examination significantly underestimates joint inflammation, with ultrasound having a higher sensitivity. The aim of this study was determined the prevalence of subclinical synovitis by musculoskeletal ultrasound in Mexican children with JIA in remission. Methods: Cross-sectional study, patients with JIA in clinical remission based on the Wallace criteria were included, with and without pharmacological treatment, we also included a control group of healthy children. The evaluation was performed by a certified Rheumatologist in Pediatric Musculoskeletal Ultrasound by EULAR. Joints clinically examined were also evaluated following the standard guidelines. Results: A total of 37 JIA patients with clinical remission and 33 healthy children were evaluated (1260 joints scanned), subclinical activity was detected in 15/37 (40.5%) patients and none of healthy children; 14 patients were still on treatment (93.3%). The subclinical activity was detected by gray scale in 22/1260 (1.7%) or by power Doppler (PD) in 15/1260 (1.1%) joints, the knee was involved in 13/22 (59%) joints. The subtype mainly affected was the rheumatoid factor-positive (FR) polyarticular (33.3%), erosions were detected in three patients (8%). In the knee, we observed slight distention of the supra patellar recess, evidenced in 19/33 healthy children (57.5%), predominantly among children aged 4 to 8 years. When comparing the groups with or without subclinical synovitis, no statistically significant differences were found with regard to age, evolution time or acute phase reactants. Conclusions: Subclinical synovitis was detected in 40.5% of the patients in clinical remission using gray scale or by power Doppler, mainly on those who were still on treatment. The most affected subtype was the rheumatoid factor-positive polyarticular, the knees were the most frequent involved. In the healthy children, a slight distention of the supra patellar recess was observed in almost half of cases.

Evaluation of the immune feature of ACPA-negative rheumatoid arthritis and the clinical value of matrix metalloproteinase-3.

Anti-citrullinated protein antibodies (ACPAs) are highly specific for the diagnosis of rheumatoid arthritis (RA). However, about one-third of RA patients are negative for ACPAs, which presents a challenge to the early diagnosis of RA. The purpose of this study was to analyze differences in lymphocyte subsets and CD4+ T cell subsets between ACPA+ and ACPA- RA patients, and to evaluate the value of matrix metalloproteinase-3 (MMP-3) as a diagnostic and monitoring marker in ACA- RA patients. A total of 145 ACPA+ RA patients, 145 ACPA- RA patients, and 38 healthy controls (HCs) were included in this study. Peripheral lymphocyte subsets were detected using flow cytometry, and serum MMP-3 was detected using chemiluminescence. Information about joint symptoms, other organ involvement, and related inflammatory markers was also collected. The results showed that, compared to ACPA- RA patients, ACPA+ cases had greater imbalances between peripheral CD4+ T cell subsets, mainly manifested as an increase in T-helper 1 (Th1) cells (p < 0.001) and decrease in regulatory T (Treg) cells (p = 0.029). This makes these patients more prone to inflammatory reactions and joint erosion. MMP-3 levels in ACPA+ and ACPA- RA patients were significantly higher than in HCs (p < 0.001), and MMP-3 could effectively distinguish between ACPA- RA patients and HCs (area under the curve [AUC] = 0.930, sensitivity 84.14%, specificity 92.11%). MMP-3 was also a serum marker for distinguishing between RA patients with low and high disease activities. Further analysis showed that MMP-3 was positively correlated with the levels of inflammatory markers and disease activity, and negatively correlated with the levels of lymphocyte subsets. In addition, with improvements in the disease, MMP-3 levels decreased, and further increased as the patients started to deteriorate. In summary, our research showed that there was a mild imbalance between peripheral CD4+ T cell subsets in ACPA- RA patients. MMP-3 may be used as a potential marker for early diagnosis of ACPA- RA. MMP-3 was an important index for RA disease evaluation, disease activity stratification, and prognosis.

Assessment of interclass and intraclass variability of specific lesions of sacroiliac magnetic resonance imaging.

Sacroiliac joint (SJ) imaging is the key point in the diagnosis of ankylosing spondylitis (AS). The curved anatomy of the SJ makes the interpretation of imaging difficult. The aim of this study is to evaluate the interclass and intraclass reliability of specific lesions (bone marrow edema [BME], joint space narrowing, erosions, effusion, ankylosis, bridging, sclerosis, fat deposition, and other additional pathologies) on SJ magnetic resonance imaging (MRI). In a total of 310 randomly chosen patients, 620 SJs were evaluated by three different radiologists with different radiology experiences of specialties other than musculoskeletal radiology. The agreement between readers for BME was fair to substantial, for active sacroiliitis was moderate to substantial, for sacroiliac narrowing was fair at best, for erosions was fair to moderate, for SJ sclerosis was none to slight, for chronic sacroiliitis was slight to fair, for degenerative sacroiliitis was none to slight, for normal SJ was slight, for SJ effusion was none to slight, and for fatty deposition was none. Intraclass correlation for readers 1 and 3 was usually good to excellent and for reader 2 was poor to fair. This study was designed to assess the agreement between radiologists who were not familiar with SJ MRI. The agreement between readers was usually fair to substantial and even intraclass correlation was poor to fair for reader 2. Future studies can be designed for standardization and validation of each MRI lesion for better interpretation of SJ MRI.