Persistent Joint Inflammation Research Articles

UNRAVELING THE GENETIC AND EPIGENETIC LANDSCAPE OF RHEUMATOID ARTHRITIS: A COMPREHENSIVE REVIEW OF PATHOGENESIS, DIAGNOSIS, AND THERAPEUTIC IMPLICATIONS

This exhaustive review delves into the genetic and epigenetic foundations of Rheumatoid Arthritis (RA), a multifaceted autoimmune disorder characterized by persistent joint inflammation. We discuss the findings of genome-wide association studies (GWAS) that have uncovered numerous genetic loci associated with RA, emphasizing the substantial impact of HLA variants on disease susceptibility and severity. The review also explores epigenetic mechanisms such as DNA methylation, histone modifications, and the regulatory role of microRNAs, all of which influence gene expression and immune response in RA. The involvement of inflammasomes in mediating inflammatory responses emphasizes potential therapeutic targets. Furthermore, the application of artificial intelligence for analyzing intricate genetic data presents promising opportunities for advancing diagnosis and treatment strategies. This article underscores the critical need for integrating multi-omics data. It emphasizes the significance of collaborative research in the field of RA, highlighting the importance of your work in this area.

Severe Pancytopenia And Urticaria Vasculitis Induced By Secukinumab In Psoriatic Arthritis: A Case Report

Psoriatic arthritis (PA) is a chronic autoimmune inflammatory disease characterized by persistent joint inflammation and severe erythemo-squamous plaques on the skin. In recent decades, biological agents such as IL-17 drugs have been applied in the treatment of PA with very good results. The treatment has its adverse effects, but severe pancytopenia is extremely rare. We report a case of а patient who was treated with secukinumab for 3 years and in the background of this treatment unlocked urticaria vasculitis and severe pancytopenia. In relation to psoriatic arthritis, there is almost complete clearing of the skin, but the joint pains are remitting in nature.

Comparison of Adenosine Deaminase, C-reactive Protein, Uric Acid, and Rheumatoid Arthritis Levels in Patients With Rheumatoid Arthritis and Those Without Arthritis: A Review.

One of the hallmarks of rheumatoid arthritis (RA) is inflammation of the synovial membrane, and oxidative stress is a mediator of tissue damage. RA is characterized by persistent joint inflammation, which leads to pain, edema, and finally joint destruction. Numerous biochemical markers can cause RAbecause of their impact on systemic and local inflammation. Numerous biomarkers have been investigated for their potential application in the diagnosis and prognosis of RA. In this review article, we evaluate the role of RAfactor or rheumatoid factor (RF), uric acid, C-reactive protein (CRP), and adenosine deaminases (ADAs) as biomarkers in patients with and without arthritis. Studies that analyze and compare the levels of uric acid, ADAs, CRP, and RF in patients with and without arthritis. Although recent research has shown higher levels of uric acid, ADA, CRP, and RA in patients with RF compared to healthy controls, these findings may indicate a role for these markers in reflecting inflammation and disease activity. In the metabolism of purines, the enzyme ADAis involved. The liver produces CRP, which is then released into the bloodstream. In inflammatory situations, there is a rise in CRPlevels. This biomarker is frequently used for systemic inflammatory assessment in RA. The pathophysiology and severity of RA have both been connected to uric acid, which has historically been linked to gout. One particular biomarker for RAis RF. When compared to a healthy control group of individuals with arthritis, this review provides valuable insights into the diagnostic and prognostic use of uric acid, CRP, ADAs, and RF.

Prediction of Major Adverse Cardiovascular Events by Triglyceride Glucose Index in Predominantly Male Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic and chronic autoimmune disease that is characterized by persistent joint inflammation. RA patients experience a considerably increased risk of cardiovascular-related morbidity and mortality. The current study investigated the association between triglyceride glucose (TyG) index and major adverse cardiovascular events (MACEs) in a predominantly male cohort of RA patients. A total of 1613 RA patients (81.53% male) were selected from the Kailuan study. The TyG index was calculated as the logarithmic product of fasting blood triglyceride and fasting blood glucose divided by two. MACEs were defined as the composite of non-fatal myocardial infarctions and non-fatal strokes. Cox proportional hazards analysis was performed to study the association between the TyG index and MACEs. A total of 59 MACEs occurred during the median follow-up time of 5.32 years. Following adjustment for age and gender, analysis by multivariable Cox proportional hazards (model 1) showed that an elevated TyG index was associated with an increased risk of MACEs (quartile 2, hazard ratio (HR): 2.741, 95% confidence interval (CI): 1.220-6.157, p = 0.015; quartile 4, HR: 2.521, 95% CI: 1.074-5.917, p = 0.034). After adjustment for other variables, Cox proportional hazards analysis (model 2) showed that an elevated TyG index was independently associated with an increased risk of MACEs (quartile 2, HR: 2.348, 95% CI: 1.009-5.465, p = 0.048). In addition, subgroup analysis showed a higher TyG index was significantly linked to an increased risk of MACEs in patients aged more than 65 years (quartile 2, HR: 6.048, 95% CI: 1.311-27.908, p = 0.021; quartile 4, HR: 12.074, 95% CI: 1.438-101.358, p = 0.022). The TyG index was associated with an increased risk of MACEs in a predominantly male cohort of RA patients. This index may be helpful for the prediction of MACEs in male patients with RA. Registration number in the Chinese clinical trial registry: ChiCTR-TNRC-11001489.

Using a collaborative learning health system approach to improve disease activity outcomes in children with juvenile idiopathic arthritis in the Pediatric Rheumatology Care and Outcomes Improvement Network.

The Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) is a North American learning health network focused on improving outcomes of children with juvenile idiopathic arthritis (JIA). JIA is a chronic autoimmune disease that can lead to morbidity related to persistent joint and ocular inflammation. PR-COIN has a shared patient registry that tracks twenty quality measures including ten outcome measures of which six are related to disease activity. The network's global aim, set in 2021, was to increase the percent of patients with oligoarticular or polyarticular JIA that had an inactive or low disease activity state from 76% to 80% by the end of 2023. Twenty-three hospitals participate in PR-COIN, with over 7,200 active patients with JIA. The disease activity outcome measures include active joint count, physician global assessment of disease activity, and measures related to validated composite disease activity scoring systems including inactive or low disease activity by the 10-joint clinical Juvenile Arthritis Disease Activity Score (cJADAS10), inactive or low disease activity by cJADAS10 at 6 months post-diagnosis, mean cJADAS10 score, and the American College of Rheumatology (ACR) provisional criteria for clinical inactive disease. Data is collated to measure network performance, which is displayed on run and control charts. Network-wide interventions have included pre-visit planning, shared decision making, self-management support, population health management, and utilizing a Treat to Target approach to care. Five outcome measures related to disease activity have demonstrated significant improvement over time. The percent of patients with inactive or low disease activity by cJADAS10 surpassed our goal with current network performance at 81%. Clinical inactive disease by ACR provisional criteria improved from 46% to 60%. The mean cJADAS10 score decreased from 4.3 to 2.6, and the mean active joint count declined from 1.5 to 0.7. Mean physician global assessment of disease activity significantly improved from 1 to 0.6. PR-COIN has shown significant improvement in disease activity metrics for patients with JIA. The network will continue to work on both site-specific and collaborative efforts to improve outcomes for children with JIA with attention to health equity, severity adjustment, and data quality.

Reversible SAHH inhibitor ameliorates MIA-induced osteoarthritis of rats through suppressing MEK/ERK pathway

Osteoarthritis (OA) is characterized by gradual articular cartilage degradation, accompanied by persistent low-grade joint inflammation, correlating with radiographic and pain-related progression. The latent therapeutic potential of DZ2002, a reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH), holds promise for OA intervention. This study endeavored to examine the therapeutic efficacy of DZ2002 within the milieu of OA. The cytotoxicity of DZ2002 was evaluated using the MTT assay on bone marrow-derived macrophages. The inhibitory impact of DZ2002 during the process of osteoclastogenesis was assessed using TRAP staining, analysis of bone resorption pits, and F-actin ring formation. Mechanistic insights were derived from qPCR and Western blot analyses. Through the intra-articular injection of monosodium iodoacetate (MIA), an experimental rat model of OA was successfully instituted. This was subsequently accompanied by a series of assessments including Von Frey filament testing, analysis of weight-bearing behaviors, and micro-CT imaging, all aimed at assessing the effectiveness of DZ2002. The findings emphasized the effectiveness of DZ2002 in mitigating osteoclastogenesis induced by M-CSF/RANKL, evident through a reduction in TRAP-positive OCs and bone resorption. Moreover, DZ2002 modulated bone resorption-associated gene and protein expression (CTSK, CTR, Integrin β3) via the MEK/ERK pathway. Encouragingly, DZ2002 also alleviates MIA-induced pain, cartilage degradation, and bone loss. In conclusion, DZ2002 emerges as a potential therapeutic contender for OA, as evidenced by its capacity to hinder in vitro M-CSF/RANKL-induced osteoclastogenesis and mitigate in vivo osteoarthritis progression. This newfound perspective provides substantial support for considering DZ2002 as a compelling agent for osteoarthritis intervention.

Association of mutations in hemochromatosis genes with clinical severity of calcium pyrophosphate arthritis

Aims: To study factors associated with the development of calcium pyrophosphate (CPP) arthritis and the severity phenotype. Methods: Transversal case-control study. Cases had to be confirmed by both X-ray chondrocalcinosis and CPP crystals in synovial fluid. Controls had neither chondrocalcinosis nor CPP crystals in synovial fluid. Patients and controls with hemochromatosis or primary hyperparathyroidism were not included. Mutations of hemochromatosis genes (HFE), magnesium (Mg), calcium (Ca), phosphate, iron (Fe), transferrin saturation, ferritin, parathyroid hormone (PTH), and calcifediol levels were studied. Results: Three hundred patients and 300 sex and age matched controls were compared. Lower serum Mg (sMg) and higher ferritin levels were found among patients. Hypomagnesemia (HypoMg) and HFE mutations were more frequent among patients. Involvement of over one joint was observed in 199 (66.4%) patients whereas persistent joint inflammation was retrieved in 154 (51.4%) of the patients. Initial analysis showed that the frequency of polyarticular and inflammatory phenotypes seemed to be progressively overrepresented in patients with HFE mutations. Further bivariate and multivariate analysis adjusted for the time from onset disclosed that the presence of genotypes with C282Y mutations was associated with polyarticular disease (hazard risk 3.501, 95% confidence interval 1.862–6.581, P < 0.001). Although C282Y mutations also seemed to be associated with inflammatory patterns, the association did not reach statistical significance (P = 0.173). Conclusions: Low sMg and high ferritin levels are associated with CPP arthritis (CPPA). In patients without hemochromatosis, HFE mutations, and specifically C282Y mutations seem to associate with the polyarticular disease phenotype, and plausibly with the chronic inflammatory phenotype.

Pro-resolving and anti-inflammatory effects of resolvins and protectins in rheumatoid arthritis.

Rheumatoid arthritis (RA) is typified by persistent joint inflammation, which leads to the deterioration of bone and cartilage and a reduction in overall quality of life. The global prevalence of pain as a primary symptom in RA is influenced by the interplay between inflammation and its resolution. The identification of a family of lipid mediators known as specialized pro-resolving mediators (SPM)s has contributed to the progress of our comprehension of inflammatory conditions. SPMs have been observed to trigger the process of inflammation resolution, thereby reinstating the homeostasis of the inflammatory response. Autacoids are synthesized through the stereo-selective transformation of essential fatty acids, resulting in molecules dynamically modulated during inflammation and possessing strong immunoregulatory properties. This review delves into the available evidence that supports the involvement of certain SPM as protective lipids, biomarkers with potential, and therapeutic targets in the context of RA.

Factors Influencing Adalimumab Treatment Response in Patients with Rheumatoid Arthritis: The Future of Clinical Expertise

Rheumatoid arthritis (RA) is characterized by persistent joint inflammation, which is a defining feature of this chronic inflammatory condition. Considerable advancements have been made in the field of disease-modifying anti-rheumatic medicines (DMARDs), which effectively mitigate inflammation and forestall further joint deterioration. Anti-tumor necrosis factor-alpha (TNF-α) drugs, which are a class of biological DMARDs (bDMARDs), have been efficaciously employed in the treatment of RA in recent times Adalimumab, a TNF inhibitor, has demonstrated significant efficacy in reducing disease symptoms and halting disease progression in patients with RA. However, its use is associated with major side effects and high costs. In addition, ongoing advancements in therapeutic development have resulted in the production of medications that exhibit enhanced efficacy and safety characteristics. However, further investigation is required before RA can be deemed a manageable pathology. This review presents an analysis of the utilization of adalimumab for the treatment of RA by synthesizing information from relevant literature and emphasizing its effectiveness and safety to improve overall outcomes along with potential cost reductions for patients with RA.

The Role of Autophagy as a Trigger of Post-Translational Modifications of Proteins and Extracellular Vesicles in the Pathogenesis of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, characterized by persistent joint inflammation, leading to cartilage and bone destruction. Autoantibody production is directed to post-translational modified (PTM) proteins, i.e., citrullinated or carbamylated. Autophagy may be the common feature in several types of stress (smoking, joint injury, and infections) and may be involved in post-translational modifications (PTMs) in proteins and the generation of citrullinated and carbamylated peptides recognized by the immune system in RA patients, with a consequent breakage of tolerance. Interestingly, autophagy actively provides information to neighboring cells via a process called secretory autophagy. Secretory autophagy combines the autophagy machinery with the secretion of cellular content via extracellular vesicles (EVs). A role for exosomes in RA pathogenesis has been recently demonstrated. Exosomes are involved in intercellular communications, and upregulated proteins and RNAs may contribute to the development of inflammatory arthritis and the progression of RA. In RA, most of the exosomes are produced by leukocytes and synoviocytes, which are loaded with PTM proteins, mainly citrullinated proteins, inflammatory molecules, and enzymes that are implicated in RA pathogenesis. Microvesicles derived from cell plasma membrane may also be loaded with PTM proteins, playing a role in the immunopathogenesis of RA. An analysis of changes in EV profiles, including PTM proteins, could be a useful tool for the prevention of inflammation in RA patients and help in the discovery of personalized medicine.

SAA as Inflammatory Marker in Rheumatoid Arthritis: Study on Standard Therapy and Moringa Extract

Rheumatoid arthritis is a chronic systemic inflammatory autoimmune disorder characterized by persistent joint inflammation leading to cartilage and bone damage, disability, and systemic complications. The levels of APR such as SAA serum increase during synovitis. Previous studies have demonstrated the anti-inflammatory effect of M.oleifera leaf extract in the treatment of RA in animals; however, research data on humans remain limited. An experimental study on pre- and post-treatment of 40 RA patients was carried out by dividing subjects into 2 groups, including a standard therapy group and a standard therapy group added with M.oleifera leaf extract. The research was conducted at Dr. Moewardi Hospital, Surakarta from October 2020 to January 2021. The SAA levels were measured using ELISA. Paired T-test was used to analyze the differences in mean SAA levels before and after treatment. There was a significant difference between pre-treatment (346.57±54.40 ng/mL) and post-treatment (314.77±37.40 ng/mL) SAA levels in the standard therapy group added with M.oleifera leaf extract with p=0.01. Pre-treatment and post-treatment SAA levels in the standard therapy group were 322.68±87.01 ng/mL and 302.93±86.51 ng/mL, respectively with p=0.04. The mean of delta SAA in the standard therapy group added with M.oleifera leaf extract (-31.81±4.04 ng/mL) was greater than delta SAA in the standard therapy group (-19.75±4.07 ng/mL) with p=0.26. There was a significant decrease in SAA levels in RA patients on standard therapy and M. oleifera leaf extract.

Mechanism of Gardeniae Fructus in ameliorating rheumatoid arthritis based on metabolomics and intestinal microbiota

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1β, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.

Intra-articular injections of biological disease-modifying anti-rheumatic drugs in inflammatory arthropathies: An up-to-date narrative review

IntroductionSince the 1990s thebiological disease-modifying anti-rheumatic drugs (bDMARDs) have revolutionized the treatment of chronic dysimmune inflammatory arthropathies such as Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondylarthritis. Nevertheless, despite a full treatment regimen, mono- and oligoarticular persistence of the synovitis is sometimes observed. The intra-articular (IA) use of bDMARD drugs could resolve the persistent joint inflammation and result in a reduction in the degree of immunosuppression of individuals; moreover, the use of these drugs intra-articularly could be associated with a reduction in the treatment-related costs. MethodsWe extensively searched via PubMed and Google Scholar articles using as keywords “etanercept”, “infliximab”, “adalimumab”, “certolizumab”, “golimumab”, “tocilizumab”, “ixekizumab”, “secukinumab”, “rituximab” each combined with “intra-articular injection”. ResultsWe found and evaluated 161 papers, and then we selected 24 that were highly related to the topic of the present work. The articles examined a total of 349 patients, 85 males (M), and 168 females (F), mean age of 44.75±12.09 years old and considered 556 treated joints. Three hundred and forty-one patients were affected by Rheumatoid Arthritis, 198 by Psoriatic Arthritis, 56 by Axial Spondylarthritis, 26 by Juvenile Idiopathic Arthritis, 19 by Undifferentiated Arthritis, 1 by arthritis associated with inflammatory bowel disease and 9 patients by an unspecified inflammatory articular disorder. All patients were treated intra-articularly with a TNFα inhibitor among Adalimumab, Etanercept or Infliximab. Side effects were documented in 9 out of 349 (2.57%) treated patients and all were mild or moderate. In some cases the effectiveness of IA bDMARDs treatment was maintained for several months, however in the few published randomized controlled trials(RCTs) the corticosteroids (GCs) appeared to act better when administered intra-articularly compared to bDMARDs. ConclusionsThe IA use of bDMARDs seems to be weakly effective in the management of resistant synovitis and not superior to GCs injections. The treatment's main limit appears to be the poor persistence of the compound in the joint.

Complement system dysregulation in synovial fluid from patients with persistent inflammation following anterior cruciate ligament reconstruction surgery

IntroductionPatients with anterior cruciate ligament injury are at high risk of posttraumatic osteoarthritis and their response to reconstructive surgery and rehabilitation vary. Proteins identified in the orchestration of the acute inflammatory response may be predictive of patient outcomes. ObjectiveAn unbiased, bottom-up proteomics approach was used to discover novel targets for therapeutics in relation to dysregulation in the orchestration of inflammatory pathways implicated in persistent joint inflammation subsequent to joint trauma. MethodsSynovial fluid was aspirated from patients at 1 week and 4 weeks after anterior cruciate ligament reconstruction (ACLR) and interleukin 6 (IL-6) concentrations were quantified by enzyme-linked immunosorbent assay. Patients were segregated into IL-6low and IL-6high groups based on IL-6 concentrations in synovial fluid at 4-weeks postoperation and proteins in synovial fluid were analyzed using qualitative, bottom-up proteomics. Abundance ratios were calculated for IL-6high and IL-6low groups as 4 weeks postoperation:1 week postoperation. ResultsA total of 291 proteins were detected in synovial fluid, 34 of which were significantly (P < .05) differentially regulated between groups. Proteins associated with the classical and alternative complement cascade pathways were increased in the IL-6high compared to IL-6low group. Insulin-like growth factor-binding protein 6 (IGFBP-6) was increased by nearly 60-fold in the IL-6low group. ConclusionsPatients segregated by IL-6 concentration in synovial fluid at 4 weeks post-ACLR demonstrated differential regulation of multiple pathways, providing opportunities to investigate novel targets, such as IGFBP-6, and to take advantage of therapeutics already approved for clinical use in other diseases that target inflammatory pathways, including the complement system.

Septic shoulder osteoarthritis post-covid-19 vaccination: A case report with literature review

This report emphasizes the relevance of MRI in non-resolving inflammation post-covid-19 vaccination in a 63-year-old female. In this patient, clinical examination was suggestive of septic arthritis confirmed by biology and MRI, which demonstrated cartilaginous damage and an extension of the infection to the bone. Therapeutical possibilities and prevention techniques are described and substantiated with a brief review of post-vaccinal arthritis cases in the literature. This report aims to delineate the utility of early MRI performance in persistent joint inflammation and the different possibilities available to the patient for optimal management at the early stages of the disease.

Metabonomics and 16S rRNA gene sequencing to study the therapeutic mechanism of Danggui Sini decoction on collagen-induced rheumatoid arthritis rats with Cold Bi syndrome

Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent joint inflammation. The development of rheumatoid arthritis is directly correlated with the disturbance of gut microbiome and its metabolites. RA can be effectively treated with the Danggui Sini decoction (DSD), a Traditional Chinese medicine (TCM) prescription from the Treatise on Febrile Diseases. Further research is needed to clarify the precise mechanism of DSD in the treatment of RA. In this study, 1H NMR metabonomics and 16 S rRNA gene sequencing techniques were used to clarify the intervention of DSD on CIA-induced RA. The results of 1H NMR metabolomics of feces revealed that five metabolites (alanine, glucose, taurine, betaine, and xylose) were disturbed, which could be regarded as potential biomarkers of RA. The intestinal microbiome of RA rats had changed, according to the results of 16 S rRNA gene sequencing; eight microbes (g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_group, g_Dubosiell, g_Lactobacillus, g_norank_f_Desulfovibrionaceae, g_Bacteroides, g_Oscillibacter, and g_Romboutsia) occurred significantly at the genus level, and DSD significantly impacted six of them (g_Dubosiell, g_Lactobacillus, g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_grou, g_Bacteroides, and g_Romboutsia). Three of them (g_norank_f_Eubacterium_ coprostanoligenes_group, g_Romboutsia, and g_Lactobacillus) were regarded as key microbiomes for DSD to treat RA, and three common metabolic pathways (taurine and hypotaurine metabolism; alanine, aspartate, and glutamate metabolism; primary bile acid biosynthesis) were discovered based on the 1H NMR metabonomics and PICRUST2 prediction of 16 S rRNA gene sequencing. Six SCFAs in feces (acetic acid, butyric acid, propionic acid, caproic acid, isobutyric acid, and valeric acid) increased significantly in RA, according to the outcomes of targeting SCFAs, while five SCFAs (acetic acid, butyric acid, propionic acid, caproic acid, and valeric acid) had decreased significantly due to DSD treatment. In conclusion, our study indicated that DSD could regulate RA’s metabolic disorder by affecting intestinal microbiome and its metabolites. It also establishes a framework for future research into exploiting gut microbes therapeutic to treat RA.

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.

Bone bruising severity after anterior cruciate ligament rupture predicts elevation of chemokine MCP-1 associated with osteoarthritis

PurposeAnterior cruciate ligament rupture is associated with characteristic bone contusions in approximately 80% of patients, and these have been correlated with higher pain scores. Bone bruising may indicate joint damage that increases inflammation and the likelihood of posttraumatic osteoarthritis. We sought to characterize the severity of bone bruising following acute anterior cruciate ligament injury and determine if it correlates with synovial fluid and serum levels of the proinflammatory chemokine monocyte chemoattractant protein-1 associated with posttraumatic osteoarthritis.MethodsThis was a retrospective analysis of data collected prospectively from January 2014 through December 2016. All patients who sustained an acute ligament rupture were evaluated within 15 days of injury, obtained a magnetic resonance imaging study, and underwent bone-patellar-tendon-bone autograft reconstruction were offered enrollment. The overall severity of bone bruising on magnetic resonance imaging was graded (sum of 0–3 grades in 13 sectors of the articular surfaces). Serum and synovial fluid levels of monocyte chemoattractant protein-1 were measured within 14 days of injury, and serum levels were again measured 6 and 12 months following surgery. Separate univariate linear regression models were constructed to determine the association between monocyte chemoattractant protein-1 and bone bruising severity at each time point.ResultsForty-eight subjects were included in this study. They had a mean age of 21.4 years and were 48% female. Median overall bone bruising severity was 5 (range 0–14). Severity of bone bruising correlated with higher synovial fluid concentrations of monocyte chemoattractant protein-1 preoperatively (R2 = 0.18, p = 0.009) and with serum concentrations at 12 months post-reconstruction (R2 = 0.12, p = 0.04).ConclusionsThe severity of bone bruising following anterior cruciate ligament rupture is associated with higher levels of the proinflammatory cytokine monocyte chemoattractant protein-1 in synovial fluid acutely post-injury and in serum 12-months following anterior cruciate ligament reconstruction. This suggests that severe bone bruising on magnetic resonance imaging after ligament rupture may indicate increased risk for persistent joint inflammation and posttraumatic osteoarthritis.Level of evidenceIII ― retrospective cohort study.

Interplay Between Iron Overload and Osteoarthritis: Clinical Significance and Cellular Mechanisms.

There are multiple diseases or conditions such as hereditary hemochromatosis, hemophilia, thalassemia, sickle cell disease, aging, and estrogen deficiency that can cause iron overload in the human body. These diseases or conditions are frequently associated with osteoarthritic phenotypes, such as progressive cartilage degradation, alterations in the microarchitecture and biomechanics of the subchondral bone, persistent joint inflammation, proliferative synovitis, and synovial pannus. Growing evidences suggest that the conditions of pathological iron overload are associated with these osteoarthritic phenotypes. Osteoarthritis (OA) is an important complication in patients suffering from iron overload-related diseases and conditions. This review aims to summarize the findings and observations made in the field of iron overload-related OA while conducting clinical and basic research works. OA is a whole-joint disease that affects the articular cartilage lining surfaces of bones, subchondral bones, and synovial tissues in the joint cavity. Chondrocytes, osteoclasts, osteoblasts, and synovial-derived cells are involved in the disease. In this review, we will elucidate the cellular and molecular mechanisms associated with iron overload and the negative influence that iron overload has on joint homeostasis. The promising value of interrupting the pathologic effects of iron overload is also well discussed for the development of improved therapeutics that can be used in the field of OA.