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ID PMID Title PublicationDate abstract
30792744 A Network Pharmacology Approach to Explore Mechanism of Action of Longzuan Tongbi Formula 2019 Longzuan Tongbi Formula (LZTB) is an effective proved prescription in Zhuang medicine for treating active rheumatoid arthritis (RA). However, its active ingredients, underlying targets, and pharmacological mechanism are still not clear in treating RA. We have applied network pharmacology to study LZTB and found that 8 herbs in LZTB and 67 compounds in the 8 herbs are involved in the regulation of RA-related genes; we have conducted pathway analysis of overlapping genes and found that 7 herbs participate in the regulations of 24 pathways associated with RA and that 5 herbs in the 7 herbs and 25 compounds in the 5 herbs participate in the regulation of hsa05323 (rheumatoid arthritis). The results indicated that all herbs in LZTB and some compounds in those herbs participate in the treatment of RA; 25 compounds are main active ingredients and hsa05323 (rheumatoid arthritis) is the major pathway in the treatment of RA. We have also found that three pathways (inflammatory mediator regulation of TRP channels, PPAR signaling pathway, and mTOR signaling pathway) might have some effect on the treatment of RA.
31360575 Fifty-Two-Week Results of Clinical and Imaging Assessments of a Patient with Rheumatoid Ar 2019 Baricitinib is a Janus kinase 1/2 (JAK1/2) inhibitor used in the treatment of rheumatoid arthritis. A 71-year-old woman with rheumatoid arthritis complicated by systemic sclerosis and type 1 diabetes that were resistant to multiple disease-modifying antirheumatic drugs started treatment with baricitinib. After baricitinib administration, the disease activity of her rheumatoid arthritis was attenuated from the early stage of treatment, and the effect was maintained for up to 52 weeks. In addition, the skin sclerosis in systemic sclerosis showed an improvement. Regarding the influence on type 1 diabetes, the required daily dose of insulin and hemoglobin A1c (HbA1c) levels decreased. To date, no studies have demonstrated the effectiveness of baricitinib on systemic sclerosis or type 1 diabetes. We report that baricitinib was effective for systemic sclerosis and type 1 diabetes, as well as for rheumatoid arthritis, for up to 52 weeks.
31681693 A rare case of Rhupus syndrome with Hashimoto's thyroiditis, associated adverse effect of 2019 Sep The term Rhupus is coded for the individuals who have rheumatoid like arthritis with erosions and fulfil the criteria for both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Abnormal Th2 cell plays a central role in SLE while Th1 participate in RA. Thus the overlap of SLE and RA has a very low incidence (0.01%-0.2%) in patient with arthritis. This 40-year-old male patient presented with complains of severe multiple joint pain with progressive deformities, diminished vision from last 2 months, redness on back, headache and swelling over scalp. As this patient had history of severe trauma that was considered as a precipitating factor for ongoing chronic inflammatory disorder. Posterior subcapsular cataract was explained by prolong use of systemic steroid and rashes on the lower back due to sulfasalazine. Radioimaging study revealed arachnoid cyst and calcified projection arising from outer table of skull, which was kept under observation.
30805340 Psoriatic Synovitis: Singularity and Potential Clinical Implications. 2019 Psoriatic arthritis (PsA) is an immuno-inflammatory disease with a heterogeneous clinical presentation as affects musculoskeletal tissues (arthritis, enthesitis, spondylitis), skin (psoriasis) and, less frequently, eye (uveitis) and bowel (inflammatory bowel disease). It has been suggested that distinct affected tissues could exhibit different immune-inflammatory pathways so complicating the understanding of the physiopathology of psoriatic disease as well as its treatment. Despite of the key pathogenic and clinical relevance that enthesitis has in PsA, peripheral arthritis is more easily perceived. At the macroscopic level, PsA synovitis has predominantly tortuous, bushy vessels, whereas rheumatoid arthritis (RA) is characterized by mainly straight, branching vessels so reflecting prominent neo-angiogenesis in PsA. Synovial biopsies have demonstrated a similar cellular and molecular picture in PsA and RA, although some differences have been reported at the group level, as higher density of vessels, CD163+ macrophages, neutrophils and mast cells in PsA. In fact, synovial IL-17+ mast cells are significantly increased in PsA and produce more IL-17A compared with RA, and a proof of concept study supports its relevant role in the synovitis of SpA, included PsA. As firstly reported in RA, synovial lymphoid neogenesis is found also in the same proportion of PsA as in RA patients, despite the lack of autoantibodies in PsA. These lymphoid structures are associated with activation of the IL-23/Th17 pathway in RA and seemly in PsA, which could be useful to stratify RA patients. Immunohistochemical and transcriptomic methodologies have still not found synovial biomarkers useful to distinguish psoriatic from rheumatoid synovitis at the patient level. However, modern methodologies, as MALDI-Mass Spectrometry Imaging, applied to the study of synovial tissue have revealed metabolic and lipid signatures which could support clinical decision-making in the diagnosis of PsA and RA and to go further toward the personalized medicine.
30733840 Crosstalk between Fas and S1P(1) signaling via NF-kB in osteoclasts controls bone destruct 2019 Nov Rheumatoid arthritis (RA) mainly affects various joints of the body, including the temporomandibular joint (TMJ), and it involves an infiltration of autoantibodies and inflammatory leukocytes into articular tissues and the synovium. Initially, the synovial lining tissue becomes engaged with several kinds of infiltrating cells, including osteoclasts, macrophages, lymphocytes, and plasma cells. Eventually, bone degradation occurs. In order to elucidate the best therapy for RA, a comprehensive study of RA pathogenesis needs to be completed. In this article, we discuss a Fas-deficient condition which develops into RA, with an emphasis on the role of sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling which induces the migration of osteoclast precursor cells. We describe that Fas/S1P(1) signaling via NF-κB activation in osteoclasts is a key factor in TMJ-RA severity and we discuss a strategy for blocking nuclear translocation of the p50 NF-κB subunit as a potential therapy for attenuating osteoclastogenesis.
33654849 A Refined Protocol for Identifying Citrulline-specific Monoclonal Antibodies from Single H 2019 Sep 5 We describe here a detailed, refined protocol for the generation of citrulline-specific monoclonal antibodies from single human B cells from rheumatoid arthritis (RA) patients. This protocol provides a detailed guide of the procedure starting from single B cells of your choice and followed by amplification of the variable region of immunoglobulin genes by RT-PCR, subsequent immunoglobulin gene cloning, recombinant IgG1 monoclonal antibody (mAb) production and quality controls. The produced mAbs can be used for further studies including reactivity towards candidate antigens and functionality both in vitro and in vivo. This protocol can be used to generate antigen-specific mAbs from B cells derived from different tissues and compartments, including peripheral blood, synovial fluid, digested biopsies, bone marrow aspirations, and bronchoalveolar lavage fluid. Notably, although examples are given on how to identify citrulline-specific autoantibodies the general methods can also be applied to other reactivities.
30775301 A Case of Rhupus-reporting of a Rare Entity. 2019 Jan Rhupus syndrome, a rare entity, is the co-existence of systemic lupus erythematosus (SLE) with rheumatoid arthritis (RA). It manifests as more RA and less SLE related damages. The duration of the disease is longer than typical RA or SLE. Controversies exist regarding the definition of Rhupus. The incidence of Rhupus in patients with arthritis is 0.01%-0.2% and <2% in patients with connective tissue diseases. However, we report a rare case of rhupus in a 55-year-old lady with polyarthritis and joint deformities of 6 year duration, presenting with features of lupus erythematosus.
31382539 Cartilage and Bone Destruction in Arthritis: Pathogenesis and Treatment Strategy: A Litera 2019 Aug 2 Arthritis is inflammation of the joints accompanied by osteochondral destruction. It can take many forms, including osteoarthritis, rheumatoid arthritis, and psoriatic arthritis. These diseases share one commonality-osteochondral destruction based on inflammation. The background includes a close interaction between osseous tissues and immune cells through various inflammatory cytokines. However, the tissues and cytokines that play major roles are different in each disease, and as a result, the mechanism of osteochondral destruction also differs. In recent years, there have been many findings regarding not only extracellular signaling pathways but also intracellular signaling pathways. In particular, we anticipate that the intracellular signals of osteoclasts, which play a central role in bone destruction, will become novel therapeutic targets. In this review, we have summarized the pathology of arthritis and the latest findings on the mechanism of osteochondral destruction, as well as present and future therapeutic strategies for these targets.
31156654 Corrigendum: Increased Binding of Specificity Protein 1 to the IL21R Promoter in B Cells R 2019 [This corrects the article DOI: 10.3389/fimmu.2018.01978.].
30408452 Therapeutic effects of polysaccharides from Anoectochilus roxburghii on type II collagen-i 2019 Feb 1 Anoectochilus roxburghii, a famous Chinese herbal medicine, has been commonly used for the treatment of liver disease, diabetes, and rheumatoid arthritis. Our study aimed to investigate the anti-rheumatoid arthritis effects of A. roxburghii polysaccharides (ARP), using the rat's model of type II collagen-induced arthritis (CIA). ARP was prepared by alcohol sedimentation and structurally characterized based on combined chemical, chromatographic and spectroscopic methods. High Performance Size Exclusion Chromatography-Multiangle Laser Light Scattering-Refrative Index (HPSEC-MALLS-RI) analysis revealed that ARP includes two peaks, and the weight-average molecular weight (Mw) of the principal one was estimated as 5.90 kDa with a relative content of 98.2%. Pharmacological results exhibited that ARP significantly decreased the arthritis index and ameliorated the inflammatory cell infiltration and the synovial tissue destruction in CIA rats. Additionally, ARP possessed significant NO production inhibitory effects and antioxidant activity. Further anti-inflammatory mechanism investigations indicated that ARP significantly inhibited the activation of nuclear factor κB (NF-κB) pathway by suppressing the phosphorylation of IκB and p65, which subsequently down-regulated the mRNA expressions of IL-1β and IL-6 in LPS-stimulated RAW 264.7 cells. These findings suggested that ARP has great potential in the development of functional foods and dietary supplements for the treatment of rheumatoid arthritis.
32707025 Surgical Management of the Lumbar Spine in Rheumatoid Arthritis. 2020 Sep STUDY DESIGN: Narrative review. OBJECTIVE: To provide an overview on the diagnosis and surgical management of rheumatoid involvement of the lumbar spine. Rheumatoid arthritis (RA) is a chronic inflammatory disease of synovial joints, most commonly appendicular followed by axial. Although cervical spine involvement of RA is well documented, data on lumbar spine involvement and surgical management remains limited. METHODS: Using PubMed, studies published prior to November 2018 with the keywords "RA, etiology"; "RA, spine management"; "RA, surgical management"; "RA, treatment"; "RA, DMARDs"; "RA, lumbar spine"; "RA, spine surgical outcomes"; "RA, imaging" were evaluated. RESULTS: The narrative review addresses the epidemiology, manifestations, imaging, surgical complications, and operative and nonoperative management of RA involvement of the lumbar spine. CONCLUSIONS: Rheumatoid involvement of the lumbar spine can present with lower back pain, neurogenic claudication, radiculopathy, spinal deformity, and instability. Patients with RA have significantly higher rates of vertebral fractures and complications following surgical intervention. However, in the setting of instability and spinal deformity, thoughtful surgical planning in conjunction with optimal medical management is recommended.
31037011 A case of an elderly hip disarticulation amputee with rheumatoid arthritis who regained th 2019 Apr [Purpose] We report a case of an elderly patient with rheumatoid arthritis who underwent hip disarticulation because of necrotizing fasciitis and regained the ability to walk independently with a prosthetic limb. [Participant and Methods] A 61-year-old female patient underwent right hip disarticulation due to severe necrotizing fasciitis of the right lower limb. Her chief complaint was that she was not able to walk inside her house or outdoors to perform instrumental activities of daily living. We applied a Canadian-type hip disarticulation prosthesis to the stump. The patient received in-hospital physical therapy, occupational therapy, and clinical psychology counselling for 145 days. As her hands and fingers were weakened by rheumatism, we made several modifications to the prosthesis to enable the patient to attach and detach it independently. [Results] The patient was able to use the prosthesis to walk continuously for 45 m, perform various housework duties, drive a car, and go out, thus accomplishing the desired daily activities. [Conclusion] Our patient, an elderly hip disarticulation amputee with rheumatoid arthritis, was able to walk independently using a prosthetic limb. The application of prosthetic limbs may be appropriate even for hip disarticulation amputees with comorbidities that make it difficult to acquire a prosthetic gait.
31719966 Rheumatoid arthritis mediator CD18 expression by Staphylococcus aureus superantigen C in r 2019 Aug BACKGROUND AND OBJECTIVES: Microbial superantigens have been reported in the blood and synovial fluid of rheumatoid arthritis patients, raising the question of whether the presence of these superantigens could provoke the induction of inflammatory biomarkers expression or not. The purpose of this study was to examine the Staphylococcus aureus superantigen C on CD18 expression. MATERIALS AND METHODS: The superantigen C was purified by ultrafiltration. Immunoblotting was performed using a specific antibody. Also, 50 micrograms of superantigens (toxin) were injected intraperitoneally and intra-articularly into separate rat groups. Blood was collected and RNA extracted. Then, the cDNA was synthesized. The expression of CD18 marker was evaluated using RT-real-time PCR, and the results were descriptively analyzed. RESULTS: The results of this study revealed that 50 μg of toxin, injected intra-articularly and intraperitoneally, showed the surplus expression of the marker CD18 in the blood of rats after 20 days. By this method, the expression of the marker CD18 was significantly different between rats that received the superantigen intra-articularly and intraperitoneally (2.10; 2.3 and 3.3 folds) and the controls (P≤ 0.05). CONCLUSION: The results indicated that the presence of Staphylococcal of superantigen C in the body of rats has enhanced the expression of the CD18 inflammatory marker more than 3 times. This valuable finding is an introduction to further research and could provide new methods to prevent and control inflammatory diseases, including rheumatoid arthritis.
32467870 Fasting mimicking diets: A literature review of their impact on inflammatory arthritis. 2019 Dec Fasting is an act of restricting, for a certain length of time, food intake or intake of particular foods, and has been part of religious rituals for centuries. Religions such as Christianity and Islam use this practice as a form of sacrifice, self-discipline, and gratitude. However, in the past decade, fasting has penetrated the mainstream as a diet trend. There are several ways of fasting; existing fast mimicking eating methods promise accelerated weight loss, and many more benefits: lower cholesterol, prevention of type 2 diabetes and a longer lifespan. Even more, it has been proposed that fasting can downregulate the inflammatory process and potentially be used as a treatment regimen for several diseases. Here, we review the effects of fasting on immune and inflammatory pathways. Also, we present current knowledge about the role of fasting in the activity of inflammatory arthritides with a focus on rheumatoid arthritis.
30697959 Juvenile Sjögren's Syndrome: Clinical Characteristics With Focus on Salivary Gland Ultras 2020 Jan OBJECTIVE: Juvenile Sjögren's syndrome (SS) is a rare, poorly defined, and possibly underdiagnosed condition affecting children and adolescents. The aim of this study was to characterize symptoms and clinical findings of juvenile SS and to explore the clinical application of major salivary gland ultrasonography (SGUS) in patients with juvenile SS. METHODS: A cross-sectional multicenter study recruited patients with disease onset until age 18 years (n = 67). Disease characteristics were recorded, and unstimulated whole sialometry and SGUS examination of the parotid and submandibular salivary glands were performed. RESULTS: The female:male ratio was 58:9. The mean age at first symptom was 10.2 years and 12.1 years at diagnosis. Ocular and oral symptoms were noted in 42 of 67 patients (63%) and 53 of 66 patients (80%), respectively. The American-European Consensus Group or American College of Rheumatology/European League Against Rheumatism classification criteria for primary SS were fulfilled by 42 of 67 patients (63%). Pathologic SGUS findings were observed in 41 of 67 patients (61%); 26 of 41 SGUS+ patients (63%) fulfilled primary SS criteria. Salivary gland enlargements/parotitis were noted in 37 of 58 patients and were nonsignificantly associated with SGUS+ status (P = 0.066). The mean levels of saliva were 5.6 ml/15 minutes in SGUS- patients compared to 3.3 ml/15 minutes in the SGUS+ patients (P = 0.049). A total of 36 of 41 SGUS+ patients (88%) were anti-Ro/La+ compared to 14 of 26 SGUS- patients (54%) (P = 0.001). In addition, 24 of 39 SGUS+ patients (62%) were positive for rheumatoid factor (RF), whereas only 5 of 25 SGUS- patients (20%) were RF+ (P = 0.001). CONCLUSION: Juvenile SS is characterized by a large spectrum of clinical symptoms and findings. Several glandular and extraglandular parameters such as hyposalivation, swollen salivary glands, and autoantibodies are associated with pathologic SGUS findings.
30834192 Effect of periodontal therapy on disease activity in patients of rheumatoid arthritis with 2019 Apr BACKGROUND: Evidence have been proposed a positive association between severity of Periodontitis and Rheumatoid arthritis (RA) activity, individuals with advanced RA are more likely to develop periodontal problems compared to their non-RA counterparts, and vice versa. Studies have been suggested that RA manifest as a result of an inflammatory imbalance and autoimmunity. In this perspective, treatment modalities that lead to inhibition of proinflammatory mediators, may prove beneficial for reducing the severity of RA. This study examined the effects of non surgical periodontal therapy (NSPT) on disease activity of RA. METHODS: Diagnosed patients of active rheumatoid arthritis with chronic periodontitis were recruited in this study and divided in to treatment and controls groups, both groups were similar in all demographics assessed. Treatment group (n = 20) and controls group (n = 20) underwent assessment for periodontal clinical parameters (plaque index, gingival index, probing pocket depth, clinical attachment level), Rheumatologic clinical (simplified disease activity index) and biochemical parameters(C-reactive protein, Rheumatoid factor, Anti-cyclic citrullinated protein) at baseline and 8 weeks. Serum levels of biochemical parameters were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The statistically significant (p < 0.001) reduction observed in mean values of PI, GI, PPD, CAL, SDAI in treatment group at 8weeks after NSPT as compare to control group. However serum level of ACCPA, CRP and RF did not show statistically significant (p > 0.05) changes from baseline to reassessment (8 weeks) in both groups. CONCLUSIONS: The improvement in RA disease activity may occurs after non surgical periodontal therapy.
32398909 Efficacy of Seetarama Vati (A Sri Lankan traditional drug) and Vatari Guggulu in the manag 2019 Apr INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease caused by type III hypersensitivity reaction due to antigen antibody complexes which deposit at the joints resulting in arthritis. As per the concept of Ayurveda, it can be co-related with Amavata, the disease arising from deranged metabolism and Vata vitiation. Despite of advancement in diagnostic approach of RA, management of it remains challenge. Vatari Guggulu and Seetarama Vati are the formulations having analgesics properties due to their Ushna (metabolism enhancing) and Tikshna Guna (micro channel cleaning) and simultaneously possess anti-inflammatory properties. AIMS AND OBJECTIVES: To evaluate and compare the efficacy of Vatari Guggulu and Seetarama Vati in the management of Amavata w.s.r. to rheumatoid arthritis. MATERIAL AND METHODS: For the present study, 58 patients were selected and divided into two groups. Patients of group A and group B were given Vatari Guggulu and Seetarama Vati respectively with warm water after meal for one month. Before administration of trial drugs in both of groups' patients were given 4-6 grams of Triphala powder depending upon the Koshtha of the patient, on empty stomach early morning for the purpose of Koshtha Shuddhi (purgation) for 3 days. In addition to assess effect on signs and symptoms of Amavata, haematological investigation, biochemical investigation including quantitative C-reactive protein (CRP) and rheumatoid factor (RA factor) and routine urinary examination were carried out before and after treatment in all the registered patients. The effect of therapy was assessed on the basis of changes in score in comparison to end point score. DISCUSSION: All the cardinal and associate complaints were statistically significant improved after the course of the trial drug. Most of the functional parameters had statistically significant improvement after treatment except left side foot pressure and DAS 28 scale in B group. Biochemical and hematological parameters were within normal limit before and after treatment. The difference of effect of trial drug on chief complaints was statistically insignificant. The difference of effect of trial drug on associate complaints was statistically insignificant. Difference of effect of trial drugs on ESR of both the groups was statistically insignificant. The difference of effect of trial drug on RA factor and CRP between groups was statistically significant. The difference of effect of trial drug on functional parameters between groups were statistically significant. CONCLUSION: The study revealed that, though both the trial drugs; Vatari Guggulu and Seetarama Vati are effective in the management of Amavata, but clinically Seetarama Vati is comparatively more effective than Vatari Guggulu in the management of Amavata.
31871961 Data on arsenic trioxide modulates Treg/Th17/Th1/Th2 cells in treatment-naïve rheumatoid 2019 Dec In this article, we share the raw protein and mRNA data obtained from basal and stimulated human peripheral blood mononuclear cells (PBMCs) derived from 15 individual treatment-naïve rheumatoid arthritis (RA) patients and synovial fluid mononuclear cells (SFMCs). In treatment-naïve RA patients, PBMCs were treated with a gradient of concentrations of As(2)O(3) (0, 0.1, 0.5, 1.0, 2.0, 4.0 μM) for 48 hours. We found that 2.0 μM As(2)O(3) promoted the apoptosis of PBMCs significantly, and 0.5 μM As(2)O(3) was the lowest and effective concentration that contributed to Treg cell generation but it prevented Th17 cell differentiation, as assessed by flow cytometry. Furthermore, As(2)O(3) decreased the transcription factor STAT3 mRNA expression of Th17 cells but increased the transcription factor Foxp3 of Treg cells. In synovial fluid from RA patients, consistent with PBMCs, As(2)O(3) inhibited Th17 cell differentiation but promoted Treg cell generation. In an animal experiment, we analyzed the body-weight of mice as the indicator of As(2)O(3) toxicity and calculated the spleen index. As(2)O(3) significantly decreased the hematoxylin and eosin score in Type II collagen-induced arthritis in mice. Furthermore, As(2)O(3) downregulated the frequency of Th1 but upregulated Th2 cells. For more insight please see Arsenic trioxide improves Treg and Th17 balance by modulating STAT3 in treatment-naive rheumatoid arthritis patients [1].
31434180 Arthritis diagnosis and early-life exposure to air pollution. 2019 Oct OBJECTIVES: Evaluate the relationship between arthritis diagnosis in those over 50 and exposure to extreme air pollution in utero or infancy (<1 year of age). METHODS: Compare rates of arthritis diagnosis between groups that experienced differential air pollution exposure in early-life due to quasi-random variation in birth location and date relative to the 1952 Great Smog in London. We use regression-estimated difference-in-differences analyses based on English Longitudinal Study of Aging (ELSA) data. RESULTS: In the 2816 respondent sample, aged 51-62, the arthritis diagnosis rate is 22.8%, with 16.4% reporting osteoarthritis and 4.6% reporting rheumatoid arthritis. We estimate that exposure to the Great Smog in infancy increases the arthritis diagnosis rate by 23.4 percentage points (95% CI: 1.97 to 44.8). Decomposing these results by type of arthritis reveals that the rheumatoid arthritis diagnosis rate increases due to infant exposure are larger and more significant than those for osteoarthritis: 14.9 percentage points (95% CI: 0.495 to 29.4) versus 9.5 percentage points (95% CI: -11.9 to 30.8). In utero exposure is not associated with significant increases in arthritis diagnosis rates. CONCLUSIONS: Our results are the first to link early-life air pollution exposure to later-life arthritis diagnoses, and suggest a particularly strong link for RA. These findings are consistent with those of shorter-term, correlational studies, and indicate that health effects of air pollution exposure can span decades and extend beyond cardiopulmonary systems.
31031529 Reliability of Ultrasound for the Detection of Rheumatoid Arthritis. 2019 Jan The aim of this review article was to investigate the pooled sensitivity and specificity of musculoskeletal ultrasound (MSUS) for the detection of synovitis and early bone erosion in the small joint in rheumatoid arthritis (RA). In addition, investigate the pooled sensitivity and specificity of Power Doppler ultrasonography (PDUS) for the detection of synovial hypervascularity in small joints in RA. A systematic literature search of PubMed, Wiley online library, Google Scholar, Research gate, E-book, BioMed Central, the Journal of Rheumatology and Springer Link were investigated from 2001 to 2017. Original researches related to the article written in English including RA, synovitis, bone erosion, grayscale, and PDUS were included in this study. The sample size, study design, sensitivity, and specificity were analyzed. The review summarizes the value of MSUS for the detection of RA as it is the first choice of modality. Results show the acceptable reliability of US for the diagnosis of early bone erosions, synovitis, and synovial hypervascularity.