Knee Joint In Rheumatoid Arthritis Research Articles

Thermal imaging in rheumatoid arthritis knee joints and its correlation with power Doppler ultrasound

BackgroundPower Doppler ultrasound (PDUS) is an established non-invasive modalities for quantification of inflammation, which has a bearing on the assessment of disease activity in rheumatoid arthritis (RA). However, PDUS has several disadvantages including cost of equipment, steep learning curve and inter-observer variability. Thermal imaging has emerged as a simple, powerful tool for mapping the heat distribution pattern and has the potential to document and quantify disease activity in RA. The objective was to study the thermal imaging pattern of inflamed knee joints in cases of RA and its correlation with PDUS. MethodsThis pilot case-control study was carried out at the rheumatology centre in India including 100 subjects (50 controls and 50 RA patients). All participants underwent thermal imaging and PDUS for the knee joints. The mean temperatures in area of interest in knee, thigh and knee–thigh differential were analysed in comparison with PDUS findings. ResultsRA subjects had significantly higher mean knee temperature and mean knee–thigh temperature differential compared with controls (p value < 0.00001). PDUS documented inflammation strongly correlated with knee–thigh temperature differential. ConclusionThere was a statistically significant difference in mean knee temperature as well as mean knee–thigh temperature differential of inflamed versus control knees. Thermal imaging has the potential to become simple, objective, cost-effective and reliable tool for diagnosis and assessment of disease activity in inflammatory arthritis.

The indexes of osteogenic stem cells activity in patients with rheumatoid arthritis and frontal knee deformities

Objective: to study the indexes of stem cells activity of bone marrow which form knee joint (lateral and medial parts of distal femur and proximal tibia part) which were cut at arthroplasty surgery in patients with rheumatoid arthritis and frontal knee deformity.Methods: spongiest bone was taken at surgery (knee arthroplasty) from medial and lateral sides of distal femur and proximal tibia. Due to cloning method of fibroblast colony forming units we studied in 37 patients with rheumatoid arthritis of knee joint. We studied 168 samples of bone marrow, 204 cultures of stem cells were growth.Results: we observed significant deceleration of reparative process in bone tissue at rheumatoid arthritis. Significant difference of fibroblast colony forming units in 1 sm 3 volume in different parts of knee joint was observed. In the medial femur condylar this index was (0,2307 ± 0,16) · 104, it exceeds values obtained in other areas in 11–20 times. It was shown that stem cells of the lateral tibia condylar had worse conditions for regenerative potential in cases of valgus deformity compare with varus. There were 4 times less amount of fibroblast colony forming units and the efficacy of its cloning was 2.6 times lower.Conclusion: significant differences were revealed in the indexes of osteogenic activity of stem cells which form knee joint (lateral and medial parts of distal femur and proximal tibia part).

Treatment Response Evaluation using Yttrium-90 in Patients with Rheumatoid Arthritis of Knee Joint.

For radiosynovectomy, we have measured the retention time of yttrium-90 (90Y) hydroxyapatite (particle size 1–10 μm) within the knee joint space and evaluated the treatment responses in knees with rheumatoid arthritis. Radioactive measurements in the region of knee after injection of 90Y hydroxyapatite into the joint space were made with a single prove system designed to monitor radioactivity and showed retention of 90Y in the knee ranged 76.6% ±5.4% after 4 days of injection. The clinical improvements in rheumatoid arthritis of knee joint with steinbroker Stages I and II were increased as time goes by, the improvement ratio is in 72% at 6th months and 76% at 12th months after injection of 90Y 185 MBq (5 mCi) per joint.

Arthritis of the Knee Joint in Rheumatoid Arthritis - Evaluation of Treatment Response by Ultrasound in Daily Clinical Practice.

Background: Rheumatoid arthritis (RA) commonly involves the knee joint in up to 30% of patients. Musculoskeletal ultrasound enables the skilled clinician to easily assess disease activity.Objective: To evaluate the sensitivity to change of the sonography score of large joints in Rheumatology (SOLAR) for different treatments of knee arthritis in RA.Method: Joints were assessed by ultrasound at 4 visits. Laboratory, immunological and clinical parameters were recorded.Results:225 RA patients were analyzed. The DAS 28 in the subgroup receiving systemic steroids was significantly higher (p < 0.001) than in patients treated with intraarticular glucocorticosteroids (GCs) at T0, comparing the values from T0 to T3 the same appeared (p=0.003). Concerning the acute GC treatment regimens, the gray scale ultrasound (GSUS) sum score was found to be significantly higher in patients receiving intraarticular GCs versus no GCs (p=0,035), as well as in patients receiving systemic versus intraarticular GCs (p=0.001). Regarding the differences from T0 and T3, similar to the baseline analysis, a high GSUS sum score was significantly associated with intraarticular GCs, a low to no GC administration (p=0.035), while a high GSUS sum score was significantly linked to intraarticular GCs, rather than systemic GCs (p=0.008).Conclusion: SOLAR score is sensitive to change in knee arthritis. Intraarticular GC administration is performed in patients with high GSUS scores. Systemic administration of GC is linked to high disease activity (DAS28) rather than GSUS or power Doppler ultrasound (PDUS) results.

Radiosynovectomy of Painful Synovitis of Knee Joints Due to Rheumatoid Arthritis by Intra-Articular Administration of (177)Lu-Labeled Hydroxyapatite Particulates: First Human Study and Initial Indian Experience.

The aim of this study is to assess the effectiveness of Radiosynovectomy (RSV) using 177Lu-labeled hydroxyapatite (177Lu-HA) in the treatment of painful synovitis and recurrent joint effusion of knee joints in rheumatoid arthritis (RA). Ten patients, diagnosed with RA and suffering from chronic painful resistant synovitis of the knee joints were referred for RSV. The joints were treated with 333 ± 46 MBq of 177Lu-HA particles administered intra-articularly. Monitoring of activity distribution was performed by static imaging of knee joint and whole-body gamma imaging. The patients were evaluated clinically before RSV and at 6 months after the treatment by considering the pain improvement from baseline values in terms of a 100-point visual analog scale (VAS), the improvement of knee flexibility and the pain remission during the night. RSV response was classified as poor (VAS < 25), fair (VAS ≥ 25-50), good (VAS ≥ 50-75) and excellent (VAS ≥ 75), with excellent and good results considered to be success, while fair and poor as failure and also by range of motion. Three phase bone scan (BS) was repeated after 6 months and changes in the second phase of BS3 were assessed visually, using a four-degree scale and in the third phase, semiquantitatively with J/B ratio to see the response. Biochemical analysis of C-reactive protein (CRP) and fibrinogen was repeated after 48 h, 4 and 24 weeks. In all 10 patients, no leakage of administered activity to nontarget organs was visible in the whole-body scan. Static scans of the joint at 1 month revealed complete retention of 177Lu-HA in the joints. All patients showed decreased joint swelling and pains, resulting in increased joint motion after 6 months. The percentage of VAS improvement from baseline values was 79.5 ± 20.0% 6 months after RS and found to be significantly related to patients' age (P = 0.01) and duration of the disease (P = 0.03). Knees with Steinbrocker's Grades 0 and I responded better than those with more advanced changes (Steinbrocker's Grades III and IV) in terms of VAS improvement (75% vs. 45.8%) (P < 0.001). The overall success rate (VAS ≥ 50) was 80%. Remission of pain during the night was achieved in 100%, and knee flexibility was improved in 80%. The changes in the blood pool phase before RSV were 3.2 ± 0.7 and after the therapy 1.4 ± 0.7 (P < 0.001). The J/B ratio was: Before RSV 2.4 ± 0.3; after treatment 1.0 ± 0.2 (P < 0.05). CRP concentration 4 and 24 weeks after the therapy was significantly lower than before treatment. The fibrinogen level was not different before and after RSV. RSV side-effects assessed for the whole follow-up period were minor and not significant. RSV with 177Lu-HA was safe and effective in patients with knee joint chronic painful synovitis of rheumatoid origin. It exhibited significant therapeutic effect after 6 months follow-up period with no significant side-effects. The preliminary investigations reveal that 177Lu-labeled HA particles hold considerable promise as a cost-effective agent for RSV. More elaborate and controlled clinical trials are necessary to evaluate the therapeutic efficacy and safety of the agent compared with the treatment with other radionuclides and glucocorticosteroids.

SAT0402 Evaluation of weight-bearing joint damage in patients with rheumatoid arthritis using a new radiographic scoring method (ARASHI)

BackgroundThe radiographic joint damage in rheumatoid arthritis (RA) is commonly evaluated by van der Heijde total Sharp score, however only small joints of hands and feet are assessed in this...

OP0015 Evaluation of Hip and Knee Joint Damage in Patients with Rheumatoid Arthritis Using a Newly Developed Radiographic Scoring Method (ARASHI)

BackgroundThe radiographic joint damage in patients with rheumatoid arthritis (RA) is commonly evaluated by van der Heijde total Sharp score, intended only for the assessment of small joints. For the...

AB0107 AKT activation by fibronectin fragment leads to NF-KB up-regulation in rheumatoid arthritic chondrocytes

BackgroundIncreased fibronectin fragments are thought to contribute to joint destruction in rheumatoid arthritis (RA). However, the mechanism whereby fibronectin fragments cause catabolic activities is not totally understood. While COOH-terminal heparin-binding...

Reliability and responsiveness of dynamic contrast-enhanced magnetic resonance imaging in rheumatoid arthritis

Objectives: To investigate the responsiveness to treatment and the reliability of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rheumatoid arthritis (RA) knee joints.Methods: DCE-MRI was performed in 12 clinically active RA knee joints before and 1, 7, 30, and 180 days after intra-articular injection with 80 mg methylprednisolone. Using semi-automated image processing software, DCE-MRI parameters, including the initial rate of enhancement (IRE) and maximal enhancement (ME), were generated for three regions of interest (ROIs): ‘Whole slice’, ‘Quick ROI’, and ‘Precise ROI’. The smallest detectable difference (SDD), the smallest detectable change (SDC), and intra- and inter-reader intraclass correlation coefficients (ICCs) were used to assess the reliability of DCE-MRI. Responsiveness to treatment was assessed by the standardized response mean (SRM).Results: In all patients clinical remission of the knee was achieved at day 7. All DCE-MRI parameters decreased from day 0 to day 7. Using the Quick and Precise ROI methods, respectively, IRE decreased by 63% and 69%, ME decreased by 11% and 11%, Nvoxel decreased by 55% and 57%, and IRE × Nvoxel decreased by 84% and 85%. The intra- and inter-reader ICCs were very high (0.96–1.00). The decrease in DCE-MRI parameters was larger than the SDC for all patients. SRM was large for all parameters, ranging from –1.04 to –2.40. When the Whole slice ROI method was used, no parameters were responsive to treatment.Conclusions: DCE-MRI analysed using semi-automatic software is a reliable and responsive tool for assessing treatment in RA knees joints. Rough manual delineation of the joint to omit enhancement artefacts is necessary.

Osmolarity regulates chondrogenic differentiation potential of synovial fluid derived mesenchymal progenitor cells

Cartilage is one of few tissues where adult stem/progenitor cells have not been putatively identified. Recent studies have provided strong evidence that a sub-population of mesenchymal progenitor cells (MPCs) derived from the synovial fluid may be able to affect some degree of cartilage repair both in vivo and in vitro/ex vivo, however this does not appear to be the case in patients with arthritis. Previously, it has been found that synovial fluid osmolarity is decreased in patients with osteoarthritis (OA) or Rheumatoid arthritis (RA) and these changes in osmolarity have been linked to changes in chondrocyte gene regulation. However, it is yet unknown if changes in osmolarity regulate the gene expression in synovial fluid MPCs (sfMPCs), and by extension, chondrogenesis of this cell population. In the present study we have collected synovial fluid samples from normal, OA and RA knee joints, quantified the osmolarity of the fluid and modified the culture/differentiation media to span a range of osmolarities (264–375mOsm). Chondrogenesis was measured with Alcian blue staining of cultures in addition to quantitative PCR (qPCR) using probes to Sox9, ACAN and Col2A1. Overall, sfMPCs from arthritic joints demonstrated decreased chondrogenic potential compared to sfMPCs isolated from normal synovial fluid. Furthermore, the sfMPCs retained increased chondrogenic potential if differentiated under the same osmolarity conditions for which they were initially derived within. In conclusion, it does appear the synovial fluid osmolarity regulates the chondrogenic potential of sfMPCs, however, further study is required to elucidate the mechanism by which the changes in osmolarity are sensed by the cells and regulate chondrogenic gene expression.

Dynamic gadolinium-enhanced magnetic resonance imaging allows accurate assessment of the synovial inflammatory activity in rheumatoid arthritis knee joints: a comparison with synovial histology

Objective: To determine whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) evaluated using semi-automatic image processing software can accurately assess synovial inflammation in rheumatoid arthritis (RA) knee joints.Methods: In 17 RA patients undergoing knee surgery, the average grade of histological synovial inflammation was determined from four biopsies obtained during surgery. A preoperative series of T1-weighted dynamic fast low-angle shot (FLASH) MR images was obtained. Parameters characterizing contrast uptake dynamics, including the initial rate of enhancement (IRE), were generated by the software in three different areas: (I) the entire slice (Whole slice); (II) a manually outlined region of interest (ROI) drawn quickly around the joint, omitting large artefacts such as blood vessels (Quick ROI); and (III) a manually outlined ROI following the synovial capsule of the knee joint (Precise ROI). Intra- and inter-reader agreement was assessed using the intra-class correlation coefficient (ICC).Results: The IRE from the Quick ROI and the Precise ROI revealed high correlations to the grade of histological inflammation (Spearman’s correlation coefficient (rho) = 0.70, p = 0.001 and rho = 0.74, p = 0.001, respectively). Intra- and inter-reader ICCs were very high (0.93–1.00). No Whole slice parameters were correlated to histology.Conclusion: DCE-MRI provides fast and accurate assessment of synovial inflammation in RA patients. Manual outlining of the joint to omit large artefacts is necessary.

Combined Arthroscopic and Radiation Synovectomy of the Knee Joint in Rheumatoid Arthritis: 14-Year Follow-Up

To investigate the long-term outcome of combined arthroscopic and radiation synovectomy of the knee joint in early cases of rheumatoid arthritis (RA) with regard to knee function and the need for surgical re-interventions. Between 1993 and 1997, a consecutive series of 38 RA patients with therapy-refractory synovitis of the knee joint and only mild cartilage lesions (not exceeding Outerbridge grade II at surgery) were treated with combined arthroscopic and radiation synovectomy. Knee function was assessed preoperatively; at 6 months, 1 year, and 5 years; and finally, at a mean of 14 years with 4 different functional scores. A Kaplan-Meier survival curve was calculated with "any re-intervention" and "total knee arthroplasty" as endpoints. Of 38 knees, 32 were available for the final 14-year follow-up with a total of 22 re-interventions: intra-articular steroid injection (n = 3), arthroscopic (n = 2) or radiation (n = 1) re-synovectomy, and total knee arthroplasty (n = 16). The remaining 10 patients with no re-intervention showed knee function not significantly different from the postoperative state. With any surgical re-intervention as the endpoint, the survival rate was 84% at 5 years (95% confidence interval [CI], 67.0% to 86.7%), 44% at 10 years (95% CI, 26.7% to 60.0%), and 32% at the 14-year assessment (95% CI, 16.0% to 49.3%). With total knee arthroplasty as the endpoint, the joint survival rate was 88.5% at 5 years (95% CI, 68.5% to 96.2%), 53.9% at 10 years (95% CI, 33.3% to 71.6%), and 39.6% at 14 years (95% CI, 18.9% to 48.6%). Combined arthroscopic and radiation synovectomy leads to a stable improvement of knee function for a minimum of 5 years, but surgical re-interventions were frequently observed at the 14-year assessment and challenge the long-term benefit of the procedure. Patients with no interventions had a significantly shorter history of disease (7 v 11 years). Level IV, therapeutic case series.

Arthroscopic Synovectomy of the Knee Joint in Rheumatoid Arthritis

Arthroscopic Synovectomy of the Knee Joint in Rheumatoid Arthritis

Hyaluronan Inhibits Prostaglandin E2 Production via CD44 in U937 Human Macrophages

Prostaglandin E(2) (PGE(2)) is one of the key mediators of inflammation in affected joints of rheumatoid arthritis (RA). Intra-articular injection of high molecular weight hyaluronan (HA) into RA knee joints relieves arthritic pain. Although HA has been shown to inhibit PGE(2) production in cytokine-stimulated synovial fibroblasts, it remains unclear how HA suppresses PGE(2) production in activated cells. Furthermore, HA effect on macrophages has rarely been investigated in spite of their contribution to RA joint pathology. This study was aimed to investigate the inhibitory mechanism of HA on lipopolysaccharide (LPS)-stimulated PGE(2) production in U937 human macrophages. Stimulation of U937 macrophages with LPS enhanced PGE(2) production in association with increased protein levels of cyclooxygenase-2 (COX-2). Pretreatment with HA of 2,700 kDa resulted in suppression of the LPS-mediated induction of COX-2, leading to a decrease in PGE(2) production. Likewise, the LPS-stimulated PGE(2) production was inhibited by the pretreatment with a specific COX2 inhibitor, NS-398, or a specific inhibitor of nuclear factor (NF)-kappaB, BAY11-7085. HA also decreased the degree of phosphorylation and nuclear translocation of NF-kappaB enhanced by LPS. Fluorescence cytochemistry demonstrated that HA bound to CD44, the principal HA receptor, on U937 macrophages. Anti-CD44 antibody reversed the inhibitory effects of HA on the LPS-mediated increase in PGE(2) production, COX-2 induction, and activation of NF-kappaB. These results indicate that HA suppresses the LPS-stimulated PGE(2) production via CD44 through down-regulation of NF-kappaB. Administration of HA into RA joints may decrease PGE(2) production by activated macrophages, which could result in improvement of arthritic pain.

CHANGES AND CORRELATION OF THE DATA OF KNEE JOINT X-RAY AND ARTHROSCOPIC STUDIES IN RHEUMATOID SYNOVITIS

Objective: to compare the data of knee joint X-ray and arthroscopic studies in the presence of rheumatoid synovitis. Subjects and methods. Sixty-seven patients who had undergone 72 arthroscopic synovectomic operations on 72 joints for chronic knee-joint synovitis in the presence of rheumatoid arthritis (RA) were examined. Preoperative knee-joint X-ray study was carried out with the standard projections in all the patients. In most cases, the magnitude of X-ray changes corresponded to grade 1 according to the Larsen classification. The degree of articular cartilage destruction was intraoperatively estimated. Repeated X-ray films were made 6 and 30-36 months after arthroscopy. Results. It has been fount that in 72,2% of cases, the true articular cartilage changes detectable by arthroscopic revision were ascertained to coincide in their magnitude with the X-ray changes determined by the Larsen classification or to exceed them. Conclusion. In knee-joint RA, arthroscopic revision can provide the fullest information on the severity of pathological changes; however, X-ray study aids to a certain degree in the prediction of arthroscopic findings, including those of articular cartilage pathology.

Activity of plasminogen activators and plasmin inhibitors in the joint capsule in various articular diseases (author's transl)

The activity of plasminogen activators and plasmin inhibitors in articular capsules of the hip and knee joints in rheumatoid arthritis, chronic traumatic inflammation, arthrosis and aseptic loosening of prosthesis was determined histochemically and correlated with the degree of mobility in osteoarthrosis of the hip. Microscopically unchanged articular capsules were employed as reference sites. In inflammatory articular diseases the plasminogen activator activity was significantly reduced, whereas it remained unchanged in arthrosis and necrosis of the heas of the femur, and significantly enhanced in aseptic loosening of prosthesis. Plasmin inhibitor activity was established in joint capsules with inflammatory changes only; in case of rheumatic inflammation, it was higher than with traumatic inflammation. In osteoarthrosis of the hip there is a positive correlation between joint mobility and plasminogen activator activity. The results point towards involvement of the local fibrinolytic system in joint diseases; however, no definite statement can be made with regard to possible causative linkups.

Value of passive postoperative mobilization treatment following knee joint synovectomy in chronic polyarthritis

One group of 17 Knee joints was treated postoperatively with continuous passive motion, while the control group received cyclical changes of the Knee's position in flexion and extension. In the postoperative period the CPM-treated patients suffered less pain than the control group. Furthermore the patients of the CPM-group reached free extension and 90 degrees of flexion earlier than the control group. The amount of liquid in the suction drainage was higher in the CPM-group than in the control group. Based on the results of our examination continuous passive motion is considered to be a useful contribution to the postoperative treatment of synovectomy of the knee joint in rheumatoid arthritis.

Arthroscopic Synovectomy of the Knee Joint in Rheumatoid Arthritis: Surgical Steps for Complete Synovectomy

For successful arthroscopic total synovectomy in rheumatoid arthritis of the knee, proper sequential steps are required. First, we resect hypertrophied synovial villi on the intercondylar notch to make a gateway for the posterior compartments. We also perform synovectomy at the posterolateral chamber because of the narrower space of the chamber than that of the posteromedial chamber and the intra-articular crowding due to swollen synovial villi with the passage of operation time. Special care should be taken not to overlook both posterior back corners and roofs, which cannot be seen through the transnotch view, even with a 70° arthroscope. The posterior back corners and roofs can be visualized by using the trans-septal approach technique. In this approach, we prefer to perforate the posterior septum in the posterolateral-to-posteromedial direction to avoid damaging the neurovascular structures because the structures are located just behind and lateral to the midline septum and the posteromedial capsule bulges a bit more posteriorly than the posterolateral capsule. Attention is then directed to the medial, lateral, and suprapatellar compartments, and finally the retropatellar compartment. Our surgical steps are safe and effective for complete synovectomy of the rheumatoid arthritic knee joint and other synovial disorders.

COOH-terminal heparin-binding fibronectin fragment induces nitric oxide production in rheumatoid cartilage through CD44.

To examine the mechanism of nitric oxide (NO) production by a COOH-terminal heparin-binding fibronectin fragment (HBFN-f) in rheumatoid arthritis (RA) cartilage. Articular cartilage slices from RA knee joints and normal hip joints were cultured with HBFN-f. Secreted NO levels in conditioned media were determined. Cultures were pretreated with anti-CD44 antibody or HBFN-f-derived synthetic peptide (peptide V; WQPPRARI) to evaluate the role of CD44 in HBFN-f action. Immunofluorescence histochemistry was performed using fluorescein isothiocyanate-conjugated anti-CD44 antibody. HBFN-f stimulated NO production in a dose-dependent manner. Whereas CD44 expression was up-regulated in RA cartilage, anti-CD44 antibody blocked HBFN-f-stimulated NO production. Peptide V with heparin-binding ability significantly reduced NO levels elevated by HBFN-f. Compared with normal cartilage, cartilage response to HBFN-f and the blocking effects of anti-CD44 antibody on HBFN-f action were stronger in RA cartilage. The present study clearly demonstrated that HBFN-f stimulated NO production through CD44 in RA cartilage. Increased expression of CD44 in RA cartilage may play a pathological role in joint destruction through enhanced NO production by binding to fibronectin fragments such as HBFN-f.

Power Doppler Sonography in the Assessment of Synovial Tissue of the Knee Joint in Rheumatoid Arthritis: A Preliminary Experience

Power Doppler Sonography in the Assessment of Synovial Tissue of the Knee Joint in Rheumatoid Arthritis: A Preliminary Experience