Osteoarthritis (OA), one of the most common rheumatic disorders, is characterized by cartilage breakdown and by synovial inflammation that is directly linked to clinical symptoms such as joint swelling, synovitis and inflammatory pain The gold-standard method for detecting synovitis is histological analysis of samples obtained by biopsy, but the noninvasive imaging techniques MRI and ultrasonography might also perform well The inflammation of the synovial membrane that occurs in both the early and late phases of OA is associated with alterations in the adjacent cartilage that are similar to those seen in rheumatoid arthritis Catabolic and proinflammatory mediators such as cytokines, nitric oxide, prostaglandin E(2) and neuropeptides are produced by the inflamed synovium and alter the balance of cartilage matrix degradation and repair, leading to excess production of the proteolytic enzymes responsible for cartilage breakdown Cartilage alteration in turn amplifies synovial inflammation, creating a vicious circle As synovitis is associated with clinical symptoms and also reflects joint degradation in OA, synovium-targeted therapy could help alleviate the symptoms of the disease and perhaps also prevent structural progression

The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis

Importance Synovitis is common and is associated with progression of structural characteristics of knee osteoarthritis Intra-articular corticosteroids could reduce cartilage damage associated with synovitis but might have adverse effects on cartilage and periarticular bone Objective To determine the effects of intra-articular injection of 40 mg of triamcinolone acetonide every 3 months on progression of cartilage loss and knee pain Design, setting, and participants Two-year, randomized, placebo-controlled, double-blind trial of intra-articular triamcinolone vs saline for symptomatic knee osteoarthritis with ultrasonic features of synovitis in 140 patients Mixed-effects regression models with a random intercept were used to analyze the longitudinal repeated outcome measures Patients fulfilling the American College of Rheumatology criteria for symptomatic knee osteoarthritis, Kellgren-Lawrence grades 2 or 3, were enrolled at Tufts Medical Center beginning February 11, 2013; all patients completed the study by January 1, 2015 Interventions Intra-articular triamcinolone (n = 70) or saline (n = 70) every 12 weeks for 2 years Main outcomes and measures Annual knee magnetic resonance imaging for quantitative evaluation of cartilage volume (minimal clinically important difference not yet defined), and Western Ontario and McMaster Universities Osteoarthritis index collected every 3 months (Likert pain subscale range, 0 [no pain] to 20 [extreme pain]; minimal clinically important improvement, 394) Results Among 140 randomized patients (mean age, 58 [SD, 8] years, 75 women [54%]), 119 (85%) completed the study Intra-articular triamcinolone resulted in significantly greater cartilage volume loss than did saline for a mean change in index compartment cartilage thickness of -021 mm vs -010 mm (between-group difference, -011 mm; 95% CI, -020 to -003 mm); and no significant difference in pain (-12 vs -19; between-group difference, -06; 95% CI, -16 to 03) The saline group had 3 treatment-related adverse events compared with 5 in the triamcinolone group and had a small increase in hemoglobin A1c levels (between-group difference, -02%; 95% CI, -05% to -0007%) Conclusions and relevance Among patients with symptomatic knee osteoarthritis, 2 years of intra-articular triamcinolone, compared with intra-articular saline, resulted in significantly greater cartilage volume loss and no significant difference in knee pain These findings do not support this treatment for patients with symptomatic knee osteoarthritis Trial registration ClinicalTrialsgov Identifier: NCT01230424

/pdf/effect-of-intra-articular-triamcinolone-vs-saline-on-knee-4nnrdiquzn.pdf

Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial.

Objective: To compare the clinical assessment of overall inflammatory activity in patients with rheumatoid arthritis (RA) with grey scale and power Doppler (PD) ultrasonography (US). Methods: Ninety four consecutive patients with RA were included. Demographic and clinical data, C reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) were recorded for each patient. The presence of tenderness, swelling, and a subjective swelling score from 1 to 3 were independently assessed by two rheumatologists, who reached a consensus in 60 joints examined in each patient. All patients underwent a US examination by a third blinded rheumatologist, using PD. US joint effusion, synovitis, and PD signal were graded from 1 to 3 in the 60 joints. Joint count and joint index for effusion, synovitis, and PD signal were recorded. A 28 joint count for clinical and US variables was calculated. Interobserver reliability of the US examination was evaluated by a fourth blinded rheumatologist. Results: US showed significantly more joints with effusion (mean 15.2) and synovitis (mean 14.6) than clinical examination (mean 11.5, p Conclusion: US is a sensitive method for assessing joint inflammatory activity in RA, complementary to clinical evaluation.

https://ard.bmj.com/content/annrheumdis/64/3/375.full.pdf

Assessment of inflammatory activity in rheumatoid arthritis: a comparative study of clinical evaluation with grey scale and power Doppler ultrasonography

Objective
To examine the significance of power Doppler sonography (PDS) in the diagnosis of synovial hypertrophy of the knee joint by verifying and comparing the PDS findings with histopathologic findings of synovial membrane vascularity.

Methods
The knee joints of 23 patients who were undergoing arthroplasty of the knee joint because of osteoarthritis or rheumatoid arthritis were examined with ultrasound before arthroplasty. The vascularity of the synovial membrane was classified semiquantitatively using PDS. A sample of synovial tissue was obtained during the arthroplasty, and the vascularity of the synovial tissue was evaluated by immunohistochemistry (factor VIII) and was graded qualitatively by a pathologist who was unaware of the PDS findings. The visual qualitative grading by the examiner was controlled by analyzing PDS images and histologic samples using a digital image evaluation system.

Results
The correlation between the qualitative PDS results and the qualitative grading of the vascularity by the pathologist was 0.89 by Spearman's ρ (P < 0.01). The Pearson correlation coefficient between the digital analysis of the PDS images and the digital analysis of the tissue sections was 0.81 (P < 0.01). Digital image analysis and qualitative grading by the examiner had a correlation of 0.89 by Spearman's ρ (P < 0.01) for the PDS images. The correlation between the qualitative estimation of vascularity by the pathologist and the digital image analysis was 0.88 by Spearman's ρ (P < 0.01).

Conclusion
In the present study, PDS proved to be a reliable diagnostic method for qualitative grading of the vascularity of the synovial tissue. In clinical practice, PDS allows further differentiation of the hypertrophic synovium.

Correlation of power Doppler sonography with vascularity of the synovial tissue of the knee joint in patients with osteoarthritis and rheumatoid arthritis

Objectives: To assess the prevalence of inflammation in subjects with chronic painful knee osteoarthritis (OA), as determined by the presence of synovitis or joint effusion at ultrasonography (US); and to evaluate the correlation between synovitis, effusion, and clinical parameters. Methods: A cross sectional, multicentre, European study was conducted under the umbrella of EULAR- ESCISIT. Subjects had primary chronic knee OA (ACR criteria) with pain during physical activity >30 mm for at least 48 hours. Clinical parameters were collected by a rheumatologist and an US examination of the painful knee was performed by a radiologist or rheumatologist within 72 hours of the clinical examination. Ultrasonographic synovitis was defined as synovial thickness >4 mm and diffuse or nodular appearance, and a joint effusion was defined as effusion depth >4 mm. Results: 600 patients with painful knee OA were analysed. At US 16 (2.7%) had synovitis alone, 85 (14.2%) had both synovitis and effusion, 177 (29.5%) had joint effusion alone, and 322 (53.7%) had no inflammation according to the definitions employed. Multivariate analysis showed that inflammation seen by US correlated statistically with advanced radiographic disease (Kellgren-Lawrence grade >3; odds ratio (OR) = 2.20 and 1.91 for synovitis and joint effusion, respectively), and with clinical signs and symptoms suggestive of an inflammatory ''flare'', such as joint effusion on clinical examination (OR = 1.97 and 2.70 for synovitis and joint effusion, respectively) or sudden aggravation of knee pain (OR = 1.77 for joint effusion). Conclusion: US can detect synovial inflammation and effusion in painful knee OA, which correlate significantly with knee synovitis, effusion, and clinical parameters suggestive of an inflammatory ''flare''.

https://ard.bmj.com/content/annrheumdis/64/12/1703.full.pdf

EULAR report on the use of ultrasonography in painful knee osteoarthritis. Part 1: Prevalence of inflammation in osteoarthritis

The potential role of sonography in evaluating the response to therapy of persistent knee joint synovitis (KJS) was assessed in a longitudinal study in pre- and post-arthroscopic (AS) synovectomy in rheumatoid and psoriatic patients. At entry to the study, ultrasound (US) detection of synovial proliferation was compared with arthroscopic visualization as the 'gold standard' reference. US joint effusion and synovial thickness measures and predominant patterns of synovial proliferation were recorded by comparing clinical and US indices before and at 2, 6 and 12 months after AS synovectomy, or after KJS relapse up to 24 months. A 12 month survival analysis of clinical and US outcomes of arthroscopic synovectomy was also performed. US detection of morphology and degree of synovial proliferation was correlated with AS macroscopic evaluation. After AS synovectomy, the clinical index and both US joint effusion and synovial thickness were significantly reduced, whereas US patterns of synovial proliferation did not show significant changes. US and clinical indices were significantly correlated in all follow-up measurements and US joint effusion was significantly increased in the relapsed compared with the non-relapsed KJS group. The probability at 12 months of reaching maximum improvement in US joint effusion and synovial thickness outcomes was 99 and 58%, respectively ; that for clinical remission of KJS was 72%. Ultrasound evaluation has proven reliable and accurate by the arthroscopic gold standard in detecting changes of rheumatoid arthritis and psoriatic arthritis knee joint synovitis. The correlation of US with clinical findings in pre- and post-synovectomy patients suggests that sonography can be used as an objective method in monitoring the response to therapy of inflammatory knee joint disease.

Long-term sonographic follow-up of rheumatoid and psoriatic proliferative knee joint synovitis

The objective of this study was to verify the accuracy of ultrasonography in assessing the topography, morphology, and extent of synovial proliferation in rheumatoid and psoriatic knee joint synovitis. Findings were compared to those obtained using prospective arthroscopy as the gold standard; in addition, topographically defined sonographic findings before and after arthroscopic synovectomy were compared. Sonographic examination was performed in 12 patients with rheumatoid arthritis (13 knees) and 13 patients with psoriatic arthritis (14 knees) who had synovitis of the knee using an electronic linear transducer (7.5 MHz) or a mechanical sector transducer (10 MHz). This examination was followed within 1 week by arthroscopy, to compare the topography (intra-articular localization) and the morphology (sonographic patterns) of synovial proliferation. In 15 knees undergoing arthroscopic synovectomy, preoperative sonographic measurement of synovial thickness in the suprapatellar, medial parapatellar, and lateral parapatellar recesses was compared with arthroscopic visualization of synovial proliferation; 13 knees were reevaluated 2 months after arthroscopic synovectomy by sonography at the same sites. Three distinct sonographic patterns of synovial proliferation were confirmed by arthroscopic examination: a villonodular aspect in 12 knees; uniform thickening in eight knees, and overlapping layers in seven knees. About 50% of the knees showed more than one sonographic pattern, with no differences in pattern distribution between rheumatoid arthritis and psoriatic arthritis patients. A significant correlation was found between sonographic and arthroscopic evaluations of synovial thickness in the suprapatellar (P<0.02) and medial parapatellar recesses (P<0.02), the sites of maximal synovial proliferation in our patients. Two months after arthroscopic synovectomy, sonographic measurement of synovial thickness in millimeters showed a significant reduction in all three knee joint recesses explored (suprapatellar: P<0.05; medial parapatellar: P<0.05; lateral parapatellar: P<0.02) Prospective arthroscopy showed that this simple method of sonographic evaluation of knee joint synovitis was sensitive and accurate in defining morphologic patterns, topography, and extent of synovial proliferation. Our data suggests that this approach also is a sensitive indicator of changes in synovial proliferation and would thus be useful for following progression in the early phases of knee joint proliferative synovitis

Prospective sonographic and arthroscopic evaluation of proliferative knee joint synovitis.

SUMMARY A long-term prospective study was performed to evaluate the safety and long-term outcome of surgical arthroscopy (AS) for persistent rheumatoid (RA) and psoriatic (PsA) knee joint synovitis (KJS). Local signs of joint inflammation (tenderness, swelling, 'ballottement') and range of motion (ROM) were scored and the sum, taken as a global outcome measure, was recorded in 17 RA and 18 PsA knees, both before and at follow-up periods of 2, 6, 12, 24 and 36 months after surgical AS (knee joint synovectomy; meniscal curettage, cartilage shaving or chondrectomy, according to the degree of cartilage damage). A survival analysis (Kaplan-Meier) of the long-term outcome of surgical AS treatment and of the predictive value of clinical parameters of knee joint involvement was also performed. No intra- or post-operativ e morbidity, pain worsening or loss of joint motion was observed and all patients were discharged within 48 h. Comparison of the parameters of knee joint evaluation showed a significant reduction of the signs of joint inflammation and a significant increase in the ROM in all follow-up periods. At 36 months, the survival curves showed a 61.2% cumulative probability of clinical remission and 72.8% of definite improvement. No significant differences in the prognostic importance of RA, compared to PsA diagnosis, were observed, although higher percentages of PsA compared to RA knees (86.3% and 45.7%, respectively) reached the end point of clinical remission at 36 months. KJS duration, radiographic severity and cartilage damage were not predictors of poor long-term outcome of AS synovectomy. Surgical AS treatment for PsA knees with more advanced cartilage damage gave a better long-term outcome. A total of 50.7% of operated knees reached the end point of a KJS relapse at 36 months, the majority (82%) within the initial 18 months of follow-up. Our study indicates that AS synovectomy is a safe procedure requiring short hospitalization which, in combination with second-line medical treatment, can reduce local inflammation in RA and PsA KJS, and preserve knee joint ROM for up to 3 yr.

/pdf/arthroscopic-synovectomy-in-rheumatoid-and-psoriatic-knee-50psdqzx76.pdf

Arthroscopic synovectomy in rheumatoid and psoriatic knee joint synovitis: long-term outcome

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Long-term sonographic follow-up of rheumatoid and psoriatic proliferative knee joint synovitis

Prospective sonographic and arthroscopic evaluation of proliferative knee joint synovitis.

Arthroscopic synovectomy in rheumatoid and psoriatic knee joint synovitis: long-term outcome