Grey Scale Synovitis Research Articles

Validity of 7-Joint Versus Simplified 12-Joint Ultrasonography Scoring Systems in Assessment of Rheumatoid Arthritis Activity.

Musculoskeletal ultrasonography (US) is an objective tool for the evaluation of disease activity in rheumatoid arthritis (RA) patients. There is no consensus on the exact number of joints that should be examined. Examination of reduced joint count is more practical than the comprehensive one. This is a cross-sectional study investigated the validity of a 7-joint US score (US7) in assessment of joint inflammation in RA patients compared with a simplified 12-joint US score (US12) and correlated both to composite disease activity indices. The activity status of 50 RA patients was assessed clinically and ultrasonographically. The disease activity was calculated using 3 composite indices. Ultrasonography was performed by 1 blinded rheumatologist, using power Doppler (PD) and gray-scale (GS) US examination. The US7 and simplified US12 were performed as originally described. However, the GS synovitis and PD synovitis of US12 were computed in 2 separate scores instead of 1. Two sum US7 scores were added, sum (GS) US7 and sum (PD) US7 after summating synovitis and tenosynovitis scores. Ultrasonography interobserver/intraobserver reliability was evaluated on 40 stored images. Correlation coefficient between the different ultrasonographic scores showed no difference. The GS scores showed no correlation with disease activity parameters; however, the PD scores did. The sum (PD) US7 was the only score that showed significant correlation with the 3 different composite disease indices. All studied US scores proved valid in assessment of disease activity status in RA. This is in favor of using the less-time-consuming US7 scores. The strongest correlation found with sum (PD) US7 confirmed the importance of incorporating the tendon in the disease activity assessment.

Associations between ultrasoundfeatures and pain across hand osteoarthritis phenotypes

Purpose: Previous hand osteoarthritis (OA) studies have shown associations between synovitis and pain, whereas few studies have explored whether these associations are present in both the interphalangeal joints and the first carpometacarpal (CMC-1) joints. Due to limited effect of steroid injections in the CMC-1 joint, it has been speculated whether pain in the CMC-1 joints is more related to subluxation and deformity rather than synovitis. Hence, the aim of this study was to explore the association between ultrasound-detected synovitis and pain in both the interphalangeal and CMC-1 joints in patients with hand OA. Methods: The Nor-Hand study is an observational study including 301 patients with hand OA (89% women, median (IQR) age of 61 (57−66) years). All participants underwent ultrasound and clinical examination of the bilateral finger joints and completed pain questionnaires. The proximal and distal interphalangeal joints and the CMC-1 joint were examined using a GE Logic S8 ultrasound machine. A trained medical student scored the joints for osteophytes, grey scale synovitis (effusion and/or synovial hypertrophy) and power Doppler activity on a 0–3 scale. A rheumatologist examined the same joints for tenderness upon palpation/movement, and patient self-reported joint pain during the last 24 h and last 6 weeks on two separate homunculi. We explored joint level associations between grey scale synovitis/power Doppler activity and pain in the same joints using logistic regression analyses with generalized estimating equations with adjustment for age, sex and body mass index (BMI). Analyses were repeated with adjustment for ultrasound-detected osteophytes. Separate models were performed for the ultrasound features as well as for the different pain outcomes. Results: The majority of patients had finger joints with presence of grey scale synovitis with a median (interquartile range, IQR) of 2 (0–5) and 0 (0–1) for the interphalangeal and CMC-1 joints, respectively. Power Doppler activity was less frequent with a median (IQR) of 0 (0–2) and 0 (0–1) for the interphalangeal and CMC-1 joints, respectively. The median (IQR) of tender joints upon palpation was 5 (2–10) and 1 (0–2) for the interphalangeal and CMC-1 joints, respectively, whereas the number of joints with self-reported pain was lower (median (IQR) of 2 (0–6) and 0 (0–2) for pain the previous 6 weeks for the interphalangeal and CMC-1 joints, respectively) Increasing severity of ultrasound-detected grey scale synovitis and power Doppler activity was associated with higher odds of tenderness upon palpation in the interphalangeal joints as well as the CMC-1 joints (Table). For self-reported pain, the strength of associations was similar (data not shown). The associations attenuated, but remained statistically significant when osteophytes were added to the models (except borderline significant for power Doppler activity and pain last 24 h in the CMC-1 joints). Conclusions: Ultrasound-detected synovitis was associated with pain in both interphalangeal joints and CMC-1 joints, and the association was independent of the severity of osteophytes. These results suggest that lowering inflammation could be a treatment target in patients with both interphalangeal OA as well as CMC-1 OA.Tabled 1Associations between ultrasound-detected synovitis and tenderness upon palpationOR (95% CI) of tenderness upon palpation (adjusted for age, sex and BMI)Bilateral DIP 2–5 and PIP 1–5 jointsBilateral CMC-1 jointsGrey scale synovitisGrade 01.00 (Ref.)1.00 (Ref.)Grade 13.10 (2.54–3.78)3.39 (1.85–6.17)Grade 2–35.74 (4.44–7.43)7.48 (3.93–14.21)Power-Doppler activityGrade 01.00 (Ref.)1.00 (Ref.)Grade 14.10 (3.14–5.35)4.46 (2.56–7.75)Grade 2–34.24 (3.24–5.53)6.40 (2.29–17.83) Open table in a new tab

Subclinical synovitis and tenosynovitis by ultrasonography (US) 7 score in patients with rheumatoid arthritis treated with synthetic drugs, in clinical remission by DAS28.

To identify synovitis and tenosynovitis active by using the Ultrasound 7 (US 7) scoring system in patients with rheumatoid arthritis (RA) in clinical remission induced by synthetic disease-modifying antirheumatic drugs (DMARDs). This is a multicentric, cross-sectional, observational study including 94 RA patients >18 years old who were in remission as defined by the 28-joints disease activity score (DAS28) <2.6 induced by synthetic DMARD during at least 6 months. Patients with a previous or current history of biologic DMARD treatment were not included in the study. Demographic and clinical data were collected by the local rheumatologist; the US evaluation was performed by a calibrated rheumatologist, who intended to detect grayscale synovitis and power Doppler (PD) using the 7-joint scale. Intra and inter-reader exercises of images between 2 ultrasonographers were realized. Patients' mean age was 49.1±13.7 years; 83% were women. The mean disease duration was 8±7 years and remission lasted for 27.5±31.8 months. The mean DAS28 score was 1.9±0.66. Grayscale synovitis was present in 94% of cases; it was mild in 87.5% and moderate in 12.5%. Only 12.8% of the patients had PD. The metatarsophalangeal, metacarpophalangeal, and carpal joints of the dominant hand were the joints more frequently affected by synovitis. Tenosynovitis by grayscale was observed in 9 patients (9.6%). The intra and inter-reading kappa value were 0.77, p<0.003 (CI 95%, 0.34-0.81) and 0.81, p<0.0001 (CI 95%, 0.27-0.83) respectively. Low percentage of synovitis and tenosynovitis active were founded according to PD US by 7 score in RA patients under synthetic DMARDs during long remission. This score has benefit because evaluate tenosynovitis, another element of subclinical disease activity.

Ultrasound verified inflammation and structural damage in patients with hereditary haemochromatosis-related arthropathy

BackgroundChronic arthropathy occurs in approximately two thirds of patients with hereditary haemochromatosis (HH). The aim was to study inflammatory and structural lesions in patients with HH with (HH-A) and without arthropathy (HH-WA) using ultrasonography.MethodsThis was a cross-sectional study of 26 patients with HH-A, 24 with HH-WA and 37 with hand osteoarthritis (HOA). Clinical examination was performed in 68 joints, and we retrieved data on hand function, pain and global disease activity (all using a visual analogue scale (VAS)), morning stiffness and ferritin levels. Standard x-ray and ultrasound were conducted in 36 joints (hands, hips, knees and ankles), and we graded grey scale synovitis (GSS), power Doppler ultrasound (PD), osteophytes, erosions, tenosynovitis and cartilage damage semi-quantitatively in accordance with prior publications.ResultsUltrasound revealed a high proportion of inflammatory changes in HH-A; GSS was found in 96.2% and PD signals in 80.8% of patients (median GSS score 9, PD score 2.5). The frequency of these findings was similar in HOA. Inflammation was also common in HH-WA, yielding GSS in 83.3% and PD signals in 50.0% of patients. Cartilage damage was most prominent in HH-A as compared to HH-WA and HOA (median scores 11.0, 2.5 and 2.0, respectively). The prevalence and extent of erosions and osteophytes were similar in all groups. None of the ultrasound scores was associated with pain or function; GSS, PD, osteophyte and cartilage scores correlated with x-ray-verified structural damage.ConclusionA high prevalence of ultrasound-verified inflammation and cartilage damage was found in HH-A, and to a lesser extent in HH-WA. These findings were associated with x-ray-verified damage but not with clinical scores of pain and function.

Relationship between serum calprotectin (S100A8/9) and clinical, laboratory and ultrasound parameters of disease activity in rheumatoid arthritis: A large cohort study.

BackgroundCalprotectin may be a sensitive biomarker of rheumatoid arthritis (RA) disease activity.ObjectivesIn the current study, we investigated whether calprotectin is a better biomarker than CRP for predicting clinical activity and ultrasound parameters in patients with RA.MethodsA total of 160 patients with RA underwent clinical (swollen joint count—SJC, tender joint count—TJC, Disease Activity Score—DAS28, Clinical Disease Activity Index—CDAI, and simplified Disease Activity Index—SDAI) and ultrasound (German US7) examination. Clinical and laboratory measures were correlated with ultrasound findings using Spearman´s correlation coefficient. Differences in serum calprotectin levels in patients with variable disease activity according to the DAS28-ESR and CDAI scores were assessed using ANOVA. Multivariate regression analysis was used to determine the predictive values of calprotectin, CRP and SJC for CDAI and PD US synovitis scores.ResultsSerum calprotectin was significantly associated with DAS28-ESR (r = 0.321, p<0.001), DAS28-CRP (r = 0.346, p<0.001), SDAI (r = 0.305, p<0.001), CDAI (r = 0.279, p<0.001) scores and CRP levels (r = 0.556, p<0.001). Moreover, calprotectin was significantly correlated with GS (r = 0.379, p<0.001) and PD synovitis scores (r = 0.419, p<0.001). The multivariate regression analysis showed that calprotectin is a better predictor of the CDAI score and PD US synovitis than CRP.ConclusionsThe results of this study support an additional role of calprotectin in assessing inflammatory activity in patients with RA.

Joint positions matter for ultrasound examination of RA patients—increased power Doppler signal in neutral versus flat position of hands

Position of joints might influence the result of US examination in patients with RA. The purpose of this work was to compare grey-scale (GS) and power Doppler (PWD) findings obtained in neutral vs flat position of hands. A cross-sectional study of 42 RA patients with active disease. Two dimensional and 3D sonography of wrists and MCP joints were conducted in two different joint positions: neutral position, which is a slight flexion of the fingers with relaxed extensor muscles; and flat position, where all palm and volar sides of fingers touch the Table. Two dimensional GS synovitis (GSS) and PWD signals were scored semi-quantitatively (0-3). For 3D sonography, the percentage of PWD voxels within a region of interest was calculated. GSS was not quantified using 3D sonography. Compared with neutral position, 2D PWD signals disappeared in 28.3% of joints upon flattening. The median global 2D PWD score (sum of all PWD scores of an individual patient) decreased from 8 to 3 ( P < 0.001), and the global 3D PWD voxel score from 3.8 to 0.9 ( P < 0.001). The reduction of PWD scores was similar in all joints (2D: minus 50%, 3D: minus 66.4-80.1%). Inter- and intrareader agreement of PWD results was good (intraclass correlation coefficient: 0.75-0.82). In RA, a neutral position of the hands is linked to a higher sensitivity of 2D and 3D sonography in detecting PWD signals at wrists and MCP joints, compared with a flat position. Standardization of the scanning procedure is essential for obtaining comparable US results in RA patients in trials and clinical routines.

Ultrasound-detectable grey scale synovitis predicts future fulfilment of the 2010 ACR/EULAR RA classification criteria in patients with new-onset undifferentiated arthritis

ObjectiveTo determine the clinical outcomes for patients with new-onset undifferentiated arthritis (UA), not fulfilling the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) classification criteria,...

Smoking and alcohol use are associated with structural and inflammatory hand osteoarthritis features

Objectives: To explore whether smoking and alcohol use are associated with hand osteoarthritis (OA) features in two different OA cohorts.Method: We studied 530 people with radiographic hand OA from the Musculoskeletal pain in Ullensaker STudy (MUST) and 187 people from the Oslo hand OA cohort [mean (sd) age 65 (8.0) and 62 (5.7) years, 71% and 91% women, respectively]. Smoking, alcohol use and hand pain were self-reported. Participants underwent conventional hand radiographs and ultrasound examination of 30 hand joints. The Kellgren–Lawrence sum score for radiographic OA severity (0–120 scale) and the proportion of participants having at least one joint with grey-scale synovitis (grade ≥1) were calculated. We studied whether smoking and alcohol use were cross-sectionally associated with radiographic OA, synovitis, and pain using adjusted linear and logistic regression analyses.Results: Smoking was associated with less radiographic OA in both cohorts [β = −4.71, 95% confidence interval (CI) −8.36 to −1.06 for current smoking in MUST and β = −0.15, 95% CI −0.29 to −0.02 for smoking pack-years in the Oslo hand OA cohort]. Stratified analyses indicated that the association was present in men only. Being a monthly drinker (examined in MUST only) was significantly associated with present synovitis compared to never drinkers (odds ratio = 2.35, 95% CI 1.27 to 4.34) (no gender differences). Neither smoking nor alcohol was associated with hand pain.Conclusions: Smoking was associated with less radiographic hand OA whereas alcohol consumption was associated with present joint inflammation in hand OA. Future longitudinal studies are needed to explore the causal associations and explanatory mechanisms behind gender differences.

The relationship between synovitis quantified by an ultrasound 7-joint inflammation score and physical disability in rheumatoid arthritis \u2013 a cohort study

BackgroundRestoring normal physical functioning is a major therapeutic aim in the management of rheumatoid arthritis (RA). It is unknown, whether the extent of synovial inflammation quantified by musculoskeletal ultrasound (US) can predict current or future capacity for physical functioning. To answer this question we investigated the longitudinal relationship between physical function assessed by the health assessment questionnaire (HAQ) and the German 7-joint ultrasound score (US7S) in a prospective cohort of patients with RA.MethodsPatients with RA (n = 185 (46 with incident and 139 with prevalent disease) were followed for 30.9 ± 9.1 months. Baseline and annual assessments comprised the disease activity score in 28 joints (DAS28), HAQ and US7S. The US7S includes semiquantitative measurements of synovitis assessed by greyscale (GS) and power Doppler (PD) in seven joints of the clinically dominant hand and foot, which are then aggregated in PD and GS synovitis sum-scores (PDsynSS and GSsynSS). A linear mixed-effect model was used to assess the longitudinal relationship between GSsynSS, PDsynSS and HAQ. We used standard and time-lag models to explore the association between HAQ, and GSsynSS, PDsynSS and DAS28 measured at the same time or at the previous visit 12 months ago, respectively.ResultsWhen the standard model was applied, in univariate analyses HAQ score was positively associated with GSsynSS and PDsynSS with β coefficients significantly higher in incident than in prevalent disease. In multivariate analysis both synSSs were individually no longer significant predictors of HAQ score. When using the time-lag model, after adjustment for the previous DAS28 or HAQ score, both PDsynSS and GSsynSS were significantly and negatively associated with the current HAQ.ConclusionsUS7 PD and GS synovitis sum-scores alone were positively associated with current functional status reflected by the HAQ in patients with RA, and this relationship was stronger in patients with early disease. When combined with the DAS28 or HAQ, US7 PD and GS synovitis sum-scores were predictive of the change in HAQ score over one year.

Calprotectin (S100A8/A9) has the strongest association with ultrasound-detected synovitis and predicts response to biologic treatment: results from a longitudinal study of patients with established rheumatoid arthritis

BackgroundCalprotectin (S100A8/A9 or MRP8/14) and S100A12 (leukocyte-derived proteins), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) are markers of inflammation and angiogenesis. Ultrasound (US) is sensitive for detection of greyscale synovitis and power Doppler (PD) vascularization. The objective of the present study was to explore the associations between calprotectin, S100A12, IL-6, VEGF, erythrocyte sedimentation rate, C-reactive protein and a comprehensive US assessment in patients with rheumatoid arthritis (RA) starting biologic disease-modifying anti-rheumatic drug (bDMARD) treatment.MethodsA total of 141 patients with RA were assessed by US, clinical examination and biomarker levels at baseline and at 1, 2, 3, 6 and 12 months after initiation of bDMARDs. US assessment of 36 joints and 4 tendon sheaths were scored semi-quantitatively (0–3 scale). European League Against Rheumatism (EULAR) response was calculated. Statistical assessments performed to explore the associations between biomarkers and US sum scores included Spearman’s rank correlation analysis as well as linear and linear mixed model regression analyses.ResultsCalprotectin showed the overall strongest correlations with both US sum scores (rs = 0.25–0.62) and swollen joint counts (of 32) (rs = 0.24–0.47) (p < 0.05 at all examinations). An association with US sum scores remained after we adjusted for age, sex, disease duration and all the other markers in a regression analysis at baseline. Decreased calprotectin at the first month was predictive of both EULAR response (p ≤ 0.001) and decreased sum PD scores at 3, 6 and 12 months (p ≤ 0.05).ConclusionsCalprotectin had the highest association with US synovitis and predicted treatment response. It may thus be considered as a marker for evaluating inflammation and responsiveness in patients with RA on bDMARD treatment.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR) identifier: ACTRN12610000284066. Registered on 8 April 2010 (retrospectively registered).

Ultrasound resistive index, power Doppler, and clinical parameters in established rheumatoid arthritis.

Ultrasonography (US) is a useful tool for the evaluation of sinovial vascularization and proliferation in rheumatoid arthritis (RA). Accordingly, resistive index (RI) on spectral Doppler (sD) US provides a quantitative analysis of vascular inflammation, but its utility in the evaluation of RA activity has not been established. Our objective was to determine the association of RI with other US parameters of synovitis and with clinical disease activity in established RA. Patients with positive power Doppler (pD) were included in a prospective cross-sectional study. Disease activity and disability were evaluated using the Disease Activity Score in 28-joints (DAS28) and Health Assessment Questionnaire (HAQ), respectively. Gray scale (GS) synovitis, pD, and sD analyses were performed by one of two examiners in wrists and the second and third metacarpophalangeal and proximal interphalangeal joints. The 10-joint GS and 10-joint pD scores and mean RI were then calculated. Weighted kappa (WK) values were employed to assess interobserver reability, and correlations were tested using the Spearman coefficient. Ninety-five RA patients (median duration of disease of 7years and mean DAS28 of 4.32±1.66) were included. WK values in real-time US were 0.77 for synovitis, 0.87 for pD, and 0.68 for RI. There were no significant correlations of RI with 10-joint GS, 10-joint pD, DAS28, joint counts, or HAQ (P>0.10 for all tests). Patients in remission had a mean RI similar to those with high disease activity (0.62±0.10, n=15 versus 0.63±0.13, n=34, respectively). The addition of the RI score did not seem to improve US performance in patients with established RA.

Rheumatoid arthritis patients with fibromyalgic clinical features have significantly less synovitis as defined by power Doppler ultrasound.

BackgroundIn patients with rheumatoid arthritis (RA) clinical measures of disease activity may not reliably discriminate between patients with active inflammatory disease and those with concomitant fibromyalgia (FM). Recent work has shown RA patients with a 28 tender joint count (TJC) minus swollen joint count (SJC) of 7 or more (joint count criteria) are more likely to meet classification criteria for FM. This study aimed to determine whether RA patients meeting clinical criteria for FM had lower levels of joint inflammation as determined by ultrasound (US).MethodsRA patients with DAS28 > 2.6 were recruited. Patients underwent clinical assessment including ultrasound examination of the hands and wrists with quantification of grey scale (GS) and power Doppler (PD) synovitis. Patients completed questionnaires to assess pain, fatigue, disability and psychological comorbidity.ResultsPatients meeting either of the FM criteria had higher scores for disease activity, depression, disability and fatigue. Those meeting both the joint count and classification FM criteria had significantly lower levels of GS and PD inflammation on US.ConclusionsRA patients with concomitant FM, as determined by widespread soft tissue tenderness but fewer clinically inflamed joints, have higher disease activity scores but may have lower levels of synovial inflammation on US. This has implications for the identification and management of these patients who may not respond to conventional therapy and hence be more suitable for alternative approaches to treatment.

Potential role of calprotectin as a monitoring biomarker for clinical and sonographic activity and treatment outcome in recent-onset rheumatoid arthritis

Calprotectin is a protein released during the activation and turnover of leukocytes. It can be used as a biomarker of inflammatory diseases such as rheumatoid arthritis (RA). The current study aimed to measure the serum level of calprotectin in RA patients, recently diagnosed and after initiation of treatment, to determine its association with clinical disease, synovial inflammation determined by Ultrasound (US), and its relation to therapy when compared with other inflammatory markers. A total of 32 patients with recent RA and 20 healthy individuals were assessed for serum calprotectin level (enzyme-linked immunosorbent assay). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were also measured in patients who were reassessed 4 months after initiation of therapy. Disease activity was evaluated by the disease activity score of 28 joints (DAS28), and US assessment was performed. The mean level of serum calprotectin was significantly higher (P<0.001) than that of controls. At baseline, there were significant (P<0.001) correlations of calprotectin serum level with DAS28, ESR, CRP, grayscale, and power Doppler (PD) synovitis scores. After therapy, all except DAS28 and ESR significantly correlated with calprotectin serum level. Calprotectin was shown to be better (P=0.001) than CRP (P=0.922) and ESR (P=0.104, r2=0.495) in predicting power Doppler synovitis score. Calprotectin results showed higher sensitivity in predicting disease activity at the stage of active inflammation. Serum calprotectin level is strongly associated with clinical, laboratory, and US parameters of inflammation in recent-onset RA. Calprotectin is a confident biomarker for monitoring the treatment outcome in RA patients.

Ultrasound-detected tenosynovitis independently associates with patient-reported flare in patients with rheumatoid arthritis in clinical remission: results from the observational study STARTER of the Italian Society for Rheumatology.

This study aimed to estimate the prevalence of US-detected tenosynovitis in RA patients in clinical remission and to explore its clinical correlates. A total of 427 RA patients in clinical remission were consecutively enrolled from 25 Italian rheumatology centres. Tenosynovitis and synovitis were scored by US grey scale (GS) and power Doppler (PD) semi-quantitative scoring systems at wrist and hand joints. Complete clinical assessment was performed by rheumatologists blinded to the US results. A flare questionnaire was used to assess unstable remission (primary outcome), HAQ for functional disability and radiographic erosions for damage (secondary outcomes). Cross-sectional relationships between the presence of each US finding and outcome variables are presented as odds ratios (ORs) and 95% CIs, both crude and adjusted for pre-specified confounders. The prevalence of tenosynovitis in clinical remission was 52.5% (95% CI 0.48, 0.57) for GS and 22.7% (95% CI 0.19, 0.27) for PD, while the prevalence of synovitis was 71.6% (95% CI 0.67, 0.76) for GS and 42% (95% CI 0.37, 0.47) for PD. Among clinical correlates, PD tenosynovitis associated with lower remission duration and morning stiffness while PD synovitis did not. Only PD tenosynovitis showed a significant association with the flare questionnaire [OR 1.95 (95% CI 1.17, 3.26)]. No cross-sectional associations were found with the HAQ. The presence of radiographic erosions associated with GS and PD synovitis but not with tenosynovitis. US-detected tenosynovitis is a frequent finding in RA patients in clinical remission and associates with unstable remission.

Ultrasound power Doppler synovitis is associated with plasma IL-6 in established rheumatoid arthritis

Background and objective: Cytokines have an important role in the pathogenesis of rheumatoid arthritis (RA). Although plasma levels of IL-6 have been related to musculoskeletal ultrasound (MSUS) synovitis in early DMARD-naïve RA, there are no similar studies in established disease. Methods: 64 RA patients treated with non-biological DMARDs and 30 healthy controls were included in this prospective cross-sectional study. A blood sample was taken before evaluation of disease activity (DAS28) and ultrasonography (all tests performed in a blinded fashion). MSUS was performed by one of two ultrasound-trained rheumatologists on 10 joints of both hands. Gray scale (GS) and pD (power Doppler) synovitis were evaluated using a semi-quantitative scale (0–3) in individual joints, and their sum (score 10) was calculated. Plasma cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF, IFN-γ, and VEGF) were quantified by flow cytometry. Results: Levels of all cytokines, excepting VEGF, were significantly higher in RA patients than in controls (P⩽0.05). In RA patients, IL-6, but not other cytokines, correlated positively with DAS28 and swollen joint count (P⩽0.01), as well as with 10-joint pD score, and GS and pD of both wrists (P<0.01 for all tests). In multiple linear regression, the association of IL-6 with 10-joint pD score was maintained even after adjustment for DAS28. However, there was no correlation of IL-6 with tender joint count, 10-joint GS score, or presence of erosions. Conclusion: We demonstrated an association of inflammatory findings on MSUS and plasma IL-6 independently of DAS28 in established RA.

Synovitis and radiographic progression in non-erosive and erosive hand osteoarthritis: is erosive hand osteoarthritis a separate inflammatory phenotype?

To compare the prevalence of synovitis, pain and radiographic progression in non-erosive and erosive hand osteoarthritis (HOA), and to explore whether the different rate of disease progression is explained by different levels of synovitis and structural damage. We included 31 and 34 participants with non-erosive and erosive HOA at baseline, respectively. Using Generalized Estimating Equations, we explored whether participants with erosive HOA had more synovitis (by MRI, ultrasound and clinical examination) independent of the degree of structural damage. Similarly, we explored whether pain at baseline and radiographic progression after 5 years were higher in erosive HOA, independent of the levels of synovitis and structural damage. All analyses were adjusted for age and sex. Power Doppler activity was found mainly in erosive HOA. Participants with erosive HOA demonstrated more moderate-to-severe synovitis, assessed by MRI (OR=1.73, 95% CI 1.11-2.70), grey-scale ultrasound (OR = 2.02, 95% CI 1.25-3.26) and clinical examination (OR=1.80, 95% CI 1.44-2.25). The associations became non-significant when adjusting for more structural damage. The higher frequency of joint tenderness in erosive HOA was at least partly explained more structural damage and inflammation. Radiographic progression (OR=2.53, 95% CI 1.73-3.69) was more common in erosive HOA independent of radiographic HOA severity and synovitis (here: adjusted for grey-scale synovitis by ultrasound). Erosive HOA is characterized by higher frequency and more severe synovitis, pain and radiographic progression compared to non-erosive HOA. The higher rate of disease progression was independent of baseline synovitis and structural damage.

Ultrasound color histogram assessment allows better view of echotexture damage

INTRODUCTION The colored ultrasound images can better highlight the joint echotexture damage. OBJECTIVE To detect echotexture changes in joints of patients with rheumatic diseases, through a color histogram, and to correlate the area measurements with the gray scale (GS). METHODS Four patients with chondrocalcinosis, 5 patients with osteoarthritis and 1 patient with psoriatic arthritis were evalutated. A total of 104 synovitis (SYN) and calcifications (calcif) measurements in cm2 were performed in the dorsal radiocarpal joint (DRR); triangular fibrocartilage complex (TFC); dorsal metacarpophalangeal joints (MCP) and lateral and medial knee suprapatellar recesses. For each GS measure, one was performed for each standard color image. Spearman was used for correlation analysis. RESULTS Mean±SD of image patterns: RGB (Red, Green and Blue) SYN 16.96±0.25cm2; indigo SYN 6.43±0.07cm2, RGB Calcif 0.03±0.00cm2; indigo Calcif 0.06±0.03cm2; GS SYN 16.13±0.35cm2 and GS Calcif 0.56±0.01cm2. Correlations of color images patterns RGB DRR SYN and indigo DRR SYN: r=1, p<0.001; indigo DRR SYN and RGB suprapattelar SYN: r=1, p<0.001; RGB MCP SYN and indigo MCP SYN: r=1, p<0.001; indigo DRR calcif and RGB TFC calcif: r=1 p<0.001; the RGB and indigo measurement standards when correlated with GS for SYN and calcifs were not statistically significant (p=0.333 to 0.667). CONCLUSION The RGB and indigo patterns seem to better define these echotexture damage.

Ultrasound detected inflammation is associated with the development of new bone erosions in hand osteoarthritis: a longitudinal study over 3.9 years

To evaluate the association between ultrasound (US) detected inflammation at baseline and the subsequent development of new bone erosions at follow-up in patients with hand osteoarthritis (HOA). 32 of the 35 (10 controls, 12 patients with non erosive HOA (non-EHOA), 13 with EHOA subjects originally studied were re-evaluated 3.9 years after the initial study, by means of standard radiography and US examination. Kellgren-Lawrence (K-L) and Kallman scores were utilized to evaluate 576 interphalangeal (IP) joints. US detected synovial inflammation features were scored as present/absent. US detected bone erosions were also investigated. The association between synovial inflammation features at baseline and the development of new bone erosions was evaluated using the generalized linear mixed model (GLMM) after adjustment for patient effect, age, gender, body mass index. In HOA patients, radiographic scores worsened and bone erosions progressed. In HOA patients similar percentages of joints with Power Doppler Signal (PDS) and gray scale (GS) synovitis were found comparing baseline and follow-up examinations, whilst a significant increase was found in the joints with effusions. Only a minority of joints were positive on both occasions (between 2 and 6 %), the majority fluctuated between positive and negative and vice versa. PDS positivity was associated with new radiographic central erosions and US-detected bone erosions, whereas GS synovitis and effusion were not. Radiographic scores and bone erosions increased over a period of about 4 years. Synovial inflammation as detected by PDS was associated with the appearance of new bone erosions.

Serum calprotectin (S100A8/9): an independent predictor of ultrasound synovitis in patients with rheumatoid arthritis.

IntroductionCalprotectin, a heterodimeric complex of S100A8/9 (MRP8/14), has been proposed as an important serum biomarker that reflects disease activity and structural joint damage in rheumatoid arthritis (RA). The objective of this cross-sectional study was to test the hypothesis that calprotectin is associated with clinical and ultrasound-determined disease activity in patients with RA.MethodsA total of 37 patients with RA (including 24 females, a mean disease duration of 20 months) underwent a clinical examination and 7-joint ultrasound score (German US-7) of the clinically dominant hand and foot to assess synovitis by grey-scale (GS) and synovial vascularity by power Doppler (PD) ultrasound using semiquantitative 0–3 grading. The levels of serum calprotectin and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were determined at the time of the ultrasound assessment. We analysed the relationship between serum calprotectin level, traditional inflammatory markers, and ultrasound-determined synovitis.ResultsThe levels of serum calprotectin were significantly correlated with swollen joint count (r = 0.465, p < 0.005), DAS28-ESR (r = 0.430, p < 0.01), ESR (r = 0.370, p < 0.05) and, in particular, CRP (r = 0.629, p < 0.001). Calprotectin was significantly associated with GS (r = 0.359, p < 0.05) and PD synovitis scores (r = 0.497, p < 0.005). Using multivariate regression analysis, calprotectin, adjusted for age and sex, was a better predictor of PD synovitis score (R2 = 0.765, p < 0.001) than CRP (R2 = 0.496, p < 0.001).ConclusionsThe serum levels of calprotectin are significantly associated with clinical, laboratory and ultrasound assessments of RA disease activity. These results suggest that calprotectin might be superior to CRP for monitoring ultrasound-determined synovial inflammation in RA patients.

O histograma de imagens coloridas permite melhor visualização de danos ecotexturais pelo ultrassom

The colored ultrasound images can better highlight the joint echotexture damage. To detect echotexture changes in joints of patients with rheumatic diseases, through a color histogram, and to correlate the area measurements with the gray scale (GS). Four patients with chondrocalcinosis, 5 patients with osteoarthritis and 1 patient with psoriatic arthritis were evalutated. A total of 104 synovitis (SYN) and calcifications (calcif) measurements in cm2 were performed in the dorsal radiocarpal joint (DRR); triangular fibrocartilage complex (TFC); dorsal metacarpophalangeal joints (MCP) and lateral and medial knee suprapatellar recesses. For each GS measure, one was performed for each standard color image. Spearman was used for correlation analysis. Mean±SD of image patterns: RGB (Red, Green and Blue) SYN 16.96±0.25cm2; indigo SYN 6.43±0.07cm2, RGB Calcif 0.03±0.00cm2; indigo Calcif 0.06±0.03cm2; GS SYN 16.13±0.35cm2 and GS Calcif 0.56±0.01cm2. Correlations of color images patterns RGB DRR SYN and indigo DRR SYN: r=1, p<0.001; indigo DRR SYN and RGB suprapattelar SYN: r=1, p<0.001; RGB MCP SYN and indigo MCP SYN: r=1, p<0.001; indigo DRR calcif and RGB TFC calcif: r=1 p<0.001; the RGB and indigo measurement standards when correlated with GS for SYN and calcifs were not statistically significant (p=0.333 to 0.667). The RGB and indigo patterns seem to better define these echotexture damage.