Karen Ellegaard

Ultrasound colour Doppler measurements in a single joint as measure of disease activity in patients with rheumatoid arthritis—assessment of concurrent validity

OBJECTIVE Colour Doppler ultrasound (CDU) displays blood flow in the tissues and is able to detect hyperaemia. Because hyperaemia is part of the inflammatory response, the amount of CDU activity in the inflamed synovium may be used to quantify the inflammatory activity in RA. It has never been investigated if the amount of CDU activity in a single joint can be used to quantify disease activity in RA. METHODS A total of 109 patients with RA and affection of the wrist joint underwent a standardized CDU examination assessing three positions in their most affected wrist at start up in biological treatment. On the same day the following measures of disease activity were collected: assessment of the number of tender and swollen joints, CRP, ESR and 28-joint disease activity score (DAS28). The amount of CDU activity was quantified by measuring the percentage of colour in the synovium--the colour fraction (CF). Correlation between CF and other measures of disease activity was calculated. RESULTS There was a significant correlation between CF and DAS28 (r = 0.29; P < 0.001), swollen joint count (r = 0.35; P < 0.001), CRP (r = 0.5; P < 0.001) and ESR (r = 0.5; P < 0.001). No other significant correlations were found. CONCLUSION A standardized ultrasound examination of a single affected wrist joint in patients with RA may be used as a measure of disease activity. More studies are needed to identify the number of joints needed to examine by CDU to obtain the best validity of Doppler measurements.

Ultrasound colour Doppler is associated with synovial pathology in biopsies from hand joints in rheumatoid arthritis patients: a cross-sectional study

Objectives Little is known regarding the association between ultrasound-determined pathological synovial blood flow and synovial pathology in rheumatoid arthritis (RA). We therefore examined the association between colour Doppler ultrasound imaging and synovitis assessed by histopathology and specific cell markers by immunohistochemistry in patients with RA. Methods 81 synovial sites from wrist and finger joints from 29 RA patients were evaluated by ultrasound colour Doppler and subsequently biopsied by needle arthroscopy. The association between ultrasound colour fraction and an overall synovitis score and immunohistochemical staining for CD3, CD68, Ki67 and von Willebrand factor was investigated, including repeated samples from the same patients. The overall synovitis score (total 0–9) assessed synovial lining hyperplasia (0–3), stromal activation (0–3) and inflammatory infiltration (0–3). Data were clustered within patients, thus a linear mixed model was applied for the statistical tests. Parsimony in the statistical models was achieved omitting covariates from the model in the case of what was judged no statistical significance (p>0.1). Results Doppler colour fraction showed an association with the overall synovitis score (approximated Spearman, approximately r=0.43, p=0.003). The density of all immunohistochemical stainings showed a significant association with Doppler colour fraction: von Willebrand factor (approximately r=0.44, p=0.01), CD68 (approximately r=0.53, p=0.02), Ki67 (approximately r=0.57, p=0.05) and CD3 (approximately r=0.57, p=0.0003). Conclusions Colour Doppler activity is associated with the extent of inflammation present in the synovial biopsies from RA patients. However, synovial pathology was also seen in biopsies taken from Doppler negative sites.

Indications of inflammation visualized by ultrasound in osteoarthritis of the knee.

Purpose: Ultrasound examination of a group of patients with osteoarthritis (OA) of the knee for signs of inflammation. Material and Methods: 71 knees in 71 patients with osteoarthritis of the knee were examined with high-resolution gray-scale ultrasound combined with color and spectral Doppler. The medial, lateral, and antero-superior compartments were examined. Hyperemia was identified as presence of color Doppler signals in the synovial membrane. Low resistance flow was defined as a resistive index <0.80 on spectral Doppler. Results: Synovial thickening was found in all knees; fluid in 61 patients; and hyperemia (color Doppler activity) in 51 patients. Of these, 44 had arterial flow on spectral Doppler – 36 with a low resistance flow. When present, fluid and color Doppler activity was found in all three compartments, but with uneven distribution. Conclusion: The finding in the majority of cases of both effusions on B-mode US and Doppler activity confirms that there is a varying degree of inflammation in knee OA as diagnosed by the ACR criteria.

Power and Color Doppler Ultrasound Settings for Inflammatory Flow: Impact on Scoring of Disease Activity in Patients With Rheumatoid Arthritis

To determine how settings for power and color Doppler ultrasound sensitivity vary on different high‐ and intermediate‐range ultrasound machines and to evaluate the impact of these changes on Doppler scoring of inflamed joints.

Ultrasound Doppler measurements predict success of treatment with anti-TNF-α drug in patients with rheumatoid arthritis: a prospective cohort study

OBJECTIVE To investigate the predictive ability of core outcomes applied in RA trials, including ultrasound (US) Doppler (USD) measurements differentiating patients who remain on anti-TNF-α therapy following 1 year. METHODS Patients with RA in anti-TNF-α therapy were followed 1 year after therapy initiation. All patients had wrist involvement. At baseline, 2 weeks, 26 weeks and 1 year a USD examination, clinical examination including tender and swollen joint count, visual analogue scale (VAS) global and HAQ, biochemical measures and 28-joint DAS (DAS28) were collected for all patients. The amount of USD signal in the synovium was quantified by measuring the percentage of colour pixels-the colour fraction (CF). Predictive validity for patients who remain on anti-TNF-α therapy after 1 year was assessed for both USD measurements and other disease measures. Baseline values of disease measures of patients who remained on treatment after 1 year was compared with those who stopped therapy. RESULTS The study cohort consisted of 109 patients. In this study, the baseline CF was the only measure predicting which patients would stay on the initial anti-TNF-α therapy for 1 year, evaluated using the square-root of CF (P = 0.024). The other disease markers could not significantly differentiate between the two groups of patients, with P-values of 0.86 and 0.98 for tender and swollen joint count, respectively, 0.86 for CRP, 0.24 for VAS, 0.10 for HAQ and 0.38 for DAS28. CONCLUSION There is now evidence to support that baseline USD, in contrast to clinical measures, can predict which patients will remain on anti-TNF-α 1 year after initiating therapy.

Associations Between Abnormal Ultrasound Color Doppler Measures and Tendon Pain Symptoms in Badminton Players During a Season: A Prospective Cohort Study

Background: Color Doppler ultrasound is widely used to examine intratendinous flow in individuals with overuse tendon problems, but the association between color Doppler and pain is still unclear. Hypothesis: Intratendinous flow is present and associated with pain in badminton players, and intratendinous flow and pain increase during a badminton season. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: Ninety-five semiprofessional badminton players were included in the study at a tournament at the start of the badminton season. All players were interviewed regarding pain. The anterior knee tendons and Achilles tendons were studied. Each tendon was scored using a quantitative grading system (grades 0-5) and a qualitative scoring system (color fraction) using color Doppler ultrasound. Eight months later, 86 of the players (91%) were retested by the same investigators during an equivalent badminton tournament (including 1032 tendon regions; 86 players with 4 tendons each with 3 regions), thus forming the study group. Results: At the start of the season, 24 players (28%) experienced pain in 37 tendons (11%), and at the end of the season, 31 players (36%) experienced pain in 51 tendons (15%), which was a statistically significant increase (P = .0002). Abnormal flow was found in 230 tendon regions in 71 players (83%) at the start of the season compared with 78 tendon regions in 41 players (48%) at the follow-up. The decrease in abnormal flow was statistically significant (P < .0001). Of the 37 painful tendons at the start of the season, 25 had abnormal flow (68%). In contrast, 131 tendons (85%) with abnormal flow at the start of the season were pain free. At the end of the season, 18 of the 51 painful tendons (35%) had abnormal flow. Ninety-six of the 131 pain-free tendons (73%) with abnormal flow at the start of the season were normalized (no pain and normal flow) at the end of the season. Conclusion: It was not possible to verify any association between intratendinous flow and pain at the start of the season or at the follow-up (end of the season). Intratendinous flow at the start of the season could not predict symptomatic outcome at the end of the season. The decrease in Doppler flow during the season might suggest that intratendinous flow could be part of a physiological adaptive response to loading and that intratendinous flow as previously believed is not always a sign of pathological changes.

Evaluation of the Benefit of Corticosteroid Injection Before Exercise Therapy in Patients With Osteoarthritis of the Knee A Randomized Clinical Trial

IMPORTANCE Osteoarthritis (OA) of the knee is the most frequent form of arthritis and a cause of pain and disability. Combined nonpharmacologic and pharmacologic treatments are recommended as the optimal treatment approach, but no evidence supports the recommendation. OBJECTIVE To assess the clinical benefits of an intra-articular corticosteroid injection given before exercise therapy in patients with OA of the knee. DESIGN, SETTING, AND PARTICIPANTS We performed a randomized, blinded, placebo-controlled clinical trial evaluating the benefit of intra-articular corticosteroid injection vs placebo injection given before exercise therapy at an OA outpatient clinic from October 1, 2012, through April 2, 2014. The participants had radiographic confirmation of clinical OA of the knee, clinical signs of localized inflammation in the knee, and knee pain during walking (score >4 on a scale of 0 to 10). INTERVENTIONS Participants were randomly allocated (1:1) to an intra-articular 1-mL injection of the knee with methylprednisolone acetate (Depo-Medrol), 40 mg/mL, dissolved in 4 mL of lidocaine hydrochloride (10 mg/mL) (corticosteroid group) or a 1-mL isotonic saline injection mixed with 4 mL of lidocaine hydrochloride (10 mg/mL) (placebo group). Two weeks after the injections, all participants started a 12-week supervised exercise program. MAIN OUTCOMES AND MEASURES The primary outcome was change in the Pain subscale of the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire (range, 0-100; higher scores indicate greater improvement) at week 14. Secondary outcomes included the remaining KOOS subscales and objective measures of physical function and inflammation. Outcomes were measured at baseline, week 2 (exercise start), week 14 (exercise stop), and week 26 (follow-up). RESULTS One hundred patients were randomized to the corticosteroid group (n = 50) or the placebo group (n = 50); 45 and 44 patients, respectively, completed the trial. The mean (SE) changes in the KOOS Pain subscale score at week 14 were 13.6 (1.8) and 14.8 (1.8) points in the corticosteroid and placebo groups, respectively, corresponding to a statistically insignificant mean difference of 1.2 points (95% CI, -3.8 to 6.2; P = .64). We found no statistically significant group differences in any of the secondary outcomes at any time point. CONCLUSIONS AND RELEVANCE No additional benefit results from adding an intra-articular injection of 40 mg of corticosteroid before exercise in patients with painful OA of the knee. Further research is needed to establish optimal and potentially synergistic combinations of conservative treatments. TRIAL REGISTRATION clinicaltrialsregister.eu Identifier: 2012-002607-18; clinicaltrials.gov Identifier: NCT01945749.

The specificity of ultrasound-detected bone erosions for rheumatoid arthritis

Background Bone erosion is one of the hallmarks of rheumatoid arthritis (RA), but also seen in other rheumatic diseases. The objective of this study was to determine the specificity of ultrasound (US)-detected bone erosions (including their size) in the classical ‘target’ joints for RA. Methods Patients fulfilling the diagnostic criteria for RA, psoriatic arthritis, osteoarthritis or gout in addition to healthy volunteers were included. The following areas were examined by US: distal radius and ulna, 2nd, 3rd and 5th metacarpophalangeal (MCP), 2nd and 3rd proximal interphalangeal (PIP) and 1st and 5th metatarsophalangeal (MTP) joints. All joints were scanned in four quadrants using both semiquantitative (0–3) and quantitative (erosion diameter) scoring systems. Results 310 subjects were recruited. The inter-reader and intrareader agreements were good to excellent. US-detected bone erosions were more frequent but not specific for RA (specificity 32.9% and sensitivity 91.4%). The presence of erosions with semiquantitative score ≥2 in four target joints (2nd, 5rd MCP, 5th MTP joints and distal ulna) was highly specific for RA (specificity 97.9% and sensitivity 41.4%). Size of erosion was found to be associated with RA. Erosions of any size in the 5th MTP joint were both specific and sensitive for RA (specificity 85.4% and sensitivity 68.6%). Conclusions The presence of US-detected erosions is not specific for RA. However, larger erosions in selected joints, especially 2nd and 5rd MCP, 5th MTP joints and distal ulna, were highly specific for and predictive of RA.

Influence of recent exercise and skin temperature on ultrasound Doppler measurements in patients with rheumatoid arthritis—an intervention study

OBJECTIVE Use of ultrasound Doppler (USD) in diagnosing and treatment monitoring of patients with RA has increased considerably. Hyperaemia is an integral part of the inflammatory response, and the amount of USD activity in an inflamed synovium may therefore be used to quantify the inflammatory activity. It is unclear, however, whether the hyperaemia alone reflects the disease activity or may be influenced by other factors. METHODS Twenty-nine patients with RA underwent USD examination of the wrist before and immediately after three interventions. The interventions were carried out on three separate days. The interventions were (i) isometric exercise of the muscles of the hand and forearm, (ii) heating and (iii) cooling of the hand. The amount of Doppler in the wrist joint was quantified by measuring the percentage of colour in the synovium-the colour fraction (CF). The CF values estimated before and after each intervention were compared to see if any intervention affected the amount of Doppler in the synovium. RESULTS The CF decreased significantly after cooling of the hand (P = 0.018 and <0.0001). Despite being highly significant, the numerical decrease in CF was only modest, 0.78-1.33 percentage points. The other interventions did not affect the CF significantly, with P-values of 0.65 and 0.59 in the heating intervention and 0.49 in the exercise intervention. CONCLUSIONS Cooling of the hand should, if possible, be avoided before a USD examination of the wrist in patients with RA, because the amount of Doppler activity might be affected by low skin temperatures.

Head-to-head comparison of quantitative and semi-quantitative ultrasound scoring systems for rheumatoid arthritis: reliability, agreement and construct validity

OBJECTIVE To evaluate the reliability and agreement of semi-quantitative scoring (SQS) and quantitative scoring (QS) systems. To compare the two types of scoring system and investigate the construct validity for both scoring systems. METHODS A total of 46 RA patients (median disease duration of 6.5 years) were enrolled in the study. They were investigated with colour Doppler ultrasound using the central position of the wrist. Disease activity score based on 28 joints (DAS-28) was determined for all patients using CRP. Two participants trained in the SQS system and two in the QS system evaluated the 46 anonymized images. All images were scored twice by each of the two assessors in order to assess both intra- and inter-reader reliability. RESULTS The reliability for the two systems were 0.964 for the QS, and 0.817 for the SQS, with a comparable inter-reader agreement for both scoring systems; 95% limits of agreement for the QS being between -7.7% and +6.7% on the colour fraction scale (0-100%), whereas SQS was between -0.8 and +0.8 on the ordinal scale from 0 to 3. There was a direct but non-linear relationship between the two modalities (Spearmans r = 0.73) and critical conceptual issues in the agreement between the scoring systems were revealed. The construct validity was poor for both systems with only a weak correlation to CRP. CONCLUSION High reliability and good agreement of both scoring systems were found when applied to the same patient cohort. Different scoring systems appear to be highly correlated.