H. Bliddal

Quantitative ultrasonography in rheumatoid arthritis: evaluation of inflammation by Doppler technique

OBJECTIVE To evaluate ultrasonographic methods, including the Doppler technique, as measures of synovial inflammation in finger joints of patients with rheumatoid arthritis. METHODS Ultrasonography was performed with a high frequency transducer (13 MHz).  Evaluation of the sonographic data was conducted by two independent observers and included measurement of synovial area and thickness (grey tone ultrasound), vascularisation (power/colour Doppler), and indices of the intra- and extrasynovial arterial flow (spectral Doppler). The flow pattern was estimated by the indices of pulsatility (PI) and resistance (RI). RESULTS The sonographic measurements of joint space were reproducible with intraobserver, intraclass correlation coefficients (ICC) 0.82–0.97 (p<0.0001) and interobserver ICC 0.81 (p<0.0001). The mean (SD) fraction of the synovium vascularised in the patients was 0.15 (0.15). The synovial blood flow was characterised by a diastolic flow—that is, the flow persisting during the diastole. The mean (SD) PI was 1.92 (1.18) and RI 0.70 (0.13). The estimated vascular fraction correlated with the erythrocyte sedimentation rate (ESR) (r s=0.53, p=0.03). The relative Pi (rPi), an estimate of an abnormally low resistance to vascularisation, correlated with both ESR (r s=−0.557, p<0.05) and Health Assessment Questionnaire score (r s=−0.584, p<0.05). After an injection of contrast Levovist the vascular fraction increased, while no difference in PI and RI was observed. CONCLUSION Ultrasonography is a reliable tool for estimating the size of the joint space and the synovial activity measured by the degree of vascularisation and pattern of flow. Ultrasonography may be useful in monitoring the synovial inflammation in rheumatoid arthritis.

Estimation of inflammation by Doppler ultrasound: quantitative changes after intra-articular treatment in rheumatoid arthritis

Objective: To evaluate the use of ultrasound, including quantitative Doppler analysis of synovial vascularisation, before and after intra-articular treatment with glucocorticosteroids in patients with rheumatoid arthritis (RA). Methods: 51 patients with RA were followed prospectively after an intra-articular glucocorticosteroid injection. Disease modifying antirheumatic drug treatment was kept unchanged and no further injections given in this observation period. At baseline, disease activity was estimated clinically by target join pain on a 100 mm visual analogue scale, on which the target joint was scored 0–3 for swelling and tenderness, and by ultrasound measurements of grey scale pixels, colour Doppler pixels, and the spectral Doppler resistive index (RI) as indicators of synovial swelling and inflammation. After four weeks, the measurements were repeated on the same joint. An observer unaware of the sequence and patient number evaluated the ultrasound images. Results: At one month follow up after the glucocorticosteroid injection, a marked decrease in the fraction of colour pixels was seen in 41/51 patients (Student’s t test p<0.001). Correspondingly, the RI increased indicating a diminished flow to the synovium (Student’s t test p<0.01). Both the fraction of colour pixels and the RI values corresponded with the clinical evaluation and with the subjective effect of the treatment. The synovial membrane volume estimated by total amount of pixels showed a significant decrease by 31% after treatment. Conclusion: Ultrasound-Doppler seems to be a promising tool for the estimation of synovial activity in arthritis. After intra-articular glucocorticosteroid, changes in RI and fraction of colour pixels may both be used as quantitative measurements of the blood flow.

Effects of treatment with etanercept (Enbrel, TNRF:Fc) on rheumatoid arthritis evaluated by Doppler ultrasonography

Objective: to estimate and visualise the efficacy of treatment with etanercept (Enbrel) in patients with rheumatoid arthritis (RA) using colour Doppler and spectral Doppler ultrasonography to determine the possible changes in synovial perfusion during a one year observation period. Methods: Eleven patients from the European multicentre trial of the efficacy and safety of etanercept were included in this study when transferred into the open label, long term safety, and efficacy study. Before a scheduled dosage increase to 50 mg/week they were examined clinically, serologically, and by ultrasonography using the colour Doppler pixels and the spectral Doppler resistance index (RI) as indicators of inflammation. The patients were re-examined at two weeks and at one year follow up Results: The clinical activity decreased significantly from baseline to week 2, but no significant changes were seen from baseline to one year. The number of coloured pixels in each region of interest decreased from baseline to week 2 with a median reduction of 60% (p=0.005). This effect on the perfusion in the synovium could not be found after one year of treatment. During the initial treatment we detected an increase in synovial RI by spectral Doppler. The median increase in peripheral resistance from baseline to week 2 as estimated by the mean RI was 22.6% (p=0.005). The increase in peripheral resistance was maintained to some extent after one year (mean RI increased by 18.8% p=0.074). Conclusion: Ultrasonography seems to be a promising tool for the detection of treatment response using spectral Doppler and pixel estimation.

Predictors of improvement in observed functional ability in patients with fibromyalgia as an outcome of rehabilitation.

OBJECTIVE To investigate predictors of improvement in observed ability to manage activities of daily living as an outcome of rehabilitation in fibromyalgia. METHODS Exploratory analyses used data from the Interdisciplinary Rehabilitation and Evaluation Programme for Patients with Chronic Widespread Pain (the IMPROvE study); a randomized controlled trial including 191 females with fibromyalgia randomized (1:1) to rehabilitation or a waiting list. The primary outcome was observed activities of daily living ability evaluated with the Assessment of Motor and Process Skills (AMPS) 6 months post-intervention. RESULTS Overall, 38.7% of subjects were AMPS responders, i.e. having a clinically meaningful improvement in AMPS activities of daily living ability measures at 6 months post-intervention. In the exploratory analysis, only 4 baseline variables out of the 52 analysed showed a statistically significant interaction with treatment allocation (at the 0.05 level) indicating possible predictive value. Statistical analyses that used continuous variables dichotomized at the median suggested a predictive value of a low intake of weak and strong analgesics, and a high score of current pain and total score on the Pain Detect Questionnaire. CONCLUSION The results of this exploratory study suggest that several subgroups of patients, specifically those with a low baseline intake of weak and strong analgesics, and more pronounced clinical signs of central sensitization, may gain most clinical benefit from specialized rehabilitation when the outcome of interest is improvement in observed activity of daily living ability.

FRI0654 Ultrasound detected pathology in the enthesis of the lower limb in an age stratified cohort of asymptomatic subjects -a prospectively designed descriptive cross-sectional study

Background Ultrasound (US) examination of the entheses is increasingly used to document pathological changes in e.g. psoriasis arthritis and spondyloarthritis. Grey-scale (GS) US is used to assess morphological changes and Doppler US to assess increased blood flow. The OMERACT expert group has agreed on the following elementary components when assessing the entheses on US examination; hypoechogenicity, increased thickness, enthesophytes/ calcifications, erosions, and Doppler activity (1). Little is known about US assessment of the entheses in asymptomatic persons, thus the frequency and distribution of the above components between genders and age groups is uncertain. Objectives To investigate the frequency of enthesitis components in the entheses of the lower limb in a group of healthy subjects. Methods We recruited 64 subjects (32 women and 32 men), eight women and eight men in four decades, from 20 to 59 years. None of the subjects had previous or present signs of tendon or joint disease in the lower extremities. None of the participants took any kind of medication. All subjects were examined by a rheumatologist and blood samples were collected to rule out any clinical signs of tendon or joint disease e.g. swollen and tender entheses or increased inflammatory markers in the blood. The dominant leg was examined with US using a Logiq 9 (GE Medical, Milwaukee, WI, USA) with a ML 6–15 MHz transducer and a fixed pre-set with Doppler settings optimised for inflammatory flow. Both GS and Doppler examination were made. The entheses were examined for hypoechogenicity, increased thickness, enthesophytes/ calcifications, erosions, and Doppler activity. Results No subjects had clinical signs of tendon or joint disease. Seven displayed various degrees of hypermobility and seven had various degrees of flatfoot; some in combination. None of the blood tests indicated any pathology. On US erosions were only seen in one Achilles insertion (not shown in table). The Doppler activity was not measured in plantar fascia due to attenuation of the heel fad pad. All other US pathology present is seen in the table below. Conclusions Only minor pathological findings in the entheses of the lower limb were present in an age stratified cohort of healthy persons. The changes most frequently seen were bony changes in the insertion of the quadriceps and Achilles tendons. A weak tendency toward more pathological findings was seen in this cohort among men, compared to women, and additionally, with increasing age. The findings suggest that US can be used to diagnose/examine subjects for pathological changes of the entheses although with caution regarding enthesophytes of the quadriceps and Achilles tendon. References Terslev L et al. Defining enthesitis in spondyloarthritis by ultrasound: results of a Delphi process and of a reliability reading exercise. Arthritis Care Res 2014 May;66:741–8. Disclosure of Interest None declared

THU0096 Correlation Between Ultrasound Doppler Imaging and Circulating Vascular Endothelial Growth Factor in Rheumatoid Arthritis Patients Following Anti-TNF-α Treatment

Background Successful anti-TNF-α treatment of rheumatoid arthritis (RA) causes a decrease in inflammation with reduced blood flow in the synovial tissue of the affected joints. Ultrasound Doppler (USD) is used as an estimate of the amount of blood flow in a tissue and is sensitive to measurements of small blood vessels. USD is used as a marker of disease activity in RA, where inflammation causes forming of new small blood vessels. Vascular Endothelial Growth Factor (VEGF) is suspected to be a main player in angiogenesis during inflammation. A role of VEGF in the pathogenesis of RA is supported by elevated serum levels in RA patients compared to healthy controls. Objectives In a cohort of anti-TNF-α treated RA patients, to investigate if a change in USD signal following treatment over a year is associated with change in VEGF, and if VEGF is correlated to disease activity. Methods 73 out of a cohort of 109 RA patients in anti-TNF-α treatment (adalimumab, etanercept or infliximab), 53 women and 20 men, age 57±13 years, with inflammation of wrist joints were assessed prior to starting anti-TNF-α therapy, and following treatment. USD examination was carried out on the most affected wrist, and fasting blood samples were collected, with no prior strenuous physical activity, at baseline, and after 180 days and 1 year of treatment. USD was measured as colour fraction (CFMean), and VEGF was measured by ELISA (Platinum, Bioscience) in EDTA-plasma at each time point. DAS28CRP was determined. Linear regression was applied, using Pearsons correlation coefficient and a significance level at 0.05. The study was approved by the local ethics committee (KF01-045/03). Results Full data set was available for 64 patients at 180 days and for 58 patients at 1 year. DAS28CRP at baseline was 5.1±1.3. VEGF was in the range earlier reported for RA patients. No correlation was found between CFMean and VEGF at baseline (R2=0.006; P>0.05), or in change in CFMean and change in VEGF at 180 days (R2=0.0016; P>0.05) and 1 year (RCRP and VEGF at baseline (R2=0.05; P>0.05). Conclusions In our cohort of RA patients, no correlation was seen between VEGF plasma level and USD activity in an affected wrist joint prior to start of an anti-TNF-α of treatment, or between changes in USD and changes in VEGF following 180 and 365 days of treatment. At baseline VEGF level did not correlate to DAS28CRP either. These results do not support a role of VEGF, although important for angiogenesis, as a determinant for the increased perfusion in RA. Acknowledgements The study was supported by the Danish Rheumatism Association and the OAK Foundation Disclosure of Interest None declared

FRI0481-HPR Assessment of validity of clinical impingement tests in patients with thickened subacromial bursa using dynamic us examination as gold standard

Background Subacromial impingement (SAI) is a common disorder of the shoulder accounting for about half of all complains of pain in the shoulder. A number of clinical tests are recommended to identify SAI, however, the accuracy of impingement tests is only moderate when compared to findings on both US and surgery (1;2). The diagnose SAI is rather unspecific but it is assumed that both tendons and bursa in the shoulder are impinged with the acromial bone in the movement of the shoulder. Impingement may be verified by dynamic US, which allows real time examination of the shoulder joint in motion Objectives The aim of this cross sectional study was to evaluate the concurrent validity of a number of clinical impingement tests in patients with thickened bursa (≥2mm on US). The validity was calculated using dynamic US examination of the shoulder as gold standard. Methods Hundred-forty subjects with unspecific shoulder pain were screened for the study. Of these 99 fulfilled the inclusion criteria of having an enlarged bursa (≥2mm) at US examination and no other conditions with could explain the shoulder pain, e.g. tendon ruptures or biceps tenosynovitis. In all subjects five different clinical impingement tests were made by an experienced physiotherapist (Neer, Hawkins, Full can, Empty can, Apprehension test) (3). Subsequent a dynamitic US examination of shoulder abduction was performed by an US specialist unaware of the results of the clinical test. The US impingement test was defined as positive if the tendon and or bursa were impinged at the acromial bone during abduction of the shoulder. Statistics: Kappa values were calculated. Results A full and valid data set was present in 93 of the 99 patients. Results are seen in Table 1. Table 1 (N=93) Positive Agreement Agreement Total Kappa impingement with US with US agreement (CI) positive test negative positive (CI) USr 41 Neer 80 33 9 0,452 -0.0005 (0.350–0.553) (-0.144-0.135) Hawkins 90 40 8 0,516 0.133 (0.415-0.618) (0.042-0.223) Full can 60 28 24 0,559 0.145 (0.458-0.660) (-0.041-0.332) Empty can 66 30 20 0,538 0.119 (0.436-0.639) (-0.057-0.295) Apprehension 88 35 4 0,419 -0.044 (0.319-0.520) (-0.154-0.067) Conclusions The concurrent validity (Kappa) for all the clinical tests of impingement was poor compared to dynamic US and absolute agreement was only seen in about half of the persons. In general the clinical tests assessed the person as having impingement much more often than US did. Misinterpretation could be due to compression of tender and swollen structures in the subacromial space during impingement test References Kelly SM, Brittle N, Allen GM. The value of physical tests for subacromial impingement syndrome: a study of diagnostic accuracy. Clin Rehabil 2010 Feb;24(2):149-58. Michener LA, Walsworth MK, Doukas WC, Murphy KP. Reliability and diagnostic accuracy of 5 physical examination tests and combination of tests for subacromial impingement. Arch Phys Med Rehabil 2009 Nov;90(11):1898-903. Cools AM, Cambier D, Witvrouw EE. Screening the athlete’s shoulder for impingement symptoms: a clinical reasoning algorithm for early detection of shoulder pathology. Br J Sports Med 2008 Aug;42(8):628-35. Disclosure of Interest None Declared

455 CHANGES IN KNEE MUSCLE STRENGTH AND MUSCLE MASS AFTER WEIGHT LOSS IN OBESE PATIENTS WITH KNEE OSTEOARTHRITIS: A PROSPECTIVE COHORT STUDY

P1, to predict the effect of the disturbance and adjusted motor output accordingly. Studies have shown that proprioceptive deficits are common in people with knee OA and it is often presumed that these deficits lead to ineffective knee stabilization strategies. However, knee sensation is tested under carefully controlled conditions whereas afferent feedback during more functional tasks is provided by the knee joint along with many other structures. The normal neuromuscular adaptation that occurred in the OA subjects in this study suggest that reduced afferent input from the knee may not have as big an influence over the control of knee stability as previously thought.

140 RELATIONSHIP BETWEEN SUBMAXIMAL QUADRICEPS FORCE CONTROL AND JOINT LOADS DURING WALKING IN KNEE OSTEOARTHRITIS

The changes in knee joint adduction moments were consistent with the changes observed in less severe OA (Figure 2), as were the changes in the sagittal plane moments. Conclusions: This study shows that pain induced changes in knee joint mechanics during walking replicate changes observed in less severe patients. The experimental model may be used to study knee OA pathomechanics and possible preventive measures against abnormal joint loading in knee OA. It is suggested that pain management regimes be tested on the basis of their influence on knee OA pathomechanics. 140

139 GAIT CHANGES IN PATIENTS WITH KNEE OSTEOARTHRITIS ARE REPLICATED BY EXPERIMENTAL KNEE PAIN

Objective. Medial knee osteoarthritis (OA) is characterized by pain and associated with abnormal knee moments during walking. The relationship between knee OA pain and gait changes remains to be clarified, and a better understanding of this link could advance the treatment and prevention of disease progression. This study investigated changes in knee moments during walking following experimental knee pain in healthy volunteers, and whether these changes replicated the joint moments observed in medial knee OA patients. Methods. In a crossover study, 34 healthy subjects were tested on 3 different days; gait analyses were conducted before, during, and after pain induced by hypertonic saline injections (0.75 ml) into the infrapatellar fat pad. Isotonic saline and sham injections were used as control conditions. Peak moments in frontal and sagittal planes were analyzed. The results were compared with data from 161 medial knee OA patients. The patients were divided into less severe OA and severe OA categories, which was based on radiographic disease severity of the medial compartment. Results. Experimental knee pain led to reduced peak moments in the frontal and sagittal planes in the healthy subjects, which were similar to the patterns observed in less severe OA patients while walking at the same speed. Conclusion. In healthy subjects, pain was associated with reductions in knee joint moments during walking in a manner similar to less severe knee OA patients. The experimental model may be used to study mechanically-driven knee OA progression and preventive measures against abnormal joint loading in knee OA.