Structural damage in rheumatoid arthritis assessed by musculoskeletal ultrasound: A systematic literature review by the Structural Joint Damage Task Force of the OMERACT Ultrasound Working Group.

OBJECTIVES: To identify and synthesize the evidence for the use and measurement properties of musculoskeletal ultrasound in assessing structural joint damage in patients with rheumatoid arthritis (RA). METHODS: A systematic literature search (SLR) of the PubMed, Embase and Cochrane Library was performed. Original articles were included published in English reporting on ultrasound of bone erosion, cartilage damage and the measurement properties of ultrasound according to the OMERACT filter 2.1. RESULTS: Of the 1.495 identified articles 149 were included in the final review, most of which reported on cross-sectional studies and used the OMERACT definitions for ultrasonographic pathology. Among these, bone erosions were assessed in 139 (93.3%), cartilage damage in 24 (16.1%), enthesophytes in 8 (5.4%), osteophytes in 15 (10.1%) and malalignment and ankylosis in a single (0.9%) study, respectively. Most studies (126/149, 84.6%) assessed the joints of the hands. The overwhelming majority of studies (127/149, 85.2%) assessed structural joint damage bilaterally. Validity, reliability and responsiveness were assessed in 21 (14.1%), 34 (22.8%) and 17 (11.4%) studies, respectively. CONCLUSION: While the results of this SLR suggest that ultrasound is a sensitive, reliable and feasible tool to detect damage in RA, they also highlight the need for further research and validation. Findings of this SLR will inform the next steps of the OMERACT Ultrasound Working Group in developing an ultrasound score for assessing structural joint damage in patients with RA.

Comorbidity clusters in generalized osteoarthritis among female patients: A cross-sectional study.

OBJECTIVES: To investigate the prevalence of comorbidities among female patients with generalized osteoarthritis (GOA) in comparison to an age- and sex matched control group. To identify clusters of comorbidities in both groups. METHODS: An observational, cross-sectional study was conducted. Consecutive female patients with hand and knee osteoarthritis according to the American College of Rheumatology (ACR) classification criteria were invited to participate in the study. A control group of participants without musculoskeletal symptoms, history or evidence of osteoarthritis or inflammatory rheumatic disease were also included. Cardiovascular, obstructive pulmonary, gastrointestinal, endocrine, neurological, malignant diseases and depression were recorded in both groups. In both study groups comorbidity cluster and factor analysis was performed. RESULTS: The study population included 200 GOA and 200 control participants. The following comorbidities were observed adjusted to Bonferroni correction with a significantly higher prevalence among individuals with GOA: hypertension, uterine leiomyoma, gastroesophageal reflux disease, diverticulosis, upper gastrointestinal tract ulcers, depression, diseases with vertigo (benign paroxysmal positional vertigo and vertebrobasilar insufficiency) and surgery due to otoclerosis. In the GOA group 5 clusters were identified with different comorbidity patterns. CONCLUSION: We report a high comorbidity rate in GOA. Cluster analysis allowed us to identify different comorbidity subsets for vascular, gastrointestinal and malignant gynaecological disorders. Further research is required to understand the links between GOA and non-musculoskeletal comorbidities.

Relationship between radiographic joint space narrowing, sonographic cartilage thickness and anatomy in rheumatoid arthritis and control joints.

OBJECTIVE: To validate ultrasound (US) for measuring metacarpal cartilage thickness (MCT), by comparing it with anatomical measurement using cadaver specimens. To correlate US MCT with radiographic joint space narrowing (JSN) or width (JSW) in patients with rheumatoid arthritis (RA). METHODS: Bilateral metacarpophalangeal (MCP) joints of 35 consecutive outpatients, with recent hand X-rays, were included in the analysis. Metacarpal and phalangeal cartilage of MCP 2-5 was assessed bilaterally by US. JSW and JSN were evaluated on X-rays by the van der Heijde modified Sharp method (vdHS). In addition, cadaver specimens of MCP 2-5 joints (n=19) were evaluated by anatomical measurement and US. RESULTS: The agreement (intraclass correlation coefficient) between sonographic and anatomical MCT on cadaver specimens of MCP joints was 0.61. MCT of individual MCP joints correlated with individual MCP JSN (r=-0.32, p<0.001) and individual MCP JSW (r=0.72, p<0.001). No correlation was found between phalangeal cartilage thickness and JSN in individual MCP joints. The US MCT summary score for MCP joints 2-5 correlated with summary scores for JSW (r=0.78, p<0.001), JSN (r=-0.5, p<0.001), erosion score of the vdHS (r=-0.39, p<0.001) and total vdHS (r=-0.47, p<0.001). CONCLUSIONS: Sonographic cartilage assessment in MCPs is closely related to anatomical cartilage thickness. Both JSW and JSN by radiography represent cartilage thickness in the MCP joints of patients with RA quite well. Thus, US is a valid tool for measuring MCT if radiographs are not available or in case of joint malalignment.

Defining enthesitis in spondyloarthritis by ultrasound: results of a Delphi process and of a reliability reading exercise.

OBJECTIVE: To standardize ultrasound (US) in enthesitis. METHODS: An initial Delphi exercise was undertaken to define US-detected enthesitis and its core components. These definitions were subsequently tested on static images taken from spondyloarthritis patients in order to evaluate their reliability. RESULTS: Excellent agreement (>80%) was obtained for including hypoechogenicity, increased thickness of the tendon insertion, calcifications, enthesophytes, erosions, and Doppler activity as core elementary lesions of US-detected enthesitis. US definitions were subsequently obtained for each elementary component. On static images, the intraobserver reliability showed a high degree of variability for the detection of elementary lesions, with kappa coefficients ranging from 0.13-1. The interobserver kappa values were variable, with the lowest kappa coefficient for enthesophytes (0.24) and the highest coefficient for Doppler activity at the enthesis (0.63). CONCLUSION: This is the first consensus-based US definition of enthesitis and its elementary components and the first step performed to ensure a higher degree of homogeneity and comparability of results between studies and in daily clinical work.

Clinical and ultrasound-based composite disease activity indices in rheumatoid arthritis: results from a multicenter, randomized study.

OBJECTIVE: To evaluate the metrologic properties of composite disease activity indices in rheumatoid arthritis (RA), utilizing information derived from clinical, gray-scale (GS), and power Doppler (PD) ultrasound examinations, and to assess the classification of patients according to disease activity using such indices. METHODS: This ancillary study utilized data from a multicenter, prospective, randomized, parallel-group study conducted in subjects with moderate RA randomized to receive etanercept and methotrexate (ETN + MTX) or usual care (various disease-modifying antirheumatic drugs [DMARDs]). In multimodal indices, the 28 swollen joint count was either supplemented or replaced by clinically nonswollen joints in which the presence of synovitis was detected either by GS and/or PD and was calculated according to the Disease Activity Score in 28 joints (DAS28) or the Simplified Disease Activity Index (SDAI). Reliability, external validity, and discriminative capacity were calculated at baseline/screening by intraclass correlation coefficient, Pearson's correlation, and standardized response mean, respectively. RESULTS: Data from 62 patients (mean ± SD age 53.8 ± 13.2 years, mean ± SD disease duration 8.8 ± 7.7 years, mean ± SD disease activity 4.6 ± 0.5 [DAS28] and 20.9 ± 5.9 [SDAI]) were analyzed, with 32 receiving ETN + MTX and 30 receiving DMARDs. The metrologic properties were at least as good for GS- and/or PD-based indices as for their clinical counterparts. Using GS- and PD-supplemented indices, an additional 67.8% and 32.3% of patients (DAS28-derived and SDAI-derived indices, respectively) could be classified as having high disease activity at the screening visit. CONCLUSION: Multimodal indices incorporating ultrasound and clinical data had similar metrologic properties to their clinical counterparts; certain indices allowed for a significantly larger number of patients to be classified to either high or moderate disease activity at the screening visit.

Ultrasound evaluation of fluid in knee recesses at varying degrees of flexion.

OBJECTIVE: Various methods are utilized in daily practice to obtain optimal information on effusion in the knee. Our aim is to investigate which scanning position provides the best information about synovial fluid in the knee by using ultrasound and to evaluate the magnitude of difference for measuring synovial fluid in 3 major recesses (suprapatellar, medial parapatellar, and lateral parapatellar) of the knee according to various degrees of flexion. METHODS: Sonographers in 14 European centers documented bilateral knee joint ultrasound examinations on a total of 148 knee joints. The largest sagittal diameter of fluid was measured in scans corresponding to the 3 major recesses at different (0°, 15°, 30°, 45°, 60°, and 90°) degrees of flexion of the knee. The difference of measurement of effusion according to transducer position, knee position, and the interaction between them was investigated by analysis of variance followed by Tukey's test. RESULTS: No correlation was noted between patient characteristics and ultrasound detection of effusion. The sagittal diameter of synovial fluid in all 3 recesses was greatest at 30° flexion. Analysis of variance and Tukey's test revealed that the suprapatellar scan and 30° flexion is the best combination for detecting effusion as confirmed by receiver operator characteristic curve analysis. CONCLUSION: The suprapatellar scan of the knee in 30° flexion was the most sensitive position to detect fluid in knee joints. Sagittal diameter of fluid in all 3 recesses increased with the knee in the 30° flexed position as compared to the extended position.

Metrologic properties of ultrasound versus clinical evaluation of synovitis in rheumatoid arthritis: results of a multicenter, randomized study.

OBJECTIVE: To evaluate the intraobserver reliability, face validity, and discriminant capacity of different global ultrasound (US) scoring systems for measuring synovitis in rheumatoid arthritis (RA). METHODS: This study was ancillary to a 52-week, multicenter, prospective, randomized, open-label, parallel-group outpatient study conducted in patients with moderate RA who were randomized to receive either etanercept combined with methotrexate or various disease-modifying antirheumatic drugs. A total of 66 different synovitis scoring systems were constructed and evaluated, including 11 different joint combinations; data derived from clinical findings, gray-scale US, and power Doppler US (PDUS); and both binary counts and semiquantitative scores. RESULTS: Due to discontinuation of the trial, only 62 patients, a subset of the initially planned number of patients, were included in this study. Reliability was found to be better for gray-scale US and PDUS than for clinical evaluation of synovitis in patients with stable disease between the screening and baseline visits (range for intraclass correlation coefficient 0.6, 0.95 for gray-scale US and 0.56, 0.93 for PDUS versus 0.31, 0.75 for clinical indices). The median (range) difference in the discriminant capacities of clinical indices versus gray-scale US and versus PDUS was 0.25 (-0.64, 0.96) and -0.025 (-0.59, 0.53), respectively, in the period from baseline to 12 weeks. No relevant differences in metrologic properties were observed regarding the number and composition of joints between the different scoring systems. Our findings suggested that a simplified scoring system referring to gray-scale US and PDUS findings might be sufficient. CONCLUSION: Our findings indicate that gray-scale US and PDUS have better reliability than generally used clinical indices for evaluating synovitis in RA. PDUS has at least as good discriminant capacity as clinical assessment of synovitis for distinguishing between treatment arms.

Validity of ultrasonography and measures of adult shoulder function and reliability of ultrasonography in detecting shoulder synovitis in patients with rheumatoid arthritis using magnetic resonance imaging as a gold standard.

OBJECTIVE: To assess the intra- and interobserver reproducibility of musculoskeletal ultrasonography (US) in detecting inflammatory shoulder changes in patients with rheumatoid arthritis, and to determine the agreement between US and the Shoulder Pain and Disability Index (SPADI) and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, using magnetic resonance imaging (MRI) as a gold standard. METHODS: Eleven rheumatologists investigated 10 patients in 2 rounds independently and blindly of each other by US. US results were compared with shoulder function tests and MRI. RESULTS: The positive and negative predictive values (NPVs) for axillary recess synovitis (ARS) were 0.88 and 0.43, respectively, for posterior recess synovitis (PRS) were 0.36 and 0.97, respectively, for subacromial/subdeltoid bursitis (SASB) were 0.85 and 0.28, respectively, and the NPV for biceps tenosynovitis (BT) was 1.00. The intraobserver kappa was 0.62 for ARS, 0.59 for PRS, 0.51 for BT, and 0.70 for SASB. The intraobserver kappa for power Doppler US (PDUS) signal was 0.91 for PRS, 0.77 for ARS, 0.94 for SASB, and 0.53 for BT. The interobserver maximum kappa was 0.46 for BT, 0.95 for ARS, 0.52 for PRS, and 0.61 for SASB. The interobserver reliability of PDUS was 1.0 for PRS, 0.1 for ARS, 0.5 for BT, and 1.0 for SASB. P values for the SPADI and DASH versus cuff tear on US were 0.02 and 0.01, respectively; all other relationships were not significant. CONCLUSION: Overall agreements between gray-scale US and MRI regarding synovitis of the shoulder varied considerably, but excellent results were seen for PDUS. Measures of shoulder function have a poor relationship with US and MRI. Improved standardization of US scanning technique could further reliability of shoulder US.

Comparison of the Psoriatic Arthritis Quality of Life (PsAQoL) questionnaire, the functional status (HAQ) and utility (EQ-5D) measures in psoriatic arthritis: results from a cross-sectional survey.

OBJECTIVES: To compare the Psoriatic Arthritis Quality of Life (PsAQoL) instrument, the Health Assessment Questionnaire (HAQ) as a measure of functional status, and the generic health status (utility) measure the EuroQoL (EQ-5D) in terms of ability to assess disease severity in psoriatic arthritis (PsA). METHODS: The differences between known groups and correlations of the PsAQoL, the HAQ and the EQ-5D with clinical measures were analysed in a sample of 183 PsA patients. RESULTS: Different severities of PsA determined by known groups were distinguished well by all three questionnaires; more severe disease was associated with significantly worse values of the instruments. The correlations revealed a strong relationship between each of the measures, and with the patients' pain on the visual analogue scale (VAS), the patient global VAS, and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and a weak relationship with the disease duration and the Psoriasis Area Severity Index (PASI). The PsAQoL also correlated strongly with the 28-joint Disease Activity Score (DAS28). CONCLUSIONS: The PsAQoL, the HAQ, and the EQ-5D are able to distinguish well across levels of PsA severity.

Protective effect of sensory denervation in inflammatory arthritis (evidence of regulatory neuroimmune pathways in the arthritic joint).

OBJECTIVE: To investigate the direct effect of joint innervation on immune mediated joint inflammation in a patient with psoriatic arthritis (PsA). CASE REPORT: The patient developed arthritis mutilans in all digits of both hands with the exception of the left 4th finger, which had prior sensory denervation following traumatic nerve dissection. Plain radiography, ultrasonography and nerve conduction studies of the hands confirmed the absence of articular disease and sensory innervation in the left 4th digit. METHODS: This relationship between joint innervation and joint inflammation was investigated experimentally by prior surgical sensory denervation of the medial aspect of the knee in six Wistar rats in which carrageenan induced arthritis was subsequently induced. Prior sensory denervation--with preservation of muscle function--prevented the development of inflammatory arthritis in the denervated knee. DISCUSSION: Observations in human and animal inflammatory arthritis suggest that regulatory neuroimmune pathways in the joint are an important mechanism that modulates the clinical expression of inflammatory arthritis.

Musculoskeletal ultrasound--a state of the art review in rheumatology. Part 1: Current controversies and issues in the development of musculoskeletal ultrasound in rheumatology.

As we begin the 21st century, musculoskeletal ultrasound (MSUS) is routinely used by an increasing number of rheumatologists throughout Europe and there is a growing interest in the application of MSUS in rheumatological practice in the UK. MSUS allows high-resolution, real-time imaging of articular and periarticular structures and has the advantages of being non-radioactive, inexpensive, portable, highly acceptable to patients and repeatable. There are a number of critical issues that need to be addressed in order to develop the role of MSUS within rheumatology. These include issues of equipment costs, training and certification and the relationship of rheumatologists and radiologists in advancing the field of MSUS. Rheumatologists must demonstrate the relevance of MSUS in their clinical practice through high-quality research. Emerging technologies such as power Doppler and 3D imaging will further improve imaging capabilities and the range of clinical applications of MSUS systems. This paper reviews how MSUS in rheumatology has evolved and the controversies and issues that rheumatologists must now address in developing MSUS as an indispensable, everyday clinical tool.

Musculoskeletal ultrasound--a state of the art review in rheumatology. Part 2: Clinical indications for musculoskeletal ultrasound in rheumatology.

Rheumatologists remain divided on whether they should introduce musculoskeletal ultrasound (MSUS) into their clinical practice. A central issue in the application of MSUS in clinical rheumatology is the need for proof of clinical relevance and improved patient care. There is now accumulating evidence that MSUS improves clinical diagnosis and intervention skills. High-resolution ultrasound is superior to clinical examination in the diagnosis and localization of joint and bursal effusion and synovitis. MSUS is the imaging modality of choice for the diagnosis of tendon pathology. MSUS is seven times more sensitive than plain radiography in the detection of rheumatoid erosions, allowing earlier diagnosis of progressive rheumatoid arthritis. Ligament, muscle, peripheral nerve and cartilage pathology can also be readily demonstrated by MSUS. There is exciting evidence that MSUS may potentially be used by rheumatologists to non-invasively diagnose and monitor not just joint and muscle disease but also nerve compression syndromes, scleroderma, vasculitis and Sjögren's syndrome. Joint aspiration and injection accuracy can be improved by MSUS, with initial evidence confirming improved efficacy. As the number of rheumatologists performing MSUS increases and the technical capabilities of MSUS improve, there is likely to be a growing number of proven clinical indications for the application of MSUS in rheumatology practice. This paper reviews the evidence for the application of MSUS in rheumatology.

Ultrasonography of entheseal insertions in the lower limb in spondyloarthropathy.

OBJECTIVE: To compare ultrasonography (US) with clinical examination in the detection of entheseal abnormality of the lower limb in patients with spondyloarthropathy (SpA). METHODS: 35 patients with SpA (ankylosing spondylitis 27; psoriatic arthritis 7; reactive arthritis 1) underwent independent clinical and ultrasonographic examination of both lower limbs at five entheseal sites-superior pole and inferior pole of patella, tibial tuberosity, Achilles tendon, and plantar aponeurosis. US was performed using an ATL (Advanced Technology Laboratories, Bothell, Washington, USA) high definition imaging 3000 machine with linear 7-4 MHz and compact linear 10-5 MHz probes to detect bursitis, structure thickness, bony erosion, and enthesophyte (bony spur). An enthesitis score was formulated from these US findings giving a possible maximum total score of 36. RESULTS: On clinical examination 75/348 (22%) entheseal sites were abnormal and on US examination 195/348 (56%) sites were abnormal. In 19 entheseal sites with bursitis on US, only five were detected by clinical examination. Compared with US, clinical examination had a low sensitivity (22.6%) and moderate specificity (79.7%) for the detection of enthesitis of the lower limbs. There was no significant correlation between the US score of enthesitis and acute phase parameters such as erythrocyte sedimentation rate (ESR) or C reactive protein (CRP). The intraobserver kappa value for analysis of all sites was 0.9. CONCLUSIONS: Most entheseal abnormality in SpA is not detected at clinical examination. US is better than clinical examination in the detection of entheseal abnormality of the lower limbs in SpA. A quantitative US score of lower limb enthesitis is proposed but further studies are required to validate it in SpA.

Metacarpophalangeal joints in rheumatoid arthritis: laser Doppler imaging--initial experience.

Laser Doppler imaging is a noninvasive method yielding a spatial perfusion map. With use of a near-infrared laser, elevated perfusion associated with the metacarpophalangeal joints was detectable in patients with active rheumatoid arthritis. Findings at laser Doppler imaging correlated with pain scores and synovitis detected at ultrasonography, whereas the power Doppler sign (red pixels inside the active green box) did not. Laser Doppler imaging has the potential to help assess soft-tissue inflammation.