Ralf G. Thiele

Reproducibility of musculoskeletal ultrasound for determining monosodium urate deposition: concordance between readers.

Criteria for sonographic diagnosis of monosodium urate (MSU) crystal deposition have been developed, but the interreader reproducibility of this modality is not well established. We therefore assessed agreement using a systematic approach.

The pathogenesis of bone erosions in gouty arthritis

The characteristic radiographic hallmarks of chronic gouty arthritis are the presence of macroscopic tophi and erosions with overhanging edges and relative preservation of the joint space. In recent years there has been more insight into the processes underlying the development of bone erosions in gouty arthritis. This review discusses the mechanical, pathological, cellular and immunological factors that may have a role in the pathogenesis of bone erosions in gouty arthritis. It highlights the evidence suggesting that monosodium urate crystal deposition is associated with the presence of underlying osteoarthritis and the important role of osteoclasts and the receptor for activation of nuclear factor κ B (RANK) and RANK ligand (RANK–RANKL) pathway in the pathogenesis of gouty erosions. Gouty arthritis is primarily driven by interleukin 1β (IL-1β). IL-1β has been implicated in bone destruction and erosions in other inflammatory arthridities. Thus, future IL-1 inhibitors may prevent and treat erosion formation due to tophaceous gouty arthritis. This review discusses imaging modalities and highlights ultrasongraphic evidence suggesting a significant relationship between the presence of the gouty tophus and bone erosions as well as the frequent presence of persistent low-grade inflammation in asymptomatic chronic tophaceous gouty arthritis on high-resolution ultrasonography. It is the tophus eroding the underlying bone that is pivotal for the development of bone erosions in gouty arthritis.

Decreased influenza-specific B cell responses in rheumatoid arthritis patients treated with anti-tumor necrosis factor

IntroductionAs a group, rheumatoid arthritis (RA) patients exhibit increased risk of infection, and those treated with anti-tumor necrosis factor (TNF) therapy are at further risk. This increased susceptibility may result from a compromised humoral immune response. Therefore, we asked if short-term effector (d5-d10) and memory (1 month or later) B cell responses to antigen were compromised in RA patients treated with anti-TNF therapy.MethodsPeripheral blood samples were obtained from RA patients, including a subset treated with anti-TNF, and from healthy controls to examine influenza-specific responses following seasonal influenza vaccination. Serum antibody was measured by hemagglutination inhibition assay. The frequency of influenza vaccine-specific antibody secreting cells and memory B cells was measured by EliSpot. Plasmablast (CD19+IgD-CD27hiCD38hi) induction was measured by flow cytometry.ResultsCompared with healthy controls, RA patients treated with anti-TNF exhibited significantly decreased influenza-specific serum antibody and memory B cell responses throughout multiple years of the study. The short-term influenza-specific effector B cell response was also significantly decreased in RA patients treated with anti-TNF as compared with healthy controls, and correlated with decreased influenza-specific memory B cells and serum antibody present at one month following vaccination.ConclusionsRA patients treated with anti-TNF exhibit a compromised immune response to influenza vaccine, consisting of impaired effector and consequently memory B cell and antibody responses. The results suggest that the increased incidence and severity of infection observed in this patient population could be a consequence of diminished antigen-responsiveness. Therefore, this patient population would likely benefit from repeat vaccination and from vaccines with enhanced immunogenicity.

Ultrasound Guidance for Intra-articular Injections of the Foot and Ankle

Background: Ultrasound has been increasingly utilized in procedures involving intra-articular injections. This studys purpose was to compare the accuracy of intra-articular injections of the foot and ankle using palpation versus dynamic ultrasound in a cadaver model. Materials and Methods: Fourteen lightly embalmed cadaver specimens without notable osteoarthritis were used. A 0.22-gauge needle was placed by a foot and ankle orthopaedic surgeon into the first and second tarsometatarsal joints, subtalar joint, and ankle joint. The needle was initially placed using palpation, evaluated with ultrasound by an experienced rheumatologist, and re-inserted if necessary. Needle placement was confirmed with injection of an Omnipaque™/methylene blue solution and examined under fluoroscopy, followed by dissection. Results: Palpation and ultrasound were 100% accurate in subtalar and ankle joint injections. Using palpation, the needle was correctly placed into the first TMT joint in three of 14 cadavers, and in four of 14 cadavers for the second TMT joint. Using ultrasound, the needle was correctly placed into the first TMT joint in ten of 14 cadavers, and into the second TMT joint in eight of 14 cadavers. When grouped, ultrasound was significantly more accurate for intra-articular needle placement compared to palpation in the midfoot (p = 0.003). On three specimens, dye extended beyond the second TMT joint. Conclusion: Intra-articular injections of the subtalar and ankle joints can be successfully performed utilizing palpation alone. Ultrasound guidance significantly increases injection accuracy into the TMT joints compared to palpation alone and therefore US or Fluoroscopy is performed when injecting these TMT joints. When using selective diagnostic injections into a TMT joint to assess for the symptomatic joint and potential need for arthrodesis, the injected anesthetic may not remain isolated within that joint. These isolated TMT injections should not be done to answer that question without fluoroscopy confirmation with radiopaue dye demonstrating the injected fluid remained within the one joint of interest.

Imaging algorithms for evaluating suspected rotator cuff disease: Society of radiologists in ultrasound consensus conference statement

The Society of Radiologists in Ultrasound convened a panel of specialists from a variety of medical disciplines to reach a consensus about the recommended imaging evaluation of painful shoulders with clinically suspected rotator cuff disease. The panel met in Chicago, Ill, on October 18 and 19, 2011, and created this consensus statement regarding the roles of radiography, ultrasonography (US), computed tomography (CT), CT arthrography, magnetic resonance (MR) imaging, and MR arthrography. The consensus panel consisted of two co-moderators, a facilitator, a statistician and health care economist, and 10 physicians who have specialty expertise in shoulder pain evaluation and/or treatment. Of the 13 physicians on the panel, nine were radiologists who were chosen to represent a broad range of skill sets in diagnostic imaging, different practice types (private and academic), and different geographical regions of the United States. Five of the radiologists routinely performed musculoskeletal US as part of their practice and four did not. There was also one representative from each of the following clinical specialties: rheumatology, physical medicine and rehabilitation, orthopedic surgery, and nonoperative sports medicine. The goal of this conference was to construct several algorithms with which to guide the imaging evaluation of suspected rotator cuff disease in patients with a native rotator cuff, patients with a repaired rotator cuff, and patients who have undergone shoulder replacement. The panel hopes that these recommendations will lead to greater uniformity in rotator cuff imaging and more cost-effective care for patients suspected of having rotator cuff abnormality.

Ultrasound and Magnetic Resonance Imaging in the Evaluation of Psoriatic Dactylitis: Status and Perspectives

Objective. Dactylitis, a characteristic feature of the spondyloarthropathies, occurs in up to 48% of patients with psoriatic arthritis (PsA). No clear consensus on the underlying components and pathogenesis of dactylitis exists in the literature. We undertook a systematic review of ultrasound (US) and magnetic resonance imaging (MRI) literature to better define imaging elements that contribute to the dactylitic digit seen in PsA. Our objectives were to determine first the level of homogeneity of each imaging modality’s definition of the components of dactylitis, and second, to evaluate the metric properties of each imaging modality according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) filter. Methods. Searches were performed in PUBMED and EMBASE for articles pertaining to MRI, US, and dactylitis. Data regarding the reported features of dactylitis were collected and categorized, and the metrological qualities of the studies were assessed. Results. The most commonly described features of dactylitis were flexor tendon tenosynovitis and joint synovitis (90%). Extratendinous soft tissue thickening and extensor tendonitis were described nearly equally as being present and absent. Discrepancy exists as to whether entheses proper contribute to the etiology of dactylitis. An increasing number of studies categorize abnormalities in several tissue compartments including the soft tissue, tendon sheaths, and joints, as well as ligaments. Conclusion. The understanding of which tissues contribute to dactylitic inflammation has evolved. However, there is a lack of literature regarding the natural history of these abnormalities. This systematic review provides guidance in defining elementary lesions that may discriminate dactylitic digits from normal digits, leading to development of a composite measure of activity and severity of dactylitis.

International Consensus for ultrasound lesions in gout: results of Delphi process and web-reliability exercise

OBJECTIVE To produce consensus-based definitions of the US elementary lesions in gout and to test their reliability in a web-based exercise. METHODS The process consisted of two steps. In the first step a written Delphi questionnaire was developed from a systematic literature review and expert international consensus. This collated information resulted in four statements defining US elementary lesions: double contour (DC), tophus, aggregates and erosion. The Delphi questionnaire was sent to 35 rheumatology experts in US, asking them to rate their level of agreement or disagreement with each statement. The second step tested the reliability by a web-exercise. US images of both normal and gouty elementary lesions were collected by the participants. A facilitator then constructed an electronic database of 110 images. The database was sent to the participants, who evaluated the presence/absence of US elementary lesions. A group of 20 images was displayed twice to evaluate intra-reader reliability. RESULTS A total of 32 participants responded to the questionnaires. Good agreement (>80%) was obtained for US definitions on DC, tophus, aggregates and erosion in the Delphi exercise after three rounds. The reliability on images showed inter-reader κ values for DC, tophus, aggregates, erosion findings of 0.98, 0.71, 0.54 and 0.85, respectively. The mean intra-reader κ values were also acceptable: 0.93, 0.78, 0.65 and 0.78, respectively. CONCLUSION This, the first consensus-based US definition of elementary lesions in gout, demonstrated good reliability overall. It constitutes an essential step in developing a core outcome measurement that permits a higher degree of homogeneity and comparability between multicentre studies.

Ultrasound as an Outcome Measure in Gout. A Validation Process by the OMERACT Ultrasound Working Group

Objective. To summarize the work performed by the Outcome Measures in Rheumatology (OMERACT) Ultrasound (US) Working Group on the validation of US as a potential outcome measure in gout. Methods. Based on the lack of definitions, highlighted in a recent literature review on US as an outcome tool in gout, a series of iterative exercises were carried out to obtain consensus-based definitions on US elementary components in gout using a Delphi exercise and subsequently testing these definitions in static images and in patients with proven gout. Cohen’s κ was used to test agreement, and values of 0–0.20 were considered poor, 0.20–0.40 fair, 0.40–0.60 moderate, 0.60–0.80 good, and 0.80–1 excellent. Results. With an agreement of > 80%, consensus-based definitions were obtained for the 4 elementary lesions highlighted in the literature review: tophi, aggregates, erosions, and double contour (DC). In static images interobserver reliability ranged from moderate to almost perfect, and similar results were found for the intrareader reliability. In patients the intraobserver agreement was good for all lesions except DC (moderate). The interobserver agreement was poor for aggregates and DC but moderate for the other components. Conclusion. These first steps in evaluating the validity of US as an outcome measure for gout show that the reliability of the definitions ranged from moderate to excellent in static images and somewhat lower in patients, indicating that a standardized scanning technique may be needed, before testing the responsiveness of those definitions in a composite US score.

Patients with Rheumatoid Arthritis in Clinical Remission Manifest Persistent Joint Inflammation on Histology and Imaging Studies

Objective. The purpose of our study was to test the hypothesis that synovitis on magnetic resonance imaging (MRI) and ultrasound (US) observed in patients with rheumatoid arthritis (RA) who meet remission criteria reflects active inflammation on histopathology. Methods. We analyzed 15 synovial specimens obtained during surgical procedures from 14 patients with RA in clinical remission as defined by the American College of Rheumatology criteria. Histological specimens were scored for hyperplasia of synovial lining and synovial stroma, inflammation, lymphoid follicles, and vascularity. The histology scores were classified as minimal, mild, moderate, or severe disease activity. US and MRI performed within a 4-month period of surgery were scored for disease activity. The correlation between histology and imaging scores was examined. Results. Four of 14 patients were receiving anti-tumor necrosis factor (TNF) therapy, 4 were receiving methotrexate (MTX) alone, 4 were taking MTX and hydroxychloroquine (HCQ), and 1 was taking HCQ and sulfasalazine. Four specimens had severe, 6 moderate, 3 mild, and 2 minimal disease activity on histology. Three of 4 specimens with minimal and mild histology were observed in subjects receiving anti-TNF therapy. Synovitis was noted on greyscale in 80% of joints and Doppler signal in 60%. MRI demonstrated synovitis and bone marrow edema in 86% of images. Positive but not significant correlations were noted between histology and synovitis scores on US. Conclusion. Despite clinical remission, histology and imaging studies documented a persistently active disease state that may explain the mechanism for radiographic progression.

Assessing Elementary Lesions in Gout by Ultrasound: Results of an OMERACT Patient-based Agreement and Reliability Exercise

Objective. To test the reliability of the consensus-based ultrasound (US) definitions of elementary gout lesions in patients. Methods. Eight patients with microscopically proven gout were evaluated by 16 sonographers for signs of double contour (DC), aggregates, erosions, and tophi in the first metatarsophalangeal joint and the knee bilaterally. The patients were examined twice using B-mode US to test agreement and inter- and intraobserver reliability of the elementary components. Results. The prevalence of the lesions were DC 52.8%, tophus 61.1%, aggregates 29.8%, and erosions 32.4%. The intraobserver reliability was good for all lesions except DC, where it was moderate. The best reliability per lesion was seen for tophus (κ 0.73, 95% CI 0.61–0.85) and lowest for DC (κ 0.53, 95% CI 0.38–0.67). The interobserver reliability was good for tophus and erosions, but fair to moderate for aggregates and DC, respectively. The best reliability was seen for erosions (κ 0.74, 95% CI 0.65–0.81) and lowest for aggregates (κ 0.21, 95% CI 0.04–0.37). Conclusion. This is the first step to test consensus-based US definitions on elementary lesions in patients with gout. High intraobserver reliability was found when applying the definition in patients on all elementary lesions while interobserver reliability was moderate to low. Further studies are needed to improve the interobserver reliability, particularly for DC and aggregates.