New Developments in Imaging in Crystalline Arthritis.

Crystalline arthropathies are among the most frequently encountered conditions in medicine. Joint aspiration and microscopy used to be the diagnostic gold standard, but recent recommendations mention that this may not be necessary if typical findings are seen on imaging. Ultrasound, dual-energy computed tomographic (CT) scan, and conventional radiography are recommended in the assessment of gout, calcium pyrophosphate crystal deposition disease, and basic calcium phosphate-related disease. Ultrasound can identify the tophus and its associated tissues that participate in the inflammatory response, and dual-energy CT can find tophaceous material in regions that are difficult to access by physical examination or ultrasound.

Efficacy of guselkumab, a selective IL-23 inhibitor, in Preventing Arthritis in a Multicentre Psoriasis At-Risk cohort (PAMPA): protocol of a randomised, double-blind, placebo controlled multicentre trial.

INTRODUCTION: Psoriatic arthritis (PsA) is a complex, immune-mediated disease associated with skin psoriasis that, if left untreated, can lead to joint destruction. Up to 30% of patients with psoriasis progress to PsA. In most cases, psoriasis precedes synovio-entheseal inflammation by an average of 5-7 years, providing a unique opportunity for early and potentially preventive intervention in a susceptible and identifiable population. Guselkumab is an effective IL-23p19 inhibitor Food and Drug Administration (FDA-approved for treatment of moderate-to-severe psoriasis and PsA. The Preventing Arthritis in a Multicentre Psoriasis At-Risk cohort (PAMPA) study aims to evaluate the efficacy of guselkumab in preventing PsA and decreasing musculoskeletal power Doppler ultrasound (PDUS) abnormalities in a population of patients with psoriasis who are at-increased risk for PsA progression. METHODS AND ANALYSIS: The PAMPA study is a multicentre, randomised, double-blind, placebo-controlled, interventional, preventive trial comparing PDUS involvement and conversion to PsA in patients with psoriasis at-increased risk for progression treated with guselkumab compared with non-biological standard of care. The study includes a screening period, a double-blind treatment period (24 weeks) and an open-label follow-up period (72 weeks). At baseline, 200 subjects will be randomised (1:1) to receive either guselkumab 100 mg (arm 1) or placebo switching to guselkumab 100 mg starting at week 24 (arm 2). Arm 3 will follow 150 at-risk psoriasis patients who decline biological therapy and randomisation. Changes from baseline in the PDUS score at week 24 and the difference in proportion of patients transitioning to PsA at 96 weeks will be examined as the coprimary endpoints. ETHICS AND DISSEMINATION: Ethics approval for this study was granted by the coordinating centre's (NYU School of Medicine) Institutional Review Board (IRB). Each participating site received approval through their own IRBs. The findings will be shared in peer-reviewed articles and scientific conference presentations. TRIAL REGISTRATION NUMBER: NCT05004727.

Imaging of crystalline arthropathy in 2020.

Crystal-related arthropathies are the result of crystal deposition in joint and periarticular soft tissues. Identification of urate crystals is mandatory to distinguish gout from other crystalline arthropathies, including calcium pyrophosphate dihydrate and basic calcium phosphate crystal deposition diseases. ACR/EULAR classification criteria for gout included dual-energy computed tomography and ultrasound with equal impact to the final score. Different diagnostic strengths of these imaging modalities depend on disease duration and scanned anatomic site. While ultrasound has been indicated as the first-choice imaging technique, especially in the early stages of the disease, dual-energy computed tomography has shown to be highly specific, allowing the detection of crystal deposits in anatomic sites not accessible by ultrasound, such as the spine. At the spinal level, MRI findings are usually nonspecific. Finally, there is preliminary evidence that at the knee, dual-energy computed tomography may discriminate calcium pyrophosphate dihydrate from basic calcium phosphate crystal deposits.

Cartilage icing and chondrocalcinosis on knee radiographs in the differentiation between gout and calcium pyrophosphate deposition.

OBJECTIVE: To determine if findings of "cartilage icing" and chondrocalcinosis on knee radiography can differentiate between gout and calcium pyrophosphate deposition (CPPD). METHODS: IRB-approval was obtained and informed consent was waived for this retrospective study. Electronic medical records from over 2.3 million patients were searched for keywords to identify subjects with knee aspiration-proven cases of gout or CPPD. Radiographs were reviewed by two fellowship-trained musculoskeletal radiologists in randomized order, blinded to the patients' diagnoses. Images were evaluated regarding the presence or absence of cartilage icing, chondrocalcinosis, tophi, gastrocnemius tendon calcification, and joint effusion. Descriptive statistics, sensitivity, specificity, positive and negative predictive values, and accuracy were calculated. RESULTS: From 49 knee radiographic studies in 46 subjects (31 males and 15 females; mean age 66±13 years), 39% (19/49) showed gout and 61% (30/49) CPPD on aspiration. On knee radiographs, cartilage icing showed a higher sensitivity for CPPD than gout (53-67% and 26%, respectively). Chondrocalcinosis also showed a higher sensitivity for CPPD than gout (50-57% versus 5%), with 95% specificity and 94% positive predictive value for diagnosis of CPPD versus gout. Soft tissue tophus-like opacities were present in gout at the patellar tendon (5%, 1/19) and at the popliteus groove in CPPD (15%, 4/27). Gastrocnemius tendon calcification was present in 30% (8/27) of subjects with CPPD, and 5% (1/19) of gout. CONCLUSION: In subjects with joint aspiration-proven crystal disease of the knee, the radiographic finding of cartilage icing was seen in both gout and CPPD. Chondrocalcinosis (overall and hyaline cartilage) as well as gastrocnemius tendon calcification positively correlated with the diagnosis of CPPD over gout.

Ultrasound characterization of pseudoerosions and dorsal joint recess morphology of the hand and wrist in 100 asymptomatic subjects.

PURPOSE: To sonographically characterize pseudoerosions and dorsal joint recess and capsule morphology of the hand and wrist in 100 asymptomatic subjects. METHOD: The metacarpal heads, and dorsal aspects of the lunate, triquetrum, and ulna were evaluated for pseudoerosions including measurements and sonographic characterization. The dorsal recesses of the metacarpophalangeal, radiocarpal, and midcarpal joints were also characterized with regards to echogenicity, fibrillar pattern, hyperemia, and measurements. RESULTS: 100 subjects were included (average age 47 years, range 19-82 years; 52% male, 48% female). Pseudoerosions of metacarpophalangeal heads were seen in every subject, in all metacarpal heads, but most commonly the second and third (99% were bilateral, 97% were multiple); 81.5% involved at least three metacarpal heads; 99% were central with maximum depth of 2.6 mm. At the wrist, in 92% of subjects a bilateral pseudoerosion was present at the dorsal triquetrum, lunate, or ulna. Dorsal joint capsules and recesses at the metacarpophalangeal joints were isoechoic to subdermal fat and fibrillar measuring 3.1-6.3 mm in maximal thickness. The dorsal capsules and recesses of the radiocarpal and midcarpal joints were hypoechoic to subdermal fat, non-fibrillar and with maximal thickness of 3.9 and 3.4 mm, respectively. No hyperemia on color Doppler imaging was noted. CONCLUSIONS: Pseudoerosions are common at the dorsal metacarpal heads, lunate, triquetrum, and ulna, which should not be mistaken for true inflammatory erosions. The characteristic appearances of dorsal joint capsules and recesses should not be confused with synovial hypertrophy.

Imaging of gout: New tools and biomarkers?

While joint aspiration and crystal identification by polarizing microscopy remain the gold standard for diagnosing tophaceous gout, agreement among medical and ancillary health personnel examining synovial fluid using polarizing microscopy for the detection of monosodium urate (MSU) crystals appears to be poor. Imaging modalities, including conventional radiography (CR), ultrasonography (US), magnetic resonance imaging (MRI), and dual-energy computed tomography (DECT), have been found to provide information on the deposition of MSU crystals in tissues, and the consequences of such deposition. CR can demonstrate typical "punched out lesions" with marginal overhangs, but the sensitivity for erosion detection is better for DECT and US. US is inexpensive and can identify tophus deposition in and around joints, erosions, and tissue inflammation if power Doppler US is used. MRI can show tophi, bone marrow edema, and inflammation, but MRI findings of tophi may be nonspecific. DECT can identify and color-code tophaceous material, and provide an overview of the tophus burden of a joint area. Because of the lower number of available studies, the strength of evidence for the newer imaging can be improved through further research.

Toward Quantitative Assessment of Rheumatoid Arthritis Using Volumetric Ultrasound.

GOAL: Rheumatoid arthritis (RA) is characterized by inflammation within the joint space as well as erosion or destruction of the bone surface. We believe that volumetric (3-D) ultrasound imaging of the joints in conjunction with automated image-analysis tools for segmenting and quantifying the regions of interest can lead to improved RA assessment. METHODS: In this paper, we describe our proposed algorithms for segmenting 1) the 3 -D bone surface and 2) the 3-D joint capsule region. We improve and extend previous 2-D bone extraction methods to 3-D and make our algorithm more robust to the intensity loss due to surface normals facing away from incident acoustic beams. The extracted bone surfaces coupled with a joint-specific anatomical model are used to initialize a coarse localization of the joint capsule region. The joint capsule segmentation is refined iteratively utilizing a probabilistic speckle model. RESULTS: We apply our methods on 51 volumes from 8 subjects, and validate segmentation results with expert annotations. We also provide the quantitative comparison of our bone detection with magnetic resonance imaging. These automated methods have achieved average sensitivity/precision rates of 94%/93% for bone surface detection, and 87%/83% for joint capsule segmentation. Segmentations of normal and inflamed joints are compared to demonstrate the potential of using proposed tools to assess RA pathology at the joint level. CONCLUSION: The proposed image-analysis methods showed encouraging results as compared to expert annotations. SIGNIFICANCE: These computer-assisted tools can be used to help visualize 3-D anatomy in joints and help develop quantitative measurements toward RA assessment.

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.

Validation of power Doppler versus contrast-enhanced magnetic resonance imaging quantification of joint inflammation in murine inflammatory arthritis.

Contrast-enhancement magnetic resonance imaging (CE-MRI) of synovial volume is the radiographic gold standard to quantify joint inflammation; however, cost limits its use. Therefore, we examined if power Doppler-ultrasound (PD-US) outcomes of synovitis in tumor necrosis factor transgenic (TNF-Tg) mice correlate with CE-MRI. TNF-Tg mice underwent PD-US of their knees to measure the joint space volume (JSV) and power Doppler volume (PDV), and the results were correlated with synovial volume determined by CE-MRI. Immunohistochemistry for CD31 was performed to corroborate the PD signal. Synovial volume strongly correlated with both JSV and PDV (p < 0.01). CD31(+) blood vessels were observed in inflamed synovium proximal to the joint surface, which corresponded to areas of intense PD signals. JSV and PDV are valid measures of joint inflammation that correlate with synovial volume determined by CE-MRI and are associated with vascularity. Given the emergence of PD-US as a nonquantitative outcome of joint inflammation, we find JSV and PDV to be feasible and highly cost-effective for longitudinal studies in animal models. Furthermore, given the increasing use of PD-US in standard clinical practice, JSV and PDV could be translated to better quantify joint flare and response to therapy in patients with rheumatoid arthritis (RA).

Musculoskeletal ultrasound training and competency assessment program for rheumatology fellows.

OBJECTIVES: The purpose of this study was to establish standards for musculoskeletal ultrasound competency through knowledge and skills testing using criterion-referenced methods. METHODS: Two groups of rheumatology fellows trained in musculoskeletal ultrasound through a standardized curriculum, which required submission of ultrasound studies for review over 8 months. Both groups then completed written and practical examinations in musculoskeletal ultrasound. Instructors, advanced users, and intermediate users of musculoskeletal ultrasound served as comparison groups. A passing score (competency) was established for the written examination by the Angoff procedure and for the practical examination by the borderline method. RESULTS: Thirty-eight fellows (19 in each group) took the final examination. Five fellows failed the written examination, and 1 failed the practical examination, whereas none of the advanced users failed. Written examination scores did not differ between the two fellow groups (74% versus 70%; P > .05), were reliable, and were able to discriminate between the intermediate and advanced groups. Practical and written examination results correlated in both groups (first group, r = 0.70; P = .0008; second group, r = 0.59; P = .009). CONCLUSIONS: Criterion-referenced methods were used for the first time to determine fellow musculoskeletal ultrasound competency. The examination used to determine competency was reproducible, was reliable, and could differentiate musculoskeletal ultrasound users with different levels of experience. Most rheumatology fellows completing our program passed the written and practical examinations, suggesting achievement of basic musculoskeletal ultrasound competency.

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.

Ultrasonography applications in diagnosis and management of early rheumatoid arthritis.

Ultrasonography is an elegant tool for the detection of tenosynovitis, synovitis, and erosions very early in rheumatoid arthritis, and the presence of a power Doppler signal is one of the best predictors of joint damage. Although clinical scores remain the mainstay of disease activity assessment, ultrasonography has proved to be a remarkably robust tool for reliable assessment of changes in rheumatoid arthritis. There is no evidence to suggest that problems with operator dependence would be greater than with other imaging modalities or physical examination, if performed by trained providers.

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

INTRODUCTION: As 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. METHODS: Peripheral 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. RESULTS: Compared 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. CONCLUSIONS: RA 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.

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

OBJECTIVE: 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. METHODS: Fifty male subjects ages 55-85 years were recruited during primary care visits to an urban Veterans Affairs hospital, and were assessed by musculoskeletal ultrasound (US) of the knees and first metatarsophalangeal (MTP) joints to evaluate for the double contour sign and tophi as evidence of MSU crystal deposition. Images were read by 2 blinded rheumatologists trained in musculoskeletal US, and the degree of concordance was determined for individual subjects, total joints, femoral articular cartilage (FAC), and first MTP joints. Subjects were further categorized into 3 diagnostic groups: gout, asymptomatic hyperuricemia (no gout, serum uric acid [UA] ≥6.9 mg/dl), and controls (no gout, serum UA ≤6.8 mg/dl), and reader concordance within these 3 groups was assessed. RESULTS: We observed almost perfect agreement between readers for 1) individual subjects (yes/no; n = 50, 100% agreement, κ = 1.000), 2) total joints (n = 200, 99% agreement, κ = 0.942), 3) FAC (n = 100, 99% agreement, κ = 0.942), and 4) first MTP joints (n = 100, 99% agreement, κ = 0.942). Furthermore, findings by side (right/left) and diagnostic group (gout, asymptomatic hyperuricemia, control) showed substantial to almost perfect concordance for all measures. MSU deposition was seen most commonly in gout patients, and deposition was also seen in some subjects with asymptomatic hyperuricemia, but in only 1 control. CONCLUSION: Musculoskeletal US is reliable for detecting MSU deposition in FAC and first MTP joints in gout and asymptomatic hyperuricemia.

Role of ultrasound and other advanced imaging in the diagnosis and management of gout.

Imaging of gout with conventional radiography has been described since shortly after roentgenography was invented. Ultrasound (US) detects more erosions than conventional radiography in rheumatoid arthritis, and the same seems to be true for gout. MRI is being used to assess articular and periarticular masses, including gouty tophi. However, MRI findings in gout can lack specificity. Monosodium urate (MSU) tophi are very echogenic when US is used. Typical US features of gout include a double-contour sign or "urate icing." The double-contour consists of the hyperechoic bony contour and a parallel hyperechoic line of MSU crystals that deposit on the hypoechoic or anechoic hyaline cartilage. Tophi can have a "wet clumps of sugar" appearance, often surrounded by an anechoic halo. Tophi are closely related to the formation of erosions. If serum urate levels are lowered consistently below 6.0 mg/dL, the disappearance of MSU crystals can be observed sonographically.

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 1ß (IL-1ß). IL-1ß 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.

Ultrasonography shows disappearance of monosodium urate crystal deposition on hyaline cartilage after sustained normouricemia is achieved.

This study aimed at determining whether lowering serum urate (SU) to less than 6 mg/dl in patients with gout affects ultrasonographic findings. Seven joints in five patients with monosodium urate (MSU) crystal proven gout and hyperuricemia were examined over time with serial ultrasonography. Four of the five patients were treated with urate lowering drugs (ULDs) (allopurinol, n = 3; probenecid, n = 1). One patient was treated with colchicine alone. Attention was given to changes in a hyperechoic, irregular coating of the hyaline cartilage in the examined joints (double contour sign or "urate icing"). This coating was considered to represent precipitate of MSU crystals. Index joints included metacarpophalangeal (MCP) joints (n = 2), knee joints (n = 3), and first metatarsophalangeal (MTP) joints (n = 2). The interval between baseline and follow-up images ranged from 7 to 18 months. Serial SU levels were obtained during the follow-up period. During the follow-up period, three patients treated with ULD (allopurinol, n = 2; probenecid, n = 1) achieved a SU level of <6 mg/dl. In two patients, SU levels remained above 6 mg/dl (treated with allopurinol, n = 1; treated with colchicine, n = 1). At baseline, the double contour sign was seen in all patients. In those patients who achieved SU levels of <6 ml/dl, this sign had disappeared at follow-up. Disappearance of the double contour sign was seen in two knee joints, two first MTP joints, and one MCP joint. In contrast, disappearance of the double contour sign was not seen in patients who maintained a SU level > or =7 mg/dl. In one patient treated with allopurinol, SU levels improved from 13 to 7 mg/dl during the follow-up period. Decrease, but not resolution of the hyperechoic coating was seen in this patient. In the patient treated with colchicine alone, SU levels remained >8 mg/dl, and no sonographic change was observed. In our patients, sonographic signs of deposition of MSU crystals on the surface of hyaline cartilage disappeared completely if sustained normouricemia was achieved. This is the first report showing that characteristic sonographic changes are influenced by ULDs once SU levels remain < or =6 mg/dl for 7 months or more. Sonographic changes of gout correlate with SU levels and may be a non-invasive means to track changes in the uric acid pool. Larger prospective studies are needed to further assess these potentially important findings.