Ultrasonography of Inflammatory and Structural Lesions in Hand Osteoarthritis: An OMERACT Agreement and Reliability Study

Objective: To standardize and assess the reliability of ultrasonographic assessment of inflammatory and structural lesions in patients with hand osteoarthritis (OA). Methods: The Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group selected synovial hypertrophy (SH), joint effusion (JE), and power Doppler (PD) signals as the main inflammatory lesions in hand OA, and suggested osteophytes in the scapho-trapezio-trapezoid (STT) and cartilage defects in the proximal interphalangeal (PIP) joints as novel additions to previous structural scoring systems. A complementary imaging atlas provided detailed examples of the scores. A reliability exercise of static images was performed for the inflammatory features, followed by a patient-based exercise with six sonographers testing inflammatory and structural features in twelve hand OA patients. We used Cohen's kappa (\u3ba) for intra-reader and Light's \u3ba for inter-reader reliability for all features except PD, in which Prevalence-Adjusted Bias-Adjusted Kappa (PABAK) was applied. Percentage agreement was also assessed. Results: The web-based reliability exercise demonstrated substantial intra- and inter-reader reliability for all inflammatory features (\u3ba>0.64). In the patient-based exercise, intra- and inter-reader reliability varied: SH \u3ba=0.73 and 0.45; JE \u3ba=0.70 and 0.55; PD PABAK=0.90 and 0.88; PIP cartilage \u3ba=0.56 and 0.45; STT osteophytes \u3ba=0.62 and 0.36. Percentage close agreement was high for all features (>85%). Conclusion: With ultrasound, substantial to excellent intra-reader reliability was found for inflammatory features of hand OA. Inter-reader reliability was moderate, but overall high close agreement between readers suggest that better reliability is achievable after further training. Assessment of osteophytes in the STT joint and cartilage in the PIP joints achieved less good reliability and the latter is not endorsed. Keywords: Hand osteoarthritis; outcome measures; ultrasonography

Personal non-commercial use only. The Journal of Rheumatology06-5.5)

ABSTRACT. Objective. To investigate criterion validity and intraobserver reliability of magnetic resonance imaging (MRI) in hand osteoarthritis (HOA). Methods. In 16 patients with HOA (median age 57 yrs, 62% women, 13 with erosive OA), 3 Tesla MRI scans with gadolinium-chelate administration of right second to fifth distal interphalangeal/proximal interphalangeal joints were scored according to the Oslo HOA scoring method for synovial thickening, bone marrow lesions (BML), osteophytes, joint space narrowing (JSN), and erosions (grade 0-3 Hand osteoarthritis (HOA) is a prevalent musculoskeletal disease that can lead to pain or functional limitations 1,2 . The OA process results in structural involvement of all compartments of the joint, including cartilage, subchondral bone, synovium, capsule, and ligaments 3 . In HOA, several subsets can be distinguished, of which nodal and erosive OA preferentially involve the interphalangeal (IP) joints 1,4 . Patients with nodal OA in the IP joints present with bony enlargements, deformities, and loss of range of motion 4 . These classical structural hallmarks of HOA can be visualized on conventional radiographs as osteophytes, malalignment, and joint space narrowing (JSN) 5 . In addition in erosive OA, subchondral erosions with widening can be seen 4 . However, radiography is an insensitive imaging modality and a more sensitive method visualizing not only structural changes but also soft tissues is needed. Ultrasound (US) has been introduced to visualize osteophytes and soft tissues in HOA. It has been shown that US is more sensitive than radiography to detect osteophytes and erosions, and moreover that synovitis is frequently seen in HO

MRI in hand OA Personal non-commercial use only. The Journal of Rheumatology06-5.5)

ABSTRACT. Objective. To investigate criterion validity and intraobserver reliability of magnetic resonance imaging (MRI) in hand osteoarthritis (HOA). Methods. In 16 patients with HOA (median age 57 yrs, 62% women, 13 with erosive OA), 3 Tesla MRI scans with gadolinium-chelate administration of right second to fifth distal interphalangeal/proximal interphalangeal joints were scored according to the Oslo HOA scoring method for synovial thickening, bone marrow lesions (BML), osteophytes, joint space narrowing (JSN), and erosions (grade 0-3 Hand osteoarthritis (HOA) is a prevalent musculoskeletal disease that can lead to pain or functional limitations 1,2 . The OA process results in structural involvement of all compartments of the joint, including cartilage, subchondral bone, synovium, capsule, and ligaments 3 . In HOA, several subsets can be distinguished, of which nodal and erosive OA preferentially involve the interphalangeal (IP) joints 1,4 . Patients with nodal OA in the IP joints present with bony enlargements, deformities, and loss of range of motion 4 . These classical structural hallmarks of HOA can be visualized on conventional radiographs as osteophytes, malalignment, and joint space narrowing (JSN) 5 . In addition in erosive OA, subchondral erosions with widening can be seen 4 . However, radiography is an insensitive imaging modality and a more sensitive method visualizing not only structural changes but also soft tissues is needed. Ultrasound (US) has been introduced to visualize osteophytes and soft tissues in HOA. It has been shown that US is more sensitive than radiography to detect osteophytes and erosions, and moreover that synovitis is frequently seen in HO

Results of a 6-week treatment with 10 mg prednisolone in patients with hand osteoarthritis (HOPE):a double-blind, randomised, placebo-controlled trial

Background Hand osteoarthritis is a prevalent joint condition that has a high burden of disease and an unmet medical need for effective therapeutic options. Since local inflammation is recognised as contributing to osteoarthritic complaints, the Hand Osteoarthritis Prednisolone Efficacy (HOPE) study aimed to investigate the efficacy and safety of short-term prednisolone in patients with painful hand osteoarthritis and synovial inflammation.Methods The HOPE study is a double-blind, randomised, placebo-controlled trial. We recruited eligible adults from rheumatology outpatient clinics at two sites in the Netherlands. Patients were considered eligible if they had symptomatic hand osteoarthritis and signs of inflammation in their distal and proximal interphalangeal (DIP/PIP) joints. For inclusion, patients were required to have four or more DIP/PIP joints with osteoarthritic nodes; at least one DIP/PIP joint with soft swelling or erythema; at least one DIP/PIP joint with a positive power Doppler signal or synovial thickening of at least grade 2 on ultrasound; and finger pain of at least 30 mm on a 100-mm visual analogue scale (VAS) that flared up during a 48-h non-steroidal anti-inflammatory drug (NSAID) washout (defined as worsening of finger pain by at least 20 mm on the VAS). Eligible patients were randomly assigned (1:1) to receive 10 mg prednisolone or placebo orally once daily for 6 weeks, followed by a 2-week tapering scheme, and a 6-week follow-up without study medication. The patients and study team were masked to treatment assignment. The primary endpoint was finger pain, assessed on a VAS, at 6 weeks in participants who had been randomly assigned to groups and attended the baseline visit. This study is registered with the Netherlands Trial Registry, number NTR5263.Findings We screened patients for enrolment between Dec 3, 2015, and May 31, 2018. Patients completed baseline visits and started treatment between Dec 14, 2015, and July 2, 2018, and the last study visit of the last patient was Oct 4, 2018. Of 149 patients assessed for eligibility, 57 (38%) patients were excluded (predominantly because they did not meet one or several inclusion criteria, most often because of an absence of synovial inflammation or of flare-ups after NSAID washout) and 92 (62%) patients were eligible for inclusion. We randomly assigned 46 (50%) patients to receive prednisolone and 46 (50%) patients to receive placebo, all of whom were included in the modified intention-to-treat analysis of the primary endpoint. 42 (91%) patients in the prednisolone group and 42 (91%) in the placebo group completed the 14-week study. The mean change between baseline and week 6 on VAS-reported finger pain was -21.5 (SD 21.7) in the prednisolone group and -5.2 (24.3) in the placebo group, with a mean between-group difference (of prednisolone vs placebo) of -16.5 (95% CI -26.1 to -6.9; p=0.0007). The number of non-serious adverse events was similar between the groups. Five serious adverse events were reported during our study: one serious adverse event in the prednisolone group (a myocardial infarction) and four serious adverse events in the placebo group (an infected traumatic leg haematoma that required surgery, bowel surgery, atrial fibrillation that required a pacemaker implantation, and symptomatic uterine myomas that required a hysterectomy). Four (4%) patients discontinued the study because of an adverse event: one (2%) patient receiving prednisolone (for a myocardial infarction) and three (7%) patients receiving placebo (for surgery of the bowel and for an infected leg haematoma and for Lyme disease arthritis of the knee).Interpretation Treatment with 10 mg prednisolone for 6 weeks is efficacious and safe for the treatment of patients with painful hand osteoarthritis and signs of inflammation. The results of our study provide clinicians with a new short-term treatment option for patients with hand osteoarthritis who report a flare-up of their disease. Copyright (C) 2019 Elsevier Ltd. All rights reserved.Clinical epidemiolog

An ultrasound negative for subclinical synovitis in arthralgia patients: is it helpful in identifying those not developing arthritis?

OBJECTIVE: To investigate the negative predictive value (NPV) of musculoskeletal US (MSUS) in arthralgia patients at risk for developing inflammatory arthritis. METHODS: An MSUS examination of hands and feet was performed in arthralgia patients at risk for inflammatory arthritis in four independent cohorts. Patients were followed for one-year on the development of inflammatory arthritis. Subclinical synovitis was defined as greyscale ≥2 and/or power Doppler ≥1. NPVs were determined and compared with the prior risks of not developing inflammatory arthritis. Outcomes were pooled using meta-analyses and meta-regression analyses. In sensitivity analyses, MSUS imaging of tender joints only (rather than the full US protocol) was analysed and ACPA stratification applied. RESULTS: After 1 year 78, 82, 77 and 72% of patients in the four cohorts did not develop inflammatory arthritis. The NPV of a negative US was 86, 85, 82 and 90%, respectively. The meta-analysis showed a pooled non-inflammatory arthritis prevalence of 79% (95% CI 75%, 83%) and a pooled NPV of 86% (95% CI 81, 89%). Imaging tender joints only (as generally done in clinical practice) and ACPA stratification showed similar results. CONCLUSION: A negative US result in arthralgia has a high NPV for not developing inflammatory arthritis, which is mainly due to the high a priori risk of not developing inflammatory arthritis. The added value of a negative US (<10% increase) was limited

An ultrasound negative for subclinical synovitis in arthralgia patients: is it helpful in identifying those not developing arthritis?

OBJECTIVE: To investigate the negative predictive value (NPV) of musculoskeletal US (MSUS) in arthralgia patients at risk for developing inflammatory arthritis. METHODS: An MSUS examination of hands and feet was performed in arthralgia patients at risk for inflammatory arthritis in four independent cohorts. Patients were followed for one-year on the development of inflammatory arthritis. Subclinical synovitis was defined as greyscale ≥2 and/or power Doppler ≥1. NPVs were determined and compared with the prior risks of not developing inflammatory arthritis. Outcomes were pooled using meta-analyses and meta-regression analyses. In sensitivity analyses, MSUS imaging of tender joints only (rather than the full US protocol) was analysed and ACPA stratification applied. RESULTS: After 1 year 78, 82, 77 and 72% of patients in the four cohorts did not develop inflammatory arthritis. The NPV of a negative US was 86, 85, 82 and 90%, respectively. The meta-analysis showed a pooled non-inflammatory arthritis prevalence of 79% (95% CI 75%, 83%) and a pooled NPV of 86% (95% CI 81, 89%). Imaging tender joints only (as generally done in clinical practice) and ACPA stratification showed similar results. CONCLUSION: A negative US result in arthralgia has a high NPV for not developing inflammatory arthritis, which is mainly due to the high a priori risk of not developing inflammatory arthritis. The added value of a negative US (<10% increase) was limited

Neuropathic-like pain symptoms in inflammatory hand osteoarthritis lower quality of life and may not decrease under prednisolone treatment

Background: Pain is common in hand osteoarthritis (OA) and multiple types may occur. We investigated the prevalence, associated patient characteristics, influence on health-related quality of life (HR-QoL) and response to anti-inflammatory treatment of neuropathic-like pain in inflammatory hand OA. Methods: Data were analysed from a 6-week, randomized, double-blind, placebo-controlled trial investigating prednisolone treatment in 92 patients with painful inflammatory hand OA. Neuropathic-like pain was measured with the painDETECT questionnaire. Associations between baseline characteristics and baseline neuropathic-like pain were analysed with ordinal logistic regression, association of baseline neuropathic-like pain symptoms with baseline HR-QoL with linear regression, painDETECT and visual analogue scale (VAS) change from baseline to week 6 and interaction of painDETECT with prednisolone efficacy on VAS pain change from baseline to week 6 with generalized estimating equations (GEE). Results: Of 91 patients (79% female, mean age 64) with complete painDETECT data at baseline, 53% were unlikely to have neuropathic-like pain, 31% were indeterminate and 16% were likely to have neuropathic-like pain. Neuropathic-like pain was associated with female sex, less radiographic damage and more comorbidities. Patients with neuropathic-like pain had lower HR-QoL (PCS-6.5 [95% CI −10.4 to −2.6]) than those without. Neuropathic-like pain symptoms remained under prednisolone treatment and no interaction was seen between painDETECT and prednisolone efficacy on VAS pain. Conclusions: In this study, 16% of inflammatory hand OA patients had neuropathic-like pain. They were more often female, had more comorbidities and had lower QoL than those without. Neuropathic-like pain symptoms remained despite prednisolone treatment and did not seem to affect the outcome of prednisolone treatment. Significance: Pain is the dominant symptom in hand OA, with an unclear aetiology. In this study, we found that neuropathic-like pain may play a role in hand OA, that it showed associations with female sex, younger age and more comorbidities and that it lowered health-related quality of life in hand OA. Neuropathic-like pain in hand OA seems resistant to prednisolone therapy but did not seem to interfere with the treatment of inflammatory pain with prednisolone

The OMERACT Ultrasound Group: A Report from the OMERACT 2016 Meeting and Perspectives

Objective To provide an update from the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group on the progress for defining ultrasound (US) minimal disease activity threshold at joint level in rheumatoid arthritis (RA) and for standardization of US application in juvenile idiopathic arthritis (JIA). Methods For minimal disease activity, healthy controls (HC) and patients with early arthritis (EA) who were naive to disease-modifying antirheumatic drugs were recruited from 2 centers. US was performed of the hands and feet, and scored semiquantitatively (0–3) for synovial hypertrophy (SH) and power Doppler (PD). Synovial effusion (SE) was scored a binary variable. For JIA, a Delphi approach and subsequent validation in static images and patient-based exercises were used to developed preliminary definitions for synovitis and a scoring system. Results For minimal disease activity, 7% HC had at least 1 joint abnormality versus 30% in the EA group. In HC, the findings of SH and PD were predominantly grade 1 whereas all grades were seen in the EA cohort, but SE was rare. In JIA, synovitis can be diagnosed based on B-mode findings alone because of the presence of physiological vascularization. A semiquantitative scoring system (0–3) for synovitis for both B-mode and Doppler were developed in which the cutoff between Doppler grade 2 and grade 3 was 30%. Conclusion The first step has been taken to define the threshold for minimal disease activity in RA by US and to define and develop a scoring system for synovitis in JIA. Further steps are planned for the continuous validation of US in these areas

EULAR recommendations for the reporting of ultrasound studies in rheumatic and musculoskeletal diseases (RMDs)

To produce European League Against Rheumatism (EULAR) recommendations for the reporting of ultrasound studies in rheumatic and musculoskeletal diseases (RMDs). Based on the literature reviews and expert opinion (through Delphi surveys), a taskforce of 23 members (12 experts in ultrasound in RMDs, 9 in methodology and biostatistics together with a patient research partner and a health professional in rheumatology) developed a checklist of items to be reported in every RMD study using ultrasound. This checklist was further refined by involving a panel of 79 external experts (musculoskeletal imaging experts, methodologists, journal editors), who evaluated its comprehensibility, feasibility and comprehensiveness. Agreement on each proposed item was assessed with an 11-point Likert scale, grading from 0 (total disagreement) to 10 (full agreement). Two face-to-face meetings, as well as two Delphi rounds of voting, resulted in a final checklist of 23 items, including a glossary of terminology. Twenty-one of these were considered ‘mandatory’ items to be reported in every study (such as blinding, development of scoring systems, definition of target pathologies) and 2 ‘optional’ to be reported only if applicable, such as possible confounding factors (ie, ambient conditions) or experience of the sonographers. An EULAR taskforce developed a checklist to ensure transparent and comprehensive reporting of aspects concerning research and procedures that need to be presented in studies using ultrasound in RMDs. This checklist, if widely adopted by authors and editors, will greatly improve the interpretability of study development and results, including the assessment of validity, generalisability and applicability