A.S. Zayat

Do non-steroidal anti-inflammatory drugs have a significant effect on detection and grading of ultrasound-detected synovitis in patients with rheumatoid arthritis? Results from a randomised study

Objectives To determine whether non-steroidal anti-inflammatory drugs (NSAIDs) have a significant effect on ultrasonographic (US) grey scale (GS) and power Doppler (PD) assessment of synovitis in rheumatoid arthritis (RA). Methods Patients with RA taking NSAIDs were randomised to either stopping (for a minimum of 5 drug half-lives) or continuing the drug. All patients had a clinical assessment and US examination of both hands and wrists before and after stopping/continuing the NSAID. Changes at follow-up were compared between groups using Mann–Whitney U tests. Results A total of 58 patients with RA were recruited. All the clinical assessment parameters (including disease activity, pain, general state of health and physician global visual analogue score and tender and swollen joints count) showed an increase in the group who stopped their NSAID treatment. The total GS and PD score showed median (first to third quartiles) increase of 9.5 (5.75 to 19.0) and 4.0 (2.0 to 6.0) per patient, respectively, in the patients who stopped their NSAID in comparison with 1.0 (–1.0 to 2.25) and 0.0 (–2.0 to 3.0), respectively, in the patients who continued their NSAID (p<0.001). There was an increase in the number of joints scoring >0 for GS and PD in the patients who stopped the NSAID. The inter- and intrareader agreement was good to excellent for the US examination. Conclusion NSAID usage may mask the GS and PD signal and result in lower scoring despite continuing disease activity. Consideration should be given to the NSAID effect in designing clinical studies which use US to assess response to therapeutic.

The specificity of ultrasound-detected bone erosions for rheumatoid arthritis

Background Bone erosion is one of the hallmarks of rheumatoid arthritis (RA), but also seen in other rheumatic diseases. The objective of this study was to determine the specificity of ultrasound (US)-detected bone erosions (including their size) in the classical ‘target’ joints for RA. Methods Patients fulfilling the diagnostic criteria for RA, psoriatic arthritis, osteoarthritis or gout in addition to healthy volunteers were included. The following areas were examined by US: distal radius and ulna, 2nd, 3rd and 5th metacarpophalangeal (MCP), 2nd and 3rd proximal interphalangeal (PIP) and 1st and 5th metatarsophalangeal (MTP) joints. All joints were scanned in four quadrants using both semiquantitative (0–3) and quantitative (erosion diameter) scoring systems. Results 310 subjects were recruited. The inter-reader and intrareader agreements were good to excellent. US-detected bone erosions were more frequent but not specific for RA (specificity 32.9% and sensitivity 91.4%). The presence of erosions with semiquantitative score ≥2 in four target joints (2nd, 5rd MCP, 5th MTP joints and distal ulna) was highly specific for RA (specificity 97.9% and sensitivity 41.4%). Size of erosion was found to be associated with RA. Erosions of any size in the 5th MTP joint were both specific and sensitive for RA (specificity 85.4% and sensitivity 68.6%). Conclusions The presence of US-detected erosions is not specific for RA. However, larger erosions in selected joints, especially 2nd and 5rd MCP, 5th MTP joints and distal ulna, were highly specific for and predictive of RA.

The role of ultrasound in assessing musculoskeletal symptoms of systemic lupus erythematosus: a systematic literature review

OBJECTIVES Musculoskeletal symptoms are common in SLE and are associated with significant morbidity. However, assessing their nature can be challenging, with implications for treatment decisions and measuring response. US has been shown to be valid and reliable for the assessment of other inflammatory arthritides, but data in SLE are more limited. The objectives of this systematic literature review were to determine the characteristics of musculoskeletal US abnormalities in SLE and to evaluate the metric properties of US in the detection and quantification of musculoskeletal symptoms. METHODS We systematically searched the literature using the PubMed, Embase and Cochrane Library databases for studies using musculoskeletal US for assessing SLE. Studies were assessed for quality using the Quality Assessment of Diagnostic Accuracy Studies tool and for their metric qualities, including reliability and validity. RESULTS Nine studies were identified. Most studies investigated construct validity. Rates of abnormality were highly variable: synovitis and tenosynovitis were reported in 25-94% and 28-65% of patients, respectively; power Doppler and erosions were reported in 10-82% and 2-41% of patients, respectively. There was poor to moderate association between US abnormalities and disease activity indices and immunological findings. There was moderate to high risk of bias and there were concerns about applicability in most studies. CONCLUSION US has potential value in the assessment of musculoskeletal symptoms in SLE. However, there is methodological variation between studies that may account for lack of consensus on US abnormalities. Studies that address these problems are required before US can used as an outcome measure in SLE.

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

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.

The effect of joint position on Doppler flow in finger synovitis

It is well recognised that one of the major limitations of musculoskeletal ultrasound (US) is its operator dependency.1 This issue is currently being addressed by the OMERACT and the EULAR Working Party in Imaging, who are working towards the production of guidelines for the acquisition and interpretation of US images particularly with respect to inflammatory arthritis.2 There are many variables that might influence an US image. These include factors pertaining to the machine (type of machine and transducer and control settings) and those that are not machine related (ambient temperature, transducer pressure3 and patient positioning). Doppler US appears particularly sensitive to all these factors as has recently been highlighted by Torp-Pedersen and Terslev4 and Teh.5 It has previously been reported that there are differences in Doppler signals within muscles4 5 and tendons4 …

Does joint position affect US findings in inflammatory arthritis

OBJECTIVE Musculoskeletal US is being increasingly used for the assessment of synovitis, although questions remain about its reliability. One potential factor affecting reliability is the lack of consensus of image acquisition methods such as using different joint positions. This may have an implication on the reproducibility of studies that use US as an outcome measure. The aim of this study was to determine whether a change in joint position might significantly alter the quantification of US-detected synovitis in patients with inflammatory arthritis (IA). METHODS IA patients with clinically swollen wrists, MCP and/or knee joints were recruited. These joints were assessed quantitatively for the presence of synovitis when they were placed in different positions. RESULTS Seventy-five patients with IA were assessed. The greatest grey scale (GS) and power Doppler (PD) scores for the MCP joints were found in the flat (0°) position (91 and 100% of cases, respectively) compared with other positions (P < 0.001). Similar results were found in the wrist joints. The greatest GS and PD scores for the knee joint were found in 30° flexion [100 and 95.6% of cases, respectively, compared with other positions (P < 0.001)]. The inter- and intra-reader reliability was good to excellent. CONCLUSION The position in which a joint is scanned for synovitis appears to significantly influence the US assessment of synovitis. Our study suggests that the standardized scanning of the hand joints in a flat position and the knees in a 30° position are associated with the highest GS and PD scores.

Prediction of autoimmune connective tissue disease in an at-risk cohort: prognostic value of a novel two-score system for interferon status

Objective To evaluate clinical, interferon and imaging predictors of progression from ‘At Risk’ to autoimmune connective tissue diseases (AI-CTDs). Methods A prospective observational study was conducted in At-Risk of AI-CTD (defined as antinuclear antibody (ANA) positive; ≤1 clinical systemic lupus erythematosus (SLE) criterion; symptom duration <12 months and treatment-naïve). Bloods and skin biopsy (non-lesional) were analysed for two interferon-stimulated gene expression scores previously described (IFN-Score-A and IFN-Score-B). Forty-nine healthy controls (HCs) and 114 SLE were used as negative and positive controls. Musculoskeletal ultrasound was performed. Progression was defined by meeting classification criteria for AI-CTDs at 12 months. Results 118 individuals with 12-month follow-up were included. Of these, 19/118 (16%) progressed to AI-CTD (SLE=14, primary Sjogren’s=5). At baseline, both IFN scores differed among At-Risk, HCs and SLE groups (p<0.001) and both were elevated in At-Risk who progressed to AI-CTD at 12 months versus non-progressors, to a greater extent for IFN-Score-B (fold difference (95% CI) 3.22 (1.74 to 5.95), p<0.001) than IFN-Score-A (2.94 (1.14 to 7.54); p=0.018). Progressors did not have significantly greater baseline clinical characteristics or ultrasound findings. Fold difference between At-Risk and HCs for IFN-Score-A was markedly greater in skin than blood. In multivariable logistic regression, only family history of autoimmune rheumatic disease, OR 8.2 (95% CI 1.58 to 42.53) and IFN-Score-B, 3.79 (1.50–9.58) increased the odds of progression. Conclusion A two-factor interferon score and family history predict progression from ANA positivity to AI-CTD. These interferon scores may allow stratification of individuals At-Risk of AI-CTD permitting early intervention for disease prevention and avoid irreversible organ damage.

Which knee and probe position determines the final diagnosis of knee inflammation by ultrasound? Results from a European multicenter study

PURPOSE To investigate which knee and probe position best identifies knee inflammation and to determine a cut-off level for abnormal synovial effusion. MATERIALS AND METHODS 18 experienced sonographers (all rheumatologists) performed ultrasound examinations of the knee joint in patients with knee symptoms and in healthy controls. Each sonographer performed longitudinal suprapatellar ultrasound scans using 9 different configurations at each knee: Midline, parapatallar lateral and parapatellar medial from midline in neutral position (0°) with and without quadriceps muscle contraction and in 30° flexion of the knee. The presence of synovial effusion (SE), the effusion measured in millimeters and the presence of synovial hypertrophy (SH) was noted. RESULTS A total of 298 knees of 149 subjects (129 patients and 20 controls) were examined. The detection of SH is more sensitive and specific than the detection of SE, independently of the knee and probe position, for the final diagnosis of abnormality. The detection of both synovial hypertrophy and effusion in the knee in neutral position (0°) with quadriceps contraction and with the probe in the midline position, are the best independent predictors for knee abnormalities. Knee effusion > 3.2 mm measured with the probe in the lateral aspect of the knee is the best diagnostic characteristics for predicting pathological SE. CONCLUSION The best combination for detecting SH and SE is obtained by placing the probe in the midline position with the knee in 0° with quadriceps contraction. A cut-off value for pathological effusion may be obtained in the lateral aspect of the knee.

Musculoskeletal manifestations of systemic lupus erythmatosus

Purpose of review Imaging studies suggest potential changes to the classification and assessment of inflammatory musculoskeletal lupus. This is important because of the burden of disease but the potential for new targeted therapies. Recent findings Using our current classification and treatment, musculoskeletal symptoms continue to impact significantly on quality of life and work disability. Ultrasound and MRI studies suggested that new approaches to the diagnosis, classification, and evaluation of these symptoms are needed. Many patients with pain but no synovitis have ultrasound-proven joint and tendon inflammation but would not qualify for clinical trials or score highly on disease activity instruments. MRI studies show that erosions are more common than previously thought and may have a different pathogenesis than RA. Immunology studies suggest differences from other autoimmune synovitis, with a complex role for type I interferons. A wide range of biologic therapies appear more consistently effective for arthritis than some other manifestations. Summary Changes to the selection of patients for therapy and stratification using musculoskeletal imaging may offer new approaches to clinical trials and the routine care of systemic lupus erythematosus patients with inflammatory musculoskeletal symptoms. Outcomes may thereby be improved using existing therapies. There are significant knowledge gaps that must be addressed to achieve these potential improved outcomes.

SAT0151 Imaging and Histopathological Changes To Tocilizumab in Patients with Moderate To Severe Ra: A Single Centre Randomized Double-Blind Placebo-Controlled Study

Background Tocilizumab (TCZ) is a well-established biologic therapy in the treatment of rheumatoid arthritis (RA). There is limited data on imaging and synovial tissue histology changes. Objectives To evaluate level of response as defined by power Doppler (PD) ultrasound (US) and synovial tissue histology changes. Methods Patients with RA, inefficacy to minimum one DMARD +/− TNFi, with DAS28≥3.2 and knee synovitis amenable to synovial biopsy were recruited to this open-label 48-week study. Patients randomised to TCZ/methotrexate (MTX) for 48 weeks or placebo (PBO)/MTX for the first 16 weeks followed by TCZ/MTX until week 48. Clinical and US hand, wrist and knee assessments with US-guided knee synovial biopsy at baseline (BL), weeks 12 and 48 (biopsy optional). US was scored accrording to OMERACT 0–3 grey scale and PD synovitis scoring system. Synovial tissue was assessed for synovial inflammatory infiltrate, stromal cell density, synovial lining on 0–3 scale and overall synovitis (0–9 scale) determined. Results 15 patients recruited: 12 (80%) females; 9 received TCZ/MTX, 6 PBO/MTX. 2 patients withdrew at each arm, one due to TCZ infusion reaction. Week 16: 33% (3/9) TCZ/MTX achieved DAS28ESR-rem vs 0 PBO+MTX, latter remaining in moderate/high disease activity. Week 48: 92% (12/13) whole group in DAS28ESR-rem. US response: 38% (3/8) TCZ/MTX group who had BL PD synovitis in hand/wrist had absence of PD synovitis at week 16 vs none PBO/MTX group. All patients with abnormal BL PD in knees (median (IQR) PD score of 2 (0–9)) had improved week 48 PD score (median (IQR) PD score of 0 (0–1)). 13 patients (8 TCZ/MTX, 5 PBO/MTX) had synovial biopsies obtained weeks 0 & 12; 21/26 samples (80%) samples useable. No difference between pre- and week 12 synovitis score in both groups. Median (IQR) total synovitis score at BL and after week 12 respectively of 3 (2.75, 4.25) and 3 (2.5–4) in the TCZ/MTX group vs 6 (4,7) and 6 (4,6) in PBO/MTX group. BL total synovitis score did not predict early or late response. Conclusions TCZ/MTX was associated with significant clinical and imaging improvement compared to MTX alone. An absence of change in synovial infiltrate with TCZ/MTX at 12 weeks suggests a different mechanism for response compared to other anti-cytokine therapies such as the TNFi. Further histochemistry analysis and investigation may potentially determine mechanism and indicators of response on a tissue level. Disclosure of Interest None declared