The Role of Musculoskeletal Ultrasound in the Rheumatoid Arthritis Continuum

Purpose of Review: Rheumatoid arthritis (RA) is no longer considered a fixed phenotype but rather a disease continuum. This review outlines the current and potential value of applying ultrasound (US) along this continuum: from the prediction of progression to RA in at-risk individuals, to confirmation of the early diagnosis of RA, as well as the consideration of differential diagnoses, and the use in disease monitoring and defining remission. Recent Findings: In individuals at-risk of RA (i.e., positive autoantibodies with symptoms but without synovitis), US has shown a promising predictive value for the development of clinical arthritis, providing the opportunity to improve risk stratification (and disease prevention) of these individuals. The detection of inflammation on US in patients with early undifferentiated arthritis, in which a definite diagnosis cannot be reached, could predict evolution to persistent arthritis, mostly RA. This, in addition to the US potential ability to identify disease specific patterns for different rheumatic conditions, might facilitate early diagnosis and, therefore, improve the management of patients with RA, or other types of inflammatory arthritides. US has also demonstrated the capability to predict radiographic progression, and relapse risk after treatment discontinuation, in RA patients in remission according to the clinical instruments, raising implications in the management, including therapy discontinuation, of these patients. Summary: US has an undeniable value in the management of patients at different stages along the RA continuum. Further research is needed to identify which groups of patients benefit the most from US imaging

Ultrasound-detectable grey scale synovitis predicts future fulfilment of the 2010 ACR/EULAR RA classification criteria in patients with new-onset undifferentiated arthritis

Objective: To determine the clinical outcomes for patients with new-onset undifferentiated arthritis (UA), not fulfilling the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) classification criteria, and the clinical and imaging predictors of disease progression in these patients. Methods: A prospective observational study was conducted in treatment-naïve UA patients. Baseline ultrasound involved semiquantitative assessment of grey scale (GS) synovitis and power Doppler activity (PD) at 26 joints. Outcomes were fulfilment of 2010 RA criteria (joint involvement determined clinically) and initiation of methotrexate over 12 months. Cox proportional hazards analysis was used to investigate predictors of outcome. Results: Of 60 patients, 13(22%) progressed to RA and 32(53%) ever received methotrexate. Analyses of predictors of outcome were conducted in the subgroup (n=41) of patients with complete baseline data. The presence of GS was associated with progression to RA and methotrexate use: HRs (95% CI) were 1.25(1.07 to 1.45) and 1.16(1.02 to 1.32), respectively, for the number of joints with GS≥ grade 2 after adjustment for swollen joints. PD was not predictive in the low levels at which it was observed. Progression to RA was also associated with fulfilment of the 2010 criteria using ultrasound synovitis for enumerating joint involvement, higher baseline disability and radiographic erosion. Conclusions: This is the first report of ultrasound findings in early UA (defined by presence of clinical synovitis and non-fulfilment of 2010 RA criteria). A significant proportion of patients with UA progressed to RA and/or required methotrexate. GS synovitis was predictive of disease progression

Reduction in stiffness of proximal leg muscles during the first 6 months of glucocorticoid therapy for giant cell arteritis: A pilot study using shear wave elastography.

Aim: To investigate muscle stiffness changes in patients treated for giant cell arteritis (GCA) with high‐dose oral glucocorticoids. Methods: Using ultrasound elastography, shear wave velocity (SWV) was measured in the quadriceps, hamstrings and biceps brachii muscles of 14 patients with GCA (4 male, mean age ± SD, 68.2 ± 4.3 years) within the first 2 weeks of initiating glucocorticoid treatment (baseline) and repeated after 3 and 6 months treatment. Muscle strength and performance tests were performed at each visit. Baseline measures were compared with those from 14 healthy controls. Linear mixed models were used to test for change in patient measures over time. Results: At baseline, muscle SWV in patients was not significantly different from controls. With glucocorticoid treatment, there was a reduction in SWV in the leg but not the arm muscles. SWV decreased by a mean of 14% (range 8.3%‐17.3%; P = .001) after 3 months and 18% (range 10.2%‐25.3%; P < .001) after 6‐months in the quadriceps and hamstrings during the resting position. The baseline, 3 and 6 months mean SWV (±SD) for the vastus lateralis were 1.62 ± 0.16 m/s, 1.40 ± 0.10 m/s and 1.31 ± 0.06 m/s, respectively (P < .001). In the patient group as a whole, there was no significant change in muscle strength. However, there were moderate correlations (r = .54‐.69) between exhibiting weaker muscle strength at follow‐up visits and a greater reduction in SWV. Conclusion: Glucocorticoid therapy in patients with GCA was associated with a significant reduction in proximal leg muscle stiffness during the first 6 months. Future research should study a larger sample of patients for a longer duration to investigate if diminished muscle stiffness precedes signs of glucocorticoid‐induced myopathy

Ultrasound erosions in the feet best predict progression to inflammatory arthritis in anti-CCP positive at-risk individuals without clinical synovitis

Objectives To investigate, in anti-cyclic citrullinated peptide antibody positive (CCP+) at-risk individuals without clinical synovitis, the prevalence and distribution of ultrasound (US) bone erosions (BE), their correlation with subclinical synovitis and their association with the development of inflammatory arthritis (IA). Methods Baseline US scans of 419 CCP+ at-risk individuals were analysed. BE were evaluated in the classical sites for rheumatoid arthritis damage: the second and fifth metacarpophalangeal (MCP2 and MCP5) joints, and the fifth metatarsophalangeal (MTP5) joints. US synovitis was defined as synovial hypertrophy (SH) ≥2 or SH ≥1+power Doppler signal ≥1. Subjects with ≥1 follow-up visit were included in the progression analysis (n=400). Results BE were found in ≥1 joint in 41/419 subjects (9.8%), and in 55/2514 joints (2.2%). The prevalence of BE was significantly higher in the MTP5 joints than in the MCP joints (p1 joint 10.6 (95% CI 1.9 to 60.4, p<0.01) and BE and synovitis in ≥1 MTP5 joint 5.1 (95% CI 1.4 to 18.9, p=0.02). In high titre CCP+ at-risk individuals, with positive rheumatoid factor and BE in ≥1 joint, the OR increased to 16.9 (95% CI 2.1–132.8, p<0.01). Conclusions In CCP+ at-risk individuals, BE in the feet appear to precede the onset of clinical synovitis. BE in >1 joint, and BE in combination with US synovitis in the MTP5 joints, are the most predictive for the development of clinical arthritis

Pragmatic randomised controlled trial of very early etanercept and MTX versus MTX with delayed etanercept in RA: the VEDERA trial

Objectives: We sought to confirm in very early rheumatoid arthritis (ERA) a much greater superiority (30%) of first-line etanercept+methotrexate (ETN+MTX) over treat-to-target MTX (MTX-TT) than previously reported in ERA (14%); and explore whether ETN following initial MTX secures a comparable response to first-line ETN+MTX. Methods: Pragmatic, open-label, randomised controlled trial of treatment-naïve ERA (≤12 months symptom), Disease Activity Score 28 joint (DAS28)-erythrocyte sedimentation rate (ESR) ≥3.2, rheumatoid factor (RF)+/−anticitrullinated peptide antibody (ACPA) positive or ultrasound power Doppler (PD) if RF and ACPA negative. Subjects were randomised 1:1 to ETN+MTX; or MTX-TT, escalated to ETN if week 24 DAS28-ESR ≥2.6 and intramuscular corticosteroid at protocolised time points. Primary endpoint of week 48 DAS28ESR remission with clinical and imaging secondary endpoints. Results: We randomised 120 patients, 60 to each arm (71% female, 73% RF/84% ACPA positive, median (IQR) symptom duration 20.3 (13.1, 30.8) weeks; mean (SD) DAS28 5.1 (1.1)). Remission rates with ETN+MTX and MTX-TT, respectively, were 38% vs 33% at week 24; 52% vs 38% at week 48 (ORs 1.6, 95% CI 0.8 to 3.5, p=0.211). Greater, sustained DAS28-ESR remission observed with ETN+MTX versus MTX-TT (42% and 27%, respectively; p=0.035). PD was fully suppressed by week 48 in over 90% in each arm. Planned exploratory analysis revealed OR 2.84, 95% CI 0.8 to 9.6) of achieving remission after 24 weeks of ETN administered first line compared with administered post-MTX. Conclusions: Compared with remission rates typically reported with first-line tumour necrosis factor inhabitor+MTX versus MTX-TT, we did not demonstrate a larger effect in very ERA. Neither strategy conferred remission in the majority of patients although ultrasound confirmed local inflammation suppression. Poorer ETN response following failure of MTX-TT is also suggested. Trial registration number: NCT0243318

Families as support and burden: a mixed methods exploration of the extent to which family identification and support predicts reductions in stress among disadvantaged neighbourhood residents

Stronger family relationships predict positive health outcomes: a relationship that is partially due to the range of emotional, practical and informational support that families can provide. Yet not all families possess these resources. A survey study in a disadvantaged community in Nottingham, UK (N=142) demonstrated that family identification positively predicts ability to cope with financial stress, but that this relationship is moderated by whether family support is present or absent. Semi-structured interviews with 10 members of different families from the same community shed further light upon the nature of this relationship: individuals report that they tend to turn to their family rather than friends or community services in times of financial hardship, even though their family are unlikely to be able to support them effectively, and that this is often due to feelings of embarrassment or finance-related stigma. Our findings highlight the complex role that families can play in finance-related issues, as well as the need to encourage individuals to seek financial support from sources which provide effective (rather than emotionally comfortable) assistance

The effect of ageing on shear wave elastography muscle stiffness in adults

Background: Skeletal muscle undergoes structural changes with ageing which may alter its biomechanical properties. Shear wave elastography (SWE) may detect these changes by measuring muscle stiffness. Aims: To investigate muscle stiffness in healthy young, middle-aged and elderly cohorts using SWE and correlate it with muscle strength and mass. Methods: Shear wave velocity (SWV) was measured in the quadriceps, hamstrings and biceps brachii of 26 young (range 20–35 years), 21 middle-aged (40–55) and 30 elderly (77–94) volunteers. The participants performed several muscle tests to evaluate their strength. The One-way ANOVA was used to test the muscle stiffness differences between the groups and the Pearson’s correlation coefficient to evaluate the relationship between SWV and muscle strength. Results: The overall resting muscle SWV gradually decreased with age but was only significantly reduced in the elderly group (p < 0.001); with the exception of the vastus lateralis SWV where a significant difference was noted (p < 0.05) between young (1.77 m/s), middle-aged (1.64 m/s) and elderly (1.48 m/s). The elderly group had on average 16.5% lower muscle stiffness compared to the young. SWV significantly correlated with muscle mass (r = 0.316), walking time (r = − 0.560), number of chair stands (r = 0.522), handgrip strength (r = 0.436) and isokinetic knee strength (r = 0.640). Sex and BMI did not explain any significant variation in SWV. Conclusions: Ageing was associated with a decline in skeletal muscle stiffness which positively correlates with muscle weakness. Further research is needed to evaluate the promising role of SWE as a biomarker for sarcopenia assessment and potential falls risk prediction in elderly individuals

Survey of ultrasound practice amongst podiatrists in the UK

Background: Ultrasound in podiatry practice encompasses musculoskeletal ultrasound imaging, vascular hand-held Doppler ultrasound and therapeutic ultrasound. Sonography practice is not regulated by the Health and Care Professions Council (HCPC), with no requirement to hold a formal qualification. The College of Podiatry does not currently define ultrasound training and competencies. This study aimed to determine the current use of ultrasound, training received and mentorship received and/or provided by podiatrists using ultrasound. Methods: A quantitative study utilising a cross-sectional, on-line, single-event survey was undertaken within the UK. Results: Completed surveys were received from 284 podiatrists; 173 (70%) use ultrasound as part of their general practice, 139 (49%) for musculoskeletal problems, 131 (46%) for vascular assessment and 39 (14%) to support their surgical practice. Almost a quarter (n=62) worked for more than one organisation; 202 (71%) were employed by the NHS and/or private sector (n=118, 41%). Nearly all (93%) respondents report using a hand-held vascular Doppler in their daily practice; 216 (82%) to support decisions regarding treatment options, 102 (39%) to provide diagnostic reports for other health professionals, and 34 (13%) to guide nerve blocks. Ultrasound imaging was used by 104 (37%) respondents primarily to aid clinical decision making (n=81) and guide interventions (steroid injections n=67; nerve blocks n=39). Ninety-three percent stated they use ultrasound imaging to treat their own patients, while others scan at the request of other podiatrists (n=28) or health professionals (n=18). Few use ultrasound imaging for research (n=7) or education (n=2). Only 32 (11%) respondents (n=20 private sector) use therapeutic ultrasound to treat patients presenting with musculoskeletal complaints, namely tendon pathologies. Few respondents (18%) had completed formal post-graduate CASE (Consortium for the Accreditation of Sonographic Education) accredited ultrasound courses. Forty (14%) respondents receive ultrasound mentorship; the majority from fellow podiatrists (n=17) or medical colleagues (n=15). Over half (n=127) who do not have ultrasound mentorship indicated they would like a mentor predominantly for ultrasound imaging. Fifty-five (19%) report they currently provide ultrasound mentorship for others. Conclusions: Understanding the scope of ultrasound practice, the training undertaken and the requirements for mentorship will underpin the development of competencies and recommendations defined by the College of Podiatry to support professional development and ensure safe practice.</p

Patterns and Predictors of Healthcare Use among Adolescent and Young Adult Cancer Survivors versus a Community Comparison Group.

Healthcare use (HCU) during survivorship can mitigate adolescent and young adult (AYA) cancer survivors' (aged 15-39 years) risk of medical and psychosocial late effects, but this is understudied. We surveyed 93 Australian AYA post-treatment cancer survivors (Mage = 22.0 years, SD = 3.5; 55.9% female) and a comparison sample of 183 non-matched AYAs (Mage = 19.7, SD = 3.2; 70.5% female) on their HCU, medication use, depression/anxiety, and general functioning. Relative to our comparison AYAs, a higher proportion of our survivor group reported medical HCU (community-delivered: 65.6% versus 47.0%, p = 0.003; hospital-delivered: 31.2% versus 20.3%, p = 0.044) and mental HCU (53.8% vs. 23.5%; p < 0.0001) in the past six months. A higher proportion of our survivors reported taking medications within the past six months than our comparison AYAs (61.3% vs. 42.1%, p = 0.003) and taking more types (p < 0.001). Vitamin/supplement use was most common followed by psychotropic medications. Our survivor group reported lower depression (p = 0.001) and anxiety symptoms (p = 0.003), but similar work/study participation (p = 0.767) to our comparison AYAs. Across groups, psychological distress was associated with higher mental HCU (p = 0.001). Among survivors, those who were female, diagnosed with brain/solid tumors and who had finished treatment more recently reported greater HCU. Future research should establish whether this level of HCU meets AYAs' survivorship needs