Rheumatology musculoskeletal ultrasound assessment of minimal synovial disease in hands, wrists and feet

Introduction Ultrasound of joints and tendons is a useful tool in the diagnosis of early inflammatory arthritis. Advances in ultrasound technology in recent years have resulted in better resolution images, facilitating the detection of minimal musculoskeletal structural abnormalities including low grades of synovial hypertrophy, power Doppler signal and joint effusions. However, currently there is no definitive guidance as to what extent these changes may be due to inflammatory arthritis, or how much they are due to the normal ageing process. Methods Systematic literature review (SLR): Pubmed, Medline and EMBASE databases were searched: ultrasound, hands, feet, wrists, metacarpophalangeal, metatarsophalangeal, metacarpal, normal, healthy, control, synovial, hypertrophy, Doppler or synovitis. Two independent groups of reviewers assessed the abstracts and subsequent full papers. Ultrasound of healthy subjects across the age range: Healthy adults (age 18 to 80 years) were recruited in 23 international centres with exclusion criteria: joint pain, hand osteoarthritis and history of inflammatory arthritis. Selected joints and tendons in hands, wrists and feet were scanned and graded according to a recent Outcome Measures in Rheumatology (OMERACT) consensus. Data from a comparison cohort of Rheumatoid Arthritis (RA) patients were taken from the Birmingham Early Arthritis Inception Cohort (BEACON). Ultrasound findings in patients with clinically suspect arthralgia: The BEACON database was searched for patients with a baseline diagnosis of inflammatory arthralgia or clinically suspect arthralgia (CSA) who underwent routine ultrasound of selected hand, wrist and foot joints and tendons at time of enrolment and had 24 month follow up. Results SLR: In the 19 full papers included there was considerable heterogeneity in recruitment and definitions of HS, and in the reporting of ultrasound data. This has made it difficult to draw firm conclusions from the evidence gathered in this systematic literature review. Ultrasound of healthy subjects across the age range: 954 healthy subjects were scanned with a mean age of 44.4 years old. There were significant differences in proportion of grade ≥1 synovial hypertrophy (SH) in metacarpophalangeal joints in older age groups. Prevalence of power Doppler grade ≥1 in all joints was low across the age range. There was variability in prevalence of grade ≥1 SH in wrist and metatarsophalangeal (MTP) joints between recruiting centres, leading to a reliability exercise and creation of new wrist and MTPJ ultrasound atlases. In the digit flexor and extensor carpi ulnaris tendons there was very low prevalence of ultrasound abnormalities with 85% of healthy having grade 0 for all tenosynovial hypertrophy (TSH), power Doppler (TPD) and effusion, with no significant differences across the age range. A comparison cohort of 144 RA patients was compared with a group of age- and sex-matched HS with significant difference in the proportion of TSH and TPD involvement between HS and RA subjects (p<0.001). Ultrasound findings in patients with clinically suspect arthralgia: 43 patients with CSA at baseline diagnosis with 24 month BEACON follow up were included. Positive Rheumatoid factor was associated with development of inflammatory arthritis at 2 years, and ACPA positivity was significantly associated with progression to RA within 2 years (p<0.05). There was significantly more grade ≥1 SH in MCPJ 2 and 3 in those patients that progressed to an inflammatory arthritis by 24 months follow up (p<0.05). Conclusions This study provides a large amount of ultrasound data on selected joints and tendons for healthy subjects across the age range, and should provide a large control cohort to help further Rheumatology ultrasound research

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The value of ultrasound-defined tenosynovitis and synovitis in the prediction of persistent arthritis.

OBJECTIVES The value of ultrasound-defined tenosynovitis in predicting the persistence of inflammatory arthritis is not well described. In particular, the predictive utility of ultrasound-defined tenosynovitis of larger tendons is yet to be reported. We assessed the value of ultrasound-defined tenosynovitis alongside ultrasound-defined synovitis and clinical and serological variables in predicting persistent arthritis in an inception cohort of disease-modifying antirheumatic drug (DMARD)-naïve patients with early arthritis. METHODS One hundred and fifty DMARD-naïve patients with clinically apparent synovitis of one or more joints and a symptom duration ⩽3 months underwent baseline clinical, laboratory and ultrasound (of 19 bilateral joints and 16 bilateral tendon compartments) assessments. Outcomes were classified as persistent or resolving arthritis after 18 months follow-up. The predictive value of ultrasound-defined tenosynovitis for persistent arthritis was compared with those of ultrasound-defined synovitis, clinical and serological variables. RESULTS At 18 months, 99 patients (66%) had developed persistent arthritis and 51 patients (34%) had resolving disease. Multivariate logistic regression analysis showed that ultrasound-detected digit flexor tenosynovitis (OR: 6.6, 95% CI: 2.0 - 22.1, p = 0.002) provided independent predictive data for persistence over and above the presence of ultrasound-detected joint synovitis and rheumatoid factor antibodies. In the RF/ACPA-negative sub-cohort, ultrasound-defined digit flexor tenosynovitis remained a significant predictive variable (OR: 4.7, 95% CI: 1.4 - 15.8, p = 0.012), even after adjusting for ultrasound-defined joint synovitis. CONCLUSION Ultrasound-defined tenosynovitis provided independent predictive data for the development of persistent arthritis. The predictive role of ultrasound-defined digit flexor tenosynovitis should be further assessed; investigators should consider including this tendon site as a candidate variable when designing imaging-based predictive algorithms for persistent inflammatory arthritis development

Additional file 1 of Predictors of quality of life, functional status, depression and fatigue in early arthritis: comparison between clinically suspect arthralgia, unclassified arthritis and rheumatoid arthritis

Supplementary Material

Very low prevalence of ultrasound-detected tenosynovial abnormalities in healthy subjects throughout the age range: OMERACT ultrasound minimal disease study.

OBJECTIVES This study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range. METHODS Adult HS (age 18-80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort. RESULTS 939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups. CONCLUSIONS Ultrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA