The RESIST Study: Examining Cognitive Change in Rheumatoid Arthritis Patients with Mild Cognitive Impairment Being Treated with a TNF-Inhibitor Compared to a Conventional Synthetic Disease-Modifying Anti-Rheumatic Drug.

Background: Evidence suggests that TNF inhibitors (TNFi) used to treat rheumatoid arthritis (RA) may protect against Alzheimer's disease progression by reducing inflammation. Objective: To investigate whether RA patients with mild cognitive impairment (MCI) being treated with a TNFi show slower cognitive decline than those being treated with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD). Methods: 251 participants with RA and MCI taking either a csDMARD (N = 157) or a TNFi (N = 94) completed cognitive assessments at baseline and 6-month intervals for 18 months. It was hypothesized that those taking TNFis would show less decline on the primary outcome of Free and Cued Selective Reminding Test with Immediate Recall (FCSRT-IR) and the secondary outcome of Montreal Cognitive Assessment (MoCA). Results: No significant changes in FCSRT-IR scores were observed in either treatment group. There was no significant difference in FCSRT-IR between treatment groups at 18 months after adjusting for baseline (mean difference = 0.5, 95% CI = -1.3, 2.3). There was also no difference in MoCA score (mean difference = 0.4, 95% CI = -0.4, 1.3). Conclusions: There was no cognitive decline in participants with MCI being treated with TNFis and csDMARDs, raising the possibility both classes of drug may be protective. Future studies should consider whether controlling inflammatory diseases using any approach is more important than a specific therapeutic intervention.

Prevalence of cognitive impairment in patients with rheumatoid arthritis: a cross sectional study.

OBJECTIVE: To explore the role of chronic inflammation in rheumatoid arthritis (RA) on cognition. METHODS AND ANALYSIS: Six hundred sixty-one men and women aged ≥55 years who fulfilled the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for RA were recruited from three healthcare trusts in the United Kingdom (UK) between May 2018 and March 2020. Study participants took part in interviews which captured sociodemographic information, followed by an assessment of cognition. RA specific clinical characteristics were obtained from hospital medical records. Participants were cognitively assessed using the Montreal Cognitive Assessment (MoCA) and were classified as cognitively impaired if they scored ≤27/30 points. Linear regression analyses were conducted to identify which demographic and clinical variables were potential predictors of cognitive impairment. RESULTS: The average age of participants was 67.6 years and 67% (444/661) were women. 72% (458/634; 95% CI 0.69 to 0.76) of participants were classified as cognitively impaired (MoCA≤27). Greater cognitive impairment was associated with older age (p = .006), being male (p = .041) and higher disease activity score (DAS28) (with moderate (DAS28 > 3.1) (p = 0.008) and high (DAS28 > 5.1) (p = 0.008)) compared to those in remission (DAS28 ≤ 2.6). There was no association between MoCA score and education, disease duration, RF status, anti-cyclic citrullinated peptide (anti-CCP) status, RA medication type or use of glucocorticoids or non-steroidal anti-inflammatory drugs (p > 0.05). CONCLUSION: This study suggests that cognitive impairment is highly prevalent in older adults with RA. This impairment appears to be associated with higher RA disease activity and supports the concept that chronic systemic inflammation might accelerate cognitive decline. This underlines the importance of controlling the inflammatory response.

The impact of rheumatologist-performed ultrasound on diagnosis and management of inflammatory arthritis in routine clinical practice.

BACKGROUND: Rheumatologists increasingly perform ultrasound (US) imaging to aid diagnosis and management decisions. There is a need to determine the role of US in facilitating early diagnosis of inflammatory arthritis. This study describes the impact of US use by rheumatologists on diagnosis and management of inflammatory arthritis in routine UK clinical practice. METHODS: We conducted a prospective study in four secondary care rheumatology clinics, each with one consultant who routinely used US and one who did not. Consenting patients aged > 18, newly referred with suspected inflammatory arthritis were included. Data were collected both retrospectively from medical records and via a prospectively-completed physician questionnaire on US use. Analyses were stratified by US/non-US groups and by sub-population of rheumatoid arthritis (RA)-diagnosed patients. RESULTS: 258 patients were included; 134 US and 124 non-US. 42% (56/134) of US and 47% (58/124) of non-US were diagnosed with RA. Results described for US and non-US cohorts, respectively as follows. The proportion of patients diagnosed at their first clinic visit was 37% vs 19% overall (p = 0.004) and 41% vs 19% in RA-diagnosed patients (p = 0.01). The median time to diagnosis (months) was 0.85 vs 2.00 (overall, p = 0.0046) and 0.23 vs 1.38 (RA-diagnosed, p = 0.0016). Median time (months) to initiation on a DMARD (where initiated) was 0.62 vs 1.41 (overall, p = 0.0048) and 0.46 vs 1.81 (RA-diagnosed, p = 0.0007). CONCLUSION: In patients with suspected inflammatory arthritis, routine US use in newly referred patients seems to be associated with significantly earlier diagnosis and DMARD initiation.

Ultrasound imaging for the rheumatologist. XLII. Assessment of hip pain in rheumatic patients: the radiologist's view.

Hip pain is a common complaint in daily practice and the identification of the underlying pathologic condition is the first step for an adequate treatment. In this review, we discuss the available evidence for the application of conventional radiography, computed tomography and magnetic resonance imaging in rheumatologic patients with painful hip, presenting the main imaging findings due to osteoarthritis, inflammatory arthritis (rheumatoid arthritis and spondyloarthritides), osteonecrosis and some other soft tissue involvement (bursitis and synovial cyst) that could be the cause of hip pain. Because different imaging techniques show different sensitivity and specificity, the choice of technique to use depends on the type and stage of the disease itself.

Ultrasound imaging for the rheumatologist XLI. Sonographic assessment of the hip in OA patients.

OBJECTIVES: To investigate the prevalence of ultrasound (US) detectable abnormalities in the hip joints of patients with osteoarthritis (OA) and correlate them with clinical findings and measures of disease severity. METHODS: Consecutive patients with hip OA were investigated by clinical and US examinations. Bilateral US of the hip joints was performed by using a Logiq9 machine, equipped with a multi-frequency linear probe, operating at 9 MHz; in addition, power Doppler (PD) was applied (frequency 7.5 MHz; PRF 750 Hz). Clinical evaluation included the registration of demographic data, disease duration, current and previous joint pain and Lequesne index. US study included the assessment of both inflammatory and structural abnormalities at the level of hip joint (joint effusion, synovial hypertrophy, local pathologic vascularisation at PD, osteophytes) and periarticular soft tissues (iliopsoas bursitis, trochanteric bursitis, iliopsoas tendinopathy, gluteus medius tendinopathy and gluteus minimus tendinopathy). RESULTS: One hundred and fifty hips of 75 patients were studied. Clinical examination demonstrated the presence of current hip pain in 80% of patients and previous hip pain in 85.7% of cases. The mean Lequesne Index was 11.9±4.9. US detected effusion in 50% of the joints, synovial hypertrophy in 41.3%, PD signal in 0.7%, osteophytes in 77.3%; at periarticular level, trochanteric bursitis was found in 24.7% of patients, gluteus tendinopathy in 22.7%, iliopsoas tendinopathy in 7.3% and finally iliopsoas bursitis in 1.3%. The presence of current and previous hip pain significantly correlated with the presence of effusion (p=0.01); age and disease duration significantly correlated with the presence of osteophytes (p=0.01). Various US-detected abnormalities were found also in asymptomatic patients. Statistically significant differences between the 2 subgroups of symptomatic and asymptomatic patients were registered for effusion (p=0.003). CONCLUSIONS: In hip OA, US is a useful imaging tool for analysing both inflammatory and structural damage lesions as well as for differentiating the involvement of joint structures and periarticular soft tissues. In addition, US was able to detect a wide set of abnormalities even in asymptomatic patients, confirming that it is more sensitive than clinical examination in detecting musculoskeletal involvement.

Ultrasound imaging for the rheumatologist XL. Sonographic assessment of the hip in rheumatoid arthritis patients.

OBJECTIVES: The aim of the present study was to correlate clinical and laboratory data with those obtained by ultrasound (US) evaluation of the hip in a cohort of patients with rheumatoid arthritis (RA). METHODS: Fifty-two RA patients attending the Rheumatology Departments involved in the present study were enrolled. Demographic (age, gender), clinical (body mass index, disease duration, treatments, history or current hip pain, tenderness by internal or external hip rotation or palpation of the greater trochanteric region), laboratory (erythrosedimentation rate, C-reactive protein, rheumatoid factor and antibodies anti-citrullinated peptides) and clinimetric data (disease activity score 28 - DAS28, Health Assessment Questionnaire - HAQ, Lequesne index) were collected. All patients underwent an US examination of both hips according to international guidelines. RESULTS: A total of 100 hips were scanned in 52 patients with RA. Approximately half of the patients reported a history of hip pain, one fourth complained of current pain, and the physical examination (internal and/or external rotation and palpation of the greater trochanteric region) evocated pain up to 19% and 22% of the patients, respectively. US examination found signs of hip joint abnormalities in 42% of the patients; US changes indicative of hip joint inflammation and damage were detected respectively in 24% and 32% of the cases. No patient presented power Doppler signal in the hip joint. A significant correlation between US pathological findings at hip level was found with clinical data (current pain and evocated pain by internal or external hip rotation). Furthermore, US cartilage lesion correlated with age of the patient, and US bone erosions with the disease duration. No correlation was found between the sonographic assessment and laboratory data, DAS 28, and Lequesne index. CONCLUSIONS: US abnormalities at hip joint level obtained in the present study correlated with clinical findings, while no correlation was found with DAS28 or laboratory data. Further investigations are encouraged to clarify the US additional value at hip level in patients with RA.

Ultrasound imaging for the rheumatologist XXXVIII. Sonographic assessment of the hip in psoriatic arthritis patients.

OBJECTIVES: The aims of our study were to investigate the prevalence of ultrasound (US) pathological abnormalities in the hip of psoriatic arthritis (PsA) patients and compare them with the clinical findings. METHODS: Sixty-five PsA patients were enrolled in the study. Bilateral examination of the hip was performed to detect joint effusion, synovial hypertrophy, irregularity of femoral head and neck profile as seen in erosions and/or osteophytes. RESULTS: Joint effusion was detected in 20 out of 130 hips (15%). Synovial hypertrophy was present in 12 out of 20 hips (60%) associated with effusion (9.3% of all hip joints) and only 1 of them showed PD signal. Small effusion without synovial proliferation was imaged in 8 out of 20 hips (40%). On the whole 14 out of 65 patients (21%) had joint effusion with or without synovial hypertrophy using US. No erosions of the femoral head and neck profile were detected whilst osteophytes were imaged in 27 joints (20%). No US abnormalities were demonstrated in 18 hips with pain/tenderness on physical examination, whilst joint effusion was seen in 8 joints which were asymptomatic. CONCLUSIONS: US is a useful imaging method to evaluate hip involvement in PsA that could be integrated into routine PsA management even if patients do not complain of hip involvement.

CS injection of tenosynovitis in patients with chronic inflammatory arthritis: the role of US.

OBJECTIVE: The main aim of this study was to investigate the short-term efficacy of CS loco-regional treatment performed under US guidance in tenosynovitis of patients with chronic inflammatory arthritis. METHODS: Thirty consecutive patients affected by chronic arthritis and with clinical suspicion of tenosynovitis were recruited to undergo US assessment. In the sonographically proven cases, US-guided CS injection was performed. A visual analogue scale for pain (ranging from 0 to 10) and a tenderness score (ranging from 0 to 3) were used for the clinical evaluation. Sonographic pathological findings indicative of tenosynovitis were scored using a semi-quantitative 4-grade scoring system, for both grey-scale and power Doppler US, at baseline and during a follow-up visit at 2 weeks after the CS injection. RESULTS: In 21 (70%) of 30 patients, the clinical suspicion of tenosynovitis was confirmed (9 with RA, 11 with PsA and 1 with ReA). In the other nine patients, US revealed synovitis of the adjacent joints, bursitis, oedema of the s.c. tissue or a partial tear. In all cases the appropriate needle placement and subsequent CS injection into the tendon sheath were obtained with US confirmation. A significant reduction in all clinical and sonographic scorings was found during the follow-up visit. CONCLUSIONS: The present study shows the efficacy of US-guided peritendinous CS injections in the management of patients with chronic inflammatory arthritis presenting as US-proven tenosynovitis.

Ultrasound imaging for the rheumatologist XXXVI. Sonographic assessment of the foot in gout patients.

OBJECTIVES: This study aims to investigate the relationship between clinical and US findings together with the prevalence and distribution of US findings indicative of monosodium urate (MSU) crystal deposition within the foot in patients with gout. METHODS: A total of 50 patients with gout attending the in-patient and the out-patient clinics of the Rheumatology Departments were prospectively enrolled in this multi-centre study. Multiplanar examination of the following 15 joints was performed: talo-navicular, navicular-cuneiform (medial, intermediate and lateral), calcaneo-cuboid, medial, intermediate and lateral cuneiform-metatarsal, cuboid-4th metatarsal, cuboid-5th metatarsal and all five metatarsophalangeal (MTP) joints. RESULTS: The following US findings were indicative of gout: enhancement of the superficial margin of the hyaline cartilage, intra-articular tophus, and extraarticular tophus. In 46 patients, a total of 1380 foot joints were investigated. In 1309 joints that were not clinically involved, US detected signs indicative of joint inflammation in 9% (121/1309). Talo-navicular joint and the first MTP joint were the joints in which the highest number of US findings were found at mid-foot and fore-foot, respectively. At MTP joint level, dorsal scans allowed the detection of a higher number of US findings indicative of joint inflammation, and MSU crystal deposits rather than on the volar plane. CONCLUSIONS: This study demonstrated that US detected a higher number of inflamed foot joints than clinical examination, and that the first MTP and the talo-navicular joints were the anatomic sites with the highest prevalence of US signs of MSU crystal aggregates.

Ultrasound imaging for the rheumatologist XXXV. Sonographic assessment of the foot in patients with osteoarthritis.

OBJECTIVES: The aims of our study were to investigate the prevalence of ultrasound (US) abnormalities in the foot of patients with osteoarthritis (OA) and to compare them with clinical findings. METHODS: Consecutive patients with foot OA were investigated by clinical and US examinations. Bilateral US of the midfoot and forefoot joints was performed by using a Logiq9 machine, equipped with a multi-frequency linear probe, operating at 14 MHz; in addition, power Doppler was applied (frequency 7.5 MHz; gain 50%; PRF 750 Hz). Clinical evaluation included the registration of demographic data, disease duration, current treatment undergone, joint swelling and tenderness. US study included the assessment of both inflammatory (joint effusion, synovial hypertrophy, local pathologic vascularisation at PD, big-toe bursitis) and structural (osteophytes, MTP joints subluxation) abnormalities. RESULTS: One hundred patients were studied. At midfoot level, clinical examination demonstrated signs suggestive for joint inflammation (tenderness and/or swelling) in at least one joint in 43/200 feet (21.5%) of 23 patients; US showed inflammatory abnormalities in 87/200 feet (43.5%) of 63 patients and structural lesions in 100/200 feet (50%) of 70 patients. At forefoot level, clinical examination found inflammatory signs in at least one joint in 128 feet (64%) of 64 patients; US showed inflammatory abnormalities in at least one joint in 176 feet (88%) of 88 patients and structural lesions in 189 feet (86%) of 86 patients. CONCLUSIONS: US is a useful imaging tool for analysing both inflammatory and structural damage lesions at foot joints level in OA. In addition, it demonstrated to be more sensitive than clinical examination in the detection of inflammatory abnormalities.

Ultrasound imaging for the rheumatologist. XXXI. Sonographic assessment of the foot in patients with rheumatoid arthritis.

OBJECTIVES: The aims of our study were to investigate the prevalence of ultrasound (US) abnormalities in the foot of patients with rheumatoid arthritis (RA) and to compare them with the clinical findings. METHODS: One hundred RA patients were enrolled in the study. Bilateral US examination of metatarsophalangeal (MTP) joints, proximal interphalangeal (PIP) joints, midfoot joints (talonavicular, calcaneo-cuboid, medial, intermediate and lateral navicular-cuneiform and cuneiform-metatarsal joints and cuboid-4th and 5th metatarsal joints) were examined for synovitis and erosion. In addition the plantar fascia and the insertion of the anterior and posterior tibialis and peroneous brevis tendons were imaged. RESULTS: Effusion with synovial proliferation was visualised only at MTP joints in 84 out of 200 (42%) feet, at MTP plus at least one joint of the midfoot in other 41 out of 200 (20%) feet (making a total of 125 out of 200 (62%) MTP joints) exclusively in one or more joints of the midfoot in 7 out 200 (3%) feet, in the PIP joint of the 2nd and 3rd toes in 3 (1.5%) and 4 (2%) feet respectively, while no effusion with synovial proliferation was visualised in the PIP joint of the 4th and 5th toes. Synovitis was present most frequently in the 2nd MTP joint whilst erosions were most frequently imaged in the 5th MTP joint. CONCLUSIONS: US examination appears to be a useful imaging technique to study joint and tendon involvement of the foot in RA patients. Moreover, US examination of the foot is more sensitive than clinical examination in the detection of joint inflammation and allows for a better understanding of the features and the progression of the disease.

Ultrasound Imaging for the rheumatologist XXVII. Sonographic assessment of the knee in patients with rheumatoid arthritis.

The aims of our study were to investigate the prevalence of ultrasound (US) pathologic abnormalities and to compare them with the clinical findings in the knee of rheumatoid arthritis (RA) patients. One hundred RA patients were enrolled in the study. Bilateral US examination of the knee was performed to visualise the presence of effusion, synovial proliferation, bone erosions, femoral cartilage abnormalities, quadricipital and/or patellar enthesopathy. The popliteal fossa and the calf region were also evacuate to detect popliteal cyst. We observed joint effusion in 140 out of 200 (70%) knees. Synovial hypertrophy was present in 115 out of 140 (82%) knees associated with effusion and in 22 out of 115 (19%) knees intra-articular power Doppler (PD) signal was found. Hyperechoic spots within the cartilage layer, suggestive of pyrophosphate crystals deposit, were detected in the knees of 3 patients. US signs of quadricipital and/or patellar enthesopathy were detected in 53 out 200 (26%) knees. Bone erosions were visualised in 16 out 200 (8%) knees. Popliteal cyst was found in 66 out of 200 (33%) joints. US examination of the knee is more sensitive than clinical examination in the detection of joint inflammation and allows for the identification of different patterns of pathologic changes at knee level, including morphostructural changes at both cartilage and tendon level.

Etanercept in the treatment of rheumatoid arthritis: clinical follow-up over one year by ultrasonography.

We evaluated clinically and sonographically the effects of etanercept therapy in patients with rheumatoid arthritis (RA) over 12 months of treatment. Eighteen patients affected by RA who were non-responders or partial responders to disease modifying therapy were commenced on Etanercept treatment. Before starting therapy (T0) and at 12 months (T1), the following parameters were evaluated: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale (VAS) for pain, number of painful and swollen joints, health assessment questionnaire (HAQ) and disease activity score in 28 joints (DAS 28). Musculoskeletal ultrasound (US) was performed in the following joints: second and fifth metacarpophalangeal, third interphalangeal, wrist and knee joints and a semiquantitative score (0-3) calculated and used to indicate the presence of a localised inflammatory process (synovitis, tenosynovitis, bursitis) and/or structural damage (bone erosion and cartilaginous change). An overall score was calculated based on the sum of the single scores to obtain a comprehensive score indicative of the global pathological change. The US global scores significantly reduced between T0 and T1 (p < 0.0001). The following laboratory and clinical parameters also significantly reduced: ESR (p < 0.0001), CRP (p < 0.02), VAS (p < 0.001), number of total swollen joints (p < 0.001), number of total painful joints (p < 0.01), HAQ scores (p < 0.05) and DAS 28 (p < 0.0001). A positive response to treatment with Etanercept was demonstrated both by US examination of several joints and by clinical evaluation of several parameters. US is a useful tool in the monitoring of biologic therapy in RA, assessing both inflammatory and destructive changes.

E-learning in ultrasonography: a web-based approach.

OBJECTIVE: To propose e-learning methods that address the fundamental problems related to sonographic training in rheumatology. METHODS: The project was designed for rheumatologists with strong motivation to learn ultrasound. A modular approach was constructed, consisting of a basic 3-day residential course, followed by a 6-month period of web-based tutoring, and culminating in a final 2-day residential course with a formal assessment of competency. RESULTS: The website (http://www.e-sonography.com) was accessed by all 60 participants. A mean of 20 (range 10-80) log-on sessions were registered for each participant, and a mean of 250 min (range 60-600 min) of web access was recorded. A total of 163 sonographic images were submitted by 18 (30%) participants. The majority of the images focused on the following anatomical areas: shoulder 49 (30%), hand 34 (21%) and knee 20 (12%). A total time investment of approximately 14 h was made by the US tutors over the 6-month period for interaction with the participants. CONCLUSIONS: The e-learning methods described in this report represent the first attempt to adopt a novel technique to circumvent several of the inherent barriers to the many facets of teaching musculoskeletal ultrasound to a wide audience.

Lack of support for the presence of an osteoarthritis susceptibility locus on chromosome 6p.

OBJECTIVE: To replicate, in a Northern Irish population, the previously reported association between a locus on chromosome 6 and hip osteoarthritis (OA). METHODS: Patients with hip OA were identified from a registry of patients who had undergone total hip replacement surgery over an 8-year period at a single large orthopedic unit in Northern Ireland. Patients identified as index cases were contacted by mail and asked to reply only if another family member also had undergone total hip replacement surgery. Using this approach, we identified 288 sibling pairs concordant for primary hip OA. DNA was extracted from peripheral blood, and microsatellite markers were amplified by polymerase chain reaction and subsequently genotyped. RESULTS: No evidence of linkage to this region was demonstrated by either 2-point analysis or multipoint analysis of 17 microsatellites. CONCLUSION: The reported association between a locus on chromosome 6 and hip OA could not be confirmed in this population. Different methods of ascertainment and phenotyping of OA may contribute to the current inability to replicate genetic associations for hip OA.

The clinical effect of dietary supplementation with omega-3 fish oils and/or copper in systemic lupus erythematosus.

OBJECTIVE: To determine the effect of dietary supplementation with omega-3 fish oils with or without copper on disease activity in systemic lupus erythematosus (SLE). Fish oil supplementation has a beneficial effect on murine models of SLE, while exogenous copper can decrease the formation of lupus erythematosus cells in rats with a hydralazine-induced collagen disease. METHODS: A double blind, double placebo controlled factorial trial was performed on 52 patients with SLE. Patients were randomly assigned to 4 treatment groups. Physiological doses of omega-3 fish oils and copper readily obtainable by dietary means were used. One group received 3 g MaxEPA and 3 mg copper, another 3 g MaxEPA and placebo copper, another 3 mg copper and placebo fish oil, and the fourth group received both placebo capsules. Serial measurements of disease activity using the revised Systemic Lupus Activity Measure (SLAM-R) and peripheral blood samples for routine hematological, biochemical, and immunological indices were taken at baseline, 6, 12, and 24 weeks. RESULTS: There was a significant decline in SLAM-R score from 6.12 to 4.69 (p < 0.05) in those subjects taking fish oil compared to placebo. No significant effect on SLAM-R was observed in subjects taking copper. Laboratory variables were unaffected by either intervention. CONCLUSION: In the management of SLE, dietary supplementation with fish oil may be beneficial in modifying symptomatic disease activity.