Ultrasonographic Synovitis Is Associated with the Development of Joint Destruction in Patients with Psoriatic Arthritis.

BACKGROUND: Psoriatic arthritis (PsA) is characterized by enthesitis. As persistent inflammation around joints results in bone and cartilage destruction and physical impairment, a detailed assessment of inflammation is essential. We previously reported the difference between clinical assessment (tenderness) and ultrasound (US) assessment (inflammation) of entheses. Herein, we investigated whether clinical or US assessment of joints and entheses can predict the progression of joint destruction in Japanese patients with PsA. METHODS: Thirty joints and 14 entheses in 47 patients were assessed using US and clinical examination. The US greyscale (GS) and power Doppler (PD) scores at the ultrasonographic synovitis, the US active enthesitis count, and the clinical tender joint/entheses count were assessed. Additionally, the yearly radiographic progression of the Sharp-van der Heijde scoring method for PsA was assessed. Their correlations were investigated. RESULTS: About half of the patients with PsA experienced joint destruction during a follow-up period of 20.4 months. Progression of joint destruction in patients with PsA only correlated with joint GS and PD scores, reflecting the severity of ultrasonographic synovitis, not with the tender joint/entheses count. CONCLUSIONS: US examinations are essential for preventing joint destruction and physical impairment in patients with PsA.

Relationship between the phase angle from bioelectrical impedance analysis and daily physical activity in patients with rheumatoid arthritis.

OBJECTIVES: This study aimed to examine the relationship between daily physical activity and the phase angle (PhA) obtained by bioelectrical impedance analysis in rheumatoid arthritis (RA) patients. METHODS: Data from a prospective cohort study of RA patients who were surveyed every year were analysed. The PhA was assessed by the bioelectrical impedance analysis method, and physical activity was assessed as the amount of time of exercise in metabolic equivalents (METs) per day using a triaxial accelerometer for 7 consecutive days. The association between physical activity and the PhA was evaluated using the isotemporal substitution model in multiple regression analysis. RESULTS: Seventy-six RA patients were included in the analysis (81% female and age 66.2 ± 13.1 years). On cross-sectional analysis, the isotemporal substitution model in multiple regression analysis showed that the PhA was 0.05 points higher every 10 minutes when activities with intensity of 1 ≤ METs < 2 were replaced by activities with intensity of ≥3 METs (P = .01). Over 1 year, the rate of change in the PhA was 0.69% higher every 10 minutes when activities with intensity of 1 ≤ METs < 2 were replaced by activities with intensity of ≥3 METs (P = .037). CONCLUSION: The PhA in RA patients may be related to physical activity level.

Lifestyle and body composition changes in patients with rheumatoid arthritis during the COVID-19 pandemic: A retrospective, observational study.

Objectives: Behavioral restrictions and staying at home during the COVID-19 pandemic have affected lifestyles. It was hypothesized that patients with rheumatoid arthritis (RA) decreased their activities of daily living (ADL) and exercise during the pandemic. The aim of this study is to investigate the changes in lifestyle and body composition. Methods: Data were obtained from an observational study (CHIKARA study). Of 100 RA patients, 70 (57 women, 13 men) were followed-up with measurements of grip strength, as well as muscle mass, fat mass, and basal metabolic rate by a body composition analyzer. Changes in ADL and exercise were evaluated using a visual analog scale. The relationships between changes in ADL or exercise and body composition were investigated. Results: Muscle mass and grip strength were significantly lower after behavioral restrictions compared to the periods before restrictions (34.0 vs 34.7 kg, P < 0.001; 16.2 vs 17.2 kg, P = 0.013, respectively). Fat mass was significantly greater after behavioral restrictions compared to the periods before restrictions (16.2 vs 15.5 kg, P = 0.014). The mean decrease in ADL was 44%, whereas that of exercise was 20%.The change in muscle mass (ß = -0.335, P = 0.007) was the only independent factor for the change in exercise on multivariate analysis. Conclusions: Muscle mass and grip strength decreased and fat mass increased in RA patients with the behavioral restrictions of the COVID-19 pandemic. Muscle mass decreased in patients without exercise. Maintenance of muscle mass may be important during the COVID-19 pandemic.

The bioimpedance phase angle may be associated with frailty in rheumatoid arthritis patients: Results from a prospective, cohort study.

OBJECTIVES: This study investigated whether the phase angle (PhA) on bioelectrical impedance analysis is related to frailty in rheumatoid arthritis (RA) patients. METHODS: Data from a prospective cohort study of RA patients were analysed. The PhA was assessed by the bioelectrical impedance analysis method, and frailty was assessed by the Kihon Check List (KCL) annually. The cut-off value of the PhA for frailty was calculated by receiver-operating characteristic analysis. The relationships between the PhA and frailty were evaluated by logistic regression analysis. The relationships between the change in PhA and frailty status and the KCL score were evaluated by analysis of covariance and multiple regression analysis. RESULTS: A total of 170 patients (81.2% female, 66.2 ± 13.1 years) were included in the analysis. A PhA of less than the cut-off for frailty was significantly associated with frailty (odds ratio: 4.75, 95% confidence interval: 1.86, 12.17). The change in the PhA was significantly associated with the change in the KCL score (ß = -0.15). In robust patients, there was a significant difference in the rate of change of the PhA between the group that became pre-frail in the next year and the group that remained robust. CONCLUSIONS: The PhA may be associated with frailty in RA patients.

The bioimpedance phase angle is more useful than sarcopenia as a predictor of falls in patients with rheumatoid arthritis: Results from a 2-y prospective cohort study.

OBJECTIVES: The phase angle (PhA) is an index derived by bioelectrical impedance analysis that reflects the fragility of cell membranes, muscle mass, muscle strength, and nutritional status, and a decrease in PhA might be associated with falls. This study aimed to investigate the relationships of the PhA with sarcopenia and falls in patients with rheumatoid arthritis (RA). METHODS: Data from a prospective cohort study of 189 patients with RA (age 66.5 ± 13.3 y; 80% women) were analyzed. PhA, muscle mass, and grip strength (GS) were evaluated. Sarcopenia was assessed using the Asian Working Group for Sarcopenia 2014 criteria. The correlation between PhA and GS was investigated, and the cutoff value of the PhA for falls during a 2-y period was estimated with a receiver operating characteristic curve analysis. The effects of the PhA and sarcopenia on falls were examined with a Cox proportional hazards model. RESULTS: Of the 189 patients, 48 (25.4%) had falls. The PhA was significantly positively correlated with GS (r = 0.58; P < 0.001). The cutoff values for the PhA for falls were 4.06° for women and 5.26° for men. In the Cox proportional hazards model adjusted for sex, age, disease activity, glucocorticoid use, and activities of daily living at baseline, the hazard ratio for falls was significantly higher when the PhA was below the cutoff value at baseline (hazard ratio: 2.29; 95% confidence interval, 1.18-4.45). Sarcopenia was not a significant risk factor for falls. CONCLUSIONS: The PhA might be a useful surrogate marker to predict falls in patients with RA.

Daily physical activity measured by a wearable activity monitoring device in patients with rheumatoid arthritis.

INTRODUCTION: Activities of daily living in patients with rheumatoid arthritis (RA) have been evaluated by patient-reported outcomes. However, it has been difficult to measure activity intensity quantitively. Calories expended, exercise, and steps were measured quantitively by a wearable activity meter, and their associations with patients' background characteristics were examined. METHODS: Data from a prospective, observational study (CHIKARA study) were used. Eighty-five of 100 RA patients were entered and wore a wearable activity meter for 7 days. The daily calories expended and exercise for both walking and housework and steps were evaluated. Total daily calories expended and exercise was defined as the sum of walking and housework. The relationships of DAS28-ESR, mHAQ, body composition, muscle function, and general status were analyzed. RESULTS: The median age was 66.0 years, and the disease duration was 5.3 years. DAS28-ESR was 3.11, and mHAQ was 0.125. Total daily calories expended, exercise, and number of steps were 461.7 kcal, 3.97 METs h, and 4,788, respectively. MHAQ, walking speed, power, locomotive syndrome, and frailty were independently related to exercise. Total daily exercise and steps of the moderate and high disease activity group were significantly lower than those of the remission group. When the number of steps was < 3,333 and < 2,468, the odds ratios for locomotive syndrome and frailty increased 14.4-fold and 8.7-fold, respectively, using Fisher's exact test (P < 0.001). CONCLUSIONS: Daily physical activity and number of steps were significantly decreased in RA patients with moderate and high disease activity as measured by a wearable activity meter. Key Points • Total daily calories expended and exercise for both walking and housework and steps in patients with rheumatoid arthritis were 461.7 kcal, 3.97 METs h, and 4,788, respectively, using a wearable activity meter. • Daily physical activity, especially total daily exercise and number of steps, was significantly decreased in RA patients with moderate and high disease activity. • When total daily steps were < 3,333 and < 2,468, the odds ratios for locomotive syndrome and frailty increased 14.4-fold and 8.7-fold, respectively.

Screening for sarcopenia and obesity by measuring thigh muscle and fat thickness by ultrasound in patients with rheumatoid arthritis.

OBJECTIVES: Sarcopenia is relatively common in rheumatoid arthritis (RA) patients. Thicknesses of the quadriceps muscle and fat are easily measured by ultrasound (US) and are known to be related to skeletal muscle mass and fat mass, respectively. METHODS: Eighty-four patients enrolled in the prospective correlation research of sarcopenia, skeletal muscle, and disease activity in rheumatoid arthritis study (UMIN000023744) underwent US examinations of anterior thigh muscle thickness (MT) and fat thickness (FT). Muscle and body fat (BF) mass were also examined by a body composition analyzer. Whether MT and FT were related to sarcopenia and obesity was examined. RESULTS: MT was significantly lower in RA patients with sarcopenia than in those without (23.8 vs 28.2 mm, P = 0.001). MT was related to sarcopenia (men: r = 0.56, P = 0.02, women: r = 0.32, P = 0.01). The cut-off value of MT for sarcopenia was 24.7 mm in men and 19.7 mm in women on receiver operating characteristic curve analyses. FT was correlated with BF percentage (%BF; men: r = 0.66, P < 0.01, women: r = 0.62, P < 0.001), which was estimated by 2.04xFT+8.53 in men and 1.2xFT+17.42 in women by a simple linear regression model. This means that FT ≥ 8.1 mm in men and FT ≥ 14.6 mm in women indicated obesity. CONCLUSIONS: US examination of the anterior thigh was useful to detect sarcopenia and obesity in RA patients.

Double-blinded randomized controlled trial to reveal the effects of Brazilian propolis intake on rheumatoid arthritis disease activity index; BeeDAI.

BACKGROUND AND AIMS: Brazilian propolis reportedly contributed to suppressing disease activity in a mouse model of rheumatoid arthritis (RA), suggesting new treatment options using Brazilian propolis. However, only results from animal experiments have been available, and the suppressive effects of Brazilian propolis on disease activity in humans with RA remain unknown. The purpose of this study was to clinically validate how Brazilian propolis intake changes disease activity in RA patients. METHODS: This study was conducted as a multicenter, double-blinded, randomized, placebo-controlled, parallel-group study of 80 women with RA (median age, 61.5 years; interquartile range, 56.0 to 67.3 years) showing moderate disease activity on Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR). Test tablets containing Brazilian propolis were used in Group P (40 patients), and Brazilian propolis-free placebo tablets were used as control in Group C (40 patients). Group P received 5 tablets of propolis (508.5 mg of propolis) daily, and Group C received 5 tablets of placebo daily. The intervention lasted 24 weeks, with change in DAS28-ESR set as the primary endpoint. As secondary endpoints, other disease activity assessment (DAS28 using C-reactive protein, simplified disease activity index, clinical disease activity index), ultrasonographic evaluation of synovitis, activities of daily living, quality of life, changes in cytokine levels, and adverse events over the course of the study were also assessed. Data were statistically analyzed by analysis of covariance. RESULTS: No significant differences in the primary endpoint were identified between groups (Group P vs Group C, effect: 0.14, 95% confidence interval: -0.21 to 0.49, p = 0.427). Likewise, no significant differences were seen between groups for any secondary endpoints. The adverse event rate during the study period was 28% in Group P and 33% in Group C. CONCLUSIONS: Brazilian propolis exerted no effects on disease activity in patients with RA.

Ultrasound assessment, unlike clinical assessment, reflects enthesitis in patients with psoriatic arthritis.

OBJECTIVES: Enthesitis is a major musculoskeletal manifestation of psoriatic arthritis (PsA). It is conventionally assessed clinically, by the presence of tenderness, despite its low reliability. However, ultrasound (US) provides a sensitive and feasible method for evaluating enthesitis. We investigated enthesitis as assessed clinically and by US in patients with PsA. METHODS: Forty-seven patients with PsA underwent US examination of the bilateral humeral medial epicondyles and insertions of the triceps, distal quadriceps, proximal/distal patellae, Achilles tendons, and plantar fascia. These 14 entheses were also clinically evaluated by tenderness. The correspondence between US and clinical enthesitis was evaluated, as well as their associations with inflammatory markers (C-reactive protein [CRP], matrix metalloproteinase-3 [MMP-3]), disease activity indices (Disease Activity in Psoriatic Arthritis [DAPSA], Disease Activity Score 28 joints [DAS28-CRP], Psoriatic Arthritis Screening and Evaluation [PASE], Psoriasis Area Severity Index [PASI]), radiographic damage (modified Total Sharp Score [mTSS]), and functional status (health assessment questionnaire [HAQ]), and axial involvement. RESULTS: Among 47 patients with PsA, 37 and 23 had US and clinical enthesitis, respectively. US and clinical enthesitis had very low concordance (kappa coefficient 0.04), with no correlation between enthesitis counts (r=0.15, p=0.30). The US enthesitis count correlated only with the MMP-3 level (r=0.41, p=0.007), whereas the clinical enthesitis count correlated with the DAPSA, DAS28-CRP, HAQ, and PASE (r=0.50, p<0.001; r=0.44, p=0.002; r=0.41, p=0.008; r=0.54, p<0.001, respectively). CONCLUSIONS: US and clinical enthesitis are completely different entities. US enthesitis, but not clinical enthesitis, reflects inflammatory conditions.

Osteosarcopenia synergistically increases the risk of falls in patients with rheumatoid arthritis.

OBJECTIVES: Osteosarcopenia is defined as osteoporosis with sarcopenia. The impacts of osteosarcopenia on falls and fractures in rheumatoid arthritis (RA) patients were investigated using 4 years of data from a longitudinal study (CHIKARA study). METHODS: The patients were divided into 4 groups by their baseline status: no sarcopenia and no osteoporosis (SP-OP-); only sarcopenia (SP + OP-); only osteoporosis (SP-OP+); and both sarcopenia and osteoporosis (SP + OP+). Survival rates and Cox hazard ratios were analyzed using falls and fractures as endpoints, adjusted by age, sex, and body mass index. RESULTS: A total of 100 RA patients (SP-OP-: 44%, SP + OP-: 17%, SP-OP+: 28%, and SP + OP+: 11%) were enrolled; 37 patients had falls, and 19 patients had fractures. The fall-free and fracture-free survival rates were significantly lower in SP + OP+ (36.4%, 54.5%) than in SP-OP- (75.0%, 86.4%). The hazard ratio of falls was significantly increased in SP + OP+, by 3.32-fold (95%CI: 1.01-10.9), whereas in SP + OP- and SP-OP+, there were no differences compared to SP-OP-. CONCLUSIONS: The survival rates with the endpoints of falls and fractures in RA patients with osteosarcopenia were lower during 4-year follow-up. The risk of falls increased with the synergistic effect of osteoporosis and sarcopenia.

Relationships of the stand-up time to falls and fractures in patients with rheumatoid arthritis: Results from the CHIKARA study.

AIM: Patients with rheumatoid arthritis (RA) have a higher risk of falls and fractures due to muscle weakness and painful joints of the lower extremities. Evaluation of muscle functions is important to predict falls and fractures. The aim was to investigate the relationships of muscle functions with falls and fractures in RA patients. METHODS: Stand-up muscle power, speed, and stabilizing time were evaluated by a muscle function analyzer in 90 RA patients in the CHIKARA study (UMIN000023744). The relationships of the muscle functions with falls, fractures, body composition, Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR), modified Health Assessment Questionnaire (mHAQ) scores, Steinbrocker class, stage, sarcopenia, and frailty were investigated in a cross-sectional study. RESULTS: Each parameter of muscle function was related to age, falls, frailty, and the leg muscle score. However, only stabilizing time was related with fractures (r = .217, P = .04). When stabilizing time was ≥ 1.13 and ≥1.36 seconds, the odds ratios for falls and fractures were increased 6.2-fold compared to < 1.13 seconds (95% CI: 1.2-20.1, P = .002) and 11.4-fold compared to <1.36 seconds (95% CI: 1.7-92.5, P = .071), respectively. Sarcopenia and skeletal muscle mass were not significantly related to each muscle function. There was a negative correlation between DAS28-ESR and power. Steinbrocker class and mHAQ had negative correlations with power and speed. CONCLUSIONS: Sarcopenia and skeletal muscle mass were not adequate indicators of muscle functions in RA patients. Analyzing muscle functions is helpful to predict falls and fractures. Patients with extended stabilizing times should recognize the increased risk of falls and fractures.

Glucocorticoid use is an independent risk factor for developing sarcopenia in patients with rheumatoid arthritis: from the CHIKARA study.

INTRODUCTION: Patients with rheumatoid arthritis (RA) are at higher risk of sarcopenia because of joint dysfunction and chronic inflammation. The present study aimed to investigate the predictors or risk factors for developing sarcopenia in RA patients using the prospective observational CHIKARA database. We hypothesized that older age, higher disease activity, lower physical function, and glucocorticoid (GC) use are risk factors for sarcopenia. METHODS: A total of 100 consecutive RA patients participated in the CHIKARA study. Their body compositions were examined using a body composition analyzer. Laboratory data, disease activity, physical function, and treatment were investigated. Sarcopenia was assessed at baseline and at 1 year. Predictors or risk factors for sarcopenia development at 1 year were investigated by univariate and multivariate analyses. RESULTS: Of 68 patients without sarcopenia at baseline, 9 (13.4%) developed sarcopenia over the year. Univariate analysis showed that age (r = 0.28, p = 0.022), average GC dose over the year (r = 0.25, p = 0.043), and body mass index (r = - 0.28, p = 0.019) were significantly associated with the development of sarcopenia. Average GC use at ≥ 3.25 mg/day was a significant factor on multivariate analysis (odds ratio 8.81, 95% confidence interval 1.14-67.9, p = 0.037). CONCLUSIONS: RA patients using GCs at an average dose ≥ 3.25 mg/day over 1 year were at higher risk for developing sarcopenia. Reduction or withdrawal of GCs may prevent sarcopenia.Key Points• Patients with RA are at higher risk of sarcopenia.• Predictors or risk factors for developing sarcopenia over 1 year in RA patients were investigated using the prospective observational CHIKARA database.• RA patients using GCs at an average dose ≥ 3.25 mg/day over 1 year were at higher risk for developing sarcopenia.• Reduction or withdrawal of GCs may be essential to prevent sarcopenia.

Correlation between frailty and disease activity in patients with rheumatoid arthritis: Data from the CHIKARA study.

AIM: Frailty is defined as the degradation of physical and cognitive function in older adults. The relationship between frailty and disease activity in patients with rheumatoid arthritis is unclear. Factors related to frailty in Japanese rheumatoid arthritis patients were investigated in a cross-sectional analysis. METHODS: Of 100 patients who entered the prospective, observational Correlation research of sarcopenia, skeletal muscle and disease activity in rheumatoid arthritis (CHIKARA) study, 95 completed a frailty check list (maximal score 25), and were classified as frail (8-25 points), pre-frail (4-7 points) and normal (0-3 points). The relationship with disease activity was investigated in the frailty, pre-frailty and normal groups. Relationships between clinical variables and frailty were evaluated by univariate and multiple logistic regression analyses. RESULTS: The prevalences of frailty, pre-frailty and normal were 18.9%, 38.9% and 42.2%, respectively. The disease activity score 28 erythrocyte sedimentation rate, matrix metalloproteinase 3 and modified health assessment questionnaire were higher in the frailty group. In remission, 66.6% were normal and 6.7% had frailty, but with moderate and high disease activity, 13.3% were normal and 46.7% had frailty. On univariate analysis, factors positively related to frailty were age, locomotive syndrome, disease activity score 28 erythrocyte sedimentation rate, matrix metalloproteinase 3, use of biological disease-modifying antirheumatic drugs or targeted synthetic disease-modifying antirheumatic drugs, Steinbrocker class and modified health assessment questionnaire; and the leg muscle score and grip strength were negatively related. Matrix metalloproteinase 3 was the only independent factor on multivariate logistic analysis. In patients aged >60 years, this tendency was similar. CONCLUSIONS: Frailty was found to be related to disease activity and physical function in rheumatoid arthritis. Control of disease activity appears important to prevent frailty. Geriatr Gerontol Int 2019; 19: 1220-1225.

Matrix metalloprotease 3 is associated with sarcopenia in rheumatoid arthritis - results from the CHIKARA study.

AIM: Patients with rheumatoid arthritis (RA) show lower muscle mass and a higher prevalence of sarcopenia than healthy individuals. Correlations between sarcopenia and disease activity, physical function, laboratory data and body composition at baseline were investigated in a prospective, observational study (CHIKARA study) of RA patients. METHODS: Body composition was measured using a bioelectrical impedance analyzer. Parameters were compared between sarcopenia and non-sarcopenia groups, and correlations between sarcopenia and Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR), modified health assessment questionnaire, treatment, and laboratory data, including matrix metalloproteinase 3 (MMP3), were investigated. RESULTS: The participants were 100 patients with RA (women, 78%; mean age, 66.1 years). Mean disease duration was 5.5 years, DAS28-ESR was 3.55 and the prevalence of sarcopenia was 28%. Median C-reactive protein (CRP) and MMP3 were significantly higher in the sarcopenia group (0.21 mg/dL and 103.4 ng/mL) than in the non-sarcopenia group (0.11 mg/dL and 70.3 ng/mL). Sarcopenia was negatively correlated with weight, body mass index (BMI), muscle mass, body fat mass, estimated bone mass and basal metabolic rate, and positively correlated with Steinbrocker stage, CRP and MMP3 on univariate analyses. BMI, body fat mass and MMP3 were independently associated with sarcopenia on multivariate logistic regression analysis. When MMP3 was ≥ 90.7 ng/mL, the odds ratio for sarcopenia was increased 3.1-fold compared with < 90.7 ng/mL (P = 0.018). CONCLUSION: The prevalence of sarcopenia was 28% in patients with RA whose disease activity was mild. Low BMI, high fat mass and high MMP3 were independently associated with sarcopenia. MMP3 might be a useful marker for sarcopenia in patients with RA.

Intradural chondroma in the cervical spine: case report.

Chondromas are benign tumors that are rarely located in the spine. The authors present a rare occurrence of a spinal chondroma that developed as an intradural but extramedullary tumor in a 60-year-old woman. The location of the tumor at C4-5 was confirmed by MRI, with hyperintensity on T2-weighted images and isointensity on T1-weighted images. The tumor was completely contained intradurally, with no continuity to any vertebrae. It adhered to the anterior dura, indicative of its likely origin from the dura mater. The tumor was completely resected, with no sign of recurrence after 3 years postoperatively. Although reports of chondromas originating from the dura mater have been previously described, these have all been intracranial tumors. To the best of the authors' knowledge, this is the first report of an intradural chondroma located in the spine. Therefore, chondromas should be considered in the differential diagnosis of intradural spinal tumors.