A close association of body cell mass loss with disease activity and disability in Chinese patients with rheumatoid arthritis

OBJECTIVES: To investigate the association of body cell mass loss with disease activity and disability in rheumatoid arthritis patients. INTRODUCTION: Rheumatoid cachexia, defined as the loss of body cell mass, is important but under-recognized and contributes to morbidity and mortality in patients with rheumatoid arthritis. METHODS: One hundred forty-nine rheumatoid arthritis patients and 53 healthy, non-rheumatoid arthritis control subjects underwent anthropometric measurements of body mass index and waist and hip circumferences. Bioelectrical impedance analysis was used to determine the subjects' body compositions, including fat mass, skeletal lean mass, and body cell mass. The disease activity of rheumatoid arthritis was assessed using C-reactive protein serum, the erythrocyte sedimentation rate and the 28-joint disease activity score, while disability was evaluated using a health assessment questionnaire. RESULTS: Rheumatoid arthritis patients had lower waist-to-hip ratio (0.86 ± 0.07 vs. 0.95 ± 0.06; p<0.001) and lower skeletal lean mass indexes (14.44 ±1.52 vs. 15.18 ± 1.35; p = 0.002) than those in the healthy control group. Compared with rheumatoid arthritis patients with higher body cell masses, those with body cell masses lower than median had higher erythrocyte sedimentation rates (40.10 ± 27.33 vs. 25.09 ± 14.85; p<0.001), higher disease activity scores (5.36 ± 3.79 vs. 4.23 ± 1.21; p = 0.022) and greater disability as measured by health assessment questionnaire scores (1.26 ± 0.79 vs. 0.87 ± 0.79; p = 0.004). CONCLUSIONS: The loss of body cell mass is associated with higher disease activity and greater disability in rheumatoid arthritis patients. Body composition determined by bioelectrical impedance analysis can provide valuable information for a rheumatologist to more rapidly recognize rheumatoid cachexia in rheumatoid arthritis patients

Effects of mycophenolate mofetil on cutaneous lupus erythematosus in (NZB × NZW) F1 mice

AbstractBackgroundFew studies have evaluated the effects and precise molecular mechanism of mycophenolate mofetil (MMF) in the treatment of human cutaneous lupus erythematosus (CLE). Our findings shed light on the therapeutic effects of MMF in a UVB-induced NZB × NZW (NZBW) F1 CLE mouse model.MethodsContinuous MMF treatment (60 mg/kg/day) was administered up to Day 50 from the beginning of UVB induction (Day 0; 20 weeks old), as the pathologic features of CLE are present after 50 days. The therapeutic effects of MMF treatment in NZBW lupus mice were examined by comparing histopathological changes, lupus band test (deposition of immune complexes at the dermal–epidermal junction) and colocalization of autoantibodies with a dermal autoantigen Dsg3, and by evaluating the associations of local matrix metalloprotease activities.ResultsMMF improved survival in the NZBW lupus mice from 35.7% to 81.8%. The proteinuria, blood urea nitrogen, and interleukin 6 levels were significantly reduced after MMF treatment. The dermal lymphocytic infiltration, deposition of immune complexes at the dermal–epidermal junction, colocalized autoantibodies with Dsg3, and epidermal matrix metalloprotease activity were also attenuated in MMF-treated NZBW F1 mice.ConclusionThe results confirmed that MMF could substantially attenuate skin damage due to CLE in the NZBW F1 mouse model

Estimation of life expectancy and healthcare cost in rheumatoid arthritis patients with and without depression: a population-based retrospective cohort study

PurposeThis study aimed to estimate the lifetime healthcare costs and loss of life expectancy (loss-of-LE) among patients with incident rheumatoid arthritis (RA) with and without depression.MethodsThis 18 years longitudinal cohort study used data from Taiwan’s National Health Insurance Research Database. In total, 43,311 patients with RA were included. Among them, 1,663 patients had depressive disorders in the year preceding the RA diagnosis. The survival function for patients with RA with or without depression was estimated and extrapolated over a lifetime using the rolling extrapolation algorithm. The loss-of-LE was calculated by comparing the sex, age, and calendar year-matched referents from vital statistics. The average monthly cost was calculated as the sum of the monthly costs for all patients divided by the number of surviving patients. Lifetime healthcare costs were estimated by multiplying the monthly average cost by the monthly survival probability.ResultsThe loss-of-LE for RA patients with and without depression was 5.60 years and 4.76 years, respectively. The lifetime costs of RA patients with and without depression were USD$90,346 and USD$ 92,239, respectively. However, the annual healthcare costs were USD$4,123 for RA patients with depression and USD$ 3,812 for RA patients without depression. Regardless of sex or age, RA patients with depression had higher annual healthcare costs than those without depression.ConclusionPatients with RA and depression have a high loss-of-LE and high annual healthcare costs. Whether treating depression prolongs life expectancy and reduces healthcare costs warrants further investigation

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ABSTRACT. Objective. To examine (1) the risk of death from cardiovascular disease (CVD) and from all causes in patients with gout who do not undergo urate-lowering therapy (ULT), and (2) the effect of ULT on mortality risk in patients with gout. Methods. In this prospective case-matched cohort study, 40,623 Taiwanese individuals aged ≥ 17 years were followed for 6.5 years. Mortality rate was compared between 1189 patients with gout who did not receive ULT and reference subjects (no gout, no ULT) matched for age, sex, and the index date of gout diagnosis (1:3 patients with gout/reference subjects), and between 764 patients with gout who received ULT and 764 patients with gout who did not receive ULT matched 1-to-1 based on their propensity score and the index date of ULT prescription

Blood lipid profiles and peripheral blood mononuclear cell cholesterol metabolism gene expression in patients with and without methotrexate treatment

<p>Abstract</p> <p>Background</p> <p>Methotrexate (MTX) is the most commonly prescribed disease-modifying antirheumatic drug (DMARD) in rheumatoid arthritis. ATP-binding cassette transporter-A1 (ABCA1) and 27-Hydroxylase (HY27) are known antiatherogenic proteins that promote cellular cholesterol efflux. In THP-1 macrophages, MTX can promote the reversal of cholesterol transport, limit foam cell formation and also reverse COX-2 inhibitor-mediated downregulation of ABCA1. Despite its antiatherogenic potential <it>in vitro</it>, the impact of clinical use of low-dose MTX on cholesterol metabolism in humans is unknown. Objective of the study was to examine whether clinical MTX use is associated with altered blood lipids and/or <it>ABCA1/HY27 </it>expressions.</p> <p>Methods</p> <p>In all, 100 rheumatoid arthritis subjects were recruited from a medical center in central Taiwan. Plasma lipid profiles and peripheral blood mononuclear cell <it>HY27 </it>and <it>ABCA1 </it>expressions were compared between subjects taking MTX (MTX+) and other disease-modifying antirheumatic drugs (DMARDs) (MTX-). Dietary intake was assessed by a registered dietician.</p> <p>Results</p> <p>Though no difference observed in the blood lipids between MTX+ and MTX- subjects, the expressions of <it>ABCA1 </it>and <it>HY27 </it>were significantly elevated in MTX+ subjects (n = 67) compared to MTX- subjects (n = 32, p < 0.05). ABCA expression correlated with MTX doses (r = 0.205, p = 0.042), and MTX+ subjects are more likely to have increased <it>HY27 </it>compared to MTX- subjects (OR = 2.5, p = 0.038). Prevalence of dyslipidemia and overweight, and dietary fat/cholesterol intake were lower than that of the age-matched population. Although no differences were observed in the blood lipids, the potential impacts of MTX on cholesterol metabolism should not be overlooked and the atheroprotective effects from MTX induced <it>HY27 </it>and <it>ABCA1 </it>expressions may still be present in those persons with pre-existing dyslipidemia.</p> <p>Conclusions</p> <p>We demonstrated novel findings on the increased gene expressions of atheroprotective protein <it>HY27 </it>and <it>ABCA1 </it>in human peripheral blood mononuclear cells (PBMCs) with clinical use of low-dose MTX. Whether MTX induced <it>HY27 </it>and <it>ABCA1 </it>expressions can protect against cardiovascular disease in patients with chronic inflammation through the facilitation of cholesterol export remains to be established. Further studies on the impacts of low-dose MTX on hypercholesterolemic patients are underway.</p

Late-onset and Rare Far-advanced Pulmonary Involvement in Patients with Sarcoidosis in Taiwan

Sarcoidosis is still considered a rare multisystem disorder in Taiwan, and data on the disease course and outcome are limited. We analyzed the clinical manifestations, disease course and complications in Taiwanese patients with sarcoidosis. Methods: A retrospective cohort design was used. Fifty-six patients with sarcoidosis diagnosed between 1985 and 2004 were included. Their clinical features, laboratory findings at initial presentation, disease course, and complications were analyzed. Results: Forty-three patients (76.8%) were female. The mean age at symptom onset was 47 years. The most common clinical symptoms were pulmonary (82.1%), cutaneous (23.2%), ophthalmic (19.6%), and articular (17.8%). Only two patients presented with Löfgren's syndrome. There was a seasonal variation in disease onset, with higher incidence in winter and early spring. No advanced pulmonary involvement was noted. Elevated levels of serum angiotensin converting enzyme (sACE) were found in 72.5% (29/40) of patients with active sarcoidosis, and significantly higher levels of sACE were found in patients with lung involvement (27.98 ± 1.71 IU/L vs. 18.2 ± 2.76 IU/L; p < 0.01). In 50% (20/40) of patients, sACE levels declined significantly in parallel with clinical remission (24.75 ± 1.53 IU/L vs. 16.33 ± 1.21 IU/L; p < 0.05). Spontaneous complete remission was found in 20.7% of patients, whereas 39.6% of patients with multiple extrapulmonary involvement responded poorly to intensive corticosteroids plus various immunosuppressants. Conclusion: In this series, the mean age of disease onset was in middle age (mean, 47 years old), there was a low incidence of Löfgren's syndrome (3.6%), and no patients had advanced pulmonary syndrome. The results of this study also suggest that sACE might be a marker of pulmonary involvement that is also useful in monitoring disease activity

sj-docx-1-taj-10.1177_20406223231168488 – Supplemental material for Lifetime risk, life expectancy, loss-of-life expectancy, and lifetime healthcare expenditures for psoriasis in Taiwan: a nationwide cohort followed from 2000 to 2017

Supplemental material, sj-docx-1-taj-10.1177_20406223231168488 for Lifetime risk, life expectancy, loss-of-life expectancy, and lifetime healthcare expenditures for psoriasis in Taiwan: a nationwide cohort followed from 2000 to 2017 by Hsien-Yi Chiu, Joung-Liang Lan and Ying-Ming Chiu in Therapeutic Advances in Chronic Disease</p

Elevated Expression of C-Type Lectin Domain Family 5-Member A (CLEC5A) and Its Relation to Inflammatory Parameters and Disease Course in Adult-Onset Still’s Disease

C-type lectin domain family 5-member A (CLEC5A) associates with adaptor DAP12 (DNAX activation protein 12) to form receptor complexes involved in inflammatory responses. We postulated a potential role of CLEC5A in the pathogenesis of adult-onset Still’s disease (AOSD) and aimed to investigate CLEC5A expression and its association with activity parameters and disease course. In 34 AOSD patients and 12 healthy controls (HC), circulating levels of CLEC5A-expressing monocytes or granulocytes were determined by flow cytometry analysis, the mRNA expression of CLEC5A and DAP12 on PBMCs by quantitative PCR, and plasma levels of proinflammatory cytokines by ELISA. AOSD patients had significantly higher percentages and mean fluorescence intensity (MFI) of CLEC5A-expressing monocytes (median 62.1% and 3.20, respectively) or granulocytes (72.6% and 3.22, respectively) compared with HC (in monocytes: 17.0% and 0.65, both p<0.001; in granulocytes: 67.3%, p<0.05 and 0.90, p<0.001; respectively). Patients also had significantly higher levels of CLEC5A mRNA expression on PBMCs compared with HC (median 1.77 vs. 0.68, p<0.05). The levels of CLEC5A-expressing monocytes or granulocytes were positively associated with activity scores and levels of IL-1β and IL-18 in AOSD patients. The patients with a systemic pattern had significantly higher levels of CLEC5A-expressing granulocytes and IL-18 compared to those with a chronic articular pattern of disease course. After 6 months of therapy, levels of CLEC5A-expressing monocytes and granulocytes significantly declined, paralleling the decrease of AOSD activity. Elevated CLEC5A levels and their positive association with activity parameters suggest that CLEC5A is involved in the pathogenesis and may serve as an activity indicator of AOSD

Th17-related cytokines in systemic lupus erythematosus patients with dilated cardiomyopathies: a possible linkage to parvovirus B19 infection.

Dilated cardiomyopathies (DCM) are a major cause of mortality in patients with systemic lupus erythematosus (SLE). Immune responses induced by human parvovirus B19 (B19) are considered an important pathogenic mechanism in myocarditis or DCM. However, little is known about Th17-related cytokines in SLE patients with DCM about the linkage with B19 infection. IgM and IgG against B19 viral protein, and serum levels of Th17-related cytokines were determined using ELISA in eight SLE patients with DCM and six patients with valvular heart disease (VHD). Humoral responses of anti-B19-VP1u and anti-B19-NS1 antibody were assessed using Western blot and B19 DNA was detected by nested Polymerase Chain Reaction (PCR). Levels of interleukin (IL)-17, IL-6, IL-1β, and tumor necrosis factor (TNF)-α were significantly higher in SLE patients with DCM (mean ± SEM, 390.99±125.48 pg/ml, 370.24±114.09 pg/ml, 36.01±16.90 pg/ml, and 183.84±82.94 pg/ml, respectively) compared to healthy controls (51.32±3.04 pg/ml, p<0.001; 36.88±6.64 pg/ml, p<0.001; 5.39±0.62 pg/ml, p<0.005; and 82.13±2.42 pg/ml, p<0.005, respectively). Levels of IL-17 and IL-6 were higher in SLE patients with DCM versus those with VHD (both p<0.01). Five (62.5%) of DCM patients had detectable anti-B19-NS1 IgG and four (50.0%) of them had anti-B19-VP1u IgG, whereas only one (16.7%) of VHD patients had detectable anti-B19-NS1 IgG and anti-B19-VP1u IgG. Serum levels of IL-17, IL-6 and IL-1β were markedly higher in SLE patients with anti-B19-VP1u IgG and anti-B19-NS1 IgG compared to those without anti-B19-VP1u IgG or anti-B19-NS1 IgG, respectively. These suggest a potential association of B19 with DCM and Th17-related cytokines implicated in the pathogenesis of DCM in SLE patients