Comparison of bone structure and microstructure in the metacarpal heads between patients with psoriatic arthritis and healthy controls: an HR-pQCT study.

Human cadaveric study has indicated that the metacarpal head (MCH) is intracapsular in location. We hypothesized that exposure to the intra-articular inflammatory milieu in psoriatic arthritis (PsA) will lead to bone loss in the MCH. INTRODUCTION: To compare the bone structure and microstructure in the MCH between patients with PsA and healthy controls by high-resolution peripheral quantitative CT (HR-pQCT), and to ascertain factors associated with bone loss in PsA patients. METHODS: Sixty-two PsA patients without joint destruction and 62 age-, gender-, and body mass index-matched healthy subjects underwent HR-pQCT imaging of the second and third MCH (MCH 2&3). The number and volume of bone erosion and enthesiophytes, as well as volumetric bone mineral density (vBMD) and microstructure at the MCH 2&3, were recorded. Correlation analysis and multivariable linear regression models were used to determine the association of demographic and disease-specific variables with compromised bone structure and microstructure in PsA. RESULTS: At the MCH 2&3, bone erosion (p = 0.003) and enthesiophyte (p = 0.000) volumes in PsA patients were significantly larger than healthy controls. In PsA patients, older age was associated with a larger erosion and enthesiophyte volume. Concerning the mean vBMD and microstructure at the MCH 2&3, PsA patients had significantly lower mean vBMD (average vBMD - 6.9%, trabecular vBMD - 8.8%, peri-trabecular vBMD - 7.7%, meta-trabecular vBMD - 9.8%), trabecular bone volume fraction (- 8.8%), and trabecular thickness (- 8.1%) compared with control subjects. Multivariable regression analysis revealed that older age and a higher C-reactive protein level were associated with trabecular bone loss. CONCLUSIONS: PsA patients had a higher burden of bone damages (erosions and enthesiophytes) and trabecular bone loss compared with healthy control at the MCH. Inflammation contributed to the deterioration in trabecular microstructure in these patients.

Solitary bees reduce investment in communication compared with their social relatives.

Social animals must communicate to define group membership and coordinate social organization. For social insects, communication is predominantly mediated through chemical signals, and as social complexity increases, so does the requirement for a greater diversity of signals. This relationship is particularly true for advanced eusocial insects, including ants, bees, and wasps, whose chemical communication systems have been well-characterized. However, we know surprisingly little about how these communication systems evolve during the transition between solitary and group living. Here, we demonstrate that the sensory systems associated with signal perception are evolutionarily labile. In particular, we show that differences in signal production and perception are tightly associated with changes in social behavior in halictid bees. Our results suggest that social species require a greater investment in communication than their solitary counterparts and that species that have reverted from eusociality to solitary living have repeatedly reduced investment in these potentially costly sensory perception systems.

Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine, for patients with osteoarthritis of the knee: a multi-site, randomized, double-blind, placebo-controlled phase II clinical trial.

OBJECTIVE: To examine the efficacy and safety of Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine (TCM), in patients with knee osteoarthritis (OA). DESIGN: A multi-site, randomized, double-blind, placebo-controlled phase II dose-escalation clinical trial was conducted. Eligible patients who fulfilled American College of Rheumatology criteria were randomized to receive either HLXL or placebo. Clinical assessments included measurement of knee pain and function with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), patient global assessment (PGA), and knee pain scores every 2 weeks. A Data and Safety Monitoring Board (DSMB) was established to review the data for ensuring the quality of the trial. RESULTS: In the first stage, 28 participants were randomized to receive either low-dose HLXL-Dan (2400 mg/day) or placebo for 6 weeks. The results showed no statistical difference between the two groups. The study was then re-designed following the recommendation of DSMB. Ninety-two patients were enrolled in the second stage and were randomized to receive either high-dose HLXL-Dan (4000 mg/day for week 1-2, and 5600 mg/day for week 3-8) or placebo for 8 weeks. All outcome assessments showed significant improvements for both groups after 8 weeks but no significant between-group differences. The change (mean ± SD) of WOMAC pain and WOMAC function scores of HLXL and placebo group after 8 weeks were -1.2 ± 1.7 vs -1.4 ± 1.5, and -1.1 ± 1.6 vs -1.3 ± 1.5 respectively. No serious adverse events were reported. CONCLUSION: Although safe to use, an 8-week treatment of HLXL-Dan was not superior to placebo for reduction in pain or functional improvement in patients with knee OA. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov (NCT00755326).

Density, structure, and strength of the distal radius in patients with psoriatic arthritis: the role of inflammation and cardiovascular risk factors.

UNLABELLED: We investigated the densitometric and microstructural features of the distal radius in psoriatic arthritis (PsA) patients using high-resolution peripheral quantitative computed tomography. PsA patients have unique bone microstructural deficits, manifested as lower cortical bone density and higher cortical porosity, which are associated with a propensity to bone fragility. INTRODUCTION: The aim of this study was to investigate the densitometric, geometric, microstructural, and biomechanical features of the distal radius in psoriatic arthritis (PsA) patients. METHODS: This study cohort consisted of 53 PsA patients (24 males and 29 females), with an average age of 53.1 years and 53 gender- and age-matched controls. Areal bone mineral density (aBMD) of the hip, lumbar spine, and ultradistal radius was measured by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed at the distal radius to obtain measures of volumetric BMD (vBMD), microstructure, and derived biomechanical indices. RESULTS: There were no significant between-group differences in aBMD at the femoral neck, total hip, and ultradistal radius, while aBMD at the lumbar spine was significantly higher in patients. The only indices indicating compromised bone quality in PsA patients were related to cortical bone quality. Cortical vBMD were -3.8% significantly lower, while cortical pore volume, porosity index, and pore diameter were 108, 79.5, and 8.6%, respectively, significantly higher in patients. Cortical stress was marginally lower (-1.3%, p = 0.077) in patients with stress significantly more unevenly distributed (4.9%, p = 0.035). Endocortical perimeter and cortical pore volume were significantly higher in patients with vertebral fracture. Deficits in cortical bone quality were associated with indices of disease activity/severity and were more prominent in patients with type 2 diabetes mellitus or hypertension. CONCLUSIONS: There is an intertwined relationship between chronic inflammation, cardiovascular risk factors, and bone loss in PsA. PsA patients seem to have unique bone microstructural deficits which are associated with a propensity to bone fragility.

Cortical thinning and progressive cortical porosity in female patients with systemic lupus erythematosus on long-term glucocorticoids: a 2-year case-control study.

UNLABELLED: In this study, we characterized longitudinal changes of volumetric bone mineral density and cortical and trabecular microstructure at the distal radius using HR-pQCT in female systemic lupus erythematosus (SLE) patients on long-term glucocorticoids. Cortical thinning and increased cortical porosity are the major features of longitudinal microstructural deterioration in SLE patients. INTRODUCTION: The study aims to characterize longitudinal changes of volumetric bone mineral density (vBMD) and bone microstructure at distal radius in female systemic lupus erythematosus (SLE) patients on long-term glucocorticoids. METHODS: This 2-year case-control study consisted of 166 premenopausal subjects (75 SLE patients and 91 controls) and 79 postmenopausal subjects (44 SLE patients and 35 controls). We obtained areal BMD (aBMD) by dual-energy X-ray absorptiometry at multiple skeletal sites and indices of vBMD and microstructure at distal radius by high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline, 12 and 24 months. RESULTS: In either premenopausal or postmenopausal subjects, changes in aBMD did not differ between patients and controls except that decrease in aBMD at total hip at 24 months in premenopausal patients was significantly higher. In premenopausal subjects, decrease in cortical area (-0.51 vs. -0.06 %, p = 0.039) and thickness (-0.63 vs. 0.02 %, p = 0.031) and increase in cortical porosity (21.7 vs. 7.16 %, p = 0.030) over study period were significantly larger in patients after adjustment of age and body mass index. Decreased in trabecular vBMD was significantly less (-0.63 vs. -2.32 %, p = 0.001) with trabecular microstructure better maintained in patients. In postmenopausal subjects, decrease in cortical vBMD (-2.66 vs. -1.56 %, p = 0.039) and increase in cortical porosity (41.6 vs. 16.3 %, p = 0.021) were significantly higher in patients, and there was no group-wise difference in change of trabecular microstructure. CONCLUSION: Longitudinal microstructural deterioration in SLE is characterized by cortical thinning and increased cortical porosity. Cortical bone is an important source of bone loss in SLE patients on glucocorticoids.

Members of the receptor for advanced glycation end products axis as potential therapeutic targets in patients with lupus nephritis.

The relationship of inflammation and the expression of full-length receptor for advanced glycation end products (flRAGE) on monocytes, plasma levels of RAGE ligand high mobility group box protein 1 (HMGB1), soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) was assessed to elucidate the effect of HMGB1/DNA/RAGE-mediated innate inflammatory responses in patients with lupus nephritis. Cell surface expression of flRAGE was elevated on the monocytes of lupus patients, correlated with plasma HMGB1 levels. Plasma sRAGE level negatively correlated with systemic lupus erythematosus (SLE) disease activity index. Plasma esRAGE level was significantly lower in SLE patients with flare while esRAGE/sRAGE ratio negatively correlated with complement C3 level. HMGB1 alone could moderately induce ex vivo IL-6 production from monocytes, resulting in activation of intracellular p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase and nuclear factor (NF)-κB. Moreover, toll-like receptor-9 ligand together with HMGB1 exhibited a synergistic effect on IL-6 and IL-12p70 secretions and the phosphorylation of p38 MAPK and NF-κB. Therefore, over-expression of flRAGE in lupus may lead to the amplification of RAGE ligands-mediated inflammatory responses through the activation of p38 MAPK and NF-κB. Plasma sRAGE may serve as a potential biomarker for disease activity and a future therapeutic target in SLE.

Incidence of and risk factors for non-vertebral and vertebral fracture in female Chinese patients with systemic lupus erythematosus: a five-year cohort study.

OBJECTIVE: The objective of this paper is to investigate the incidence of both non-vertebral and vertebral fracture in female patients with systemic lupus erythematosus (SLE) and to identify risk factors for incident fracture. METHODS: In a five-year prospective study of 127 female Chinese SLE patients with an average age of 46.9 years (SD: 10.1 years), information on potential risk factors, including demographics, clinical data and bone mineral density (BMD) at lumbar spine and hip by dual-energy X-ray absorptiometry was collected at baseline. At follow-up, participants reported incident non-vertebral fracture during the study period. Semi-quantitative analysis was used to determine incident vertebral fracture on lateral thoracic and lumbar radiographs, defined as any vertebral body graded normal at baseline and at least mildly deformed (20%-25% reduction or more in any vertebral height) at follow-up. RESULTS: Nine incident non-vertebral fractures occurred in eight patients during the study period. Six patients had one or more incident vertebral fractures. The incidence of non-vertebral and vertebral fracture was 1.26 and 0.94 per 100 patient-years, respectively. In multivariate logistic analyses, independent variables associated with incident non-vertebral fracture were duration of glucocorticoid use and prevalent lumbar spine osteoporosis, while risk factors associated with incident vertebral fracture were higher organ damage and prevalent lumbar spine osteoporosis. CONCLUSIONS: The incidence of fracture in SLE patients is lower than the prevalence reported in cross-sectional studies. Lumbar spine BMD appears to have a stronger relationship with incident fracture than hip BMD. This warrants further investigation regarding the optimal site of BMD measurement when predicting fracture risk in SLE patients.

Alterations of bone geometry, density, microarchitecture, and biomechanical properties in systemic lupus erythematosus on long-term glucocorticoid: a case-control study using HR-pQCT.

UNLABELLED: Compared to controls, HR-pQCT at distal radius of SLE patients on chronic glucocorticoid (SLE/GC) revealed reduced bone area, vBMD, deteriorated microarchitecture, and unevenly distributed stresses limited to cortical bone. Despite similar trabecular quality, whole bone strength decreased in patients. These alterations may partly explain high fracture rates in SLE/GC. INTRODUCTION: To assess bone geometric, densitometric, microarchitectural, and biomechanical properties in patients with systemic lupus erythematosus (SLE) on long-term glucocorticoid (GC) (SLE/GC) as compared with healthy controls. METHODS: A total of 180 female SLE patients and 180 healthy controls were in this cross-sectional study to assess areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) and microfinite element analysis (µFEA) was performed at distal radius. RESULTS: In addition to significantly lower aBMD at femoral neck, total hip and lumbar spine, cortical area, average volumetric BMD (vBMD) and cortical vBMD also significantly reduced by 5.3, 5.7, to 1.9 % in SLE patients, respectively. Deteriorations of cortical microarchitecture were pronounced in patients, with 6.3 % reduction in cortical thickness and 13.6 % higher in cortical porosity. Local stresses were more unevenly distributed through cortical bone in patients. SLE/GC patients had decreased whole bone stiffness, estimated failure load, and apparent modulus. Parameters related to trabecular bone density and microarchitecture were comparable between patients and controls. CONCLUSION: In SLE/GC patients, despite a reduction in bone area, vBMD and deteriorated microarchitecture and unevenly distributed stresses limited to the cortical compartment, whole bone strength decreased. HR-pQCT and µFEA were promising in elucidating the potential underlying pathophysiology of bone loss and propensity to fracture in SLE/GC and provide us additional information about alterations of bone quality which might better predict fracture risk beyond aBMD in SLE/GC.

SLE disease per se contributes to deterioration in bone mineral density, microstructure and bone strength.

OBJECTIVE: The objective of this report is to assess the effect of systemic lupus erythematosus (SLE) disease itself on deterioration of bone mineral density (BMD), microstructure and bone strength. METHOD: Thirty age-matched SLE patients on long-term glucocorticoids (GC) (SLE/GC), 30 SLE patients without GC (SLE/non-GC) and 60 healthy controls were examined. Areal BMD (aBMD) was measured by dual-energy X-ray absorptiometry. Bone geometry, volumetric BMD (vBMD), and architectural parameters at the nondominant distal radius were assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). Bone strength was estimated by HR-pQCT-based micro-finite element analysis. RESULTS: Adjusted for menopausal status and adjusted calcium level, when compared with controls, SLE/non-GC patients had significantly lower aBMD at femoral neck and total hip, and diminished radial total vBMD, cortical area, vBMD and thickness, respectively, by 8.3%, 8%, 2.7% and 9.2%, as well as significant compromised bone strength (stiffness, failure load and apparent modulus) by 8.3%, 9.1% and 9.5%, respectively. Similar alterations were also found in SLE/GC patients when compared to controls. In the premenopausal subgroup analysis, when compared with controls, total hip aBMD and radial cortical area were significantly lower in SLE/non-GC patients, and cortical area and thickness were significantly deficit in SLE/GC patients. However, no significant difference in any bone variables was present between SLE/GC and SLE/non-GC patients in the entire cohort or in the premenopausal subgroup. CONCLUSION: SLE disease per se contributes to the deterioration in bone density, cortical microstructure and bone strength. This might help to explain the considerably higher fracture risk seen in SLE patients.

Urinary sediment ICAM-1 level in lupus nephritis.

BACKGROUND: Urinary intercellular adhesion molecule-1 (ICAM-1) level is potentially a valuable biomarker of lupus nephritis (LN), but because ICAM-1 is a cell-surface molecule, soluble ICAM-1 level in urinary supernatant measured by ELISA may not be biologically relevant. METHODS: The ICAM-1 level in urine sediment of 12 LN patients, 10 patients with pauci-immune necrotizing glomerulonephritis (NecGN), and six healthy controls were determined with a polymerase chain reaction (PCR)-based assay. The urinary sediment levels of miR-221, miR-222, miR-339-3P and miR-339-5P, which are involved in the regulation of ICAM-1 production, were also quantified. RESULTS: LN patients had lower urinary sediment ICAM-1 levels than the other two groups (overall p = 0.034). In addition, urinary sediment ICAM-1 level inversely correlated with the estimated glomerular filtration rate (GFR) (r = -0.474, p = 0.026) but not other markers of lupus activity, or urinary sediment levels of miR-221, miR-222, miR-339-3P, or miR-339-5P. However, serum anti-dsDNA level inversely correlated with urinary sediment levels of miR-221 (r = -0.591, p = 0.043) and miR-222 (r = -0.689, p = 0.013), while urinary sediment miR-221 level also correlated with serum C3 level (r = 0.658, p = 0.02). CONCLUSIONS: We conclude that urinary sediment ICAM-1 level was significantly reduced in LN, and the level inversely correlated with renal function. Urinary sediment miR-221 and miR-222 levels correlate with lupus disease activity and may serve as biomarkers of LN.

SLICC/ACR damage index independently associated with left ventricular diastolic dysfunction in patients with systemic lupus erythematosus.

Left ventricular (LV) diastolic dysfunction has been reported in both active and inactive systemic lupus erythematosus (SLE) patients without clinical evidence of cardiovascular disease. However, the relationship between the long-term inflammatory burden reflected by the SLICC/ACR damage index and LV diastolic function has not been studied. Eighty-two SLE patients and 82 controls matched for age, sex, body mass index, blood pressure and heart rate underwent echocardiography with tissue Doppler imaging (TDI). LV diastolic function was estimated by the myocardial early diastolic velocity (E') at the lateral annulus. There were 51 patients (62.2%) with nephritis, 23 patients (28.0%) with hypertension, 21 patients (25.6%) with vasculitis, 16 patients (19.5%) with pulmonary hypertension, 4 patients (4.9%) with cerebrovascular disease and 2 patients (2.4%) with diabetes mellitus. Sixty-two patients (75.6%) were taking prednisone and 35 patients (42.7%) used a immunosuppressant. Forty-five patients (54.8%) had active disease and suffered from disease-related end-organ damage. Patients with SLICC/ACR damage index ≥1 had more evidence of LV diastolic dysfunction with lower lateral annulus E' (9.6 ± 3.4 vs 12.9 ± 3.5 cm/s, p < 0.001) than those without. In addition, the proportion of patients with abnormal LV myocardial relaxation (defined as lateral E' < 10.0 cm/s) (51.1% vs 16.2%, χ(2) = 10.8, p = 0.001) were significantly higher. Multivariate analysis showed that the SLICC/ACR damage index ≥1 was independently associated with LV diastolic dysfunction (OR = 3.80, 95%CI: 1.21-11.95, p = 0.023) after adjusting for hypertension, disease duration and medical therapy. This may suggest that the overall inflammatory burden in SLE, as reflected by SLICC/ACR damage index, is associated with the development of diastolic dysfunction in SLE patients.

Serum and urinary free microRNA level in patients with systemic lupus erythematosus.

MicroRNAs circulating in body fluid have been suggested as biomarkers of various diseases. We studied the serum and urinary level of several miRNA species (miR-200 family, miR-205 and miR-192) in patients with systemic lupus erythematosus (SLE). We studied 40 SLE patients. Serum and urinary miRNA levels were determined and compared with that of healthy controls. The serum levels of miR-200a, miR-200b, miR-200c, miR-429, miR-205 and miR-192, and urinary miR-200a, miR-200c, miR-141, miR-429 and miR-192 of SLE patients were lower than those of controls. Glomerular filtration rate (GFR) correlated with serum miR-200b (r = 0.411, p = 0.008), miR-200c (r = 0.343, p = 0.030), miR-429 (r = 0.347, p = 0.028), miR-205 (r = 0.429, p = 0.006) and miR-192 (r = 0.479, p = 0.002); proteinuria inversely correlated with serum miR-200a (r = -0.375, p = 0.017) and miR-200c (r = -0.347, p = 0.029). SLE disease activity index (SLEDAI) inversely correlated with serum miR-200a (r = -0.376, p = 0.017). Serum miR-200b (r = 0.455, p = 0.003) and miR-192 (r = 0.589, p < 0.001) correlated with platelet count, while serum miR-205 correlated with red cell count (r = 0.432, p = 0.005) and hematocrit (r = 0.370, p = 0.019). These pilot results suggested that miRNA may take part in the pathogenesis of SLE. Further studies are needed to validate the role of serum miRNA as a biomarker of SLE.

Effects of rosuvastatin on subclinical atherosclerosis and arterial stiffness in rheumatoid arthritis: a randomized controlled pilot trial.

OBJECTIVE: To ascertain the effect of rosuvastatin on carotid atherosclerosis and arterial stiffness in patients with rheumatoid arthritis (RA). METHODS: Fifty RA patients were randomized in a double-blind placebo-controlled trial to receive 10 mg rosuvastatin (n = 24) or placebo (n = 26). Patients were followed prospectively every 3 months for 12 months. Intima-media thickness (IMT), augmentation index (AIx), and subendocardial viability ratio (SEVR) were measured at baseline, 6 and 12 months. RESULTS: Rosuvastatin resulted in statistically significant reductions of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and urate levels vs. placebo. However, rosuvastatin had no significant effect on changes in inflammatory markers, including C-reactive protein (CRP) levels [from 2.9 (1.4-11.0) to 3.1 (0.9-13.3) mg/L in the rosuvastatin group compared with from 5.8 (2.6-14.2) to 4.4 (1.2-12.3) mg/L in the placebo group]. Nonetheless, a significant improvement in the Disease Activity Score (DAS) and a reduction in fibrinogen level was observed at 6 and 12 months compared with baseline in the rosuvastatin group. The treatment group exhibited a significant increase in SEVR (from 157 ± 28% to 163 ± 33% in the rosuvastatin group compared with from 143 ± 18% to 143 ± 26% in the placebo group, p = 0.023), but no significant effect was observed in the changes in IMT and AIx. CONCLUSION: Our data suggest that rosuvastatin has a modest anti-inflammatory effect in RA patients with low disease activity in terms of reduction in DAS and fibrinogen level. Rosuvastastin may also improve subendocardial perfusion and lower the urate level.

Activation profile of Toll-like receptors of peripheral blood lymphocytes in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with aberrant activation of T and B lymphocytes for the production of inflammatory cytokines and autoreactive antibodies. Animal studies of SLE have indicated that Toll-like receptors (TLR) are important in the pathogenesis of murine lupus. In the present clinical study, differential protein expressions of TLR-1-9 of monocytes and different lymphocyte subsets from patients with SLE and normal control subjects were determined by flow cytometry. Results showed that the expression of intracellular TLRs (TLR-3, -8, -9) and extracellular TLRs (TLR-1, -2, -4, -5, -6) were elevated in monocytes, CD4(+) T lymphocytes, CD8(+) T lymphocytes and B lymphocytes of SLE patients compared to control subjects (all P < 0.001). Moreover, cell surface expression of TLR-4 on CD4(+) T lymphocytes and CD8(+) T lymphocytes, and TLR-6 on B lymphocytes, were correlated positively with SLE disease activity index (SLEDAI) (TLR-4 on CD4(+) T lymphocytes and CD8(+) T lymphocytes: r = 0.536, P = 0.04; r = 0.713, P = 0.003; TLR-6 in B lymphocytes: r = 0.572, P = 0.026). In concordance with the above results, there is an observable increased relative induction (%) of inflammatory cytokine interleukin (IL)-1beta, IL-6, IL-10 and IL-12, chemokines CCL2, CXCL8, CCL5 and CXCL10 from peripheral blood mononuclear cells (PBMC) upon differential stimulation by PolyIC (TLR-3 ligand), lipopolysaccharide (TLR-4 ligand), peptidoglycan (TLR-2 ligand), flagellin (TLR-5 ligand), R837 (TLR-7 ligand) and CpG DNA (TLR-9 ligand) in SLE patients compared to controls. These results suggest that the innate immune response for extracellular pathogens and self-originated DNA plays immunopathological roles via TLR activation in SLE.

Lupus organ damage: what is damaged in Asian patients?

Assessment of organ damage has become the standard outcome measure for morbidity and mortality in patients with lupus. Ethnicity is thought to be a marker for genetic, environmental, behavioral, and other variables that may affect disease outcomes. Previous studies suggest that Asians residing in western countries had significantly higher prevalence of damage compared with Whites. In contrast, studies performed in Chinese, Korean and Arab patients showed that the overall prevalence of damage and the most commonly involved organs (neuropsychiatric and musculoskeletal) were similar to Whites. Compared with their Asian counterparts, Pakistani and Jewish patients appeared to have a higher prevalence of damage, most likely secondary to longer disease duration. Chinese patients had an increased prevalence of premature gonadal failure, whereas patients residing in western and southern Asia had more skin damage. When compared with Whites, Asian patients had more renal damage but less ocular and cardiovascular damage. Risk factors associated with organ damage in Asian lupus patients included older age, higher disease activity, and the use of cyclophosphamide and steroids. Further investigations into other determinants such as genetic predisposition, socioeconomic factors, prevalence and severity of disease manifestations, and treatment, is needed in order to understand the variation in damage accrual in lupus patients from different ethnicities.

Risk of tuberculosis in patients with rheumatoid arthritis in Hong Kong--the role of TNF blockers in an area of high tuberculosis burden.

OBJECTIVES: To elucidate the incidence rate and relative risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) compared to the general population in Hong Kong between 2004 and 2008, and to assess whether this risk is associated with exposure to tumour necrosis factor (TNF) blockers after adjusting for other known risk factors. METHODS: We reviewed all the medical records of RA patients to determine the standardised incidence ratio (SIR) of TB in RA patients. Independent explanatory variables associated with active TB in RA were ascertained using the Cox regression model. RESULTS: A total of 2441 RA patients followed at the 5 centres were recruited. The mean age at the start of follow up was 56±14 years. The median follow-up duration was 6,616 and 185 patient-years for the TNF naive and TNF treated groups, respectively. Compared to age- and sex-matched population controls, the SIR of active TB in RA was significantly increased (SIR for TNF naïve RA: 2.35, 95% CI 1.17-4.67, p=0.013, SIR for TNF treated RA: 34.92, 95% CI 8.89-137.20, p<0.001). Independent explanatory variables associated with an increase risk of active TB included older age at study entry (RR 1.05, p=0.013) a past history of pulmonary TB (RR 5.48, p=0.001), extra-pulmonary TB (RR 16.45, p<0.001), Felty's syndrome (RR 43.84, p=0.005), prednisolone>10mg daily (RR 4.44, p=0.009) and the use of TNF blockers (RR 12.48, p<0.001). CONCLUSIONS: Exposure to TNF blockers remained to be an independent risk factor for TB in RA after adjusting for other known risk factors.

Involvement, satisfaction and unmet health care needs in patients with psoriatic arthritis.

OBJECTIVE: To examine the involvement in care, participation in medical decision, satisfaction of health care and unmet needs in patients with PsA. To explore factors related to involvement and satisfaction with care. METHODS: One hundred and five patients with PsA attending four regional hospital rheumatology outpatient clinics were invited and consented to self-administer questionnaires, including socio-demographic data, quality of life with SF-12, involvement in medical decision, satisfaction with care and unmet health care needs. RESULTS: The overall perceived knowledge of disease was moderate. Good disease knowledge and good physical functioning were positively associated with involvement in care. Age, sex and pain scores were not associated with involvement in multivariate analysis. A low score in at least one question on involvement was the single independent negative predictor for satisfaction with health care. Only a minority (9%) was actively participating in medical decision-making. Among non-participants, 61.5% expressed the wish to participate. In aspects of education of disease, advice for exercise, psychological support and social support, respectively, 68.3, 73.3, 29.3 and 41.6% of the patients expressed unmet needs. CONCLUSION: Low involvement is negatively associated with satisfaction with health care in PsA. Good knowledge of disease and good physical functioning is positively associated with involvement. The current study supports patient education as an important factor associated with involvement of and satisfaction with care in PsA patients. Such patients have a high desire for information and numerous unmet health care needs. There is a need for improvement in the delivery of care to patients with PsA.

Decreased expression of T lymphocyte co-stimulatory molecule CD26 on invariant natural killer T cells in systemic lupus erythematosus.

CD26, a T cell co-stimulatory molecule and dipeptidyl peptidase IV for the degradation of interferon-gamma-induced chemokine, participates in multiple immunopathological roles in leukocyte homing and inflammation. Decreased circulating concentration of soluble (s)CD26 in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis and murine model of arthritis and encephalomyelitis have been reported. In the present study, the plasma concentration of sCD26 and chemokines, and cell surface expression of CD26 on monocytes, CD4+T lymphocytes, CD8+T lymphocytes, CD19+B lymphocytes and invariant natural killer T (iNKT) lymphocytes were analyzed using ELISA and flow cytometry, respectively, in 23 SLE patients and 14 sex- and age-matched control subjects. Although there was no significant difference between plasma concentrations of soluble CD26 in SLE patients with controls (p > 0.05), there was significant elevated Th1 chemokines CXCL10 and CXCL9 but not Th2 chemokine CCL2, and down-regulation in iNKT lymphocytes number and cell surface expression of CD26 on CD4+T and iNKT lymphocytes of SLE patients compared with controls (all p < 0.05). Decreased circulating number of iNKT cells and CD26 on iNKT cells can be important for the immunopathogenesis by exacerbating Th1-related inflammation in SLE.

Tacrolimus for the treatment of systemic lupus erythematosus with pure class V nephritis.

OBJECTIVES: The treatment of pure membranous (class V) lupus nephropathy remains unsatisfactory. We studied the efficacy and safety of tacrolimus in the treatment of membranous nephritis secondary to SLE. METHODS: We recruited 18 consecutive SLE patients (tacrolimus group) with recently confirmed biopsy-proven class V lupus nephritis. They were treated with a tailing dose of oral prednisolone and tacrolimus 0.1-0.2 mg/kg/day for 6 months, followed by maintenance prednisolone and AZA. The rate of resolution of proteinuria and SLEDAI were compared with 19 historical controls treated with oral cyclophosphamide or AZA (control group). All patients were followed for 12 months. RESULTS: Baseline clinical characteristics were comparable between the groups. For the tacrolimus group, the complete and partial remission rates were 27.8 and 50.0%, respectively at 12 weeks; for the control group, they were 15.8 and 47.4%, respectively (overall chi-square test, P = 0.5). However, tacrolimus group had faster resolution of proteinuria than the control group by the general linear model with repeated measures (P = 0.032). At 12 weeks, proteinuria was reduced by 76.2 +/- 17.0% for the tacrolimus group and 47.1 +/- 51.1% for the control group (P = 0.028). Serial change in renal function and SLEDAI score did not differ between the groups. During the study period, four patients of the tacrolimus group, and 11 of the control group, developed lupus flare (P = 0.027). There was no serious adverse effect in the tacrolimus group. CONCLUSIONS: A 6-month course of tacrolimus is a safe and effective treatment of pure class V (membranous) lupus nephritis. As compared with conventional cytotoxic treatment, tacrolimus possibly results in a faster resolution of proteinuria, and a lower risk of lupus flare within 1 yr. The long-term effect and optimal regimen of tacrolimus require further study.

Costs and quality of life of patients with ankylosing spondylitis in Hong Kong.

OBJECTIVES: To assess the annual direct, indirect and total societal costs, quality of life (QoL) of AS in a Chinese population in Hong Kong and determine the cost determinants. METHODS: A retrospective, non-randomized, cross-sectional study was performed in a cohort of 145 patients with AS in Hong Kong. Participants completed questionnaires on sociodemographics, work status and out-of-pocket expenses. Health resources consumption was recorded by chart review. Functional impairment and disease activity were measured using the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), respectively. Patients' QoL was assessed using the Short Form-36 (SF-36). RESULTS: The mean age of the patients was 40 yrs with mean disease duration of 10 yrs. The mean BASDAI score was 4.7 and BASFI score was 3.3. Annual total costs averaged USD 9120. Direct costs accounted for 38% of the total costs while indirect costs accounted for 62%. Costs of technical examinations represented the largest proportion of total cost. Patients with AS reported significantly impaired QoL. Functional impairment became the major cost driver of direct costs and total costs. CONCLUSION: There is a substantial societal cost related to the treatment of AS in Hong Kong. Functional impairment is the most important cost driver. Treatments that reduce functional impairment may be effective to decrease the costs of AS and improve the patient's QoL, and ease the pressure on the healthcare system.