Chondrocalcinosis of the Knee and the Risk of Osteoarthritis Progression: Data From the Knee and Hip Osteoarthritis Long-term Assessment Cohort.

OBJECTIVE: To assess the impact of knee chondrocalcinosis (CC) on the 5-year risk of joint replacement and disease progression in patients with knee osteoarthritis (OA). METHODS: Patients with symptomatic knee OA without previous total joint (knee or hip) replacement (TJR) were recruited from the Knee and Hip Osteoarthritis Long-term Assessment cohort. Cox proportional hazards regression and generalized estimating equation models were used to compare the time from inclusion or OA diagnosis to total knee replacement (TKR) or TJR between patients with and those without knee CC at inclusion. In patients without incident TKR, logistic regression was performed to examine the association between CC and radiographic progression (Kellgren/Lawrence [K/L] grade) or worsening of Western Ontario and McMaster Universities Arthritis Index (WOMAC) subscores for OA pain or function between years 0 and 5. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated. Analyses were adjusted for age, sex, body mass index, WOMAC subscores, and K/L grade. RESULTS: Among the 656 patients included, 93 (14.2%) had knee CC, and 91 (13.9%) underwent TKR during the follow-up. Risk of TKR was not affected by the presence of knee CC (HR 1.26 [95% CI 0.74-2.17]). Similar results were obtained for the risk of incident TJR. For patients without incident TKR, knee CC did not affect the risk of worsening of K/L grade (odds ratio [OR] 0.9 [95% CI 0.4-1.7]), WOMAC pain subscore (OR 1.1 [95% CI 0.7-1.4]), or WOMAC function subscore (OR 0.9 [95% CI 0.4-2.0]). CONCLUSION: In patients with symptomatic knee OA, the presence of knee CC did not affect the risk of arthroplasty or disease progression at 5 years.

Body composition and clinical symptoms in patients with hip or knee osteoarthritis: Results from the KHOALA cohort.

OBJECTIVE: To analyze the associations between body composition, notably low lean mass, and clinical symptoms [pain, physical function, quality of life (QoL)] in patients with symptomatic hip and/or knee OA. METHODS: Cross-sectional study using data from the 3-year follow-up visit of the Knee and Hip OsteoArthritis Long-term assessment (KHOALA) cohort. Skeletal muscle and fat mass were measured by dual X-ray absorptiometry (DXA). Fat mass index (FMI) was defined as total fat mass/height2. Appendicular lean mass was adjusted on body mass index (ALM/BMI), and low lean mass was defined according to the definition of FNIH Sarcopenia Project recommendations. Pain and function were measured by the WOMAC index and QoL by the SF-36. RESULTS: In total, 358 patients underwent DXA (67% women, mean [SD] age 63.4 [8.4] years, mean BMI 29.5 [5.6]kg/m2). The visual analog scale (0-100) pain score was 38.0 [24.7] and 25.4% had hip and 74.6% knee OA. Low lean mass and ALM/BMI were associated with impaired QoL and WOMAC scores on bivariate analysis (all p ≤ 0.001) but not on multivariate analysis after adjustment for FMI. For patients with normal BMI, mean [SD] WOMAC scores were higher (greater impairment) with low lean mass than normal body composition (WOMAC function 33.4 [23.3] and 24.0 [17.4], p = 0.02), and mean SF-36 physical component score was lower (greater impairment) 40.3 [10.2] and (44.3 [8.4], p = 0.04). Among patients with obesity, low lean mass had no additional effect. CONCLUSION: For patients with OA and normal BMI, QoL and function were more impaired for those with than without low lean mass. Conserving muscle mass in people with OA could have functional and antalgic benefits especially for those with normal BMI.

Association between hip morphology and prevalence, clinical severity and progression of hip osteoarthritis over 3 years: The knee and hip osteoarthritis long-term assessment cohort results.

OBJECTIVE: To assess the effects of variations in hip morphology on prevalence, clinical severity and progression of hip osteoarthritis. METHODS: From 2007 to 2009, we conducted a study of 242 patients aged between 40 and 75 years with symptomatic lower limb osteoarthritis, as part of a population-based osteoarthritis cohort study in France. Standard radiographs of both hips were obtained at baseline and at three years. The progression of hip osteoarthritis was evaluated according to the radiological Kellgren-Lawrence score (KL) and clinical severity from the scores on a Visual Analogic Scale (VAS) for pain recorded yearly. Five measures were used to describe hip morphology: centre edge angle, acetabular index (AI), vertical centre anterior angle, acetabular depth and neck-shaft angle. RESULTS: Of the 484 hips studied, 205 (42%) showed osteoarthritis at baseline and 16 (11 right and 5 left) underwent joint replacement during the follow-up. AI was the morphological measure most consistently and strongly associated with radiographic osteoarthritis at baseline (odds-ratio=1.05, 95% CI: 1.01-1.08 per degree of angle change), clinical severity (correlation coefficient with VAS during 3 years=0.15, P=0.004), radiological progression (odds-ratio=1.05, 95% CI: 1.00-1.10 per degree) and joint replacement (hazard ratio=1.18, 95% CI: 1.07-1.29 per degree). CONCLUSIONS: Acetabular obliquity and especially AI is strongly, and likely causally, associated with the existence, severity and progression of hip osteoarthritis.

Femoro-tibial knee osteoarthritis: One or two X-rays? Results from a population-based study.

OBJECTIVE: Our objective was to compare the use of both anteroposterior (AP) extended-knee X-ray and semi-flexed X-ray (current gold standard) versus the use of semi-flexed X-ray alone to detect femoro-tibial osteoarthritis (OA). METHODS: Individuals 40 to 75 years of age with symptomatic hip and/or knee OA (Kellgren/Lawrence [KL] score≥2) were recruited using a multiregional prevalence survey in France. Both AP and schuss X-rays were performed and read; two years later, the same examiner, blinded to the results of the first reading, performed a second reading of the schuss X-ray. We compared the KL stages of each knee and analyzed osteophyte detection and localization, joint space narrowing (JSN), and the relationship to obesity. RESULTS: The analysis included 350 participants with OA of various stages. Comparing the two readings showed that a higher proportion of patients had KL≥2 when the two X-ray views were combined (right knee: P<0.0001; left knee: P<0.001). There were no differences when using the schuss X-ray alone versus in combination with an AP X-ray in terms of detecting JSN, osteophytes. A comparison of schuss X-ray alone versus AP X-ray alone demonstrated the superiority of the schuss view for evaluating JSN (P=0.0001 and P=0.0001) and no difference in osteophyte detection. CONCLUSION: Our study shows that the schuss view alone was sufficient for detecting knee osteophytes and JSN. Using one X-ray rather than two will reduce medical costs and irradiation burden. Using two views seems preferable for epidemiological studies.

Randomised, controlled trial of avocado-soybean unsaponifiable (Piascledine) effect on structure modification in hip osteoarthritis: the ERADIAS study.

OBJECTIVE: To assess the ability of avocado-soybean unsaponifiable-Expanscience (ASU-E) to slow radiographic progression in symptomatic hip osteoarthritis (OA). METHODS: Prospective, randomised, double blind, parallel group, placebo controlled 3 year trial. Patients with symptomatic (painful ≥1 year, Lequesne Index between 3 and 10) hip OA (American College of Rheumatology criteria) and a minimum joint space width (JSW) of the target hip between 1 and 4 mm on a pelvic radiograph were randomly assigned to 300 mg/day ASU-E or placebo. Standing pelvis, target hip anteroposterior (AP) and oblique views were taken annually. The primary outcome was JSW change at year 3, measured at the narrowest point on pelvic or target hip AP view (manual measure using a 0.1 mm graduated magnifying glass). The full analysis dataset (FAS) included all patients having at least two successive radiographs. An analysis of covariance Mixed Model for Repeated Measurements with Missing at Random (for missing data) was performed to compare adjusted 3 year JSW changes (primary outcome) and the percentages of 'progressors' (JSW loss≥0.5 mm) between groups. RESULTS: 399 patients were randomised (345 kept in the FAS), aged 62 (35-84) years, 54% women, mean body mass index 27 (SD 4) kg/m(2), mean symptom duration 4 (SD 5) years, 0-100 normalised Lequesne Index 30 (SD 9) and global pain visual analogue scale 37 (SD 23) mm. Mean baseline JSW was 2.8 (0.9) mm. There was no significant difference on mean JSW loss (-0.638 mm vs -0.672 mm, p=0.72, in the ASU-E and placebo groups, respectively) but there were 20% less progressors in the ASU-E than in the placebo group (40% vs 50%, respectively, p=0.040). No difference was observed on clinical outcomes. Safety was excellent. CONCLUSIONS: 3 year treatment with ASU-E reduces the percentage of JSW progressors, indicating a potential structure modifying effect in hip OA to be confirmed, and the clinical relevance requires further assessment.

Relationship between hip dysplasia, pain, and osteoarthritis in a cohort of patients with hip symptoms.

OBJECTIVE: The relationship between acetabular dysplasia (HD) and hip osteoarthritis (OA) remains unclear, especially for mild forms of dysplasia. Our objectives were to estimate the prevalence of HD in a population-based sample with symptoms and to evaluate potential associations linking HD, hip OA, and hip pain. METHODS: Individuals 40 to 75 years of age with symptoms in 1 or both hips were recruited during a multiregional prevalence survey. All study participants underwent examination and radiographs. Radiographs were evaluated using Kellgren-Lawrence staging (with stages ≥ 2 indicating hip OA) and HD measures [center-edge (CE) angle, acetabular inclination angle (HTE), acetabular depth (AD), and vertical center-anterior margin angle]. RESULTS: We studied both hips of 842 individuals (1684 hips), among whom 203 had hip OA. Compared to left hips, right hips had significantly smaller CE angles and significantly greater AD and HTE values (p ≤ 0.001). Overall, the prevalence of HD ranged from 7.6% to 22.2% of the hips depending on the measure used. The prevalence of HD was higher in individuals with hip OA, with significant differences for abnormal HTE (19.1% vs 11.4%; p < 0.0001) and abnormal CE (11.3% vs 7.5%; p = 0.04). By logistic regression, only abnormal HTE remained associated with OA. Same-side hip pain was not statistically more common in individuals with HD after stratification on OA status (p = 0.12). CONCLUSION: Our study confirms the relationship between OA and HD, particularly as defined based on the HTE angle.

Diffuse idiopathic skeletal hyperostosis (Forestier-Rotes-Querol disease): what's new?

Diffuse idiopathic skeletal hyperostosis (DISH), also known as Forestier-Rotes-Querol disease, is characterized by the ossification of the entheses (i.e., enthesopathy). The diagnosis of DISH requires at least two (according to Forestier) or three (according to Resnick) contiguous intervertebral bridges, without severe disk alterations (in contrast to degenerative spinal disease) or ankylosis of the sacroiliac or facet joints (in contrast to spondylarthritis). Although prevalence estimates vary with the number of bridges used to define the disease, the prevalence of DISH is consistently high and increases with age and obesity. Peripheral involvement is common but difficult to ascribe to DISH in the absence of typical spinal changes. Cervical spine ossification is the most extensively studied manifestation, as dysphagia due to esophageal compression may require surgery. As with spondylarthritis, vertebral fractures on a hyperostotic fused spine may escape recognition, placing the patient at risk for complications in the event of subsequent displacement. These fractures are particularly severe, as they often involve the cervical spine and can therefore, cause major neurological impairments. DISH is associated with an increased risk of metabolic syndrome (odds ratio, 3.88). Research into the pathophysiology of DISH has established that serum levels of the natural osteogenesis inhibitor Dickkopf-1 (DKK-1) are low in patients with DISH or spondylarthritis. Although this abnormality might contribute to the entheseal ossification, it has not been found consistently.

Reproducibility of radiographic hip measurements in adults.

INTRODUCTION: Hip dysplasia may cause pain and premature hip osteoarthritis. Here, our objective was to assess the inter- and intraobserver reproducibility of radiographic hip parameter measurement in adults. METHODS: We used anteroposterior pelvic radiographs and false-profile lateral hip radiographs from 30 individuals (60 hips) enrolled in a prevalence study of hip osteoarthritis. For each hip, two independent observers recorded five parameters twice, at an interval of 1 month. The five parameters were the vertical-center-edge angle (VCE), the anterior center-edge angle (vertical-center-anterior angle, VCA), the acetabular roof angle (HTE), the neck-shaft angle (CC'D), and acetabulum depth (AD). Reproducibility was assessed using Bland-Altman plots, intraclass correlation coefficients (ICCs), and kappa coefficients for the radiographic diagnosis of hip dysplasia using widely accepted cutoffs. RESULTS: Of the 60 hips, 51 were assessable. Intraobserver ICC values ranged from 0.72 to 0.94 and interobserver ICC values from 0.68 to 0.84. Kappa coefficients were between 0.60 and 1.00, except for the VCA angle (κ=0.41). CONCLUSION: In this study, reproducibility of the main radiographic hip parameters was good according to all evaluation methods used. However, CC'D and, to an even greater extent, the VCA angle seemed challenging to measure.

Rituximab treatment for spondyloarthritis. A nationwide series: data from the AIR registry of the French Society of Rheumatology.

OBJECTIVE: To evaluate the efficacy and safety of rituximab (RTX) in several subsets of spondyloarthritis (SpA) using the data of the AIR (Autoimmunity and Rituximab) registry. METHODS: All patients receiving RTX for SpA, and prospectively included in the AIR registry from September 2005 to September 2010, were retrospectively analyzed. The response to treatment was evaluated by the Bath Ankylosing Spondylitis Disease Activity Index for axial disease, joint count for peripheral disease, and C-reactive protein reduction. RESULTS: Among the 595 patients included in the AIR registry, 26 patients with SpA from 13 centers were reported: ankylosing spondylitis (10), undifferentiated SpA (7), and psoriatic arthritis (9). Mean disease duration was 8.8 years (range 1-40). The extraarticular features found were psoriasis, 12 cases; uveitis, 4 cases; and Crohn's disease, 3 cases. The mean number of disease-modifying antirheumatic drugs before RTX was 2.4; previous anti-tumor necrosis factor (TNF) agents were taken in 23 cases. The mean number of RTX courses was 1.5 (range 1-5), with a total of 35.6 patient-years. Efficacy was noted in 11/23 cases: 3 out of 3 anti-TNF-naive patients and 8 out of 20 anti-TNF nonresponder patients. No predictive factors of response could be identified, particularly in diagnosis subsets or clinical presentation (axial or peripheral). CONCLUSION: In this nationwide study of several subsets of SpA, RTX had only a moderate efficacy that was more marked in patients who were anti-TNF-naive.

The KHOALA cohort of knee and hip osteoarthritis in France.

OBJECTIVES: This study aimed to describe the prevalence of symptomatic knee and hip osteoarthritis (OA) and its course over time, as well as identify prognostic factors of OA course and determinants of costs and access to care in France in a patient cohort. METHODS: Subjects aged 40 to 75 years, with uni- or bilateral symptomatic hip and/or knee OA (ACR criteria), Kellgren and Lawrence (KL) stage 2 or greater, were recruited from a French national prevalence survey for the multicenter KHOALA cohort study. Data collected at baseline included sociodemographic and clinical data; WOMAC, IKS and Harris scores for pain and function; MAQ score for physical activity; functional comorbidity index; GHQ28 score for psychological status; and SF-36 (generic) and OAKHQOL (specific) scores for quality of life. Blood and urine samples were collected. RESULTS: Eight hundred and seventy-eight subjects were included, 222 with OA of the hip (mean age 61.2±8.8 years), 607 knee (mean age 62.0±8.5 years) and 49 both hip and knee (mean age 64.9±7.9 years). Mean body mass index was 26.9±4.5 for hip OA and 30.3±6.3 for knee OA. Hip and knee OA patients had 1.99 and 2.06 comorbidities, on average, respectively. Disease severity on X-rays for KL stages 2, 3 and 4 for hip OA was 69.8, 26.1 and 4.1%, respectively, and for knee OA, 44.5, 30.3, and 25.2%. As compared with population norms, age- and sex-standardized SF-36 scores were greatly decreased for both knee and hip OA in all dimensions, particularly physical and emotional dimensions. PERSPECTIVES: Patients will be followed up annually, alternately by mail and clinical visit. This cohort of representative patients with knee and hip OA will be an opportunity for future collaborative research.

Efficacy and safety of rituximab in the treatment of refractory inflammatory myopathies in adults: results from the AIR registry.

OBJECTIVES: To assess the efficacy and safety of rituximab (RTX) in patients with refractory idiopathic inflammatory myopathies (IIMs). METHODS: RTX efficacy was based on improvement in three criteria: creatine phosphokinase (CPK) level, daily CS dose and physicians' opinion. A decrease in CPK level or CS dose was significant if it was >25%. RESULTS: Thirty patients were studied (21 women; age 52.5 years, disease duration 6.1 years). All had previously received immunosuppressors (ISs). Twenty-five patients received 1 g of RTX twice 2 weeks apart and five received 4 weekly RTX infusions (375 mg/m(2)). RTX was given in association with IS in 21 patients. Twenty-eight patients received CS (mean dose 21.2 mg/day). Mean follow-up was 17.2 months. Thirteen adverse events were reported, including seven infections and one serious infection (pyelonephritis). RTX was effective in 16 patients. Duration of efficacy was 15.5 months. Of the 20 patients with baseline CPK level ≥2 × upper limit of normal (ULN), 11 (55%) improved. The main level fell from 20.7 to 11 × ULN. CS decreased in 15 patients, stopped in 4, remained stable in 8 and increased in the remaining 3. The CS dose decreased from 21.2 to 9.9 mg/day. The physicians' opinion was favourable in 21 patients. Manual muscle testing was performed in only five patients: it increased from 87 to 91/100 at 6 months. CONCLUSIONS: RTX was well tolerated and had some beneficial effects on patients with IIM, the main limitation of this study resulted in a lack of manual muscle testing.

Self-reported prevalence of psoriasis and evaluation of the impact on the natural history of hip osteoarthritis: results of a 10 years follow-up study of 507 patients (ECHODIAH study).

OBJECTIVE: The objective of the present study was to assess the frequency of self-reported psoriasis in a hip osteoarthritis (OA) cohort, and a secondary objective was to assess the course of hip OA with psoriasis. METHODS: ECHODIAH was a 3-year, randomised double-blind controlled trial evaluating diacerein vs. placebo in hip OA. During the 36 months of the trial, the Lequesne algofunctional index and pain visual analog scale (VAS) and joint space width (JSW) were assessed every 3 months. From month 36 to 120, the requirement for total hip replacement (THR) was collected annually via a phone call. At the end of 10 years of follow-up, the prevalence of self-reported psoriasis, family psoriasis was assessed by letter, retrospectively--(retrolective design). RESULTS: Of the 507 ECHODIAH patients, 279 were followed-up 10 years; 192 (68.8%) answered the psoriasis questionnaire. Twenty-two (11.4%) of 192 patients had self-reported psoriasis. Eighteen patients (9.4%) had family history of psoriasis. Eleven (50%) of 22 patients were diagnosed by a dermatologist. Baseline characteristics were similar between responders and non-responders, and between psoriasis and no psoriasis patients. The disease course was not different according to the presence of psoriasis, though total hip replacement was more frequent with psoriasis (77.2% after 10 years) than without (58.8%), no statistical difference (p=0.10). CONCLUSION: The prevalence of self-reported psoriasis was high in this cohort, almost twice the frequency reported in the general population. The disease course was not modified by the presence of psoriasis. These data should be further confirmed.

Effect of hyaluronic acid in symptomatic hip osteoarthritis: a multicenter, randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and tolerability of a single intraarticular (IA) injection of hyaluronic acid (HA) for the treatment of hip osteoarthritis (OA). METHODS: A multicenter, randomized, parallel-group, placebo-controlled trial was conducted over 3 months. Patients (older than 30 years) with symptomatic hip OA (pain score of >40 mm on a visual analog scale [VAS]) and a Kellgren/Lawrence grade of 2 or 3 were randomly assigned to receive 1 fluoroscopically guided IA injection of HA (2.5 ml) or placebo (2.5 ml). Patients were followed up for 3 months. The main outcome measure was pain score on a VAS (100 mm) at month 3 compared with baseline. Secondary outcome measures were the proportion of responders defined by Osteoarthritis Research Society International criteria; Western Ontario and McMaster Universities Osteoarthritis Index subscores for pain, stiffness, and disability; and patient and physician global assessment. Randomization was computer generated. HA and placebo preparations were placed in numbered identical containers, and syringes were covered with masking tape. Physicians assessing outcomes were blinded with regard to group assignment. RESULTS: Eighty-five patients were randomized to the HA group (n = 42) or placebo group (n = 43). Baseline characteristics were similar between the 2 groups. At 3 months, the decrease in pain score did not differ between the HA and placebo groups in the intent-to-treat analysis (mean +/- SD decrease 7.8 +/- 24.9 mm with HA versus 9.1 +/- 27.4 mm with placebo; P = 0.98). The responder rates were 33.3% and 32.6% in the HA and placebo groups, respectively (P = 0.94). Other secondary end points did not differ between the groups, nor did use of rescue medication or frequency of adverse events. CONCLUSION: Our findings indicate that a single IA injection of HA is no more effective than placebo in treating the symptoms of hip OA.

Adherence to, and results of, physical therapy programs in patients with hip or knee osteoarthritis. Development of French clinical practice guidelines.

OBJECTIVE: To develop recommendations regarding adherence to physical therapy programs by patients with hip or knee osteoarthritis. METHODS: We used the method recommended by the French Society for Physical and Rehabilitation Therapy (SOFMER), which combines a systematic literature review, a practice survey, and validation by a multidisciplinary panel of experts. RESULTS: When setting up exercise programs for patients with lower limb osteoarthritis, measures should be taken to increase effectiveness by optimizing adherence. Patient selection is among these measures, as exercise programs are more likely to succeed in patients with a history of being physically active, a positive view of the suggested program, and/or favorable social and material conditions. Regardless of the type of exercise, the program should be tailored to exercise capacity and pain level (professional consensus). Patient adherence can be improved by explaining the expected results to the patient, asking the patient to keep a self-evaluation diary, conducting long-term evaluations (by phone or mail), and providing follow-up visits. CONCLUSION: Studies of adherence according to the type of exercise are needed. The relevance of widely used incentives in patients with hip or knee osteoarthritis should be evaluated in new therapeutic trials.

Medicoeconomic evaluation of hyaluronic acid for knee osteoarthritis in everyday practice: the MESSAGE study.

INTRODUCTION: Medicoeconomic data on treatments for osteoarthritis are scant. We investigated the impact of hyaluronic acid therapy on the cost of management of knee osteoarthritis. Our primary objective was to compare medical costs (admissions, outpatient visits, investigations, and treatments) and non-medical costs (sick leaves and transportation) from the perspective of the national health insurance system during the 3 months before and the 6 months after three intraarticular injections of hyaluronic acid. Our secondary objective was to evaluate treatment benefits in terms of pain, function, and quality of life. METHODS: Observational, multicenter, longitudinal, before-after study of the medical and economic effects of hyaluronic acid therapy for symptomatic knee osteoarthritis. RESULTS: Of the 296 assessable patients (mean age, 69 years; 30% with obesity; 65% women), only 5% of patients were withdrawn prematurely from the study. Significant improvements in the Lequesne index were found 3 and 6 months after treatment; the improvement was greater than 50% in over half the patients. Pain and quality-of-life scores improved significantly. Total cost of the disease decreased from 334 euros for the 3 pretreatment months to 295 euros and 233 euros for posttreatment months 1-3 and 4-6, respectively. CONCLUSION: The costs of knee osteoarthritis decreased during the 6 months after Suplasyn therapy, indicating that the cost of the medication was more than offset by the decreased need for other treatments. Concomitantly, clinical benefits were obtained. Under the conditions of everyday practice, hyaluronic acid may provide medical benefits at an acceptable cost.

Tumor necrosis factor alpha and adalimumab differentially regulate CD36 expression in human monocytes.

In chronic inflammatory diseases, such as rheumatoid arthritis, inflammation acts as an independent cardiovascular risk factor and the use of anti-inflammatory drugs, such as anti-tumor necrosis factor alpha (anti-TNFalpha), may decrease this risk. The phagocytosis of oxidized low density lipoproteins (LDLs) accumulated in the subendothelium by mononuclear cells influences atherosclerosis and depends on CD36 expression. We investigated the role of TNFalpha and adalimumab, a human anti-TNFalpha monoclonal antibody widely used in human pathology, in CD36 expression in human monocytes. Human monocytes were prepared by adherence from whole-blood buffy-coat fractions from healthy donors. CD36 expression was assessed by RT-PCR and flow cytometry, with various TNFalpha or adalimumab concentrations. Implication of peroxisome proliferator-activated receptor (PPAR)gamma in the regulation of CD36 expression was assessed using specific inhibitor or gel shift assays. The impact of redox signaling was investigated using quantification of reactive oxygen species, antioxidant and a NADPH oxidase inhibitor. The F(ab')2 fragment of adalimumab was isolated and its effect was analyzed. TNFalpha inhibits both CD36 membrane expression and mRNA expression. This inhibition involves a reduction in PPARgamma activation. In contrast, adalimumab increases both CD36 membrane expression and mRNA expression. This induction is independent of the Fc portion of adalimumab and involves redox signaling via NADPH oxidase activation. CD36 expression on human monocytes is inhibited by TNFalpha and independently increased by adalimumab. These data highlight that pro-inflammatory cytokines and their specific neutralization influence the expression of cellular receptors implicated in atherosclerosis. Further studies are needed to investigate the clinical implications of these results in accelerated atherosclerosis observed in rheumatoid arthritis.

A new classification of HLA-DRB1 alleles differentiates predisposing and protective alleles for autoantibody production in rheumatoid arthritis.

The HLA-DRB1 gene was reported to be associated with anticitrullinated protein/peptide autoantibody (ACPA) production in rheumatoid arthritis (RA) patients. A new classification of HLA-DRB1 alleles, reshaping the shared epitope (SE) hypothesis, was recently found relevant in terms of RA susceptibility and structural severity. We investigated the relevance of this new classification of HLA-DRB1 SE+ alleles in terms of rheumatoid factor (RF) and ACPA production in a sample of French RA patients. We studied 160 early RA patients included in a prospective longitudinal cohort of French Caucasian patients with recent-onset arthritis. RF, anticyclic citrullinated peptide 2 (anti-CCP2) and antideiminated human fibrinogen autoantibodies (AhFibA) were assessed in all patients at inclusion. The HLA-DRB1 gene was typed by PCR-sequence specific oligonucleotides probes (PCR-SSOP), and SE+ alleles were classified into four groups (S1, S2, S3P, S3D) according to the new classification. The new classification of HLA-DRB1 SE+ alleles distinguishes predisposing and protective alleles for RF, anti-CCP2 or AhFibA production. The presence of S2 or S3P alleles is associated with both RF, anti-CCP2 or AhFibA positivity, whereas the presence of S3D or S1 alleles appears to be protective for RF, anti-CCP2 or AhFibA positivity. The new classification of HLA-DRB1 SE+ alleles is relevant in terms of autoantibody production in early RA patients by differentiating predisposing and protective alleles for RF or ACPA production.

Effect of chondroitin sulphate in symptomatic knee osteoarthritis: a multicentre, randomised, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and tolerability of chondroitin sulphate (chondroitin sulphate) in knee osteoarthritis. PATIENTS AND METHODS: A 24-week, randomised placebo-controlled trial of chondroitin sulphate (1 g/day) in patients with symptomatic knee osteoarthritis as measured on a visual analogue scale. Pain on daily activities and Lequesne's Index were the primary efficacy criteria. Secondary outcomes included the rate of responders according to the outcome measures in rheumatoid arthritis clinical trials of the Osteoarthritis Research Society International (OMERACT-OARSI) criteria, quality of life, patient's/physician's global assessments and carry-over effect after treatment. Biochemical markers of bone (CTX-I), cartilage (CTX-II) and synovium (hyaluronic acid) metabolism were also measured. Safety was assessed by recording adverse events (AEs). Statistical analysis was performed on the inter-group differences in the intention-to-treat population. RESULTS: 307 patients were included in the study. 28 (9%) patients discontinued the study because of lack of efficacy or AEs. At the end of treatment, the decrease in pain was -26.2 (24.9) and -19.9 (23.5) mm and improved function was -2.4 (3.4) (-25%) and -1.7 (3.3) (-17%) in the chondroitin sulphate and placebo groups, respectively (p = 0.029 and 0.109). The OMERACT-OARSI responder rate was 68% in the chondroitin sulphate and 56% in the placebo group (p = 0.03). The investigator's assessments and short form 12 (SF-12) physical component reported improvement more frequently in the chondroitin sulphate than in the placebo group (p = 0.044 and 0.021, respectively). No significant difference was observed between treatment groups for changes in biomarkers over 24 weeks. However, there was a significant difference between non-responders and responders according to the OARSI criteria for 24-week changes of CTX-I (p = 0.018) and CTX-II (p = 0.014). Tolerance was considered to be satisfactory. CONCLUSION: This study failed to show an efficacy of chondroitin sulphate on the two primary criteria considered together, although chondroitin sulphate was slightly more effective than placebo on pain, OMERACT-OARSI response rate, investigator's assessment and quality of life.

Systemic vasculitis revealing a benign tumor: a paraneoplastic syndrome?

Systemic vasculitis is a rare event in the course of malignant tumors and has not been described in association with benign tumors. We report a case of renal oncocytoma in a patient who presented with digital necrosis, arthralgia, myalgia, and a decline in general health. The symptoms resolved fully after tumor excision, supporting a diagnosis of paraneoplastic syndrome.