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Job 941988 Rheumatologist needed for exceptional metro Illinois location - HUGE earning potential in year one. Group practice with very low corporate overhead. Join three others for call 1:4. One infusion

Arthritis Research & Therapy - Latest Articles

Vaccination under TNF blockade: less effective, but worthwhile
Martin Aringer Mon, 14 May 2012 00:00:00 -0000
Only after biological response modifiers have become available have we begun to understand some of the complex functions of TNF in the human immune system. TNF is clearly essential for fighting intracellular pathogens, but probably not essential for fighting tumors. TNF influence on the humoral immune response, in contrast, has been more complicated to decipher, since TNF blockade is associated with both autoantibody formation and (somewhat) reduced responses to vaccination. Novel data now show that TNF is good for the humoral immune response. Vaccinations still work, however, and should be strongly recommended.
High-density lipoprotein cholesterol subfractions HDL2 and HDL3 are reduced in women with rheumatoid arthritis and may augment the cardiovascular risk of women with RA: a cross-sectional study
Elke ArtsJaap FransenHeidi LemmersAnton StalenhoefLeo JoostenPiet van RielCalin Popa Mon, 14 May 2012 00:00:00 -0000
IntroductionHigher levels of HDL subfractions HDL3-chol and particularly HDL2-chol protect for cardiovascular disease (CVD), but inflammation reduces HDL level and may impair its anti-atherogenic effect. Changed HDL composition through the impact of inflammation on HDL subfractions may contribute to the excess risk of CVD in RA. In this study, we investigated whether HDL2-chol and HDL3-chol concentrations differ between RA patients and healthy controls, and whether these levels are related to the level of RA disease activity. Methods: Non-fasting blood samples were collected from 45 RA patients and 45 healthy controls. None of the participants had a history of CVD, diabetes, or used lipid-lowering drugs. HDL2-chol and HDL3-chol concentrations were obtained by ultracentrifugation. Regression modeling was used to compare HDL subfraction levels between RA patients and healthy controls, and to analyze the effect of disease activity on HDL2-chol and HDL3-chol. Results: HDL2-chol and HDL3-chol were significantly lower in RA patients compared to healthy controls (p=0.01, p=0.005). The HDL2:HDL3 ratio was significantly lower in patients compared to controls (p=0.04). Reduced HDL2-chol and HDL3-chol levels were primarily present in female RA patients and not in male RA patients. A modest effect of DAS28 on HDL2-chol concentrations was found, after correction for disease duration, glucocorticosteroid use and BMI, with a 0.06 mmol/L decrease with every point increase in DAS28 (p=0.05). DAS28 did not significantly affect HDL3-chol concentrations (p=0.186). Conclusions: Both HDL subfractions but particularly HDL2-chol concentrations were decreased in RA, primarily in women. This seems to be associated with disease activity and is of clinical relevance. The reduction of the HDL subfraction concentrations, particularly the supposedly beneficial HDL2-chol, may negatively impact the cardiovascular risk profile of women with RA.
Body mass index influences the response to infliximab in ankylosing spondylitis
Sebastien OttavianiYannick AllanoreFlorence TubachMarine ForienAnais GardetteBlandine PasquetElisabeth PalazzoMarine MeunierGilles HayemChantal Job-DeslandreAndre KahanOlivier MeyerPhilippe Dieude Mon, 14 May 2012 00:00:00 -0000
IntroductionThe excess of adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetic consequences. The aim of this study was to determine whether body mass index (BMI) affects response to infliximab (IFX) in ankylosing spondylitis (AS) patients. Methods: In 155 patients retrospectively included with active AS, the BMI was calculated before initiation of IFX treatment (5 mg/kg intravenously). After 6 months of treatment, changes from baseline in BASDAI, Visual Analogue Scale (VAS) pain, C-reactive protein (CRP) level and total dose of Nonsteroidal anti-inflammatory drug (NSAID) was dichotomized with a threshold corresponding to a decrease of 50% of initial level of the measure, into binary variables assessing response to IFX (BASDAI50, VAS50, CRP50, NSAID50). Whether BMI was predictive of response to IFX therapy according to these definitions was assessed with logistic regression. Results: Multivariate analysis found a higher BMI was associated with a lower response for BASDAI50 (P=0.0003, OR 0.87 95%CI0.81-0.94VAS50 (P<0.0001, OR 0.87 95%CI[0.80-0.93]), CRP50 (P=0.0279, OR 0.93 95%CI0.88-0.99) and NSAID50 (P=0.0077, OR 0.91 95%CI0.85-0.97criteria. According to the 3 WHO BMI categories, similar results were found for BASDAI50 (77.6%, 48.9% and 26.5%, P<0.0001), VAS50 (72.6%, 40.4% and 16.7%, P<0.0001), CRP50 (87.5%, 65.7% and 38.5%, P=0.0001) and NSAID50 (63.2%, 51.5% and 34.6%, P=0.06). Conclusions: This study provides the first evidence that a high BMI negatively influences the response to IFX in AS. Further prospective studies, including assessment of the fat mass, pharmacokinetics and adipokines dosages are mandatory to elucidate the role of obesity in AS IFX response.
Elevated levels of fibrinogen-derived endogenous citrullinated peptides in synovial fluid of rheumatoid arthritis patients
Reinout RaijmakersJoyce van BeersMahmoud El-AzzounyNatasja VisserBorut BozicGer PruijnAlbert Heck Mon, 14 May 2012 00:00:00 -0000
IntroductionRheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the joints and the presence of autoantibodies directed against proteins containing the non-standard arginine-derived amino acid citrulline. The protein fibrinogen, which has an essential role in blood clotting, is one of the most prominent citrullinated autoantigens in RA, particularly because it can be found in the inflamed tissue of affected joints. Here, we set out to analyze the presence of citrullinated endogenous peptides in the synovial fluid of RA and arthritic control patients. Methods: Endogenous peptides were isolated from the synovial fluid of RA patients and controls by filtration and solid phase extraction. The peptides were identified and quantified using high resolution liquid chromatography-mass spectrometry. Results: Our data reveal that the synovial fluid of RA patients contains soluble endogenous peptides derived from fibrinogen, containing significant amounts of citrulline residues and in some cases also phosphorylated serine. Several citrullinated peptides are found to be more abundantly present in the synovial fluid of RA patients compared to patients suffering from other inflammatory diseases affecting the joints. Conclusions: The increased presence of citrullinated peptides in RA patients points towards a possible specific role of these peptides in the immune response at the basis of the recognition of citrullinated peptides and proteins by RA patient autoantibodies.
Increased type II collagen cleavage by cathepsin K and collagenase activities with aging and osteoarthritis in human articular cartilage
Valeria DejicaJohn MortSheila LavertyJohn AntoniouDavid ZukorMichael TanzerA Poole Mon, 14 May 2012 00:00:00 -0000
IntroductionThe intra-helical cleavage of type II collagen by proteases including collagenases and cathepsin K is increased with aging and osteoarthritis (OA) in cartilage as determined by immunochemical assays. The distinct sites of collagen cleavage generated by collagenases and cathepsin K in healthy and OA human femoral condylar cartilages were identified and compared. Methods: Fixed frozen cartilage sections were examined immunohistochemically, using antibodies that react with the collagenase-generated cleavage neoepitopes, C2C and C1,2C, and the primary cleavage neoepitope (C2K) generated in type II collagen by the action of cathepsin K and possibly by other proteases but not by any collagenases studied to date. Results: In most cases the staining patterns for collagen cleavage were similar for all three epitopes: weak to moderate mainly pericellular staining in non-OA cartilage from younger individuals and stronger, more widespread staining in ageing and OA cartilages that often extended from the superficial to the mid/deep zone of the tissue. In very degenerate OA specimens, with significant disruption of the articular surface, staining was distributed throughout most of the cartilage matrix. Conclusions: Cleavage of collagen by proteases usually arises pericellularly around chondrocytes at and near the articular surface, subsequently becoming more intense and extending progressively deeper into the cartilage with ageing and OA. The close correspondence between the distributions of these products suggests that both collagenases and cathepsin K, and other proteases that may generate this distinct cathepsin K cleavage site, are usually active in the same sites in the degradation of type II collagen.
Low-dose oral prednisone improves clinical and ultrasonographic remission rates in early rheumatoid arthritis. Results of a 12 month open-label randomized study.
Carlomaurizio MontecuccoMonica TodoertiGarifallia SakellariouCarlo Alberto ScireRoberto Caporali Mon, 14 May 2012 00:00:00 -0000
IntroductionIn early rheumatoid arthritis (RA), low-dose oral prednisone (PDN) co-medication yields better clinical results than monotherapy with disease modifying antirheumatic drugs (DMARDs). In addition, ultrasonographic (US) evaluation reveals rapid and significative effects of glucocorticosteroids on subclinical synovitis. No data currently exists which examines the clinical and US results offered by GC co-medication over DMARD monotherapy in early RA patients. Methods: Two hundred and twenty (220) patients with early RA (<1 year from clinical onset) were treated according to a low disease activity (LDA) targeted step-up protocol including methotrexate (MTX) and, in the active treatment arm, low-dose (6.25 mg/d) oral PDN over 12 months. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of hands was performed at baseline, 6 and 12 months. Grey-scale (GS) and power Doppler (PD) synovitis were scored (0 to 3) for each joint. At 12 months, clinical remission, according to disease activity score 28 (DAS28), was defined as clinical outcome, and total joint PD score=0 (PD negativity) as imaging outcome. Results: Each group included 110 patients with comparable demographic, clinical, laboratory and US characteristics. At 12 months, LDA rate was similar in the 2 groups, whilst clinical remission rate (RR 1.61 [95%CI 1.08, 2.04]) and PD negativity rate (RR 1.31 [95%CI 1.04, 1.64]) were significantly higher in MTX+PDN group. Conclusions: In early RA, despite a similar response rate in terms of LDA, low-dose oral PDN co-medication led to a higher proportion of clinical remission and PD negativity compared to MTX monotherapy, thus ensuring a better disease activity control.Trial Registration: Current Controlled Trials ISRCTN2486111

Annals of the Rheumatic Diseases current issue

The risks of smoking in patients with spondyloarthritides
Braun, J., Sieper, J., Zink, A. Mon, 07 May 2012 09:17:26 -0700
The smoking prevalence in Europe varies from 14% in Sweden to nearly 38% in Greece.1 In the USA it is now approximately 20%, with large differences between states and according to social class and ethnic background.2 The proportions of men and women smoking is rather variable, but the relative risk of cardiovascular diseases seems to be higher in women.3 Smoking prevalence decreases with higher educational level and higher family income. Smoking is a major risk factor for lung, cardiovascular and other diseases.4 5 Smokers double their risk of having a heart attack compared with non-smokers4 and many people die from diseases related to smoking. The effects of nicotine, like those of other drugs with the potential for abuse and dependence, are centrally mediated. The impact of nicotine on the central nervous system is neuroregulatory in nature, affecting...
Progression of joint damage despite control of inflammation in rheumatoid arthritis: a role for cartilage damage driven synovial fibroblast activity
Lafeber, F. P., Van der Laan, W. H. Mon, 07 May 2012 09:17:26 -0700
Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes progressive joint destruction and consequently functional disability due to the combined effect of chronic synovitis and progressive joint damage. Treatment with disease-modifying drugs and biological agents improves pain, fatigue and disability. More recently, the concept of tight control has been introduced in the treatment of RA. Tight control may be defined as a treatment strategy tailored to the disease activity of individual patients, with the aim of achieving a predefined level of low disease activity or preferably remission within a reasonable period of time.1 A goal of remission is reasonably to halt joint damage. However, patients with RA in remission by any established criteria can still experience radiographic progression.2 In current clinical practice, as well as in most clinical trials, joint destruction is not the explicit target for treatment. Also more recent strict criteria for...
Carotid ultrasound in the cardiovascular risk stratification of patients with rheumatoid arthritis: when and for whom?
Gonzalez-Gay, M. A., Gonzalez-Juanatey, C., Llorca, J. Mon, 07 May 2012 09:17:26 -0700
Adequate stratification of cardiovascular (CV) risk is one of the major points of interest in the management of patients with rheumatoid arthritis (RA). A task force of the European League Against Rheumatism has proposed to adapt CV risk management calculated in RA patients according to the systematic coronary risk evaluation (SCORE) function by application of a multiplier factor of 1.5 in those patients with two of the following three criteria: disease duration >10 years, rheumatoid factor (RF) or anticyclic citrullinated peptide (anti-CCP) antibody positivity, and presence of severe extra-articular manifestations. However, a major concern when using the modified SCORE is to know whether the effect of chronic inflammation on the CV risk of RA patients can be fully determined using this tool. As increased carotid intima–media thickness (IMT) and carotid plaques have been proved to predict the development of CV events in RA, the authors suggest performing carotid ultrasound when SCORE does not yield results indicating high CV risk in RA patients with extra-articular manifestations, RF or anti-CCP positivity as well as in patients with 10 years disease duration or longer. The presence of abnormal carotid IMT (>0.90 mm) or carotid plaques would lead to these patients being considered as having high CV risk regardless of the results derived from the modified SCORE.
After treat-to-target: can a targeted ultrasound initiative improve RA outcomes?
Wakefield, R. J., D'Agostino, M. A., Naredo, E., Buch, M. H., Iagnocco, A., Terslev, L., Ostergaard, M., Backhaus, M., Grassi, W., Dougados, M., Burmester, G. R., Saleem, B., de Miguel, E., Estrach, C., Ikeda, K., Gutierrez, M., Thompson, R., Balint, P., Emery, P. Mon, 07 May 2012 09:17:26 -0700
For patients with rheumatoid arthritis (RA), remission can be achieved with tight control of inflammation and early use of disease modifying agents. The importance of remission as an outcome has been recently highlighted by European League Against Rheumatism recommendations. However, remission when defined by clinical remission criteria (disease activity score, simplified disease activity index, etc) does not always equate to the complete absence of inflammation as measured by new sensitive imaging techniques such as ultrasound (US) . There is evidence that imaging synovitis is frequently found in these patients and associated with adverse clinical and functional outcomes. This article reviews the data regarding remission, ultrasound imaging and outcomes in patients with RA to provide the background to a consensus statement from an international collaboration of ultrasonographers and rheumatologists who have recently formed a research network - the Targeted Ultrasound Initiative (TUI) group. The statement proposes that targeting therapy to PD activity provides superior outcomes compared with treating to clinical targets alone and introduces the rationale for a new randomised trial using targeted ultrasound in RA.
Smoking and risk of incident psoriatic arthritis in US women
Li, W., Han, J., Qureshi, A. A. Mon, 07 May 2012 09:17:26 -0700
Objectives Psoriatic arthritis (PsA) is an inflammatory arthritis that is associated with psoriasis. Previous studies have found an association between smoking and psoriasis, but the association with PsA is unclear. The authors aimed to evaluate the association between smoking and the risk of incident PsA in a large cohort of women. Methods 94 874 participants were included from the Nurses' Health Study II over a 14-year period (1991–2005). Information on smoking was collected biennially during follow-up. The incidence of clinician-diagnosed PsA was ascertained and confirmed by self-reported questionnaires. Results During 1 303 970 person-years' follow-up, the authors identified 157 incident PsA cases. Among total participants, smoking was associated with an elevated risk of incident PsA. Compared with never smokers, the RR was 1.54 for past smokers (95% CI 1.06 to 2.24) and 3.13 for current smokers (95% CI 2.08 to 4.71). With increasing smoking duration or pack-years, the risk of PsA increased monotonically (p for trend <0.0001). The increase in risk was particularly significant for PsA cases with more severe phenotypes. Secondary analysis among participants developing psoriasis during the follow-up replicated the association, demonstrating an increased risk of PsA among psoriasis cases. The risk was significant for those with higher cumulative measures of smoking or PsA cases with more severe phenotypes. Conclusion In this study smoking was found to be associated with a risk of PsA and cumulative measures of smoking were also associated with a higher risk of PsA among women.
Smokers in early axial spondyloarthritis have earlier disease onset, more disease activity, inflammation and damage, and poorer function and health-related quality of life: results from the DESIR cohort
Chung, H. Y., Machado, P., van der Heijde, D., D'Agostino, M.-A., Dougados, M. Mon, 07 May 2012 09:17:26 -0700
Objectives To investigate the association of smoking with various clinical, functional and imaging outcomes in patients with early axial spondyloarthritis (SpA). Methods 647 patients with early inflammatory back pain (IBP) fulfilling at least one of the internationally accepted SpA criteria and with available smoking data were included in the analyses. Clinical, demographic and imaging parameters were compared between smokers and non-smokers at a cross-sectional level. Variables with significant differences in univariate analyses were used as dependent variables in multivariate linear and logistic regression models adjusted for potential confounding/contributing factors. Results Multivariate analysis showed that smoking was associated with an earlier onset of IBP (regression coefficient (B)=(–1.46), p=0.04), higher disease activity (ankylosing spondylitis disease activity score B=0.20, p=0.03; Bath ankylosing spondylitis disease activity index B=0.50, p=0.003), worse functional status (Bath ankylosing spondylitis functional index B=0.38, p=0.02), more frequent MRI inflammation of the sacroiliac joints (OR 1.57, p=0.02) and the spine (OR 2.33, p<0.001), more frequent MRI structural lesions of the sacroiliac joints (OR 1.54, p=0.03) and the spine (OR 2.02, p=0.01), and higher modified Stoke ankylosing spondylitis spine score (B=0.54, p=0.03) reflecting radiographic structural damage of the spine. Smoking was also associated with poorer quality of life (Euro-quality of life questionnaire B=1.38, p<0.001, short form 36 physical B=(–4.89), p<0.001, and mental component score B=(–5.90), p<0.001). Conclusion In early axial SpA patients, smoking was independently associated with earlier onset of IBP, higher disease activity, increased axial inflammation on MRI, increased axial structural damage on MRI and radiographs, poorer functional status and poorer quality of life.

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