Rheumatoid Arthritis

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There are only a few studies dealing with the detection and clinical impact of calcium pyrophosphate (CPPD) crystals in patients with rheumatoid arthritis (RA) published to date. In particular, data determined by the cytospin technique, which is an effective tool to enhance the crystal detection rate, are lacking. The objectives of this study were to determine the prevalence of CPPD crystals in the synovial fluid (SF) of patients with RA and to investigate whether the detection of CPPD crystals is correlated with demographic, clinical and serological features. We examined 113 consecutive SF samples of patients with RA, obtained from therapeutic arthrocentesis of knee joints. After cytocentrifugation, the sediments were examined by polarized microscopy for the occurrence of CPPD crystals. Demographic, clinical and serological data, acquired from the medical records, were compared between crystal-positive and crystal-negative subjects. CPPD crystals were observed in 20 of the 113 cases, representing 17.7 %. CPPD-positive and CPPD-negative subjects did not differ significantly in sex, duration of disease, Steinbrocker radiologic stage, disease activity score 28, as well as serum rheumatoid factor and anti-CCP positivity. Patients positively tested for CPPD crystals had a significantly higher age than CPPD-negative patients (p \ 0.0001). An age-independent association of long-time treatment with diuretics and CPPD crystal formation was not found. In conclusion, demographic, clinical and serological characteristics of patients with RA were not associated with the occurrence of CPPD crystals. Age was the only significant influencing factor on CPPD crystal formation in patients with RA.

With the aim of developing a new enzyme-linked immunosorbent assay test to detect autoantibodies in the sera of rheumatoid arthritis patients with a high sensitivity and specificity using synthetic citrullinated peptides of fibrin (which is abundant in rheumatoid synovium) as antigenic substract, peptides belonging to α- and β-fibrin chains were selected by computer-aided prediction of antigenicity and epitope mapping and synthesized in solid phase. We analysed by enzyme-linked immunosorbent assay 133 sera from patients with well-characterized rheumatic diseases, including 67 patients with rheumatoid arthritis. The results of the immunoassays reported highlight the usefulness of fibrin-related peptides in rheumatoid arthritis diagnosis and, especially, the ability and specificity of the [Cit621,627,630]α-fibrin(617–631) (αfib617) peptide sequence to recognize the autoantibodies that are present in rheumatoid arthritis patients.

We analyzed the CT appearances of degenerative change in the atlanto-odontoid joint (AOJ) in patients with rheumatoid arthritis (RA) and evaluated the effect of these changes on atlanto-axial joint (AAJ) rotation by dynamic CT. This revealed that 9 patients (24%) treated with methotrexate had degenerative features in the AOJ. The ratio of AAJ rotation to the total rotation of the cervical spine was significantly higher in normal subjects (54±3%) than in patients (38±12%). The degree of AAJ rotation was significantly lower in the patient group with degenerative features in the AOJ (20.9±8.4°) than in patients without degenerative features (28.5±7.4°). RA patients with a history of longstanding disease and treatment with antirheumatic drugs may develop AO OA. Although secondary OA was described as healing phenomena in the joints of RA patients, it can limit rotation in the AAJ and cause suboccipital neck pain. A regular check-up of the AAJ and AOJ by means of dynamic CT in all RA patients is proposed to avoid possible antirheumatic drug complications.

This study investigated primary and secondary stressors of distress in rheumatoid arthritis patients and partners, analysing data of 61 couples. Patients' disability was found to be a primary stressor of their distress. In addition, it also had an indirect effect on partners' distress through partners' primary stressor, perceived burden. Marital quality and negative transactions can be considered joint secondary stressors for partners, not for patients. An indication of an indirect effect of marital quality on patients' distress was found, through partners' burden. Using a multilevel model, which takes into account the dependence between patients' and partners' distress, 36% of the variance in patients' distress could be explained, whereas 68% of partners' distress variance was explained. More knowledge on how patient and partner influence each other's distress is needed to develop psychosocial interventions that will help patients and partners minimize their psychological distress and prevent deterioration of their marital quality.

To describe patients' functional uses of 3 commercial wrist orthoses, to describe patients'preference patterns for the orthoses, and to clarifv orthotic attributes that are viewed positively and negatively Methods. Using a cross-over design, 42patients with definite rheumatoid arthritis used each of 3 commercial orthoses for one week. There was a one-week washout between each week of use. At the end of the study, private semi-structured interviews were conducted with each participant. Data from close-ended questions were tabulated. Open-ended data were analyzed using qualitative methods.

To compare the EULAR and SDAI50 response measures (RMs) and their impact on future response to treatment in patients with early rheumatoid arthritis (ERA). Biologic naïve ERA patients from the Canadian early ArThritis CoHort (CATCH) with complete data at baseline, 3 and 6 months were evaluated. Kappa statistics were used to evaluate the agreement between the EULAR (moderate or good response) and SDAI50 RMs. The RMs at 3 months were also compared for their ability to predict low disease activity state (LDAS) or remission (REM) at 6 months. A total of 1124 patients were evaluated. Of those, 215 (30%) and 294 (45%) patients failed to achieve a EULAR and SDAI50 RMs respectively. There was a good agreement between EULAR and SDAI50 RMs with a Kappa of 0.59 (95% CI 0.53- 0.66). Throughout the range of disease activity, the SDAI50 response was shown to be more stringent than the EULAR response. Multivariable linear regression analysis demonstrated that both RMs at 3 months were associated w...

Objective: To describe the clinical characteristics, histopathologic features, and outcomes of patients in whom vasculitis developed in association with use of tumor necrosis factor-␣ (TNF-␣) inhibitors. Patients and Methods: This is a retrospective review of patients evaluated at Mayo Clinic, Rochester, Minnesota, from January 1, 1998, through March 31, 2011, with a diagnosis of vasculitis induced by anti-TNF-␣ therapy. Results: Of 8 patients with vasculitis associated with anti-TNF-␣ therapy (mean age, 48.5 years), 6 (75%) were female. Four (50%) had rheumatoid arthritis, 1 (13%) had Crohn disease, and 3 (38%) had ulcerative colitis. Five (63%) were treated with infliximab, 2 (25%) with etanercept, and 1 (13%) with adalimumab. The mean duration of treatment before development of vasculitis was 34.5 months. The skin was the predominant organ affected (5 patients [63%]), with the most common cutaneous lesion being palpable purpura (4 of 5 [80%]). Two organs involved in systemic vasculitis were the peripheral nervous system (4 patients [50%]) and kidney (1 patient [13%]). All cases of vasculitis were histopathologically confirmed. Seven of 8 patients improved with discontinuation of therapy (mean time to resolution, 6.9 months) and adjuvant treatment (all 8 received prednisone; another agent was also used in 7); rechallenge with anti-TNF-␣ therapy was not attempted in any patient. At last follow-up, no patients had experienced a recurrence of vasculitis after therapy discontinuation. Conclusion: Cutaneous small-vessel vasculitis was the most common finding, but systemic vasculitis, including peripheral nerve and renal vasculitis, was also frequently observed.

This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the ...

Progression of Rheumatoid arthritis (RA) and osteoarthritis (OA) is associated with inflammation and oxidative stress. Previous studies have shown that there was no difference between RA and OA patients regarding the percentages of the different lymphocytes subsets reflecting the abnormalities in T cells and its subsets that may contribute to the pathogenesis of OA as in RA. Therefore, the present study was aimed to analyze that whether disease activity of OA is able to affect a few serological and biochemical parameters in the same way as RA does or differently. The study was done on 36 asymptomatic controls (25 women), 28 patients with OA (20 women), 36 patients with RA (22 women). Patients with OA were screened according to radiological and clinical finding of Kellgren and Lawrence grade and ACR criteria and assessed by VAS and WOMAC score. Patients with RA were selected who were fulfilling 4/5 symptoms of ACR criteria, and their DAS28-CRP, VAS score, and RF positivity were evaluated. Participants of the groups were matched for sex, age, weight, and height (body mass index). The BMI of all three groups was also found to be the same (P > 0.05). The mean level of LDL, Cholesterol, MDA, CRP, and Triglyceride was significantly (P < 0.05 or P < 0.01) higher in both OA and RA as compared to control. The mean level of total lipid, cholesterol, MDA, CRP, and triglyceride was found to be significantly (P < 0.05 or P < 0.01) higher in RA as compared to OA. The pre-treatment CRP level of both groups of patients showed significant and direct relation with total lipid (r = 0.27, P < 0.05) and cholesterol (r = 0.66, P < 0.01). Inverse relation was observed between Uric acid and Creatinine (r = −0.26, P < 0.05) and cholesterol and HDL (r = −0.34, P < 0.01). Our study shows the similar trend in lipid profile and other parameters studied in both patients with OA and patients with RA with more pronounced changes in RA.

Objective. Since fibroblasts in the synovium of patients with rheumatoid arthritis (RA) express the serine proteases fibroblast activation protein (FAP) and dipeptidylpeptidase 4 (DPP-4)/CD26, we undertook the current study to determine the functional role of both enzymes in the invasion of RA synovial fibroblasts (RASFs) into articular cartilage.

A Artrite Reumatóide (AR) é considerada uma doença inflamatória crônica, de origem auto-imune e etiologia desconhecida. Além do tratamento fisioterápico e farmacológico, fortes evidências apontam benefícios no uso de exercícios físicos (EF) na sua terapêutica. Porém, ainda ...

Objective. To estimate the nationwide incidence of rheumatoid arthritis (RA) in Sweden, including its variation across age, sex, geography, and demography, and to describe the sensitivity of register-based incidence estimates to different RA case definitions. Methods. Incident RA patients were identified using the Swedish National Patient Register. In the base case, incident RA was defined as first-ever inpatient or nonprimary outpatient care visit listing an RA diagnosis in 2006 -2008, with a second visit listing RA within 1 year. Patients prescribed disease-modifying antirheumatic drugs more than 6 months prior to the first visit listing RA were not regarded as incident. The robustness of this definition was evaluated by more liberal and strict criteria, and by penetration of antirheumatic treatment. individuals were identified as incident RA patients. The overall incidence was 41 per 100,000 (56 for women, 25 for men). The incidence increased with age and peaked in the 70 -79 years age group for both women and men. The age-and sex-standardized incidences were lower in densely populated areas and in individuals with high educational level. No geographic trends were noted. More liberal and strict definitions of RA only altered the observed incidence by approximately 14%. Conclusion. The overall nationwide register-based incidence of RA was robust across different case definitions. In a country with universal access to care, RA displayed demographic and socioeconomic, but no geographic, variations in incidence, and peaks at an older age than most commonly reported, with no difference in peak age at RA onset between sexes.

The co-occurrence of autoimmune diseases such as rheumatoid arthritis (RA) and type 1 diabetes mellitus (DM) has been reported in individuals and families. In this study, the strength and nature of this association were investigated at the population level in a Swedish case-control cohort. Methods. For this case-control study, 1,419 patients with incident RA diagnosed between 1996 and 2003 were recruited from university, public, and private rheumatology units throughout Sweden; 1,674 matched control subjects were recruited from the Swedish national population registry. Sera from the subjects were tested for the presence of antibodies to cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), and the 620W PTPN22 allele. Information on a history of diabetes was obtained by questionnaire, telephone interview, and/or medical record review. The prevalence of type 1 DM and type 2 DM was compared between patients with incident RA and control subjects and further stratified for the presence of anti-CCP, RF, and the PTPN22 risk allele. Results. Type 1 DM was associated with an increased risk of RA (odds ratio [OR] 4.9, 95% confidence interval [95% CI] 1.8-13.1), and this association was specific for anti-CCP-positive RA (OR 7.3, 95% CI 2.7-20.0), but not anti-CCP-negative RA. Further adjustment for the presence of PTPN22 attenuated the risk of anti-CCP-positive RA in patients with type 1 DM to an OR of 5.3 (95% CI 1.5-18.7). No association between RA and type 2 DM was observed. Conclusion. The association between type 1 DM and RA is specific for a particular RA subset, anti-CCPpositive RA. The risk of developing RA later in life in patients with type 1 DM may be attributed, in part, to the presence of the 620W PTPN22 allele, suggesting that this risk factor may represent a common pathway for the pathogenesis of these 2 diseases. Autoimmune diseases such as rheumatoid arthritis (RA) and type 1 diabetes mellitus (DM) have been observed to co-occur within individuals and families (1-4). Although the exact etiologies of RA and type 1 DM are unknown, they are likely attributable to a combination of genetic susceptibility and interactions between environmental risk factors and genes. Thus far, one established genetic risk factor is shared by RA and type 1 DM: the 620W allele of the protein tyrosine phosphatase N22 gene (PTPN22) (5-9). Other genes involved in the pathogenesis of RA and type 1 DM have

Rheumatoid arthritis (RA) is characterized by inflammation of the synovial membrane, which can lead to deformities and functional disability. Unlike the dorsal and lumbar spine, the cervical spine is often affected by RA. The objective of this paper is to assess cervical pain and function in patients with RA and correlate these variables with overall function, quality of life, and radiographic findings on the cervical spine. One hundred individuals aged 18 to 65 years were divided into study group (50 patients with rheumatoid arthritis) and control group (50 healthy individuals, paired for gender and age). Patients with prior surgery, prior trauma or other symptomatic cervical spine condition were excluded. The visual analogue pain scale (VAS), Neck Pain and Disability Scale (NPDS), SF-36, HAQ and X-rays were used for evaluation purposes. Mean disease duration was 11.1 years. The cervical VAS was 2.4 cm and 1.3 cm for the study and control groups, respectively (p=0.074). Statistical differences were found in NPDS scores, mean=26.7 and 6.9, and HAQ scores, mean=1.1 and 0.1, for the study and control groups, respectively (p<0.001). SF-36 scores were statistically worse in the study group, except for the vitality, social aspects and mental health subscales. There was a positive correlation between the NPDS and VAS (r=0.54) and between the NPDS and HAQ (r=0.67). There was a negative correlation between the NPDS and SF-36 functional capacity domain (r=−0.53) and physical limitation domain (r=−0.58). The radiographic findings revealed more prevalent anterior atlanto-axial subluxation (p= 0.030), listhesis in neutral posture (p=0.037), listhesis in extension (p=0.007), degenerative alteration of C4-C5 segment (p=0.023), size of C2 spinal canal (p=0.002) and C3 spinal canal (p=0.029) in the study group. Patients with RA have poorer cervical function than healthy individuals, although there is no difference in cervical pain.

Objective Methotrexate (MTX) is the drug of choice for rheumatoid arthritis (RA) but is effective only in around 60% of treated patients. Bioavailability of MTX may be a major determinant of response status and this may be governed by variations in MTX receptor and transporter genes and genes responsible for polyglutamation and deconjugation. We investigated the contribution of single nucleotide polymorphisms (SNPs) in RFC, FOLR1, FPGS, GGH and MDR1 genes to MTX response in RA patients from North India.

It was reported that lipid peroxidation (LPO) products increase in rheumatoid arthritis (RA) patients and increased LPO products reduce many antioxidants. Lipid hydroperoxides (LOOHs) are byproduct of LPO. Paraoxonase (PON), arylesterase (ARE), free sulfhydryl (SH) groups, and ceruloplasmin (CP) are enzymes or proteins with antioxidant characteristics. This study aims to determine the levels of LOOHs and SH, and the activities of PON1, ARE, and CP in RA patients. The study included 47 active RA cases and 23 healthy volunteers. The levels of LOOHs and SH, and the activities of PON1, ARE, and CP were determined using appropriate methods. Student's t test and Spearman's correlation analysis methods were employed in the statistical evaluation. The level of LOOHs was found to be higher (p<0.001), while the level of SH and the activities of PON1, ARE, and CP were found to be lower (p<0.001, <0.001, <0.01, and <0.01, respectively) in the RA patient group when compared with the control group. There was a negative correlation between the level of LOOHs and the activity of PON1 in the patient group (r=−0.420 and p<0.01). The results of our study indicate increased oxidant and decreased antioxidant presence in RA patients. PON1 and ARE are known to have antiatherosclerotic effects in addition to their antioxidant characteristics. As the decrease in these antioxidants, resulting from increased oxidative stress in RA patients, development of atherosclerosis besides tissue injury seems inevitable.

Four hundred and forty unrelated British Caucasoid patients with rheumatoid arthritis (RA) have been HLA typed for class I and class II antigens. Analyses of HLA antigen associations were performed on the overall group and in patient subsets selected according to particular disease parameters or sex, or both. The results confirm previously reported positive associations of HLA-DR4, Dw4, and DRw53 and negative associations of HLA-DR2 and DR7 with RA. Patients subsets with severe erosions, seropositivity, and features of extra-articular disease showed a stronger association, also confirming earlier reports. The link between HLA and disease severity was emphasised by a significant trend of increased Dw4 frequency with increasing severity of radiological erosions. In addition, a positive association of RA with HLA-A2 was observed and a strong negative association with DR3. The frequency of HLA-B27 was significantly increased in patients with subluxation of the spine. Differences were observed between male and female patients in relation to the HLA association. In men an increase in the frequency of the haplotype HLAIDw4/DR4/Bw62/Cw3/A2 was observed. This showed no relationship with parameters of disease severity other than extra-articular disease. In women only class II antigens (DRw53/Dw4/DR4) showed an increased frequency. This increase was strongly associated with disease severity. A significant decrease of this class II association was observed with increasing age of disease onset; this was not seen in men.

Despite aggressive immunosuppression with biologics and traditional DMARDs, achieving disease remission remains an unmet goal for most rheumatoid arthritis (RA) patients. In this context, there is a demand for novel treatment strategies, with kinase inhibitors expected to enrich the existing therapeutic armamentarium. In RA some kinases participate in the generation of pathogenic signaling cascades. Pharmacologic inhibition of kinases that mediate pathogenic signal transduction heralds a new era for RA therapeutics. Oral inhibitors of JAKs, Syk, PI3Ks, MAPKs and Btk are under development or in clinical trials in patients with RA. In this review, we discuss the scientific rationale for the use of kinase inhibitors in RA and summarize the experience from clinical trials.

Ursolic acid (UA), a pentacyclic triterpene acid found in apple peels (Malus domestica, Borkh, Rosaceae), has a large spectrum of pharmacological effects. However, the vegetal matrix usually produces highly viscous and poorly soluble extracts that hamper the isolation of this compound. To overcome this problem, the crude EtOH-AcOEt extract of commercial apple peels was exhaustively treated with diazomethane, after which methyl ursolate (MU) was purified by column chromatography and characterized spectrometrically. The anti-inflammatory effects of UA and MU (50 mg/kg) were analyzed by zymosaninduced paw edema, pleurisy and in an experimental arthritis model. After 4 h of treatment with UA and MU, paw edema was reduced by 46 and 44 %, respectively. Both UA and MU inhibited protein extravasation into the thoracic cavity; tibio-femoral edema by 40 and 48 %, respectively; and leukocyte influx into the synovial cavity after 6 h by 52 and 73 %, respectively. Additionally, both UA and MU decreased the levels of mediators related to synovial inflammation, such as KC/CXCL-1 levels by 95 and 90 %, TNF-a levels by 76 and 71 %, and IL-1b levels by 57 and 53 %, respectively. Both the compounds were equally effective when assayed in different inflammatory models, including experimental arthritis. Hence, MU may be considered to be a useful anti-inflammatory derivative to overcome the inherent poor solubility of UA for formulating pharmaceutical products.

IL-15 is a proinflammatory cytokine that acts early in the inflammatory response and has been associated with several autoimmune diseases including rheumatoid arthritis, where it had been proposed as a therapeutic target. We recently reported an IL-15 antagonist peptide corresponding to sequence 36-45 of IL-15 (KVTAMKCFLL) named P8, which specifically binds to IL-15Ra and inhibits IL-15 biological activity with a half maximal inhibitory concentration (IC50) of 130 µM in CTLL-2 proliferation assay. In order to improve binding of peptide P8 to the receptor IL-15Rα, we used an Ala scan strategy to study contribution of each individual amino acid to the peptide's antagonist effect. Here, we found that Phe and Cys are important for peptide binding to IL-15Rα. We also investigated other single site mutations and replaced the second Lys in the sequence by the polar non-charged amino acid threonine. The resulting peptide [K6T]P8 exhibited a higher activity than P8 with an IC50 of 24 µM. We also found that this peptide was more active than peptide P8 in the inhibition of TNFα secretion by synovial cells from rheumatoid arthritis patients. The peptide [K6T]P8 described in this work is a new type of IL-15 antagonist and constitutes a potential therapeutic agent for rheumatoid arthritis.

Cervical spine involvement commonly occurs in patients with rheumatoid arthritis (RA), especially those with inadequate treatment or severe disease forms. The most common site affected by RA is the atlantoaxial joint, potentially resulting in atlantoaxial instability, with cervical pain and neurological deficits. The second most common site of involvement is the subaxial cervical spine, often with subluxation, resulting in nerve root or spinal cord compression. In this paper, the authors review the most commonly used plain radiographic criteria to diagnose cervical instabilities seen with RA. Finally, we discuss the advantages and disadvantages of cervical CT and MRI in the setting of cervical involvement in RA.

Rheumatoid arthritis affects 0.5-1% of the general population. The prediction and prognosis of the disease varies for each individual and its course can detrimentally affect the psychosocial condition of the patient. Clinicians and Therapists aim to quickly diagnose and treat those with this debilitating disease. Detection relies heavily on manual evaluation methods that are dependent on training and can vary between observers. Angle measuring instrument, tape measure and grip strength dynamometer are used to assess the joint range and strength of a patient to determine their hand function. Joint stiffness can be a determining factor when diagnosing the advancement and improvement of Rheumatoid Arthritis (RA). This paper outlines the development of a hand movement measurement tool to accurately quantify patients&#39; flexion, extension, abduction and adduction movement of each finger joint and quantifies the symptom of &quot;early morning stiffness&quot;. It also describes the probl...

Objectives.-To develop recommendations for the information and education of patients with rheumatoid arthritis (RA) seen in everyday practice, using evidence from the literature, supplemented with expert opinion when needed. Methods.-A scientific committee developed eight questions using the Delphi consensus procedure. A task force reviewed the literature for answers to these questions, using the PubMed Medline database (1980-2004) and the 2002-2004 databases of the annual meetings held by the French Society for Rheumatology (SFR), the European League Against Rheumatism (EULAR), and the American College of Rheumatology (ACR); the indexing terms for the search were rheumatoid, arthritis, patient, education, information, knowledge, general practitioner, family doctor, and continuing medical education. Only articles in French or English were included. A panel of rheumatologists used the evidence thus compiled to develop recommendations for each question; gaps in evidence were filled by calling on the panelists' expert opinion. For each recommendation, the level of evidence and extent of agreement among panelists were specified. Results.-There were four general questions about the objectives, supports, and mode of delivery (group or one-on-one) of patient information and education, as well as on evaluating knowledge, and four specific questions on program content. The search identified 1235 articles; 144 were selected on the title and 118 of those on the abstract. Three abstracts presented at meetings were also kept. The evidence from the literature was presented to the panelists during interactive workshops. The panelists then developed eight recommendations, all of which were grade D because no published studies specifically addressed everyday clinical practice. Agreement among panelists ranged across recommendations from 85.7% to 100%. Conclusion.-Recommendations about educating and informing patients with RA in everyday practice were developed. They should increase practice uniformity and ultimately optimize the management of patients with RA.

The differentiation of mouse T H 17 cells requires transforming growth factor β and iL-6, whereas human naive T cells can develop into T H 17 cells in the presence of iL-1β and iL-23 alone, transforming growth factor β having an indirect role in their development via the selective inhibition of T H 1 cell expansion. in both mice and humans, a late developmental plasticity of T H 17 cells towards the T H 1 lineage has been shown. Mainly based on mouse gene knockout studies, T H 17 lymphocytes have been found to have a pathogenic role in several autoimmune disorders; however, whether human autoimmune disorders, including rheumatoid arthritis (rA) and psoriasis, are prevalently T H 1-mediated or T H 17-mediated, is still unclear. research suggests that both T H 1 and T H 17 cells are involved in rA pathogenesis, raising the possibility that interventions that target both the iL-23-iL-17 (T H 17) and the iL-12-interferon γ (T H 1) axes might be successful future therapeutic approaches for rA.

Background: The mechanisms underlying tolerance induction and maintenance in autoimmune arthritis remain elusive. In a mouse model of rheumatoid arthritis, collagen type II (CII)-induced arthritis, we explore the contribution of B cells to antigen-specific tolerance. Methods: To generate expression of the CII-peptide specifically on B-cell major histocompatibility complex type II, lentiviral-based gene therapy including a B-cell-specific Igk promoter was used. Results: Presentation of the CII-peptide on B cells significantly reduced the frequency and severity of arthritis as well as the serum levels of CII-specific IgG antibodies. Further, both frequency and suppressive function of regulatory T cells were increased in tolerized mice. Adoptive transfer of regulatory T cells from tolerized mice to naïve mice ameliorated the development of CII-induced arthritis. Conclusion: Our data suggest that endogenous presentation of the CII-peptide on B cells is one of the key contributors to arthritis tolerance induction and maintenance.

Objective. To evaluate the sensitivity and specificity of the Gait, Arms, Legs, and Spine (GALS) examination to screen for signs and symptoms of rheumatoid arthritis (RA) when used by family physicians and nurse practitioners. Methods. Participating health care professionals (2 rheumatologists, 3 family physicians, and 3 nurse practitioners) were trained to perform the GALS examination by viewing an instructional DVD and attending a training workshop. One week after training, the health care professionals performed the GALS examination on 20 individuals with RA and 21 individuals without RA. All participants were recruited through 2 rheumatology practices, and each participant was assessed by 4 health care professionals. The health care professionals were asked to record whether observed signs and symptoms were potentially consistent with a diagnosis of RA. The health care professionals understood the study objective to be their agreement on GALS findings among one another and were unaware that one-half of the participants had RA. Sensitivity and specificity were calculated to determine the ability of the GALS examination to screen for RA using the rheumatologist as the standard for comparison. Results. Sensitivity and specificity values varied from 60-100% and 70-82%, respectively, for the 3 family physicians, and 60-90% and 73-100%, respectively, for the 3 nurse practitioners. Conclusion. Following a very short training period, family physicians and nurse practitioners appeared to be able to use the GALS examination as a screening tool for RA signs and symptoms, particularly for identifying an individual with positive results who will benefit from further investigation or rheumatology referral.

Undifferentiated arthritis (UA) is a label applied to patients with joint complaints which cannot be classified according to current criteria, which implies a need for precision diagnostic technologies. We studied serum galectin-3, a proinflammatory mediator, and seromarkers of structural joint elements in patients with early, UA and their associations with disease profile and biochemical and imaging findings. One hundred and eleven UA patients were followed-up for at least 12 months and reclassified according to appropriate criteria (TUDAR). At baseline, demographics and laboratory and clinical disease measures, as well as wrist magnetic resonance imaging (MRI) synovitis, erosion, and bone marrow edema scorings, were recorded. Galectin-3, the type IIA collagen N-terminal propeptide (PIIANP), which is a marker of regenerative cartilage formation, and hyaluronan (HYA), which is prevalent in synovial tissue swellings, were measured by enzyme-linked immunosorbent assay (ELISA). Receive...

Background & Aims: Rheumatoid arthritis (RA) is complicated by cytokine-driven alterations in protein and energy metabolism and consequent muscle wasting (cachexia). The aim of this randomised controlled trial was to investigate the efficacy of a mixture of b-hydroxy-b-methylbutyrate, glutamine and arginine (HMB/ GLN/ARG) as nutritional treatment for rheumatoid cachexia. Methods: Forty RA patients supplemented their diet with either HMB/GLN/ARG or a nitrogen (7.19 g/day) and calorie (180 kcal/day) balanced mixture of alanine, glutamic acid, glycine, and serine (placebo) for 12 weeks. Body composition and other outcomes were assessed at baseline and follow-up, and analysed by mixed ANOVA. Results: Dietary supplementation with HMB/GLN/ARG was not superior to placebo in the treatment of rheumatoid cachexia (group  time interactions P40:05 for all outcomes). Both amino acid mixtures significantly increased (main effect of time) fat-free mass (72771186 g, Po0:01), total body protein (71971703 g, P ¼ 0:02), arms (1127183 g, Po0:01) and legs (2837534 g, Po0:01) lean mass, and some measures of physical function. No significant adverse event occurred during the study, but patients in the HMB/GLN/ARG group reported fewer gastrointestinal complaints compared to placebo. Conclusions: Dietary supplementation with HMB/GLN/ARG is better tolerated but not more effective in reversing cachexia in RA patients compared to the mixture of other non-essential amino acids used as placebo. Further controlled studies are necessary to confirm the beneficial anabolic and functional effects of increased nitrogen intake in this population.

This study aimed to identify subgroups with distinct trajectories of functional (HAQ) progression over 10 years following diagnosis of RA and identify baseline characteristics associated with the trajectories and their prognostic value for mortality. Between 1986 and 1998, 1460 patients with RA symptoms &lt;2 years and prior to disease-modifying treatment (DMARDs) were recruited to an inception cohort (Early RA Study). Standard clinical, functional and laboratory assessments were performed at presentation and annually. Deaths were tracked by the National Health Service Central Register. Growth mixture modelling was used to identify distinct trajectories of HAQ score progression and survival analysis employed to compare all-cause mortality across the trajectory classes. Four HAQ score progression classes were identified: moderate increasing (46%), low stable (6%), moderate stable (28%) and high stable (20%). Only the moderate-increasing class exhibited an accelerated decline in funct...

To compare the outcomes of wrist arthrodesis and arthroplasty in the treatment of rheumatoid arthritis using validated outcome patient surveys and a review of surgical complications in 2 matched cohorts. Methods: Forty-six patients with 51 operated wrists (24 arthrodeses and 27 arthroplasties) were reviewed retrospectively at a follow-up range of 1 to 5 years. Patients completed the Disabilities of the Arm, Shoulder and Hand (DASH) inventory, the Patient-Rated Wrist Evaluation (PRWE), and a questionnaire designed specifically for this study. Surgical complications were obtained by chart review. Results: Treatment groups were well matched by patient characteristics and radiographic staging. There were no statistical differences in the survey scores between the 2 groups. Patients in the arthroplasty group, however, reported a trend toward greater ease with personal hygiene and fastening buttons. Complication rates were similar with a 56% complication rate in the arthrodesis group (22% major, 35% minor) and a 52% complication rate in the arthroplasty group (11% major, 41% minor). Conclusions: The DASH and PRWE may not be designed properly to measure impairment caused by wrist disease in patients with generalized arthritis. The results show that patients with rheumatoid arthritis can and do accommodate to a wrist arthrodesis. It should not be construed, however, that these patients would not prefer or obtain greater benefit from a wrist arthroplasty or that they would not obtain greater benefit from an arthrodesis. (J Hand Surg 2003;28A:570 -576.

The diagnosis of osteoporosis is based on the measurement of bone mineral density (BMD). There are a number of clinical risk factors that provide information on fracture risk over and above that given by BMD. The assessment of fracture risk thus needs to be distinguished from diagnosis to take account of the independent value of the clinical risk factors. These include age, a prior fragility fracture, a parental history of hip fracture, smoking, use of systemic corticosteroids, excess alcohol intake and rheumatoid arthritis. The independent contribution of these risk factors can be integrated by the calculation of fracture probability with or without the use of BMD. Treatment can then be offered to those identified to have a fracture probability greater than an intervention threshold.

A reduction of plasma fibrinogen has been suggested as one mechanism through which physical activity would protect against coronary heart disease (CHD). Therefore, we investigated the association of conditioning leisure time physical activity (CLTPA), assessed quantitatively by a 1Zmonth history, and maximal oxygen uptake (V,,,) with plasma fibrinogen concentration in eastern Finnish men aged 42-60 years. A high mean intensity of CLTPA (standardized multivariate regression coefficient /3 -0.059, p = 0.020) and a high maximal oxygen uptake (/I -0.163, p < 0.001) were associated with reduced plasma fibrinogen when adjusting for the strongest covariates. The adjusted relative difference in plasma fibrinogen concentration was 6.6% between men with a mean CLTPA intensity of < 4 and > 8 METS and 9.1% between the extreme quartiles of Vo,_ (< 2.21 vs >2.96 l/min). The association between the mean intensity of CLTPA (p = 0.030 for interaction) and V,,, (p = 0.033) and plasma fibrinogen was stronger for smokers than for non-smokers. These data indicate that a reduction of plasma fibrinogen concentration may be one mechanism through which moderate to high intensity CLTPA and high cardiorespiratory fitness reduce the risk of CHD.

Patients with antineutrophil cytoplasm antibodies (ANCA)-associated vasculitis (AASV) commonly suffer from arthralgias and, sometimes, polyarthritis during disease flares. Although rheumatoid factor (RF) can be detected in up to 37-50% of AASV patients, anti-cyclic citrullinated peptide (anti-CCP) antibodies are rare. Herein, we describe the clinical features of five P-ANCA-positive vasculitis patients, who had persistent and/or high anti-CCP levels and, more importantly, suffered from remittent non-destructive arthralgias and polysynovitis, independently of the vasculitis course and without evidence of RA. Two were initially thought to have RA rather than microscopic polyangiitis and, at AASV diagnosis, all had kidney involvement and three had alveolar hemorrhages. With a median follow-up of 30 months, one suffered vasculitis relapses, preceded by polysynovitis, and others had remittent arthralgias and polysynovitis, while their vasculitides remained in remission. None of these patients had radiological destructive arthritis. We discuss the challenge of diagnosing these patients positive for anti-CCP and ANCA, and with dominant articular manifestations. AASV patients with anti-CCP antibodies may experience relapsing polysynovitis and non-erosive polyarthritis prior to vasculitis flares, but also independently of the vasculitis course, which is uncommon in AASV, and might represent a small subgroup of AASV patients.