Rheumatology, a subspecialty of internal medicine, is devoted to the diagnosis and treatment of rheumatic diseases. The term originates from the Greek rheuma, meaning "that which flows as a river or stream" and the suffix -ology, meaning "the study of". Rheumatologists mainly deal with problems involving the muscles and/or joints.

Diseases

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Diseases diagnosed or managed by the rheumatologist include:

• rheumatoid arthritis
• lupus erythematosus
• Sjögren's syndrome
• scleroderma (systemic sclerosis)
• dermatomyositis
• polychondritis
• polymyositis
• polymyalgia rheumatica
• osteoarthritis
• septic arthritis
• gout, pseudogout
• spondyloarthropathies
  • ankylosing spondylitis
  • reactive arthritis (Reiter's syndrome)
  • psoriatic arthropathy
  • enteropathic spondylitis
  • reactive arthropathy
• vasculitis
  • polyarteritis nodosa
  • Henoch-Schönlein purpura
  • serum sickness
  • Wegener's granulomatosis
  • giant cell arteritis
  • temporal arteritis
  • Takayasu's arteritis
  • Behçet's syndrome
  • Kawasaki's disease (mucocutaneous lymph node syndrome)
  • Buerger's disease (thromboangiitis obliterans)

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Arthritis Research & Therapy - Latest Articles

An in vivo investigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis
David McErlainVeronica UliciMark DarlingJoe GatiVasek PitelkaFrank BeierDavid Holdsworth Fri, 03 Feb 2012 00:00:00 -0000
IntroductionSubchondral bone cysts (SBC) have been identified in patients with knee Osteoarthritis (OA) as a cause of greater pain, loss of cartilage and increased chance of joint replacement surgery. Few studies monitor SBC longitudinally, and clinical research using three-dimensional imaging techniques, such as magnetic resonance imaging (MRI), is limited to retrospective analyses as SBC are identified within an OA patient cohort. The purpose of this study was to use dual-modality, preclinical imaging to monitor the initiation and progression of SBC occurring within an established rodent model of knee OA. Methods: Eight rodents underwent anterior cruciate ligament transection and partial medial meniscectomy (ACLX) of the right knee. In vivo 9.4 T MRI and micro-computed tomography (micro-CT) scans were performed consecutively prior to ACLX and 4, 8, and 12 weeks post-ACLX. Resultant images were co-registered using anatomical landmarks, which allowed for precise tracking of SBC size and composition throughout the study. The diameter of the SBC was measured, and the volumetric bone mineral density (vBMD) was calculated within the bone adjacent to SBC. At 12 weeks, the ACLX and contralateral knees were processed for histological analysis, immuno-histochemistry, and OARSI pathological scoring. Results: At 4 weeks post-ACLX, 75 % of the rodent knees had at least 1 cyst that formed in the medial tibial plateau; by 12 weeks all ACLX knees contained SBC. Imaging data revealed the SBC originate in the presence of a subchondral bone plate breach, with evolving composition over time. The diameter of the SBC increased significantly over time (p = 0.0033) and the vBMD significantly decreased at 8 weeks post-ACLX (p = 0.033). Histological analysis demonstrated positive staining for bone resorption and formation surrounding the SBC, which were consistently located beneath the joint surface with the greatest cartilage damage. Trabecular bone adjacent the SBC lacked viable osteocytes and - combined with bone marrow changes - indicated osteonecrosis. Conclusions: This study provides insight into the mechanisms leading to SBC formation in knee OA. The expansion of these lesions is due to stress-induced bone resorption from the incurred mechanical instability. Therefore we suggest these lesions can be more accurately described as a form of OA-induced osteonecrosis, rather than 'subchondral cysts'.
Specific post-translational histone modifications of neutrophil extracellular traps as immunogens and potential targets of lupus autoantibodies
Chih Long LiuStephanie TangsombatvisitJacob RosenbergGil MandelbaumEmily GillespieOr GozaniAsh AlizadehPaul Utz Thu, 02 Feb 2012 00:00:00 -0000
IntroductionAutoreactivity to histones is a pervasive feature of several human autoimmune disorders including systemic lupus erythematosus (SLE). Specific post-translational modifications (PTMs) of histones within neutrophil extracellular traps (NETs) may potentially drive the process by which tolerance to these chromatin-associated proteins is broken. We hypothesized that NETs and their unique histone PTMs might be capable of inducing autoantibodies that target histones. Methods: We developed a novel and efficient method for the in vitro production, visualization, and broad profiling of histone-PTMs of human and murine NETs. We also immunized Balb/c mice with murine NETs and profiled their sera on autoantigen and histone peptide microarrays for evidence of autoantibody production to their immunogen. Results: We confirmed specificity toward acetyl-modified histone H2B as well as to other histone PTMs in sera from patients with SLE known to have autoreactivity against histones. We observed enrichment for distinctive histone marks of transcriptionally silent DNA during NETosis triggered by diverse stimuli. However, NETs derived from human and murine sources did not harbor many of the PTMs toward which autoreactivity was observed in patients with SLE or in MRL/lpr mice. Further, while murine NETs were weak autoantigens in vivo, there was only partial overlap in the IgG and IgM autoantibody profiles induced by vaccination of mice with NETs and those seen in patients with SLE. Conclusions: Isolated in vivo exposure to NETs is insufficient to break tolerance and may involve additional factors that have yet to be identified.
Therapy of lupus nephritis: lessons learned from clinical research and daily care to patients
Frédéric Houssiau Tue, 31 Jan 2012 00:00:00 -0000
Despite numerous randomized clinical trials over the last three decades for identifying the optimal treatment option for lupus nephritis, renal involvement still significantly impacts the survival and quality of life of patients with lupus and the search for the ideal immunosuppressive regimen is far from complete. The purpose of this review is to summarize the major recent achievements in the field. More specifically, the following topics will be discussed: intravenous cyclophosphamide versus mycophenolate mofetil (MMF) for induction; azathioprine versus MMF for maintenance; targeted therapies. The review will address clues for optimal global care, such as the need for complete initial evaluation, the importance of patient education, the unmasking of non-compliance to therapy, the reason for an early treatment switch in non-responding patients, the need for prolonged immunosuppression, optimal renal protection, and prevention of cardiovascular disease and other comorbidities.
A profile of immune response to herpesvirus is associated with radiographic damage in rheumatoid arthritis
John DavisKeith KnutsonJohn SkinnerMichael StrausbauchCynthia CrowsonTerry TherneauPeter WettsteinEric MattesonSherine Gabriel Tue, 31 Jan 2012 00:00:00 -0000
IntroductionProgression of joint damage despite appropriate therapy remains a significant problem for patients with rheumatoid arthritis (RA). This study was undertaken to identify profiles of immune response that correlate with radiographic joint damage as a first step toward the discovery of new pathogenic mechanisms of joint destruction in RA. Methods: The study included 58 patients with RA and 15 healthy controls. The profiles of cytokine release from peripheral blood mononuclear cells (PBMC) in response to stimulation for 48 hours with one of six stimuli, or in media alone, were measured. Immune response profiles identified for each stimulus were correlated with radiographic joint damage as defined by the Sharp-van der Heijde score (SHS), before and after multivariable adjustment. For profiles correlated with the SHS, the distributions of individual cytokines were evaluated in patients according to the severity of joint damage and compared to healthy controls. Results: The immune response profile for cytomegalovirus (CMV) / Epstein-Barr virus (EBV) stimulation was correlated with both the SHS total and erosion scores (r = 0.31, p = 0.018 and r = 0.33, p = 0.011, respectively). After adjusting for age, sex, disease duration, autoantibody status, CMV/EBV serological status, current disease activity, disability, and treatments, the correlation of the CMV/EBV immune response and the SHS erosion score became stronger (r = 0.43, p < 0.003). The CMV/EBV immune response correlated with CMV IgG (r = 0.44, p < 0.001), but not with EBV IgG. The most important cytokines for the CMV/EBV immune response profile were IFN-gamma, IL-2, IL-4, IL-5, IL-13 and IL-17A, all of which are associated with T-cell immunity. Both the summary immune response score and the individual responses of IFN-gamma and IL-13 to CMV/EBV stimulation were associated with greater joint damage. Conclusions: A profile of immune response to purified CMV/EBV lysates is associated with radiographic joint damage. The correlation of this immune response to CMV serology implies possible involvement of latent CMV infection. Therefore, the findings suggest that the immune response to latent CMV infection could play a fundamental role in the progression of inflammation and structural joint damage in patients with RA.
Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis?
Yves HenrotinAli MobasheriMarc Marty Mon, 30 Jan 2012 00:00:00 -0000
Glucosamine in its acetylated form is a natural constituent of some glycosaminoglycans (for example, hyaluronic acid and keratan sulfate) in the proteoglycans found in articular cartilage, intervertebral disc and synovial fluid. Glucosamine can be extracted and stabilized by chemical modification and used as a drug or a nutraceutical. It has been approved for the treatment of osteoarthritis (OA) in Europe to promote cartilage and joint health and is sold over the counter as a dietary supplement in the United States. Various formulations of glucosamine have been tested, including glucosamine sulfate and glucosamine hydrochloride. In vitro and in vivo studies have uncovered glucosamine's mechanisms of action on articular tissues (cartilage, synovial membrane and subchondral bone) and justified its efficacy by demonstrating structure-modifying and anti-inflammatory effects at high concentrations. However, results from clinical trials have raised many concerns. Pharmacokinetic studies have shown that glucosamine is easily absorbed, but the current treatment doses (for example, 1,500 mg/day) barely reach the required therapeutic concentration in plasma and tissue. The symptomatic effect size of glucosamine varies greatly depending on the formulation used and the quality of clinical trials. Importantly, the effect size reduces when evidence is accumulated chronologically and evidence for the structure-modifying effects of glucosamine are sparse. Hence, glucosamine was at first recommended by EULAR and OARSI for the management of knee pain and structure improvement in OA patients, but not in the most recent NICE guidelines. Consequently, the published recommendations for the management of OA require revision. Glucosamine is generally safe and although there are concerns about potential allergic and salt-related side effects of some formulations, no major adverse events have been reported so far. This paper examines all the in vitro and in vivo evidence for the mechanism of action of glucosamine as well as reviews the results of clinical trials. The pharmacokinetics, side effects and differences observed with different formulations of glucosamine and combination therapies are also considered. Finally, the importance of study design and criteria of evaluation are highlighted as new compounds represent new interesting options for the management of OA.
Extracellular nicotinamide phosphoribosyltransferase (NAMPT/visfatin) inhibits insulin-like growth factor-1 signaling and proteoglycan synthesis in human articular chondrocytes
Raghunatha YammaniRichard Loeser Mon, 30 Jan 2012 00:00:00 -0000
IntroductionObesity is one of the major risk factors for the development of osteoarthritis (OA). Although the mechanical factors appear to be critical, recent studies have suggested a role for adipokines in cartilage degradation. Chondrocytes from osteoarthritic cartilage respond poorly to Insulin-like growth factor-1 (IGF-1) and the molecular mechanism(s) involved is not clearly understood. The purpose of this study was to determine the role of nicotinamide phosphoribosyltransferase (eNAMPT/visfatin), a newly described adipokine, in regulating IGF-1 function in chondrocytes. Methods: Human articular chondrocytes isolated from normal ankle cartilage were pretreated with (0.1-5.0 ug/ml) eNAMPT overnight followed by stimulation with IGF-1(50 ng/ml) for 24 hours and proteoglycan (PG) synthesis was measured by [35S] sulfate incorporation. Chondrocytes were pretreated with eNAMPT overnight followed by IGF-1 for 10 minutes, and the cell lysates were immunoblotted for various signaling proteins that are activated by IGF-1 by using phospho-specific antibodies. In addition, chondrocytes were pretreated with MEK inhibitor (U0126) prior to stimulation with eNAMPT and IGF-1. Results: Pre-treatment of chondrocytes with eNAMPT inhibited IGF-1-stimulated PG synthesis in a dose-dependent manner. Treatment of chondrocytes with eNAMPT inhibited IGF-1-induced phosphorylation of signaling molecules, including IRS-1 and AKT. Interestingly, pretreatment of chondrocytes with eNAMPT did not inhibit IGF-1-mediated phosphorylation of the IGF-1 receptor; however, it stimulated a sustained phosphorylation of the extracellular signal-regulated kinase (ERK)/ mitogen activated protein kinase (MAPK) signaling pathway. Inhibition of the ERK/MAPK signaling pathway restored IGF-1-mediated IRS-1 and AKT phosphorylation. Conclusions: Our study demonstrates that eNAMPT/visfatin inhibits IGF-1 function in articular chondrocytes by activating the ERK/MAPK pathway independent of the IGF-1 receptor. Since eNAMPT levels are elevated in the synovial fluid of OA patients, the signaling pathway activated by eNAMPT could contribute to IGF-1 resistance in OA.

Annals of the Rheumatic Diseases current issue

Canes for knee osteoarthritis: is a randomised trial necessary?
Hagen, K. B. Wed, 28 Dec 2011 19:58:21 -0800
In this issue of the Annals, Jones et al1 (pp 172) report the results of a randomised clinical trial (RCT) of canes for knee osteoarthritis. Current recommendations on the management of hip and knee osteoarthritis emphasise non-pharmacological interventions, with sticks or canes universally recommended in existing guidelines.2 According to the Osteoarthritis Research Society International (OARSI) recommendations for the management of hip and knee osteoarthritis one of 25 treatment propositions recommended is ‘Walking aids can reduce pain in patients with hip and knee OA. Patients should be given instruction in the optimal use of a cane or crutch in the contralateral hand. Frames or wheeled walkers are often preferable for those with bilateral disease.’3 In the National Institute for Health and Clinical Excellence (NICE) guideline for care and management of osteoarthritis in adults, assistive devices (such as walking sticks) are considered as...
The effect of biological agents on work participation in rheumatoid arthritis patients: a systematic review
ter Wee, M. M., Lems, W. F., Usan, H., Gulpen, A., Boonen, A. Wed, 28 Dec 2011 19:58:21 -0800
This study reviewed the effect of biological agents on participation in paid work among patients with rheumatoid arthritis (RA). A systematic literature search was performed to identify published articles reporting the effect of biological agents on employment status, sick leave and/or presenteeism. The quality of included articles was assessed according to the guidelines as proposed by the Dutch Cochrane Centre. Narrative summaries were used to present the data separately for randomised controlled trials (RCTs) as well as controlled and uncontrolled cohort studies. 19 studies (six uncontrolled cohorts, seven controlled cohorts and six RCTs) were included, in which 11 259 patients were treated with biological agents. Employment status improved in four out of 13 studies, absence from work in all 10 studies and presenteeism in seven out of nine studies that reported this outcome. For absenteeism and presenteeism the statistical significance of change or difference was not always provided and results within studies were sometimes conflicting when using different time frames or alternative outcomes. The large heterogeneity in terms of population, design, analyses and most important in outcome measures limits interpretation of the data. RCTs as well as cohort studies showed positive results of biological agents on both absenteeism and presenteeism compared with other disease-modifying antirheumatic drugs (DMARD), continuing the failing DMARD, the general population or the situation before the start of biological agents. The effect on employment status was more conflicting, but 50% of studies that addressed patients with early methotrexate-naive RA showed a positive result on employment status.
Impact of cane use on pain, function, general health and energy expenditure during gait in patients with knee osteoarthritis: a randomised controlled trial
Jones, A., Silva, P. G., Silva, A. C., Colucci, M., Tuffanin, A., Jardim, J. R., Natour, J. Wed, 28 Dec 2011 19:58:21 -0800
Objective To assess the impact of daily cane use during gait in relation to pain, function, general health and energy expenditure among patients with knee osteoarthritis. Method Sixty-four patients were randomly assigned to an experimental group (EG) or control group (CG). The EG used a cane every day for 2 months, whereas the CG did not use a cane in this period. The first outcome was pain and the second were function (Lequesne and WOMAC), general health (SF-36) and energy expenditure (gas analysis during the 6-minute walk test (6MWT) with and without a cane). Evaluations were performed at baseline, 30 and 60 days. Results The groups were homogeneous for all parameters at baseline. Compared with the CG, the EG significantly improved pain (ES 0.18), function - Lequesne (ES 0.13), some domains of SF-36 (role physical, ES 0.07 and bodily pain, ES 0.08) and distance on the 6MWT with the cane (ES 0.16). At the end of the 6MWT with the cane, the EG significantly improved energy expenditure (ES 0.21), carbon dioxide production (ES 0.12) and metabolic equivalents (ES 0.15) compared with the CG. Conclusion A cane can be used to diminish pain, improve function and some aspects of quality of life in patients with knee osteoarthritis. The prescription of a cane should take into account the substantial increase in energy expenditure in the first month of use, whereas energy expenditure is no longer a factor for concern by the end of the second month due to adaptation to cane use. The trial was registered in clinicaltrials.gov (NCT00698412).
Safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the monoclonal antibody ASK8007 blocking osteopontin in patients with rheumatoid arthritis: a randomised, placebo controlled, proof-of-concept study
Boumans, M. J. H., Houbiers, J. G. A., Verschueren, P., Ishikura, H., Westhovens, R., Brouwer, E., Rojkovich, B., Kelly, S., den Adel, M., Isaacs, J., Jacobs, H., Gomez-Reino, J., Holtkamp, G. M., Hastings, A., Gerlag, D. M., Tak, P. P. Wed, 28 Dec 2011 19:58:21 -0800
Objectives Osteopontin is an extracellular matrix protein with diverse immunomodulatory functions. The authors assessed the safety, tolerability, pharmacokinetics, pharmacodynamics and initial efficacy of the humanised monoclonal antibody ASK8007, which blocks osteopontin. Methods In this double-blind, multicentre, combined first-in-man, single-dose escalation (phase I, part A) and proof-of-concept, multiple-dose (phase IIA, part B) study, rheumatoid arthritis (RA) patients with active disease were randomly assigned to receive ASK8007 or placebo intravenously. Safety monitoring, pharmacokinetic and pharmacodynamic analyses and clinical assessments were performed throughout the study. The expression of phenotypic cell markers was evaluated in synovial tissue biopsy samples obtained at baseline and 43 days after initiation of treatment (part B) by immunohistochemistry and digital image analysis. Two co-primary efficacy endpoints were the change from baseline in the disease activity score evaluated in 28 joints (DAS28) and the change from baseline in the number of CD68 synovial sublining macrophages, both assessed on day 43 (part B). Results ASK8007 was overall safe and well tolerated up to the highest studied dose (20 mg/kg). Quantifiable concentrations of ASK8007 were detected in synovial fluid. No differences were observed for changes from baseline in DAS28 and CD68 sublining macrophages between ASK8007 and placebo-treated patients. Within the ASK8007 treatment group, there were also no apparent clinical responses or changes in sublining macrophages. In addition, ASK8007 treatment did not change other assessed biomarkers. Conclusions Osteopontin blockade is well tolerated and not related to safety concerns. These results consistently show that osteopontin blockade is unlikely to induce robust clinical improvement in RA patients.
In early rheumatoid arthritis, patients with a good initial response to methotrexate have excellent 2-year clinical outcomes, but radiological progression is not fully prevented: data from the methotrexate responders population in the SWEFOT trial
Rezaei, H., Saevarsdottir, S., Forslind, K., Albertsson, K., Wallin, H., Bratt, J., Ernestam, S., Geborek, P., Pettersson, I. F., van Vollenhoven, R. F. Wed, 28 Dec 2011 19:58:21 -0800
Objective To investigate the 2-year clinical and radiological outcomes of patients with early rheumatoid arthritis (RA; symptom duration <1 year) who had initially responded well to methotrexate monotherapy. Methods In the SWEFOT trial, all 487 patients started methotrexate (target dose 20 mg/week). After 3–4 months, 147 had low disease activity, 28-joint based disease activity score (DAS28) ≤3.2. These patients were not randomly selected but were followed in regular care for 2 years. Clinical outcomes and radiographic progression according to the van der Heijde modified Sharp (SvdH) score were analysed. Results The majority of the 147 patients continued on methotrexate monotherapy. After 1 and 2 years, DAS28 remission was achieved in 59.6% and 71.8% and mean observed DAS28 values were 2.53 and 2.25, respectively. Despite the favourable clinical course, a proportion of the patients progressed radiographically with a mean (SD) increase in the SvdH score after 2 years of 3.90 (6.84). There was no significant difference in progression between patients in DAS28 remission versus not in remission (p=0.73). At baseline, approximately half the patients had no radiographic damage, while after 2 years the proportion was approximately 20%. Conclusion Most early RA patients who achieve low disease activity after 3–4 months of methotrexate monotherapy continue to have low disease activity during 2 years follow-up, and additional treatment is needed infrequently. Some radiological progression occurs in most patients, and may be marked or severe in some, even despite sustained DAS28 remission. Close monitoring for radiological progression is thus warranted.
The prospective association between psychological distress and disease activity in rheumatoid arthritis: a multilevel regression analysis
Overman, C. L., Bossema, E. R., van Middendorp, H., Wijngaards-de Meij, L., Verstappen, S. M., Bulder, M., Jacobs, J. W., Bijlsma, J. W., Geenen, R. Wed, 28 Dec 2011 19:58:21 -0800
Background Cross-sectional associations suggest a mutual Subscribe to Rheumatology RSS feed