Gourt > Health > Medicine > Medical Specialties > Rheumatology (3)
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
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
- vasculitis
Musculoskeletal Disorders
Musculoskeletal Disorders
Internal Medicine
Orthopedics
All Rheumatology Jobs
Rheumatology Physician Jobs in Eastern North Carolina. :: North Carolina :: MedPro Search - Recruiting For Physician Jobs
Rheumatology Physician Jobs in Eastern North Carolina. Our Rheumatology division has an immediate opening. We currently have three board certified rheumatologists. MRI, CT, nuclear, BMD, x-ray, ultrasound,
Rheumatology Physician Job for Coastal North Carolina :: North Carolina :: MedPro Search - Recruiting For Physician Jobs
Med Pro Search is seeking a Rheumatologist (Rheum) to join a Rheumatology Division with a premier multi-specialty group in Eastern North Carolina. We now have more than 50 providers and our new; state
Metro Western Louisiana :: Louisiana :: Medical Search International
A prestigious Regional Medical Center located in a metropolitan community in Western Louisiana is seeking a BC/BE Rheumatologist to join their specialty group. State license is preferred but eligibility
Arthritis Research & Therapy - Latest Articles
SAPHO syndrome: is a range of pathogen-associated rheumatic diseases extended?
Alexander Rozin Thu, 05 Nov 2009 00:00:00 -0000
SAPHO syndrome, representing a constellation of synovitis, acne, palmo-plantar pustulosis, hyperostosis and osteitis, is now recognized as a distinct medical entity, a reactive infectious osteitis. Genetic, immunological and bacterial mechanisms are implicated in the development of the disease. Diagnostic problems may rise due to non complete manifestations of SAPHO: acne and arthritis, or acne and anterior wall osteitis with an unclear pustulosis history. The interventional study of Assman et al. is a significant addition to a long range of publications, showing an association of SAPHO with P. acnes. Randomized control studies are needed to confirm the effects of antibiotic therapy.
Effect of small interference RNA for ADAMTS5 on intervertebral disc degeneration in the rabbit anular needle puncture model
Shoji SekiYumiko Asanuma-AbeKoichi MasudaYoshiharu KawaguchiKunihiro AsanumaCarol MuehlemanAkiko IwaiTomoatsu Kimura Wed, 04 Nov 2009 00:00:00 -0000
IntroductionThe etiology of degenerative disc disease is unknown. Several investigators have reported the presence of proteolytic enzymes, such as the matrix metalloproteinase (MMP) and ADAMTS (a disintegrin and metalloprotease with thrombospondin-like repeats) families, in degenerated human discs. Glasson et al. have recently reported that there is a significant reduction in the severity of cartilage destruction in ADAMTS5 knockout mice compared with wild-type mice. The purpose of this study was to evaluate the suppressive effects of injections of ADAMTS5 small interference RNA (siRNA) oligonucleotide on intervertebral disc degeneration in the rabbit anular needle puncture model. Methods: Rabbit nucleus pulposus (NP) cells were transfected with siRNA oligonucleotides specific for ADAMTS5 or the control. The suppression of the ADAMTS5 gene by siRNA transfection was assessed using real-time polymerase chain reaction (PCR), both in monolayer and alginate bead cultures with or without interleukin-1beta (IL-1beta) stimulation. The effect of siRNA was determined in vivo using the rabbit anular needle puncture model (control group: n=8; ADAMTS5 group: n=8). One week after the initial anular puncture, the animals received an injection of the control or anti-ADAMTS5 oligonucleotide (100 ug each at the L2/3 and L4/5 level; 16 discs/group). Disc height, magnetic resonance imaging (MRI) (Thompson classification and signal intensity) and safranin-O staining (histological grade) were assessed. Results: IL-1beta treatment significantly increased the ADAMTS5 mRNA level in NP cells (P<0.01). ADAMTS5 gene suppression was 70% compared with the control oligonucleotide in both monolayer and alginate bead culture with or without stimulation with IL-1beta. The injection of anti-ADAMTS5 oligonucleotide in vivo resulted in improved MRI scores with increased signal intensity and improved histological grade scores with statistical significance (P<0.05). No significant change in disc height was observed. Conclusions: A single injection of ADAMTS5 siRNA induced the suppression of degradation in NP tissues as shown by significantly improved MRI and histological grades. The mechanism of response to siRNA may be worthy of exploration for possible therapeutic purposes.
Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of interleukin-1beta-induced nuclear factor-kappaB-mediated inflammation and apoptosis
Constanze CsakiAli MobasheriMehdi Shakibaei Wed, 04 Nov 2009 00:00:00 -0000
IntroductionCurrently available treatments for osteoarthritis (OA) are restricted to non-steroidal anti-inflammatory drugs (NSAIDs), which exhibit numerous side effects and are only temporarily effective. Thus novel, safe and more efficacious anti-inflammatory agents are needed for OA. Naturally occurring polyphenolic compounds, such as curcumin and resveratrol, are potent agents for modulating inflammation. Both compounds mediate their effects by targeting the nuclear factor-kappaB (NF-kappaB) signalling pathway. Methods: We have recently demonstrated that in chondrocytes resveratrol modulates the NF-kappaB pathway by inhibiting the proteasome, while curcumin modulates the activation of NF-kappaB by inhibiting upstream kinases (Akt). However, the combinational effects of these compounds in chondrocytes has not been studied and/or compared with their individual effects. The aim of this study was to investigate the potential synergistic effects of curcumin and resveratrol on interleukin (IL)-1beta-stimulated human chondrocytes in vitro using immunoblotting and electron microscopy. Results: Treatment with curcumin and resveratrol suppressed NF-kappaB regulated gene products involved in inflammation (cyclooxygenase-2 (COX-2) and matrix metalloproteinase (MMP)-3, -9, vascular endothelial growth factor (VEGF)), inhibited apoptosis (Bcl-2, Bcl-xL, and tumor necrosis factor receptor-associated factor 1 (TRAF1)) and prevented activation of caspase-3. IL-1beta-induced NF-kappaB activation was suppressed directly by cocktails of curcumin and resveratrol through inhibition of Ikappakappa- and proteasome-activation, inhibition of Ikappa-Balpha phosphorylation and degradation and inhibition of nuclear translocation of NF-kappaB. The modulatory effects of curcumin and resveratrol on IL-1beta-induced expression of cartilage-specific matrix and pro-inflammatory enzymes are mediated in part by the cartilage specific transcription factor Sox-9. Conclusions: We propose that combining these natural compounds may be a useful strategy in OA therapy as compared to separate treatment with each individual compound.
Sinus aspergilloma in rheumatoid arthritis before or during tumor necrosis factor-alpha antagonist therapy
Ariane LeboimeJean-Marie BerthelotYannick AllanoreLama Khalil-KallouchePhilippe HermanPhilippe OrcelFrederic Liote Tue, 03 Nov 2009 00:00:00 -0000
IntroductionIn 2008, the FDA required manufacturers of tumor necrosis factor-alpha (TNF-alpha) antagonists to strengthen their warnings about the risk of serious fungal infections in patients with rheumatoid arthritis (RA). Sinus aspergilloma occurs occasionally in RA patients and can progress to invasive Aspergillus disease. The purpose of this study was to describe symptomatic sinus aspergilloma in RA patients treated with TNF-alpha antagonists. Methods: Retrospective descriptive study of symptomatic cases of sinus aspergilloma in patients with RA followed in three French university hospitals. A systematic literature review was performed. Results: Among 550 RA patients treated with TNF-alpha antagonists, 6 (1.1%) had symptomatic maxillary aspergilloma diagnosed by computed tomography before or during TNF-alpha antagonist therapy. None had chronic neutropenia. Aspergilloma treatment was with surgery only in all 6 patients. In the literature, we found 20 reports of Aspergillus infection in patients with chronic inflammatory joint diseases (including 10 with RA). Only 5/20 patients were treated with TNF-alpha antagonists (invasive lung aspergillosis, n=3; intracranial aspergillosis, n=1; and sphenoidal sinusitis, n=1). Conclusions: Otorhinolaryngological symptoms must be evaluated before starting or switching TNF-alpha antagonists. Routine computed tomography of the sinuses before starting or switching TNF-alpha antagonists may deserve consideration.
ACR70-disease activity score remission achievement from switches between all the available biological agents in rheumatoid arthritis: a systematic review of the literature
Stefano AliverniniAntonella LariaElisa GremeseAngelo ZoliGianfranco Ferraccioli Tue, 03 Nov 2009 00:00:00 -0000
IntroductionThe aim of our analysis was to compare the gaining of a major response (disease activity score (DAS) remission or ACR 70) by switching between all the available biological therapies in rheumatoid arthritis. Methods: A systematic review was performed including studies, published before December 2008, in which a second biological agent was used and clinical outcomes were evaluated after a first biological failure. Results: 9 articles were included: switch from etanercept and/or infliximab and/or to adalimumab is effective with an ACR70 response from 5% to 33%. Rituximab may be slightly more effective than switching to a second anti-tumor necrosis factor alpha (TNF-alpha) reaching an ACR70 or DAS remission response in 12% and 9% respectively. Clinical trials confirmed the efficacy in switching to abatacept (gain of effect 10.2%). Tocilizumab allows to reach DAS28 remission in 30.1% but ACR70 only in 12.4% of patients refractory to anti-TNFalpha. Conclusions: The efficacy of a second biologic agent, irrespective of the mode of action, in reaching an ACR70 or DAS-remission after a first biologic is observed from 5 to 15% and from 9% to 15.4% respectively (except in two studies).
Dual energy X-ray absorptiometry analysis contributes to the prediction of hip osteoarthritis progression
Martha Castano BetancourtJacqueline Van der LindenFernando RivadeneiraRianne RozendaalSita Bierma-ZeinstraHarrie WeinansJan Waarsing Mon, 02 Nov 2009 00:00:00 -0000
IntroductionThe objective was to determine if structural bone parameters obtained from dual energy X-ray absorptiometry (DXA) contribute to the prediction of progression of hip osteoarthritis (OA) and to test if the difference between the most affected (OA) hip and the contralateral hip adds to this prediction. Methods: The study group involves a prospective cohort of 189 patients that met the ACR classification criteria for hip osteoarthritis. Progression was defined as 20% joint space narrowing or total hip replacement within a two years follow up. Software was developed to calculate geometrical aspects and bone mineral density (BMD) in different regions of interest of the proximal femur. Logistic regression was used to test if Kellgren and Lawrence (K-L) scores and DXA parameters can predict "progression" of OA. Models were compared using -2log likelihood tests, R^2 Nagelkerke and areas under the Receiver Operator Characteristic curves, assessed using 10-fold cross validation. Results: The model that included the DXA variables was significantly better in predicting hip OA progression than the model with K-L score of the affected side alone (P<0.01). The addition of the differences in DXA parameters between the most affected and contralateral hip in the superior part of the femoral head, trochanteric and intertrochanteric area further improved the prediction of progression (P<0.05). K-L score of the affected side was still the most significant single variable in the models. Conclusions: DXA parameters can significantly contribute to the prediction of progression in patients with hip osteoarthritis. The analysis of the DXA differences between the hips of the patient represents a small but significant contribution to this prediction. These analyses show the importance of bone density changes in the etiology of OA.
Annals of the Rheumatic Diseases current issue
Despair on disparities
Carmona, L., Loza, E.
Musculoskeletal manifestations of lysosomal storage disorders
Aldenhoven, M, Sakkers, R J B, Boelens, J, de Koning, T J, Wulffraat, N M Lysosomal storage disorders (LSDs), a heterogeneous group of inborn metabolic disorders, are far more common than most doctors presume. Although patients with a severe LSD subtype are often readily diagnosed, the more attenuated subtypes are frequently missed or diagnosis is significantly delayed. The presenting manifestations often involve the bones and/or joints and therefore these patients are frequently under specialist care by (paediatric) rheumatologists, receiving inadequate treatment. Since effective disease-specific treatments, including enzyme replacement therapy and stem cell transplantation, have become available for certain LSDs and timely initiation of these treatments is necessary to prevent the development of severe, disabling and irreversible manifestations, early diagnosis has become essential. The challenge is to raise awareness for better recognition of the presenting signs and symptoms of LSDs by all doctors who may encounter these patients, including rheumatologists.
Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database
Sokka, T, Kautiainen, H, Pincus, T, Toloza, S, da Rocha Castelar Pinheiro, G, Lazovskis, J, Hetland, M L, Peets, T, Immonen, K, Maillefert, J F, Drosos, A A, Alten, R, Pohl, C, Rojkovich, B, Bresnihan, B, Minnock, P, Cazzato, M, Bombardieri, S, Rexhepi, S, Rexhepi, M, Andersone, D, Stropuviene, S, Huisman, M, Sierakowski, S, Karateev, D, Skakic, V, Naranjo, A, Baecklund, E, Henrohn, D, Gogus, F, Badsha, H, Mofti, A, Taylor, P, McClinton, C, Yazici, Y Objective: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. Methods: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST–RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP" countries with GDP per capita greater than US$24 000 and 11 "low GDP" countries with GDP per capita less than US$11 000. Results: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = –0.78, 95% CI –0.56 to –0.90, r2 = 61%). Disease activity levels differed substantially between "high GDP" and "low GDP" countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. Conclusions: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP" than in "high GDP" countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.
Association of bone scintigraphic abnormalities with knee malalignment and pain
Kraus, V B, McDaniel, G, Worrell, T W, Feng, S, Vail, T P, Varju, G, Coleman, R E Objective: The information content of knee bone scintigraphy was evaluated, including pattern, localisation and intensity of retention relative to radiographic features of knee osteoarthritis, knee alignment and knee symptoms. Methods: A total of 308 knees (159 subjects) with symptomatic and radiographic knee osteoarthritis of at least one knee was assessed by late-phase 99mTechnetium methylene disphosphonate bone scintigraph, fixed-flexion knee radiograph, full limb radiograph for knee alignment and for self-reported knee symptom severity. Generalised linear models were used to control for within-subject correlation of knee data. Results: The compartmental localisation (medial vs lateral) and intensity of knee bone scan retention were associated with the pattern (varus vs valgus) (p<0.001) and severity (p<0.001) of knee malalignment and localisation and severity of radiographic osteoarthritis (p<0.001). Bone scan agent retention in the tibiofemoral, but not patellofemoral, compartment was associated with severity of knee symptoms (p<0.001) and persisted after adjusting for radiographic osteoarthritis (p<0.001). Conclusion: To the authors’ knowledge, this is the first study describing a relationship between knee malalignment, joint symptom severity and compartment-specific abnormalities by bone scintigraphy. This work demonstrates that bone scintigraphy is a sensitive and quantitative indicator of symptomatic knee osteoarthritis. Used selectively, bone scintigraphy is a dynamic imaging modality that holds great promise as a clinical trial screening tool and outcome measure.
Elaboration of the preliminary Rheumatoid Arthritis Impact of Disease (RAID) score: a EULAR initiative
Gossec, L, Dougados, M, Rincheval, N, Balanescu, A, Boumpas, D T, Canadelo, S, Carmona, L, Daures, J-P, de Wit, M, Dijkmans, B A C, Englbrecht, M, Gunendi, Z, Heiberg, T, Kirwan, J R, Mola, E M, Matucci-Cerinic, M, Otsa, K, Schett, G, Sokka, T, Wells, G A, Aanerud, G J, Celano, A, Dudkin, A, Hernandez, C, Koutsogianni, K, Akca, F N, Petre, A-M, Richards, P, Scholte-Voshaar, M, Von Krause, G, Kvien, T K Background: Current response criteria in rheumatoid arthritis (RA) usually assess only three patient-reported outcomes (PROs): pain, functional disability and patient global assessment. Other important PROs such as fatigue are not included. Objective: To elaborate a patient-derived composite response index for use in clinical trials in RA, the RA Impact of Disease (RAID) score. Methods: Ten patients identified 17 domains or areas of health relevant for inclusion in the score, then 96 patients (10 per country in 10 European countries) ranked these domains in order of decreasing importance. The seven most important domains were selected. Instruments were chosen for each domain after extensive literature research of psychometric properties and expert opinion. The relative weight of each of the domains was obtained from 505 patients who were asked to "distribute 100 points" among the seven domains. The average ranks of importance of these domains were then computed. Results: The RAID score includes seven domains with the following relative weights: pain (21%), functional disability (16%), fatigue (15%), emotional well-being (12%), sleep (12%), coping (12%) and physical well-being (12%). Weights were similar across countries and across patient and disease characteristics. Proposed instruments include the Health Assessment Questionnaire and numerical ratings scales. Conclusion: The preliminary RAID score is a patient-derived weighted score to assess the impact of RA. An ongoing study will allow the final choice of questionnaires and assessment of validity. This score can be used in clinical trials as a new composite index that captures information relevant to patients.
Adaptation and cross-cultural validation of the rheumatoid arthritis work instability scale (RA-WIS)
Gilworth, G, Emery, P, Gossec, L, Vliet Vlieland, T P M, Breedveld, F C, Hueber, A J, Schett, G, Tennant, A Background: Despite recent advances, work disability in rheumatoid arthritis (RA) remains common. Work disability is frequently preceded by a period of work instability characterised by a mismatch between an individual’s functional abilities and job demands. This could raise the risk of work disability if not resolved. A work instability scale for RA (RA–WIS) has previously been developed to screen for this risk. The objective of this study was the adaptation of this scale into French, Dutch and German. Method: Different language versions of the RA–WIS were produced through a process of forward and back translations. The new scales were tested for face validity. English data from the original developmental study was pooled with data generated through postal surveys in each country. The internal construct and cross-cultural validity of the new scales were assessed using Rasch analysis, including differential item functioning (DIF) by culture. Results: The pooled data showed good fit to the Rasch model and demonstrated strict unidimensionality. DIF was found to be present for six items, but these appeared both to cancel out at the test level and have only a marginal effect on the test score itself. Conclusions: The RA–WIS was shown to be robust to adaptation into different languages. Data fitted Rasch model expectations and strict tests of unidimensionality. This project and the continuing work on further cross-cultural adaptations have the potential to help ensure clinicians across Europe are able to support RA patients to achieve their potential in work through early identification of those most at risk.
Arthritis Care & Research
Health insurance and out-of-pocket expenses
Wei Zhang, Aslam H. Anis Thu, 29 Oct 2009 10:41:00 -0000
No abstract.
US bone and joint decade prepares for the future
Joshua J. Jacobs, Toby King Thu, 29 Oct 2009 10:41:00 -0000
No abstract.
Anti-citrullinated peptide antibody assays and their role in the diagnosis of rheumatoid arthritis
Rohit Aggarwal, Katherine Liao, Raj Nair, Sarah Ringold, Karen H. Costenbander Thu, 29 Oct 2009 10:41:00 -0000
No abstract.
Arthritis & Rheumatism
In this issue
Thu, 29 Oct 2009 10:39:00 -0000
No abstract.
Interpreting registry-derived drug studies: Does societal context matter?
Joel M. Kremer, Jeffrey Greenberg Thu, 29 Oct 2009 10:39:00 -0000
No abstract.
Human osteoclastogenic T cells and human osteoclastology
Shigeru Kotake, Yuki Nanke, Toru Yago, Manabu Kawamoto, Hisashi Yamanaka Thu, 29 Oct 2009 10:39:00 -0000
No abstract.
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Rheumatology Physician Jobs in Eastern North Carolina. :: North Carolina :: MedPro Search - Recruiting For Physician Jobs
Rheumatology Physician Jobs in Eastern North Carolina. Our Rheumatology division has an immediate opening. We currently have three board certified rheumatologists. MRI, CT, nuclear, BMD, x-ray, ultrasound,
Rheumatology Physician Job for Coastal North Carolina :: North Carolina :: MedPro Search - Recruiting For Physician Jobs
Med Pro Search is seeking a Rheumatologist (Rheum) to join a Rheumatology Division with a premier multi-specialty group in Eastern North Carolina. We now have more than 50 providers and our new; state
Metro Western Louisiana :: Louisiana :: Medical Search International
A prestigious Regional Medical Center located in a metropolitan community in Western Louisiana is seeking a BC/BE Rheumatologist to join their specialty group. State license is preferred but eligibility
Arthritis Research & Therapy - Latest Articles
SAPHO syndrome: is a range of pathogen-associated rheumatic diseases extended?
Alexander Rozin Thu, 05 Nov 2009 00:00:00 -0000
SAPHO syndrome, representing a constellation of synovitis, acne, palmo-plantar pustulosis, hyperostosis and osteitis, is now recognized as a distinct medical entity, a reactive infectious osteitis. Genetic, immunological and bacterial mechanisms are implicated in the development of the disease. Diagnostic problems may rise due to non complete manifestations of SAPHO: acne and arthritis, or acne and anterior wall osteitis with an unclear pustulosis history. The interventional study of Assman et al. is a significant addition to a long range of publications, showing an association of SAPHO with P. acnes. Randomized control studies are needed to confirm the effects of antibiotic therapy.
Effect of small interference RNA for ADAMTS5 on intervertebral disc degeneration in the rabbit anular needle puncture model
Shoji SekiYumiko Asanuma-AbeKoichi MasudaYoshiharu KawaguchiKunihiro AsanumaCarol MuehlemanAkiko IwaiTomoatsu Kimura Wed, 04 Nov 2009 00:00:00 -0000
IntroductionThe etiology of degenerative disc disease is unknown. Several investigators have reported the presence of proteolytic enzymes, such as the matrix metalloproteinase (MMP) and ADAMTS (a disintegrin and metalloprotease with thrombospondin-like repeats) families, in degenerated human discs. Glasson et al. have recently reported that there is a significant reduction in the severity of cartilage destruction in ADAMTS5 knockout mice compared with wild-type mice. The purpose of this study was to evaluate the suppressive effects of injections of ADAMTS5 small interference RNA (siRNA) oligonucleotide on intervertebral disc degeneration in the rabbit anular needle puncture model. Methods: Rabbit nucleus pulposus (NP) cells were transfected with siRNA oligonucleotides specific for ADAMTS5 or the control. The suppression of the ADAMTS5 gene by siRNA transfection was assessed using real-time polymerase chain reaction (PCR), both in monolayer and alginate bead cultures with or without interleukin-1beta (IL-1beta) stimulation. The effect of siRNA was determined in vivo using the rabbit anular needle puncture model (control group: n=8; ADAMTS5 group: n=8). One week after the initial anular puncture, the animals received an injection of the control or anti-ADAMTS5 oligonucleotide (100 ug each at the L2/3 and L4/5 level; 16 discs/group). Disc height, magnetic resonance imaging (MRI) (Thompson classification and signal intensity) and safranin-O staining (histological grade) were assessed. Results: IL-1beta treatment significantly increased the ADAMTS5 mRNA level in NP cells (P<0.01). ADAMTS5 gene suppression was 70% compared with the control oligonucleotide in both monolayer and alginate bead culture with or without stimulation with IL-1beta. The injection of anti-ADAMTS5 oligonucleotide in vivo resulted in improved MRI scores with increased signal intensity and improved histological grade scores with statistical significance (P<0.05). No significant change in disc height was observed. Conclusions: A single injection of ADAMTS5 siRNA induced the suppression of degradation in NP tissues as shown by significantly improved MRI and histological grades. The mechanism of response to siRNA may be worthy of exploration for possible therapeutic purposes.
Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of interleukin-1beta-induced nuclear factor-kappaB-mediated inflammation and apoptosis
Constanze CsakiAli MobasheriMehdi Shakibaei Wed, 04 Nov 2009 00:00:00 -0000
IntroductionCurrently available treatments for osteoarthritis (OA) are restricted to non-steroidal anti-inflammatory drugs (NSAIDs), which exhibit numerous side effects and are only temporarily effective. Thus novel, safe and more efficacious anti-inflammatory agents are needed for OA. Naturally occurring polyphenolic compounds, such as curcumin and resveratrol, are potent agents for modulating inflammation. Both compounds mediate their effects by targeting the nuclear factor-kappaB (NF-kappaB) signalling pathway. Methods: We have recently demonstrated that in chondrocytes resveratrol modulates the NF-kappaB pathway by inhibiting the proteasome, while curcumin modulates the activation of NF-kappaB by inhibiting upstream kinases (Akt). However, the combinational effects of these compounds in chondrocytes has not been studied and/or compared with their individual effects. The aim of this study was to investigate the potential synergistic effects of curcumin and resveratrol on interleukin (IL)-1beta-stimulated human chondrocytes in vitro using immunoblotting and electron microscopy. Results: Treatment with curcumin and resveratrol suppressed NF-kappaB regulated gene products involved in inflammation (cyclooxygenase-2 (COX-2) and matrix metalloproteinase (MMP)-3, -9, vascular endothelial growth factor (VEGF)), inhibited apoptosis (Bcl-2, Bcl-xL, and tumor necrosis factor receptor-associated factor 1 (TRAF1)) and prevented activation of caspase-3. IL-1beta-induced NF-kappaB activation was suppressed directly by cocktails of curcumin and resveratrol through inhibition of Ikappakappa- and proteasome-activation, inhibition of Ikappa-Balpha phosphorylation and degradation and inhibition of nuclear translocation of NF-kappaB. The modulatory effects of curcumin and resveratrol on IL-1beta-induced expression of cartilage-specific matrix and pro-inflammatory enzymes are mediated in part by the cartilage specific transcription factor Sox-9. Conclusions: We propose that combining these natural compounds may be a useful strategy in OA therapy as compared to separate treatment with each individual compound.
Sinus aspergilloma in rheumatoid arthritis before or during tumor necrosis factor-alpha antagonist therapy
Ariane LeboimeJean-Marie BerthelotYannick AllanoreLama Khalil-KallouchePhilippe HermanPhilippe OrcelFrederic Liote Tue, 03 Nov 2009 00:00:00 -0000
IntroductionIn 2008, the FDA required manufacturers of tumor necrosis factor-alpha (TNF-alpha) antagonists to strengthen their warnings about the risk of serious fungal infections in patients with rheumatoid arthritis (RA). Sinus aspergilloma occurs occasionally in RA patients and can progress to invasive Aspergillus disease. The purpose of this study was to describe symptomatic sinus aspergilloma in RA patients treated with TNF-alpha antagonists. Methods: Retrospective descriptive study of symptomatic cases of sinus aspergilloma in patients with RA followed in three French university hospitals. A systematic literature review was performed. Results: Among 550 RA patients treated with TNF-alpha antagonists, 6 (1.1%) had symptomatic maxillary aspergilloma diagnosed by computed tomography before or during TNF-alpha antagonist therapy. None had chronic neutropenia. Aspergilloma treatment was with surgery only in all 6 patients. In the literature, we found 20 reports of Aspergillus infection in patients with chronic inflammatory joint diseases (including 10 with RA). Only 5/20 patients were treated with TNF-alpha antagonists (invasive lung aspergillosis, n=3; intracranial aspergillosis, n=1; and sphenoidal sinusitis, n=1). Conclusions: Otorhinolaryngological symptoms must be evaluated before starting or switching TNF-alpha antagonists. Routine computed tomography of the sinuses before starting or switching TNF-alpha antagonists may deserve consideration.
ACR70-disease activity score remission achievement from switches between all the available biological agents in rheumatoid arthritis: a systematic review of the literature
Stefano AliverniniAntonella LariaElisa GremeseAngelo ZoliGianfranco Ferraccioli Tue, 03 Nov 2009 00:00:00 -0000
IntroductionThe aim of our analysis was to compare the gaining of a major response (disease activity score (DAS) remission or ACR 70) by switching between all the available biological therapies in rheumatoid arthritis. Methods: A systematic review was performed including studies, published before December 2008, in which a second biological agent was used and clinical outcomes were evaluated after a first biological failure. Results: 9 articles were included: switch from etanercept and/or infliximab and/or to adalimumab is effective with an ACR70 response from 5% to 33%. Rituximab may be slightly more effective than switching to a second anti-tumor necrosis factor alpha (TNF-alpha) reaching an ACR70 or DAS remission response in 12% and 9% respectively. Clinical trials confirmed the efficacy in switching to abatacept (gain of effect 10.2%). Tocilizumab allows to reach DAS28 remission in 30.1% but ACR70 only in 12.4% of patients refractory to anti-TNFalpha. Conclusions: The efficacy of a second biologic agent, irrespective of the mode of action, in reaching an ACR70 or DAS-remission after a first biologic is observed from 5 to 15% and from 9% to 15.4% respectively (except in two studies).
Dual energy X-ray absorptiometry analysis contributes to the prediction of hip osteoarthritis progression
Martha Castano BetancourtJacqueline Van der LindenFernando RivadeneiraRianne RozendaalSita Bierma-ZeinstraHarrie WeinansJan Waarsing Mon, 02 Nov 2009 00:00:00 -0000
IntroductionThe objective was to determine if structural bone parameters obtained from dual energy X-ray absorptiometry (DXA) contribute to the prediction of progression of hip osteoarthritis (OA) and to test if the difference between the most affected (OA) hip and the contralateral hip adds to this prediction. Methods: The study group involves a prospective cohort of 189 patients that met the ACR classification criteria for hip osteoarthritis. Progression was defined as 20% joint space narrowing or total hip replacement within a two years follow up. Software was developed to calculate geometrical aspects and bone mineral density (BMD) in different regions of interest of the proximal femur. Logistic regression was used to test if Kellgren and Lawrence (K-L) scores and DXA parameters can predict "progression" of OA. Models were compared using -2log likelihood tests, R^2 Nagelkerke and areas under the Receiver Operator Characteristic curves, assessed using 10-fold cross validation. Results: The model that included the DXA variables was significantly better in predicting hip OA progression than the model with K-L score of the affected side alone (P<0.01). The addition of the differences in DXA parameters between the most affected and contralateral hip in the superior part of the femoral head, trochanteric and intertrochanteric area further improved the prediction of progression (P<0.05). K-L score of the affected side was still the most significant single variable in the models. Conclusions: DXA parameters can significantly contribute to the prediction of progression in patients with hip osteoarthritis. The analysis of the DXA differences between the hips of the patient represents a small but significant contribution to this prediction. These analyses show the importance of bone density changes in the etiology of OA.
Annals of the Rheumatic Diseases current issue
Despair on disparities
Carmona, L., Loza, E.
Musculoskeletal manifestations of lysosomal storage disorders
Aldenhoven, M, Sakkers, R J B, Boelens, J, de Koning, T J, Wulffraat, N M Lysosomal storage disorders (LSDs), a heterogeneous group of inborn metabolic disorders, are far more common than most doctors presume. Although patients with a severe LSD subtype are often readily diagnosed, the more attenuated subtypes are frequently missed or diagnosis is significantly delayed. The presenting manifestations often involve the bones and/or joints and therefore these patients are frequently under specialist care by (paediatric) rheumatologists, receiving inadequate treatment. Since effective disease-specific treatments, including enzyme replacement therapy and stem cell transplantation, have become available for certain LSDs and timely initiation of these treatments is necessary to prevent the development of severe, disabling and irreversible manifestations, early diagnosis has become essential. The challenge is to raise awareness for better recognition of the presenting signs and symptoms of LSDs by all doctors who may encounter these patients, including rheumatologists.
Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database
Sokka, T, Kautiainen, H, Pincus, T, Toloza, S, da Rocha Castelar Pinheiro, G, Lazovskis, J, Hetland, M L, Peets, T, Immonen, K, Maillefert, J F, Drosos, A A, Alten, R, Pohl, C, Rojkovich, B, Bresnihan, B, Minnock, P, Cazzato, M, Bombardieri, S, Rexhepi, S, Rexhepi, M, Andersone, D, Stropuviene, S, Huisman, M, Sierakowski, S, Karateev, D, Skakic, V, Naranjo, A, Baecklund, E, Henrohn, D, Gogus, F, Badsha, H, Mofti, A, Taylor, P, McClinton, C, Yazici, Y Objective: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. Methods: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST–RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP" countries with GDP per capita greater than US$24 000 and 11 "low GDP" countries with GDP per capita less than US$11 000. Results: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = –0.78, 95% CI –0.56 to –0.90, r2 = 61%). Disease activity levels differed substantially between "high GDP" and "low GDP" countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. Conclusions: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP" than in "high GDP" countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.
Association of bone scintigraphic abnormalities with knee malalignment and pain
Kraus, V B, McDaniel, G, Worrell, T W, Feng, S, Vail, T P, Varju, G, Coleman, R E Objective: The information content of knee bone scintigraphy was evaluated, including pattern, localisation and intensity of retention relative to radiographic features of knee osteoarthritis, knee alignment and knee symptoms. Methods: A total of 308 knees (159 subjects) with symptomatic and radiographic knee osteoarthritis of at least one knee was assessed by late-phase 99mTechnetium methylene disphosphonate bone scintigraph, fixed-flexion knee radiograph, full limb radiograph for knee alignment and for self-reported knee symptom severity. Generalised linear models were used to control for within-subject correlation of knee data. Results: The compartmental localisation (medial vs lateral) and intensity of knee bone scan retention were associated with the pattern (varus vs valgus) (p<0.001) and severity (p<0.001) of knee malalignment and localisation and severity of radiographic osteoarthritis (p<0.001). Bone scan agent retention in the tibiofemoral, but not patellofemoral, compartment was associated with severity of knee symptoms (p<0.001) and persisted after adjusting for radiographic osteoarthritis (p<0.001). Conclusion: To the authors’ knowledge, this is the first study describing a relationship between knee malalignment, joint symptom severity and compartment-specific abnormalities by bone scintigraphy. This work demonstrates that bone scintigraphy is a sensitive and quantitative indicator of symptomatic knee osteoarthritis. Used selectively, bone scintigraphy is a dynamic imaging modality that holds great promise as a clinical trial screening tool and outcome measure.
Elaboration of the preliminary Rheumatoid Arthritis Impact of Disease (RAID) score: a EULAR initiative
Gossec, L, Dougados, M, Rincheval, N, Balanescu, A, Boumpas, D T, Canadelo, S, Carmona, L, Daures, J-P, de Wit, M, Dijkmans, B A C, Englbrecht, M, Gunendi, Z, Heiberg, T, Kirwan, J R, Mola, E M, Matucci-Cerinic, M, Otsa, K, Schett, G, Sokka, T, Wells, G A, Aanerud, G J, Celano, A, Dudkin, A, Hernandez, C, Koutsogianni, K, Akca, F N, Petre, A-M, Richards, P, Scholte-Voshaar, M, Von Krause, G, Kvien, T K Background: Current response criteria in rheumatoid arthritis (RA) usually assess only three patient-reported outcomes (PROs): pain, functional disability and patient global assessment. Other important PROs such as fatigue are not included. Objective: To elaborate a patient-derived composite response index for use in clinical trials in RA, the RA Impact of Disease (RAID) score. Methods: Ten patients identified 17 domains or areas of health relevant for inclusion in the score, then 96 patients (10 per country in 10 European countries) ranked these domains in order of decreasing importance. The seven most important domains were selected. Instruments were chosen for each domain after extensive literature research of psychometric properties and expert opinion. The relative weight of each of the domains was obtained from 505 patients who were asked to "distribute 100 points" among the seven domains. The average ranks of importance of these domains were then computed. Results: The RAID score includes seven domains with the following relative weights: pain (21%), functional disability (16%), fatigue (15%), emotional well-being (12%), sleep (12%), coping (12%) and physical well-being (12%). Weights were similar across countries and across patient and disease characteristics. Proposed instruments include the Health Assessment Questionnaire and numerical ratings scales. Conclusion: The preliminary RAID score is a patient-derived weighted score to assess the impact of RA. An ongoing study will allow the final choice of questionnaires and assessment of validity. This score can be used in clinical trials as a new composite index that captures information relevant to patients.
Adaptation and cross-cultural validation of the rheumatoid arthritis work instability scale (RA-WIS)
Gilworth, G, Emery, P, Gossec, L, Vliet Vlieland, T P M, Breedveld, F C, Hueber, A J, Schett, G, Tennant, A Background: Despite recent advances, work disability in rheumatoid arthritis (RA) remains common. Work disability is frequently preceded by a period of work instability characterised by a mismatch between an individual’s functional abilities and job demands. This could raise the risk of work disability if not resolved. A work instability scale for RA (RA–WIS) has previously been developed to screen for this risk. The objective of this study was the adaptation of this scale into French, Dutch and German. Method: Different language versions of the RA–WIS were produced through a process of forward and back translations. The new scales were tested for face validity. English data from the original developmental study was pooled with data generated through postal surveys in each country. The internal construct and cross-cultural validity of the new scales were assessed using Rasch analysis, including differential item functioning (DIF) by culture. Results: The pooled data showed good fit to the Rasch model and demonstrated strict unidimensionality. DIF was found to be present for six items, but these appeared both to cancel out at the test level and have only a marginal effect on the test score itself. Conclusions: The RA–WIS was shown to be robust to adaptation into different languages. Data fitted Rasch model expectations and strict tests of unidimensionality. This project and the continuing work on further cross-cultural adaptations have the potential to help ensure clinicians across Europe are able to support RA patients to achieve their potential in work through early identification of those most at risk.
Arthritis Care & Research
Health insurance and out-of-pocket expenses
Wei Zhang, Aslam H. Anis Thu, 29 Oct 2009 10:41:00 -0000
No abstract.
US bone and joint decade prepares for the future
Joshua J. Jacobs, Toby King Thu, 29 Oct 2009 10:41:00 -0000
No abstract.
Anti-citrullinated peptide antibody assays and their role in the diagnosis of rheumatoid arthritis
Rohit Aggarwal, Katherine Liao, Raj Nair, Sarah Ringold, Karen H. Costenbander Thu, 29 Oct 2009 10:41:00 -0000
No abstract.
Arthritis & Rheumatism
In this issue
Thu, 29 Oct 2009 10:39:00 -0000
No abstract.
Interpreting registry-derived drug studies: Does societal context matter?
Joel M. Kremer, Jeffrey Greenberg Thu, 29 Oct 2009 10:39:00 -0000
No abstract.
Human osteoclastogenic T cells and human osteoclastology
Shigeru Kotake, Yuki Nanke, Toru Yago, Manabu Kawamoto, Hisashi Yamanaka Thu, 29 Oct 2009 10:39:00 -0000
No abstract.
Family Practice Notebook - Rheumatology - Comprehensive database of rheumatological disorders.
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