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ID PMID Title PublicationDate abstract
17052673 Triptolide inhibits CC chemokines expressed in rat adjuvant-induced arthritis. 2006 Dec 5 Triptolide, a diterpenoid triepoxide from Tripterygium wilfordii Hook F (TWHF), has been proven to have potent immunosuppressive and anti-inflammatory activities. It has been clinically used to treat patients with rheumatoid arthritis (RA), in which chemokines play an important role in immune and inflammatory responses. To investigate the effect of triptolide on MCP-1, MIP-1alpha and RANTES, we used complete Freund's adjuvant to induce adjuvant-induced arthritis (AA) in rats. AA in rat is a useful experimental model of human RA. Our data show that the thickness of arthritic ankle decreases with administration of triptolide. Both mRNA and protein levels of MCP-1, MIP-1alpha and RANTES in synovial tissue of rats with AA are significantly higher than those in normal rats. mRNA levels of MIP-1alpha and RANTES increase in peripheral blood mononuclear cells of rats with AA in comparison with those in normal rats, whereas no MCP-1 mRNA can be detected. Triptolide can significantly inhibit rat AA induced over-expression of MCP-1, MIP-1alpha and RANTES at both mRNA and protein levels in a dose-dependent manner. These results may contribute to the therapeutic effects of triptolide in rheumatoid arthritis.
17393418 Analysis of vascular gene expression in arthritic synovium by laser-mediated microdissecti 2007 Apr OBJECTIVE: In rheumatoid arthritis (RA), formation of new blood vessels is necessary to meet the nutritional and oxygen requirements of actively proliferating synovial tissue. The aim of this study was to analyze the specific synovial vascular expression profiles of several angiogenesis-related genes as well as CD82 in RA compared with osteoarthritis (OA), using laser-mediated microdissection (LMM). METHODS: LMM and subsequent real-time polymerase chain reaction were used in combination with immunohistochemical analysis for area-specific analysis of messenger RNA (mRNA) and protein expression of vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGFR-1), VEGFR-2, hypoxia-inducible factor 1alpha (HIF-1alpha), HIF-2alpha, platelet-derived growth factor receptor alpha (PDGFRalpha), PDGFRbeta, inhibitor of DNA binding/differentiation 2 (Id2), and CD82 in RA and OA synovial microvasculature and synovial lining. RESULTS: Expression of Id2 mRNA was significantly lower in RA synovial vessels compared with OA synovial vessels (P=0.0011), whereas expression of VEGFR-1 was significantly higher in RA (P=0.0433). No differences were observed for the other parameters. At the protein level, no statistically significant differences were observed for any parameter, although Id2 levels were 2.5-fold lower in RA (P=0.0952). However, the number of synovial blood vessels and the number of VEGFR-2-expressing blood vessels were significantly higher in RA compared with OA. CONCLUSION: Our results underscore the importance of area-specific gene expression analysis in studying the pathogenesis of RA and support LMM as a robust tool for this purpose. Of note, our results indicate that previously described differences between RA and OA in the expression of angiogenic molecules are attributable to higher total numbers of synovial and vascular cells expressing these molecules in RA rather than higher expression levels in the individual cells.
16701135 Thumb metacarpophalangeal arthritis: arthroplasty or fusion? 2006 May The human thumb assumes 50% of the workload of the human hand, and is therefore the most important digit. As such, the thumb has a propensity for the development of osteoarthritis. Moreover, the thumb is also often diseased, in anywhere from 68% to 80%of patients who have rheumatoid arthritis. Much attention over the years has been given to the carpalmetacarpal joint of the thumb, whereas the metacarpophalangeal (MP) joint of the thumb remains largely unstudied. The purpose of this article is to review the etiology of thumb MP joint arthritis, and discuss the different treatment options of this condition.
18759262 How accurate are diagnoses for rheumatoid arthritis and juvenile idiopathic arthritis in t 2008 Sep 15 OBJECTIVE: To identify characteristics that predict a valid rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA) diagnosis among RA- and JIA-coded individuals in the General Practice Research Database (GPRD), and to assess limitations of this type of diagnostic validation. METHODS: Four RA and 2 JIA diagnostic groups were created with differing strengths of evidence of RA/JIA (Group 1 = strongest evidence), based on RA/JIA medical codes. Individuals were sampled from each group and clinical and prescription data were extracted from anonymized hospital/practice correspondence and electronic records. American College of Rheumatology and International League of Associations for Rheumatology diagnostic criteria were used to validate diagnoses. A data-derived diagnostic algorithm that maximized sensitivity and specificity was identified using logistic regression. RESULTS: Among 223 RA-coded individuals, the diagnostic algorithm classified individuals as having RA if they had an appropriate GPRD disease-modifying antirheumatic drug prescription or 3 other GPRD characteristics: >1 RA code during followup, RA diagnostic Group 1 or 2, and no later alternative diagnostic code. This algorithm had >80% sensitivity and specificity when applied to a test data set. Among 101 JIA-coded individuals, the strongest predictor of a valid diagnosis was a Group 1 diagnostic code (>90% sensitivity and specificity). CONCLUSION: Validity of an RA diagnosis among RA-coded GPRD individuals appears high for patients with specific characteristics. The findings are important for both interpreting results of published GPRD studies and identifying RA/JIA patients for future GPRD-based research. However, several limitations were identified, and further debate is needed on how best to validate chronic disease diagnoses in the GPRD.
16450152 [Radiosynoviorthesis]. 2006 May Intraarticular therapy is an established form of therapy in chronic inflammatory joint diseases. Besides the injection of glucocorticoids, radiosynoviorthesis is a frequently used procedure. Intraarticular injected beta-emitting radionuclides are indicated in chronic synovitis with recurrent joint effusions in rheumatoid arthritis, seronegative spondyloarthritis, villonodular synovitis after surgery and for bleeding prophylaxis in haemophilic arthropathy. The value of radiosynoviorthesis in activated osteoarthritis is not yet clarified.
18846014 [Familiar chondrocalcinosis: a story for two brothers]. 2008 Jul Calcium pyrophosphate dihydrate crystal deposition is frequently an asymptomatic disease. However it may cause severe acute attacks of inflammatory arthritis as well as chronic arthropathies. The authors present two case reports of two brothers with chondrocalcinosis and an unusual presentation that mimics rheumatoid arthritis. Special considerations are made about the differences between the familiar and idiopathic forms.
16871531 Classification criteria for psoriatic arthritis: development of new criteria from a large 2006 Aug OBJECTIVE: To compare the accuracy of existing classification criteria for the diagnosis of psoriatic arthritis (PsA) and to construct new criteria from observed data. METHODS: Data were collected prospectively from consecutive clinic attendees with PsA and other inflammatory arthropathies. Subjects were classified by each of 7 criteria. Sensitivity and specificity were compared using conditional logistic regression analysis. Latent class analysis was used to calculate criteria accuracy in order to confirm the validity of clinical diagnosis as the gold standard definition of "case"-ness. Classification and Regression Trees methodology and logistic regression were used to identify items for new criteria, which were then constructed using a receiver operating characteristic curve. RESULTS: Data were collected on 588 cases and 536 controls with rheumatoid arthritis (n = 384), ankylosing spondylitis (n = 72), undifferentiated arthritis (n = 38), connective tissue disorders (n = 14), and other diseases (n = 28). The specificity of each set of criteria was high. The sensitivity of the Vasey and Espinoza method (0.97) was similar to that of the method of McGonagle et al (0.98) and greater than that of the methods of Bennett (0.44), Moll and Wright (0.91), the European Spondylarthropathy Study Group (0.74), and Gladman et al (0.91). The CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria consisted of established inflammatory articular disease with at least 3 points from the following features: current psoriasis (assigned a score of 2; all other features were assigned a score of 1), a history of psoriasis (unless current psoriasis was present), a family history of psoriasis (unless current psoriasis was present or there was a history of psoriasis), dactylitis, juxtaarticular new bone formation, rheumatoid factor negativity, and nail dystrophy. These criteria were more specific (0.987 versus 0.960) but less sensitive (0.914 versus 0.972) than those of Vasey and Espinoza. CONCLUSION: The CASPAR criteria are simple and highly specific but less sensitive than the Vasey and Espinoza criteria.
18403061 [B lymphocytes in Sjögren's syndrome]. 2008 Dec INTRODUCTION: Sjögren's syndrome (SS) is an autoimmune epithelitis hallmarked by a disruption of epithelial cells, the subsequent lymphocytic infiltration of lachrymal and salivary glands (SGs), and their ensuing dryness. One may posit that SS is triggered by viruses, and/or modulated by sex steroid hormones, and there is indeed a consensus that its aetiology is multifactorial, with genetic factors interacting with environmental agents. CURRENT KNOWLEDGE AND KEY POINTS: T-cells have long occupied central stage of the debate on the type of lymphocytes involved in the pathogenesis of SS. The relevance of B cells has, however, been emphasized over the past five years and new insights into their functions revealed. Furthermore, increased levels of the B-cell activating factor (BAFF) may be responsible for quantitative and qualitative anomalies of B-cells found in SS such as emergence of self reactive B-cells. This review reports compelling evidence that B-cells are involved in the pathophysiology of SS. PROSPECTS: Since SS may thus be conceived as a model for B-cell-induced autoimmunity, it is no surprise that B-cell ablative-treatment has proven to be relatively effective in SS.
17535407 Primary localized cutaneous amyloidosis with unusual clinical features in a patient with S 2007 Jun A 69-year-old woman presented with a 2-year history of an eczematous lesion covering the genital area. Histopathological examination showed deposits of amorphous, eosinophilic material and an infiltrate of plasma cells through the entire dermis into the subcutaneous fatty tissue. Congo red-stained deposits showed apple-green birefringence with polarizing microscopy. On immunohistochemistry, the deposited material was positively stained with anti-lambda light chain antibodies but not with anti-lambda light chain. A diagnosis of primary localized cutaneous amyloidosis (PLCA) was made, and the patient was also diagnosed as having Sjögren's syndrome (SjS) based on clinical and laboratory findings. The lesion of PLCA has spontaneously regressed over a period of 18 months. We report a unique case of PLCA and SjS that clinically demonstrated genital eczematous features and spontaneous involution, and we also describe a possible association between PLCA and SjS.
16986677 [Two cases of myelitis associated with Sjögren syndrome without xerosis: characteristic M 2006 Aug We report two cases of myelitis associated with Sjögren syndrome without xerosis. Case 1: A 30-year old woman developed dysesthesia on both upper extremities and weakness of the right arm. A T2-weighted MRI examination showed a high-intensity signal and a swollen lesion between the first and seventh cervical vertebral levels. She was diagnosed as having primary Sjögren syndrome based on the positive finding of a Saxon test, typical salivary gland scintigraphy findings, and an elevated anti-SS-A antibody titer. We suspected that her myelitis was associated with Sjögren syndrome and treated her using steroid therapy. Although her symptoms were alleviated, her myelitis relapsed at the same location after the cessation of steroid therapy. Case 2: A 31-year-old woman developed dysesthesia on her neck and both upper extremities and exhibited tonic spasm. A T2-weighted MRI examination showed a high-intensity signal and a swollen lesion between the first and sixth cervical vertebral levels. She was diagnosed as having primary Sjögren syndrome based on the positive findings of a Rose Bengal test, a Schirmer's test, and a Saxon test as well as typical salivary gland scintigraphy findings and elevated titers of anti-SS-A and anti-SS-B antibodies. We suspected that her myelitis was associated with Sjögren syndrome and treated her using steroid therapy. Her symptoms improved after steroid therapy. Based on these two cases, we concluded that MRI findings for myelitis associated with Sjögren syndrome are characterized by a swollen lesion of more than three vertebral segments in length, and the relapse tends to occur at the same location.
17983259 Celecoxib: a review of its use in the management of arthritis and acute pain. 2007 Celecoxib (Celebrex), the first cyclo-oxygenase (COX) 2-selective inhibitor (coxib) to be introduced into clinical practice, has been available for almost a decade. It is approved in one or more countries worldwide for the relief of the signs and symptoms of osteoarthritis (OA), rheumatoid arthritis (RA), juvenile rheumatoid arthritis (in patients aged > or =2 years) and ankylosing spondylitis (AS), the management of acute pain in adults, the treatment of primary dysmenorrhoea and the reduction in the number of adenomatous colorectal polyps in familial adenomatous polyposis. Celecoxib remains an effective and useful altenative to nonselective NSAIDs in the treatment of acute or chronic musculoskeletal pain. In the latter setting, it offers the prospect of improved gastrointestinal (GI) tolerability and, in patients not taking aspirin for cardioprophylaxis, a GI safety advantage. Currently available evidence of an increase in cardiovascular (CV) risk with celecoxib is inconsistent; any increase in risk is likely to be small and similar to that with nonselective NSAIDs. As with all NSAIDs, the potential GI, CV and renal risks of celecoxib must be weighed against the potential benefits in each individual; it is a rational choice for patients at low CV risk who require NSAID therapy, especially those at increased risk of NSAID-induced GI toxicity, but also those unresponsive to, or intolerant of, other NSAIDs. If selected, celecoxib, like all NSAIDs, should be used at the lowest effective dose for the shortest possible duration.
17659755 Autonomic and orthostatic dysfunction in primary Sjögren's syndrome. 2007 Sep OBJECTIVE: Exocrine function always is and autonomic nervous function may be impaired in primary Sjögren's syndrome (pSS). Since autonomic nervous signaling is a prerequisite for exocrine secretion we wanted to assess autonomic nervous function in pSS and relate it to diagnostic measures of exocrine function. METHODS: Autonomic nervous function was determined in 46 patients with pSS using the deep breathing test [expiration/inspiration (E/I) ratio], orthostatic test [acceleration index (AI), orthostatic systolic and diastolic blood pressure response (lSBP ratio and lDBP ratio)], and finger skin blood flow test [vasoconstrictory (VAC) score]. The results were corrected for age and expressed as z-scores by comparison with 3 control groups (E/I ratio and AI, n = 56; lSBP ratio and lDBP ratio, n = 238; and VAC score, n = 80). Exocrine gland function was determined in patients with pSS using the objective functional Schirmer-I test and rose-bengal staining (van Bijsterveld score) for the lacrimal glands and unstimulated whole sialometry for the salivary glands. RESULTS: The E/I ratio and orthostatic systolic and diastolic blood pressures were significantly decreased and the VAC score was significantly increased in patients with pSS compared to controls, indicating both parasympathetic and sympathetic dysfunction. Autonomic and exocrine function measures were found to associate poorly. CONCLUSION: Patients with pSS showed signs of both parasympathetic and sympathetic dysfunction. However, an association between cardiovascular autonomic and exocrine function in pSS was not detected.
16897120 Lymphocytic interstitial pneumonitis (LIP) in Sjögren's syndrome: a case report and a rev 2007 Aug Sjõgren's disease is one of the most common rheumatological diseases and can present with a variety of extra-glandular manifestations. Lymphocytic Interstitial Pneumonitis (LIP) is the most common lung pathology in these patients. It is important to know and recognize this condition because it is potentially treatable. It is also frequently misdiagnosed and treated as infectious pneumonia multiple times before the correct diagnosis is made. It is a benign lymphoproliferative disorder characterized histologically by interstitial infiltration with polyclonal lymphocytes and plasma cells. High-resolution CT scan of the lungs shows extensive areas of ground-glass attenuation and interlobular septal thickening with scattered thin-walled cysts. An open-lung biopsy is the best method of diagnosing this condition, as less invasive techniques do not provide an adequate tissue specimen. LIP occurs in a wide variety of settings such as autoimmune disease, HIV disease, and as an adverse reaction to some medications; it is, therefore, considered to be a nonspecific response to many stimuli. The treatment usually consists of corticosteroids and other immunosuppressants, though there have been no controlled trials to date. Establishment of a registry may help better evaluate and treat this disease. We present the case of a patient who was diagnosed with LIP secondary to Sjögren's syndrome and also review the literature available.
16821272 Epidemiology of juvenile idiopathic arthritis in Alsace, France. 2006 Jul OBJECTIVE: To determine the incidence, prevalence, and principal characteristics of the different forms of juvenile idiopathic arthritis (JIA) in the region of Alsace, northeastern France, using the new classification of the International League of Associations for Rheumatology (ILAR). METHODS: In 2002 we performed a retrospective epidemiologic study pertaining to the year 2001. The pediatricians, rheumatologists, ophthalmologists, orthopedic surgeons, and physicians involved in functional reeducation in the Alsace region were interviewed, and all patients were classified according to the new ILAR classification using the criteria revised in Durban in 1997. RESULTS: Among the 361 clinicians contacted, the participation rate was 97.8%. The study identified 67 children followed for JIA in Alsace in 2001, from a total population of 1.8 million inhabitants including 339,095 children under age 16 years. The incidence was calculated to be 3.2 cases/100,000/year and the prevalence 19.8 cases/100,000 children under age 16 years. Among these 67 cases of JIA, the most frequent forms were oligoarthritis (n = 27, 40.3%), polyarthritis without rheumatoid factor (RF; n = 15, 22.4%), and enthesitis related arthritis (n = 12, 17.9%). Other forms, notably systemic arthritis (n = 6, 8.9%) and psoriatic arthritis (n = 3, 4.5%), were more rare and in this study there was no case of polyarthritis with RF. Only 4 patients (6%) were classified in the undifferentiated arthritis group using the new classification. Antinuclear antibodies (ANA; by indirect immunofluorescence, HEp >/= 1/80) were detected in patients with oligoarthritis (81%) and polyarthritis without RF (79%). Uveitis occurred in 41% of children with oligoarthritis and in 14% of those with polyarthritis without RF. CONCLUSION: Our results are comparable to those of other studies carried out in Caucasian populations with regard to incidence and prevalence. This work also highlights the frequent presence of ANA and uveitis in patients with oligoarthritis or polyarthritis without RF.
18780116 Insufficient flexion of the metacarpophalangeal joint of the little finger following Swans 2008 Mar Twenty-one patients with rheumatoid arthritis who underwent Swanson metacarpophalangeal (MP) arthroplasty from 1994 to 1999 were assessed for active flexion of individual MP joints an average of 59 months (range 27-114 months) postoperative. Published articles of Swanson MP arthroplasty were reviewed. Experienced hand surgeons were surveyed regarding outcomes of metacarpophalangeal arthroplasty. The MP joint of the little finger displayed significantly less flexion than that of the middle and index finger. Seven of eight published studies which present active MP flexion by individual digit demonstrated less flexion in the little finger compared to the index, middle, and ring finger. Half of surgeons surveyed reported that MP range of motion is shifted toward a more extended position, that MP flexion is limited in the ulnar digits, and that an implant that encourages MP flexion would be helpful. Our experience with this cohort, a review of published literature, and a survey of international experts suggest that Swanson arthroplasty frequently results in a range of flexion of the MP joint of the little finger that may be insufficient for its principal functions.
21794559 [Infections in Patients With Rheumatoid Arthritis Undergoing Anti-TNFα Drug Therapy]. 2008 Oct Infections are more frequent in patients with rheumatoid arthritis (RA). The capacity of the anti-TNF drugs (infliximab, etanercept, and adalimumab) to increase the risk of infections has been a motive of discussion during the past years. Only in two of the trials that have allowed the marketing of the infliximab and adalimumab more serious infections were observed. TB was not observed in the trials. Nevertheless, later they have been published not controlled studies that show infections and TB in patients with RA that receive anti-TNFα drugs. The disagreement between the trials and the not controlled studies has been the motive of the accomplishment of metaanalysis which study the frequency of infections in patients with RA that receive anti-TNFα drugs. The three metaanalysis published show an increase of the risk of infections in patients with AR in treatment with infliximab and with adalimumab, specially when they administer high doses. This risk does not seem to increase with etanercept, probably due to the fact that doses superior to the recommended ones have not been used in the analyzed trials. Increased risk of infections was not detected in the trials, but the metaanalysis increases the statistical power and allow demonstrating increased risk of infections. A causal relation exists between the administration of anti-TNFα and the development of infections, fulfilling all the criteria of causality.
21794414 [Magnetic resonance of the hand in rheumatoid arthritis. Review of methodology, and its us 2007 May The ideal aim of treatment in rheumatoid arthritis (RA) is to suppress synovial inflammation and to stop or reduce structural joint damage progression. To evaluate joint damage in RA, radiographic assessment of hands and feet is the traditional method. Nevertheless, plain film radiography can only evaluate bone damage (erosion) and, indirectly, joint cartilage. Magnetic resonance imaging presents important advantages since allows to study, not only the cortical bone and the marrow, but also the synovial membrane, tendon and ligament structures,and adjacent soft tissue that usually are involved in early disease. Moreover, hand-magnetic resonance (h-MRI) has shown to be more sensitive than plain radiography in detecting early erosions and predicting progression of bone damage, allowing a rapid diagnosis and to start the most efficient therapy as well as to achieve better outcomes for this disease.
17311555 Inflammatory caspases: targets for novel therapies. 2007 This review provides an overview of the biochemistry and activation of inflammatory caspases, and focuses on their therapeutic potential as disease targets in pathologies such as sepsis, Crohn's disease, rheumatoid arthritis, traumatic brain injury and amyotrophic lateral sclerosis (ALS). We summarize the proof-of-principal evidence obtained by studies in several corresponding experimental disease models confirming the validity of strategies targeting inflammatory caspases. We discuss the use of inflammatory caspase inhibitors, such as VX-740 (Pralnacasan) and VX-765, in clinical studies for rheumatoid arthritis and osteoarthritis. Finally, we point out recent approaches identifying novel peptidomimetic or non-peptide caspase inhibitors with suitable clinical profiles.
21136610 In pursuit of B-cell synovial autoantigens in rheumatoid arthritis: Confirmation of citrul 2007 Jan We aimed to investigate potential synovial autoantigens in rheumatoid arthritis (RA) that could trigger the induction of B-cell autoantibodies. Total protein extract of synovial tissue obtained from seven RA patients was pooled and separated by 1-DE and 2-DE. The corresponding blots were probed with sera from RA (n = 30) and disease control samples (n = 30). Protein spots showing a sensitivity of >15% were identified by MS. 1-D immunoblots revealed one protein band with a specificity in RA of 100%, a sensitivity of 43%, which was identified as fibrinogen β chain. 2-D analysis revealed the subunits of fibrinogen, especially the β and γ chain, as the most prominent synovial autoantigens. We also identified vimentin, the Sa-antigen and carbonic anhydrase I as a potentially new synovial autoantigen. The protein patterns of these immunoreactive spots were observed as trains. The spots showing the highest autoimmune reactivity occurred at the acidic side of these trains and were recognized by anticitrullinated protein/peptide antibodies positive RA sera. Antimodified citrulline staining of these patterns confirmed protein citrullination. Therefore, PTMs such as citrullination due to alterations of peptidylarginine deiminase activity or generation of RA-specific epitopes, should be considered as a trigger in tolerance break.
17550930 The autoantibody rheumatoid factor may be an independent risk factor for ischaemic heart d 2007 Oct BACKGROUND: Subjects with rheumatoid arthritis have an increased prevalence of ischaemic heart disease (IHD). This is most likely in those people with the autoantibody rheumatoid factor (RF). RF is strongly associated with rheumatoid arthritis (RA) but is also present in up to 15% of all adults. OBJECTIVE: To determine whether RF might identify people in a general population who also share an increased likelihood of developing IHD. METHODS: Subjects from the Hertfordshire Cohort Study were investigated for the presence of RF. Subjects completed a questionnaire and attended a clinic where a history of IHD was recorded (ECG, coronary artery bypass grafting, Rose chest pain). Associations between the presence of RF, antinuclear antibodies (ANA), anticardiolipin antibodies (ACA) and IHD in 567 men and 589 women were investigated and compared with traditional risk factors for IHD. RESULTS: RF was associated with an increased likelihood of IHD in men (odds ratio (OR) = 3.1, 95% CI 1.7 to 5.4, p<0.001). This increased risk could not be explained by traditional risk factors for IHD (mutually adjusted OR for RF 2.9 (95% CI 1.6 to 5.3), p<0.001). There was no significant association between RF in women or between ANA or ACA with IHD in men or women. CONCLUSION: This work suggests that RF is an independent risk factor for IHD in the general population. It lends support to the importance of inflammation in atherosclerosis and suggests that autoimmune processes may be involved. In addition, it raises the intriguing possibility that RF may have a direct role in the pathogenesis of IHD in some subjects.