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ID PMID Title PublicationDate abstract
17668696 Total hip and knee arthroplasty for juvenile rheumatoid arthritis. 2006 We performed 23 total hip and knee arthroplasties (15 total hip and 8 total knee arthroplasties) in 18 children with juvenile rheumatoid arthritis between 1984 and 2001. The mean age at surgery was 17.8 years (range 13 to 24 years). The age of presentation of the disease was from 4 to 10 years with average 7.3 years. The average length of follow-up was 9.7 years (range 7 to 16 years). All patients conformed with the American Rheumatism Association criteria for juvenile rheumatoid arthritis. All patients had complete loss of joint space and various combination of subchondral sclerosis, flattening of the femoral head, anterior inclination of the neck. Three knees were diagnosed with bony ankylosis. Follow-up was based on the Merle d'Aubigne et Postel scale modified by Charnley. One acetabular component has been revised to date. No femoral or tibial components have been revised. No patient had pain post-operatively and function was very satisfactory. Total hip and knee arthroplasties are technically difficult to execute in this age and should be performed in specialized centers. With appropriate indications pain relief,decrease of deformity and improvement of quality of life can be achieved in most patients.
18466553 Joint linkage and imprinting analyses of GAW15 rheumatoid arthritis and gene expression da 2007 BACKGROUND: Genomic imprinting is a mechanism in which the expression of a gene copy depends upon the sex of the parent from which it was inherited. This mechanism is now well recognized in humans, and the deregulation of imprinted genes has been implicated in a number of diseases. In this study, we performed a genome-wide joint linkage and imprinting scan using two data sets provided by Genetic Analysis Workshop 15 (GAW15). RESULTS: The first data set was high-risk rheumatoid arthritis families collected by the North American Rheumatoid Arthritis Consortium. We used both model-based and model-free methods of joint linkage and imprinting analyses. Although a genome scan of rheumatoid arthritis families using GENEHUNTER-MODSCORE suggested regions that might be imprinted, further analyses using variance-components method failed to obtain significant signals of imprinting. The second data set was Problem 1 of GAW15, which included single-nucleotide polymorphism genotypes and gene expression data for Centre d'Etude du Polymorphisme Humain pedigrees. A previous genome-wide linkage scan identified loci that may be regulators of gene expression: our genome-wide joint linkage and imprinting scan using a variance-components approach found significant signals for linkage. CONCLUSION: Our linkage scan results suggest that imprinted genes are unlikely to be involved in susceptibility to rheumatoid arthritis. However, for expression level of TGFBR3 gene, we found a point-wise p-value of 0.03 for imprinting, but increase in the LOD score did not meet the required threshold to reliably identify imprinting as the correct mode of inheritance in genome-wide linkage scans.
17045106 Pathophysiology of Sjögren's syndrome. 2006 Nov The term Sjögren's syndrome refers to keratoconjunctivitis sicca and xerostomia due to lymphocytic infiltrates of lachrymal and salivary glands. The current used criteria for diagnosis of primary Sjögren's syndrome is the American-European consensus. Primary Sjögren's syndrome is an autoimmune disorder characterized by lymphocytic infiltrates and destruction of the salivary and lachrymal glands and systemic production of autoantibodies to the ribonucleoprotein particles SS-A/Ro and SS-B/La. The infiltrating cells (T- and B-cells, dendritic cells) interfere with glandular function at several points: destruction of glandular elements by cell-mediated mechanisms; secretion of cytokines that activate pathways bearing the signature of type 1 and 2 interferons; production of autoantibodies that interfere with muscarinic receptors; and secretion of metalloproteinases (MMPs) that interfere with the interaction of the glandular cell with its extracellular matrix, which is necessary for efficient glandular function. As the process progresses, the mucosal surfaces become sites of chronic inflammation and the start of a vicious circle. Despite extensive study of the underlying cause of Sjögren's syndrome, the pathogenesis remains obscure. In broad terms, pathogenesis is multifactorial; environmental factors are thought to trigger inflammation in individuals with a genetic predisposition to the disorder.
17983148 The use of animal models for rheumatoid arthritis. 2007 Rheumatoid arthritis (RA) is a description of classical symptoms that can be grouped together to be recognized as a common entity. However, the disease is more heterogeneous and is likely composed of many different, distinct diseases. This heterogeneity is of two types. First, the disease can be classified into several subtypes, and second, the underlying cause of each disease group may be attributable to different genetic and environmental factors, each contributing to a distinct disease phenotype. This is an important starting point when discussing animal models for RA. Thus, there is not one model for RA. There are, and must be, several different models with different symptoms and different pathogenic mechanisms, controlled by different genes.
16462517 Malignancy and autoimmunity. 2006 Mar PURPOSE OF REVIEW: The association of cancer with autoimmune disease has been under investigation for several years. Reports have appeared suggesting increased cancer risk in autoimmune rheumatic diseases. Evidence has been accumulating recently in rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, and scleroderma/systemic sclerosis. This review focuses on recent publications regarding risk of cancer in these conditions. RECENT FINDINGS: Despite a lack of a strong association between rheumatoid arthritis and cancer overall, studies show an increased risk for the development of lymphoma in rheumatoid arthritis. There are data suggesting an increased risk for rheumatoid arthritis patients regarding lung cancer. In Sjogren's syndrome-related malignancies, most publications in the past year relate to non-Hodgkin's lymphomas, and suggest possible mechanisms driving the association. Data substantiate an increased risk of certain cancers in systemic lupus erythematosus; the risk appears to be most heightened for lymphoma. A recent cohort study examined cancer risk in scleroderma; the estimates were lower than previous studies had suggested, and the confidence intervals relatively imprecise, making a definitive conclusion difficult. SUMMARY: There have been several papers published related to cancer in the rheumatic diseases, particularly inflammatory arthritis, Sjogren's syndrome, systemic lupus erythematosus, and scleroderma/systemic sclerosis. Continuing interest in the association between autoimmune rheumatic diseases and malignancy is likely, given the potential impact in terms of understanding both rheumatic diseases and cancer.
17332090 Autoimmune diseases and Sjogren's syndrome: an autoimmune exocrinopathy. 2007 Mar Autoimmune diseases include a diverse group of over 80 conditions. Sjögren's syndrome is the second most common autoimmune rheumatic disease, with an estimated prevalence in the United States of 2-4 million persons. There are prominent and consistent oral and dental findings in Sjögren's syndrome related to the autoimmune-mediated loss of normal salivary function. Additionally, nonoral clinical manifestations of Sjögren's syndrome include: dry eyes (with specific ocular surface changes termed keratoconjunctivitis sicca); other xeroses, such as dryness of the nose, throat, skin, and vagina; peripheral (and less frequently central) neuropathies; myalgias and arthralgias; thyroid disorders (particularly autoimmune thyroiditis); pulmonary disorders; renal disorders; and lymphoma. There is a significant (20- to 40-fold) increase in the incidence of malignant lymphoma, particularly in primary Sjögren's syndrome. Establishing the diagnosis of Sjögren's syndrome has been difficult in the light of its nonspecific symptoms (dry eyes and mouth), disagreement on diagnostic criteria, and a lack of both sensitive and specific laboratory markers. Many serum and salivary biomarkers for Sjögren's syndrome have been proposed although, to date, none has proven to be sufficiently specific for diagnostic purposes or has been well correlated with disease activity measures. Investigators have recently begun to apply modern genomic and proteomic approaches to identify candidate biomarkers in Sjögren's syndrome. The results of these investigations promise to provide a wealth of information on candidate biomarkers and possible etiopathological mechanisms underlying this disorder. Further, this information will improve clinical outcomes by fostering the design of new rational therapeutics and assisting in the monitoring of clinical disease.
17014637 The prognostic value of nailfold capillary changes for the development of connective tissu 2006 Sep To assess the prognostic value of capillaroscopy findings for the development of connective tissue disease in children and adolescents with Raynaud phenomenon, we followed up a group of 250 (mean age 15 years) for 1 to 6 years after the first capillaroscopy was performed. Every 6 months they were screened for signs and symptoms of connective tissue disease. Analysis was performed on capillary changes registered 6 months before the development of connective tissue disease. Capillary changes were classified into three types: normal, nonspecific, and sclerodermatous. At the end of the follow-up period, 191 (76%) subjects had primary Raynaud phenomenon, 27 (10.8%) were diagnosed as having undifferentiated connective tissue disease, and 32 (12.8%) fulfilled the criteria for a diagnosis of a specific connective tissue disease. Systemic lupus erythematosus was found in nine (3.6%) patients, rheumatoid arthritis in 10 (4%) patients (six of them with juvenile onset rheumatoid arthritis), and scleroderma spectrum disorders in 13 (5.2%). The mean time for the evolution of Raynaud phenomenon into undifferentiated connective tissue disease or a form of the disease was 2 years. Most of the subjects with primary Raynaud phenomenon (173/191, 91%), undifferentiated connective tissue disease (22/27, 81%), juvenile onset rheumatoid arthritis/rheumatoid arthritis (7/10, 70%), and systemic lupus erythematosus (6/9, 67%) had normal capillary findings. Nonspecific capillary changes occurred in 3 of 10 (30%) patients with rheumatoid arthritis, 2 of 9 (22%) with systemic lupus erythematosus, 4 of 27 (15%) with undifferentiated connective tissue disease, and 18 of 191 (9%) with primary Raynaud phenomenon. Of all the subjects, only 10 (4%) showed sclerodermatous disease type capillary changes 6 months before the expression of a particular disease: eight (62%) of these developed scleroderma spectrum disorders, one expressed systemic lupus erythematosus, and one had undifferentiated connective tissue disease. We concluded that there were no specific capillary changes predictive for future development of systemic lupus erythematosus, juvenile onset rheumatoid arthritis/rheumatoid arthritis, and undifferentiated connective tissue disease in children and adolescents with Raynaud phenomenon. Most of our study subjects with Raynaud phenomenon who developed these diseases had normal capillary findings or nonspecific changes. Children and adolescents who developed scleroderma spectrum disorders showed a sclerodermatous type of capillary changes 6 months before the expression of the disease, indicating that this type of capillary changes in children and adolescents with Raynaud phenomenon highly correlated with further development of scleroderma spectrum disorders.
18818751 Eicosapentaenoic Acid suppresses the proliferation of synoviocytes from rheumatoid arthrit 2008 Sep Eicosapentaenoic acid (EPA) is essential for normal cell growth, and may play an important role in inflammatory and autoimmune disorders including rheumatoid arthritis. We investigate that EPA could suppress the proliferation of fibroblast like synoviocytes in vitro. We treated synoviocytes with 1 to 50 microM EPA and measured cell viabilities by the modified MTT assay. We sorted the number of them in sub G1 stage by fluorescence-activated cell sorting caliber. And we stained them by light green or Hoechst 33258, and investigate microscopic appearance. The cell viabilities were decreased at 30 microM, 40 microM, and 50 microM of EPA comparing to 0 microM of EPA. The half maximal concentration of synoviocytes inhibition was approximately 25 microM. At day 1 and day 3, cell number was also decreased at 50 microM EPA comparing to control. FACS caliber indicated the number of synoviocytes in sub G1 stage did not increase in each concentration of EPA. Hoechst staining indicated normal chromatin pattern and no change in a nuclear morphology both in EPA treated synoviocytes and in untreated synoviocytes. These findings suggest that EPA could suppress the proliferation of synoviocytes in vivo dose dependently and time dependently, however, the mechanism is not due to apoptosis.
18466564 A two-dimensional genome scan for rheumatoid arthritis susceptibility loci. 2007 We performed a genome-wide search for pairs of susceptibility loci that jointly contribute to rheumatoid arthritis in families recruited by the North American Rheumatoid Arthritis Consortium. A complete two-dimensional (2D) non-parametric linkage scan was carried out using 380 autosomal microsatellite markers in 511 families. At each 2D peak we obtained the most likely underlying genetic model explaining the two-locus effects, defining epistasis as a departure from an additive or a multiplicative two-locus penetrance function. The highest peak in the surface identified an epistatic interaction between loci 6p21 and 16p12 (two-locus lod score = 18.02, epistasis P < 0.012). Significant and suggestive two-locus effects were also obtained for region 6p21 in combination with loci 18q21, 8p23, 1q41, and 6p22, while the highest 2D peaks excluding region 6p21 were observed at locus pairs 8p23-18q21 and 1p21-18q21. The 2D peaks were further examined using combined microsatellite and single-nucleotide polymorphism (SNP) marker genotypes in 744 families. The two-locus evidence for linkage increased for region pairs 6p21-18q12, 6p21-16p12, 6p21-8p23, 1q41-6p21, and 6p21-6p22, but decreased for pairs of regions that did not include locus 6p21. In conclusion, we obtained evidence for multi-locus interactions in rheumatoid arthritis that are mediated by the major susceptibility locus at 6p21.
19707303 Targeted therapies in rheumatoid arthritis: Focus on rituximab. 2007 Dec B-cell depletion is a new strategy for treating patients with rheumatoid arthritis (RA). In the past years, several studies have proven the efficacy of anti-CD20 mediated B-cell depletion with rituximab (Mabthera((R))) in RA patients who failed TNF-blocking therapy. The important role of B-cells in the pathogenesis of RA is deducted from the specific detection of autoantibodies in RA and infiltration of B-cells and plasma cells in inflamed synovium. Pharmacological studies in RA patients treated with rituximab showed that half-life was approximately 3 weeks leading to a 6- to 8-month period of B-cell depletion in peripheral blood. Rituximab treatment led to significant improvements in disease activity of RA patients and the current review summarizes the results from phase III, randomized clinical trials that have been performed. Lastly, data on safety and quality of life are summarized. Although relatively low numbers of RA patients have been treated and long-term data are lacking, current data thus far suggest a relatively good safety profile for rituximab. Future studies will need to focus on predicting responsiveness to rituximab, investigating efficacy of re-treatment with rituximab and extending data on safety and patient-focused outcomes.
18466459 Modeling the complex gene x environment interplay in the simulated rheumatoid arthritis GA 2007 Rheumatoid arthritis is a complex disease that appears to involve multiple genetic and environmental factors. Using the Genetic Analysis Workshop 15 simulated rheumatoid arthritis data and the structural equation modeling framework, we tested hypothesized "causal" rheumatoid arthritis model(s) by employing a novel latent gene construct approach that models individual genes as latent variables defined by multiple dense and non-dense single-nucleotide polymorphisms (SNPs). Our approach produced valid latent gene constructs, particularly with dense SNPs, which when coupled with other factors involved in rheumatoid arthritis, were able to generate good fitting models by certain goodness of fit indices. We observed that Gene F, C, DR, sex and smoking were significant predictors of rheumatoid arthritis but Genes A and E were not, which was generally, but not entirely, consistent with how the data were simulated. Our approach holds promise in unravelling complex diseases and improves upon current "one SNP (haplotype)-at-a-time" regression approaches by decreasing the number of statistical tests while minimizing problems with multicolinearity and haplotype estimation algorithm error. Furthermore, when genes are modeled as latent constructs simultaneously with other key cofactors, the approach provides enhanced control of confounding that should lead to less biased effect estimates among genes as well as between gene(s) and the complex disease. However, further study is needed to quantify bias, evaluate fit index disparity, and resolve multiplicative latent gene interactions. Moreover, because some a priori biological information is needed to form an initial substantive model, our approach may be most appropriate for candidate gene SNP panel applications.
16997789 Design of a new line in treatment of experimental rheumatoid arthritis by artesunate. 2006 This study was aimed to evaluate the therapeutic potency of a new antimalarial drug, artesunate, in an experimental model of rheumatoid arthritis. Collagen-induced arthritis (CIA) was induced in Lewis rats.The intraperitoneally administration of artesunate (ARS) and methotrexate (MTX) were started on day 25 postimmunization and continued until final assessment on day 35. During this period, clinical examination was intermittent. The anticollagen type II antibody (CII Ab) and nitric oxide synthesis were measured. The paws and kness were then removed for histopathology and radiography assay. The biocompatibility of ARS and MTX were assessed using fibrosarcoma cell line. Our results showed that i.p. injection of artesunate to arthritic rats induced a significant reduction in paw edema. This beneficial effect was associated with a significant decrease in anti-CII antibody response compared with untreated rats. Histopathological assessment showed reduced inflammatory cells infiltrate in joints of treated rats, and tissue edema and bone erosion in the paws were markedly reduced following ARS therapy. Moreover, our radiographic results paralleled histological findings. Cytotoxicity analysis of ARS showed greater tolerability compared with MTX. Treatment with ARS significantly diminished nitric oxide formation in treated rats compared with untreated controls. Our findings revealed the therapeutic efficacy of artesunate in experimental rheumatoid arthritis compared with a choice drug (methotrexate). This result may recommend it as a second-line drug in the treatment of rheumatoid arthritis.
18364117 Effect of local viral transfer of interleukin 10 gene on a rabbit arthritis model induced 2008 Mar 5 BACKGROUND: Interleukin 1beta (IL-1beta) is the principal mediator in the pathogenesis of rheumatoid arthritis. Continuous injection of interleukin 1beta (IL-1beta) into the knee articular cavities of animals can induce models that resemble rheumatoid arthritis. The objective of this study was to evaluate the feasibility of local recombinant retrovirus viral interleukin 10 (rRV-vIL-10) gene transfer treatment of a rabbit model of arthritis induced by IL-1beta. METHODS: An hIL-1beta-induced rabbit rheumatoid arthritis model was established using the MFG-hIL-1beta-neo-HIG-82 cell line, which is capable of continuous secretion of hIL-1beta. After transfecting the rabbit synovial fibroblast cell line (MFG-hIL-1beta-neo-HIG-82) with rRV-vIL-10, G418 was then added to identify the positive clone. The rRV-vIL-10 positive clone was injected into the established rabbit rheumatoid arthritis model through intra-articular injection. Successful gene transfer was determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The levels of IL-1beta before and after treatment were determined by enzyme- linked immunosorbent assay. RESULTS: Retrovirus vector was an effective vector both to synoviocytes in vitro and synovium tissue in vivo as confirmed by RT-PCR and immunohistochemistry. The rabbit arthritis model treated with rRV-vIL-10 showed a dramatic remission of arthritis and a decline in the level of cytokines such as IL-1beta. CONCLUSIONS: Retrovirus-mediated transfection of vIL-10 successfully transferred the gene into rabbit synovium ex vivo and was able to suppress intra-articular inflammation response to IL-1beta.
18754076 Adult-onset Still's disease: a report of 28 cases and review of the literature. 2008 Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology. It is characterized by fever, skin rash, polyarthralgias or polyarthritis, sore throat, hepatosplenomegaly, lymphadenopathy, leukocytosis, liver enzyme elevation, and high serum level of ferritin. Several kinds of skin lesions have been reported in this condition. The aim of this study was to assess the clinical and laboratory aspects of 28 patients with AOSD in central Iran. According to the diagnostic criteria of AOSD, we identified 28 patients between 2002 and 2007. We intended to describe the clinical characteristics, treatment, and outcome of our patients with AOSD. Of 28 patients with AOSD, 21 (75%) were female, 7 (25%) were male. Fever (100%), sore throat (92%), Arthralgia (92%), dermatographism (92%), typical rash (85%) and arthritis (60%) were the most common findings. The mean values of laboratory findings were as follows; C-reactive protein (CRP) level of 14.4 mg/dl, erythrocyte sedimentation rate (ESR) of 91.5 mm/h, leukocyte count of 15744.4/microl. Abnormal levels of aspartate aminotransferase and alanine aminotransferase were observed in 25 (89%) patients. Twenty patients (71%) had high ferritin values (>500 ng/ml). The clinical characteristics were similar to previous series. A febrile polyarthritis was the most frequent presentation form. Dermatographism was frequently encountered phenomenon in our patients with AOSD. Being that dermatographism is a simple inducible skin reaction, along with its sensitivity in active disease, we suggest more controlled studies to validate accuracy and positive predictive value of it in convenient clinical setting in the diagnosis of AOSD and to consider including it in diagnostic criteria.
17273698 [Sjögren's syndrome: diagnosis and treatment]. 2006 Nov Sjögren's syndrome is a systemic inflammatory autoimmune disease with worldwide distribution, responsible for considerable impact on the patient's quality of life. The aim of this article is to describe its main symptoms, the currently used different diagnostic criteria and the available treatment for the syndrome.
17938028 Neutrophilic panniculitis in infancy: a cutaneous manifestation of juvenile rheumatoid art 2007 Nov Neutrophilic panniculitis is rare and is classified as a panniculitic member of the neutrophilic dermatoses spectrum. In affected patients, an underlying systemic disease, such as myelodysplasia, is often present. We describe an infant with juvenile rheumatoid arthritis who developed neutrophilic panniculitis. Neutrophilic panniculitis clinically mimics other panniculitides and biopsy specimen can be diagnostic. Identification of this entity can aid the diagnosis of the underlying systemic process.
16440136 Juvenile rheumatoid arthritis manifesting in only limping due to flexion contraction of th 2007 Mar Juvenile rheumatoid arthritis (JRA) is a relatively uncommon condition. The damage to the cartilaginous tissue is often irreversible and responsible for much of the morbidity. Timely diagnosis and appropriate aggressive treatment of patients improve quality of life and outcome. A reported case of JRA is presented in which limping associated with flexion contraction of the knee developed without any systemic symptoms. Magnetic resonance imaging and arthroscopic examination were helpful with early diagnosis. Aspirin was effective. There have been no recurrence to date.
18377323 Endonasal endoscopic resection of the odontoid process in a nonachondroplastic dwarf with 2008 Apr The authors report a case of a nonachondroplastic dwarf with severe basilar invagination and compression of the cervicomedullary junction (CMJ) due to juvenile rheumatoid arthritis. Initially excellent reduction of the invagination and decompression of the CMJ was achieved using posterior fixation. However, 1 month postoperatively symptoms recurred and the authors found imaging evidence of recurrence as well. The patient subsequently underwent an endoscopic transnasal resection of the dens with assistance of Iso-C navigation. He recovered well and tolerated regular diet on postoperative Day 2.
18523733 Clinical pharmacology of gold. 2008 Jun Since the dawn of civilization, elemental gold and gold compounds have been revered and utilized by Shamen and medical practitioners alike for many varied pathological problems. In the 20(th) century following the observations of Jacques Forestier, injectable gold compounds were successfully used for the treatment of rheumatoid arthritis. Of the many compounds developed, gold sodium thiomalate has been the most extensively studied by basic scientists and by clinicians. In the1980s, the oral gold compound auranofin showed promise as a therapeutic contender to injectable gold, but the clinical side effect profile and fear of long term effects of immune suppression by auranofin, resulted in gold sodium thiomalate continuing as the preferred gold compound for rheumatoid treatment. However, the increased use and demonstration of effectiveness of low dose Methotrexate (MTX) in rheumatoid treatment over the last 20 years has resulted in a significant decline in the use of injectable gold sodium thiomalate, this despite the claims and evidence that it remains a useful agent in the management of rheumatoid arthritis. Several authors still contend that the injectable gold compounds can still play a valuable role, and indeed may be the correct first choice in the management of rheumatoid arthritis.
18955284 Potential Use of Plectranthus amboinicus in the Treatment of Rheumatoid Arthritis. 2010 Mar Plectranthus amboinicus (P. amboinicus) is a folk herb that is used to treat inflammatory diseases or swelling symptoms in Taiwan. We investigated therapeutic efficacy of P. amboinicus in treating Rheumatoid Arthritis (RA) using collagen-induced arthritis animal model. Arthritis was induced in Lewis rats by immunization with bovine type II collagen. Serum anti-collagen IgG, IgM and C-reactive protein (CRP) were analyzed. To understand the inflammation condition of treated animals, production of TNF-α, IL-6 and IL-1β from peritoneal exudates cells (PEC) were also analyzed. P. amboinicus significantly inhibited the footpad swelling and arthritic symptoms in collagen-induced arthritic rats, while the serum anti-collagen IgM and CRP levels were consistently decreased. The production of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β were also decreased in the high dosage of P. amboinicus group. Here, we demonstrate the potential anti-arthritic effect of P. amboinicus for treating RA, which might confer its anti-rheumatic activity. This differs the pharmacological action mode of indomethacin.