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ID PMID Title PublicationDate abstract
12677240 The Role of IL-17 in Joint Destruction. 2002 Jan Interleukin-17 (IL-17) is a recently cloned cytokine secreted by activated memory CD4(+) T cells and modulates the early stage of immune responses. IL-17 stimulates epithelial, endothelial and fibroblastic stromal cells to secrete several cytokines such as IL-6, IL-8 and granulocyte colony-stimulating factor, as well as prostoglandin E2. IL-17 also stimulates the production and expression of proinflammatory cytokines, IL-1beta and tumor necrosis factor-alpha by human macrophages. IL-17 may be involved in osteoclastic bone resorption in rheumatoid arthritis patients. Recently, several groups have reported that IL-17 plays important roles in both the immune response and joint destruction in patients with rheumatoid arthritis. The control of IL-17 expression in these patients could provide directions for the development of new treatment strategies for joint destruction. (c) 2002 Prous Science. All rights reserved.
19807535 Cost effectiveness of leflunomide in the treatment of rheumatoid arthritis in Japan. 2004 Dec Macro-level economic evaluations of drugs are expected to provide useful information for making the decision of whether to approve a newly developed drug as a first-line treatment. Leflunomide has been hoped to be an alternative to existing disease-modifying antirheumatic drugs, but has also raised questions about its cost effectiveness due to the high drug cost and high percentage of withdrawals due to adverse events. A method of cost-effective analysis using disability-adjusted life years, which makes it possible to assess the cost effectiveness of a drug at the macro level, is proposed. Using the proposed method, the cost effectiveness of leflunomide in the treatment of rheumatoid arthritis in Japan is determined.
24384007 Association of subacute cutaneous lupus erythematosus in a rheumatoid arthritis patient wi 2002 Dec Abstract In this paper, we report a case of rheumatoid arthritis (RA) with Sjögren's syndrome (SS) in which the patient developed subacute cutaneous lupus erythematosus (SCLE). A 72-year-old woman, who had a 10-year history of RA and SS, developed annular erythematosus skin lesions involving her face, neck, and extremities. Serological tests showed that anti-SS-A/Ro antibodies and anti-DNA antibodies were elevated. Histological examination of the skin lesions demonstrated the liquefaction degeneration of the epidermal basal layer and perivascular mononuclear cell infiltration. The diagnosis of SCLE was made based on the clinical features and skin histological findings. The disease was well controlled with intralesional and systemic corticosteroids and became quiescent. This case report demonstrates the concurrence of sero-positive RA, SS, and SCLE, which seems to be quite rare.
15301253 Autoantibodies to chromatin: prevalence and clinical significance in juvenile rheumatoid a 2004 Jul OBJECTIVE: To determine the prevalence of anti-chromatin antibodies (Abs) in juvenile rheumatoid arthritis (JRA) and to assess any association between the presence of anti-chromatin Abs and clinical subsets of the disease. METHODS: IgG anti-chromatin Abs and anti-extractable nuclear antigens (ENA) Abs were detected by an enzyme-linked immunosorbent assay (ELISA), and antinuclear Abs (ANA) by indirect immunofluorescence in sera of 89 children with JRA. Ten children with systemic, 32 with polyarticular and 47 with pauciarticular disease onset (uveitis occurred in 17/47 children) were studied. As a control group, 12 sera of patients suffering from idiopathic uveitis and 31 age- and-sex-matched healthy children (HC) were examined. RESULTS: Abs to chromatin were detected in 14/47 (29.8%) of children suffering from pauciarticular onset JRA and in this group the higher prevalence of anti-chromatin Abs has been found in children with chronic uveitis (p = 0.002). Anti-chromatin positivity was observed in 2/10 (20%) of systemic and in 3/32 (9.3%) of polyarticular onset JRA. Furthermore, none of the patients with idiopathic uveitis and HC had Abs to chromatin. anti-chromatin Abs titers remained relatively stable over a 6-month control period. CONCLUSION: Our results confirm previous data about the presence of circulating anti-chromatin Abs in juvenile arthritis. Interestingly, anti-chromatin Abs were significantly higher in the group of patients with pauciarticular onset with past or present history of uveitis, than in patients without ocular involvement. A long-term follow-up study could be useful to demonstrate the potential utility of these autoantibodies in diagnosing, classifying and treating children affected.
15034067 Immunization with glucose-6-phosphate isomerase induces T cell-dependent peripheral polyar 2004 Apr 1 Rheumatoid arthritis is a chronic inflammatory disease primarily affecting the joints. The search for arthritogenic autoantigens that trigger autoimmune responses in rheumatoid arthritis has largely focused on cartilage- or joint-specific Ags. In this study, we show that immunization with the ubiquitously expressed glycolytic enzyme glucose-6-phosphate isomerase (G6PI) induces severe peripheral symmetric polyarthritis in normal mice. In genetically unaltered mice, T cells are indispensable for both the induction and the effector phase of G6PI-induced arthritis. Arthritis is cured by depletion of CD4(+) cells. In contrast, Abs and FcgammaR(+) effector cells are necessary but not sufficient for G6PI-induced arthritis in genetically unaltered mice. Thus, the complex pathogenesis of G6PI-induced arthritis in normal mice differs strongly from the spontaneously occurring arthritis in the transgenic K/B x N model where Abs against G6PI alone suffice to induce the disease. G6PI-induced arthritis demonstrates for the first time the induction of organ-specific disease by systemic autoimmunity in genetically unaltered mice. Both the induction and effector phase of arthritis induced by a systemic autoimmune response can be dissected and preventive and therapeutic strategies evaluated in this model.
13130482 Expression of myeloid-related proteins 8 and 14 in systemic-onset juvenile rheumatoid arth 2003 Sep OBJECTIVE: To analyze which cellular compartments are involved in the initial phase of systemic-onset juvenile rheumatoid arthritis (JRA), and to investigate the role that myeloid-related protein 8 (MRP-8) and MRP-14, two S-100 proteins that are primarily expressed in phagocytes, play in the disease. METHODS: Skin biopsy samples obtained during patients' acute episodes of systemic-onset JRA were analyzed by immunohistochemistry and in situ hybridization. Concentrations of MRP-8/MRP-14 in serum were determined by enzyme-linked immunosorbent assay. RESULTS: By analyzing biopsy samples from cutaneous rashes during the initial phase of systemic-onset JRA, we discovered infiltration of leukocytes expressing MRP-8 and MRP-14. Surprisingly, keratinocytes also showed de novo synthesis of these proinflammatory proteins, indicating activation of epithelial cells during systemic-onset JRA. Serum concentrations of MRP-8/MRP-14 were 120-fold higher compared with healthy controls and approximately 12-fold higher compared with patients with other inflammatory diseases. Concentrations of MRP-8/MRP-14 in patients with systemic-onset JRA fell dramatically after remission was induced. CONCLUSION: The exceptionally high serum levels of MRP-8 and MRP-14 in active systemic-onset JRA make them prime candidates as markers for monitoring disease activity and response to treatment. Since MRP-8/MRP-14 exhibit direct effects on leukocyte adhesion to the vascular endothelium, their extensive expression in the epidermis indicates an active role for these S-100 proteins in the initial phase of this systemic autoimmune disease.
12906020 Etanercept: new preparation. Useful after methotrexate failure in inflammatory rheumatism. 2003 Aug There is no reference second-line treatment for patients with rheumatoid arthritis, juvenile chronic arthritis, psoriatic arthropathy or ankylosing spondylitis after failure or intolerance of a slow-acting antirheumatic drug such as methotrexate. Etanercept, a immunosuppressant targeting TNF-alpha (like infliximab), is now approved in France for use in these situations, with the exception of spondylitis. In the second-line treatment of adults with rheumatoid arthritis, the clinical evaluation dossier on etanercept contains data from dose-finding studies and two placebo-controlled trials involving patients in whom several single-agent treatments had failed. At a dose of 25 mg subcutaneously twice a week, etanercept worked partially in about half the patients. Without direct comparisons, the place of etanercept relative to other slow-acting antirheumatic drugs is difficult to establish. From indirect comparisons, etanercept seems a slightly better treatment option than infliximab. In the first-line treatment of rheumatoid arthritis, one trial showed that etanercept worked faster than methotrexate, but there was no significant difference between the two treatments after two years. Little is known about the efficacy of etanercept in patients with juvenile chronic arthritis who do not respond adequately to methotrexate. There are no comparative trials. One double-blind placebo-controlled trial showed that etanercept, when it worked, remained active for at least 7 months. In one trial, etanercept was more effective than placebo in patients with psoriatic arthropathy and ankylosing spondylitis who continued to receive their usual treatment, which included a slow-acting antirheumatic drug in about 50% of cases. More than 50% of patients treated with etanercept have a cutaneous reaction to the injection. These reactions are usually mild or moderate. Active pharmacovigilance is needed, given its mechanism of action, and previous notifications of a wide variety of adverse effects (even though it is sometimes difficult to establish a foolproof link between etanercept and the adverse effect). Long-term studies of large numbers of patients are needed to determine the precise risk of side effects including haematological, infectious, neurological, oncological and immunological effects. In practice, methotrexate remains the first-line treatment for inflammatory arthritis. Etanercept can be a useful second-line treatment, especially in juvenile chronic arthritis.
11994038 Juvenile rheumatoid arthritis: therapeutic perspectives. 2002 Juvenile rheumatoid arthritis (JRA) is the most common childhood chronic systemic autoimmune inflammatory disease. The therapeutic approach to JRA has, to date, been casual and based on extensions of clinical experiences gained in the management of adult rheumatoid arthritis (RA). The physiology of inflammation has been systemically studied and this has led to the identification of specific therapeutic targets and the development of novel approaches to the management of JRA. The classical treatments of the disease such as methotrexate, sodium aurothiomalate and sulfasalazine, are not always effective in controlling RA and JRA. This has necessitated the development of novel agents for treating RA, most of which are biological in nature and are targeted at specific sites of the inflammatory cascades. These biological therapeutic strategies in RA have proved successful and are being applied in the management of JRA. These developments have been facilitated by the advances in molecular biology which have heralded the advent of biodrugs (recombinant proteins) and gene therapy, in which specific genes can be introduced locally to enhance in vivo gene expression or suppress gene(s) of interest with a view to down-regulating inflammation. Some of these biodrugs, such as anti-tumor necrosis factor alpha (anti-TNFalpha), monoclonal antibodies (infliximab, adalimumab), TNF soluble receptor constructs (etanercept) and interleukin-1 receptor antagonist (IL-1Ra) have been tested and shown to be effective in RA. Etanercept has now been licensed for JRA. Clinical trials of infliximab in JRA are planned. Studies show that the clinical effects are transient, necessitating repeated treatments and the risk of vaccination effects. Anti-inflammatory cytokines such as IL-4, IL-10, transforming growth factor-beta and interferon-beta (IFN-beta) are undergoing clinical trials. Many of these agents have to be administered parenterally and production costs are very high; thus, there is a need, especially for pediatric use, to develop agents that can be taken orally. Long-term studies will be required to assess the tolerability and toxicity of these approaches in JRA, since cytokines and other mediators play important roles in host defenses, and the chronic inhibition, exogenous administration or constitutive over-expression of some cytokines/mediators may have undesirable effects.
12022323 Preliminary definition of disease flare in juvenile rheumatoid arthritis. 2002 May OBJECTIVE: To develop preliminary criteria for defining disease flare in patients with polyarticular-course juvenile rheumatoid arthritis (JRA). METHODS: Data from a randomized clinical trial of etanercept in JRA (51 patients) and the 6 core response variables (CRV) for JRA were used to derive flare definitions. The criterion standard of flare was treatment with placebo. Candidate flare definitions were assessed by receiver-operator characteristic (ROC) curve properties and other statistics for diagnostic tests. RESULTS: Of the possible flare definitions tested with acceptable statistical properties, the one that seemed to be the most useful was worsening in any 2/6 CRV by > or = 40% without improvement in more than 1 of the remaining CRV by > or = 30%. Two other superior flare definitions were (1) worsening in 3/6 CRV by > or = 30% and (2) any worsening of the Childhood Health Assessment Questionnaire, worsening of erythrocyte sedimentation rate by > or = 30% and worsening of the active joint count by > or = 10%. CONCLUSIONS: CRV are useful for defining flare in JRA. Worsening in any 2/6 CRV by > or = 40% without concomitant improvement of more than one of the remaining CRV by > or = 30% appears to be the most suitable preliminary flare definition. Because the proposed flare criteria were derived from a small number of patients, it is essential to perform more definitive testing of this and several alternative flare definitions in larger patient populations.
14503100 Sternoclavicular joint septic arthritis manifesting as a neck abscess: a case report. 2003 Aug Septic arthritis of the sternoclavicular joint is an uncommon condition, and the diagnosis can be missed until a complication occurs. The sternoclavicular joint is more often involved in ankylosing spondylitis, degenerative arthritic conditions (i.e., rheumatoid arthritis and osteoarthritis), and primary and secondary metastatic conditions. The patient described in this case report came to the otolaryngology department on two occasions for treatment of a unilateral cutaneous neck abscess. The correct diagnosis was not made until the second visit. The author reviews the clinical course, diagnosis, and treatment of this uncommon disease.
17143665 Power Doppler sonography for detection of intraarticular vascularization in knee joints of 2004 A series of 47 knee joints in 24 patients with rheumatoid arthritis were examined for intraarticular vascularization by power Doppler sonography. The intensity of vascularization was compared with the synovial effusion and proliferation evaluated by gray-scale sonography and the clinical findings in the patients. Vascularization was graded from 0 to 3 by counting the number of color-flow signals: grade 0, no signals; grade one, 1-4 signals; grade two, 5-8 signals; grade three, 9 or more signals. The grade of vascularization correlated with the grade of synovial effusion (P < 0.01), the grade of synovial proliferation (P < 0.05), and the serum levels of C-reactive protein (P < 0.05). It correlated inversely with disease duration (P < 0.01). Consistent with improvement of articular inflammation, a decrease in the number of color-flow signals was observed in two patients. Power Doppler sonography is suitable for evaluating the intensity of synovitis and for monitoring the clinical activity of rheumatoid patients.
14707051 TNF deficiency fails to protect BAFF transgenic mice against autoimmunity and reveals a pr 2004 Jan 15 TNF is well characterized as a mediator of inflammatory responses. TNF also facilitates organization of secondary lymphoid organs, particularly B cell follicles and germinal centers, a hallmark of T-dependent Ab responses. TNF also mediates defense against tumors. We examined the role of TNF in the development of inflammatory autoimmune disorders resembling systemic lupus erythematosus and Sjögren's syndrome induced by excess B cell-activating factor belonging to the TNF family (BAFF), by generating BAFF-transgenic (Tg) mice lacking TNF. TNF(-/-) BAFF-Tg mice resembled TNF(-/-) mice, in that they lacked B cell follicles, follicular dendritic cells, and germinal centers, and have impaired responses to T-dependent Ags. Nevertheless, TNF(-/-) BAFF-Tg mice developed autoimmune disorders similar to that of BAFF-Tg mice. Disease in TNF(-/-) BAFF-Tg mice correlates with the expansion of transitional type 2 and marginal zone B cell populations and enhanced T-independent immune responses. TNF deficiency in BAFF-Tg mice also led to a surprisingly high incidence of B cell lymphomas (>35%), which most likely resulted from the combined effects of BAFF promotion of neoplastic B cell survival, coupled with lack of protective antitumor defense by TNF. Thus, TNF appears to be dispensable for BAFF-mediated autoimmune disorders and may, in fact, counter any proneoplastic effects of high levels of BAFF in diseases such as Sjögren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis.
11891190 Differing roles for urokinase and tissue-type plasminogen activator in collagen-induced ar 2002 Mar The plasminogen activators, urokinase PA (u-PA) and tissue-type PA (t-PA), are believed to play important roles in inflammatory cell infiltration, fibrin deposition, and joint destruction associated with rheumatoid arthritis; however, their precise roles in such processes, particularly u-PA, have yet to be defined. Using gene-deficient mice we examined the relative contribution of the PAs to the chronic systemic collagen-induced arthritis model. Based on clinical and histological assessments, u-PA-/- mice developed significantly milder disease and t-PA-/- mice more severe disease compared with the relevant wild-type mice. Fibrin deposition within joints paralleled disease severity and was particularly pronounced in t-PA-/- mice. Likewise, cytokine levels in the synovium reflected the severity of disease, with interleukin-1beta levels in particular being lower in u-PA-/- mice and increased in t-PA-/- mice. The antibody response to type II collagen was normal in both knockouts; however, T cells from u-PA-/- mice had a reduced proliferative response and produced less interferon-gamma on antigen stimulation in vitro. These results indicate that the major effect of u-PA in the collagen-induced arthritis model is deleterious, whereas that of t-PA is protective. Our data highlight the complexities of PA function, and suggest that approaches either to target u-PA or to enhance local t-PA activity in joints may be of therapeutic benefit in rheumatoid arthritis.
12504611 Mycobacterium malmoense septic arthritis. 2003 Jan We report a case of septic arthritis of an interphalangeal joint and osteomyelitis of the phalanx due toMycobacterium malmoense in a 61-year-old man with a 20 year history of rheumatoid arthritis treated with steroids and azathioprine. This was successfully treated with ethambutol, rifampicin and clarithromycin. To our knowledge this is the only reported case of septic arthritis due to this pathogen which is usually associated with respiratory disease or cervical lymphadenitis.
24387649 Correlation between severity of rheumatoid arthritis and manner and extent of cervical les 2004 Sep Abstract To determine the proper management of treatment for rheumatoid cervical lesions, we investigated the clinical course of the cervical spine in rheumatoid arthritis (RA). The severity of RA was classified into three groups according to the disease subsets advocated by Ochi et al.: the less erosive subset (LES), the more erosive subset (MES), and mutilating disease (MUD). Then the following radiographic assessments were performed on cervical roentogenograms: atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS). One hundred and seventy-four patients were available for this study. The mean age of the patients was 60.9 years (19-85 years). The average duration from the onset of RA was 19.1 years (10-40 years). Eighty-seven patients were classified as LES, 69 were MES, and 18 were MUD. We found that few patients in the LES group had required an operation on the cervical spine. AAS was seen in about 60% of the MES patients, but few cases had VS or SAS, and most operations were atlantoaxial fusion. All patients in the MUD group had some cervical instabilities. Not only VS but also SAS were seen in more than half of these patients, and many patients had required occipitothoracic fusion.
15554369 Epidemiology and diagnostics of primary Sjögren's syndrome. 2004 This review paper contains selected aspects of Sjögren's syndrome. It consists of epidemiology, ultrasound of salivary glands and antimuscarinic antibodies. The first part present studies aimed to determine the prevalence and the incidence of the disease with special emphasize on epidemiological studies performed in Slovenia. This is followed by the demonstration of the role of ultrasound of salivary glands in the diagnosis of Sjögren's syndrome and the value of antimuscarinic antibodies in global assesment of the secretory failure.
12739384 [Primary Sjögren's syndrome presenting with choreo-athetosis]. 2002 Oct A 69-year-old man presenting with choreo-athetosis was proved to have primary Sjögren's syndrome. Choreo-athetosis suddenly appeared in the bilateral legs and the right arm; it was predominant in the right limbs. On the neurological examinations, there was no abnormal finding except for this involuntary movement. Brain MRI showed no abnormal finding. 18F-Fluorodeoxyglucose PET revealed that glucose metabolism was relatively increased in the bilateral striatum and thalamus (left side dominant). Dry eye and thirst were present for 4 years, and a diagnosis of primary Sjögren syndrome was confirmed by ophthalmological examinations, lip biopsy and sialography. Choreo-athetosis disappeared after thioridazine hydrochloride was started, while steroid was not effective.
12738120 Newly diagnosed adult-onset Still disease in pregnancy. 2003 May BACKGROUND: Adult-onset Still disease is a rare febrile disorder that can present for the first time during pregnancy. It is a diagnosis of exclusion with nonspecific laboratory results. Good maternal and fetal outcomes can be expected after initial diagnosis and treatment. CASE: A 21-year-old (gravida 2, para 1) at 20 weeks' gestation presented with fever, malaise, arthralgias, and cough. She had an extensive evaluation that led to the diagnosis of adult-onset Still disease. She was treated with prednisone and had immediate improvement. She delivered a viable infant at 34 weeks after suspected intrauterine growth restriction and continued to have recurrent symptoms postpartum. The second woman, 38 years old and gravida 3, para 1, aborta 1, presented at 22 weeks' gestation with similar symptoms and also had a similar diagnostic evaluation. She was diagnosed with adult-onset Still disease and started on prednisone, with immediate improvement, delivering a viable infant at 41 weeks' gestation. CONCLUSION: Adult-onset Still disease in pregnancy can be confused with many other diseases, but its diagnosis, after exclusion of other infectious, malignant, and rheumatic conditions, can portend good maternal and fetal outcomes.
17143674 Posterior interosseous nerve palsy secondary to rheumatoid cyst of the elbow joint: case r 2004 A 73-year-old woman with rheumatoid arthritis had lost the ability to extend the digits on her right hand. A rheumatoid cyst in the elbow caused the posterior interosseous nerve palsy. Decompression was performed, and she recovered extension of the thumb and fingers completely within 3 weeks after the operation.
14552024 Primary Sjögren's syndrome. 2003 Aug Columbia University's Salivary Gland Center (SGC) has examined more than 6,000 patients with a variety of concerns stemming from salivary gland disease and/or salivary secretory dysfunction. Not unexpectedly, the most common patient complaint centers around symptoms associated with dry mouth. Such patients are usually first seen by the dental practitioner. Because Sjögren's syndrome (SS) causes dry mouth, and because it is a relatively common entity--encountered in about three million Americans--and because the dental profession has become aware of its classic manifestation of xerostomia, patients experiencing SS are referred in increasing numbers to the SGC for evaluation. Therefore, the authors wish to call attention to the methodology used in accurately diagnosing SS and to illustrate its signs and symptoms with a case report.