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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
15991933 Do antivirals have any utility in the treatment of arthritis? 1998 Nov Viruses have been linked to arthritides by several pathways. Apart from the ability of different viral pathogens to cause arthritic symptoms directly, only some circumstantial evidence for the involvement of (retro)viruses in the pathogenesis of rheumatoid arthritis has been presented in recent years. Therefore, the question of whether antiviral agents can be used to treat arthritis has become of interest. However, the mechanisms by which exogenous retroviral infection as well as activation of endogenous retroviral sequences may potentially lead to the induction of rheumatoid arthritis is just beginning to emerge. Moreover, the hypothesis that persistent viral infection may account for some hitherto unclassified, chronic arthritides, still needs to be confirmed. Therefore, the use of antiviral agents in the treatment of arthritides has been limited to viral complications of anti-arthritic therapy and to some experimental approaches. In this review, we will focus on current concepts of viral involvement in arthritis and point to future directions in the use of antiviral agents for arthritis.
10503658 Immunopathogenesis of juvenile rheumatoid arthritis. 1999 Sep The immunopathogenic mechanisms of juvenile rheumatoid arthritis (JRA) have been debated. A possible cellular-mediated hypothesis versus a possible B cell hyperreactivity have been entertained. This review will focus on some recent cellular work in JRA and also further evaluation of cytokine levels and their role in inflammation in JRA. Recent studies have evaluated the interrelationship of Th1/Th2 immune responses in the immunopathogenesis of JRA, and their effect on cytokine release. Studies have indicated a pro-inflammatory response in systemic-onset JRA manifested by increased secretion of interleukin-6, whereas an anti-inflammatory response has been noted by increases of IL-4 mRNA and IL-10 mRNA in pauciarticular-onset JRA. The continued finding of elevated levels of tumor necrosis factor-alpha (TNF-alpha) and its receptors in association with inflammatory activity has been seen. The recent use of a TNF fusion protein to block TNF-alpha activity in JRA has further contributed to this finding. Further studies on specific cytokines will be helpful in the future in trying to determine the different roles cytokines play in JRA subtypes and would contribute to the development of better therapeutic regimens.
10676778 Advances in the medical treatment of juvenile rheumatoid arthritis. 2000 Feb Juvenile rheumatoid arthritis (JRA) remains a challenge for clinicians. Nonsteroidal anti-inflammatory drugs and corticosteroids remain the mainstays of therapy, but concerns persist about side effects and the ability of these agents to prevent progression of bony disease. In recent years, novel treatments have been developed and quickly discarded because of unexpected toxicities or lack of efficacy. However, recent studies have shown that methotrexate and sulfasalazine are relatively safe and effective for JRA. Newly developed drugs, such as selective cyclooxygenase-2 inhibitors and soluble tumor necrosis factor receptor, whose development has stemmed from a more basic understanding of pathophysiology, may provide better disease control with fewer side effects. Finally, novel therapies, such as stem cell transplantation, may offer hope for children with JRA, especially systemic-onset JRA, whose disease has been refractory to conventional therapy.
11803746 [Occipitocervical fusion in rheumatoid arthritis]. 2001 Dec A case of spontaneous occipitocervical fusion is discussed. The authors believe that fusion at the occipitocervical junction will occasionally occur in rheumatoid arthritis in the adult population. As a result of fusion, the dens axis is unable to exert compression on the spinal cord with increased neck flexion.
24383528 Interactions between T cells and synovial fibroblasts. 2000 Mar Abstract T lymphocytes, synovial macrophages, and synovial fibroblasts are the three most abundant cell populations in rheumatoid arthritis synovial tissue, and each is believed to play an important role in the pathogenesis of joint inflammation and destruction. While interactions between T cells and macrophages and between macrophages and fibroblasts have been carefully studied, less attention has been paid to potential interactions between T lymphocytes and synovial fibroblasts. In this review we consider available data which suggests that cell-cell contact between T lymphocytes and synovial fibroblasts may lead to activation of each cell type. This interaction is likely to be significant in the pathophysiology of rheumatoid arthritis.
10872987 Advanced dental maturity in children with juvenile rheumatoid arthritis. 2000 Jun The subjects of the investigation comprised 95 girls and 73 boys with juvenile rheumatoid arthritis (JRA), and 102 girls and 66 boys representing healthy controls, all with a chronological age from 6.3 to 14.4 yr. The dental development was assessed from panoramic radiographs using a seven-tooth model. The radiographs were evaluated on three separate occasions with a minimum interval of one month in a randomized order, and blind with respect to absence or presence of JRA. In both JRA patients and healthy controls, dental maturity was ahead of chronological age. In addition, dental maturity was significantly advanced in JRA patients with 0.26 yr in girls and 0.28 yr in boys. It is tentatively suggested that the advanced dental development in JRA patients compared with healthy children was partly an effect of treatment with cortisone, while the influence of the disorder per se remains to be elucidated.
11958283 Suppression of type II collagen-induced arthritis by a new isocoumarin, NM-3. 2000 Nov The anti-arthritic effect of NM-3, a new isocoumarin, was examined using a type II collagen-induced arthritis model for human rheumatoid arthritis in DBA/1J mice. NM-3 by oral administration suppressed dose-dependently (2-20 mg/kg/day) not only macroscopic changes such as erythema and swelling of limbs but also histopathologic changes and radiographic changes such as bone lesions. The efficacy of NM-3 was greater than those of disease-modifying anti-rheumatoid drugs (DMARDs), auranofin (40 mg/kg/day) and bucillamine (10 mg/kg/day). NM-3 failed to suppress carageenan-induced edema and to inhibit the activities of inflammation-related enzymes including cyclooxygenase-1 and -2, 5-lipoxygenase and phospholipase A2, suggesting that the mode of anti-arthritic action of NM-3 may be different from those of non-steroidal anti-inflammatory agents (NSAIDs). Since NM-3 inhibits angiogenesis in a mouse dorsal air-sac model, the observed anti-arthritic effect of NM-3 might be partly attributed to the antiangiogenic activity. Thus, NM-3 is a potential orally active therapeutic agent for the treatment of human rheumatoid arthritis.
9259435 New-onset juvenile dermatomyositis: comparisons with a healthy cohort and children with ju 1997 Aug OBJECTIVE: To determine, in a case-control study, if patients with new-onset juvenile dermatomyositis (juvenile DM) have increased symptoms prior to onset, exposure to certain environmental conditions, frequency of familial autoimmune diseases, or antibody titers, compared with 2 control groups. METHODS: A structured interview with the families of 80 children with juvenile DM, 40 children with juvenile rheumatoid arthritis (JRA), or 23 healthy children, from the same geographic area as the children with juvenile DM, was conducted. All children's sera were tested for antibody to Toxoplasma gondii, herpes simplex virus (HSV), or coxsackievirus B (CVB). RESULTS: A high proportion of children with juvenile DM had constitutional symptoms 3 months before the disease-onset date (P = 0.013 versus control children). Children with JRA had more relatives with rheumatoid arthritis (P = 0.0001) and pernicious anemia (P = 0.003) than did children with juvenile DM or healthy children. Among children < or =7 years of age, elevated enteroviral titers were more frequent in those with juvenile DM (81%) and in healthy controls (90%) than in those with JRA (64%), suggesting a common environmental exposure. Titers to T gondii, HSV, or CVB 1-6 were normal. CONCLUSION: Frequencies of familial autoimmune disease, exposure to environmental factors, or elevated antibody titers to T gondii, HSV, or CVB are not increased in juvenile DM. Children with juvenile DM do have symptoms of illness 3 months before the disease-onset date, and young patients have elevated enteroviral titers, as do young geographic controls.
12973436 Characterization of the hyporesponsiveness of synovial T-Cells in rheumatoid arthritis: ro 1999 Apr It is commonly thought that autoreactive T-cells fulfill a central role in the chronic inflammatory response that occurs in the joints of patients with rheumatoid arthritis (RA). However, the accumulated T-cells in the joints of patients with RA are functionally suppressed compared with peripheral blood T-cells. The mechanism that underlies this synovial T-cell hyporesponsiveness and the possible role of this phenomenon in the pathogenesis of RA is the subject of this article.
24383723 The osteoclast: a potential therapeutic target of bone and joint destruction in rheumatoid 2001 Sep Abstract There is accumulating evidence that osteoclasts, the primary cells responsible for bone resorption, are involved in bone and joint destruction in rheumatoid arthritis (RA). Recent progress in bone cell biology has revealed the molecular mechanism of osteoclast differentiation and bone resorption by mature osteoclasts. We here highlight the potential role of RANKL-RANK pathways in bone destruction in RA. We also describe our recent trials on gene therapy of arthritic joint disease targeting osteoclasts by regulating Src kinase activity in the cells.
15775565 [Drug therapy for osteoporosis associated with rheumatoid arthritis (vitamin D)]. 2001 May A various factors are related to osteoporosis with Rheumatoid Arthritis (RA) complicatedly. Improvement of bone decrease does not become only the bone fracture prevention and leads to the prevention of joint destruction. Osteoporosis in RA causes by increase of bone resorption. However, the decrease of bone formation has been found to osteoporosis in many RA patients containing steroid induced osteoporosis. The treatment for osteoporosis in RA with vitamin D may be letting the bone formation decreased in RA normalize by regulatory of immunity. The vitamin D would become the useful drug for promoting the bone formation by examination of new agents, method and dosage of treatment for osteoporosis in RA patients.
24383696 A case of psoas abscess in a patient with systemic sclerosis and rheumatoid arthritis. 2001 Jun Abstract We report a case of psoas abscesses associated with systemic sclerosis and rheumatoid arthritis. A 61-year-old woman had been sufferring from high fever. A computed tomography (CT) scan revealed bilateral psoas abscesses from which Peptostreptococcus spp. were detected by a culture of the pus. The abscesses were ameliorated by performing CT-guided percutaneous drainage and using appropriate antibiotics. Although psoas abscess is relatively rare, it can be a cause of fever of unknown origin in collagen diseases.
11037918 Secondary glaucoma in patients with juvenile rheumatoid arthritis-associated iridocyclitis 2000 Oct PURPOSE: The prevalence and management of glaucoma were evaluated in patients with juvenile rheumatoid arthritis (JRA)-associated iridocyclitis. METHODS: The records of 69 patients with JRA-associated iridocyclitis were reviewed. RESULTS: Twenty-nine (42%) of these patients had secondary glaucoma or ocular hypertension. Glaucoma was controlled with topical treatment in only 7 of the 41 affected eyes (17%); systemic carbonic anhydrase inhibitor therapy resulted in control of another 8 eyes. Surgery controlled all but one of the remainder. CONCLUSION: Glaucoma is a common complication of JRA-associated iridocyclitis. It results from prolonged, inadequately treated intraocular inflammation and in some instances, from steroid use. Medical and surgical therapy for the glaucoma associated with JRA-uveitis is challenging and incompletely effective. We suspect that a more aggressive approach to the treatment of JRA-associated uveitis, earlier in the course of the disease may reduce this vision robbing contribution to the process.
10501775 Bone mass change during methotrexate treatment in patients with juvenile rheumatoid arthri 1999 Thirty-two children affected by juvenile rheumatoid arthritis (JRA) were studied with serial measurements of bone mass for an average of 18 months, to evaluate the effects of long-term methotrexate (MTX) treatment on bone. Bone mineral density (BMD) was measured on lumbar spine and total body. During MTX therapy some increase in BMD was observed, though this was smaller than in a control group of healthy children. Axial (spine and trunk) and appendicular (upper and lower limbs) BMD showed similar increases. BMD, either as an absolute value or as a percent variation from baseline, did not correlate with either MTX dose or length of therapy. In children treated also with corticosteroids, these drugs negatively influenced bone mass increase. The main determinant of absolute spine BMD value appeared to be weight, while height and lean mass seemed to be the determinants of total body BMD. Pubertal stage and disease activity significantly influenced the yearly change in BMD. In conclusion, our data suggest that long-term, low-dose therapy with MTX does not induce osteopenia in children with JRA.
9710321 Standardized assessment of disease status in patients with primary Sjögren's syndrome: th 1998 Jun Primary Sjögren's syndrome (pSS) is increasingly acknowledged as a disease entity with consistent pathogenesis and clinical presentation. This has encouraged proposals for uniform nomenclature, as well as for classification of disease subsets and clinical disease manifestations. The purpose of this literature survey is to analyse present pathogenetic and clinical data on pSS from the viewpoint of their usability for developing criteria for activity and damage. It appears that the routinely used tests for evaluating clinical disease manifestations in pSS probably measure both activity and damage. Moreover, no immunopathogenic marker has been shown to adequately represent all aspects of disease activity in pSS. The survey demonstrates the need for longitudinal studies in which potential markers of disease activity and damage are validated.
11490519 Therapy of Sjögren's syndrome. New aspects and future directions. 1998 Feb Therapy of Sjögren's syndrome remains empirical and symptomatic. The main goals are to treat the disease related features, especially sicca manifestations, since the immunosuppressive therapy has not given promising results. For the treatment of keratoconjunctivitis sicca: local stimulators of tear secretion, protective bicarbonate buffered solutions, replacement therapy or supportive operative procedures should be tried. For oral manifestations: stimulators of salivary secretion such as pilocarpine, or agents changing the consistency of saliva such as bromhexine orally should be tried. Saliva substitutes have a transient effect. Frequent ingestion of sugar free liquids may help. Oral hygiene is important to avoid oral candidiasis and dental caries. Treatment of parotid gland swelling is not necessary. Pulmonary manifestations include pulmonary infiltrates in perialveolar areas, nodular or cavitary lesions which may represent lymphoma. Hilar adenopathy, solid or cavitary lesions should be biopsied. In case of vasculitis prednisolone 1 mg/kg/day with progressive tapering should be tried. Renal involvement is manifested mainly as interstitial disease. Administration of NaHCO3 or sodium citrate is important to prevent acidosis and nephrocalcinosis. Vasculitis, when it is of the leukoclasic form, does not need therapy; when it is manifested with severe major organ involvement corticosteroids and/or cytotoxic therapy should be tried. Lymphoma is treated as in the patients without Sjögren's in close collaboration with the oncology department.
11093602 Adult Still's disease as a paraneoplastic manifestation of breast cancer. 2000 We treated a patient who developed symptoms and findings indistinguishable from those of adult Still's disease as a manifestation of metastatic breast cancer 7 years after treatment for a stage 1 tumor. Although clinical features fulfilled diagnostic criteria for adult Still's disease, examination of a bone marrow biopsy specimen indicated that the apparent adult Still's disease was a paraneoplastic manifestation associated with diffuse marrow infiltration by breast cancer. The fever and polyarthralgia resolved with administration of prednisolone, and antiestrogen therapy with tamoxifen citrate was also started.
11605978 A review and update of Sjögren's syndrome: manifestations, diagnosis, and treatment. 2001 Sep Sjögren's syndrome is an autoimmune disorder that affects approximately 1% of the population. It is a disease that in recent years has not been studied extensively, but for which much study is needed. Diagnosis of this disease is extremely difficult. Until recently no strong consensus on diagnostic criteria has been published. The disease can cause dry eyes, dry mouth, vasculitis, and neurologic disease, and each symptom may be at times correctly attributed to Sjögren's or incorrectly attributed to another disease. Because it affects many different areas, many specialists (rheumatologists, primary care physicians, ophthalmologists, and dentists) have to be educated about Sjögren's syndrome's pathogenesis, manifestations, diagnosis, and treatments to manage this disease and help improve these patients' quality of life.
10522316 [Still's disease in adults: treatment with intravenous immunoglobulins]. 1999 INTRODUCTION: Adult onset Still's disease is a rare systemic disorder of unknown etiology occurring in young adults. The diagnosis is based upon Yamaguchi criteria. Treatment is difficult and not well codified. CURRENT KNOWLEDGE AND KEY POINTS: Non steroidal anti-inflammatory drugs (salicylates, indomethacin) are used as first-line therapy but are not efficient. Steroids are needed in 80% of cases to control systemic manifestations of adult onset Still's disease. Immunosuppressive agents, such as methotrexate, are necessary when a high dose of steroids are required. The use of intravenous immunoglobulin was rarely reported, in particular in patients refractory to non steroidal anti-inflammatory drugs. Intravenous immunoglobulin was administered at 2 g/kg of body weight during two or five days. Infusion was given monthly for four-six cycles. Long-term remission was obtained in half of the patients. Precise mechanisms of action of intravenous immunoglobulin in adult onset Still's disease remain unclear. FUTURE PROSPECTS AND PROJECTS: Intravenous immunoglobulin may represent a new treatment, particularly in patients refractory to non steroidal anti-inflammatory drugs before the use of steroids. Further prospective works are needed to confirm these preliminary optimistic data.
15989642 Future therapies for rheumatoid arthritis: remedies from the horns of a dilemma? 1997 Jul Drugs used to treat arthritis can be broadly classified into either anti-inflammatory or immunosuppressive/immunomodulatory agents. Non-steroidal anti-inflammatory drugs (NSAIDs) are used for both osteoarthritis (OA) and rheumatoid arthritis (RA), while drugs with an immunological mechanism of action are only applicable to RA. The total market value for anti-arthritic drugs is estimated to be 8.4 bn dollars, with the OA segment worth 6.9 bn dollars. In contrast, the major RA markets are valued at approximately 1.5 bn dollars. Drugs currently in late phase development reflect the accepted approaches towards treating the symptoms of arthritis, or suppressing immunological mechanisms considered to be the driving force for the underlying disease process in RA. The size of both the RA and OA markets, however, creates an incentive to develop new therapeutics which do not conform to these two approaches, but target new molecular mechanisms. Compounds currently in preclinical development demonstrate that it may be possible to combine anti-inflammatory and slow-acting antirheumatic activity into a single therapeutic. This new generation of anti-arthritic compounds has the potential to redefine the way in which common forms of arthritis, mixed connective tissue diseases and musculoskeletal diseases are treated in the future.