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ID PMID Title PublicationDate abstract
26981698 Celecoxib for the treatment of pain and inflammation: the preclinical and clinical results 1999 Nov 1 Inflammation and pain, the principal signs and symptoms of arthritis along with swelling and stiffness, are routinely controlled by treatment with a nonsteroidal antiinflammatory drug (NSAID). Celecoxib, an anti-inflammatory and analgesic agent indicated for the treatment of osteoarthritis and rheumatoid arthritis, is the first cyclooxygenase (COX) inhibitor with well-defined cyclooxygenase-2 (COX-2) specificity. Preclinical studies of celecoxib in vitro and in vivo support the COX-2 hypothesis that the therapeutic effects of NSAIDs are due to the inhibition of COX-2, and the adverse events associated with NSAID therapy are due to the inhibition of cyclooxygenase-I (COX-I), the constitutively expressed isoform of COX. Clinical trials in patients with osteoarthritis or rheumatoid arthritis found that the efficacy of celecoxib is superior to that of placebo and comparable to that of naproxen, a conventional NSAID. Clinical studies also found celecoxib to be safe and well tolerated, with no evidence of alteration in platelet aggregation or gastrointestinal ulceration.
11139831 Tachykinin receptor modulators: novel therapeutics for rheumatoid arthritis. 1999 Nov The activation of a cellular immune response in a genetically susceptible individual is widely recognised as a main step in triggering rheumatoid arthritis (RA). The tachykinins, substance P (SP) and neurokinin A (NKA), can play a major role in different immune diseases. In patients with inflammatory joint disease, elevated levels of SP have been demonstrated in the synovial fluid of affected joints. It is well known that SP and, to a lesser extent, NKA are deeply involved in the processing of nociceptive signals and exert many pro-inflammatory actions, which may be elicited by an increased neuronal neurokinin release in arthritis; the mechanism behind this increase remains to be fully elucidated. Different observations suggest that one approach to the treatment of RA might be to inhibit the local effects of neurokinins in the affected joints. This review will summarise the more relevant aspects of this topic.
10573767 Trace elements in the treatment of rheumatic conditions. 1999 Nov The role of trace metallic elements (copper, selenium, zinc, gold) in chronic inflammatory states is of great interest because many of them are co-factors in metabolic processes involving articular tissues and immune system function. Deficiencies of several of these have been documented in patients with rheumatoid arthritis. Other than for the clinically approved gold compounds, there exists only inconsistent evidence for a therapeutic role of trace metallic elements in the management of rheumatoid arthritis.
9135916 Behavioral and social research in rheumatology. 1997 Mar The recent literature on behavioral and social research in rheumatology covers the descriptive epidemiology of the behavioral, psychologic, and social impact of rheumatic diseases, the identification of risk factors and predictors of psychosocial outcomes, and cognitive and behavioral interventions used in the management of rheumatic disease. Past studies focused primarily on behavioral and social outcomes in rheumatoid arthritis and osteoarthritis. Recent work has continued to explore these issues in rheumatoid arthritis and osteoarthritis, but a number of studies are examining psychosocial impact and interventions in other rheumatic conditions, such as fibromyalgia and systemic sclerosis. The continued understanding of these consequences of rheumatic disease will enhance the quality of life in individuals who have these conditions.
9141266 Clinical analysis of 570 cases with juvenile rheumatoid arthritis: results of a nationwide 1997 Apr The purpose of the present study was to investigate the incidence of juvenile rheumatoid arthritis (JRA) among Japanese children and to evaluate the clinical features of this disease. A questionnaire was sent to the department of pediatrics of 1290 hospitals in Japan, in 1994, asking for the number of rheumatic patients during the past 10 years. Subsequently, a second questionnaire was sent asking for the type of onset, clinical features, treatment, and other details. The results of 570 cases were obtained. Of these, 310 cases (54%) were the systemic onset type, 140 cases were the polyarticular onset type (25%), and 120 cases (21%) were the pauciarticular onset type. Hence, in the present series of children, the proportion of the pauciarticular type was less than the other two types of JRA. In the laboratory findings of the systemic onset type, hyperferritinemia and thrombocytosis were noted, in addition to leukocytosis, positive C- reactive protein (CRP) and accentuated erythrocyte sedimentation rate (ESR). The rheumatoid factor was positive in 50% of patients with the polyarticular onset type. Chronic uveitis was recognized in 13 cases (10.8%) of the pauciarticular onset type. In four girls, uveitis started before the onset of arthritis. Non-steroidal anti-inflammatory drugs were used in almost one-third of cases, and methotrexate (MTX) was used in 12.8% of cases. The quality of life of children with JRA was disturbed in almost 20% of cases. Therefore, for the early and definitive diagnosis of the systemic type of JRA, diagnostic procedures including thrombocyte counts and serum ferritin level, should be performed. In order to obtain good results and to avoid side effects, a protocol for the use of disease modifying anti-rheumatic drugs and immunosuppressants, especially for the use of MTX, must be established.
9309197 Clinical aspects of juvenile rheumatoid arthritis. 1997 Sep This paper reviews studies in epidemiology, differential diagnosis, clinical manifestations, and treatment of juvenile rheumatoid arthritis (JRA) that have appeared during the past year. One epidemiologic study suggested a decreased incidence recently; however, changes over time in the ethnic and racial characteristics of the patients studied may also have played a role. Findings from an Australian study suggested that some studies may underestimate the true incidence of JRA if visits of physicians are the only basis for the studies. Finally, a Canadian study of incidence showed no seasonal correlations--except for the Prairie region--raising the possibility that the disease varies by region because of environmental factors or variations in ethnic background. Differential diagnostic issues were covered in several reports. One study suggested that elevations in lactate dehydrogenase levels identified children with malignancies who presented with musculoskeletal symptoms. Another study of children with Lyme disease failed to find any patients with asymmetric joint involvement, in contrast to JRA patients. Two studies from Europe reached opposite conclusions regarding whether the incidence of celiac disease was increased in JRA patients. Clinical studies included a French study showing increased production of interleukin-6 and interleukin-1-Ra during fever spikes in children with systemic JRA. An Italian study explored the potential role of interleukin-6 in the anemia of JRA patients. An American study confirmed decreases in markers of bone formation in JRA patients. Two treatment studies addressed the use of intravenous gamma globulin in JRA. Another report described two JRA patients who developed nodules while receiving methotrexate. Finally, a report added confirmation to the successful use of cyclosporine for macrophage activation syndrome in JRA.
9010185 Total hip arthroplasty with cement for juvenile rheumatoid arthritis. Results at a minimum 1997 Jan We retrospectively reviewed the clinical and radiographic results of total hip arthroplasty with cement in patients with juvenile rheumatoid arthritis who were less than thirty years old at the time of the index procedure. Thirty-nine patients (sixty-six hips) were managed with this procedure at our institution between 1971 and 1983. Six patients (eleven hips) died before a minimum of ten years of follow-up; the remaining thirty-three patients (fifty-five hips) were followed for at least eleven years. Twenty-eight patients (forty-six hips) had at least one original component in situ after an average duration of clinical follow-up of 15.1 years, and twenty-three of these patients (thirty-eight hips) were followed radiographically for an average of 14.7 years. At the time of the latest follow-up examination, all twenty-eight patients were able to walk outside the home; twenty of these patients (thirty-five hips; 76 per cent) had no pain with activity, and eight patients (eleven hips; 24 per cent) had mild-to-moderate pain with activity. Over-all, twelve (18 per cent) of the sixty-six femoral components and twenty-three (35 per cent) of the sixty-six acetabular components were revised after an average of 12.8 and 11.8 years, respectively. The fifteen-year survival rate for the femoral components was 85 per cent with revision or radiographic loosening as the end point. The fifteen-year survival rate for the acetabular components was 70 per cent with revision as the end point and 61 per cent with revision or radiographic loosening as the end point. The benefits of total hip arthroplasty were maintained over the long term in most of our patients who had juvenile rheumatoid arthritis. However, the durability of the components in these young patients remains a concern.
10599320 Prognosis in juvenile arthritis. 1999 Juvenile arthritis implies an onset of disease under 16 years with arthritis persisting in one or more joints for at least six weeks, and with the active exclusion of well defined illnesses, such as systemic lupus erythematosus. Prognosis implies the ability to predict outcome. Its accuracy depends on many factors with early recognition and appropriate care being important. However, response to treatment may be variable. In general, those with involvement of a few joints do better than those with systemic disease or seropositive juvenile rheumatoid arthritis both with regard to persistence of disease activity and complications. These include not just joint deformities, but osteoporosis, amyloidosis, alterations in growth with overall failure and local anomalies, chronic iridocyclitis and psychosocial problems. More aggressive therapy was only introduced in the 1990's, so it is important that multicentre studies are properly assessed in the context of the suggested International diagnostic criteria. One hundred years ago, George Fredric Still drew attention to the systemic form of the disease as distinct from pure polyarthritis [1], but it was only in the 1970s, as follow-up proceeded, that the separate identity of variants became clinically evident [2]. At the Park City meeting [3] and at the EULAR meeting in 1977 [4] when three subgroups (notably systemic, polyarthritis and pauci-articular onset) were defined, that subclassification became regularly used. However, since there were no absolute diagnostic tests there had to be exclusions. At that time the most common medications were aspirin and corticosteroids, although a few patients received gold or penicillamine. In their large group Wallace and Levinson (1990) [5] found that at the 10 year follow-up between 31% and 55% still had active disease. Girls appeared to have a five-fold greater risk for persistent activity than boys; disease duration was probably the most important factor influencing disease activity at follow-up as suggested previously [6]. It was not until the 1990's that the more aggressive therapy in the form of methotrexate--which Giannini had shown to be effective when given in appropriate dosage [7]--and sulphasalazine [8] and the long acting local corticosteroid triamcinolone hexatonide became regularly employed [9, 10]. At the ILAR Meeting in 1993 an international task force was set up under the chairmanship of Dr. C. Fink [11] to develop a classification for the idiopathic arthritides in children, defining childhood as up to 16 years of age. Active exclusion of well-recognised disorders such as rheumatic fever or systemic lupus erythematosus, still had to be made. The first proposed types, which are mutually exclusive, are shown in Table 1. A more recent meeting in Durban under the chairmanship of Dr. R. Petty is yet to be published, but considerable advances have been made, particularly in the definition of subgroups.
9228144 Evolution of the T cell receptor beta repertoire from synovial fluid T cells of patients w 1997 Jul OBJECTIVE: To determine the level of T cell clonal expansion and the proportion of T cells that persist over time in the synovial fluid (SF) of patients with juvenile onset rheumatoid arthritis (JRA). METHODS: We collected SF samples from each of 3 patients with JRA at 2 to 3 year intervals. To measure expression across the entire spectrum of Vbeta families in each of 7 fluids examined, we synthesized and amplified dscDNA from all 24 Vbeta families with a single reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: The proportion of clonally expanded T cells and persistent T cells is low and variable among patients. CONCLUSION: The data are supportive of disease models not centered on T cells but centered on the changing nature of the disease over time.
9293060 Reactive arthritis: is it a useful concept? 1997 Apr Reactive arthritis (ReA) is one of the most common arthritides affecting young adults. In most cases it follows urogenital or enteric bacterial infection, but its pathogenesis is not fully understood. It is generally considered a sterile arthritis which appears to involve immune response to bacterial organisms and genetic host susceptibility associated with the presence of HLA-B27 antigen. New findings suggest that in some ReA cases, viable bacteria are present inside the joints, and these organisms may cause the disease and trigger the inflammatory response. ReA manifests clinically as a rheumatoid factor negative oligoarthritis associated with enthesopathy and certain mucosal and skin lesions. Laboratory findings in ReA are non-specific. Although concepts of its pathogenesis are still evolving, so-called ReA remains an important condition to be distinguished from rheumatoid arthritis. Prognosis is generally better. Treatments with known effects in some cases include non-steroidal anti-inflammatory drugs, intra-articular corticosteroids, oral tetracyclines and sulphasalazine. The occasional chronic and severe ReA may be very difficult to treat.
11051275 Gene therapy for autoimmune disorders. 2000 Sep Although many autoimmune disorders do not have a strong genetic basis, their treatment may nevertheless be improved by gene therapies. Most strategies seek to transfer genes encoding immunomodulatory products that will alter host immune responses in a beneficial manner. Used in this fashion, genes serve as biological delivery vehicles for the products they encode. By this means gene therapy overcomes obstacles to the targeted delivery of proteins and RNA, and improves their efficacy while providing a longer duration of effect, and, potentially, greater safety. Additional genetic strategies include DNA vaccination and the ablation of selected tissues and cell populations. There is considerable evidence from animal studies that gene therapies work: examples include the treatment of experimental models of rheumatoid arthritis, multiple sclerosis, diabetes, and lupus. Pre-clinical success in treating animal models of rheumatoid arthritis has led to the first clinical trial of gene therapy for an autoimmune disease. In this Phase I study, a cDNA encoding the interleukin-1 receptor antagonist was transferred to the knuckle joints of patients with advanced rheumatoid arthritis. Two additional clinical trials are in progress. It is likely that gene therapy will provide effective new treatments for a wide range of autoimmune disorders.
11260966 [Diagnosis and classification of primary Sjögren syndrome. Comparison of 3 criteria sets 2001 Jan In spite of all recent years' international meetings, the question of diagnostic criteria of primary Sjögren's syndrome (pSS) is still under debate. The aim of our study is to define sensitivity, specificity and diagnostic accuracy of 3 sets of criteria: those of the European Community Study Group (ECSG), those proposed by Fox, and those proposed by Daniels. We considered 219 subjects complaining of dry mouth and/or dry eyes and/or parotid swelling, evaluated for pSS. The following parameters were considered golden standard for the diagnosis of pSS: focus score > or = 2 foci/mm2, double positivity for SSA and SSB antibodies, and a sialographic grade > or = 2. Our study demonstrates that ECSG criteria show a high sensitivity and a good specificity, resulting in a diagnostic accuracy similar, and sometimes higher, than that obtained with Fox and Daniels' criteria.
9294323 [Adult onset Still's disease with a brainstem lesion demonstrated on MRI]. 1997 May We report a 39-year-old man with seven-year history of adult onset Still's disease (AOSD) who developed left abducens palsy and ataxic gait. T2-weighted MRI demonstrated high-intensities in the left side of the lower pons, including nucleus abducens and the inferior cerebellar peduncle, and in the right anteromedial portion of the thalamus corresponding to his neurological abnormalities. He responded favorably to corticosteroid treatment, and the high-intensities in the T2-weighted MRI diminished subsequently. Previously, he had developed bilateral sensorineural hearing loss which had responded to corticosteroid treatment during an exacerbation of the disease. There was no evidence of multiple sclerosis or other systemic diseases affecting the central nervous system (CNS) in the laboratory findings. Although the precise reason for the MRI lesions was unclear, we thought they were CNS manifestations of Still's disease. We suggest that AOSD is one of the causes of focal CNS involvement in young adults, particularly who has a history of fever of unknown origin.
18031184 How does leflunomide modulate the immune response in rheumatoid arthritis? 1999 Oct Leflunomide has recently been approved by the US Food and Drug Administration for the treatment of rheumatoid arthritis. This approval was based on data from double-blind multicentre trials in the US (US 301; leflunomide versus methotrexate versus placebo) and multicentre European trials (leflunomide versus sulfasalazine versus placebo, and leflunomide versus methotrexate versus placebo). In these trials, leflunomide was superior to placebo and similar to methotrexate or sulfasalazine in efficacy and adverse effects. Both methotrexate and leflunomide retarded the rate of radiological progression, entitling them to qualify as disease-modifying agents (DMARDs). Leflunomide is an immunomodulatory drug that may exert its effects by inhibiting the mitochondrial enzyme dihydro-orotate dehydrogenase (DHO-DH), which plays a key role in the de novo synthesis of the pyrimidine ribonucleotide uridine monophosphate (rUMP). The inhibition of human DHO-DH by A77-1726, the active metabolite of leflunomide, occurs at concentrations (approximately 600 nmol/L) that are achieved during treatment of rheumatoid arthritis. We propose that leflunomide prevents the expansion of activated and autoimmune lymphocytes by interfering with cell cycle progression. This is mediated by inadequate production of rUMP and utilises mechanisms involving the sensor protein p53. The relative lack of toxicity of A77-1726 on nonlymphoid cells may be due to the ability of these cells to fulfil their ribonucleotide requirements by use of the salvage pyrimidine pathway, which makes them less dependent on de novo synthesis.
10754334 A role for complement in antibody-mediated inflammation: C5-deficient DBA/1 mice are resis 2000 Apr 15 Collagen-induced arthritis (CIA) represents an animal model of autoimmune polyarthritis with significant similarities to human rheumatoid arthritis that can be induced upon immunization with native type II collagen. As in rheumatoid arthritis, both cellular and humoral immune mechanisms contribute to disease pathogenesis. Genotypic studies have identified at least six genetic loci contributing to arthritis susceptibility, including the class II MHC. We have examined the mechanism of Ab-mediated inflammation in CIA joints, specifically the role of complement activation, by deriving a line of mice from the highly CIA-susceptible DBA/1LacJ strain that are congenic for deficiency of the C5 complement component. We show that such C5-deficient DBA/1LacJ animals mount normal cellular and humoral immune responses to native type II collagen, with the activation of collagen-specific TNF-alpha-producing T cells in the periphery and substantial intra-articular deposition of complement-fixing IgG Abs. Nevertheless, these C5-deficient mice are highly resistant to the induction of CIA. These data provide evidence for an important role of complement in Ab-triggered inflammation and in the pathogenesis of autoimmune arthritis.
9699025 Oxidant-antioxidant imbalance in blood of children with juvenile rheumatoid arthritis. 1998 Juvenile rheumatoid arthritis (JRA) is the most commonly diagnosed rheumatic disease in children and may represent not a single disease, but rather a syndrome of diverse aetiologies in which inflammation is an exceedingly complex process. Oxidative free radical production at inflammation sites contributes to tissue damage and could also play a significant role in the pathogenesis of JRA. The aim of this study was to evaluate the antioxidant status and lipid peroxidation parameters related to the clinical form of JRA. Plasma malondialdehyde and hydroperoxide concentrations in children with polyarticular and systemic JRA subtypes were significantly higher than in controls. Plasma vitamin E and beta-carotene levels of the JRA children were lower in the three forms compared with healthy children. Patients with JRA present an imbalance in the oxidant-antioxidant system that manifests clearly in the polyarticular and systemic forms through an increase in lipoperoxidation products and significant decrease in the lipid-soluble antioxidants vitamin E and beta-carotene.
19078393 A perspective on the use of minocycline for rheumatoid arthritis. 1999 Aug Although a number of clinical trials have shown minocycline to be effective in the treatment of rheumatoid arthritis, its use is limited and may become more limited with the recent introduction of new agents. The clinical studies providing the evidence for the efficacy of minocycline are reviewed. Laboratory investigations that support a possible anti-arthritic action of tetracyclines through their effect on nitric oxide generation, matrix metalloprotease inhibition, and chondrocyte apoptosis are discussed. A personal perspective is that minocycline may fit into the current therapeutic repertoire as an additional drug for patients who are not adequately responding to other disease-modifying agents.
17039101 Salmonella group D septic arthritis and necrotizing fasciitis in a patient with rheumatoid 2001 Apr Necrotizing fasciitis is an uncommon manifestation of Salmonella infection. We report a case of Salmonella group D septic arthritis complicated with necrotizing fasciitis in a 51-year-old man who had noninsulin dependent diabetes mellitus and rheumatoid arthritis. He presented with fever and severe right hip pain complicated with septic shock and disseminated intravascular coagulation. Crepitation was noticed upon physical examination, and plain films showed numerous air bubbles in the soft tissue around the hip joint. Prompt antibiotic therapy and surgical management were performed with a successful response. The causative organism was Salmonella group D. Antibiotic was given in the total course of 3 months, and there was no relapse of salmonellosis after 2 years follow up. The differential diagnosis of causes of non-clostridial crepitant soft tissue and muscle infections must include Salmonella, especially in patients who have underlying diseases or are taking immunosuppressive drugs. Prompt management is needed to reduce mortality and morbidity. Long-term suppressive therapy may be needed to prevent relapse.
19078446 Blau syndrome (familial granulomatous arthritis, iritis, and rash) in an african-american 2000 Feb Blau syndrome (familial granulomatous arthritis, iritis, and rash) was originally described in 1985, in 11 members of a family of Dutch ancestry. Inheritance is autosomal dominant. Several more Caucasian families have been described since. Skin and synovial biopsy specimens show noncaseating sarcoid like granulomas, but the lung is not involved as in classic sarcoidosis. This report describes 3 members of an African American family with Blau syndrome. It is important to differentiate this genetic disorder from other childhood arthritides, such as, juvenile rheumatoid arthritis, juvenile spondyloarthropathies, and early-onset sarcoidosis, because of the need for genetic counseling, treatment and differing potential for selective involvement of other organs (eye, skin, and tendons/joints). All children of an affected individual have a 50% chance of inheriting the disease. Unaffected children do not have to be concerned about subsequent generations being affected. The response to conventional treatments used in juvenile rheumatoid arthritis and to etanercept in our patients has not been satisfactory. Joint disease responds to corticosteroids, but these agents are not suitable for a disease that is lifelong. The eye involvement is aggressive and can lead to blindness. These patients need close follow-up by an ophthalmologist.
9200919 [Superantigens and autoimmune diseases]. 1997 Jun Superantigens are potent immunomodulators derived from microorganisms such as bacteria, viruses and mycoplasmas. Their effects on immune systems are obtained through their binding both to outer portion of binding grooves of an MHC on antigen presenting cells and to non-recognizing structure of hypervariable region of T cell antigen receptors. X-ray crystallography revealed precise structures of some superantigens, a beta barrel domain as a ligand to MHC class II alpha chain and a beta grasp domain to TCRV beta chain. Superantigens induce not only T/B cell activation but also immunological tolerance through oligoclonal deletion and/or anergy. Contribution of superantigens to the pathogenesis of autoimmune diseases has been discussed since a superantigen, mycoplasma arthritis T cell mitogen revealed to be arthritogenic to mice, and the murine arthritis resembled human rheumatoid arthritis in the pathological findings. Rheumatoid arthritis as well as Kawasaki Disease, Sjögren syndrome, and multiple sclerosis is now well studied through the oligoclonal expression of TCR beta specificities on infiltrating T cells. Application of superantigens to the treatment of autoimmune diseases is also discussed.