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ID PMID Title PublicationDate abstract
9266138 Effects of cyclosporin on joint damage in rheumatoid arthritis. The Italian Rheumatologist 1997 May According to the most recent literature, few antirheumatic drugs can claim disease-controlling properties over the anatomical joint damage in rheumatoid arthritis (RA). A small number of studies have favored one or another of the available agents, in particular parenteral gold salts, sulphasalazine and methotrexate, but the evidence regarding their efficacy is not convincing when analysed using methodological criteria known to be important in evaluating radiologic evidence of joint damage. The radiologic results in long-standing RA patients have shown that CsA may be of benefit in reducing disease progression. Data from the second year of a clinical trial designed to compare the disease-controlling, anti-rheumatic properties of CsA with those of conventional disease-modifying anti-rheumatic drugs (DMARDs) in early RA support the hypothesis that CsA may be useful in delaying the appearance of new joint erosion.
11394619 Surgical treatment of the rheumatoid elbow. 2001 May In rheumatoid arthritis, the elbow is involved in 20 to 50% of the cases. Surgical treatment for rheumatoid arthritis is proposed to patients in whom an appropriate and adequate attempt at medical management has failed. Improvements in surgical technique and prosthetic design have led to more predictable results in the surgical treatment of the rheumatoid elbow. Surgical treatment of the patient with rheumatoid arthritis continues to evolve. Synovectomy continues to be an effective palliative procedure, preferred in the early stages of disease (I, II, IIIA) with or without radial head resection. Further investigation into the use of arthroscopic techniques may result in decreased morbidity and a quicker recovery. In more advanced stages (IIIA, IIIB, IV), total elbow replacements by experienced surgeons employing contemporary designs, unconstrained or semiconstrained, and surgical techniques are associated with a high degree of success with long-term follow-up, approaching that fortotal hip and knee replacement. Finally, interposition arthroplasty can be proposed for young adults with stage II or IIIA rheumatoid arthritis in whom the elbow is mainly stiff and painful.
9648488 [Osteoporosis in rheumatoid arthritis]. 1998 Jun Patients with rheumatoid arthritis (RA) develop both periarticular and generalized osteoporosis. Periarticular osteopenia in appendicular bones occurs early in the course of RA and is one of the earliest radiological signs of RA. An uncoupled state in bone resorption-formation linkage, contributes to the development of periarticular osteopenia and it might be mediated through an increased productions of cytokines and prostaglandins by synovium and bone marrow. Accordingly, early suppression of rheumatoid synovitis is necessary for the prevention of periarticular osteopenia. Generalized osteoporosis is also common in RA and leads to increased risk of fractures. Generalized osteoporosis considered to be multifactorial and factors contributing to lumbar osteoporosis might be different from those to loss of appendicular bones, such as femur and radius. Corticosteroids and menopausal state are important risk factors for lumbar osteoporosis. Rheumatoid activity and reduced physical activity are also important determinants. According to the previous studies, however, the influence of functional impairment is more prominent in the femoral BMD compared to spinal BMD. In addition to control of RA and maintenance of physical activity, hormone replacement therapy (HRT) and bisphosphonate are possible agents for the treatment of osteoporosis in RA patients, especially postmenopausal women.
11123030 Biologic therapies in rheumatoid arthritis. 1999 Dec Our growing understanding of the immune response mechanism has created a wave of novel biologic agents for the treatment of rheumatoid arthritis. The domain of biologic agents includes: 1) Recombinant regulatory cytokines; 2) engineered molecules and monoclonal antibodies that target proinflammatory cytokines; 3) monoclonal antibodies against lymphocyte cell-surface proteins; 4) fusion proteins and monoclonal antibodies that block the second signal and induce anergy; 5) vaccines comprised of specific proteins from lymphocytes and antigen presenting cells; 6) monoclonal antibodies that block intercellular adhesion; and 6) gene therapy whereby antiarthritis genes are introduced directly into the joint. Most treatments remain under investigation; however, in 1998 two antagonists of tumor necrosis factor were approved marking the first approvals of antirheumatic biologic agents. For the first time anti-rheumatic therapies are being designed instead of borrowed.
11795111 [Biological therapy in rheumatoid arthritis]. 2001 Sep Rheumatoid arthritis is an autoimmune disease of unknown etiology. It represents a public health problem since it affects 2% of economically active population. Treatment with cytotoxic drugs has improved quality of life in these patients. However, a significant amount of patients do not respond or do not tolerate this treatment modality. Biotechnology advances have given rise to a new treatment approach known as biological therapy. This new approach has opened a new therapeutical perspective in these patients. The objective of this publication is to review the different aspects of biological therapy, as well as to inform the initial results of clinical trials in patients with rheumatoid arthritis.
10081354 [Rheumatoid arthritis and heart disease]. 1999 Jan 20 Rheumatoid arthritis is a chronic inflammatory disease that usually involves the joints, tendons and bursae. The disease is systemic and may involve the brain, peripheral nerves, lungs, kidneys, heart and blood-vessels. All anatomical structures of the heart may be involved. Most reports on rheumatoid arthritis and heart disease are case reports and autopsy studies. Sonography studies from recent years show pathology in some heart structures at about the same rate as autopsy studies. Mortality studies from the last ten years provide evidence of increased cardiovascular mortality. The frequency of reported rheumatoid heart disease differs according to the method applied in the studies. Clinically significant disease is infrequent. We describe two cases with pericarditis and give a review of the literature.
11177770 Radiography of rheumatoid arthritis in the time of increasing drug effectiveness. 2001 Feb Recent clinical development programs for new therapeutic agents in rheumatoid arthritis have included assessment of radiographic progression comparing changes with treatment to placebo and active controls. Studies now use reliable methods of assessment and sufficient study length to detect radiographic changes. Although patient populations and characteristics differ, and radiographic scoring methods vary, the direction of a series of studies appears to indicate that leflunomide (LEF), methotrexate (MTX), sulfasalazine (SSZ), etanercept, infliximab, and IL-1ra are all effective in retarding radiographic progression, as measured by erosions and joint space narrowing. Interpretation of radiograph data in future trials will be aided by utilization of common reading methods and by continuing comparison across differing rheumatoid arthritis protocol populations.
10227098 [Treatment of rheumatoid polyarthritis: evolution of concepts and strategies]. 1999 Feb INTRODUCTION: The treatment of rheumatoid arthritis includes non-steroid anti-inflammatory drugs (NSAID), low-dose steroids and drugs which modify the evolution of the disease (disease modifying anti-rheumatic drugs, [DMARD]). In the last few years, the long-term efficiency of the recommended treatment strategies in rheumatoid arthritis has been a matter of debate and their basic assumptions have been challenged. Numerous studies were undertaken to settle the question. They tried to delineate the rules for an optimal use of current drugs and other therapeutic means. CURRENT KNOWLEDGE AND KEY POINTS: Rheumatoid arthritis is a crippling disease. It decreases life expectancy and irreversible bone and joint damage may develop even in the first months of evolution. The sooner the prescription of DMARD, the higher the frequency and quality of rheumatoid arthritis improvement and, in the long-term, the lesser the functional impairment. Low dose steroids, when administered early, can slow down the development of radiologic lesions. Some of their effects are thus closer to those of DMARD than to those of symptomatic treatment. NSAID are at least as equally dangerous as DMARD and possibly more so in terms of the potential number of severe side effects. The combination of several DMARD does not increase their overall toxicity. An evaluation of the most efficient combinations and of the clinical situations in which combinations show promise of improved results is in progress. FUTURE PROSPECTS AND PROJECTS: At present, the tendency is to treat early and intensively, in order to obtain complete remission, improve evolution and reduce functional impairment. This strategy requires early diagnosis and early evaluation of prognosis of rheumatoid arthritis. Rheumatoid arthritis with benign evolution would not warrant intensive treatment. Studies are in progress to evaluate the prognostic factors in early rheumatoid arthritis that would enable us to adapt the strength of initial treatment to the disease's putative severity.
10090189 Pathogenesis of joint damage in rheumatoid arthritis. 1999 Mar Rheumatoid arthritis (RA) is characterized by the appearance of progressive joint damage that may be identified only months after the onset of symptoms. Early cartilage and bone erosion is associated with the accumulation of several cell populations in the synovial membrane (SM) and the formation of a proliferating pannus. The synovial sublining layer contains several cell populations including macrophages, T and B lymphocytes, dendritic cells, and polymorphonuclear leukocytes. The lining layer contains large numbers of macrophages and fibroblast-like synoviocytes. The interface between pannus and cartilage is occupied predominantly by activated macrophage populations and synoviocytes capable of secreting destructive proteases in abundance. We have observed that macrophages aggregate preferentially adjacent to the cartilage-pannus junction (CPJ) and express differentiation phenotypes that are absent from the lining layer macrophages of more remote SM. Moreover, in a prospective study, the number of SM macrophages correlated with the degree of joint damage occurring over one year. Similar results were obtained when SM biopsy samples were analyzed and correlated with clinical and radiological changes occurring over 6 years. Macrophages and synoviocytes at the CPJ express matrix metalloproteinase and cathepsin mRNA from the earliest stage of RA. The mechanisms involved in the secretion of tissue degrading enzymes by macrophages and synoviocytes are undergoing further investigation and preliminary results suggest that different regulation pathways may exist.
10331124 Surgical correction of the rearfoot in rheumatoid arthritis. 1999 Apr With proper patient selection and perioperative planning, selective rearfoot arthrodesis in the patient with rheumatoid arthritis is effective in relieving pain and restoring ambulatory status. The overwhelming majority of current literature supports the early fusion of involved rearfoot joints in an effort to arrest the compensatory progression, which yields a rigidly deformed lower extremity. In keeping the patient with rheumatoid arthritis ambulatory, we can positively affect his or her quality of life and prevent the degradation into a sedentary disposition, and therefore heighten the long-term prognosis.
9441465 [Systemic rheumatoid arthritis]. 1997 Nov 30 The term systemic rheumatoid disease refers to patients with rheumatoid arthritis who have clinical or histological evidence of vasculitis or serositis, or both. Males are affected more often than females, and vasculitis may develop in almost any organ. Rheumatoid nodules, joint deformities and erosions are often present, even though the arthritis may be inactive. The condition is associated with high titers of IgG rheumatoid factor. An intermittent bolus regimen of cyclophosphamide and corticosteroids appears to be effective. Two patients with systemic rheumatoid arthritis are presented.
9143371 New insights into the pathogenesis and treatment of rheumatoid arthritis. 1997 May Rheumatoid arthritis (RA) is a chronic multisystemic inflammatory disease with autoimmune features, and of unknown cause, associated with characteristic joint deformities and increased mortality rate. The pathogenesis of this serious disease seems to be multifactorial, where several cytokines, particularly interleukin-1 and tumor necrosis factor-alpha, are strongly involved in the induction and perpetuation of the chronic inflammatory process of the joints in RA and in the systemic manifestations of the disease. Other factors, such as reactive oxygen species and metalloproteinases, may also participate in the destruction of the rheumatoid joint. Current treatments of RA are inadequate in that they only partially control established RA, and despite optimal use of current antirheumatic agents, the outcome of many patients with RA consists of pain, severe functional decline, and premature death. The gloomy recent data regarding the prognosis of RA with the use of the current treatments stress the need for new therapeutic regimens with the ability to effectively control the inflammatory process in the rheumatoid joint and to induce long-term remission or even cure. Controlling the production and the activity of the factors involved in the pathogenesis of the disease represents the major therapeutic goal. Since several factors are involved in the pathogenesis of RA, neutralizing one or some of these factors may be of only limited benefit. In this regard, interleukin-4 may be a very promising agent for an effective treatment of RA, because this cytokine is not limited by its inhibitory effects to a single factor, but rather it inhibits most of the main factors involved in the pathogenesis of the disease. Although recent data strongly support this approach with interleukin-4, controlled long-term clinical trails should be undertaken in order to prove the validity and the effectiveness of this promising approach.
9510939 Mechanism of joint destruction in rheumatoid arthritis. 1998 The synovium in rheumatoid arthritis (RA) is characterized by an increase in lining layer thickness and infiltration of inflammatory cells into the sublining area. Fibroblasts in the lining layer develop the appearance of "transformed cells", under the influence of proto-oncogenes involved in the regulation of the cell cycle. Fibroblast and macrophage-derived cytokines such as IL-1 and TNF-alpha are present abundantly in the rheumatoid synovium and stimulate these cells to produce destructive enzymes. Other cytokines such as IL-4 and IL-10 represent a physiological attempt to reverse the inflammatory process. Adhesion molecules facilitate both the migration of cells to the joint as well as the attachment of synovium to bone and cartilage. Joint destruction is mediated by enzymes such as serine proteases, matrix metalloproteinases (MMPs) and the cathepsins. Treatments directed against various components of the inflammatory cascade have shown promise. Inhibition of MMPs or adhesion molecules, blockade of IL-1 or TNF-alpha and the use of anti-Fas antibodies to induce apoptosis offer new possibilities for the treatment of RA. More recently, the employment of genes with antiarthritic properties has shown therapeutic potential.
11094426 Rheumatoid arthritis viewed using a headache paradigm. 2000 Results and new hypotheses in animal models often stimulate development of new paradigms in how we view rheumatoid arthritis (RA). The complexity of RA does, however, eventually lead to the rejection of these hypotheses. Here, it is argued that the large number of so-far described animal models, when taken together, also reveals a complex disease. Fortunately, detailed study of each of the animal models will reveal this complexity, and may also be helpful in elucidating the complexity of the human disease. Benoist and Mathis [1] recently contributed a new animal model in which an autoimmune response to a ubiquitous antigen leads to an antibody-mediated inflammatory attack in the joints. It is argued that this new model, as with other animal models, is unlikely to explain RA, but it will add to the tools available to reveal the complexity of RA.
9197831 Rheumatoid neutrophilic dermatitis. 1997 Jun BACKGROUND: Rheumatoid neutrophilic dermatitis (RND) is a recently recognized, rare cutaneous manifestation of rheumatoid arthritis. It occurs in patients with severe rheumatoid arthritis and is typically asymptomatic. Rheumatoid neutrophilic dermatitis was originally described by Ackerman in 1978. Since that time, 8 patients with this disease have been described in the literature. OBSERVATIONS: We report 2 cases of RND. Findings of skin biopsy specimens from both patients revealed characteristic signs of dermal leukocytosis and leukocytoclasia without vasculitis. The pathogenesis of the neutrophilic infiltrate is unclear. Processes that may play a role in the pathogenesis of RND include immune complex activations, cell adhesion and migration, and cytokine release. CONCLUSIONS: Rheumatoid neutrophilic dermatitis falls into the spectrum of neutrophilic vascular reactions described by Jorizzo and Daniels. Although early reports suggest that prominent leukocytoclasia is not a feature of RND, our findings confirm the observations of Lowe et al that leukocytoclasia can be seen in RND and may be striking. It is important for dermatologists to be aware of this rare manifestation of rheumatoid arthritis.
11291464 Infliximab: a new treatment for rheumatoid arthritis. 2001 Mar Infliximab, a chimeric mouse human monoclonal antibody, is an anti-TNF treatment for rheumatoid arthritis. In the past there was a sizeable group of people who had exhausted disease-modifying antirheumatic drugs (DMARDs) and were left largely untreated. This has been revolutionized by treatments such as infliximab which have been shown to be effective for patients in whom standard DMARDs have failed.
9569729 [Cytokines in rheumatoid arthritis: new therapeutic possibilities]. 1998 Apr 5 The ingress of inflammatory leukocytes into the synovium is important for the pathogenesis of rheumatoid arthritis. Soluble inflammatory mediators regulate the inflammatory, chemotactic, adhesive, angiogenic events, as well as osteopenia associated with this disease. In this review authors discuss the role of a number of inflammatory mediators, such as cytokines, chemokines and growth factors in these processes. The outcome of arthritis is highly dependent on the imbalance between pro-inflammatory and anti-inflammatory mediators. Cytokine-related research also has important clinical relevance. Many of these proteins are detectable in the serum of rheumatoid patients and may eventually serve as useful laboratory markers of disease activity. Antirheumatic therapy currently used for the treatment of rheumatoid arthritis is often limited. Therefore, we need to consider alternative therapeutic regimens, such as the inhibition of cytokines and other soluble mediators, in order to prevent severe joint destruction. While there are many complex interactions involving cytokine networks and cascades in the arthritic joint, there are promising attempts to eliminate a single cytokine in clinical trials, such as ablation of tumor necrosis factor-alpha. Hopefully, the study of cytokines and their networks will lead to specific immunomodulatory therapies that will benefit rheumatoid patients by preventing joint destruction.
9306868 Cigarette smoking and rheumatoid arthritis severity. 1997 Aug OBJECTIVES: Cigarette smoking may influence rheumatoid arthritis (RA) disease incidence and may have direct biological effects on the lungs and systemically. This study sought to determine if cigarette smoking is associated with RA disease severity. METHODS: Clinical evaluations of patients seen in the University of Iowa rheumatology and orthopaedic ambulatory clinics were conducted. A letter of interest was mailed to 1701 patients who were first assigned an ICD-9-CM diagnostic code for RA in one of these clinics. A total of 857 patients expressed interest and were offered a clinical examination and 395 were evaluated over an 18 month period. Of these, 336 satisfied examiner criteria for prevalent RA and were included in the analysis. The disease characteristics and arthritis care utilisation of these patients seemed representative of prevalent cases in the general community. RA disease severity was assessed by radiographic bone erosions (graded as either present/ absent and using the Larsen system), rheumatoid factor seropositivity, and presence of subcutaneous rheumatoid nodules. RESULTS: Pack years of cigarette smoking was significantly associated with rheumatoid factor seropositivity (p = 0.0001), radiographic erosions (p = 0.024), and nodules (p = 0.051). After adjustment for potential confounders, smokers with > or = 25 pack years were 3.1 times more likely to be rheumatoid factor positive (95% CI 1.7, 5.6) and 2.4 times more likely to show radiographic erosions (95% CI 1.2, 4.5) than never smokers. Less severe radiographic disease seemed to be more strongly associated with cigarette smoking than more severe disease. CONCLUSION: Cigarette smoking may adversely influence the severity of RA in a potentially dose dependent fashion.
9549225 Angiogenesis in rheumatoid arthritis: pathogenic and clinical significance. 1998 Feb In summary, angiogenesis, the formation of new blood vessels, is important in leukocyte extravasation and thus the pathogenesis of RA. The outcome of neovascularization highly depends on the imbalance between angiogenic and angiostatic mediators produced in the rheumatoid synovium. Therefore, angiogenesis research is important for the understanding of the pathogenesis of inflammatory arthritis. In addition, existing and potential angiostatic drugs may be useful for future therapy of RA.
10529149 Two cases of methotrexate induced lymphomas in rheumatoid arthritis: an association with i 1999 Oct We describe 2 patients with rheumatoid arthritis (RA) in whom non-Hodgkin's lymphomas developed during low dose pulsed methotrexate (MTX) treatment. The tumors regressed after discontinuation of MTX with no additional treatment. Serum levels of IgE increased concomitantly with the development of lymphoma, and decreased along with the regression of the lymphoma in both patients. These 2 cases and a review of the literature suggest that measuring serum IgE may have a predictive value for monitoring lymphoma in patients with RA treated with MTX.