To identify preliminary core sets of outcome variables for disease activity and damage assessment in juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM).

To investigate the clinical characteristics of patients with tuberculous myositis.

The recombinant interleukin-1 receptor antagonist, anakinra (Kineret; Amgen Inc., Thousand Oaks, CA), has been approved by the US Food and Drug Administration and the European Commission for the treatment of patients with active rheumatoid arthritis (RA). Approval was granted following the extensive evaluation of anakinra in five pivotal clinical trials that assessed its efficacy and safety in RA patients. These studies have indicated that anakinra has a favourable risk-benefit profile, producing rapid and sustained reductions in the signs and symptoms of RA, as measured by improvements in the American College of Rheumatology response criteria, particularly in patient-reported indicators of function and disability. The data from these trials suggest that anakinra is likely to provide a useful therapeutic option to clinicians and also meet the treatment expectations of patients with RA; however, further studies are underway to investigate additional benefits that anakinra may offer, particularly in patients with existing co-morbidities.

Anakinra (Kineret; Amgen Inc., Thousand Oaks, CA) is the first and only recombinant human interleukin-1 receptor antagonist available for therapeutic use. It has been approved by the US Food and Drug Administration and the European Commission for the treatment of patients with rheumatoid arthritis (RA). Anakinra, as an anti-rheumatic therapy, has been assessed in five placebo-controlled clinical trials, either alone or in combination with methotrexate. These trials have shown anakinra to be efficacious and well tolerated by most patients, with the most frequently reported adverse events being mild-to-moderate injection-site reactions that generally resolved rapidly. One of these trials was a large, prospective safety study, which included typical RA patients with a wide variety of co-morbid conditions and receiving concomitant medications. This confirmed that anakinra is a well-tolerated treatment in an RA population representative of that seen by the practising rheumatologist.

Interleukin-1 (IL-1) is a proinflammatory cytokine that plays a pivotal role in the pathophysiology of rheumatoid arthritis (RA). Inhibiting the activities of IL-1 at the receptor level with the recombinant human IL-1 receptor antagonist anakinra (Kineret; Amgen Inc., Thousand Oaks, CA) is a new therapeutic option for the management of patients with RA. Randomized, placebo-controlled trials have demonstrated that anakinra, alone and in combination with methotrexate, improves the signs and symptoms of RA. Anakinra also produces improvements in patient functionality and health-related quality of life, as measured by the Health Assessment Questionnaire and the Nottingham Health Profile, and reduces the number of productivity days missed due to illness. Furthermore, an initial study indicates that anakinra retards the progression of radiographic joint damage. Such clinical findings suggest that anakinra is an important addition to the rheumatology treatment armamentarium.

Rheumatoid arthritis (RA) is a chronic, debilitating disease that follows a progressive course characterized by persistent inflammation and erosive joint damage leading to functional disability. The Health Assessment Questionnaire is now viewed as a key instrument to measure physical function, based on its reliability and ease of use. It has been demonstrated that multiple variables affect physical function, of which those most frequently indicated are disease activity, joint damage and the psychosocial characteristics of the patient. When these variables are pooled together the variation observed in a patient's physical function over the long term can be explained mainly by disease activity, partially by joint damage and additionally by psychosocial factors. Therefore, to maintain or improve physical function in long-standing RA, it is imperative to control disease activity and joint damage by early initiation of treatment.

Proinflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha), have been implicated in the dysregulation of bone and cartilage remodelling characteristic of rheumatoid arthritis (RA). With respect to bone remodelling, both of these cytokines have been shown to up-regulate the production of the receptor activator of nuclear factor-kappaB ligand, which acts to enhance osteoclastic bone resorption. TNFalpha stimulates differentiation of osteoclast progenitors into mature osteoclasts and IL-1 acts directly on osteoclasts to increase the bone-resorbing capacity of these cells. IL-1 and TNFalpha also adversely affect cartilage remodelling, although IL-1 is more potent on a molar basis. This cytokine not only increases production of factors that stimulate cartilage matrix degradation, but also inhibits the synthesis of type II collagen and proteoglycans. Enhanced understanding of the mechanisms underlying the processes of joint destruction will allow more selective and specific application of therapeutic agents that target these proinflammatory cytokines and, thus, more effective management of patients with RA and other inflammatory disorders.

The role of the cytokine network in mediating inflammation and joint destruction in rheumatoid arthritis (RA) has been investigated extensively in recent years. Interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha) are two pivotal proinflammatory cytokines that have been shown to contribute to the clinical manifestations of RA. The ability of IL-1 to drive inflammation and joint erosion and to inhibit tissue repair processes has been clearly established in in vitro systems and animal models. Under physiological conditions, the activity of IL-1 is balanced by IL-1 receptor antagonist (IL-1R alpha). Understanding of the respective roles of IL-1 and IL-1R alpha in conditions of health and disease has led to the development of a recombinant IL-1ra, anakinra (Kineret; Amgen Inc., Thousand Oaks, CA), which offers a new therapeutic modality for RA.

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy characterized by the association of arthritis with psoriasis. Many agents have been proposed for the treatment of PsA, but their use is based more on clinical experience than on sound scientific evidence.

After many years out of the limelight, massage therapy is now experiencing a revival. The aim of this systematic review is to evaluate its potential for harm.

To assess the prevalence of pregnancy in 28 females with dermatomyositis (DM) and polymyositis (PM), assess the outcome in those who became pregnant after the onset of the disease and review the literature of all published cases.

Experimental models seeking to explore how susceptible individuals develop rheumatoid arthritis (RA) propose that genetic and environmental factors shape a complex series of molecular and cellular interactions leading to a chronic inflammatory response. T lymphocytes and MHC class II genes have featured prominently in these models. More recent studies have suggested that perpetuation of inflammation in a disease-susceptible host might occur through failure to down-regulate the inflammatory process. One prediction from this model is that effective mechanisms of immunoregulation might be most easily investigated in non-susceptible individuals. However, this has been difficult to study in man. Based on the observation that extended MHC haplotypes are strongly associated with RA in different ethnic groups, I have explored the function of human MHC-encoded genes in transgenic mice using two different experimental approaches. First, by comparing the molecular interactions between disease-associated or non-associated HLA-DR4 molecules and CD4+ T lymphocytes, it has been possible to gain insight into how immune responses in non-susceptible individuals might differ from T-cell responses observed in a susceptible host. This has been achieved using transgenic mice expressing RA disease-associated and non-associated human HLA class II molecules. Secondly, the effects of prolonged exposure of T cells to the proinflammatory cytokine tumour necrosis factor alpha (TNF) have been studied in vitro and in vivo, focusing on T-cell receptor (TCR) signalling and effector responses. In studies of HLA class II transgenic mice, the major differences between disease-associated and non-associated alleles in terms of T-cell responses occur at the level of presentation of antigenic peptides, and the sustained expression of inflammatory cytokines such as TNF. Chronic exposure of T cells to inflammatory cytokines such as TNF induces a phenotype which resembles RA synovial T cells, including the induction of non-deletional and reversible hyporesponsiveness to TCR ligation and uncoupling of proximal TCR signal transduction pathways. The experimental findings are consistent with a model in which HLA class II-driven inflammatory cytokine expression uncouples TCR signalling pathways in the susceptible host in such a way as to profoundly suppress proliferative and immunoregulatory cytokine responses, while at the same time promoting cell survival and effector responses.

With the growing interest in herbal therapies among persons with rheumatoid arthritis, there exists a need for investigation into their safety and efficacy. The purpose of this study was to conduct a systematic review to examine the evidence for the use of herbal medicines for RA based on randomized clinical trials (RCTs).