Review Articles

Although environmental factors have been implicated as risk factors for the development of rheumatic disease, our understanding of which exposures are important in disease pathogenesis and possible mechanisms by which these factors might act remains limited, as discussed in this Review.

No increased risk of adverse pregnancy outcome has been reported in patients with inflammatory arthropathies treated with tumor necrosis factor antagonists. More data are required, however, before firm conclusions can be drawn regarding the safety of these agents during pregnancy, childbirth and lactation, as outlined in this article.

Research into the epidemiology of and risk factors for osteoarthritis has been inconclusive. This Review focuses on data from systematic reviews on risk, incidence and prognostic factors of knee and hip osteoarthritis, and provides insight into how these findings can be interpreted in clinical practice.

Multiplex antigen microarrays can profile the high titers of autoantibodies found in the biological fluids of patients with many autoimmune diseases, which enables rapid identification of antibody and antigen biomarker sets. The potential applications of this technology for improved diagnosis, prognosis and selection of targeted therapies are reviewed in this article.

Many genes, as well as environmental factors, contribute to complex diseases such as rheumatoid arthritis. Inbred rat and mouse strains have a similar genetic system to humans and can provide relevant disease models. This article outlines the potential use of animal models for identifying the genetic basis of arthritis.

The clinical benefits associated with rituximab therapy in patients with B-cell lymphomas or autoimmune diseases are well established. Rituximab has been hypothesized to act by promoting elimination of B cells, but in this Review the authors propose another theory to explain how this agent works in autoimmune diseases—the immune-complex decoy hypothesis.

The incidence of Lyme disease continues to increase despite the availability of effective prevention strategies for this disease. In this article the authors outline the various prevention strategies and discuss a rationale for promoting the use of preventative behaviors in people who are at risk of contracting this disease.

Most ultrasound machines can now perform color and power Doppler ultrasonography, which can be used to assess synovitis, tenosynovitis, enthesitis and vascular disease. This Review discusses musculoskeletal and vascular Doppler ultrasonography and provides advice for the rheumatologist on how to make the most of these techniques.

High mobility group box 1 protein is a dual function alarmin that can activate innate immune responses. Extracellular levels of this protein are increased in patients and animals with inflammatory diseases and it might, therefore, represent a new target for therapy of inflammatory arthritis, as outlined in this Review.

Disease-modifying antirheumatic drugs are commonly used to treat rheumatoid arthritis, but prolonged usage often results in drug related toxicity, loss of effi cacy, or both. The molecular mechanisms that might be involved in the development of resistance to such drugs, and strategies to overcome this phenomenon, are outlined.

The leading cause of mortality in patients with systemic sclerosis is scleroderma interstitial lung disease. Leukotrienes and lipoxins are thought to be key mediators of the inflamatory response, and how these lipoxygenase-derived eicosanoids might contribute to the pathogenesis of scleroderma interstitial lung disease is discussed in this article, along with possible approaches for treatment.

Targeting the co-stimulatory signals that accompany antigen-derived signals involved in the activation of T cells represents a possible therapeutic approach for patients with rheumatoid arthritis. This Review focuses on abatacept, a fusion protein that interrupts the co-stimulatory signal mediated through the CD28–CD80/CD86 pathway, and discusses its proposed mechanism of action and outlines data from clinical trials in rheumatoid arthritis.

Research into the pathogenesis of systemic scleroderma has highlighted the important role for activated immune cells in this process. These cells and the soluble mediators they produce, therefore, represent logical targets for therapeutic intervention in this disease, as discussed in this Review.

The etiology of fibromyalgia, a syndrome characterized by widespread persistent pain, is unclear. In this article, evidence for familial aggregation, and hence a genetic basis, is outlined. There are significant associations between the incidence of fibromyalgia and polymorphisms in genes encoding components of pain transmission and processing pathways.

The presence of antibodies against neutrophil cytoplasmic constituents (antineutrophil cytoplasmic autoantibodies) is a characteristic of pauci immune vasculitides. A pathogenic role for antineutrophil cytoplasmic autoantibodies in Wegener's granulomatosis and microscopic polyangiitis, and recent therapeutic developments, are outlined in this Review.

Practical, reliable measures of disease activity and treatment responses for individual patients are needed. Although outcome measures used in randomized controlled trials can be time consuming and impractical in daily practice, the authors of this Review recommend how the findings of trials can be applied to improve practice.

A number of new strategies using biologic therapy for the treatment of rheumatoid arthritis have been developed to target the early stages of disease. In this Review, Dr Keystone highlights the substantial positive effects of these strategies on patient outcomes and discusses the concept that the optimum management of RA involves aggressive early anti-tumor necrosis factor therapy combined with close monitoring of disease progression and modification of ineffective therapeutic strategies.

Disruption of the regulation of the cytokine interleukin 6 can induce inflammatory diseases, many of which have proven refractory to conventional therapies. The clinical use of a humanized monoclonal antibody to block signaling from the interleukin 6 receptor is discussed in this Review.

Tumor necrosis factor inhibitors have been linked with a variety of infections in some patients; of most concern from a public heath perspective is the development of active tuberculosis. In this Review the tuberculosis screening and treatment strategies that should be followed in patients receiving anti-tumor necrosis factor agents are discussed.

Chronic low back pain is a common condition that has significant economic consequences for patients and their communities. In this Technology Insight, the author discusses the imaging methods available for the diagnosis of low back pain, and highlights the need for the development of a noninvasive, low-risk technique.