Reviews & Analysis

Imaging techniques such as MRI and musculoskeletal ultrasound are becoming increasingly important in the management of patients with rheumatic disease. In this Viewpoint, Dr Freeston and Dr Emery discuss the role of advanced imaging modalities with regards to the use of biologic therapy in patients with rheumatic disease.

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.

Juvenile rheumatoid arthritis is one of the most common chronic diseases of childhood. In this Viewpoint, Dr Connelly and Dr Schanberg discuss the limited knowledge regarding the widespread occurrence of pain in children with arthritis. Research into treatment with opioids in these patients has fostered clinical myths inhibiting optimum patient care.

Systemic lupus erythematosus is a disease triggered by environmental factors in individuals with a genetically predetermined alteration of the threshold for induction or maintenance of immune tolerance. In this Viewpoint, Professor Davidson discusses the immune activation pathways involved in systemic lupus erythematosus, and highlights the importance of understanding these pathways and their role in disease activity.

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.

Tumor necrosis factor (TNF) inhibitors have changed the therapeutic standard of treatment for patients with rheumatoid arthritis. Despite the efficacy of these agents, a significant proportion of patients demonstrate an inadequate response to one or more TNF inhibitor. In this Viewpoint, Dr Keystone discusses the outstanding issues related to the scientific and clinical rationale for switching TNF inhibitors.

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.

Although sciatica is usually caused by a mechanical abnormality, pathophysiologic considerations provide a sound rationale for local corticosteroid therapy. There is evidence that this treatment should be started early to prevent persistent nerve-root pain due to peripheral and central sensitization. In this Viewpoint, Dr Valat discusses the use of epidural corticosteroid injections in early sciatica.