Review Articles in 2006

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.

There is increasing insight into the impact of ankylosing spondylitis on employment and the costs of illness associated with this disease. Standardization of cost-effectiveness studies will improve the quality and comparability of these costs. This Review summarizes the literature on work participation, costs of illness and cost-effectiveness of treatment in patients with ankylosing spondylitis.

Improvements in treatments for systemic lupus erythematosus have led to longer survival times, but complications including osteoporosis and osteonecrosis often occur. This Therapy Insight provides an overview of the pathophysiology of osteoporosis and osteonecrosis in these patients, and recommends preventive measures and treatments.

In this Review, the authors discuss how early diagnosis of spondyloarthritis can be achieved for patients with predominantly axial or predominantly peripheral symptoms. The importance of identifying differences between diagnosis and classification, and how this disparity might influence clinical practice, are highlighted.

Many forms of functional decline are preventable, treatable or manageable, but a screening tool that can identify frail or vulnerable patients is much needed. This Review describes the methods currently available for non-specialist evaluation of patients at risk of functional decline, including behavioral, interview and questionnaire assessments.

Neutrophils are powerful mediators of tissue inflammation, and the balance between neutrophil survival and clearance is crucial to the resolution of inflammation. The cytokine granulocyte colony-stimulating factor is an important regulator of neutrophil production and survival. This Review discusses the roles of neutrophils and granulocyte colony-stimulating factor in chronic inflammatory diseases.

The creation of specific immune tolerance would allow autoimmune disease to be reversed without the need for nonspecific and potentially harmful immunosuppressive therapy. Important progress in research into immune tolerance is summarized in this Review, and the potential use of this technique in immunotherapy of autoimmune disease is discussed.

Pattern recognition molecules belonging to the innate immune response participate in the clearance of apoptotic cells. Among these molecules are the collectins C1q and mannose-binding lectin, and the pentraxins C-reactive protein, serum amyloid P component, and pentraxin 3. This Review discusses the prevalence, actions and clinical significance of these molecules in autoimmune conditions.

A variety of retinal signs can occur in patients who have systemic vasculitides. Although retinal signs are usually treated by treatment of the systemic disease, specific therapy is indicated occasionally to preserve vision. This Review describes the pathogenesis, clinical features and treatment of retinal manifestations of systemic vasculitides.

In this Review, Lars Klareskog and colleagues discuss the experimental approaches that are used to address the issue of gene–environment interactions in the etiology of RA, focusing on the roles of the HLA-DR shared-epitope genes, smoking and anticitrulline immunity in this process.

There is increasing interest in the role of transcription factors in the pathogenesis of inflammatory arthritis. Biologic and genetic studies are adding to current knowledge, and revealing potential targets for anti-inflammatory therapies that aim to modulate transcription factor activity.

Initially used in the treatment of mood disorders, this form of psychotherapy has been extended to other conditions such as chronic pain states. This Review evaluates the role of cognitive behavioral therapy, alone or in combination with other modalities, in the management of patients with fibromyalgia.