Review Articles in 2006

Progress in our understanding of fibromyalgia has identified aberrant central pain processing as a key abnormality in affected individuals. This Review describes a multimodal approach to treating this central pain syndrome, using neuroactive drugs that modulate sensory processing, and nonpharmacologic therapies such as exercise and cognitive behavioral therapy.

The pathogenesis of the spondyloarthropathies is thought to relate to interactions between genes, including HLA-B27, bacteria, and innate and acquired immune responses. This Review provides an insight into the validity of the genes–bacteria–immune response paradigm, and explores how interactions between these factors might result in disease.

To achieve goodin vivofunction, engineered cartilage needs to exhibit biological and physical properties similar to those of native articular cartilage. Adult multipotent stem cells are considered the cell type of choice for cartilage tissue engineering; this emerging technology shows high promise for producing transplantable cartilage constructs to improve the function of degenerated joints.

Our comprehension of the role of the complement system in autoimmunity and tissue injury in systemic lupus erythematosus has progressed since mice lacking early components of the complement pathway were developed. Elucidation of these disease mechanisms might lead to the development of improved therapeutic approaches.

Both systemic and local biomechanical factors contribute to joint degeneration in osteoarthritis, and diverse molecular mechanisms of the disease pathogenesis are being uncovered. Can mechanism-based treatments be developed for patients with this disease, as has happened with rheumatoid arthritis, and what are the challenges in drug development?

Nonpharmacological treatments cannot be assessed according to the same standards used for pharmacological treatments. This Review gives guidance on trial designs that address specific methodological issues encountered in assessment of nonpharmacological treatments, and on interpretation of data from such trials.

The risk of cardiovascular disease is increased in patients with rheumatoid arthritis, as discussed in this Review. Joan M Bathon and colleagues outline some preliminary recommendations for how these complications can be prevented and managed by aggressive control of both synovitis and conventional cardiovascular risk factors.

Despite extensive research, the etiopathogenesis of primary Sjögren's syndrome is not well understood. In this article, the hypothesis that activation of the type I interferon system contributes to the disease process is outlined and potential new therapeutic targets from this system for Sjögren's syndrome are discussed.

Paget's disease of bone, which is the second most common metabolic bone disorder and is characterized by focal increases in bone turnover, has a strong genetic component. As discussed in this Review, mutations in four genes have been described that cause Paget's disease of bone or related disorders, and all affect the receptor activator of nuclear factor κB signaling pathway.

The secretory functions of the exocrine glands are impaired in patients with Sjögren's syndrome, resulting in symptoms of dry eyes and dry mouth. This Review discusses the currently available treatments for the glandular and extraglandular manifestations of this chronic autoimmune disorder, and describes potential future therapies.

Tumor necrosis factor is a key cytokine in the pathogenesis of ankylosing spondylitis. As discussed in this Review, data from randomized controlled trials show that anti-tumor-necrosis-factor agents can control symptoms effectively and possibly prevent the progression of this chronic inflammatory disorder.

Advances in our understanding of the signaling pathways involved in the pathogenesis of polymyositis, dermatomyositis and inclusion-body myositis offer promise for the development of future therapies for these inflammatory myopathies, as discussed in this Review.

In this Review, Cornelia Weyand and Jörg Goronzy introduce the key role that T cells have in the pathogenesis of rheumatoid arthritis and discuss the development and application of T-cell-targeted therapies for this disease, focusing on approaches that block T-cell co-stimulation.

Although effective at inducing and maintaining remission in the majority of patients with Wegener's granulomatosis, agents such as cyclophosphamide and high-dose glucocorticoids are associated with severe toxic effects. In this Review, Peter Wung and John Stone discuss the progress that is being made in the search for alternative treatments for this common form of systemic vasculitis.

Currently available therapies for systemic lupus erythematosus are limited by side effects and poor response rates. A number of large-scale, double-blind, randomized, controlled trials assessing new treatments for this disease commenced in 2005, which, as discussed in this Review, suggests that we are about to enter a new era for the management of systemic lupus erythematosus.

Although bacterial infections are implicated in the pathogenesis of reactive arthritis, the role of pathogens in the development of other spondyloarthropathies is unresolved. In this Review, the natural history of infection-triggered arthritis, the mechanisms of disease development, and the potential for antibiotic therapy to modify the course of the disease are discussed.

As our understanding of the molecular and biochemical events that underlie the development of systemic sclerosis advances, so does our ability to develop novel targeted therapies for this complex, autoimmune, connective-tissue disease. In this Review, Christopher Denton and colleagues provide an overview of the pathogenesis of systemic sclerosis and discuss the current treatment approaches for managing organ-based complications of this disease.

Gene-transfer techniques applied in animal models have provided valuable insights into the mechanisms of disease pathogenesis in rheumatoid arthritis. This Review discusses gene-transfer methods, provides an overview of the potential therapeutic targets that have been identified, and introduces the barriers that need to be overcome before these approaches can be successfully applied in clinical practice.

Patients with osteoarthritis often turn to complementary or alternative medicines as a substitute to, or to supplement, conventional therapies. This Review discusses the best available evidence for or against these approaches as treatments for osteoarthritis and highlights areas that warrant further investigation in large-scale randomized clinical trials.

Patients with autoimmune rheumatic diseases are at a high risk of developing premature atherosclerosis and subsequent cardiovascular disease. This Review discusses the role of the immune system in this process and highlights potential ways in which the development of atherosclerosis can be immunomodulated in experimental models.