Review Articles

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.

Catastrophic antiphospholipid syndrome, a severe form of antiphospholipid syndrome, is associated with a high mortality rate; approximately 50% of patients die from thrombotic diathesis. As discussed in this Review, efforts to facilitate early diagnosis, institute effective treatments in a timely manner, and to better understand the causes of this extreme condition are needed to improve patient outcome.

The pathogenesis of pain in patients with fibromyalgia syndrome is complex and incompletely understood. In this Review, Roland Staud and Miguel E Rodriguez discuss the abnormalities of pain processing that occur in these patients, focusing on the role of deep-tissue nociception, peripheral and central pain processing, temporal summation of pain (or wind-up) and central sensitization.

Given the central role that B cells have in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus, interest in approaches that therapeutically target B cells is considerable. This review provides an update on B-cell-depleting therapies for these diseases, as well as other approaches that target co-stimulatory signals, cytokines and other B-cell surface molecules.

Medical treatment for children with severe systemic juvenile idiopathic arthritis is unsatisfactory at present, and affected patients suffer from significant morbidity throughout their lives. Research into the pathogenesis of this disease should allow for the identification of new molecular targets and the development of improved therapies for this serious form of childhood arthritis.

Autoimmune responses are an inherent consequence of the wide repertoires of T-cell and B-cell receptors, which are needed in order for these cells to recognize a broad range of pathogens. This review explains the strategies used by the immune system to prevent and regulate the generation of autoreactive receptors and maintain immunologic tolerance.

Osteoporosis results from decreased osteoblast function, increased osteoclast function and increased adiposity of the bone marrow with age. Regulation of the balance between fat and bone in the bone marrow is complex and involves genetic, hormonal and environmental influences. Here, Clifford Rosen outlines a hypothesis that skeletal fragility has its pathogenic roots in pleuripotent marrow stromal cells and their fate as either fat or bone cells.

The improved prognosis of children with systemic lupus erythematosus over the past 50 years means that rheumatologists now focus on preventing the long-term complications associated with this disease and its treatment. As discussed in this review, a specialized multidisciplinary approach is needed to ensure optimum family education, treatment and patient outcome in pediatric systemic lupus erythematosus.

Pulmonary arterial hypertension is particularly common in individuals with systemic sclerosis, but is also seen in other rheumatic diseases. A number of treatment optionsfor this serious complication are available, including selective and unselective endothelin-receptor antagonists, which are the subject of this review.

Molecular biology techniques have enabled the pathophysiologic pathways involved in joint destruction in rheumatoid arthritis to be elucidated at the cellular and molecular level. In this review, the authors discuss the various cell-to-cell and cell-to-matrix interactions, highlighting the role of cytokine-independent pathways and the innate immune system in these processes.

The link between chronic inflammation and bone loss has been the subject of intense research over the past decade. This has led to the identification of key molecules that bridge the gap between immune function and bone turnover, including receptor activator of NFκB ligand, which represents a potential therapeutic target for patients with chronic inflammatory arthritis, and is the subject of this review.