Reviews & Analysis

Evidence-based medicine and, primarily, data from randomized controlled clinical trials are continually regarded as the only valid sources for all clinical knowledge. This Viewpoint discusses the merits of 'practice-based evidence' and how this important information is currently undervalued in the clinical community.

There has been significant progress in the development of biological markers to assess joint and tissue damage in osteoarthritis. In this Viewpoint, Patrick Garnero discusses the developments in this field and how they will affect the future management of patients with osteoarthritis.

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.

Trials investigating T-cell targeted therapies for rheumatoid arthritis have been of limited success. This Viewpoint considers whether or not the hypothesis that T cells are involved in the pathogenesis of rheumatoid arthritis is true and, if so, why trials so far have not led to an applicable therapy.

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.

Pharmacogenetics is the study of the genetic characteristics that dictate drug response and toxicity. This Viewpoint discusses this rapidly advancing field that might improve the clinician's ability to match a patient with the right drug or drugs for their disease.

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.

Choosing the correct management strategy for patients with rheumatoid arthritis in order to achieve the best possible outcome is a challenge to all rheumatologists. This Viewpoint considers current progress in the field of outcomes research in rheumatoid arthritis, along with future prospects of predicting individual patient response to therapy.