Review Articles in 2011

Our understanding of the role of adipokines in inflammation and the immune response has improved markedly in the past decade. These proteins, produced by adipose tissue, form complex networks that contribute to the pathogenesis of rheumatic diseases. In this Review, the authors provide an update on the current state of adipokine research in these diseases, with a focus on rheumatoid arthritis and osteoarthritis.

Cartilage damage frequently occurs during aging, and represents a known risk factor for the development of osteoarthritis (OA). In this Review, the authors discuss the homeostatic processes that maintain cartilage, how these become defective with age, and how these malfunctions can contribute to the development of disease. The tantalizing prospect of augmenting homeostatic mechanisms as a new therapeutic strategy against joint aging and OA is introduced.

As much as the pathology of fibromyalgia has informed therapy, the treatment of this disorder has provided insights into its underlying pathophysiology. In this article, the authors provide an overview of key aspects of the epidemiology and pathophysiology of fibromyalgia, and discuss both pharmacological and nonpharmacological treatment options.

Genetic data suggest an inherited susceptibility, mycobacterial and propionibacterial species are implicated as triggers, innate immunity and misfolded proteins are involved. Yet the etiology of sarcoidosis remains a mystery and no therapies are approved. This Review is a guide to the features and mechanisms of, and consensus treatment approaches and emerging therapies for, this diagnostically challenging and potentially life-threatening disease.

Compared with other medical imaging techniques, ultrasonography is inexpensive, safe, and increasingly valuable. Nevertheless, its use is—so far—recommended in only one preliminary classification criteria. As this situation looks set to change rapidly, this Review provides an overview of the use of ultrasonography in rheumatology, both now and in future.

Advances in genetic research and technology have provided great insights into the pathogenesis of inherited diseases of the innate immune system. In this article, the authors review the contributions of genetic studies to the understanding of the mechanisms underlying these autoinflammatory disorders, and outline the challenges that remain.

Adapting to life with a chronic illness is difficult—rheumatic diseases can have profound effects on long-term quality of life. A patient's resilience to the challenges of chronic illness is determined by a number of factors that are increasingly understood, and which are outlined in this Review. The authors summarize developments in the psychological care of patients in clinical rheumatology practice, and describe novel approaches to optimizing this care.

Emerging data from cohorts of patients with recent-onset arthritis provide valuable information about the incidence and outcomes of early inflammatory disease, and about the risk factors for transition to full-blown rheumatoid arthritis, which could help improve the diagnosis and therapy of such conditions.

The cysteine protease cathepsin K has an important role in initiating the process of bone resorption by osteoclasts, and its potential as a therapeutic target in patients with bone resorption disorders, such as osteoporosis, has become a major focus of research in recent years. In this Review, the authors describe the development of cathepsin K inhibitors and the promising data that have emerged from clinical studies of these agents.

Several models for the pathogenesis of systemic juvenile idiopathic arthritis have been proposed, but the mechanisms underlying this disease are unclear. As outlined in this Review, intensive research in these areas has provided intriguing new insights, but numerous issues remain to be addressed.

Anti-citrullinated peptide antibodies (ACPA) are an important feature of rheumatoid arthritis (RA), and the presence of these autoantibodies is associated with a more-erosive disease course. In this Review, the authors provide an overview of the discovery and development of ACPA as a biomarker in RA, and discuss the future research directions that might further enhance its clinical utility.

Patients with autoimmune rheumatic diseases have long been known to be at increased risk of developing non-Hodgkin lymphoma (NHL). In this Review, the authors evaluate the new data that has emerged since 2006 regarding the clinical factors that contribute to the increased risk of the different B-cell NHL subtypes in patients with rheumatoid arthritis, systemic lupus erythematosus and Sjögren's syndrome.

Traditional cardiovascular risk factors combine, in the context of inflammatory rheumatic diseases, with disease-related and treatment-related risk factors, to determine a patient's overall risk of cardiovascular disease (CVD). These competing risks are explored in this Review, which summarizes why CVD risk is increased in these patients, and what remains to understand before patients can be offered the best advice about CVD risk management.

Pathogenic autoantibodies trigger thromboses in antiphospholipid syndrome (APS), through several mechanisms that favor blood clotting and act in concert with inflammatory events. APS-associated fetal loss, however, is not fully explained by thrombogenic mechanisms, and other, direct actions of the autoantibodies are proposed. This Review summarizes the autoantibody-mediated pathways in APS, with a focus on the causes of pregnancy complications.

The use of intravenous immunoglobulin for rheumatic diseases is explored in the Review, with a focus on the conditions for which its use is best indicated, those for which it shows promise but remains unproven, and the future developments that might help to clarify its potential as a first-line therapy.

Although glucocorticoids are used for the treatment of as many as 50% of patients with inflammatory disorders such as rheumatoid arthritis, their use is associated with adverse effects. Beaulieu and Morand review the evidence that the glucocorticoid-induced leucine zipper protein (GILZ) might be a target that can be exploited to provide the beneficial anti-inflammatory effects of glucocorticoids without their negative metabolic repercussions.

This Review provides an overview of what is currently known about the biological roles of IL-33, both as a cytokine and as a nuclear factor, and discusses the possible applicability of anti-IL-33 approaches to the treatment of several inflammatory diseases.

As the number of patients with childhood-onset rheumatic diseases who survive into adulthood has improved markedly over the past few decades, the long-term effects of these diseases have become an important focus of research. In this Review, the authors describe the most recent outcome data for several pediatric rheumatic diseases in terms of disease activity, functional and quality of life outcomes.

Serum level of C-reactive protein (CRP) is commonly measured in rheumatology practice, but it is perhaps less widely appreciated that CRP level is influenced not only by underlying inflammation but also by genetic variation, with possible consequences for clinical decision-making. Mounting functional and genetic evidence also implicates this protein in the pathogenesis of systemic lupus erythematosus.

Stratifying patients with myositis into clinically meaningful subtypes would be ideal for enabling research into pathogenic mechanisms and targeted therapies. Incomplete knowledge of the molecular pathways that underlie myositis, inappropriate classification criteria and a lack of specific agents have all been mutually hindering progress in treating these diseases, but, as the authors explain in this Review, insights into the mechanisms—immune and nonimmune—involved in myositis are precipitating wider progress in the field.