Reviews & Analysis

The use of biologic agents has revolutionized treatment in a number of rheumatic and non-rheumatic autoimmune and inflammatory disorders. In this Review, the authors discuss whether rheumatologists can learn lessons from the application of biologic agents in non-rheumatic diseases such as psoriasis, asthma and multiple sclerosis.

Autoantibodies, produced by autoreactive B cells, are involved in the pathology of rheumatic diseases including systemic lupus erythematosus (SLE). Modulation of B-cell function by inhibiting cytokines active on B cells or even eliminating B-cell populations can effectively treat SLE and other diseases. So far so simple, yet—as explored in this Perspective—the relationships between the effects of such therapies on B cells, the levels of individual autoantibodies, and clinical outcomes are fiendishly complex. Better knowledge of B-cell biology is needed to understand the effects of agents that target B cells, and to increase their efficacy.

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.

A new single cell detection technology allows simultaneous measurement of up to 100 surface markers and signaling proteins of immune cells. This method provides the opportunity to make great advances into the scientific understanding of rheumatic disease and the provision of individualized patient care.

New guidelines for the management of ankylosis spondylitis provide evidence-based disease management recommendations, which aim to be the ideal standard practice. How robust are these suggestions and are they applicable to the worldwide community of rheumatologists practicing in very different clinics around the globe?

A new patient self-assessment tool shows promise as a simple measure of the overall impact of rheumatoid arthritis on a patient, but will it be able to gain the international acceptance required to become a clinical standard?

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.

Joint injury represents a major risk factor for the development of osteoarthritis, but a link between severity of injury and the level of cartilage damage is difficult to test in humans. However, promising advances in our understanding of this relationship have been made with the aid of animal models of joint injury.

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.

The assessment of children with juvenile idiopathic arthritis is a challenge for the clinician, in particular with regard to the ability to elicit patients' subjective values. The development of a new tool that provides an efficient and thorough overview of a patient's status could provide an important step forward.

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.

A proportion of patients with lupus nephritis, a serious complication of systemic lupus erythematosus, progress to end-stage renal disease (ESRD). Despite major advances in treatment, the results of two new studies show that the incidence of lupus nephritis-associated ESRD has increased and outcomes have not improved in recent years.

A vast quantity of individual-level molecular data, including gene expression and genetic variation data, has become available in the past decade. Sirota and Butte discuss how integrative computational strategies can be applied to analyze this data across different rheumatic and autoimmune disorders. They outline the implications of such analyses, and discuss the current challenges and future directions of these approaches.

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.

New data unexpectedly suggest that sera from patients with PR3-ANCA-associated vasculitis are less reactive than those of healthy controls to the 'antisense' product of the PR3 gene. How does this result fit with the theory of autoantigen complementarity, and the proposed role of anti-idiotypic antibodies in the development of ANCA-associated vasculitis?

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.