Reviews & Analysis

Studies of mouse models of lupus provided the rationale for targeting BAFF in the treatment of patients with systemic lupus erythematosus, and could also help explain why individuals might differ in their response to this therapeutic approach.

Treatment guidelines are an increasingly prominent topic of discussion in medicine. Can rheumatologists avoid the 'fatal flaw' inherent in attempts to standardize treatment decision-making—in which overly strict adherence to guidelines might be pursued at the expense of optimizing individual patients' outcomes?

Regulatory T (T_REG) cells, which function as suppressors of autoimmune responses, are defective in patients with rheumatoid arthritis (RA). In this article, the authors describe the interplay between T_REG cells and inflammation in the context of RA, and how a subset of highly potent but unstable T_REGcells seems to be induced following tumor necrosis factor blockade.

Biologic agents are emerging as an important treatment for juvenile idiopathic arthritis (JIA), but the long-term safety of these therapies is a major concern and currently not completely understood. This Review examines available data for the safety of biologic therapies for JIA and details the serious adverse events associated with each agent as well as outlining the safety issues that need further study.

Pregnancy in women with systemic lupus erythematosus (SLE) can be associated with substantial morbidity and mortality for both the mother and the unborn fetus. Findings from several studies have indicated that CD4⁺CD25⁺regulatory T cells have an important role in supporting a healthy pregnancy. In this article, the authors provide an overview of how regulatory T cells function in both SLE and pregnancy, as well as providing an insight into how therapeutic agents that induce these cells could promote successful pregnancy in women with SLE.

The mechanical effect of excess weight is commonly thought to be the direct cause of osteoarthritis. In this Perspectives article, the author questions whether the evidence actually supports this prevalent view, and instead proposes that the increase in adipose tissue associated with obesity might drive the development of widespread osteoarthritis.

The role of the transcription factor NFκB in osteoclasts and bone degradation is well understood. In this Perspectives article, the authors discuss its newly described inhibitory function in osteoblasts and bone formation, and how therapies that target NFκB might be beneficial in osteoporosis and other inflammatory bone diseases.

Morphological and functional assessments of the cutaneous microvasculature have important roles in the diagnosis, prognosis and therapy of systemic sclerosis and secondary Raynaud phenomenon. The implications of these evaluations, in particular nailfold videocapillaroscopy and laser Doppler imaging, are discussed in this Review.

Heterotopic ossification is the formation of extraskeletal bone within soft tissues in the body. In two inherited heterotopic ossification disorders, fibrodysplasia ossificans progressiva and progressive osseous heteroplasia, specific gene mutations have been identified and, as outlined in this Review, result in aberrant bone formation and abnormal regulation of cell-fate signaling pathways in patients with these disorders.

Technological innovations have contributed greatly to advancing our knowledge of the genetic basis of osteoporosis. This article reviews the current understanding of osteoporosis genetics with a focus on developments since 2007. The potential clinical implications of this information and future directions for research are also discussed.

Sjögren's syndrome (SS) is a chronic autoimmune disorder that affects the exocrine glands, but the pathogenesis of this disease is not fully understood. This Review article describes the available evidence on the important pathogenetic mechanisms involved in the development of SS with a particular focus on how the disease is initiated and perpetuated. The authors also discuss the disease outcome and survival of patients with SS.

Pediatric-onset systemic lupus erythematosus (pSLE) is associated with higher disease severity and damage accrual compared with adult-onset SLE. In this Review, the authors describe specific features of pSLE, including epidemiology, disease activity and outcomes, and the effects of the disease on patients' quality of life, bone health and comorbidities.

A systematic review of randomized controlled trials reveals some differences in the effects and indications of the three pharmalogical treatments for fibromyalgia. What can prescribing physicians glean from the results?

Tapering or even discontinuation of drug therapy for rheumatoid arthritis is a desirable goal, given patient preferences in addition to safety and financial concerns, but the implications of this approach are far from clear. A multicenter study conducted in Japan has explored whether stopping treatment with a tumor necrosis factor inhibitor is a viable option once a state of low disease activity has been attained.

Early diagnosis is critical to reduce the risk of visual impairment in patients with giant cell arteritis. A report on the guidelines for the management of this disease offers practical recommendations; however, further efforts that incorporate collaborative multicenter studies might be needed to reach agreement among clinicians.

The mechanisms involved in musculoskeletal pain include peripheral and central sensitization, the latter of which might cause the chronification of widespread pain conditions. These mechanisms are discussed in this Review, along with methods to assess muscloskeletal pain, such as pressure algometry, cuff-algometry and repeated pressure stimulation.

After decades during which little has changed with respect to the therapeutic options available to clinicians treating patients with lupus nephritis, the use of targeted biologic agents is emerging as a possible treatment strategy. The authors discuss the potential of these agents, including both B-cell-directed and T-cell-directed therapies, and consider the specific circumstances in which they should be used, either alone or combined with conventional or other new therapies.

The persistent inflammation in patients with rheumatoid arthritis can cause cardiovascular disease and accompanying morbidities. The role of rheumatoid cachexia in this process is unknown, owing in part to the lack of an accepted operational definition. In this Review, the authors provide an update on rheumatoid cachexia, which they suggest represents the 'worst of both worlds' with respect to cardiovascular outcome due to the convergence of high grade inflammation and obesity.

The onset of spondyloarthropathy extends well into the pediatric age range, with most cases of the juvenile form of the disease being classified as enthesitis-related arthritis. This Review summarizes the clinical features, genetic susceptibility factors and outcomes of juvenile spondyloarthritis, and discusses some of the issues around the approach to the classification of this disease in adults and children.

The nonbiologic DMARD leflunomide was approved for use in the treatment of rheumatoid arthritis in 1998. After being in use for more than a decade, which has also seen the introduction of highly effective biologic agents, a review of the benefits and risks of leflunomide therapy sheds light on the role of this drug in the treatment arsenal.