Reviews & Analysis

Biologic therapies, which have transformed the treatment of rheumatoid arthritis (RA) in the 21^stCentury, have the potential to modulate immune responses and thus are associated with a risk of infection, as well as other adverse events. This Review summarizes the available safety data for all such agents approved for the treatment of RA, to assist clinicians in weighing potential risks and therapeutic benefits.

Assigning osteoporosis treatment on the basis of bone mineral density alone is difficult, and incorporating even simple clinical risk factors into the decision-making process is challenging. When launched, the FRAX^® risk assessment tool was met, unsurprisingly, with both enthusiasm and skepticism; despite improvements, some obstacles still prevent its universal implementation.

Systemic sclerosis is associated with a high level of patient mortality. A promising prognostic model that could enable more effective management and improve survival was recently validated; however, the results demonstrate that choosing the best cohorts for development and validation of predictors of mortality is essential.

Developmental processes are emerging as a key element in the etiology and pathogenesis of osteoarthritis. In this Review, the authors describe the latest supporting evidence that links skeletal development with osteoarthritis, including the roles of chondrogenesis, patterning and joint formation in cartilage development and predisposition to osteoarthritis, and chondrocyte hypertrophy in cartilage degeneration.

Dermatomyositis is a connective tissue disease within the group of idiopathic inflammatory myopathies. Although juvenile and adult dermatomyositis share some disease features, they differ in several key aspects. In this Review, Robinson and Reed discuss the unique characteristics that differ between juvenile and adult disease, including clinical features, pathogenesis and treatment.

Neutrophils, increasing evidence suggests, play an important part in the development and perpetuation of autoimmunity in patients with systemic lupus erythematosus (SLE). In this Review, the author highlights defects in the phenotype and function of SLE-derived neutrophils. Intriguing links between aberrant neutrophil death, production of proinflammatory mediators, and the presentation of and response to autoantigens are explored. The potential contribution of defective neutrophil activity to organ dysfunction is also discussed.

Repair of bone erosions in rheumatoid arthritis has been considered a difficult goal to achieve. However—with better therapies at hand to control synovial inflammation—sensitive μCT imaging techniques now available confirm that repair of bone erosion is possible, and begins at the base of erosive lesions.

The diverse clinical symptoms associated with systemic lupus erythematosus (SLE) probably reflect its complex genetic underpinnings. Evidence from a new study indicates that analysis of common risk alleles can predict susceptibility to several end-organ manifestations of SLE, which could influence patient screening and support personalized approaches to treatment.

Advances in our understanding of bone remodelling have revealed a number of potential therapeutic targets in metabolic bone disorders such as postmenopausal osteoporosis. In this Review, Dr Michael Lewiecki describes these novel targets and the relevant experimental therapies that are at various stages of clinical development.

'Re-setting' autoimmunity through autologous hematopoietic stem cell transplantation is undergoing extensive clinical testing. A small randomized clinical trial in patients with systemic sclerosis now reports positive outcomes in all those treated with the therapy, compared with those receiving cyclophosphamide. Nevertheless, major questions about toxicity and long-term efficacy remain unanswered.

An individual's risk of developing cardiovascular disease is somewhat dependent on their ethnic origin, and is increased by the presence of inflammatory rheumatic disease. However, little is known about the relative contributions of ethnicity and rheumatic disease activity to a patient's overall risk of cardiovascular morbidity and mortality. This Review explores known risk factors for, surrogate markers of, and the epidemiology of heart disease in Asian and non-Asian patients with rheumatic diseases.

Untreated psoriatic arthritis can have severe long-term consequences, and patients benefit from early intervention. The disease typically presents as psoriasis initially, so dermatologists are ideally placed to manage such interventions, and should coordinate with rheumatologists to ensure optimum patient care. Treatment guidelines and assessment tools from dermatology consortia are among the patient management aspects discussed in this Review.

Periprosthetic osteolysis is a common reason for failure or revision of joint replacement surgery, and is a result of the inflammatory reaction to debris particles generated by wearing of the implant over time. In this Review, the authors describe the cellular and molecular mediators of this process and how it might be prevented or treated.

Rituximab has emerged as an alternative to cyclophosphamide for remission induction in anti-neutrophil cytoplasmic antibody-associated vasculitides, with recommendations now developed to direct its use in these diseases. However, data from extended clinical trials are required to determine whether rituximab is safer or more efficacious than cyclophosphamide in the long term.

Irksome to debilitating, fatigue is a frequent symptom of rheumatoid arthritis (RA). Patients regard it as an important, neglected facet of the disease. An analysis of the effect of biologic therapies on fatigue has yielded disappointing results—do current treatments lack efficacy, or are we failing to measure adequate parameters?

Systemic lupus erythematosus is frequently associated with neuropsychiatric syndromes, which can have a serious impact on the quality of a patient's life. Several methods are used to characterize cognitive impairment in these patients; however, studies have identified flaws in these assessments, highlighting the careful consideration needed when undertaking neuropsychological testing.

The microbes that inhabit our bodies play an important part in regulating the homeostasis of the immune system—disequilibrium in this symbiotic relationship can lead to development of disease. In this Review, the authors present an overview of the historical evidence implicating microbes in the development of rheumatoid arthritis (RA), and describe how the use of DNA sequencing techniques and germ–free animal models of disease are elucidating the role of host–microbial interactions in the pathogenesis of RA.

Who will not respond adequately to traditional DMARDs? Which patients would benefit most from expensive, sometimes-effective biologic agents, and who is most likely to experience adverse events? Although firm answers to these questions are pending, pharmacogenetic studies offer insight into how an individual's genetic identity determines the metabolic fate and outcome of drug therapies. In this article the authors summarize the extent of such knowledge in rheumatology today, and discuss the hurdles remaining before the ultimate goal of personalized therapy can be achieved.

Cyclo-oxygenase (COX) inhibitors are associated with increased cardiovascular risk, and are, therefore, contraindicated in patients with a previous myocardial infarction (MI). Although NSAIDs might induce a similar cardiovascular risk, some guidelines suggest that they can be administered safely for a short period of time. But is this really true?

Early symptoms of arthritis either resolve spontaneously or progress into erosive disease; being able to predict the disease course would inform decisions about intensive early therapy. One predictive factor, according to a new multicenter study, is the season of first symptoms—so how does the Earth's movement influence disease progression?