Reviews & Analysis

Advances in the therapeutic management of systemic lupus erythematosus (SLE) have greatly improved life expectancy in patients with this disease, exposing their increased risk of cardiovascular disease (CVD) compared with the general population. In this Review, the authors discuss the influence that pathogenic processes and therapeutic interventions might have on the accelerated atherosclerosis observed in patients with SLE, as well as the potential approaches to reduction of CVD risk in these individuals.

Allocation of therapy for systemic lupus erythematosus (SLE) remains complex, as most drugs used to treat this disease are used off-label—a situation compounded by the emergence of new therapeutics. In this rapidly changing clinical setting, organ-specific therapeutic guidelines might be useful for 'real world' management of patients with SLE.

Increasing evidence implicates metabolic dysfunction in the development and progression of osteoarthritis (OA). Large-scale 'omics' studies, particularly metabolomics, have the potential to answer many questions relating to the pathogenesis of so-called 'metabolic OA' and other OA phenotypes, and could be key to the identification of novel biomarkers for these conditions.

Patients with systemic sclerosis (SSc) are at considerable risk of developing pulmonary arterial hypertension, which has a dramatic impact on the natural history of the disease and overall survival of the patient. Modern imaging modalities, such as novel echocardiographic techniques and cardiac MRI, are highly sensitive, quantitative and reproducible methods that allow noninvasive assessment of regional and global myocardial performance without relying on geometric assumptions. In this Review, the authors describe the standard clinical tests and evolving technologies, which can provide comprehensive and quantitative data on myocardial status that are useful in the clinical management and evaluation of patients with SSc.

Highly specific for rheumatoid arthritis (RA), anti-citrullinated protein antibodies (ACPA) are emerging as suspects in the disease pathogenesis. Do these autoantibodies define a subtype of RA, how does their presence and maturation relate to the course and characteristics of the disease, and how can we use them to improve patient outcomes? Essential facts about ACPA are explained in this Review.

HMGB1 is a non-histone nuclear protein that can serve as an alarmin to promote inflammation. In this Review, the authors present an overview of the structure and function of HMGB1. They also describe the role of HMGB1 in autoimmune and inflammatory diseases, including rheumatoid arthritis and systemic lupus erythematosus.

The interplay between the cells that regulate bone architecture and the immune system is increasingly recognized. In this Review, as well as providing an overview of fracture treatment and healing, the authors discuss our current knowledge of the part played by inflammation in the fracture repair process. The influence of biomechanical and biological factors on bone healing is also considered, focusing on the effects of excessive local and systemic inflammation, as occurs in autoimmune diseases such as rheumatoid arthritis.

The role of inflammation in rheumatoid arthritis (RA) is well characterized, but how hypoxia affects RA and the potential interplay between inflammation, angiogenesis and hypoxia in this disease is less defined. Here, the authors describe how hypoxia affects RA, in terms of both inflammation and angiogenesis, and provide insights as to how depleted oxygen levels affect the RA synovium. Potential therapies for RA that target angiogenesis will also be discussed.

In the two decades between publication, in 1990 and 2010, of the American College of Rheumatology criteria for fibromyalgia, research proliferated and substantial headway was made in understanding this complex, chronic disorder. So what was learned in the wake of the 1990 criteria, and how are the 2010 criteria changing the landscape of research, understanding and management, in patients with fibromyalgia?

Radiographic joint damage is strongly associated with disability in patients with rheumatoid arthritis, but the relative importance of the two major measures of radiographic damage—bone erosions and joint space narrowing—is not clearly understood. In this article, the authors discuss this issue, and describe how imaging modalities that allow detailed visualization of cartilage might lead to improved understanding.

Patients over the age of 50 years who present with a fracture seem to have the highest risk of subsequent fracture and also mortality immediately after the initial fracture is incurred. In this Review, the authors summarize the evidence that demonstrate this trend and discuss the factors that influence fracture risk. Finally, they propose a five-step systematic approach to management of patients who present with a fracture, aimed at preventing subsequent fracture, decreasing mortality rates and reducing undertreatment or overtreatment.

That primary osteoarthritis (OA) is an age-related disorder is undoubted, but how aging contributes to OA is poorly understood. New insights from 2011 offer potential explanations, novel models for study, and the suggestion that a deeper understanding of what 'aging' actually is might pave the way to everlasting joints.

In 2011, the year that subtypes of ANCA-associated vasculitis (AAV) were officially renamed according to key pathological characteristics, important progress was made not only in differentiating these subtypes, but also in understanding—and treating—their eponymous manifestations.

In 2011, new treatment recommendations for juvenile idiopathic arthritis (JIA) were proposed, inroads were made towards understanding the heterogeneity of this disease, and data were presented demonstrating the potential efficacy of DMARD combination therapies for JIA treatment. These advances hold promise for improved management of JIA in 2012 and beyond.

Evidence presented in 2011 suggests that rheumatoid arthritis might comprise two separate diseases—each with different etiological underpinnings—and that kinase inhibitors could soon be added to the therapeutic armamentarium. Together with new definitions of remission, these advances could aid the development of personalized, treat-to-target strategies.

Findings from ongoing studies of imatinib in systemic sclerosis (SSc) were eagerly awaited in 2011, but results from these clinical trials have so far been disappointing. However, progress in the understanding of the mechanisms that underlie SSc pathogenesis could provide clues to novel targets for 2012 and beyond.

From neutrophil extracellular traps to genetic networks that underlie the disease and new targeted therapies, important advances in 2011 improve our understanding of the pathogenesis of systemic lupus erythematosus and mark the beginning of our ability to treat it effectively.

Susceptibility to osteoarthritis (OA) is influenced by genetic mutations, many of which occur in genes associated with the development of synovial joints. In this Review, Linda Sandell proposes a theory that these mutations can be placed on a continuum—from obvious alterations that result in mild chondrodysplasia associated with early-onset OA to subtle changes that predispose to 'primary OA' later in life. This view is explained in the context of our current etiological understanding of OA, and how this knowledge could improve screening and treatment of patients is discussed.

Advances in the fields of cell biology and imaging have allowed researchers to dig deeper into the underlying mechanisms of joint damage in patients with tophaceous gout. This Review describes some of the recent advances in our understanding of bone erosion and cartilage damage in this disease.