Reviews & Analysis

2013 has witnessed the maturation of imaging science with rheumatology research, in part due to large, public databases. Using imaging in osteoarthritis (OA) as an example, breakthroughs include further elucidation of the relationship between obesity and OA, and identification of the importance of bone and meniscus shape in OA development.

Concerns have been raised over an association between biologic agents used in the treatment of rheumatoid arthritis (RA) and noninfectious serious respiratory adverse events, particular in patients with pre-existing RA-associated interstitial lung disease (RA-ILD). In this Review, the current evidence regarding the comparative pulmonary safety of the available biologic therapies is discussed and a framework to guide treatment decisions is provided. The authors also identify the considerable gaps in our understanding of the associations between biologic agents and RA-ILD, and propose a research agenda aimed at addressing them.

Clinical, basic and translational research in systemic lupus erythematosus are fast-moving fields. 2013 has seen the publication of some potentially landmark papers, which not only explore the potential of novel agents but also glean new insights from past trials.

New studies demonstrate the development of anti-flagellin antibodies in patients with ankylosing spondylitis. Does their presence point to mucosal dysregulation as a pathogenic mechanism of the disease?

Rheumatoid arthritis is associated with a number of extra-articular complications, including inflammatory ophthalmological manifestations. In this Review, the authors describe the key features of episcleritis, scleritis and peripheral ulcerative keratitis in the context of rheumatoid arthritis, as well as provide insights into the management of each condition.

The 2013 update of the EULAR recommendations for the treatment of rheumatoid arthritis has evolved in several domains, and has, for the first time, elevated non-TNF-inhibitor biologic agents to the same status as TNF inhibitors. These transparently derived and scholarly recommendations will contribute to the evolving dialogue on the proper use of these agents.

Autoantibodies associated with systemic lupus erythematosus are also frequently observed in apparently healthy individuals. In this Opinion article, the authors consider the implications of this benign autoimmunity with regard to the normal immune response and the development of disease.

Awareness of IgG4-related disease, which shares many clinical, and potentially pathogenetic, similarities with certain rheumatic disorders, is increasing worldwide. This Review provides an overview of this disease entity, with particular focus on pathogenesis, clinical features, diagnosis and treatment, for the benefit of rheumatologists, who are increasingly likely to be involved in the diagnosis and management of patients with IgG4-related disorders.

In 2013, much progress has occurred in gout research. Imaging continues to help elucidate aspects of pathophysiology and now suggests that healing of erosions could occur when urate levels are reduced dramatically. New genetic loci associated with hyperuricaemia have been identified and management strategies for prophylaxis of gout flares continue to evolve.

Autoantibody testing is key for the diagnosis, classification and management of systemic autoimmune rheumatic diseases; however, issues regarding the reproducibility and reliability of these tests currently limit their usefulness. Approaches to harmonize autoantibody tests, including the development of technical guidelines and the availability of suitable reference materials for calibration and quality control, are discussed in this Review.

Juvenile-onset fibromyalgia (JFM) is a complex chronic pain syndrome that can have debilitating effects, but is poorly understood. Here, the authors provide a timely update on the current research in JFM, outlining the latest understanding in the clinical characteristics, prognosis, pathophysiology and management of this condition.

Evidence of possible molecular crosstalk between inflammation and insulin resistance suggests that treatments for diabetes might be useful in patients with rheumatoid arthritis (RA), or vice versa. However, in a new trial of a PPARγ agonist in RA, the clinical effect was at most modest. So, does such an approach have a future?

Autoinflammatory diseases are associated with abnormal activation of the innate immune system and resultant inflammation. Here, the authors provide a clinical and practical guide to autoinflammatory diseases, describing classification, insights into pathogenesis, diagnosis and management of these conditions.

The association of environmental dietary factors and polymorphisms of urate transporters with an increased risk of gout has been well established. Nevertheless, the influence of genetics and diet on serum urate concentrations, and the clinical relevance to individual patients, seems to be limited.

Musculoskeletal ultrasonography is a routine diagnostic tool in rheumatological practice. The technique has only recently been used to evaluate articular and periarticular structures. In systemic sclerosis, different aspects of hand and wrist involvement have now been described, offering hope for the transfer of ultrasonography for this condition to the clinic.

Mesenchymal stem cells (MSCs) have shown some degree of therapeutic benefit and MSC-based therapies are currently offered at many centres worldwide; nevertheless, firm scientific evidence of the effectiveness and safety of such therapies is severely lacking, and a number of issues regarding the characterization and manipulation of MSCs remain to be adequately clarified. Alan Tyndall discusses these issues and provides his opinion on the optimism shown to such therapies to date.

Although advances in therapy of rheumatoid arthritis (RA) have greatly improved disease outcomes, a considerable portion of patients still do not attain clinical remission. Thus, new treatments targeting a range of cytokines and cell types are being explored. This Review outlines these novel approaches to RA therapy.

Pulmonary arterial hypertension (PAH) is a lethal complication in connective tissue diseases (CTDs) with varying frequency of occurrence; the highest incidence is in systemic sclerosis. Data for PAH screening by echocardiography in other CTDs are not strong. Should we only investigate symptomatic patients or perform regular screening for PAH in CTDs?

Giant cell arteritis (GCA) is the most frequent form of large-vessel vasculitis. In this Review, Weyand and Goronzy discuss the aberrant immune pathways that underlie medium and large-vessel vasculitis, focusing on new understanding of the IL-6–IL-17 and IL-12–IFN-γ cytokine clusters in the development of GCA. Immunostromal interactions are introduced as mechanisms of tissue tropism and disease amplification, and therapeutic interventions targeting vascular instead of immune cells are considered.

If a drug is intended to work in a joint, then direct injection seems likely to be an appropriate route of delivery, to minimize adverse events and limit the amount of therapeutic agent required. Ensuring such a drug remains in the joint long enough to produce an effect, however, is another matter. Successes seen, lessons learned, and developmental prospects in intra-articular therapy are explored in this Review.