Reviews & Analysis

Since the 1990s, patients with rheumatoid arthritis have been treated with at least one DMARD. Methotrexate, which is usually the first-line treatment, elicits good or even excellent clinical results in 20–30% of patients—but in most patients it does not. Thus, an important question is what to do after methotrexate failure.

Skeletal abnormalities of the hip can place unnecessary stress on structures within the hip. One of these abnormalities, in which the head of the femur develops a cam-shaped outgrowth, has been associated with the subsequent development of osteoarthritis. In this Perspectives, the etiology of cam abnormalities and their contribution to osteoarthritis are discussed.

Nanotechnology, building on advances in nanoscience, has developed substantially over the past decade. In this Review, Cameron Brown outlines applications of nanotechnology that are advancing understanding in rheumatology and musculoskeletal research, including labelling, imaging and targeting techniques used to probe and manipulate cell behaviour. Nanoscale therapeutics might also enter the rheumatology clinic in future, but the potential for adverse events must first be explored; data accumulated in life-threatening illnesses will inform developments for chronic conditions.

Encouraging data from preclinical studies, and ongoing clinical trials, suggest that mesenchymal stem cells (MSCs) might provide the disease-modifying therapy that has long been lacking in osteoarthritis. If the potential of these multipotent cells is to be fully realized, subtleties such as minor phenotypic differences between specific MSC populations as well as the paracrine responses that transplanted MSCs elicit from joint-resident cells, must be better understood. MSC-related changes that occur in OA, the regenerative capacity of transplanted MSCs, and progress toward clinical use of such therapy are reviewed in this article.

Beneficial effects of bone-acting drugs in osteoarthritis (OA) are increasingly reported, but reliable conclusions regarding their efficacy are hindered by methodological drawbacks in study design. Identifying patients with osteoporotic OA, a phenotype defined by decreased density associated with high remodelling in subchondral bone, might improve the success of bone-directed agents.

In the past decade, knowledge of the pathogenesis of primary Sjögren's syndrome and the lymphomagenesis associated with this disease has advanced considerably. This Review summarizes our current understanding of these processes, highlighting the importance of crosstalk between the innate and adaptive immune systems.

A number of issues limit the utility of the definitions and classifications of autoinflammatory disease proposed to date. In this Perspectives, the authors propose a new clinically-based definition and classification of autoinflammatory diseases. In addition, a potential future approach to classification of the entire spectrum of immunological diseases is discussed.

Systemic lupus erythematosus (SLE) is a heterogeneous condition characterized by a wide range of symptoms, rendering its diagnosis an often difficult task. In this article, the authors highlight the current approaches and challenges in SLE diagnosis, propose an algorithm to facilitate this process, and argue for the development of endorsed diagnostic criteria.

Many advances in the treatment of juvenile idiopathic arthritis have been underpinned by the development of organizations such as PRINTO and PRCSG. This Perspectives provides a timeline for these advances, including clinical trial designs and diagnostic criteria essential to performing research in this small group of patients whose age necessitates a cautious approach to treatment.

Biologic medications are highly efficacious in juvenile idiopathic arthritis. However, a recent study found that a subgroup of children treated with anti-TNF agents had persistent pain despite good disease control. This finding highlights the importance of monitoring pain symptoms during treatment with modern DMARDs.

Fibromyalgia is a controversial condition, and opinions are divided over whether psychocultural factors explain fibromyalgia content or whether it is largely a product of disordered central pain processing. In this article, Wolfe and Walitt describe how the definition of fibromyalgia has changed during its history, and discuss the factors that have enabled it to persist despite the ongoing debate.

Vaccinating children with underlying rheumatic diseases is important to reduce their risk of acquiring infectious diseases. These vaccines are safe to use in this patient group, with the exceptions of profoundly immunosuppressed pateints or those with malevonate kinase deficiency. Some vaccines also induce lower than normal immune responses in these children.

The ankylosing spondylitis disease activity score (ASDAS) is a measure of axial spondyloarthritis (SpA) disease activity endorsed by the Assessment of SpA International Society and Outcome Measures in Rheumatology. Accumulating evidence supports the utility of ASDAS in axial SpA. So, is it time to replace the Bath ankylosing spondylitis disease activity index (BASDAI)?

Prevention and recognition of mycobacterial disease is of increasing importance to the practicing rheumatologist. Tuberculosis remains a well-known problem for patients and clinicians wishing to use immunosuppressive therapies. Less well recognized, and yet perhaps more important to consider in this context, is nontuberculous mycobacterial disease. Epidemiological data and mechanistic explanations for the increased risk of mycobacterial infection in patients with RA are reviewed herein, and appropriate strategies to prevent and manage these comorbidities are outlined.

Imaging is central for the classification and diagnosis of axial spondyloarthritis, as well as for monitoring disease progression and predicting response to treatment. Xenofon Baraliakos and Jürgen Braun provide an overview of the role of imaging for patients with axial spondyloarthritis and discuss how imaging techniques might influence research and clinical practice in the future.

The population of elderly patients with rheumatoid arthritis (RA) is growing, primarily as a consequence of increasing life expectancies. In addition, processes linked to ageing of the immune system might directly contribute to development of this disease. This Review discusses the evidence supporting this hypothesis, as well as the challenges facing management of RA in elderly patients.

Despite having increased cardiovascular risk, patients with rheumatoid arthritis (RA) often have low serum cholesterol levels. In this Review, the authors discuss this putative 'lipid paradox', highlighting the relationships of inflammation and anti-inflammatory therapy with lipid profiles in RA.

Periarticular bone erosions are a central feature of rheumatoid arthritis (RA) and their exact assessment is crucial for diagnosis, monitoring responses to therapy and aiding decision-making. High-resolution peripheral quantitative CT and MRI—two imaging modalities with the potential to improve the diagnosis and monitoring of RA—have now been compared.

Multiple genes have been associated with susceptibility to systemic lupus erythematosus (SLE), but how do they promote disease development? In this Review, the authors examine the roles of a selected set of genes in the pathogenesis of SLE, and discuss how epigenetic modifications and microRNAs can mediate pathogenic changes in gene expression.

When nonsurgical options for osteoarthritis of the glenohumeral joint are exhausted, total shoulder arthroplasty has been well studied and carries the most predictable outcome. For patients wishing to remain active, however, proven shoulder-preserving options have been less predictable. A new study now adds to preliminary evidence supporting the complete arthroscopic management procedure.