Opinion

Rheumatoid arthritis (RA) and metabolic syndrome share several pathologic characteristics, such as changes in body composition, lipid levels and insulin sensitivity, that may increase cardiovascular mortality. Here, Kerekes and co-authors discuss associations between these components in RA and metabolic syndrome and propose that optimal therapeutic control of RA might attenuate adverse effects of metabolic syndrome in patients with RA.

Active systemic lupus erythematosus (SLE) can manifest in heterogeneous clinical forms, making description of SLE clinical states difficult in patients with high disease activity. In this Opinion article, the authors argue the time has come to change the way SLE is managed by defining a treatment goal based on defining a low disease activity state, and they suggest possible inclusions in, and obstructions to, such a goal.

Strategies to repair damaged intervertebral discs rely on the premise that these structures can be regenerated using cellular-based approaches. Here, Huang and colleagues highlight the importance of nutrient balance for maintenance of disc cell function and question whether disc repair can be successfully achieved in degenerate human discs where nutrient supply is compromised.

With the continued focus on evidence-based medicine, new randomized controlled trials (RCTs) are needed in vasculitis to improve management of these conditions. In this Opinion article, using antineutrophil cytoplasmic antibody-associated and large-vessel vasculitis as examples, Tarzi and colleagues discuss RCTs performed to date and outline important issues in trial design and future directions for the field.

The most common symptom of osteoarthritis is pain, but current treatments do not identify or treat different types of osteoarthritis-associated pain. In this Opinion article the authors argue that some patients with osteoarthritis have neuropathic pain, and that analgesic drugs generally prescribed for neuropathic pain that is unrelated to osteoarthritis should also be used to treat this subset of patients.

The concepts of comorbidity and multimorbidity consider a patient with multiple diseases from different perspectives, which affects how a clinician approaches treatment. In this Perspectives article, Radner and colleagues discuss the concept of multimorbidity and how its integration into daily clinical practice can improve the care of patients with rheumatic conditions.

The transfer of young patients with rheumatic disease from paediatric to adult health-care provision, usually during adolescence, can have adverse effects on disease in individuals who might already be vulnerable. Herein, the authors discuss transitional health-care procedures that support and encourage young patients to take responsibility for their own health-care requirements, which might improve patient coping and disease outcomes in the long term.

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.

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.

Comparative effectiveness research (CER) takes the clinical characteristics of patients into account to determine the most beneficial treatments. Here, the methodological approaches and the analytical challenges of CER are described, as well as the considerations needed to ensure high-standards of CER in rheumatology.

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.

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.

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.

Myositis results from the combined activities of immune-specific and muscle-specific cell types. Immune muscle precursors could have a pivotal role, as they stimulate inflammation and the generation of autoantigens. Tournadre and Miossec explain this phenomenon.

The contribution of epigenetic mechanisms, primarily comprising microRNAs and modifications of DNA and histones, to rheumatoid arthritis (RA) is increasingly recognized. In this article, the authors discuss the role of the epigenetic machinery in this disease, with a particular focus on the enzymes that regulate protein acetylation, and the therapeutic potential of targeting these factors in RA. The authors suggest that returning to the original, broader definition of epigenetics, comprising all nongenetic regulatory mechanisms, might improve our understanding of disease and facilitate the development of novel therapeutic strategies.

The proinflammatory cytokine IL-17 is known to be an important factor in the pathogenesis of autoimmune joint diseases such as rheumatoid arthritis and spondyloarthritis, and therapies targeting this cytokine have shown promise. Although type 17 T helper cells are generally considered to be the main source of IL-17 in these diseases, the range of cell types that secrete this cytokine continues to expand; in particular, mast cells are receiving increased attention. Herein, the authors discuss the potential contribution of IL-17-secreting mast cells to inflammatory joint disease.

Early aggressive immunosuppressive regimens have fundamentally changed the treatment and management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). However, how to maintain remission in these patients is debated. Here, Raashid Luqmani considers how best to achieve maintenance of clinical remission in patients with AAV.

The IL-12 family cytokines contribute to immune-mediated inflammation and have an important role in determining T-cell fate. Evidence from preclinical and clinical studies suggests a role of these cytokines in the pathogenesis of rheumatoid arthritis (RA). The authors discuss these data and their potential clinical implications for patients with RA.

Small interfering RNAs (siRNAs) are a useful experimental tool to silence gene activity. The challenge, however, remains to optimize delivery and imbue 'drug-like' properties to siRNAs for therapeutic use. Here, the authors discuss advances in siRNA therapeutics and their potential application in treating rheumatic disease.