Reviews & Analysis

Complex interactions between obesity, which can predispose to the development of osteoarthritis (OA), and OA, which can curtail weight-management efforts, challenge the managing physician. Nevertheless, weight loss is possible—and advisable—at all stages of the disease. Anita Wluka and colleagues unpick the interconnections between obesity and OA, review strategies for weight loss, and call for a societal approach to the management of these comorbid conditions.

Despite exciting progress in the understanding and treatment of gout, management of this condition remains suboptimal. In the face of this inadequacy, new guidelines provide recommendations both for therapeutic approaches to hyperuricaemia and for the management and anti-inflammatory prophylaxis of acute gouty arthritis.

Advances in imaging have improved our understanding of the relationship between pathology and the structural changes to joints affected by osteoarthritis. New research indicates that subchondral bone marrow lesions might represent a potential imaging biomarker to quantify such structural changes.

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.

The tremendous improvements in the survival of patients with systemic lupus erythematosus (SLE) in the past several decades have led to increased prevalence of lupus-related organ damage in these patients, which has slowed down the survival improvement and reduced the quality of life of patients. Anselm Mak and colleagues discuss the global pattern, potential mechanisms and advances in tools for early detection of organ damage.

New data demonstrate that cobalt ions promote immune system activation through Toll-like receptor 4 signalling. This finding adds to our understanding of the adverse innate and adaptive immune reactions evoked by debris released from metal-on-metal total or resurfacing joint replacement implants, which have provoked recommendations against their use.

The emphasis placed on HLA-B27 positivity in classification criteria for axial spondyloarthritis has generated some concern over potential misclassification of patients with chronic back pain. The results of a recent study suggest that these worries could have some foundation, at least in regions with high HLA-B27 prevalence.

Identifying facet joint pathology as the source—as it frequently is—of neck or back pain involves the use of diagnostic blocks, which also aid in selecting patients who will respond to radiofrequency denervation treatment. How best to administer and interpret the results of anaesthetic injection blocks are described in this Review, alongside current shortfalls and future prospects in the clinical management of facetogenic pain.

In the wake of publication of clinical data for new drugs in the management of lupus nephritis, European rheumatology and renal societies have issued new recommendations for management of this condition. Coming hot on the heels of American guidelines, how does this latest advice compare?

Physical activity is paramount in the treatment of juvenile fibromyalgia, although some interventions use indirect methods to increase activity levels rather than address physical dysfunction head-on. New research explores the effects of a psychotherapeutic approach on levels of physical activity in adolescents with fibromyalgia.

Arthropathy is a common manifestation of systemic lupus erythematosus (SLE), but remains poorly understood. Recent ultrasonographic evidence demonstrating high levels of joint and tendon pathology in SLE challenges our previous concepts of arthritis subtypes in this multisystem 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 association between coagulation and the immune system has been increasingly recognised to have a role in the development of inflammatory rheumatic diseases. The fact that the risk of venous thromboembolism is increased in patients with rheumatoid arthritis (RA) and citrullinated fibrinogen is an early autoantigen in RA indicates an adaptive immune response to coagulation factors in inflammatory rheumatic diseases. In this article, Hoppe and Dörner describes the pathophysiology of an induced procoagulatory state in inflammatory rheumatic diseases, discussing the roles of endothelial cell and platelet activation, and coagulation and fibrinolytic systems, and providing insights into future research for innovative therapeutic interventions.

Fibroblast-like synoviocytes (FLS) are cellular effectors of the inflammatory milieu that characterizes and precedes joint destruction in rheumatoid arthritis (RA). But what role do these cells have in creating the same environment to which they respond? Bottini and Firestein delve into the double life of FLS in RA pathogenesis.

The peripheral nervous system has a complex and important role in regulating the immune system. With a focus on the sympathetic nervous system, the authors of this Review discuss evidence for neuroimmune regulation of the inflammatory response in the context of autoimmune arthritis.

Anaemia as a result of chronic inflammation is common in patients with rheumatic disease. In this Review, Weiss and Schett provide a broad overview of the topic, covering the pathogenesis, diagnosis, treatment and management of anaemia in inflammatory rheumatic disease, offering practical guidance for clinicians.

The management of patients with systemic sclerosis (SSc) is often challenging. As curative therapies are not yet available, the current goal in clinical practice is prevention of disease progression and end-organ damage. In this Review, the authors discuss approaches to screening patients with SSc for internal organ involvement and monitoring disease activity, as well as the management of patients with SSc and specific complications, including interstitial lung disease, pulmonary arterial hypertension and gastrointestinal disease.

Spinal osteoarthritis primarily manifests as disease of the facet joints of the posterior spine. This Review presents the latest information about the prevalence, presentation, and nature of facet joint osteoarthritis, an important cause of spinal pain that should be viewed as failure of the whole joint rather than a disease of articular cartilage loss and bony hypertrophy.

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.