Review Articles in 2013

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.

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.

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.

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.

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.

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.

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.

Diffuse idiopathic skeletal hyperostosis (DISH) is a poorly understood condition characterized by ossification of ligaments and entheses. This comprehensive Review explains the epidemiology and clinical manifestations of DISH, as well as highlighting the latest insights into pathogenic mechanisms. The authors also argue for the development of new classification criteria that can identify early disease.

This Review presents a comprehensive guide to nonpharmacological management strategies and current therapies for systemic lupus erythematosus (SLE). The authors offer insights to help the clinician select appropriate, individualized treatments, according to disease severity, symptoms and organ involvement.

Intervertebral disc (IVD) degeneration is a common cause of back, neck, and radicular pain. High levels of a number of inflammatory cytokines that are secreted by IVD cells characterize, and are involved in the pathogenesis of, IVD degeneration. In this comprehensive Review, the authors describe the key inflammatory cytokines that are involved in different phases of disc degeneration, and they describe the outcomes of the clinical studies that have investigated blocking cytokine function.

Despite our increased knowledge of the complex pathways of immune dysregulation that occur in systemic lupus erythematosus, advanced-phase clinical trials of new biologic agents have repeatedly failed to achieve their clinical end points. In this Review, the authors discuss the progress and pitfalls that have been faced by some of the investigational treatments in this field.

What is oxidative stress and how is it implicated in the pathogenesis of systemic lupus erythematosus (SLE)? Complex molecular pathways leading to and from redox imbalance in the context of SLE, including oxidative modification of autoantigens, are reviewed in this manuscript, alongside developmental approaches that aim to tackle and/or exploit oxidative stress in the clinical management of this disease.

Platelet-rich plasma has anti-inflammatory properties and is an important source of molecules that are involved in the repair and regeneration of tissues. PRP therapy, therefore, has great potential for aiding the healing response and repairing joint damage in patients with osteoarthritis. In this comprehensive Review, the authors describe the biological processes of PRP tissue engineering as well as the novel applications and approaches of PRP therapy in the context of targeting joint degeneration.

In this Review, Malfait and Schnitzer provide an accessible discussion of the peripheral and central mechanisms involved in OA pain, and explain how NSAIDs, antidepressants and anti-NGF antibodies modulate these pain pathways to exert their analgesic effects. They propose that an enhanced understanding of such mechanisms might permit a more targeted and individualized approach to pain management in the future.

Despite substantial improvements, our current treatments for systemic lupus erythematosus (SLE) still have many limitations, so will new biologic agents be the answer? In this comprehensive Review, William Stohl discusses the myriad opportunities biologic agents provide for targeting B cells, T cells and cytokines, and their future potential in SLE therapy.

Low back pain is a common health problem that is usually attributable to mechanical disorders of the spine. In this comprehensive Review, David Borenstein outlines the usual characteristics and pathology of mechanical low back pain—from a Rheumatologist's perspective—as well as describing the available diagnostic technologies and treatment options for patients.

Biologic agents have now been studied in over 200 randomized controlled trials and 100 subsequent meta-analyses in rheumatic diseases. This Review highlights the shortcomings in the evidence derived from such studies. The authors discuss how the issues identified could be addressed in the future by revisiting trial design and improving reporting of findings; the responsibilities of the regulatory authorities, the pharmaceutical industry and academia are also debated.

Annexin A1 mediates many of the anti-inflammatory actions of glucocorticoids. This Review describes our current understanding of the biological activities of this protein and their relevance to the pathogenesis of rheumatoid arthritis (RA). The possibility that targeted approaches to potentiation of annexin A1 signalling could enable steroid sparing in RA and other inflammatory diseases is also discussed.