Reviews & Analysis

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.

Takayasu arteritis is an understudied disease but a recent article emphasizes the heavy burden it imposes on patients. New assessments devised to improve disease understanding are based on physicians' concepts of disease severity. However, wide differences exist between patient and physician priorities and more work is now needed to improve patient quality-of-life.

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.

Clinical findings and responses to biologic agents are increasing the evidence that undifferentiated spondyloarthritis (SpA) may represent the earliest stage of ankylosing spondylitis and psoriatic arthritis. New results also lend support to the hypothesis that the SpA spectrum represents one clinical condition, but hurdles in improving classification and diagnosis remain.

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.

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.

Recent progress in our understanding of the pathogenesis of primary Sjögren's syndrome (pSS) and the development of indices to measure disease activity in patients with this condition, offer us ample possibilities for treatment with biologic DMARDs. New biomarkers further aid selection of patients with pSS for appropriate treatment options.

Consensus guidelines for patient management can increase disease awareness and education, and facilitate evidence-based clinical decision-making. Nevertheless, new gout recommendations leave a 'déjà vu' impression. Novel evidence from clinical trials is needed to robustly advance patient care and build the next generation of guidelines.

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.

The mind and body are thought to interact in a manner that influences health, but modelling the right aspects of each so as to best inform treatment is a tricky proposition. A new study discusses how stress can affect rheumatoid arthritis symptoms.

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.

In this Review, the authors analyse the genetic loci associated with osteoarthritis to identify biological pathways that might be involved in the disease pathogenesis. In particular, they highlight the potential importance of certain regulators of skeletogenesis, endochondral ossification and gene transcription in this disease.

An incident fracture sustained during treatment for osteoporosis does not necessarily represent treatment failure, an outcome that was redefined in 2012. Predictors of the new definition have now been reported and include ≥2 falls within the past year. Preventing fractures in the most at-risk patients, however, requires improved management strategies.

Clinicians now have the therapies and outcome tools to implement treat-to-target strategies aimed at achieving and maintaining adequate function and control of symptoms in spondyloarthritis and psoriatic arthritis. However, validation of surrogate markers of structural progression is a prerequisite for treat-to-target strategies aimed at improving long-term outcomes such as joint damage.