Reviews & Analysis

Biomarkers and surrogate outcome measures can be used to monitor disease development, but what can biomarkers tell us about disease processes in axial spondyloarthritis? New research suggests that some biomarkers might be useful in monitoring patients with ankylosing spondylitis, but greater understanding of the pathological mechanisms is needed.

Lessons from the study of other rheumatic diseases are improving our understanding of diffuse idiopathic skeletal hyperostosis (DISH). New data implicate Dickkopf-1 in the evolution of the most severe manifestations of the condition. Nevertheless, real insights into the pathogenesis—and treatments that might result from them—are still lacking.

Inflammatory brain disease can affect patients of all ages, and are becoming increasingly recognized. Central nervous system (CNS) vasculitis is one such disease. Here, the authors describe the current knowledge on this devastating inflammatory brain disease and provide a direct comparison of CNS vasculitis in adults and children. Clinical features, diagnosis, treatment, mimics and the spectrum of the disease are also discussed.

Peripheral neuropathy can be a manifestation of small-vessel vasculitides such as antineutrophil cytoplasmic antibody-associated vasculitis. Diagnosing vasculitic neuropathy is, however, difficult in many cases. Early treatment focused on achieving remission of the underlying vasculitic process is important as chronic neuropathy has a major influence on a patient's quality of life.

The reproducibility and reliability of ELISA assays used to detect autoantibodies that recognize cardiolipin or β₂-glycoprotein I remain unacceptable, which can complicate the diagnosis of antiphospholipid syndrome. Now, much needed international consensus guidelines have been proposed for the development and use of these diagnostic tests, which should improve their performance.

Osteonecrosis of the jaw (ONJ) is associated with high-dose bisphosphonate therapy in patients with cancer, and has also been linked to bisphosphonate use in patients with osteoporosis. In this Review, the authors examine the epidemiology and pathogenesis of ONJ.

Reactive arthritis is a form of inflammatory arthritis associated with bacterial infection. In this article, the authors describe the current state of our knowledge regardingChlamydia-induced reactive arthritis, including chlamydial persistence in joints, susceptibility factors and host and pathogen biology, and discuss future research priorities in this disease.

Hand osteoarthritis (OA) is a prevalent, heterogeneous disorder that was, until recently, often overlooked in clinical research. In this Review, the authors provide an overview of hand OA, describing the diagnosis, clinical burden, disease course and associated risk factors, with particular attention to the key features of the hand OA subsets thumb base OA and erosive OA.

New data—this time from genetic association studies—again implicate the Wnt signaling pathway in the etiology of Dupruyten Disease. Nevertheless, functional studies, and cohorts of different ethnic backgrounds, are needed to distinguish cause and effect in this enigmatic fibrosing disorder.

Measuring bone structure could improve prediction of bone strength, but the clinical feasibility of available imaging technologies is limited. The trabecular bone score—a dual-energy X-ray absorptiometry texture algorithm—has shown promise in fracture prediction in a large cohort study, and might provide a practical means of assessing bone quality.

Comorbid cardiovascular disease is a substantial problem in rheumatoid arthritis (RA). Disease-related factors such as inflammation combine with traditional risk factors to produce an interrelated excess of risk that can be pharmacologically modified. Here, the authors summarize the evidence—and knowledge gaps—regarding the influence of biologic therapies on cardiovascular risk parameters in patients with RA.

The perioperative management of patients with rheumatic diseases who are due to undergo surgical procedures presents unique challenges, such as the increased cardiovascular risk associated with these diseases, the effect on infection risk associated with drugs used for their treatment, and the altered coagulation state associated with antiphospholipid antibodies. In this Review, the authors present a decision-support system intended to aid the rheumatologist faced with this clinical scenario.

Psoriasis and psoriatic arthritis (PsA) are interrelated: PsA is a 'disease within a disease', and research into psoriasis can inform understanding of its less frequent inflammatory comorbidity. Genetic studies in both conditions are revealing substantial genetic heterogeneity in PsA, and how susceptibility, pathogenesis and treatment response are thereby affected, as summarized in this Review.

The precise role that basic calcium phosphate microcrystals have in the pathogenesis of osteoarthritis (OA) is controversial. The recent paper by Jin et al. provides new insights into the potential mechanisms that link these microcrystals to joint damage, and highlights the role of the NLRP3 inflammasome in the pathogenesis of OA.

The value of biomarkers in clinical decision marking is increasingly recognized, and numerous studies aimed at identifying or validating potential new biomarkers are underway. In this Review, the authors appraise six promising candidate biomarkers, covering diagnosis, disease activity assessment, and prognosis, in order to highlight study design features that are important for biomarker validation.

Fibrosis of the skin and other organs is a key feature of systemic sclerosis (SSc). Studies performed during the past decade have provided a more detailed insight to the cellular and immune mechanisms underlying the fibrotic process in SSc. In this Review, the authors describe these important recent findings, and how our improved understanding of SSc fibrosis has facilitated the development of potential targeted therapies.

Increasing evidence suggests that extracellular DNA plays a part in the pathogenesis of systemic lupus erythematosus (SLE) independently of the involvement of anti-DNA autoantibodies. In this Perspectives article, the authors discuss the findings that have led to this conclusion, and explore the new therapeutic avenues that this discovery has opened. Specifically, the interesting prospect of targeting treatments at the structural manipulation of extracellular DNA is introduced and the strategies for achieving this goal that have shown promise in animal studies are presented.

Targeted therapies for chronic joint diseases are now able to control many of the disease symptoms—the research focus has now shifted towards the structural damage that occurs in skeletal tissues. Lories provides a timely update on the current knowledge in osteoimmunology, with a discussion of the role of tissue repair and remodeling in chronic arthritis such as ankylosing spondylitis and rheumatoid arthritis.

The use of biologic therapies for off-label conditions in daily clinical practice is increasing, yet few studies have detailed the safety of these agents with regards to infection in patients with systemic autoimmune disease. New research offers a glimpse at the infection rates in these vulnerable patients.

Juvenile systemic sclerosis (JSSc) is a relatively rare disease compared to its adult equivalent. As a result, much of our knowledge of the disease is derived from studies in adult. Our understanding of JSSc has improved over the past 5 years, but considerable challenges remain in determining the optimal diagnostic and therapeutic protocols in these patients.