Review Articles in 2015

Fibromyalgia and complex regional pain syndrome (CRPS) share many pathophysiological mechanisms. Central mechanisms predominate in both disorders, although peripheral mechanisms such as neurogenic neuroinflammation also contribute to their clinical features, albeit to differing degrees. This article discusses the evidence suggesting that neurogenic neuroinflammation is an important and potentially targetable link between the two disorders.

Ultraviolet light, immune cells, cytokines and deposition of immunoglobulins all seem to have a role in the development of skin lesions in SLE. This Review discusses recent advances in understanding of the cellular, cytokine and molecular processes underlying the cutaneous manifestations of SLE, focussing on processes or molecules that could potentially be exploited therapeutically.

Osteoarthritis (OA) and rheumatoid arthritis (RA) are disorders of the joints that involve degradation of the extracellular matrix of cartilage, and proteases and inflammatory mediators are common to both conditions. However, different cells are affected in OA (chondrocytes) and RA (synoviocytes), and treating these diseases requires an understanding of their differences as well as their similarities.

This comprehensive overview brings together the latest data on the epidemiology of gout in various parts of the world. The authors discuss regional and temporal patterns in gout prevalence and incidence as well as known risk factors for the disease.

Epidemiological research—the study of the distribution and determinants of disease in populations—relies on knowledge of different data sources, solid study designs and the accurate interpretation of study results. Understanding the methodology of population and clinical epidemiology studies is vital for the study of the distribution and determinants of outcomes in patients with rheumatic diseases.

Some aspects of the management of antiphospholipid syndrome (APS) are supported by abundant high-quality evidence, but, in certain scenarios, decisions are based on clinical judgement and experience. This comprehensive Review surveys the current recommendations for treating thrombotic and obstetric manifestations of APS, and addresses several areas of controversy in APS diagnosis and management.

The focus of translational research approaches on complex multifactorial diseases has enabled a deeper understanding of the pathophysiological mechanisms involved, and translated into new therapies that advanced management of autoinflammatory diseases considerably. In parallel to these developments, the successful use of strategies such as IL-1-blockade to treat patients with systemic-onset juvenile idiopathic arthritis or TNF receptor-associated periodic syndrome has led, through reverse translational approaches, to a better understanding of the pathophysiological role of these cytokines in autoinflammatory conditions. In this Review, Holzinger et al. describe how forward and reverse translational research have yielded important insights into the pathogeneses of autoinflammatory diseases, and explores the future challenges in the field.

This article discusses the role of hedgehog signalling in bone health and disease. Targeting this pathway could retard the rate of degeneration in osteoarthritis, promote bone repair, and inhibit cartilage tumour viability. As such, hedgehog signalling could be manipulated to safeguard skeletal health.

Musculoskeletal conditions are major contributors to the global burden of disease, but research to improve musculoskeletal health care is underfunded, not optimally planned, and the results often do not change clinical practice. Evidence suggests that improving the validity of clinical research and the implementation of practice change can improve health care.

Conditions such as diabetes, metabolic syndrome and chronic inflammation can induce extensive post-translational modifications in cartilage structural proteins, with consequences for the molecular structure and, ultimately, the function of cartilage. This article reviews the biochemical changes to articular cartilage matrix proteins driven by metabolic and oxidative stress as well as their relationship with cartilage degeneration.

RNA sequencing and mass cytometry are exciting new technologies that could revolutionize the analysis of immune cells. In this article, these developments and parallel advances in the analysis of big data are reviewed with the aim of advancing biomarker discovery.

Anti-DNA antibodies were first described in the 1930s in the context of infectious diseases and only later associated with autoimmune disorders such as systemic lupus erythematosus. Despite intense research into the pathogenic mechanisms of anti-DNA antibodies, many questions remain regarding their nature. Ole P. Rekvig provides an overview of what we know about the different types of anti-DNA antibodies, and highlights how this knowledge helped our understanding of the immune system and tolerance mechanisms.

Intriguing parallels can be drawn between the immune mechanisms leading to rheumatoid arthritis and coeliac disease, which point to a crucial role for T cell–B cell cooperation in both diseases. This article highlights recent developments in understanding the contributions of specific HLA molecules and antibodies against post-translationally modified protein antigens to these diseases.

The distinction between autoimmunity and autoinflammation has become an important issue in rheumatic diseases. The mechanisms by which the immune system is tolerant to self-antigens—and how this tolerance can be lost in some situations—is a central point in this distinction. In this Review, van Kempen et al. explores the different pathways at work in autoimmune and autoinflammatory diseases, and how this knowledge might help improve treatment strategies.

Considerable progress has been made in understanding the pathologic processes and pathophysiology of Kawasaki disease. This article also discusses genetic susceptibility to Kawasaki disease and describes current approaches to treatment of the acute stage of the disease.

Fibromyalgia symptoms include nonrestorative sleep and fatigue, and patients with fibromyalgia have showed reduced short-wave sleep and abnormal α-rhythms, which are suggestive of poor-quality sleep. Conversely, sleep deprivation in healthy individuals can cause symptoms of fibromyalgia and is a risk factor for developing chronic widespread pain. In this Review, Choy describes pain pathways that have been associated with sleep deprivation, and explores the hypothesis that sleep dysfunction is a pathogenic stimulus of fibromyalgia.

New technologies to identify loci associated with diseases are enabling classification of diseases according to genetic 'architectures'. In this Review, the authors show that patients with seronegative and seropositive rheumatic diseases have distinct genetic signatures, enabling an alternative classification to serology and providing hope for personalizing medicine.

This article reviews what is known about the role of the IL 23–IL 17 immune pathway at different stages in the development and progression of chronic immune-mediated inflammatory diseases, in particular rheumatoid arthritis and spondyloarthritis. The author draws on findings from disease-specific animal models and humanex vivostudies as well as data from clinical trials of therapies targeting the IL 23–IL 17 axis.

This article discusses the many heritable and nonheritable factors contributing to primary osteoporosis, focusing on osteogenesis imperfecta, juvenile osteoporosis and other monogenic disorders associated with increased bone fragility. Understanding these conditions not only illuminates the pathogenesis of osteoporosis, but could also lead to the discovery of new therapeutic targets.

The most common form of eye inflammation associated with juvenile idiopathic arthritis (JIA) is chronic anterior uveitis, which, if inadequately treated, can lead to ocular complications, including blindness. Sen and colleagues discuss the epidemiology, immunopathogenesis and management of JIA-associated uveitis, and describe the potential for biomarkers to improve its treatment.