Reviews & Analysis

The immunomodulatory properties of vitamin D suggest it plays a central part in inflammatory diseases such as rheumatoid arthritis, a link that has been reinforced by findings from epidemiological andin vitro studies. In this Review, Jeffery et al. provide an overview of the known effects of vitamin D in the immune system and discuss how manipulation of the vitamin D pathway might be used for therapeutic purposes.

Technological advances over the past decade have revolutionized many areas of rheumatology, ranging from diagnosis, prognosis and therapeutic development to the mechanistic understanding of rheumatic diseases. This overview highlights key technological innovations and discusses the major impact that these developments are having on research and clinical practice.

Several genetic associations have been identified in patients with spondyloarthropathies, particularly ankylosing spondylitis (AS). The most recent associations uncovered which involve genes in the IL-17/IL-23 pathway enabled a better understanding of the aetiology of spondyloarthropathies, and informed the use of previously existing drugs to treat patients with these diseases—an example of how translation of hypothesis-free medical research can yield new therapeutic strategies.

Osteoarthritis (OA) is a chronic condition that is associated with pain and disability. In this Review, Roos and Arden consider the strategies that are available for modification of risk factors contributing to the development of knee OA. Interventions for prevention and early care of knee OA could help to avoid joint-replacement surgery.

In the development of rheumatoid arthritis, which factors govern the transition from systemic autoimmunity to synovitis? A study combining findings from human disease and animal models suggests that autoantibodies to neutrophil-derived citrullinated histone 2B are important for this transition; however, a 'second hit' involving intra-articular inflammation and citrullination could also be crucial to this process.

Although a generally safe and effective drug that is widely used in the treatment of gout, allopurinol can in rare instances be associated with severe adverse events. The presentation, risk factors and mechanisms of allopurinol-induced hypersensitivity are the focus of this Review, as well as strategies to avoid or minimize such reactions.

Defining key advances in any medical discipline can be challenging, but is especially so in rheumatology—a rapidly advancing field so broad that it defies traditional classifications. Here, we approach the Sisyphean task of summarizing the translational advances in rheumatology in the past decade within several broad categories of basic research.

The study of rheumatic diseases that affect children has thrived in the past 10 years. A look at several important advances in this area illustrates how organized collaborations and advanced technologies are contributing to the understanding and, ultimately, to improving the treatment of these disorders.

Comorbidities affect outcomes and treatment decisions in patients with immune-driven systemic inflammatory disorders. New recommendations for the management of comorbidities in rheumatoid arthritis, psoriasis and psoriatic arthritis might help optimize the management of these diseases and improve patient outcomes, but several considerations are relevant to their clinical implementation.

Gout is caused by the precipitation of monosodium urate monohydrate (MSU) crystals in the joints and in other tissues. Although direct observations of MSU crystals as they form on tissues are lacking, morphological findings and comparison with the physiological process of biomineralization suggests possible mechanisms of pathological MSU crystal formation and the conditions that might favour the nucleation and growth of crystals at particular anatomical sites.

Most core sets of outcomes in rheumatology include some patient-reported outcomes (PROs), most commonly pain, function, and patient global assessment of disease activity. According to van Tuyl and Boers, further research is needed to understand the value of the patient assessment and to define how these three key PROs contribute to the broader concept of health-related quality of life.

Although new therapeutic options are available for patients with autoinflammatory diseases, evidence-based treatment guidelines are lacking. An initiative in European paediatric rheumatology aims to develop best-practice recommendations for the management of these rare disorders.

The burden of cardiovascular disease is high in patients with inflammatory joint disease, owing to the presence of inflammation and traditional cardiovascular risk factors. Current management of cardiovascular risk factors and control of disease activity are unsatisfactory, and patients could benefit from improvements in screening and coordination between the cardiology and rheumatology branches of health care.

The increasing use of biosimilars in the context of rheumatic diseases has been met with several challenges unique to this type of drugs. In this Review, Dörner and Kay describe the fast adoption of biosimilar agents worldwide, highlighting the different approaches to regulation implemented by national and supranational health care policy-makers. Issues such as extrapolation of indications and the definition of strategies for adequate postmarketing pharmacovigilance are also discussed.

Early identification of secondary Raynaud phenomenon is essential to treat the underlying disease—most frequently systemic sclerosis (SSc). Integrated therapeutic approaches and monitoring systems that offer improved modalities of care feature in the new best practice recommendations for the treatment of digital vasculopathy in SSc.

Inflammation can be initiated by exogenous pathogen-associated molecular patterns (PAMPs) or by endogenous damage-associated molecular patters (DAMPs), but the contribution of each activation mechanism to reduction–oxidation (redox) stress and, ultimately, to the immunopathogenesis of autoinflammatory diseases remains elusive. In this Review, Varga and colleagues discuss how improved knowledge of mechanisms of inflammation initiation and propagation might help identify new therapeutic targets for patients with autoinflammatory diseases.

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.

The treatment recommendations for rheumatoid arthritis (RA) have been updated. Among the changes included, rheumatologists are advised to share treatment decision-making with patients and to maximize patients' quality of life by aiming for clinical remission. The update is based on scientific evidence, but more research is needed to strengthen RA treatment strategies.

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.