Review Articles in 2014

Next-generation sequencing is at the forefront of the identification and characterization of clonal families of antibodies that are involved in immune responses to infection, cancer and autoimmune disease. In this article, cutting-edge antibody repertoire sequencing technologies are described as a means of paving the way forward for research and discovery in rheumatology.

This article places Raynaud phenomenon in the context of a mechanistic understanding of cutaneous vasoconstrictive and thermoregulatory processes, describing how these processes might regulate the pathogenesis of Raynaud phenomenon and ultimately inform new approaches to its treatment.

Despite having a poor intrinsic capacity for repair, articular cartilage has been shown to contain a population of self-renewing, multipotent cells that express stem-cell-related surface markers. In this article, Jiang and Tuan review what is known about these cartilage-derived stem/progenitor cells, with a focus on their origin, function and therapeutic potential in osteoarthritis.

Disease-modifying osteoarthritis (OA) drugs (DMOADs) are needed as current OA therapies only relieve pain and do not alter the course of disease. In this article, Toll-like receptor 4 (TLR4) signalling, which is involved at various stages of pathogenesis, is reviewed, as is the potential for candidate TLR4-specific DMOADs.

Promising biomarkers are being developed to predict disease outcome and response to therapy in children with juvenile idiopathic arthritis, childhood lupus nephritis and juvenile idiopathic inflammatory myopathies. These advances are expected to facilitate risk stratification, diagnosis and management of these patients, and thereby lead to more rational and effective clinical care.

Patients with autoimmune inflammatory rheumatic diseases have an impaired immune system that can be exacerbated by medication, making them susceptible to infectious diseases. This article reviews this problem and the potential compounding issue that vaccinating these patients against common infectious diseases is not always safe and effective.

Contrary to earlier beliefs, evidence now exists that exercise does not exacerbate systemic inflammatory diseases, such as rheumatoid arthritis. In this Review of exercise therapy for rheumatic diseases, the authors propose that, by interrupting a cycle of local inflammation, obesity, metabolic dysregulation and systemic inflammation, exercise is medicine.

Glucocorticoid therapy is associated with bone loss and increased risk of fracture, but these deleterious effects can be avoided or mitigated with appropriate treatment. When to initiate anti-osteoporosis therapy and what form this preventive therapy should take is the focus of this Review.

The ASAS classification criteria for axial and peripheral subgroups are beginning to alter our understanding of spondyloarthritis. In this article, Astrid van Tubergen discusses how these criteria are changing not only our clinical understanding, but also the epidemiology, including prevalence and incidence calculations.

In comparison with traditional surgery techniques, arthroscopic surgeries induce less tissue damage and can reduce morbidity and complications. In this Review, Carr and colleagues focus on the increased use of therapeutic arthroscopy as a tool for excision, reconstruction and replacement of damaged or abnormal tissue, and signal the need for additional studies to allow this surgical approach to reach its full potential.

Pulmonary complications are an important extra-articular manifestation of connective tissue disease (CTD) and a major cause of mortality. Here, the authors provide a broad overview of interstitial lung disease in the context of CTD, providing insights into pathogenesis, classification and management of the disease.

In osteoarthritis (OA), chronic, low-grade inflammatory processes promote the symptoms and progression of the disease. In this Review, the authors discuss the inflammatory pathophysiology in OA, including networks of inflammatory mediators in OA joints, transcriptional reprogramming of chondrocytes, and abnormal bioenergetics and proteostasis mechanisms, and consider the potential to target these processes for the treatment of OA.

In this Review, skeletal ontogeny is compared to fracture healing mechanisms. The authors describe developments in our understanding of the different stages of fracture healing as well as the latest therapies tested in animal models and in clinical trials, focusing on bone morphogenetic proteins or parathyroid hormone based treatments.

Although osteoarthritis can be slowed by biologic therapy, surgical interventions are necessary to recover cartilage function. In this Review of cartilage repair techniques, the authors outline how currently accepted methods can fall short in providing a long-term solution of hyaline cartilage regeneration and discuss preclinical and clinical trials of new cell scaffold-based, cell-free scaffold-based and scaffold-free procedures.

In this Review, Martinon and Aksentijevich highlight the latest developments in research into the pathogenesis of autoinflammatory diseases. Newly discovered disease-causing mutations and molecular pathways underlying inherited autoinflammatory diseases are discussed.

Sex steroid hormones are likely to influence risk and expression of autoimmune diseases through modulation of key immune pathways. In this Review, Hughes and Choubey discuss the immunomodulatory mechanisms behind the sexual dimorphism observed in patients with systemic lupus erythematosus and rheumatoid arthritis, and focus on how oestrogen and progesterone affect manifestation of these diseases.

Elevated serum uric acid levels and gout are linked with the development of several comorbid conditions including hypertension, metabolic syndrome, chronic kidney disease and cardiovascular disease. In this Review, the authors explore the mechanisms underlying these associations and discuss the potential of appropriate treatment strategies to improve cardiovascular and renal outcomes in patients with hyperuricaemia and gout.

Systemic sclerosis (SSc) is a complex autoimmune disease. Here, the authors describe the current understanding of the genetics of SSc and how genetic risk factors can influence disease pathogenesis. Available evidence of the role of epigenetic factors (including microRNAs and DNA methylation patterns) in disease development is also discussed.

Although paraneoplastic syndromes are rare, it is important that rheumatologists can recognise the typical clinical patterns of these syndromes in their rheumatic disease patients to allow for timely diagnosis and potentially life-saving therapy. Here, the authors focus on well-defined paraneoplastic musculoskeletal syndromes for which the evidence of a causal relationship to an underlying tumour is not only based on a temporal relationship but also on underlying pathomechanisms.

IL-6 has been linked to numerous inflammatory conditions (such as rheumatoid arthritis), and many IL-6-directed therapies are currently in development. The authors outline the basic biology of IL-6 and IL-6 signalling pathways before discussing the clinical implications of targeting IL-6 in the context of rheumatic diseases. Current and future indications for the use of IL-6-targeted therapies and safety of these agents are discussed.