Reviews & Analysis

Technologies such as high-throughput DNA genotyping, microarray-based gene-expression profiling and mass-spectrometry-facilitated protein profiling enable DNA sequence variants to be analyzed and changes in global gene and protein expression to be assessed. By such methods, molecular pathways that link specific gene variants to cell dysfunction and disease, such as rheumatoid arthritis and systemic lupus erythematosus, can be defined.

Neuropsychiatric manifestations are present in approximately 70% of patients with systemic lupus erythematosus, and are often associated with a poor prognosis. In this Viewpoint, Dr Strous and Dr Shoenfeld discuss the potential role for autoimmune factors in contributing to neuropsychiatric expressions via direct and indirect autoantibody-induced neuronal damage.

Systemic scleroderma is one of the most severe chronic autoimmune connective tissue diseases. In this Viewpoint, Dr Deleuran and Dr Abraham discuss the importance of understanding the development, regulation and function of the type 17 T-helper subpopulation of CD4⁺T cells in order to explore treatment possibilities in systemic scleroderma.

Regional pain syndrome is a common syndrome that manifests as a characteristic set of clinical features localized to one region of the musculoskeletal system. Psychosocial factors are thought to significantly affect regional pain syndrome, which varies in clinical severity and can be difficult to manage once established.

Epigenetic mechanisms, including DNA methylation and histone modifications, control regional chromatin structure and thereby influence gene expression. In this Review, Dr Richardson discusses the association between epigenetics, environmental factors, and the development of autoimmune diseases, in particular systemic lupus erythematosus, in genetically predisposed individuals.

In their Review, Dr Sengupta and Dr Stone outline the assessment of ankylosing spondylitis in the ambulatory care setting and in response to treatment with tumor necrosis factor inhibitors. Although advances have been made in creating and validating outcome measures in this disease, the authors discuss the persistent need for suitable biomarkers to help with diagnosis and disease activity monitoring, in order to improve patient outcomes.

Changes in the levels of serum components facilitate the evaluation of the inflammatory reaction. In this article, the use of novel markers of the inflammation process, such as procalcitonin, ferritin and cytokines, and classic markers, such as C-reactive protein, is reviewed.

Although the prognosis of patients with systemic lupus erythematosus (SLE) has improved over the past few decades, the increased occurrence of atherosclerotic vascular disease in these patients has become apparent. This Viewpoint discusses the increased risk of cardiovascular disease in patients with SLE, and how levels of risk can be assessed in order to determine the group of SLE patients most suited to preventative therapy with statins.

A suitable infrastructure and adherence to regulatory requirements are required to establish a successful clinical trial unit. Once in place, studies must be acquired, contracts negotiated and patients recruited before the clinical investigation can begin. These aspects, which, if successfully carried out, will improve the chances of obtaining future studies, are discussed in this article.

The changing prevalence of the risk factors for gout, which include genetic factors, excess alcohol consumption, purine-rich diet, the metabolic syndrome, diuretic use, and osteoarthritis, are influencing the prevalence and clinical presentation of this common crystal deposition disorder. In addition, as is discussed in this Review, suboptimum management is contributing to the rise in the prevalence of clinically significant symptomatic chronic gout.

Numerous antiangiogenesis drugs have been developed for the treatment of patients with malignancies. These agents, which include vascular-endothelial-growth-factor inhibitors, microtubule disrupters and fumagillin analogues, might also represent new therapeutic options for patients with proliferative synovitis, as is discussed in this Review.

The knee is generally seen as the easiest joint to inject or aspirate; however, a 'dry tap' can occur, when fluid seems to be present but the initial attempt to aspirate it fails. This Primer Review outlines why such difficulties occur when performing arthrocentesis of the knee and suggests ways in which an operator might adjust their technique to deal with this situation.

A widely used alternative to biologic therapy for treating rheumatoid arthritis is treatment using disease-modifying antirheumatic drugs (DMARDs). Methotrexate and sulfasalazine are the most commonly prescribed DMARDs, each of which can be used on its own, or in combination with other DMARDs, in a step-up, step-down, or parallel approach, as is outlined in this Review.

Many rheumatologists and other rheumatology health professionals find the management of patients with fibromyalgia syndrome (FMS) difficult. In this Viewpoint, Dr Scarbrough and Dr Crofford discuss whether or not rheumatologists should have a role in the diagnosis and management of FMS patients, and if so, how their improved knowledge of this condition can help patients receive optimal care.

Damage-associated molecular pattern molecules, such as heat shock proteins and S100 proteins, represent tissue danger signals, which mediate inflammatory responses after being released from activated or necrotic cells. These danger signals, and their receptors, could be targets for novel approaches in the treatment of rheumatic diseases, as discussed in this article.

Subgroup analyses are often included in clinical trial papers, but there are numerous pitfalls associated with this approach. Specific guidelines as to how to perform and interpret subgroup analyses should be followed to ensure that appropriate conclusions are drawn and correct clinical decisions are made.

Most pregnant women with rheumatoid arthritis suffer a disease flare within 3 months of delivery of their baby. At present, due to the lack of data on the effects of antirheumatic drugs on the infant, patients feel they have to choose between postpartum disease control and lactation. These issues, and the need for further studies in this area, are highlighted in this Review.