Review Articles in 2007

Observational database studies provide important information on the safety and benefit of approved medications. As discussed in this Review, the limitations of these studies, and the nature of their design and analysis, should be taken into account when results are interpreted.

White adipose tissue-derived adipokines are closely associated with obesity-related exogenous factors, such as nutrition and lifestyle, and the molecular events that lead to metabolic syndrome, inflammatory and/or autoimmune conditions, and rheumatic diseases. In this Review, Dr Gualillo and colleagues discuss the progress in adipokine research, focussing on the roles of leptin, adiponectin, resistin, visfatin, and other recently identified adipokines.

Cigarette smoking, in combination with genetic factors, creates a significant risk of developing systemic lupus erythematosus and rheumatoid arthritis, and can affect both the course and outcome of these rheumatic diseases. Also outlined in this article are the potential mechanisms by which smoking modulates the immune system.

Psoriatic arthritis is a central feature of psoriatic disease, a systemic disorder that includes a range of musculoskeletal manifestations as well as features such as colitis, duodenitis, uveitis and metabolic syndrome. Evidence that psoriatic arthritis is distinct from rheumatoid arthritis and other spondyloarthropathies is outlined in this article.

Regulatory T cells have a key role in immune homeostasis and in suppressing unwanted inflammatory responses toward self-antigens. In this Review the authors discuss the function of regulatory T cells in human autoimmune disease, focusing primarily on rheumatoid arthritis and systemic lupus erythematosus.

Studies on the genetics of rheumatic diseases, such as rheumatoid arthritis and systemic lupus erythematosus, have identified multiple polymorphisms related to disease susceptibility. The findings on rheumatoid arthritis-associated genes are reported in this Review, which focuses on the differences in the frequency of polymorphisms between various ethnic groups.

Although randomized controlled trials and observational studies often reach the same conclusions, observational studies are often considered second rate. The uses, limitations, and methodological problems associated with observational studies are outlined in this article.

Inflammation of synovial tissue is a hallmark of rheumatoid arthritis. Synoviocytes express receptors for glucocorticoids, androgens and estrogens, which thereby creates a potential link between the immune reaction and the endocrine systems at a local level. There are also changes in the peripheral nervous system at the site of local inflammation. The complex interactions that occur between the endocrine, nervous and immune systems are outlined in this article.

Patients with inflammatory bowel disease often suffer from joint inflammation; conversely, gut inflammation often occurs in patients with primary spondyloarthropathies. Pathogenic mechanisms common to these inflammatory diseases, and approaches to their treatment, are outlined in this Review.

Angiogenesis might have a key role in the pathogenesis of inflammatory disorders such as rheumatoid arthritis. The basic mechanisms, mediators and inhibitors of inflammation-associated angiogenesis are outlined in this Review, and the possible clinical application of therapeutics that target angiogenesis are discussed.

Although measuring pain in patients with low back pain is not simple, for pain to be effectively managed it needs first to be accurately assessed. In this Review, the authors describe the various instruments that have been developed for the evaluation of pain and provide recommendations for their use in daily clinical practice.

Cells can respond to diverse external stimuli through the transmission of information to their interior by signal transduction cascades. In some cases, the results can be detrimental and lead to chronic inflammatory disease. This article highlights several pathways involved in the pathogenesis of immune-mediated diseases, and their therapeutic potential.

Lipoxins and aspirin-triggered lipoxins have emerged as important factors in anti-inflammatory and proresolution pathways, the absence of which might cause chronic inflammation. The newly discovered resolvins and protectins, derived from omega-3 polyunsaturated fatty acids, are also potent locally acting agonists of endogenous anti-inflammation, and promote resolution. The functions of these lipid mediators, and their potential beneficial use in rheumatoid arthritis, are outlined in this Review.

Patients with chronic inflammatory rheumatic diseases, such as primary Sjögren's syndrome, systemic lupus erhythematosus and rheumatoid arthritis, are at higher risk of developing B-cell non-Hodgkin lymphomas compared with the general population. In their Review, Dr Hansen, Dr Lipsky and Dr Dörner discuss the risk of lymphoma, the common and disease-specific mechanisms of B-cell lymphoma development, and the clinical consequences in patients with inflammatory rheumatic diseases.

Controversy has surrounded the use of cyclo-oxygenase-2 (COX2) inhibitors following the observation that long-term use of these drugs is associated with an increased rate of cardiovascular adverse effects. As discussed in this Review, however, COX2 inhibitors are associated with a similar cardiovascular risk to traditional NSAIDs. The pharmacology of COX2 inhibitors is discussed and potential mechanisms underlying the cardiovascular adverse effects associated with the long-term use of COX2 inhibitors and NSAIDs are outlined.

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.

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.