Review Articles in 2010

Morphological and functional assessments of the cutaneous microvasculature have important roles in the diagnosis, prognosis and therapy of systemic sclerosis and secondary Raynaud phenomenon. The implications of these evaluations, in particular nailfold videocapillaroscopy and laser Doppler imaging, are discussed in this Review.

Heterotopic ossification is the formation of extraskeletal bone within soft tissues in the body. In two inherited heterotopic ossification disorders, fibrodysplasia ossificans progressiva and progressive osseous heteroplasia, specific gene mutations have been identified and, as outlined in this Review, result in aberrant bone formation and abnormal regulation of cell-fate signaling pathways in patients with these disorders.

Technological innovations have contributed greatly to advancing our knowledge of the genetic basis of osteoporosis. This article reviews the current understanding of osteoporosis genetics with a focus on developments since 2007. The potential clinical implications of this information and future directions for research are also discussed.

Sjögren's syndrome (SS) is a chronic autoimmune disorder that affects the exocrine glands, but the pathogenesis of this disease is not fully understood. This Review article describes the available evidence on the important pathogenetic mechanisms involved in the development of SS with a particular focus on how the disease is initiated and perpetuated. The authors also discuss the disease outcome and survival of patients with SS.

Pediatric-onset systemic lupus erythematosus (pSLE) is associated with higher disease severity and damage accrual compared with adult-onset SLE. In this Review, the authors describe specific features of pSLE, including epidemiology, disease activity and outcomes, and the effects of the disease on patients' quality of life, bone health and comorbidities.

The mechanisms involved in musculoskeletal pain include peripheral and central sensitization, the latter of which might cause the chronification of widespread pain conditions. These mechanisms are discussed in this Review, along with methods to assess muscloskeletal pain, such as pressure algometry, cuff-algometry and repeated pressure stimulation.

The persistent inflammation in patients with rheumatoid arthritis can cause cardiovascular disease and accompanying morbidities. The role of rheumatoid cachexia in this process is unknown, owing in part to the lack of an accepted operational definition. In this Review, the authors provide an update on rheumatoid cachexia, which they suggest represents the 'worst of both worlds' with respect to cardiovascular outcome due to the convergence of high grade inflammation and obesity.

The onset of spondyloarthropathy extends well into the pediatric age range, with most cases of the juvenile form of the disease being classified as enthesitis-related arthritis. This Review summarizes the clinical features, genetic susceptibility factors and outcomes of juvenile spondyloarthritis, and discusses some of the issues around the approach to the classification of this disease in adults and children.

Takayasu arteritis is associated with considerable morbidity and premature mortality, which could potentially be avoided if this rare granulomatous vasculitis could be diagnosed and treated at an earlier stage. The challenges currently faced in the diagnosis and management of Takayasu arteritis are discussed here, with a focus of the potential utility of noninvasive imaging techniques.

Vascular disease is a major feature of systemic sclerosis (SSc), and leads to tissue ischemia and fibrosis as the disease progresses. This Review describes the cellular and molecular mechanisms involved in SSc vasculopathy, including defective angiogenesis, endothelial dysfunction and dysregulation of transcription factors.

In this article, the authors review the global burden of autoimmune rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome and ankylosing spondylitis, across regions and ethnic populations, and discuss how evidence from geoepidemiological studies could provide insights into the genetic and environmental determinants of these conditions.

Several studies have shown that the gene encoding endoplasmic reticulum aminopeptidase 1 (ERAP1) is associated with ankylosing spondylitis (AS). ERAP1 and the closely related ERAP2 are involved in trimming peptides within the endoplasmic reticulum for loading onto major histocompatibility complex molecules; ERAP1 also has a role in releasing some membrane-bound cytokine receptors. The potential contributions of these aminopeptidases to the pathogenesis of AS are outlined in this Review.

Amyloidosis is a potential complication of chronic rheumatic diseases, particularly rheumatoid arthritis; in addition, patients with systemic amyloidosis can develop musculoskeletal and articular symptoms. This Review discusses the clinical features and therapy of systemic amyloidosis in light of novel approaches to diagnosis and treatment.

B cells promote the pathogenesis of SLE in a number of ways. In this article, the authors provide an overview of the role of B cells in SLE, review the rationale for targeting these cells and highlight the limitations and challenges of this approach. Current and future agents for globally or selectively targeting B cells in SLE are also outlined.

MicroRNAs have a central role in the regulation of gene expression and are important in a wide range of physiological and pathological processes. As discussed in this Review, they might also be promising as candidate biomarkers of diagnosis, prognosis, disease activity and severity in rheumatic diseases.

Numerous hypotheses abound with regards to the mechanisms involved in the pathogenesis of ankylosing spondylitis, which is, at its core, a genetic disease. This Review outlines the main theories and also provides a deeper look at the processes of bone erosion and syndesmophyte formation that are key to disease progression.

Neuropsychiatric manifestations are common in patients with SLE, encompass a wide range of neurologic and psychiatric features, and can lead to considerable morbidity and mortality. This Review discusses the challenges associated with the diagnosis and treatment of neuropsychiatric SLE.

Recent advances have shed light on the biochemical and molecular aberrations that lead to the characteristic cytokine production pattern and altered behavior of T cells in systemic lupus erythematosus (SLE). This article reviews how this knowledge helps explain the nature of the SLE T cell, identifies therapeutic targets that deserve further development, and identifies biomarkers of disease activity.

A number of cytokine pathways are important in the disease process of SLE, and several biological agents for SLE have been developed that target different cytokines or their receptors. This Review discusses the rationale for the use of anticytokine therapies in SLE, reviews the different agents tested to date, and presents future directions for therapy.

Research in mouse models has revealed the complex role of specific loci and genetic interactions in influencing lupus susceptibility and expression, implicating various pathways in the immunopathogenesis of systemic lupus erythematosus (SLE). This article provides an overview of this complex area and highlights how unraveling the genetic basis of the disease will depend on studies in both mice and humans.