Review Articles in 2012

Risk factors-genetic and environmental-for rheumatoid arthritis (RA) are gradually becoming clear, leading to considerable heterogeneity in the pathological processes and clinical features of this disease. Preclinical abnormalities can precede manifestation of symptoms by a decade. Precisely how endogenous predisposing factors interact with environmental triggers to produce clinical disease remains unclear, but the authors of this Review unite diverse strands of research to present a state-of-the-art mechanism for RA pathogenesis.

Peripheral neuropathy is a common neurological disorder that can be observed in the context of a range of rheumatic diseases. In this Review, Vallat and colleagues provide a broad overview of the different types of peripheral neuropathy that can be associated with rheumatic disease, with a particular emphasis on recognition and diagnosis of the condition.

Pregnancy in women with systemic lupus erythematosus (SLE) is increasingly common, as patients' survival and quality of life improve. However, these pregnancies are associated with substantially higher risk of maternal and fetal morbidity and mortality than those in healthy women. Especially in the presence of anti-Ro, anti-La and antiphospholipid antibodies, increased fetal loss, premature births and neonatal syndromes including congenital heart block are major issues. Although success rates of pregnancies have increased considerably, pregnancy management in women with SLE is not optimal. This Review discusses the risk factors and outcomes and proposes a pregnancy planning strategy for women with SLE.

Osteoporosis and vascular calcification share a number of pathogenetic mechanisms. In this article, the authors discuss the pathophysiology of the interaction between these two processes, and review clinical evidence that confirms the correlation between osteoporosis and cardiovascular disease.

MicroRNAs (miRNAs) function in several chronic diseases—miRNA-mediated fine control of genetic networks involved in tissue development and homeostasis becomes disrupted. Participating in production and maintenance of articular chondrocytes and skeletogenesis, miRNA are increasingly implicated in the pathogenesis of osteoarthritis. Data from animal and cell studies are discussed in this Review, alongside the potential for targeting miRNA in the clinic.

Platelets have an established function in haemostasis, but their role in the development of rheumatic disease is only now emerging. In this focused Review, Boilard and colleagues describe how platelets, and platelet-derived microparticles, contribute to the development of arthritis and systemic lupus erythematosus, highlighting the key advances in the literature and the future of this field.

Subchondral bone remodelling in osteoarthritis (OA) is biphasic and spatially variable. Early-stage disease is associated with bone loss owing to increased bone remodelling. As disease progresses, the remodelling rate slows down leading to densification of the subchondral plate and complete loss of cartilage. In this article, Burr and Gallant review the current knowledge on OA and discuss the role of subchondral bone in the initiation and progression of disease. They also present a hypothetical model of OA pathogenesis.

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are inflammatory disorders that commonly occur in the elderly and whose disease patterns variably overlap. In this Review, Salvarani and colleagues describe the main clinical features of both PMR and GCA, detailing the pathogenesis, diagnosis, classification and management of these disorders, offering practical guidance to clinicians.

Antimalarial agents are mainstays in the clinical management of systemic lupus erythematosus, and have been in routine use for more than 50 years. This Review summarizes recent insights into the mechanisms of action of these agents and their clinical implications.

Osteoporosis can be secondary to an underlying metabolic, nutritional, pharmacologic or disease-related cause; in such cases the triggering factor should be identified and treated. Approaches to the identification and management of patients with secondary osteoporosis are outlined in this Review, alongside mechanistic insights into the bone pathology.

Recent advances in pathogenesis and diagnosis of Raynaud phenomenon have driven, and are driving, new therapeutic strategies for this phenomenon. In this Review, Ariane Herrick provides an update of the pathogenesis, diagnosis and treatment of primary and systemic sclerosis-related Raynaud phenomenon. Current and future treatment approaches are discussed and key unanswered questions are highlighted.

Although glucocorticoids are central to the treatment of idiopathic inflammatory myopathies, these drugs, paradoxically, have catabolic effects on skeletal muscle. Mechanisms that govern the beneficial and adverse effects of these agents are increasingly understood; as the authors explain, glucocorticoid therapy will be optimized as a result, but new targets that will lead to much-needed alternative therapeutic options are also expected to emerge.

The complement system is vital to both innate and adaptive immunity, but also has the potential to damage host tissues. In this Review, the authors focus on the mechanisms of action of complement in the pathogenesis of rheumatic diseases, and discuss the therapeutic potential that disrupting these actions might offer patients with these disorders.

Analyzing bone turnover markers—an approach boosted by the advent of automated analysis—can guide clinical decision making and the development of new therapies in osteoporosis. How such markers are, ought to be, and might be, used to understand osteoporosis and to optimize its treatment form the focus of this Review.

Multiplexed assay technologies at the gene, protein, and cellular levels have enabled the identification of 'actionable biomarkers' that can inform clinical practice. Powerful new methods, including mass cytometry and protein arrays, are reviewed.

Angiogenesis facilitates inflammation and contributes to structural disease progression in osteoarthritis (OA). As new blood vessel growth is coupled with innervation, inappropriate vascularization might sensitize tissues that are usually impervious to pain. In this article, the authors describe sites of angiogenesis and mechanisms of nerve and new blood vessel growth in the synovial joint. They discuss the neurovascular interactions that might contribute to pain in OA, as well as potential targets for new therapies.

Loss of meniscal function is one of the strongest identified risk factors for knee osteoarthritis (OA). However, the best therapeutic strategy for patients with meniscus damage remains controversial. The authors explain the role of meniscus pathology in OA and discuss the current options for treatment of degenerative and traumatic meniscal tears.

Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is a global health problem. Management of patients with co-existing rheumatic disease and viral hepatitis can be challenging, given that immunosuppressive and biologic agents used to treat rheumatic disease can have serious complications. This Review provides a guide to viral hepatitis for the rheumatologist, describing the characteristics, complications and treatment of chronic HBV or HCV infection in rheumatic disease.

Alphaviruses can cause rheumatic manifestations (usually polyarthralgia and/or polyarthritis) in humans. Arthritogenic alphaviruses are distributed globally and include chikungunya virus, Ross River virus, Barmah Forest virus, Sindbis virus, o'nyong nyong virus and Mayaro virus. In this Review, the authors provide an overview of these viruses, describing epidemiology, pathogenesis, disease manifestations, diagnosis and interventions.

Aberrant T-cell help has been implicated in the expansion of self-reactive B-cell clones and subsequent autoantibody production in many systemic autoimmune diseases, including systemic lupus erythematosus. In this Review, Joseph Craft discusses the T-helper-cell populations, particularly follicular helper T cells, which are key regulators of B-cell survival and maturation during normal immune responses and in autoimmunity.