Review Articles in 2008

Since 1998, six new drugs have been approved for the treatment of rheumatoid arthritis, with the hope of at least two more in the next year—a unique success story in terms of drug approval for one indication. In this Review, Dr Schwieterman discusses the history of clinical trial design for new rheumatoid arthritis therapeutics, what we have learnt and the challenges that lie ahead.

Tuberculosis is one of the most common severe infections seen in patients receiving tumor necrosis factor inhibitors, and nontuberculous mycobacterial infection is an increasingly recognized condition in this setting. In this Review article, van Ingen et al. highlight the drug-related risks, clinical presentation, and screening and prevention of mycobacterial disease in patients undergoing treatment with biological agents.

Evidence from animal models indicates that B cells have both pathogenic and protective functions in autoimmune diseases. In this Review, the authors highlight recent insights into the suppressive functions of activated B cells in mice, describe the potential of B cells for use as cell-based therapy for experimental autoimmune diseases, and finally discuss the possibility of translating this cellular approach to treat human autoimmune diseases.

Bone mineral density testing is used to diagnose osteoporosis, assess the associated fracture risk and monitor changes over time. In this Review, the authors describe the common technical and interpretation errors that are encountered in the clinical use of bone densitometry, with a primary focus on DXA.

Hypovitaminosis D, encompassing both vitamin D insufficiency and deficiency, is highly prevalent in the general population and has potentially deleterious musculoskeletal effects. In this Review, the authors focus on the pathophysiology, clinical correlates, evaluation and treatment of hypovitaminosis D.

For many years, patients with chronic inflammatory disease of joints or muscles were advised to rest; however, exercise is now known to result in improved muscle performance, soft tissue integrity and health outcomes in these patients. In this Review, Dr Lundberg and Dr Nader discuss the systemic effects of exercise, as well as local effects in skeletal muscle and cartilage, in patients with rheumatic disease.

Osteoarthritis is a progressively degenerative joint condition that is influenced by various metabolic and structural factors. In this third in a series of three Reviews on Wnt–β-catenin signaling, Dr Corr provides insights into recent advances in research into the role of Wnt signaling in the pathogenesis of osteoarthritis, and discusses some of the genetic and regulatory factors involved.

The role of dietary antioxidants in the prevention and amelioration of symptoms in inflammatory joint disease has been of interest for many years. In this Review, the authors provide an overview of current evidence and discuss the potential prophylactic and therapeutic effects of antioxidants in arthritis.

Rheumatic diseases are typified by aberrant cellular immune responses. The advent of antibody engineering has now led to the development of anti-inflammatory therapy to target these responses. In this Review, Rothe and colleagues highlight advances in recombinant technologies for the development of novel biologic therapies in rheumatology.

'Growing pains' is a term that has been applied for almost 200 years to describe and diagnose some forms of childhood limb pain. To date no clear mechanism has been identified. The authors present a thorough historical Review of the physical presentation, differential diagnoses, potential causative factors and management options for this phenomenon.

Glucocorticoids are powerful and cost-effective drugs for the treatment of patients with rheumatic disease; however, currently available glucocorticoids have several adverse effects. This Review describes the genomic and nongenomic mechanisms of glucocorticoid action; detailed knowledge of these mechanisms is crucial for researchers to develop novel glucocorticoid receptor ligands and/or to further improve the use of currently available conventional glucocorticoids.

The introduction of mycophenolate mofetil to the treatment armamentarium for lupus nephritis raised the hope that the use of cyclophosphamide, with its toxic effects, would decrease. In this Review, the authors summarize the current knowledge of therapies for proliferative and membranous lupus nephritis and propose a treatment scheme, not of one therapy over another, but one that is tailored to the individual patient profile.

In this second in a series of three Reviews on Wnt–β-catenin signaling, Prof. Schett and colleagues discuss the molecular regulation of joint remodeling associated with chronic arthritis and the role of Wnt proteins in determining the differences in clinical presentation of inflammatory arthropathies, as well as implications for future therapy.

Although autoantibodies occur in healthy individuals, pathogenic autoantibodies are the key etiologic agent in many autoimmune diseases in humans, most notably lupus erythematosus. In this Review the authors explore how these autoantibodies become pathogenic, what accounts for their specificity, how they cause disease and whether they have a clinical role as biomarkers of disease.

MicroRNAs (miRNAs) have been implicated in the pathogenesis of rheumatic disease and are, therefore, a potential target for drug development. This Review describes the well-established roles of miRNAs in hematopoiesis and the immune response, the molecular action of miRNAs in the simultaneous post-transcriptional regulation of multiple targets, and the evidence for roles of specific miRNAs in rheumatic disease.

Familial cold autoinflammatory syndrome, Muckle–Wells syndrome and chronic infantile neurologic cutaneous articular syndrome (also known as neonatal-onset multisystemic inflammatory disease) are rare autoinflammatory diseases classified as cryopyrin-associated periodic syndromes or cryopyrinopathies. Clinical characteristics, mechanisms of disease and new treatment options for these syndromes are outlined in this Review.

The vitamin D system has both pathophysiological and therapeutic importance for autoimmune disease. In this Review, the authors discuss the role of the vitamin D system in autoimmunity, the mechanistic basis for this role, and present the potential of vitamin D receptor agonists to treat or prevent autoimmune diseases.

High concentrations of intact aggrecan are required for effective weight-bearing in healthy cartilage. Aggrecanases from the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) enzyme family, particularly ADAMTS-4 and ADAMTS-5, are thought to be involved in the pathogenesis of osteoarthritis. In this Review, Drs Fosang and Little discuss potential disease-modifying agents for osteoarthritis that could trigger the downregulation of ADAMTS enzymes.

The impact of the global HIV pandemic continues to grow and rheumatologists need to be aware of the spectrum of rheumatic diseases that occur in HIV-positive individuals, as outlined in this Review. Changes in the patterns of rheumatic diseases that have developed since the introduction of highly active antiretroviral therapy and the management of treatment of rheumatic diseases in HIV-positive patients are also discussed.

The canonical Wnt/β-catenin signaling pathway regulates multiple biological events, including embryonic bone development and fracture repair. In this Review, the authors discuss the role of this pathway in fracture repair at the molecular, cellular and physiological levels, and its potential as a therapeutic target.