Reviews & Analysis

Epidemiologic, genetic and immunophenotypic evidence suggests that oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis are distinct etiopathologic conditions with some overlapping pathogenic pathways. As discussed in this Review, further research is needed before we can generate a full molecular picture of these chronic childhood arthropathies.

Psoriatic arthritis follows a chronic, progressive course in most patients and joint damage can occur early in the disease. This article discusses advances in early diagnosis of this inflammatory musculoskeletal disorder, the various therapies that are available, as well as general guiding principles for treatment.

A rare but often fatal viral disease has been reported in a number of patients treated with rituximab, but how the risk of this complication should affect prescription practices demands consideration of several important factors.

Biologic therapies that target interleukin (IL)-1 are known to dramatically improve symptoms of a group of rare, heritable chronic inflammatory diseases. The results of a phase III trial confirm the place of canakinumab in the treatment arsenal for these disorders.

Why are female athletes more susceptible to knee ligament injuries than male athletes performing the same activities? Several theories have been put forward to explain this phenomenon.

Current therapies for RA focus on inhibition of synovitis, but do not adequately repair the bone damage that results from the imbalance of the osteoblast–osteoclast axis. Targeting key molecules involved in osteoclastogenesis and osteoblastogenesis might reduce bone destruction and enhance repair of erosions in this disease.

Tumor necrosis factor (TNF) is expressed at high levels in synovial tissue from patients with RA. Through preclinical studies, animal model studies and human trials, this cytokine was the first to be fully validated as a therapeutic target for RA. Several approaches to blocking TNF have been developed, demonstrating considerable benefit in most of the patients treated.

Interleukin-17 has been implicated in the pathogenesis of inflammatory arthritis. Evidence from animal models and preliminary results from trials in human disease highlight the emergence of this proinflammatory cytokine as a target for RA therapy.

Regulatory T cells are critically involved in immune homeostasis. Several established and experimental treatments for RA might work via effects on regulatory T cells. This Review discusses the potential benefits and pitfalls of targeting these cells to control autoimmunity.

Dendritic cells have a crucial role in inducing immunity and mediating immune tolerance. Current biologic therapies for RA target some of the cytokine products of dendritic cells, whereas emerging therapies are aimed at exploiting their tolerogenic capacity.

Premature aging of the immune system, driven by defective DNA maintenance and repair, could be responsible for the pathogenesis of RA. The authors discuss the phenomenon of premature immunosenescence in RA, and suggest that 'resetting' the immune system could be a novel therapeutic concept.

G-CSF and GM-CSF are well-known regulators of hematopoiesis, but these cytokines also have proinflammatory activity and are expressed in the joints of patients with rheumatoid arthritis. Antagonism of G-CSF or GM-CSF might represent a novel, safe and effective way of treating this disease.

Monoclonal antibodies directed against CD20 have emerged as an effective therapy for RA. Using this approach to target CD19 could provide a greater breadth of B-cell depletion with additional therapeutic benefits.

The therapeutic options for patients with rheumatoid arthritis (RA) have changed dramatically over the past two decades, as discussed in this Review. The current landscape of RA therapy in terms of available therapeutics is described, and accepted principles of RA management and some important controversies in this field are outlined.

Advances in imaging technologies such as MRI and ultrasonography have improved the evaluation of tissue injury and repair, providing better diagnostics of cartilage lesions. Various surgical procedures and nonoperative treatments can be used to treat cartilage lesions. New developments in the field of tissue engineering have defined a 'second generation' of potential repair strategies for cartilage defects. Many combinations of scaffolding materials, cell sources and bioactive factors are being investigated for the engineering of a successful cartilage tissue replacement.

Much progress has been made in understanding the pathogenesis of early inflammatory arthritis and in diagnosing and treating this disease, mainly through detection of the presence of anti-citrullinated protein antibodies and early implementation of combination therapy. However, early inflammatory arthritis still presents a challenge to clinicians in terms of individual patient prognosis, an improvement in which might facilitate earlier and more personalized therapeutic intervention and achieve increased rates of remission.

The results of two new studies suggest mutations in the gene encoding the interleukin (IL)-1 receptor antagonist (IL-1Ra) are responsible for a spectrum of childhood inflammatory disorders characterized by an imbalance in IL-1 expression. What implications do these intriguing results have for the diagnosis and management of IL1-driven inflammatory disorders?

New research reports that primary human dermal fibroblasts seeded into a three-dimensional biodegradable matrix can differentiate in vitro into osteoblasts and chondrocytes, and form three-dimensional bone-like and cartilage-like constructs, respectively. Is skeletal tissue engineering from skin biopsy tissue on the horizon?

The latest guidelines from the American Pain Society (APS) provide a comprehensive analysis of the evidence on the use of interdisciplinary rehabilitation and surgical and interventional procedures for the treatment and diagnosis of chronic low back pain. But will they have any impact on clinical practice?

What is the relationship between genetic and environmental risk factors in predisposing for rheumatoid arthritis (RA)? A new study provides more details on the interaction between the HLA DRB1 shared epitope (SE) alleles and smoking in conferring the risk of autoantibody-positive RA.