Reviews & Analysis

The natural history of untreated Lyme arthritis is rarely observed as most cases are successfully treated with antibiotics. This Case Study discusses a patient with Lyme disease who refused antibiotic therapy during the first 4 years of her illness and demonstrates that antibiotic therapy is still likely to be effective, even following a long-term infection withBorrelia burgdorferi.

The effect of biological therapies on cancer risk in JIA is controversial owing to confounding factors such as the use of concomitant immunosuppressants. A study has shed new light on this association, but questions still remain on the effect of the disease itself and biological therapies on cancer risk.

Osteoarthritis (OA) is a disease of the whole joint, at the centre of which lies the interface between cartilage and bone. Altered transfer of mechanical stress across this boundary is thought to result from, and to exacerbate, OA, but molecular crosstalk was presumed to be minimal. Accumulating data challenge this assumption, and this Review explores the biology and pathology of the bone–cartilage functional unit.

Despite preclinical evidence of the safety and efficacy of gene therapy for arthritis, few clinical trials have been undertaken. What are the constraints on the development of this therapeutic strategy, and are these barriers likely to be overcome?

Tissue engineering to repair diseased or injured cartilage could be revolutionized by the development of a novel cell-homing strategy that overcomes several barriers inherent in the use of existing techniques.

The link between glucocorticoid use and bone loss, with increased fracture risk, necessitates care in prescribing these potent anti-inflammatory drugs. What impact will new ACR recommendations—incorporating new clinical trial data and modern methodology for guideline development—have on ensuring that patients receive proper management to reduce the negative impact of glucocorticoids on bone health?

Macrophages have important roles in the induction and resolution of inflammation, but the intracellular pathways from inflammatory signals to pain response remain unclear. A recent study demonstrates that the P2X4 receptor mediates inflammatory pain by inducing formation of the potent lipid mediator prostaglandin E₂.

Genome-wide association studies of human diseases have uncovered large numbers of common genetic variants with small effect sizes; however, rare genetic variants with large effect sizes might have greater relevance with respect to disease heritability. The identification and characterization of rare variants—such as those recently discovered in SIAE—is, therefore, likely to be a major endeavor in the field in the coming years.

Glucocorticoids are widely used anti-inflammatory and immunosuppressive drugs for rheumatoid arthritis. This Review outlines the indications for and benefits of glucocorticoids as co-therapy with other DMARDs, describes the adverse effects that are predominantly associated with high-dose or long-term therapy, and considers the impact of patients' and doctors' perceptions of glucocorticoid therapy on prescribing and adherence to treatment.

Digital ulcers in patients with systemic sclerosis (SSc) can cause considerable disability; however, clinical trials addressing the treatment and prevention of digital ulcers in SSc are rare. A study has evaluated the potential benefit of the endothelin receptor antagonist bosentan in the treatment of SSc-related digital ulcers.

The etiology and pathogenesis of osteoarthritis (OA) are poorly understood, although proinflammatory cytokines are known to be critically implicated in the disease. In this Review, the authors discuss the current knowledge regarding the role of proinflammatory cytokines, particularly interleukin (IL) 1β, tumor necrosis factor and IL 6 in the pathophysiology of OA, and give an overview of efforts to develop adequate and specific anticytokine therapies.

The factors that trigger osteoarthritis (OA) have been difficult to identify, as the earliest molecular changes substantially precede clinical presentation of symptoms. Nevertheless, we are beginning to piece together the processes that occur in articular cartilage, and new tools promise to expedite completion of the puzzle. This Review outlines some of the events in early stages of OA development, focusing on the changes that occur in cartilage both before and after substantial loss of the tissue occurs.

Research into the effects of lower-extremity muscle weakness on osteoarthritis onset and progression has increased over the past decade, owing to its potential for modification using exercise training interventions. Similarly, afferent sensory dysfunction has also been suggested as an important yet modifiable risk factor for OA progression. In this Review, the authors provide an overview of these risk factors, and discuss the effectiveness of preventive or therapeutic neuromuscular and exercise training interventions.

Chondrocalcinosis, the calcification of cartilage, is caused by the deposition of calcium pyrophosphate crystals (CPPD). This Review describes regulators of pyrophosphate metabolism, and discusses the mutations and mechanisms that underlie familial CPPD.

Current therapeutic strategies for osteoarthritis (OA) are mostly palliative; modifying the structural progression of OA has, therefore, become a focus of drug development. This Review discusses the challenges involved in the discovery and development of disease-modifying OA drugs, and describes specific agents that have shown promise in phase II and III trials.

Severe osteoarthritis (OA) is the main cause of an increasing need for joint replacements and is, therefore, a large burden on both patients and the health-care sector. This Review discusses the genetic contribution to hip and knee OA and the authors suggest that identifying individuals at a high risk of OA with a combination of genetic markers might aid preventive and disease-management strategies.

Advances in genotyping technology, such as genome-wide association studies, have identified many robust genetic associations with systemic lupus erythematosus (SLE) in various ethnic groups. In this Review, the authors describe established and novel SLE-associated loci and discuss how genetic risk factors that are shared between autoimmune diseases can help to identify common disease pathways.

Dupuytren disease is a common disorder but its cause remains unknown and the treatment of its symptoms is often unsatisfactory. This article provides an overview of the current understanding of the genetics, pathogenesis and proposed etiology of this disease, as well as a discussion of current and emerging therapies.

Familial Mediterranean fever (FMF) is characterized by episodes of acute inflammation; however, in approximately 30% of patients with FMF inflammation persists even during the attack-free periods. In this Review, the authors discuss the markers and risk factors for persistent chronic inflammation in these patients, summarize the clinical outcomes of such inflammation, and suggest a new potential treatment strategy.

Advances in the field of MRI have given rise to sophisticated imaging modalities that allow the visualization of molecular pathologic processes that might precede overt structural damage seen on conventional imaging. In this Review, the authors summarize these advances and new directions in MRI in the context of synovial, bone and cartilage changes in rheumatoid arthritis.