Reviews & Analysis

Epigenetic alterations are increasingly being associated with the pathogenesis of inflammatory rheumatic diseases. In this Review, Ballestar and Li outline the current state of research into the role of epigenetics in such diseases and the possibility of epigenetic-targeting therapies.

An unmet need exists for effective glucocorticoid-sparing agents for the treatment of giant cell arteritis (GCA). Tocilizumab, the first intervention to demonstrate substantial therapeutic benefits for patients with newly diagnosed or relapsing GCA, is changing the landscape of treatment and ushering in a new era of biologic therapy.

A new publication by the ACR provides clear recommendations for the prevention and treatment of osteoporosis in patients being treated with glucocorticoids, but will they improve the historically inadequate management of this patient population?

Interpreting existing patient-reported outcome measures for the experience of remission by patients with rheumatoid arthritis is not straightforward. The challenge is to find a better, more accurate measure.

Autoantibodies are known to regulate the function of G protein-coupled receptors (GPCRs), but the involvement of such functional autoantibodies in autoimmune disorders is not fully understood. In this Review, the author discuss evidence showing agonistic and antagonistic effects of anti-GPCR functional autoantibodies in the pathogenesis of different rheumatic diseases.

The amount of clinical, serological and experimental evidence linking periodontitis to rheumatoid arthritis is constantly increasing. In this Review, Potempa and colleagues lay out the case for periodontal pathogens in the pathogenesis of rheumatoid arthritis.

Increasing evidence points to a mechanistic link between gut and joint pathology as the gut contains the largest number of immune cells of any tissue and trillions of commensals that contribute to immune development and homeostasis. New research is putting the role of Ruminococcus gnavus in arthritic disease in the spotlight.

The newly published findings from the Chondroitin Versus Celecoxib Versus Placebo Trial (CONCEPT) underscore the complexity of performing clinical trials in the field of knee osteoarthritis. But do the results of CONCEPT merit the consideration of chondroitin sulfate as a first-line therapy?

The DRESS study has shown that safety and efficacy were maintained for up to 3 years upon disease activity-guided dose reduction of TNF inhibitors. However, which patients are ideally suited for de-escalation remains to be investigated.

Regeneration of articular cartilage has been a long-standing challenge in the field of regenerative medicine. In the past 2 years, several studies have genetically identified the presence of stem cells in the surface of articular cartilage, but questions remain as to the healing properties of these cells.

In this Consensus Statement, an expert panel compares and contrasts recommendations for the management of gout produced by rheumatology organizations and the American College of Physicians (ACP), and present the G-CAN position on the ACP guideline.

In this review, the authors evaluate the association of complement activation with a variety of rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus and small-vessel vascultis, and discuss whether complement inhibition has therapeutic potential in these diseases.

Targeting IL-5 could improve outcomes and have steroid-sparing effects in the management of eosinophilic granulomatosis with polyangiitis. However, some questions remain about how this approach affects specific aspects of the disease.

Opioids provide some modest pain relief for patients with rheumatoid arthritis, but prescription of these drugs is influenced by their association with risks for the individual and for society. Is denial of a treatment, even if that treatment is imperfect, justified when patients experience considerable pain and other treatment options are limited?

The range of clinical manifestations and autoantibodies that are recognized as important in antiphosphlipid syndrome (APS) is constantly increasing. How can disease manifestations and autoantibodies that fall outside of the classic APS criteria be incorporated into diagnosis in the future?

Intra-articular corticosteroid injections are a long-established treatment for knee osteoarthritis (OA), but new findings indicate they are not effective, and even potentially harmful. Is it time to rethink the use of this treatment?

Like the mythical eagle devouring Prometheus's liver as fast as it regrew, chronic inflammation hinders cartilage regeneration in inflammatory arthritis. Using stem cells engineered to secrete anti-inflammatory molecules in response to local inflammatory factors could provide a way to keep the eagle at bay as the stem cells differentiate into chondrocytes.

Antigen-specific immunotherapies (ASIs) aim to modulate autoreactive cells and/or induce immune tolerance to self-antigens, and have the potential to be used in the treatment of rheumatic diseases. This Review summarizes current strategies for ASIs, progress in applying these strategies to rheumatic diseases and their limitations and future prospects.

Advances in synovial tissue research have improved our understanding of inflammatory arthritides, particularly rheumatoid arthritis, and have identified potential biomarkers that could be used for diagnosis, disease stratification, and predicting disease course and treatment response.

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) requires accurate diagnosis and staging to identify patients with the highest risk of disease progression, who might benefit from treatment with immunosuppressants. New insights into predictors of mortality in patients with SSc-ILD should improve patient care and inform the design of future clinical trials.