Reviews & Analysis

Research in osteoarthritis (OA) is among the most collaborative in rheumatology, and the Osteoarthritis Initiative is championing efforts to pool expertise and data in imaging studies in OA. The rationale for, undertaking of, and emerging results from this project are outlined in this Perspectives article, with an emphasis on how they will advance the understanding and treatment of OA.

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.

Recent studies have highlighted a potentially important role for Wnts as profibrotic mediators, and implicated increased Wnt activity in systemic sclerosis and other fibrotic diseases. Strikingly, new data indicates that Wnts have a central role in the profibrotic activity of TGF-β.

The attitudes and beliefs of older adults toward the role of exercise for knee pain suggest that considerable barriers need to be overcome if the benefits of exercise are to be realized.

The concept of remission in rheumatoid arthritis can at present be defined by use of a number of different criteria, which often reflect different levels of disease control. Various factors, including how much emphasis is placed on the patient's perspective, can influence the usefulness of remission criteria in daily practice.

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.

A new multinational guideline for treating pain in the setting of inflammatory arthritis highlights the absence of well-designed studies to answer the myriad questions faced by clinicians. To use the recommendations as a starting point for alleviating this common condition, clinicians will need to read between the lines.

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.

In the past decade, the introduction of targeted biologic therapies has revolutionized the treatment of rheumatic diseases. Patents for many of these key biologic agents will soon expire, and the introduction of biosimilar versions is likely to lead to substantial cost savings. Focusing on targeted therapies for rheumatic diseases, the authors describe biosimilar agent manufacture, safety and efficacy concerns, and the current worldwide status of regulations for the approval of biosimilar drugs.

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.

Rheumatoid arthritis (RA) is partly heritable; genetic and serological markers are known to confer risk of developing pathology. But given clinical heterogeneity in RA, can we predict who will develop severe disease? Substantial heritability of erosive progression rates has now been identified, but better prognostic biomarkers remain wanting.

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.

Accumulating data from clinical practice hint that an alternative class of biologic agent may be the best choice when anti-TNF therapy for rheumatoid arthritis fails to produce the desired effect. Furthermore, evidence suggests that non-anti-TNF biologic agents should perhaps also be considered as the initial choice of biologic agent.

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.

Although methotrexate is the most widely used medication for psoriatic arthritis (PsA), evidence for its effectiveness is scant. The recent MIPA trial failed to show disease-modifying effects. Was this outcome due to true inefficacy, or to trial issues? Data on symptom-modulating and disease-modifying effects of methotrexate in PsA are explored.

Coronary artery aneurysms affect a substantial proportion of patients with Kawasaki disease, especially when standard therapy fails. Adjunctive primary corticosteroid treatment reduces inflammation and might reduce the incidence of coronary artery disease in a subset of patients at high risk of this comorbidity, but reliably identifying such individuals is a challenge.

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.