Review Articles in 2012

Both sicca and systemic symptoms affect quality of life in patient with Sjögren's syndrome, and their management is complicated by the low level of evidence supporting the available therapeutic options. Here, the authors comprehensively review the data on the efficacy of treatments for the glandular and extraglandular manifestations of this disease. Ramos-Casals and colleagues also recommend treatment approaches tailored to different clinical scenarios that patients with Sjögren's syndrome can present.

Why does chronic inflammation manifest not only in the joints but also in the gut in a substantial proportion of patients with SpA? Insights into the genetic and environmental factors that link inflammatory bowel disease and SpA are provided in this Review. Furthermore, the authors present a transition model, describing a phase in the disease process during which acute inflammation is transformed into chronic pathology, and suggest that it might present the opportunity for effective therapeutic intervention.

Although NSAIDs and physical therapy remain the first-line treatment recommendations for SpA, therapy options are evolving rapidly with advances in understanding, classifying and diagnosing the disease. TNF blockers are effective in NSAID-resistant disease but other biologic agents have thus far failed to deliver results. New capacities to enroll patients at an earlier stage in the disease, and to stratify studies by SpA subtype, will facilitate further therapeutic developments.

Spondyloarthritis in childhood (juvenile SpA) is distinct from the disease in adults, typically affecting the lower extremities (peripheral arthritis and enthesitis) with spinal or sacroiliac joint involvement rare at disease onset. This Review provides an update on the advances in diagnosis and management of juvenile SpA, summarizing classification and diagnostic criteria, clinical features, outcomes and guidelines for treatment.

Overlapping heredity in ankylosing spondylitis, psoriasis and inflammatory bowel disease indicates common pathological pathways between these diseases. Modern genetic techniques are unraveling the similarities—and differences—in the genetic backgrounds of these complex inflammatory disorders, and promising new approaches to tackle them. How the association ofHLA-B27with SpA might contribute to the disease process is among the factors discussed in this Review.

Owing to the long diagnostic delay in spondyloarthritis (SpA), the effective identification of those individuals who are likely to have axial SpA among patients with chronic back pain in primary care and their subsequent referral to a rheumatologist for establishing a correct diagnosis is worth pursuing. In this article, the authors discuss potential referral criteria and present clinical studies in which their effectiveness in identifying patients with SpA has been examined.

Imaging modalities are vital for the accurate assessment of joint disease. In this Review, the authors focus on imaging in paediatric rheumatic disease, which presents unique challenges. They discuss the utility and limitations of various imaging techniques—including MRI, ultrasonography and conventional radiography—in the assessment and treatment of children with juvenile idiopathic arthritis.

Oxygen is thought to be an indispensable regulatory signal in tissue development and homeostasis, via its controlling of specific genetic programs. Hypoxia-inducible transcription factors (HIFs), which are regulated by oxygen tension, are central mediators of the homeostatic response that enables cells to survive and differentiate in low-oxygen conditions. In this Review, the authors summarize the current knowledge of HIF signalling in cartilage, bone and blood, and pay particular attention to the complex relationship between HIF and VEGF in these tissues based on data collected from animal models, which can also be relevant in diseases like cancer and ischemia.

The heterogeneity and interrelatedness of the conditions comprising spondyloarthritis (SpA) complicate diagnosis and patient classification; however, a number of criteria sets have been developed to aid these processes. Here, the authors critically review the currently available SpA classification criteria and highlight the important part that MRI will play in facilitating early diagnosis of this disease.

Rheumatoid diseases such as rheumatoid arthritis are associated with accelerated atherosclerosis, increased cardiovascular morbidity and mortality. The early signs of cardiovascular disease therefore need to be recognized in these patients so that effective cardiovascular protection can be introduced. In this Review the authors discuss validated techniques that are currently available to determine subclinical atherosclerosis in patients with rheumatic conditions.

Advances in the therapeutic management of systemic lupus erythematosus (SLE) have greatly improved life expectancy in patients with this disease, exposing their increased risk of cardiovascular disease (CVD) compared with the general population. In this Review, the authors discuss the influence that pathogenic processes and therapeutic interventions might have on the accelerated atherosclerosis observed in patients with SLE, as well as the potential approaches to reduction of CVD risk in these individuals.

Patients with systemic sclerosis (SSc) are at considerable risk of developing pulmonary arterial hypertension, which has a dramatic impact on the natural history of the disease and overall survival of the patient. Modern imaging modalities, such as novel echocardiographic techniques and cardiac MRI, are highly sensitive, quantitative and reproducible methods that allow noninvasive assessment of regional and global myocardial performance without relying on geometric assumptions. In this Review, the authors describe the standard clinical tests and evolving technologies, which can provide comprehensive and quantitative data on myocardial status that are useful in the clinical management and evaluation of patients with SSc.

Highly specific for rheumatoid arthritis (RA), anti-citrullinated protein antibodies (ACPA) are emerging as suspects in the disease pathogenesis. Do these autoantibodies define a subtype of RA, how does their presence and maturation relate to the course and characteristics of the disease, and how can we use them to improve patient outcomes? Essential facts about ACPA are explained in this Review.

HMGB1 is a non-histone nuclear protein that can serve as an alarmin to promote inflammation. In this Review, the authors present an overview of the structure and function of HMGB1. They also describe the role of HMGB1 in autoimmune and inflammatory diseases, including rheumatoid arthritis and systemic lupus erythematosus.

The interplay between the cells that regulate bone architecture and the immune system is increasingly recognized. In this Review, as well as providing an overview of fracture treatment and healing, the authors discuss our current knowledge of the part played by inflammation in the fracture repair process. The influence of biomechanical and biological factors on bone healing is also considered, focusing on the effects of excessive local and systemic inflammation, as occurs in autoimmune diseases such as rheumatoid arthritis.

The role of inflammation in rheumatoid arthritis (RA) is well characterized, but how hypoxia affects RA and the potential interplay between inflammation, angiogenesis and hypoxia in this disease is less defined. Here, the authors describe how hypoxia affects RA, in terms of both inflammation and angiogenesis, and provide insights as to how depleted oxygen levels affect the RA synovium. Potential therapies for RA that target angiogenesis will also be discussed.

In the two decades between publication, in 1990 and 2010, of the American College of Rheumatology criteria for fibromyalgia, research proliferated and substantial headway was made in understanding this complex, chronic disorder. So what was learned in the wake of the 1990 criteria, and how are the 2010 criteria changing the landscape of research, understanding and management, in patients with fibromyalgia?

Patients over the age of 50 years who present with a fracture seem to have the highest risk of subsequent fracture and also mortality immediately after the initial fracture is incurred. In this Review, the authors summarize the evidence that demonstrate this trend and discuss the factors that influence fracture risk. Finally, they propose a five-step systematic approach to management of patients who present with a fracture, aimed at preventing subsequent fracture, decreasing mortality rates and reducing undertreatment or overtreatment.

Susceptibility to osteoarthritis (OA) is influenced by genetic mutations, many of which occur in genes associated with the development of synovial joints. In this Review, Linda Sandell proposes a theory that these mutations can be placed on a continuum—from obvious alterations that result in mild chondrodysplasia associated with early-onset OA to subtle changes that predispose to 'primary OA' later in life. This view is explained in the context of our current etiological understanding of OA, and how this knowledge could improve screening and treatment of patients is discussed.

Advances in the fields of cell biology and imaging have allowed researchers to dig deeper into the underlying mechanisms of joint damage in patients with tophaceous gout. This Review describes some of the recent advances in our understanding of bone erosion and cartilage damage in this disease.