Reviews & Analysis

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.

Systems level analysis using stimulus–response modelling could increase our understanding of the interplay between biochemical, structural and functional variables that influence the development and manifestation of osteoarthritis. Furthermore, surrogate markers of clinical responses identified might enable early diagnosis, improve therapy, and facilitate development of new treatments and end points.

New evidence suggesting an X chromosome effect underlies the development and progression of male systemic lupus erythematosus comes from a study of sex chromosome aneuploidy in men with this disease. The description of a number of immunoregulatory mechanisms encoded on the X chromosome support this hypothesis; however, further studies are warranted.

Severity scoring systems for adult familial Mediterranean fever (FMF) are established and used as important clinical and analytical tools in disease management and research. A recent paper highlights the need for a paediatric FMF severity measure. How should such a score be built and what challenges might be faced?

Recently reported associations between synovitis, cartilage damage and plasma levels of omega-3 and omega-6 fatty acids in patients with osteoarthritis suggest that fish oil supplements might be beneficial additions to the therapeutic regime in this disease; however, questions remain regarding the details of this approach, and controlled trials are required.

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.

Although systemic lupus erythematosus is the prototype multisystem disease, many other inflammatory diseases are also promiscuous, with symptoms manifesting in many organs. Now, new data emphasize the extra-articular involvement in spondyloarthritis, predominantly affecting the eye; however, the factors that account for the observed organ involvement remain unknown.

Effective osteoarthritis (OA) therapies would delay the need for total joint replacement (TJR). Recently, a committee of researchers attempted to develop a threshold for virtual TJR to be used as a standardized outcome for OA trials; their failure highlights challenges that complicate the measurement of OA and provision of TJR.

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.

Despite their different targets, biologic agents used for blockade of TNF and IL 6, inhibition of T cell co-stimulation and B cell depletion all have similar beneficial effects on the outcome of rheumatoid arthritis (RA). This observation raises questions as to whether the targets of these therapies might all be involved in a common pathogenetic pathway. In this Perspective, the authors discuss the disparities in RA therapy and whether clinical trial data can be used to determine at which point a biologic agent might interfere with the pathogenetic RA cascade.

Early diagnosis and treatment of rheumatoid arthritis improves long-term outcomes and reduces or halts joint damage progression. However, delays at the patient and medical system levels remain a barrier to early diagnosis and therapy, despite the presence of early arthritis clinics designed to expedite treatment.

New consensus treatment plans state that the combination of glucocorticoids and immunosuppression is treatment of choice for newly diagnosed pediatric patients with proliferative lupus nephritis. However, variations exist in the steroid protocol and in the type of immunosuppressant used, indicating that a gold-standard treatment protocol is yet to be achieved.

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.

In an age in which immunosuppression is the standard of care for many pediatric rheumatic diseases, balancing the risks and benefits of vaccinations is forefront. Three main issues—addressed in new guidelines—surround vaccination practices in these patients: safety, immunogenicity and effects of the vaccine on the underlying rheumatic disease.