Reviews & Analysis

Current guidelines for the treatment of osteoarthritis involve exercise and lifestyle modifications as well as pharmaceutical therapeutics for effective pain management. Is this message reaching patients, and are they exercising enough?

Both spondyloarthritis and uveitis are associated with HLA-B27 positivity. This Review discusses this overlap and how the intestinal microbiome and dysbiosis might contribute to the development of both diseases.

Seropositive RA can present with two different types of autoantibodies that have distinct features: anti-citrullinated protein antibodies (ACPAs) and rheumatoid factors (RFs). With a single-cell approach, researchers provide evidence that the underlying B cell subsets of these autoantibody specificities develop in parallel by different mechanisms.

The IL-23–IL-17 signalling pathway has paradoxical effects on bone remodelling in psoriatic arthritis and ankylosing spondylitis. In this Review, Gravallese and Schett examine the evidence for and outline the reasons behind this paradox.

Adult-onset Still’s disease (AoSD) is not easily diagnosed, and treatment options are limited. This Review provides an overview of the disease and its pathogenesis, clinical trial results, therapeutic options and a plan to diagnose and clinically manage these patients.

Environmental changes can sometimes be too rapid for genetic adaptation and result in a mismatch between our genetics and the environment. Osteoarthritis should be considered a mismatch disease owing to a rapid increase in prevalence that is associated with the modern lifestyle, diet and patterns of physical activity.

The deposition of calcium-containing crystals can result in various acute and chronic arthropathies. Understanding the biological effects of these crystals and underlying pathogenic mechanisms might inform on the development of future therapeutic strategies for these conditions.

Tight regulation of signalling cascades is vital for the correct development and function of bones and joints. A new study suggests that Notch signalling might join the likes of the transforming growth factor superfamily and Wnt signalling cascades as having an important function in joint homeostasis and disease.

Using mice with targeted deletion of the glucocorticoid receptor, a new study has examined the cell types that mediate the anti-arthritic effects of therapeutic glucocorticoids. Surprisingly, in the serum transfer-induced arthritis model, glucocorticoids target stromal cells rather than immune cells.

Inappropriate activation of Toll-like receptor 4 (TLR4) on resident fibroblasts, through the binding of damage-associated molecular patterns, is a potential driver of fibrosis in systemic sclerosis. New evidence suggests that targeting fibroblast-specific TLR4 or an accessory molecule MD2 could have therapeutic value.

Cancer immunotherapies that function as checkpoint inhibitors are an exciting development but are associated with immune-related adverse events that can occur in almost any organ. Among these events are complications that mirror established rheumatic diseases, so oncologists and rheumatologists must work together.

The two major lung complications in systemic sclerosis, lung fibrosis and pulmonary arterial hypertension, share some pathogenic mechanisms. Strategies for managing patients with these complications have greatly advanced in the past decade, and many tools and treatments are now available.

Preclinical rheumatoid arthritis (RA) is characterized by the presence of RA-related autoantibodies in the serum in the absence of clinical symptoms. This Review discusses the relationships during this period between mucosal alterations and the initiation of local and systemic anti-citrullinated protein antibody production.

Stimulator of interferon genes (STING), an important component of the cytosolic DNA sensing pathway, is an attractive therapeutic target for ameliorating interferon-driven systemic inflammation. New findings are shedding light on how STING functions and on a strategy to target STING therapeutically.

B cell depletion has become standard-of-care for the treatment of ANCA-associated vasculitis, but can more be done to target B cells? In this Review, the authors look beyond rituximab to alternative B cell-targeting therapies and novel therapeutic combinations.

Mental health symptoms are a common and functionally impairing feature of rheumatoid arthritis, and increasingly seem to represent an integral part of the inflammatory process. Could treatment with DMARDs affect physical as well as mental health outcomes?

Combining TNF inhibition with methotrexate treatment is an effective therapeutic approach for patients with rheumatoid arthritis and reduces the likelihood of the patient developing ‘resistance’ to the TNF inhibitor. But how does methotrexate suppress the production of anti-drug antibodies and how can we tell which patients will develop resistance?

S100 proteins have many intracellular functions, as well as being extracellular signalling molecules in inflammation. A deeper understanding of this family of proteins could lead the way to diagnostic and prognostic biomarkers and novel therapeutic strategies.

Large-scale genetic studies have highlighted the retinoic acid pathway as a contender in the pathogenesis of hand osteoarthritis. Functional studies are offering further insights into the role of retinoic acid that might translate into future therapies.

Evidence from genetic, experimental and clinical studies has accumulated to indicate a role for the IL-17 pathway in the pathogenesis of spondyloarthritis. This Review discusses how IL-17A and IL-17F and their cellular sources contribute to the immunopathology of these diseases.