Reviews & Analysis

Mendelian randomization analysis makes use of random inheritance of genetic variants to limit confounding in tests for causal relationships between risk factors and disease outcomes. This Review considers the current and future applications, as well as the limitations, of Mendelian randomization in rheumatology.

Mental health-related comorbidities can negatively affect the quality of life of patients with rheumatoid arthritis. In this Review, the authors discuss how psychological manifestations interact with disease processes, new insights into neurological processing in chronic pain, and psychological interventions.

Radiographic joint-space width is the standard structural outcome for trials in knee osteoarthritis (OA), but MRI provides comprehensive 3D insights into the multi-tissue pathology of OA and could provide a superior means of monitoring disease progression and response to treatment. A new study highlights bone as an imaging biomarker.

Glucocorticoids are cost-effective drugs that exert strong anti-inflammatory and immunosuppressive effects. However, there is increasing awareness of their potential adverse effects. Although Cushingoid appearance and weight gain have been known for decades, modern measurements of body composition now enable detailed insights into glucocorticoid-induced changes in fat mass and redistribution.

Macrophages, which have roles in the pathogenesis and resolution of rheumatoid arthritis, consist of a heterogeneous population of cells with different origins and functions. This Review describes these properties, and considers the potential for therapeutic targeting of specific macrophage subtypes.

Statin treatment is a cornerstone in the prevention of cardiovascular disease, but questions remain regarding its effects in patients with ankylosing spondylitis. Is there enough evidence supporting the use of statins in these patients?

Autoantibodies against end products of lipid peroxidation have unexpected effects on atherosclerosis in systemic lupus erythematosus (SLE). The discovery of their effects could lead to new theories about the role of the adaptive immune system in SLE.

Autophagy underlies the cellular pathology of several rheumatic diseases. Targeting the signalling pathways involved has shown promise in recent clinical trials. Rockel and Kapoor discuss the key regulators involved in autophagy and therapeutic strategies currently in use and under development.

Cases of systemic lupus erythematosus with onset during childhood seem to be more severe than adult-onset disease, possibly because of genetic influences. But is more-detailed information about the molecular heterogeneity of the disease needed in order to tailor treatments and improve prognosis?

Diagnostic algorithms for axial spondyloarthritis (SpA), and classification criteria for use in clinical trials, are being developed and refined. But can axial SpA be ruled out in young patients with only one clinical feature of SpA prior to imaging studies and HLA-B27 testing?

A growing body of evidence implicates the human gut microbiota in health and in disease, including spondyloarthritis, psoriatic arthritis and rheumatoid arthritis. This article explores the ways in which the microbiota influences innate and adaptive immune responses in the host.

Emerging evidence suggests the nervous system, including the circadian timing system, influences susceptibility to osteoarthritis (OA) via direct and indirect effects. This Review describes the interactions between the brain and the joints in the context of OA, ageing, obesity and inflammation, and outlines therapeutic and research opportunities in this field.

This Review provides an overview of new discoveries that are changing our understanding of the complex role of the human gut microbiota and its metabolites in health and disease, including their effects on rheumatic diseases. Factors that modulate the microbiota, such as diet and probiotics, and advances in pharmacomicrobiomics are also discussed.

Besides their well-known role in cell death mechanisms, CD8⁺ T cells are now emerging as critical mediators of autoimmune diseases. CD8⁺T-cell homeostatic changes under inflammatory conditions, such as phenotypic variation and impaired regulation, provide insights into the pathogenesis of autoimmune arthritis and potential therapeutic targets.

Type I interferon (IFN) is an attractive therapeutic target in systemic lupus erythematosus (SLE), a notion bolstered by the positive results of a recent clinical trial of the anti-IFN antibody sifalimumab in patients with SLE. Interestingly, sifalimumab worked best in patients with high expression of IFN-induced genes, supporting the idea that subgroups of patients might be targeted specifically.

Non-radiographic axial spondyloarthritis (nr-axSpA) and radiographic axial spondyloarthritis (r-axSpA) are considered to be different spectra of the same disease. Accumulating data suggest a low transition rate from nr-axSpA to r-axSpA in patients with early disease and identify inflammation, smoking and HLA-B27 positivity as factors associated with transition.

In this article, the authors provide a comprehensive and timely review of the mechanisms and consequences of hypoxia in the biology of inflammatory arthritis, with a focus on mitochondrial function, hypoxia signalling pathways in rheumatoid arthritis, and therapeutic implications.

Although paracetamol is widely used and recommended for the management of pain in osteoarthritis, accumulating data indicate that it lacks efficacy and is associated with severe adverse effects. A new meta-analysis adds further weight to calls for clinical practice and treatment guidelines to be updated to reflect the evidence.

Clinical trial data suggest the IL-6-targeted drug clazakizumab ameliorates the symptoms of psoriatic arthritis (PsA), in particular the musculoskeletal manifestations of the disease. Could this new treatment hold promise for a certain subgroup of patients with PsA?

Although changes associated with ageing promote the development of osteoarthritis (OA), ageing and OA are independent processes. In this Review, the authors discuss the mechanisms by which age-related factors contribute to OA through effects on articular cartilage and propose that future improvements in our understanding of these mechanisms will inform new therapies to slow or stop the progression of OA.