Reviews & Analysis

Early identification of osteoarthritis (OA) prior to the development of symptoms is challenging. Post-traumatic OA provides a model for the development of OA following a defined event. In this Review, the authors describe the existing knowledge relating to the biomarkers of post-traumatic OA, which might also be applicable to the identification of early non-traumatic OA.

This Review discusses joint-specific memory (the tendency of arthritis to recur in previously inflamed joints), explores the involvement of resident memory T cells and other contributors, and evaluates how arthritis might spread to new joints, emphasizing the important of sustained treatment.

Rheumatoid arthritis has a substantial genetic component, some of which is associated with the presence of low-frequency or rare variants. Next-generation sequencing in large and well-defined cohorts can continue to identify these variants and thereby contribute to the future prediction, diagnosis and treatment of rheumatoid arthritis.

EULAR’s 2023 updated recommendations for the non-pharmacological treatment of hip and knee osteoarthritis reiterates and confirms, in an abbreviated form, what we have known for more than a decade. Unfortunately, the abbreviated format of the updated recommendations lacks specificity and clinical usefulness. More detailed guidance could have facilitated wider uptake and improved care.

In this Evidence-Based Guideline article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents recommendations for the diagnosis, monitoring and treatment of osteoporosis in men.

Gout is associated with various cardiometabolic–renal comorbidities that increase the risk of mortality. Sodium–glucose cotransporter type 2 (SGLT2) inhibitors show promise in both addressing the symptoms of gout and managing relevant comorbidities to help prevent premature mortality.

Characteristic patterns of joint involvement exist in different forms of arthritis. Research now indicates that epigenetic programming of synovial fibroblasts diversifies their response to inflammatory cascades, leading to this anatomical variation in arthritis and its response to treatment.

In 2006, a linear immunological continuum of autoinflammatory and autoimmune disorders ranging from monogenic diseases of innate immunity at one end to monogenic diseases of adaptive immunity at the other end was proposed to classify these conditions. Deep immunophenotyping has now revealed a cell-based nosology of these disorders.

Tyrosine kinase 2 (TYK2), a Janus kinase family member, is involved in immune signalling and is implicated in autoimmune diseases such as systemic lupus erythematosus; inhibitors of TYK2 show promise in treating various diseases and potentially offer advantages over other Janus kinase inhibitors.

Beyond the traditional classification of monogenic or complex, many genetic diseases can be considered genetically transitional disease. In this Perspective, the authors consider the application of the genetically transitional disease model to rheumatic diseases and the potential implications for patient care, genetic counselling and research.

Immunoengineering involves the design of materials with specific properties relating to the immune system. In this Review the authors consider the application of immunoengineering to systemic autoimmune diseases via site-specific and antigen-specific immunoregulation, the facilitation of immune cell therapy, novel approaches to immunodiagnostics and the generation of models to study autoimmunity.

The World Health Organization (WHO) has published new guidelines for the non-surgical management of chronic primary low back pain in adults in primary and community care settings. Although the guidelines are commendable, they lack guidance on when to suspect and how to avoid missing important secondary causes of back pain.

Deep learning is a powerful technique with great potential for the analysis and interpretation of rheumatological images. To successfully use deep learning, rheumatologists should understand the tasks involved in image processing and the potential confounders and limitations that can affect the analysis of clinical data.

Juvenile idiopathic arthritis treatment has evolved with new therapies, early remission goals and global efforts, including randomized trials and a treat-to-target strategy. This Review summarizes current evidence and therapeutic approaches to the management of non-systemic phenotypes of juvenile idiopathic arthritis.

This Review discusses the interplay of the gut microbiome and the immune system in the context of systemic lupus erythematosus. Dysbiosis and gut-barrier dysfunction are implicated in promoting disease and are potential therapeutic targets.

New findings suggest that current cell therapy approaches are not superior to a simple corticosteroid injection for the treatment of osteoarthritis, calling into question the role of existing cell therapies and highlighting the need for further research and development in this field.

Re-establishing tolerance to autoantigens is an important aim for the treatment of rheumatoid arthritis (RA). Immunization of HLA-DR4 transgenic mice with citrullinated self-antigens can induce immune tolerance, which suggests that such antigens could have a therapeutic role in anti-citrullinated peptide antibody-positive RA.

This Review explores the potential of emerging RNA-based technologies and cell-engineering strategies, including those that incorporate small interfering RNA, microRNA, mRNA and synthetic receptor-mediated gene editing, to provide innovative and targeted approaches to osteoarthritis therapy.

The identification of novel risk variants in the largest genome-wide association study of Raynaud phenomenon to date provides insights into the pathophysiology of the condition, including the potential role for α_2A-adrenoceptors, and suggests opportunities for drug repurposing.

Concerns have been raised about the safety of Janus kinase (JAK) inhibitors. This Review summarizes the evidence regarding the risks and benefits of JAK inhibitors to clarify which patients are most at risk of adverse events and guide clinical decision-making.