Reviews & Analysis

Analysis of regional variations in the epidemiology of rheumatoid arthritis (RA) over the past 40 years indicates that the age-standardized incidence of RA has increased — and is expected to continue rising — while the mortality and morbidity of the disease are decreasing. As a result, the number of years lived with disability and the overall disease burden attributable to RA have increased and are projected to rise further.

Immune-mediated inflammatory diseases (IMIDs) are associated with cancer risk through mechanisms involving disrupted immune tolerance and dysregulated immune responses. Deng et al. investigated how the timing of IMID diagnosis relative to cancer diagnosis affects patient survival outcomes.

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with high prevalence in Mediterranean populations. Considerable advances in the management of FMF have been made in the past decade, with respect to the use of biologic drugs and understanding colchicine resistance. The 2024 updated FMF management recommendations are timely and reflect these advances.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is caused by somatic mutations in UBA1 arising in hematopoietic stem cells, resulting in systemic autoinflammation and clonal outgrowth of these mutant cells. New research provides insights into the paradoxical mechanism behind this clonal hematopoietic dominance.

The increased incidence of deep vein thromboses and pulmonary emboli has long been noted in rheumatoid arthritis and has been ascribed to the effects of chronic inflammation and disease activity, as well as to specific biologic DMARDs and JAK inhibitors. Reporting in ACR Open Rheumatology, Zavoriti and Miossec provide data that might explain the prothrombotic effects of the JAK inhibitor tofacitinib.

Separate guidelines are needed for the management and diagnosis of rheumatic diseases in low- and middle-income countries, especially with the advent of expensive biological therapies and monitoring techniques. The lack of robust data on the efficacy of low-cost drugs and biosimilars in these countries limits the development of data-driven guidelines.

In joints with osteoarthritis, angiogenesis and neuronal growth occur at the osteochondral junction, a process that can contribute to structural joint damage and pain. Targeting this neurovascularization process represents a possible strategy for the development of disease-modifying drugs for osteoarthritis.

A simple blood test that can diagnose or predict one’s risk for autoimmune diseases would revolutionize medicine and transform patient care. Published in Science, Zaslavsky et al. advance this vision with a powerful machine learning framework that leverages immune receptor sequences from T cells and B cells for disease classification.

Molecular imaging techniques such as PET with the leukocyte-targeted probe ⁸⁹Zr-CD45 are promising tools for rheumatology, providing a non-invasive whole-body assessment of the mechanisms that drive tissue inflammation. These techniques could improve diagnosis and disease monitoring, but further research is required before clinical implementation.

Treating people with inflammatory arthritis and cancer is challenging given concerns around suppressing anti-tumour immunity. Targeted therapies, such as TNF inhibitors, can be safely used in patients with cancer who are in remission, but whether these treatments are safe for individuals with newly diagnosed or active cancer remains unclear.

Hasegawa et al. reveal how synovial joints detect systemic inflammation through specialized fenestrated blood vessels at the synovial periphery. Three distinct macrophage populations and nociceptor neurons form a sentinel unit around these vessels, coordinating immune responses and pain signalling through interleukin-1β (IL-1β) and calcitonin gene-related peptide (CGRP) signalling.

The first expert consensus recommendations for the treatment and diagnosis of adult sterile bone inflammation have been developed, in which the term ‘chronic non-bacterial osteitis’ is proposed as a disease definition. Will these recommendations pave the way for better diagnosis, management and treatment of this rare disease?

The mechanisms that drive the diverse disease manifestations and increased cancer risk associated with systemic sclerosis are unclear. Investigating the genomic alterations observed in patients with systemic sclerosis could contribute towards untangling this complex disease.

Results of the STEP 9 trial show that semaglutide leads to improvements in knee osteoarthritis-related symptoms. The findings support weight-management pharmacotherapies as a feasible option for management of knee osteoarthritis, but cost-effectiveness, risk of toxicity and likelihood of rebound must be considered.

The updated 2023 EULAR recommendations for treatment of systemic sclerosis bring notable changes to recommendations for skin, peripheral vascular disease, interstitial lung disease and pulmonary arterial hypertension therapies, based on newer evidence. These updates provide the first glimmer of personalized patient management.

The role of proteases in cartilage degradation and the development of osteoarthritis is undeniable. Despite over two decades of research on protease inhibitors, however, the transition from preclinical promise to clinical success remains elusive, underscoring the urgent need to critically appraise the challenges and limitations inherent in preclinical studies.

The identification of shared molecular mechanisms across systemic inflammatory autoimmune diseases with overlapping clinical manifestations has prompted research into the underlying genetics that could be driving these manifestations; elucidating these genes could aid in the diagnosis, treatment and outcome prediction of these complex diseases.

EULAR and the Paediatric Rheumatology European Society (PReS) now view systemic juvenile idiopathic arthritis and adult-onset Still’s disease as a single disease — Still’s disease — given their overlapping biomarkers, clinical manifestations and complications. This consensus provides valuable insights into Still’s disease diagnosis and management across age groups, and also highlights research priorities.

New classification criteria for axial disease in juvenile spondyloarthritis aim to enhance the identification and study of this condition in affected youth, offering a tool for future non-interventional studies and interventional trials. Better understanding of the efficacy of various interventions in the axial domain could help tailor treatment strategies.

Type I interferon has a crucial role in the immunopathogenesis of systemic lupus erythematosus (SLE). Analysis of CD4⁺ T cells from individuals with SLE now shows that type I interferon intervenes with the transcriptional regulators AHR and JUN to downregulate expression of IL-22, which promotes tissue regeneration, and upregulate the expression of CXCL13, which supports lymphoid structure formation.