Juvenile idiopathic arthritis (JIA) is the commonest group of childhood arthritides. Despite the availability of advanced therapeutics, many children and young people (CYP) with JIA experience disease flares, and in some, chronic joint damage. Tailoring treatment based on unique biological profiles would benefit CYP with JIA given their variable clinical presentation and disease course. To date, biomarkers to predict treatment response are lacking. With advances in single cell technologies, we are now able to profile the genes and proteins of target tissues at unprecedented resolution to define the biological basis of disease and guide novel treatment approaches. The complex analyses and combination of biological and clinical outcome data from large datasets across disease phenotypes have become possible with the development of computational and machine learning methods. Here, we summarise the strategies to integrate data through enable multimodal based approaches to maximise precision medicine and research priorities for CYP with JIA.

In the past 3 years key recommendations for the management of systemic sclerosis (SSc) have been published, including updated EULAR recommendations and British Society for Rheumatology (BSR) guidelines. These recommendations are generally aligned but also reflect differences in the methodology and scope of the responsible organizations. For both EULAR and BSR, the methodology is robust and aligns with recommendations and guidelines developed for other rheumatic conditions and produced by other specialist societies. Advances in treatment and a growing evidence base for management of interstitial lung disease (ILD), a frequent complication of SSc, have informed additional relevant recommendations that include SSc-ILD. Some of these cover a broad range of ILDs that occur across systemic autoimmune rheumatic diseases, including those developed by the ACR-American College of Chest Physicians and the 2025 European Respiratory Society-EULAR clinical-practice guidelines. The American Thoracic Society has also developed recommendations for SSc-ILD. Taken together, a comparison of these published guidelines provides an overview of best practice evidence-based management that is supported by expert opinion and relevant stakeholders. By considering the overlap and similarity in recommendations and highlighting differences in approach and scope, this article helps readers to navigate an evolving treatment landscape of SSc.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies and characterized by blood and tissue eosinophilia, severe respiratory manifestations, and multiorgan involvement. The management of newly diagnosed EGPA still relies on therapeutic strategies that were initially validated for other forms of anti-neutrophil cytoplasmic antibody-associated vasculitis, including microscopic polyangiitis and granulomatosis with polyangiitis. Whereas the long-term prognosis of microscopic polyangiitis and granulomatosis with polyangiitis depends primarily on controlling initial organ involvement and preventing relapses, EGPA is distinguished by chronic involvement of both upper and lower respiratory airways, which often necessitates prolonged glucocorticoid therapy. Data from clinical trials suggest that targeting the IL-5 pathway with mepolizumab or benralizumab can effectively control persistent respiratory symptoms and reduce the need for glucocorticoids, yet the role of these agents in the management of EGPA at the time of diagnosis and in the long term remains to be defined. Emerging retrospective data on therapies targeting other type 2 cytokines (such as IL-4, IL-13 and thymic stromal lymphopoietin) suggest potential benefits for relapsing respiratory symptoms; however, prospective evidence remains limited and safety has yet to be established. This Review discusses the role of these new targeted therapies in the management of EGPA, alongside historical treatments.

Sex differences in the prevalence, clinical phenotypes and therapeutic responses of rheumatic diseases have been recognized for decades, but the underlying mechanisms remain largely unknown. Accumulating evidence highlights the critical roles of both immune and non-immune cells in disease pathogenesis and the influence of sex hormones on cellular function. In addition, factors such as sex chromosomes, hormonal regulation, antiviral immune response, the gut microbiome and genetic and epigenetic variation probably contribute to the divergent features of rheumatic diseases between women and men. A deeper understanding of these intersecting pathways might uncover novel therapeutic targets. Thus far, treatment strategies for rheumatic diseases largely focus on immunomodulation; however, elucidating the biological basis of sex differences could enable the development of preventative therapies that target hormonal pathways and the gut microbiome, with the potential to avert both the onset and progression of these debilitating diseases to improve health for all patients.

Rheumatoid arthritis (RA) disproportionately affects adults over 50 years of age, highlighting how age-related immune remodelling undermines tolerance and promotes autoreactivity. In later adulthood, immune cells progressively lose metabolic resilience because of impaired nutrient sensing, reduced metabolic flexibility and disrupted anabolic-catabolic balance. In RA, these vulnerabilities are compounded by mitochondrial insufficiency across innate and adaptive immune lineages, creating a state of nutrient deprivation characterized by NAD[+] and ATP scarcity and diversion of carbon away from oxidative phosphorylation. Mechanistic studies identify this bioenergetic fragility as a core defect that limits cellular longevity and promotes inflammatory, non-apoptotic death pathways, including pyroptosis and PANoptosis. The hypoxic, nutrient-restricted synovial environment adds pressure that exceeds the diminished metabolic adaptability of aged immune cells. In RA T cells, accelerated mitochondrial injury initiates maladaptive stress responses, disrupts mitochondria-lysosome-endoplasmic reticulum communication and induces gasdermin D-dependent pore formation and inflammatory lysis. Synovial MerTK[+] reparative macrophages undergo a parallel metabolic crisis, whereby autocrine C1q sensing activates mitochondrial SARM1, causing NAD[+] degradation, ATP depletion and PANoptotic cell death. Together, these findings position ageing-associated metabolic exhaustion and organelle disintegration as unifying mechanisms that convert immune cells into tissue-damaging effectors and explain the heightened susceptibility to RA in older adults.

Psoriatic arthritis (PsA) develops in up to 30% of individuals with psoriasis, but the mechanisms that drive progression from skin-limited disease to musculoskeletal disease remain incompletely understood. Emerging evidence supports a functional skin-joint axis in which psoriatic plaques function not only as sites of local inflammation but also as sources of immune cells capable of shaping musculoskeletal pathology. Myeloid progenitors that reside in the inflamed skin can migrate to synovial compartments; however, cell trafficking alone is insufficient to induce arthritis, as the fate of these cells is dictated by the stromal microenvironment of the musculoskeletal niche. Data from single-cell RNA sequencing, imaging mass cytometry and mitochondrial DNA lineage tracing now provide direct evidence that skin-derived myeloid precursors populate synovial tissue in people with early PsA. In parallel, T cell receptor analyses indicate that clonally related T cells are shared between psoriatic skin and inflamed joints, indicating that skin-derived T cells migrate between tissues. Together, these findings fuel a model in which PsA emerges through the convergence of high-risk skin lesions, a systemic milieu permissive to immune cell trafficking and a receptive joint stromal niche, with implications for biomarker discovery, risk stratification and disease interception.