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.

RA is associated with a markedly increased risk of venous thromboembolism (VTE), reflecting a complex interplay between chronic inflammation, immune dysregulation and haemostatic imbalance. Large population-based studies consistently demonstrate a 50-100% excess risk of deep vein thrombosis and pulmonary embolism in RA, with the highest incidence early after diagnosis and during flares. Mechanistically, inflammatory cytokines, endothelial dysfunction, platelet activation, impaired fibrinolysis and autoantibody-driven immune responses promote a state of chronic immunothrombosis. RA-specific factors such as disease activity, seropositivity, disability and treatment exposures further modify thrombotic risk; some targeted therapies may amplify the risk in a subset of patients. Despite these insights, current VTE risk stratification and prevention strategies are extrapolated from the general population and fail to incorporate RA-specific factors. Improved understanding of the reason(s) behind the increased VTE risks reported with certain immune-modulatory drugs, and development of integrated clinical and biomarker-based stratification tools, are therefore both essential to enable effective thromboprophylaxis in RA.

Inflammatory arthritis is characterized by neovascularization, leukocyte extravasation and synovial hyperplasia, leading to joint destruction and functional disability. Although increased synovial angiogenesis is a hallmark of synovial inflammation, efficiency of the oxygen supply to the synovium is poor, leading to a hypoxic gradient that impacts differential cellular responses. This hypoxic gradient occurs as infiltrating cells and cells that reside within the joint increase their metabolic demand beyond what the highly dysregulated vasculature can supply. This hypoxic environment favours an increase in reactive oxygen species, leading to oxidative damage that further promotes inflammation. In this adverse microenvironment, synovial cells adapt to generate energy and switch their cellular metabolism from a resting regulatory state to a highly metabolically active state, enabling them to produce essential building blocks to support their proliferation. This metabolic shift results in the accumulation of metabolic intermediates that function as signalling molecules, which further dictate the inflammatory response. However, the synovium is a complex multicellular tissue, and the specific cellular reliance on oxygen and metabolites differs across the synovium. Cellular demands depend on anatomical location, cell-cell interactions and competition for nutrients. Understanding the complex interplay between hypoxia-induced signalling pathways, oxidative stress and inflammatory responses will provide a better insight into the underlying mechanisms of disease pathogenesis.

Medical nutrition therapy significantly impacts cardiovascular risk and overall health, but effects on muscle diseases remain unclear. This systematic review evaluates the safety and efficacy of dietary interventions and supplements on muscle disease outcomes.

Autoantibodies are central to the diagnosis, classification, and stratification of many autoimmune diseases, particularly those characterised by B-cell activation and MHC class II associations. However, a substantial proportion of patients have historically been labelled as seronegative, creating diagnostic uncertainty and suggesting either technical limitations in autoantibody detection or genuinely distinct pathogenic mechanisms. Advances in laboratory assays, encompassing the adoption of recombinant antigens, high-throughput autoantibody profiling, and autoantigen discovery, have progressively reduced the boundaries of seronegativity across several autoimmune diseases. In this Personal View, we discuss how improved autoantibody detection and the identification of novel specificities have reshaped concepts of seronegative disease across different clinically relevant examples of autoimmune diseases. We further examine how autoantibodies inform patient stratification, influence cancer-associated autoimmunity, and even reverse translational immunology implications and pathogenic hints, while highlighting contexts in which genuinely seronegative autoimmunity might still exist.

Pain is a frequent symptom in people with inflammatory arthritis (IA), which has substantial impact on their quality of life. Analyses of electronic health record data indicate that UK pain care in people with IA often involves prescribing long-term opioids and gabapentinoids, despite absent trial evidence for efficacy. Patient survey data suggest that non-pharmacological pain care with supportive trial evidence is underused. A UK-specific guideline on pain management for people with IA is required to address this. This comprehensive life-course guideline is the first British Society for Rheumatology Guideline to specifically address pain in people with IA. It provides evidence-based recommendations on how pain can be best managed in people with IA. It was developed using the methods outlined in the British Society for Rheumatology's 'Creating Clinical Guidelines' protocol by a multidisciplinary Guideline Working Group, comprising healthcare professionals with expertise in paediatric and adult rheumatology and people with lived experience. By undertaking and considering the evidence from several systematic literature and umbrella reviews, 23 recommendations were developed. These address how pain should be assessed in people with IA alongside the role of the following treatments in IA pain management: DMARDs, glucocorticoids, analgesics, neuromodulators, exercise and physical activity, psychological interventions, ergonomic and orthotic interventions (excluding orthoses for foot pain), education, weight management and diet, addressing sleep problems, fatigue management, digital technologies and medical devices, complementary therapies, and support from others. An audit tool is provided to support the Guideline's implementation, and key recommendations made for future research.

Although the diagnosis of rheumatoid arthritis can usually be made once clinical arthritis appears, this moment does not represent the biological onset of disease. Rheumatoid arthritis develops over a period of years in preclinical phases that precede the emergence of persistent joint inflammation. In this narrative Review, we examine how chronicity develops along this trajectory by integrating temporal and tissue perspectives. We discuss early disease phases characterised by the emergence and maturation of autoimmunity and systemic inflammatory shifts, followed by stages marked by subclinical and subsequently clinical joint inflammation, in both anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative rheumatoid arthritis. We consider how some immune perturbations could resolve in some individuals, while others progress to self-sustaining disease, highlighting that reversibility might differ across disease trajectories. Lastly, we examine how evolving multi-hit hypotheses, recent omics studies, and results from prevention trials inform the identification of checkpoints at which progression to chronic disease might still be modifiable.

The IL-1 family comprises key pro-inflammatory cytokines that are central to host defence against noxious stimuli, as evidenced by their prominent expression at barrier tissues and their shared myeloid differentiation primary response 88 (MyD88)-dependent signalling pathways with Toll-like receptors. The generation of biologically active IL-1 agonists is tightly controlled by proteolytic processing (including inflammasome-dependent and independent mechanisms), which converts inactive precursors into mature cytokines or substantially amplifies the activity of selected family members. IL-1 signalling is further regulated at multiple levels by endogenous inhibitors, decoy receptors and receptor antagonists, ensuring a finely tuned balance between pro-inflammatory and anti-inflammatory responses; this balance is essential for effective antimicrobial immunity while limiting immunopathology. Converging evidence from human studies and experimental disease models demonstrates that disruption of this regulatory balance underlies a broad spectrum of inflammatory diseases. Numerous therapies that target IL-1 cytokines have been approved for the treatment of inflammatory diseases or are in development, and the clinical efficacy of these therapies provides compelling validation of their pathogenic role in numerous disease contexts.

Current guidelines recommend influenza and pneumococcal vaccination in the majority of patients with rheumatic diseases. This study aimed to summarize the coverage of influenza and pneumococcal vaccines among these patients.

ANCA-associated vasculitides (AAVs) are rare diseases characterized by small-vessel necrotizing vasculitis, multiorgan involvement and positivity for ANCAs. The main phenotypes are granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis, representing distinct yet partially overlapping entities in terms of pathogenesis, clinical expression and therapeutic management. Patients with AAV face a substantial cardiovascular (CV) and thrombotic risk, with higher rates of myocardial infarction, ischaemic stroke and venous thromboembolism than the general population. The excess CV burden reflects a complex, time-dependent interplay between disease-related inflammation, traditional CV risk factors and treatment-related toxicity, with inflammatory activity emerging as a key driver of early CV events. Across the disease course, this evolving risk profile requires multidisciplinary management to limit CV damage accrual and related mortality. This review integrates evidence on pathogenesis, clinical manifestations and management of CV disease in AAV, highlighting its time-dependent trajectory and key unmet needs.

Systemic Lupus Erythematosus (SLE) is a severe autoimmune disorder that impacts multiple organ systems, with African American (AA) adults having worse outcomes and poor prognoses compared to other ethnic groups. Ineffective patient-provider communication and inadequate screening for modifiable risk factors contribute to poorer SLE outcomes and ongoing health disparities. This scoping review evaluated the influence of patient-provider communication among adults with SLE, with particular attention to implications for African American populations, to inform the development of strategies to mitigate SLE health disparities.

To provide a meta-level comparison of standardized safety profiles ('gestalt') of currently licensed biologic and targeted synthetic disease-modifying anti-rheumatic drugs (bDMARDs and tsDMARDs) in rheumatoid arthritis (RA) from pivotal clinical trials.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that impacts patients' quality of life. Evidence regarding the effectiveness of metformin use as an adjunct therapy in RA is limited and fragmented. This systematic review and meta-analysis aimed to evaluate the effectiveness of metformin as an adjunct therapy in RA and to quantitatively synthesize available evidence.

SLE is a chronic autoimmune disease associated with substantial cardiovascular, metabolic and renal morbidity. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially developed for type 2 diabetes (T2D), have demonstrated beneficial effects beyond glucose lowering, including improvements in metabolic, cardiovascular and renal outcomes. These effects span multiple domains, including glycaemic control, body weight and blood pressure reduction, heart failure and atherosclerotic cardiovascular disease outcomes, kidney function preservation and potential immunomodulatory pathways. This narrative review summarizes the metabolic, cardiovascular, renal and immunomodulatory effects of SGLT2i relevant to SLE. Evidence from the general population supports cardiometabolic and renal benefits, while observational studies and early-phase trials in SLE and LN suggest potential benefits in selected patients. However, SLE-specific evidence remains limited, and important gaps persist regarding efficacy and safety in active disease. Further studies are needed to define the role of SGLT2i in SLE.

Systemic lupus erythematosus (SLE) is a lifelong autoimmune condition with multi-system involvement that is associated with morbidity, mortality, and poor quality of life. The key aim of management should be to empower individuals with SLE to manage their condition, suppressing systemic disease activity, and preventing organ damage. This guideline builds on and expands the recommendations developed for the first guideline published in 2017 for adults living with SLE. This comprehensive life-course guideline was developed according to the British Society for Rheumatology Guidelines Protocol by a Guideline Working Group (GWG) comprising healthcare professionals with expertise in paediatric and adult SLE, and people with lived experience. The GWG reviewed published guidelines, undertook a systematic literature review and utilised expertise from specialist lupus centres across the UK and patient representatives to formulate a list of 102 recommendations with corresponding strength of recommendations and agreement scores. These recommendations encompass advances in the assessment, diagnosis, monitoring, general approaches to management, non-pharmacological and pharmacological management of SLE, organ-specific treatment including lupus nephritis and cutaneous lupus erythematosus, as well as the delivery of care in the context of the UK healthcare system. Furthermore, we have provided research and audit recommendations to support equitable access to care and improve health outcomes in SLE.

Anti-MDA5 antibody-positive DM (MDA5+DM) is frequently complicated by rapidly progressive interstitial lung disease (RP-ILD). The current study aims to identify predictors for the development of RP-ILD in MDA5+DM, thereby providing an objective basis for early intervention strategies.