New research suggests that tissue-resident macrophages occupy a fibrin-rich niche and actively remodel the synovial lining in rheumatoid arthritis, providing insights into the mechanisms underlying pannus formation and joint destruction.
Antibiotics cause gut dysbiosis and exacerbate alphavirus-induced arthritis in mice by altering immune cell populations in the joints.
Intracellular succinate promotes inflammatory macrophage responses through mitochondrial GPR91 signalling, linking metabolic dysregulation to macrophage-driven inflammation in rheumatoid arthritis.
Patients with autoimmune rheumatic diseases (ARDs) are at increased risk of numerous vaccine-preventable infections owing to a combination of disease-related immune dysregulation, immunosuppressive therapies - including glucocorticoids - and comorbidities. Age-related immunosenescence further increases this susceptibility in older patients. The SARS-CoV-2 (COVID-19) pandemic and measles outbreaks have underscored the importance of optimizing vaccination strategies and improving adherence to recommendations. Nevertheless, coverage for routinely recommended vaccines, including influenza and pneumococcal vaccines, remains suboptimal in this population. Vaccine hesitancy is an important barrier driven by concerns regarding safety, tolerability, disease flares and the potential induction of new autoimmune phenomena. Advanced therapies - including B cell-depleting agents, chimeric antigen receptor T cell therapy and bispecific T cell engagers - can substantially impair vaccine-induced immune responses, highlighting the importance of optimizing vaccination timing in relation to treatment. Although most studies focus on humoral and cellular immune responses, evidence on the long-term durability of vaccine-induced immunity, the need for booster doses and real-world vaccine effectiveness in patients with ARDs remains limited. Ethical considerations are important. Although vaccination in adults is generally not mandatory, improving vaccine uptake reduces the burden of infections in patients with ARDs, contributes to herd immunity and provides indirect protection for other vulnerable populations.
Three studies report novel variants that promote autoinflammatory disease by enhancing CDC42–pyrin interactions leading to inflammasome activation.
Clinical trials in Sjögren disease have evolved from broad enrolment strategies to enriched populations with active systemic disease, which has facilitated important therapeutic breakthroughs. However, many patients remain outside therapeutic development programmes. Patient stratification and improved outcome assessment now offer an opportunity to develop precision trials across the disease spectrum.
Researchers identified 11 ADAR1 variants in patients with psoriatic disease, which were associated with a strong type I interferon signature.
IgA vasculitis (IgAV) is an immune complex-mediated small-vessel vasculitis that typically affects the skin, gastrointestinal tract, kidneys and joints. Childhood-onset IgAV is a common disease and usually follows a self-limiting course, whereas adult-onset IgAV is considerably less frequent and is associated with a poorer prognosis. The diagnosis, assessment and management of adult-onset IgAV remain challenging owing to the absence of validated diagnostic criteria for adults and lack of IgAV-specific standardized disease activity scores. Short-term outcomes are mainly determined by gastrointestinal complications, whereas kidney involvement and the risk of progression to chronic kidney disease are the major determinants of long-term prognosis. The treatment of adult-onset IgAV is limited by the paucity of high-quality clinical trials and standardized therapeutic approaches. Here, we present evidence-based, multidisciplinary guidelines for the diagnosis and management of adult-onset IgAV that reflect advances in understanding of pathogenesis, differential diagnoses and treatment over the past two decades. Developed by a panel of leading European experts on the basis of systematic literature review and expert opinion, these guidelines comprise 14 recommendation statements and overarching principles that provide a structured and pragmatic clinical framework for the diagnosis, treatment and follow-up of adult-onset IgAV.
In the phase III POETYK PsA-2 trial, deucravacitinib improved outcomes across multiple domains of psoriatic arthritis and had a favourable safety profile.
A smart contact lens enables the estimation of serum uric acid from tears and supports device-free prediction of uric acid dynamics by using personalized digital twins.
Global gout management remains profoundly suboptimal despite readily available treatments. Restructuring care through device-facilitated, nurse-led frameworks challenges traditional medical protectionism and offers a highly effective, scalable strategy to bridge systemic healthcare gaps and optimize patient outcomes.
Lymphoma is a severe complication of Sjögren disease, but two challenges remain unresolved: predicting individual risk with precision and defining specific treatment strategies. Now, international collaborative efforts and close partnership with haematologists make the possibility of addressing these challenges a reality.
Studies in adult rheumatic illnesses have shown that treat-to-target strategies improve disease control, physical function and long-term outcomes compared with conventional management. Recommendations for adopting this approach in paediatric rheumatic disorders have now been developed, and emerging evidence suggests that their application could improve care and health outcomes.
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.
The identification of IRAK2 deficiency reveals how impaired Myddosome signalling can paradoxically promote interferon-driven inflammation, which expands the spectrum of monogenic immune dysregulation and underscores the importance of detecting structural variants in unsolved inborn errors of immunity.
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.
An osteoimmunomodulatory implant that enables finely tuned release of magnesium ions could offer a way to enhance osteoporotic bone repair.
