Current Rheumatology Reports最新文献

Purpose of this review: Still's disease exemplifies systemic inflammatory disorders existing on a continuum between autoinflammation and autoimmunity. This review examines Still's disease through this spectrum lens, integrating recent advances in pathogenesis, clinical heterogeneity, and therapeutic approaches.

Recent findings: Emerging mechanistic insights reveal complex innate-adaptive immune interactions. Type I interferon signalling and neutrophil extracellular trap formation drive inflammation, while hyperferritinemia actively perpetuates disease through Msr1-mediated signaling. mTORC1 has emerged as a central integration hub converging multiple cytokine signals. Adaptive mechanisms increasingly contribute to complications: both macrophage activation syndrome and lung disease demonstrate IFNγ-dominant pathology with T cell hyperactivation. Clinical phenotyping identifies distinct patient clusters-from hyperferritinemic monocyclic to catastrophic multiorgan phenotypes-reflecting varying innate-adaptive contributions. Current classification criteria permit considerable diagnostic latitude and may inadvertently group mechanistically distinct conditions under a single diagnostic label. IL-1 and IL-6 receptor blockade remain therapeutic cornerstones, with evidence supporting early intervention during a window of opportunity. Novel approaches including IL-18 binding protein, JAK inhibitors, and IFNγ blockade show promise in refractory disease. Still's disease predominantly reflects autoinflammatory pathology driven by innate immune dysregulation, yet adaptive mechanisms contribute meaningfully to disease heterogeneity and complications. Recognition as a spectrum disorder-with variable innate-adaptive contributions across patients and disease phases-supports unification of pediatric and adult forms, guides mechanistically targeted therapies, and emphasizes the need for biomarker-driven patient stratification to enable personalized treatment approaches.

Purpose of review: This review summarizes recent advances in understanding the pathogenesis and therapeutic landscape of juvenile-onset systemic lupus erythematosus (jSLE), with a focus on how emerging genetic and immunologic insights inform patient stratification, targeted treatments, and Treat-to-Target (T2T) approaches in pediatric care.

Recent findings: Studies of (ultra-)rare gene variants (e.g., affecting TLR7, UNC93B1, PLD4, PTPN2, BACH2) aided in understanding key pathogenic pathways, and allowed linking these to associated clinical phenotypes. Multi-ancestral genomic studies and cumulative genetic metrics are refining links between patient ancestry, disease expression, genetic burden and variability, supporting personalized management. The therapeutic armamentarium has expanded with the approval of the first two biologic agents for SLE, belimumab and anifrolumab, alongside emerging molecular therapies such as protein kinase inhibitors (including JAK inhibitors), and new approaches to lupus nephritis induction using multitarget regimens that combine standard therapy with belimumab or calcineurin inhibitors. Early experience with CD19-directed CAR-T cells promises remarkable efficacy with sustained drug-free remission and good short-term safety in refractory SLE, although long-term outcomes remain under evaluation. Pediatric T2T strategies have been adapted to jSLE, and achievement of these targets are associate with improved disease control and reduced long-term damage. Recent findings confirm that converging genetic variants and immune pathway dysregulation underlie the heterogeneity of jSLE, supporting precision management. Advances in biologic and cellular therapies, together with paediatric T2T strategies, promise to improve outcomes. Future priorities include integrating genomic stratification into clinical practice and conducting dedicated pediatric trials of novel targeted therapies.

Purpose of review: An international multi-disciplinary initiative resulted in the development of 2023 ACR/EULAR Antiphospholipid Syndrome (APS) Classification Criteria to identify patients with high likelihood of APS for research. Phase I/II resulted in 27 candidate criteria organized into six clinical and laboratory domains. Here, we summarize early Phase III efforts to better define and structure candidate criteria within clinical and laboratory domains.

Recent findings: Using comprehensive literature reviews and expert consensus, domain subcommittees developed definitions for candidate criteria. Prevalence information was incorporated when available. Definitions were finalized and approved by the Steering Committee for future use during real-world case collection (derivation cohort), multi-criteria decision analysis, and validation. Clinical domain items defined were: (a) macrovascular thrombosis (venous thromboembolism including superficial venous thrombosis, arterial thrombosis, and transient ischemic attack) and associated provoking risk factors; (b) microvascular disease (livedo racemosa, livedoid vasculopathy, antiphospholipid-antibody-nephropathy, diffuse alveolar hemorrhage, cardiac microthrombosis, adrenal hemorrhage, and acute ischemic encephalopathy); (c) pregnancy morbidity (pre-fetal death, fetal death, and pre-eclampsia and placental insufficiency with severe features); (d) cardiac valve disease (thickening or vegetation); and (e) thrombocytopenia. Laboratory domain items defined were coagulation-based functional assay (lupus anticoagulant) and solid phase-based assays (anticardiolipin antibody IgG/M and anti-β₂-Glycoportein-I antibody IgG/M). Based on comprehensive literature review and Steering Committee consensus, we defined and structured APS clinical and laboratory domains. Preliminary definitions were subsequently evaluated and confirmed in late Phase III using the derivation cohort and multicriteria decision analysis prior to validation the 2023 ACR/EULAR APS Classification Criteria.

Purpose of this review: Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are the two main forms of large-vessel vasculitis (LVV), defined by inflammation of the aorta and its primary branches. Use of vascular imaging, including FDG-PET, has been increasingly incorporated into the assessment of patients with LVV. FDG-PET detects metabolic activity in the walls of the large arteries as a surrogate for vascular inflammation. In this article we review the use of FDG-PET to diagnose and monitor disease activity in different forms of LVV.

Recent findings: Use of FDG-PET to diagnose GCA by assessing vascular FDG uptake in the aorta and branch arteries is well-established. More recently, newer generation PET/CT scanners have also been used to assess metabolic activity in the cranial arteries, including the temporal arteries. In TAK, non-invasive angiography is used to assess for luminal damage at diagnosis, while FDG-PET can provide complementary information about whether active vascular inflammation is present. Recent studies have focused on the use of FDG-PET to monitor disease activity in LVV and the prognostic value of FDG-PET scans. Use FDG-PET in LVV remains an area of active ongoing research. While use at time of diagnosis in LVV has become well established, more studies are needed to evaluate the prognostic value of FDG-PET when monitoring disease activity in patients with LVV. Additional future directions for use of FDG-PET in LVV include employment of novel radiotracers, use of newer generation PET scanners, and incorporation into clinical trials to assess treatment response at the vascular level.

Purpose of review: Until recently, the absence of validated, pediatric-specific classification criteria for juvenile spondyloarthritis (JSpA) limited targeted clinical trials evaluating treatment efficacy and advancements in understanding the natural history in pediatric-onset disease. There is an urgent need for efficacy and effectiveness studies in this understudied group.

Recent findings: Most children with JSpA continue to experience disease activity despite current therapies and generally have worse outcomes than those with other juvenile arthritis forms. Fewer than 20% achieve remission within five years of diagnosis. Axial involvement is a distinct manifestation warranting separate study and management, as it does not respond to conventional agents like methotrexate used for peripheral arthritis. Comparative effectiveness data are lacking, and no medications are FDA-approved specifically for "juvenile spondyloarthritis" or "juvenile ankylosing spondylitis." The only FDA-approved therapy for enthesitis-related arthritis (ERA) is secukinumab. In 2024, pediatric classification criteria for axial disease in JSpA were published. These criteria include seven domains: MRI inflammation, MRI structural lesions, pain chronicity, pain pattern, pain location, stiffness, and genetic association. Imaging evidence of axial disease is necessary but not sufficient for classification. This review provides an overview of JSpA epidemiology, current and emerging classification criteria, and highlights the key features of the newly validated pediatric axial JSpA classification criteria.

Purpose of review: Osteoporosis, the most common metabolic bone disease and a global health problem, is the result of abnormal bone architecture and bone loss, leading to bone fragility and an increased risk of fractures. A fragility or low-trauma fracture is the first clinical sign of osteoporosis and is typically associated with a significant risk of future fractures. Practical screening tools and guidelines are critical for fracture prevention. Dual X-ray absorptiometry (DXA) is the gold standard for risk stratification and diagnosis of osteoporosis. In this review, we report recent advances in in DXA screening and bone density evaluation for patients at risk of fragility fracture.

Recent findings: DXA measures bone density as an absolute measure (g/cm2) and also reports the patient's bone mineral density (BMD) as a comparison to a standard population, which is the basis of the World Health Organization (WHO) classification for osteoporosis. DXA also provides vertebral fracture assessment (VFA), an additional tool to assess vertebral fracture presence and increased fracture risk. Understanding the methodology, reporting, and limitations of DXA use is critical for appropriate utilization of the test. BMD is validated as a predictor of fracture risk and may be used with or without clinical risk factors as part of the FRAX fracture risk assessment tool to accurately assess an individual's fracture risk. In this review, we discuss the role of DXA in screening, diagnosis, and treatment of osteoporosis. We include FRAX and its limitations, trabecular bone score (TBS), quantitative computed tomography (qCT) the American College of Rheumatology (ACR) updates on the management of glucocorticoid-induced osteoporosis, the updated International Society of Clinical Densitometry (ISCD) Position Statements, and report the key features of DXA testing, reporting, and utilization in clinical practice. DXA plays a critical role in BMD evaluation and fracture risk assessment. Appropriate utilization of this tool in clinical practice, through accurate interpretation and application of results, is essential for effective fracture prevention.

Purpose of review: We present information on the burden of vaccine-preventable diseases in people with rheumatoid arthritis (RA), the latest evidence on vaccine immunogenicity in disease-modifying antirheumatic drug (DMARD) users, and expert and guideline-based immunization recommendations. We focus on infections with the highest morbidity and mortality, and those relevant due to new developments or current outbreaks.

Recent findings: Following the license expansion for two respiratory syncytial virus (RSV) vaccines, GSK's Arexvy and Pfizer's Abrysvo, the Advisory Committee for Immunization Practices (ACIP) expanded the recommendation for vaccination in adults at increased risk of severe RSV disease. In the spring of 2025, the Center for Disease Control lowered the cutoff for immunization in high-risk groups from ≥ 60 to ≥ 50 years. There are new 2024-2025 SARS-CoV-2 vaccines and updated ACIP recommendations for SARS-CoV-2 immunization that address new viral strains and the known waning immunity from vaccines. All individuals who are moderately to severely immunocompromised (including those with RA) should receive at least one additional vaccine dose compared to the general population. The ACIP has updated its recommendations for pneumococcal immunization, aiming to lower pneumococcal disease incidence in adults. Following the approval of the 21-valent pneumococcal conjugate vaccine, designed to target the serotypes commonly affecting adults, the cutoff for vaccination in the general population changed from ≥ 65 to ≥ 50 years. Recommendations for vaccination in RA patients (everyone age ≥ 18 years) remain unchanged. Vaccine recommendations for RA patients constantly evolve as new DMARDs and vaccines are developed, and our understanding of their interaction with DMARDs vis a vis immunogenicity improves. It is essential to stay current with the latest recommendations from the ACIP and rheumatologic society guidelines.