Current opinion in rheumatology最新文献

Purpose of review: Psoriasis is an immune-mediated pro-inflammatory skin condition that is associated with an increase in risk factors for cardiovascular disease, risk of ischemic heart disease, and cardiovascular death. Despite this, traditional modifiable atherosclerotic cardiovascular disease (ASCVD) risk factors are underdiagnosed and undertreated in patients with psoriasis.

Recent findings: At a cellular level, psoriasis and atherosclerosis are driven by a host of shared inflammatory pathways, such as pro-inflammatory cytokines (TNF, IL-6), immune cells, and platelets which act synergistically to drive endothelial damage and atherosclerosis progression.

Summary: Optimal prevention of cardiovascular disease in psoriasis centers around modifying known risk factors for the development of ASCVD and emerging data highlight the promise of treating inflammation to further decrease the risk of ASCVD.

Purpose of review: This review summarizes important mouse models of psoriatic arthritis (PsA), shedding light on their advantages and disadvantages in modeling human disease.

Recent findings: Two newly created mouse models of PsA validate NF-κB signaling as disease-causing and identify pathogenic roles for CD8 + and CD4 + FoxP3 + T cells in the development of specific PsA phenotypes. The IkbkbGoF/GoF model demonstrates that homozygosity for a gain-of-function mutation in Ikbkb results in expansion of FoxP3 + CD25 + IL-17A + Tregs that lead to the development of dactylitis, spondylitis and PsA-like changes to the nails and skin, and when transferred to wildtype mice, reproduce these outcomes. The humanized mouse PsA model (Hu-PsA) establishes that introduction of PsA patient sera and PBMCs into NSG-SGM3 mice has the capacity to elicit distinct subtypes of PsA and identifies a critical role for CD8 + IL-32 + CXCL14 + T cells and immunoglobulins in disease development.

Summary: Mouse models of PsA are powerful research tools for elucidating pathogenesis of disease, biomarker identification and may assist in the discovery of a cure.

Purpose of review: To discuss the varies outcome measure instruments for the assessment of different domains for psoriatic arthritis (PsA) both in trial and clinical practice settings.

Recent findings: PsA is a multifaceted chronic inflammatory disease with diverse manifestations. This pose challenges of comprehensive assessment of the outcome of PsA. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) had developed the core domain set and in the progress of selecting the core outcome measurement set for trials and clinical practice for PsA, using the framework set by Outcome Measures in Rheumatology (OMERACT). In brief, the core set of "what to measure" has been endorsed, and a standardized way of "how to measure" them are under review. Composite outcome measures for PsA may provide a solution to measuring multiple domains in a nutshell for various purposes in trials and clinical practice.

Summary: This provides a succinct summary of the current state of outcome measurement in PsA and provides a quick and comprehensive perspective to select relevant outcome measure to use in busy rheumatology clinical settings.

Purpose of review: This review provides a critical analysis of the management of axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) in Latin America, emphasizing regional challenges, genetic diversity, healthcare disparities, and efforts to optimize patient care in resource-limited settings.

Recent findings: Recent literature highlights significant differences in treatment accessibility, healthcare infrastructure, and disease burden across Latin America considering the management of axSpA and PsA. Pan American league of associations for rheumatology (PANLAR) has established region-specific treatment recommendations adapted to the region that address these disparities while complementing international guidelines from assessment of spondyloarthritis international society - European alliance of associations for rheumatology (ASAS-EULAR) and group for research and assessment of psoriasis and psoriatic arthritis (GRAPPA). Limited access to biologics, high rates of diagnostic delay, and unique genetic and environmental factors shape disease management in this region. From the clinical perspective, the higher frequency of peripheral manifestations and the low frequency of HLA-B27 are remarkable.

Summary: Latin America faces distinct obstacles in axSpA and PsA management, requiring tailored strategies that integrate regional epidemiological characteristics, healthcare system disparities, and economic constraints. Supporting collaborative research networks across all countries and increasing access to advanced therapies are critical to enhance patient outcomes in SpA and PsA. Implementation of management strategies in the continent are required.

Purpose of review: Psoriasis, a chronic skin condition, characterized by scaly erythematous plaques, is prevalent in around 2% of the population. Around 25% of psoriasis patients have psoriatic arthritis (PsA), an inflammatory musculoskeletal disease that often leads to progressive joint damage and disability. Psoriatic diseases (PsD) encompassing psoriasis and PsA, are often associated with pathophysiologically related conditions like uveitis and inflammatory bowel disease as well as comorbidities such as cardiovascular disease. Due to the heterogeneous nature of PsD, diagnosis and treatment is a challenge. Biomarkers can objectively measure variables, such as disease state, disease progress, and treatment outcomes, thus offering the possibility for better management of disease. This review focuses on some of the biomarker research that was carried out in PsD in the past year.

Recent findings: Diverse biomarker types ranging from SNPs, mRNA, proteins, metabolites and immune cell profiles have been categorized as per the Biomarkers, EndpointS and other Tools (BEST) resource developed by the FDA/NIH. Some of the latest research has focused on multiomic assays and these along with advanced bioinformatic tools can help in better disease management.

Summary: Recent developments in PsA biomarker research show promise in identifying markers that can help in diagnosis, assess disease activity and predict treatment response. However, most studies are in the early discovery and verification state. Large-scale studies to replicate findings and develop and validate predictive algorithms are required.

Purpose of review: Anatomical variations of the sacroiliac joints (SIJ) pose challenges in the diagnosis of axial spondyloarthritis (axSpA). Increased reliance on magnetic resonance imaging (MRI) for early detection has led to concerns about specificity, as anatomical variants can mimic inflammatory changes. This review highlights common SIJ variations and their implications for rheumatologists interpreting imaging findings.

Recent findings: Recent studies emphasize the high prevalence of SIJ anatomical variations, particularly in females, and their potential to influence imaging interpretation. Variations such as crescent-shaped ileum, intraarticular dysmorphisms, and accessory joint facets can lead to bone marrow edema and sclerosis, mimicking sacroiliitis. Additionally, lumbosacral transitional vertebrae alter SIJ biomechanics, potentially exacerbating symptoms in axSpA patients. Advances in MRI and computed tomography (CT) imaging protocols provide improved differentiation between anatomical variants and true inflammatory changes.

Summary: Recognizing SIJ anatomical variations is crucial for avoiding misinterpretation of imaging findings and overdiagnosis of axSpA. MRI protocols incorporating additional imaging planes and CT correlation can enhance diagnostic accuracy. Awareness of these variations can refine patient management strategies, ensuring appropriate treatment for inflammatory and biomechanical SIJ pathologies.

Purpose of review: This review examines recent advancements in psoriasis research through single-cell technologies, including single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. These methods have uncovered the cellular diversity underlying psoriasis, identifying immune cell, keratinocyte, and fibroblast subtypes that play pivotal roles in disease progression. Such insights are vital for addressing the complexity and heterogeneity of psoriasis, paving the way for targeted therapies.

Recent findings: Recent studies emphasize the roles of IL-17-producing T cells (T17), keratinocytes, and fibroblasts in driving inflammation. T-cell cytokines, including IL-17A and IL-17F, induce keratinocyte hyperproliferation and amplify inflammation through an IL-36 feed-forward loop. Fibroblast subsets, such as SFRP2+ and WNT5A+/IL24+ fibroblasts, contribute to extracellular matrix remodeling and cytokine release, worsening the inflammatory environment. These studies also reveal the intricate fibroblast-keratinocyte crosstalk via the IL-17/IL-36 and PRSS3-F2R pathways. More recently, advancement with spatial transcriptomics has uncovered metabolic dysregulation in psoriatic keratinocytes, highlighting HIF1α-driven glycolysis and lactate production as critical in sustaining chronic inflammation. Furthermore, nonlesional skin from severe psoriasis patients exhibits transcriptomic changes resembling lesional skin, suggesting systemic "prelesional" state with the upregulation of lipid metabolism genes.

Summary: These discoveries have significant clinical implications. Integrating single-cell and spatial technologies into psoriasis research offers promising avenues for developing tailored treatments and improving patient outcomes. Specifically, with spatial transcriptomics revealing immune signatures and cell-cell colocalization that may serve as early indicators of disease severity and systemic involvement. Targeting metabolic pathways in keratinocytes and localized immune microenvironments may enhance precision therapies for psoriasis.