Current opinion in rheumatology最新文献

Purpose of review: Epidemiology of vasculitides exhibit geographic variation and data from some parts of the world are still scarce. Increased recognition of these rare diseases and improvement in diagnosis and patient care may lead to changes in their epidemiology. In this review, we aimed to highlight the most recent work on the epidemiology of systemic vasculitis.

Recent findings: New data from countries where information on the epidemiology of giant cell arteritis, Takayasu arteritis and Behçet syndrome were limited have revealed that these conditions are not as rare as previously believed. The incidence rates during the coronavirus disease 2019 pandemic highlight the link between Kawasaki disease and respiratory pathogens. The use of different classification criteria hampers the comparison of true incidence and prevalence rates in antineutophil cytoplasmic antibody (ANCA)-associated vasculitis and its subtypes between geographies and over time.

Summary: Recent studies have highlighted the epidemiology of vasculitides in different parts of the world and changing trends. Standardization of study design and disease definitions is needed to improve the reliability and comparability of the results.

Purpose of review: Synovial fibroblasts are the central cells of connective tissue homeostasis. In rheumatoid arthritis (RA) tissue, synovial fibroblasts are activated because of the proinflammatory environment very early in the disease. Epigenetic alterations in RASF result in a permanently activated stage, and activated RASF are involved in many processes of RA pathophysiology. Therefore, several recent findings of the last 18 months with focus on RASF activation and function are summarized.

Recent findings: RASF activation because of a profoundly altered epigenome leads to an invasive phenotype with increased migration, adhesion and invasion into cartilage, which was further characterized in several studies. RASF subtypes and subtype dynamics were evaluated using high-resolution techniques to better understand RASF pathophysiology. Many studies addressing interactions with immune or stromal cell types have been published showing that RASF interact with many different cell types contributing not only to their own activation and pro-inflammatory response but also to the activation of the other cells.

Summary: Highly interesting findings revealing mechanisms of RASF activation and altered functions have been published, RASF subsets further characterized, and interactions with cell types elucidated, which all contribute to a better understanding of the role of RASF in RA development and progression.

Purpose of review: Large language models (LLMs) have grown rapidly in size and capabilities as more training data and compute power has become available. Since the release of ChatGPT in late 2022, there has been growing interest and exploration around potential applications of LLM technology. Numerous examples and pilot studies demonstrating the capabilities of these tools have emerged across several domains. For rheumatology professionals and patients, LLMs have the potential to transform current practices in medicine.

Recent findings: Recent studies have begun exploring capabilities of LLMs that can assist rheumatologists in clinical practice, research, and medical education, though applications are still emerging. In clinical settings, LLMs have shown promise in assist healthcare professionals enabling more personalized medicine or generating routine documentation like notes and letters. Challenges remain around integrating LLMs into clinical workflows, accuracy of the LLMs and ensuring patient data confidentiality. In research, early experiments demonstrate LLMs can offer analysis of datasets, with quality control as a critical piece. Lastly, LLMs could supplement medical education by providing personalized learning experiences and integration into established curriculums.

Summary: As these powerful tools continue evolving at a rapid pace, rheumatology professionals should stay informed on how they may impact the field.

Purpose of review: In systemic sclerosis (SSc) primary heart involvement (pHI) is frequent, even though often unrecognized due to its occult nature and to the lack of a specific diagnostic algorithm. The purpose of this review is to report the state of the art of the evidence in the current literature, as well as the overall diagnostic modalities and therapeutic strategies for primary heart involvement in SSc.

Recent findings: SSc-pHI is defined by the presence of cardiac abnormalities that are predominantly attributable to SSc rather than other causes and/or complications; it may be sub-clinical and must be confirmed through diagnostic investigations. Novel electrocardiographic analysis and cardiac magnetic resonance (CMR) with mapping techniques have been recently proposed, showing a great utility in the early identification of SSc-pHI and in the noninvasive characterization of myocardial tissue. Immunosuppressive therapy emerged as fundamental to curb myocardial inflammation, and recent preclinical and clinical data support the role of antifibrotic drugs to treat SSc-pHI.

Summary: our review will help clinicians to properly integrate the available diagnostic modalities for the assessment of SSc-pHI. The ultimate goal is to propose a feasible diagnostic algorithm for the early identification of patients with SSc-pHI, and a schematic therapeutic approach to manage SSc-pHI.

Purpose of review: Tissue fibrosis is an increasingly prevalent condition associated with various diseases and heavily impacting on global morbidity and mortality rates. Growing evidence indicates that common cellular and molecular mechanisms may drive fibrosis of diverse cause and affecting different organs. The scope of this review is to highlight recent findings in support for an important role of vascular endothelial cells in the pathogenesis of fibrosis, with a special focus on systemic sclerosis as a prototypic multisystem fibrotic disorder.

Recent findings: Although transition of fibroblasts to chronically activated myofibroblasts is widely considered the central profibrotic switch, the endothelial cell involvement in development and progression of fibrosis has been increasingly recognized over the last few years. Endothelial cells can contribute to the fibrotic process either directly by acting as source of myofibroblasts through endothelial-to-myofibroblast transition (EndMT) and concomitant microvascular rarefaction, or indirectly by becoming senescent and/or secreting a variety of profibrotic and proinflammatory mediators with consequent fibroblast activation and recruitment of inflammatory/immune cells that further promote fibrosis.

Summary: An in-depth understanding of the mechanisms underlying EndMT or the acquisition of a profibrotic secretory phenotype by endothelial cells will provide the rationale for novel endothelial cell reprogramming-based therapeutic approaches to prevent and/or treat fibrosis.

Purpose of review: This review focuses on treatments for anti-MDA5 antibody-positive dermatomyositis (MDA5-DM), which is a subgroup of dermatomyositis and characterized by frequent rapidly progressive interstitial lung disease and the high mortality rate. Despite conventional immunosuppressive therapies, there are still refractory cases. Newer treatment options are needed.

Recent findings: The triple combination therapy (high-dose glucocorticoids, calcineurin inhibitor, and intravenous cyclophosphamide) improved patient survival compared to high-dose glucocorticoids and step-wise addition of the immunosuppressants. The triple therapy now has been widely used, but there are still refractory cases. In addition to the conventional-type immunosuppressants, recently the efficacy of Janus kinase inhibitors, biologic agents such as rituximab, plasma exchange, and polymyxin B perfusion for refractory MDA5-DM patients have been reported. However, the majority of those reports regarding new treatments are limited to case series, retrospective studies, and small single-arm studies. Adding antifibrotic drugs to immunosuppressive therapies might have some ancillary benefits.

Summary: Several new therapies for MDA5-DM patients have emerged, although the optimal use of those therapies is still unknown. Further research and evidence accumulation will be needed. It is also noted that the intensive immunosuppressive therapies are associated with the higher infection risk.

Purpose of review: This review will attempt to summarize the most potentially impactful new data on the way ANCA-associated vasculitis (AAV) is diagnosed, treated, and monitored.

Recent findings: The newly developed classification criteria for AAV have serious methodological issues that need to be addressed before they are widely adopted. The newly approved drugs and studies into both achieving remission and maintaining it have added to our overall knowledge of managing AAV and should hopefully contribute to improving outcomes in AAV.

Summary: The diagnosis, treatment and monitoring of AAV have seen major improvements in the last two years. The remaining issues outlined in this review still need to be addressed to best serve AAV patients.

Purpose of review: Cryoglobulinemic vasculitis (CV) is an immune complex mediated small vessel vasculitis characterized by the presence of cryoglobulins in serum, often associated with hepatitis C infection, systemic autoimmune diseases or hematological conditions. The focus of this review is to provide an update on new insights into pathogenesis, epidemiology and therapies of infectious and noninfectious type II and type III CV.

Recent findings: The introduction of new antiviral drugs for treatment of hepatitis C infection implied major changes in HCV-related CV, allowing to shed new lights on CV pathogenesis and mechanisms of relapse and, therefore, to increase the relevance of autoimmune diseases in CV epidemiology. Specific B-cell clones are involved in the production of pathogenic immune complexes that leads to small-vessel vasculitis. Therefore, both antiviral treatments [direct-acting antivirals (DAAs) and oral nucleot(s)ide analogues] and targeted anti-CD20 therapies (rituximab) prove to be safe and effective options, leading to a better prognosis. Association of Sjögren syndrome and CV defines a specific phenotype of patients, characterized by severe manifestations and poor outcome.

Summary: Removing viral stimulation on B-cells through direct-acting antivirals and blocking B-cells proliferation and differentiation with rituximab are the goals of treatment of CV. However, further research is needed to identify prognostic factors of refractory and relapsing disease.

Purpose of review: The purpose of this review was to comprehensively summarize recent phenotype research findings in Behçet's syndrome.

Recent findings: Cluster analysis has recently been employed as a phenotype research tool in Behçet's syndrome. Studies reported different clustering patterns caused by biological variation and some degree of artificial heterogeneity. However, some clusters were more consistent than others: 1) oral ulcers, genital ulcers, and skin lesions 2) oral ulcers, genital ulcers, skin lesions, and arthritis 3) oral ulcers, genital ulcers, skin lesions, and uveitis 4) oral ulcers, genital ulcers, skin lesions, and gastrointestinal involvement. A number of loci suggestive of differential risk for individual disease manifestations were proposed. Peripheral blood gene expression profile and plasma proteome exhibited significant differences in patients with different organ involvements and were able to differentiate between disease phenotypes. However, these observations require further validation and functional studies.

Summary: Clustering patterns in Behçet's syndrome is highly heterogeneous. Artificial heterogeneity might obscure the true biological variation of disease expression. Preliminary genetic, transcriptomic and proteomic data suggest that different pathogenetic mechanisms may operate in different phenotypes of Behçet's syndrome.

Purpose of review: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of arthritis of unknown origin occurring in children under 16 years of age and persisting for at least 6 weeks. Given that JIA is an inflammatory disorder, treatment strategies, including also biologicals, are focused on suppressing excessive inflammation. The finding that different patients display different responses to biological drugs supports the concept that different pathogenic mechanisms can exist in JIA, with specific cellular and molecular mechanisms driving inflammation in each patient. The aim of this review is to highlight the most recent advances in understanding the role of immune cells in JIA pathogenesis.

Recent findings: This review encompasses the role of the different cell subsets involved in sustaining inflammation in JIA, with a particular emphasis on T cells, as they orchestrate both innate and adaptive auto-reactive immunity in affected joints.

Summary: The characterization of the cellular and molecular pathways supporting inflammation will be crucial to design novel therapeutic approaches in the context of personalized medicine.