Visual analysis of the current status and trends of VEXAS syndrome research based on Citespace

Visual analysis of the current status and trends of VEXAS syndrome research based on Citespace | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Visual analysis of the current status and trends of VEXAS syndrome research based on Citespace mengke mao, Yifei Shao, Shan Liu, Shu Deng This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6353181/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background: Understanding the current research status and hotspots of VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Syndrome) syndrome provides reference and guidance for the diagnosis and treatment of VEXAS syndrome. Method: Using the Web of Science Core Collection (WOSCC) literature retrieval platform, we filtered literature related to VEXAS syndrome and conducted a visual analysis of the publication volume, authors, publishing institutions, countries, and keywords of VEXAS syndrome based on CiteSpace 6.3.R1. Conclusion: A total of 382 articles were obtained through the results filtering. The first article on VEXAS syndrome was published in 2020, and 136 articles were published in 2024. According to the author collaboration network analysis, Beck David B from the United States had the highest number of publications, with 27 articles. Institution and country analysis revealed that APHP and the National Institutes of Health had the highest number of publications, while the United States had the highest publication count (n=121). The top ten keywords ranked by co-occurrence mainly revolve around the definition, mechanism, and clinical manifestations of VEXAS syndrome. Keyword cluster analysis indicates that the main features of VEXAS syndrome are inflammatory and hematological manifestations, with its mechanisms and clinical characteristics being relatively complex. In terms of treatment, azacitidine and interferon-gamma inhibitors, IL-1 receptor antagonists, tumor necrosis factor inhibitors, stem cell transplantation, and biological agents were mentioned in succession. The primary publication format is case analysis reports. The timeline shows the sustained intensity of inflammatory and hematological manifestations from the onset of the disease to the present. Burstness analysis revealed that the research focus in 2020 was on the definition and classification of VEXAS syndrome. From 2021 to 2022, the research hotspots shifted to clinical manifestations, including hematological and immunological diseases such as myelodysplastic syndromes (MDS), chronic monocytic leukemia, systemic lupus erythematosus, and polyarteritis nodosa. Conclusion: VEXAS syndrome has gradually attracted the attention of researchers, with an overall upward trend in annual publications, although the total number of publications is relatively low. Collaboration between authors and institutions is relatively dispersed, primarily based on collaboration among their affiliated institutions, lacking cross-border cooperation. Currently, the research focus on VEXAS syndrome lies mainly in genetic mutations, immune regulation, and multi-system pathologic presentations, which show high correlation with MDS in hematology. The lack of guidance for treatment plans and standardized protocols may be related to the short research duration on VEXAS syndrome and the absence of large-scale clinical trials. At present, the main published format is case analyses. In summary, this disease still requires more attention in clinical practice, and the mechanisms, clinical features, and treatment strategies of VEXAS syndrome should be explored in depth to lay a solid foundation for more effective prevention and treatment in the future. VEXAS syndrome CiteSpace visual analysis Myelodysplastic syndrome Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction VEXAS syndrome is an adult-onset autoinflammatory syndrome first reported in 2020. The name of the syndrome is derived from the initial letters of its distinct features: Vacuoles, E1 enzyme, X-linked, Autoinflammatory, and Somatic. Its pathogenic mechanism involves mutations in the UBA1 gene in hematopoietic progenitor cells, leading to decreased ubiquitination through p.Met41, resulting in reduced protein degradation, disrupted cellular homeostasis, and increased endoplasmic reticulum stress, ultimately causing a systemic inflammatory response [1-4]. The clinical manifestations are diverse, commonly characterized by fever, progressive cytopenias, myeloid and erythroid vacuolation, myelodysplastic syndrome (MDS), chondritis, and pulmonary infiltration [5]. Most patients with VEXAS syndrome are male, with an onset age typically over 40 years [1]. Currently, due to the limited detection methods for VEXAS syndrome, its incidence and prevalence remain unclear, and there is a lack of standard treatment options in clinical practice, making the diagnosis and treatment of VEXAS syndrome a significant challenge [6-7]. Currently, no visual analysis has been conducted specifically for VEXAS syndrome. CiteSpace is a knowledge mapping software based on co-citation analysis and path network algorithms, capable of performing multifaceted, time-sliced, and dynamic visual analysis through authors, institutions, keywords, cited literature, and more. It helps researchers gain a deeper understanding of the organizational structure, research frontiers, and the interrelationships between different research topics within a specific field, and has broad application prospects in academic research and research management [8]. It has been widely used in many endocrine system diseases and traditional Chinese medicine fields [9-10]. This study conducts an in-depth analysis of the literature on VEXAS syndrome using the visualization software CiteSpace, based on the publications, authors, institutions, countries, keywords, and other dimensions from the Web of Science Core Collection (WOSCC). It creates visual network maps to explore the current status, hotspots, and development trends in VEXAS syndrome research, thereby laying a solid foundation for more effective prevention and treatment strategies for this disease in the future. Data and Methods Data sources Relevant publications were retrieved from WOSCC, including SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, BKCI-SSH, ESCI, CCR-EXPANDED, and IC. Search method: all fields=VEXAS syndrome. No time span was set. Inclusion and exclusion criteria Include literature pertaining to VEXAS syndrome. Given the limited availability of Chinese literature on VEXAS syndrome, it was not included in the scope of this search. Exclusion criteria: irrelevance to the topic and duplicate literature. Data processing Download the selected studies and export them in plain text format, saving them as 'download.txt', and use CiteSpace (6.3 R1) and Microsoft Excel (2021) for further analysis. Each study includes a complete record and all cited references. CiteSpace conducts a visual analysis of keywords, authors, institutions, countries, disciplines, cited literature, cited authors, and cited journals. The parameters for CiteSpace are: time span (2020 to 2024), duration (1 year), gindex (k=25), with 'pathfinder', 'pruning sliced networks', and 'pruning the network' checked, while other parameters remain at their system default values. Use Microsoft Excel to create a line chart showing the trend of published articles by year. The core authors are calculated based on Price's Law (where Mmax is the publication volume of the highest producing author). Results Analysis of Publishing Trends and Journals A total of 470 articles were retrieved through the initial search. Articles classified as conference abstracts, revisions, and news were excluded, leaving 382 articles for further analysis. Using Excel to statistically analyze the annual publication volume, the publication trend is shown in the line graph (Fig. 1). The first article on VEXAS syndrome was published in 2020, and the annual publication volume has shown a year-on-year growth trend, with the fastest growth occurring between 2021 and 2022, indicating that VEXAS syndrome has gradually become one of the research hotspots among scholars. As of now, the peak publication volume in 2024 has reached 136 articles. Overall, VEXAS syndrome, as a recently discovered autoinflammatory disease, has a relatively low overall publication volume but is showing an upward trend; VEXAS syndrome is slowly entering the public eye and receiving increasing attention. Author Collaboration Network Analysis Analysis reveals that from 2020 to the present, a total of 235 authors have published research on VEXAS syndrome. A node represents an author, the size of the node represents the number of papers published by the author, and the connections between nodes reflect collaborations among authors. There are a total of 782 connections between authors, with a network density of 0.0236, indicating that there is communication and collaboration among authors, but it is relatively dispersed and not very close-knit. Many authors have only published one or two papers each. According to Price's Law, authors with a publication count of ≥4 are considered core authors in the field, thus authors with a publication count of ≥4 are displayed, as seen in Fig. 2. David B. Beck from the United States ranks first with 27 publications, followed by Arsene Mekinian (n = 23) and Olivier Kosmider (n = 21) from France, and Peter C. Grayson (n = 20) and Marcela A. Ferrada (n = 16) from the United States, ranking 4th and 6th respectively. High-output authors from the same country exhibit some collaborative relationships, for instance, the team centered around David B. Beck, Peter C. Grayson, and Marcela A. Ferrada mainly focuses on VEXAS syndrome research, covering mechanisms, clinical manifestations, diagnosis, and treatment, among other topics [1,11-12], with published literature from 2020 to 2024. Overall, there is a stable collaboration among Beck David B, Grayson Peter C, and Ferrada Marcela A, while other authors tend to be relatively independent. Analysis of publishing institutions and national cooperation networks The results are shown in Fig. 3(a), with a total of 184 nodes and 486 connections, resulting in a network density of 0.0208. This indicates that a total of 184 institutions have published related articles, with limited collaboration between them. Among these, 31 institutions have published 10 or more articles, with the highest number being 53 articles, making it the only institution with more than 50 publications, which is Assistance Publique Hopitaux Paris (APHP). Furthermore, 5 of the 31 institutions are part of APHP, while another 8 institutions that are also part of APHP have published fewer than 10 articles. A relatively stable collaborative relationship has formed among these institutions, with major research directions including pustular psoriasis, endocrinology, and several other fields. The second highest number of publications comes from the National Institutes of Health (NIH) – USA (n=48), followed by NIH National Human Genome Research Institute (NHGRI) (n=24), NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) (n=21), and NIH National Heart Lung & Blood Institute (NHLBI). (n=19) all belong to research institutions under the National Institutes of Health (NIH) in the United States. A comprehensive analysis reveals that collaboration among institutions is mainly between affiliated entities. This collaborative model has the advantage of facilitating the allocation and utilization of internal resources, demonstrating significant synergistic effects. However, it lacks the integration of resources across organizations, which may lead to data being singular and lacking breadth and depth. A total of 40 countries have published literature related to VEXAS syndrome, with a connection count of 104 and a network density of 0.1103, as shown in Fig. 3(b). Among these countries, only 9 have published more than 10 articles, accounting for 77.5% of the total publication volume. The country with the highest number of publications is the United States (n=121), followed by France (n=89), Italy (n=30), Japan (n=28), and the United Kingdom (n=24). The country with the highest centrality is the United Kingdom (0.86), followed by Italy (0.81) and the United States (0.57), with these three countries playing a significant role in international cooperation. In summary, there is little connectivity among authors, and the connections between institutions mainly involve affiliated entities. Transnational communication and cooperation are primarily concentrated between Italy and the United States, which significantly hinders the development of research in this field. Keyword co-occurrence analysis Co-occurrence network analysis An analysis of the literature keywords reveals a total of 196 nodes and 503 connections, with a network density of 0.0193. Keywords that occur with a frequency of five or more times are labeled, with larger nodes indicating a higher frequency of occurrence [13-14]. The keyword co-occurrence graph is presented in Fig. 4. Among the 196 keywords, 17 have a frequency of occurrence of ten or more times, and the top ten keywords are listed in Table 1. Somatic mutations, autoinflammatory diseases, and the e1 enzyme are among the primary characteristics of VEXAS syndrome, which explains their higher frequency. Furthermore, VEXAS syndrome, an autoimmune disease associated with mutations in the UBA1 gene, most commonly presents with myelodysplastic syndrome in hematology. Meanwhile, manifestations, which are among the most concerning issues, appeared 48 times, while relapsing polychondritis and clonal hematopoiesis may represent significant clinical manifestations aside from the primary characteristics. Table 1 Top Ten Keywords in VEXAS Comprehensive Essay Contest Number Keywords Frequency The earliest year of publication 1 vexas syndrome 108 2021 2 somatic mutations 77 2022 3 myelodysplastic syndrome 59 2021 4 manifestations 48 2022 5 autoinflammatory diseases 44 2021 6 relapsing polychondritis 27 2020 7 autoimmune diseases 26 2021 8 uba1 25 2022 9 clonal hematopoiesis 25 2021 10 e1 enzyme 21 2020 Centrality analysis Centrality Betweenness (CB) is an indicator that assesses the significance of a node within a network, with values ranging from 0 to 1. A node with a CB greater than 0.1 can be classified as a core node, where higher values signify greater influence [13]. In the context of VEXAS syndrome, there are 23 keywords with high centrality, the top five being acute myeloid leukemia (0.49), risk (0.38), adult-onset Still's disease (0.29), familial Mediterranean fever (0.26), and stem cell transplantation (0.26). This indicates that VEXAS syndrome frequently manifests with clinical symptoms or laboratory evidence of AML, adult Still's disease, or familial Mediterranean fever prior to achieving a definitive diagnosis. Stem cell transplantation is the predominant treatment utilized for VEXAS syndrome, occupying a crucial role, while risk has emerged as one of the primary areas of concern since 2021. Cluster analysis Citespace clustering analysis classifies keywords related to similar topics and evaluates clustering effectiveness based on the modularity value (Q) and average silhouette value (S). A Q value exceeding 0.3 indicates significant clustering results, whereas an S value greater than 0.5 suggests reasonable clustering outcomes [15]. Different colored blocks represent distinct clusters, with the size of each cluster being inversely proportional to its number; thus, a larger cluster corresponds to a smaller numerical designation [16]. In VEXAS syndrome, a total of 13 clusters are identified (Fig. 5), with Q = 0.7945 and S = 0.9052, indicating that the clustering results are both reasonable and significant. The number of nodes in each cluster and the top four keywords are presented in Table 2. Cluster 0# encompasses e3 ubiquitin ligase, protein, autophagy, and skp2, suggesting that the mechanisms associated with interstitial lung disease, one of the primary manifestations of VEXAS syndrome, may be linked to these keywords. Cluster 1# includes terms such as germline susceptibility, autoinflammatory diseases, and complexity, indicating that VEXAS syndrome is related to germline susceptibility, with its mechanisms and clinical features being relatively complex. Clusters #2, #3, #4, #5, #7, #8, and #9 primarily consist of keywords related to the clinical manifestations of VEXAS syndrome and various differential diagnoses, suggesting that VEXAS syndrome clinically presents mainly as inflammation and hematological issues, including arteritis, chondritis, renal injury, adult Still's disease, Sweet's syndrome, and myelodysplastic syndrome, among others. Cluster 6# mainly includes treatment-related terms such as Jak inhibitors, indicating a high thrombotic risk associated with VEXAS syndrome; studies suggest that approximately 35% to 56% of patients with VEXAS syndrome may experience venous thromboembolism (VTE), primarily manifesting as venous thrombosis rather than arterial thrombosis [17]. The activation of the coagulation system may lead to systemic inflammatory responses. JAK inhibitors are a class of non-receptor tyrosine kinases that alleviate inflammation caused by excessive cytokine production by inhibiting the activity of one or more JAKs, thus blocking the corresponding JAK-STAT signaling pathways, demonstrating promising prospects in inflammatory diseases such as rheumatoid arthritis (RA), atopic dermatitis (AD), and inflammatory bowel disease (IBD) [18]. Clusters 10# and 11# include terms such as somatic mutations, vacuolization, Schnitzler syndrome, Still's disease, anti-collagen antibodies, inflammation, relapsing polychondritis, VEXAS syndrome, and Schnitzler syndrome, indicating an association between bone marrow and cartilage in VEXAS syndrome, with bone marrow playing an irreplaceable role in diagnosis; systemic inflammatory responses also frequently occur in cartilage. Cluster 12# primarily includes venous thromboembolism, IL-6, VEXAS syndrome, and cerebral sinus vein thrombosis, suggesting that VEXAS syndrome, as a newly identified disease, is primarily documented in case analyses, with a notable lack of large-scale clinical data. Table 2 Keyword Clustering Table of VEXAS Syndrome Literature Cluster number Nodes Years Cluster labels Keywords #0 20 2023 interstitial lung disease e3 ubiquitin ligase; protein; autophagy; skp2 #1 20 2022 association disease; germline predisposition; autoinflammatory disorder; complex #2 19 2021 acute kidney injury relapsing polychondritis; nosology; web of science; spinal muscular atrophy (sma) #3 18 2022 giant cell arteritis myelodysplastic-myeloproliferative diseases; systemic; large vessels vasculitis; neurosensory hearing loss #4 17 2022 familial mediterranean fever schnitzler syndrome; stills disease; adult-onset; pfapa syndrome #5 16 2022 differential diagnosis fibroinflammatory disease ; primary immunodeficiency disease; connective tissue disease; pan #6 15 2021 coagulation diagnositc; treatment; janus kinase (jak) inhibitors; monocyte #7 13 2022 hemophagocytic lymphohistiocytosis ventriculitis; daptomycin; proteins; a20 #8 11 2023 sweets syndrome sweet syndrome; clonal hematopoiesis; bone marrow failure syndromes; immune regulation #9 10 2021 dysbiosis schnitzler; drug reaction with eosinophilia and sys-temic symptoms; multisystem inflammatory syndrome in children; common variable immune defi-ciency #10 10 2023 bone marrow somatic mutations; vacuolization; schnitzler syndrome; stills disease #11 7 2023 cartilage anti-collagen antibodies; inflammation; relapsing polychondritis; vexas syndrome #12 5 2023 case report venous thromboembolism; il-6; veaxs syndrome; cerebral sinus vein thrombosis Timeline analysis The timeline chart (Fig. 6) visually illustrates the time span of each cluster and the interconnections among different clusters, thereby effectively demonstrating the evolutionary trajectory of VEXAS syndrome. The keyword timeline chart indicates the initial appearance of each keyword within the selected time frame, as well as the evolving trends of research hotspots over time [19]. Cluster #2, concerning acute kidney injury, has been investigated as early as 2020, while cluster #10, related to bone marrow, gained prominence upon its emergence, attracting considerable attention. Research interest in cluster #1, pertaining to association, cluster #6, focusing on coagulation, and cluster #10, concerning bone marrow, began to decline around 2021. In contrast, clusters #0, addressing interstitial lung disease, #2, concerning acute kidney injury, #3, related to giant cell arteritis, #4, focusing on familial Mediterranean fever, #5, dealing with differential diagnosis, #7, concerning hemophagocytic lymphohistiocytosis, #8, related to Sweet's syndrome, #9, addressing dysbiosis, #11, focusing on cartilage, and #12, pertaining to case reports, have continued to be the subject of research from their year of emergence to the present. This indicates that these areas have been consistently explored and remain prominent research hotspots. Burstness analysis Emergence refers to the sudden increase in the frequency of keywords over a specified period, which can be utilized to comprehend shifts in research frontiers, focal points, and the latest trends in research hotspots [20]. As illustrated in Fig. 7, the study of VEXAS syndrome has emerged as a hotspot beginning in 2021. In terms of emergence intensity, the highest-ranking keyword is 'autoimmune disease' (2.12), which, despite having a duration of only one year, exhibits the greatest intensity, indicating that it was the primary focus of researchers in 2021. Conversely, the lowest-ranking keyword is 'classification' (1.38), with a duration spanning from 2020 to 2021. Analyzing the research timeline reveals that the emphasis in 2020 was on defining VEXAS syndrome and its related disease classification. From 2021 to 2022, the research hotspots transitioned to clinical manifestations and associated hematological and immunological diseases, including hematological disorders (myelodysplastic syndromes) and immune system diseases (systemic lupus erythematosus, polyarteritis nodosa), among others. The keywords 'prevalence' and 'immunodeficiency' have persisted in research since 2023, suggesting that they may evolve into future research hotspots. VEXAS syndrome and MDS Through the analysis of keyword co-occurrence networks, it is evident that MDS is the most frequently occurring keyword (59 occurrences), alongside somatic mutations in VEXAS syndrome. Furthermore, MDS appears in the keywords associated with cluster label #3 and in the keyword burst analysis, indicating that MDS is one of the common clinical manifestations of VEXAS syndrome, demonstrating a strong correlation with MDS in the hematological context and garnering widespread attention. Patients diagnosed with VEXAS syndrome are predisposed to hematological malignancies, including MDS and plasmacytoid malignancies [21]. A prospective multicenter study conducted in France revealed that 49% of 116 patients with VEXAS syndrome were diagnosed with MDS. In this study, the median follow-up period was 3 years, and the mortality rate was recorded at 15.5%, with 3 out of 18 deaths attributed to the progression of MDS [22]. MDS is typically defined by three criteria: 1. Clonal hematopoietic stem cell disorder; 2. The presence of dysplastic features; 3. Ineffective hematopoiesis resulting in at least one peripheral blood cytopenia [23]. Ineffective hematopoiesis refers to morphological abnormalities observed in more than 10% of red blood cells, granulocytes, and/or megakaryocyte lineages. The prevalence of hematopoietic clones identified through next-generation sequencing (NGS) blurs the distinction between normal and pathological states, rendering clonality no longer a definitive characteristic of MDS [24]. Bone marrow characteristics in patients with VEXAS syndrome, including myeloid proliferation, vacuolization, and the presence of macrocytic hyperplasia [1,25], suggest that VEXAS is associated with ineffective hematopoiesis, similar to MDS. Gutierrez-Rodrigues found that patients with VEXAS syndrome exhibit both UBA1 mutations and other typical myeloid mutations, primarily including DNMT3A and TET2, which are independent of inflammatory and hematological manifestations. Cells harboring UBA1 mutations are the principal contributors to systemic inflammation and bone marrow failure [26-27]. Some patients with VEXAS syndrome exhibit ineffective hematopoiesis and display dysplastic features in the bone marrow lineage, thus fulfilling some of the minimal criteria for MDS. However, there is relatively no increase in blasts or progression to AML, which appears to be a critical unmet criterion for classification within the MDS spectrum at this stage [28]. Approximately 20-50% of MDS patients associated with VEXAS exhibit low-risk features and are diagnosed as MDS-MLD or MDS-SLD, with or without ringed sideroblasts (RS), and their somatic mutation profiles do not align with those typical of MDS, lacking genes associated with poor prognosis in MDS (such as TP53, RUNX1, etc.) [29-30]. This indicates that the MDS associated with UBA1 mutations represents a unique clinical and molecular entity, distinct from classic MDS. Multiple retrospective studies have validated the effectiveness of AZA for MDS-related VEXAS, which can prolong the 'time to next treatment', stabilize or improve cytopenias, and even achieve complete clearance of UBA1 mutation clones along with complete remission of MDS [31-37]. Nevertheless, the precise relationship between UBA1 mutation clones and the onset of MDS remains undetermined. It is still unclear whether myeloid tumors are primarily driven by UBA1 mutation clones or if a highly inflammatory microenvironment facilitates clonal selection. Discussion The trend of published articles shows that in 2020, research on VEXAS syndrome was in its early stages, with only 2 articles published. Since then, the number of publications has increased year by year, with the largest annual growth occurring between 2021 and 2022. In 2024, the number of publications reached its peak at 136 articles. This indicates that with the development of society, the field of VEXAS syndrome is receiving more and more attention. The co-occurrence analysis of authors, institutions, and countries found that there are few connections between authors, while high-output authors tend to have collaborative relationships within their country. The institutions with the highest publication output are APHP and the National Institutes of Health in the United States, with the United States (n=121) being the country with the most publications. Collaboration between institutions mainly occurs among affiliated institutions, with a lack of inter-institutional and cross-national flow and cooperation, which greatly hinders the progress of research in this field and provides a reference for future researchers in this area. From the analysis of the keyword co-occurrence map, it can be seen that somatic mutations, autoinflammatory diseases, and E1 enzyme are among the main features of VEXAS syndrome. Clinical manifestations are the topics of greatest concern for researchers studying VEXAS syndrome, primarily including autoinflammatory reactions and hematological manifestations. Myelodysplastic syndromes have become one of the most commonly mentioned hematological manifestations of VEXAS syndrome. At the same time, recurrent polychondritis and clonal hematopoiesis may be comparatively important clinical manifestations apart from the main features. The keyword clustering and keyword timeline chart reflect the hot topics and development trends in VEXAS syndrome research. Since the discovery of VEXAS syndrome in 2020, research has mainly focused on the pathogenesis of the disease (e1 enzyme, immune dysregulation, etc.). After 2021, this disease became a research hotspot, and from 2021 to 2024, the research content mainly revolved around mechanisms and clinical manifestations. The clinical manifestations primarily include inflammatory responses (fever, polyarthritis, vasculitis, thrombosis, etc.) and hematological manifestations (MDS, macrocytic anemia, thrombocytopenia, etc.). There is a high correlation with MDS in hematological aspects. In terms of treatment, azacitidine, interferon gamma inhibitors, IL-1 receptor antagonists, tumor necrosis factor inhibitors, stem cell transplantation, and biological agents have been mentioned successively. Overall, VEXAS syndrome, as a new autoimmune disease, has garnered increasing attention since its discovery in 2020. The main research focus is on the mechanisms and clinical manifestations of the disease. Currently, over 70% of published VEXAS cases have the p.Met41 substitution, loss of exon 3 from the cytoplasmic isoform of UBA1 (UBA1b), and the formation of a subtype enzyme (UBA1c) with reduced catalytic activity, leading to decreased cell ubiquitination, accumulation of misfolded proteins, and endoplasmic reticulum stress. The activation of the unfolded protein response ultimately triggers inflammation. Recent studies have also reported non-classical somatic UBA1 mutations that are neither Met41 nor exon 3 [38-41]. Research into the mechanisms of VEXAS syndrome is still gradually being explored. Limitations of this study: 1. The data used in this article is solely from the WOSCC database, which may exclude some valuable information; 2. The absence of references in the obtained data restricts the visualization analysis to the co-occurrence level and does not allow for citation analysis to explore the intrinsic relationships between authors and topics; 3. There may be some errors due to the involvement of a large number of foreign vocabulary when manually combining synonyms of keywords. 4. The literature visualization analysis is only conducted using CiteSpace software, which has a considerable degree of subjectivity in threshold selection. Future research could combine various visualization methods for in-depth exploration from multiple perspectives and corroborate each other to ensure the objectivity of the research results. Conclusion This study conducted a visual analysis utilizing Citespace software on all pertinent literature regarding VEXAS syndrome retrieved from the WOSCC database. The analysis revealed that while the publication volume associated with VEXAS syndrome has been increasing annually, the level of attention towards VEXAS syndrome remains relatively low. Furthermore, there is limited collaboration across institutions and nations among various authors and institutions, and currently, no standard treatment protocol exists for VEXAS syndrome. Given the hematological and immunological manifestations of VEXAS syndrome, it is susceptible to misdiagnosis in clinical practice, which has led to heightened interest in VEXAS. With the advancement of global medical standards, targeted therapies are anticipated to emerge as a new focal point for research. It is expected that in the future, targeted treatments for VEXAS syndrome associated with UBA1 mutations will undergo more comprehensive investigations. We hope that more researchers will accord sufficient attention to this matter and engage in in-depth discussions regarding mechanisms, treatments, and other aspects to provide valuable references for clinical practice. Building on this foundation, large-sample, cross-provincial clinical research should be undertaken for the benefit of humanity. Declarations Acknowledgements Not applicable. Funding This study was supported by The Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project (ZJ-TCM-Major Projects) (Project number: GZY-ZJ-KJ-24013). Availability of data and materials The data generated in the present study may be requested from the corresponding author. Authors' contributions Conceptualization: Mengke Mao, Shao Yifei. Data curation: Shan Liu. Formal analysis: Mengke Mao, Shao Yifei. Methodology: Shan Liu. Software: Mengke Mao. Supervision: Shu Deng. Writing–original draft: Mengke Mao. All authors read and approved the final version. Ethics approval and consent to participate Not applicable. Competing interests The authors declare that they have no competing interests. Open Access This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution, and reproduction in any medium or format, provided that appropriate credit is given to the original author(s) and source, a link to the Creative Commons license is provided, and it is indicated whether any modifications were made to the licensed material. Under this license, you do not have the right to share adapted material derived from this article or any parts thereof. Images or other third parties. The materials in this article are covered under the article's Creative Commons license, unless otherwise indicated in the acknowledgments of the materials. If the materials are not included under the article's Creative Commons license, and your intended use is not permitted by statutory regulations or exceeds the permitted use, you need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. References Beck DB, Ferrada MA, Sikora KA, et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease[J]. N Engl J Med, 2020,383(27):2628-2638. Beck DB, Werner A, Kastner DL, et sl. Disorders of ubiquitylation: unchained inflammation[J]. Nat Rev Rheumatol, 2022,18(8):435-447. Lacombe V, Prevost M, Bouvier A, et al. Vacuoles in neutrophil precursors in VEXAS syndrome: diagnostic performances and threshold[J]. Br J Haematol, 2021, 195(2):286-289. Poulter JA, Savic S. Genetics of somatic auto-inflammatory disorders[J]. Semin Hematol, 2021,58(4):212-217. Huang H, Zhang W, Cai W, et al. VEXAS syndrome in myelodysplastic syndrome with autoimmune disorder[J]. Exp Hematol Oncol, 2021,10(1):23. Bourbon E, Heiblig M, Gerfaud VM, et al. Therapeutic options in VEXAS syndrome: insights from a retrospective series[J]. Blood, 2021,137 (26) :3682-3684. Padureanu V, Marinas CM, Bobirca A, et al. Clinical manifestations in vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: A narrative review[J]. Cureus, 2024,16(1): e53041. Chen CM. CiteSpace II: Detecting and visualizing emerging trends and transient patterns in scientific literature[J]. J Am Soc Inf Sci, 2006,57(3):359-377. Jiao YT, Qin XM, Wu XK. Visualization analysis of research status and trend of traditional Chinese medicine in treatment of senile depression based on Citespace [J]. Chin Med Herbal Drugs,2024,55(21):7409-7418. Ren YY, Hou Y, Zhe BB. Based on VOSviewer and CiteSpace, visual analysis of research on non-drug intervention of traditional Chinese medicine in diabetes in recent 10 years[J/OL]. J Trad Chin Med. Obiorah IE, Patel BA, Groarke EM, et al. Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1. Blood Adv,2021,5(16):3203-3215. Ferrada MA, Sikora KA, Luo YM, et al. Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS[J]. ARTHRITIS RHEUMATOL‌‌,2021,73(10):1886-1895. Liang GC. Research hotspots and application patterns of Earthworms based on CiteSpace and data mining analysis[D]. Yichun Univ, 2023. Chen YQ, Xing XF, Cheng DL, et al. Construction of National Agricultural Informatization Knowledge Graph Based on Citespace and Intermediary Centrality Algorithm [J]. J SW Univ Natls (Nat Sci Ed), 2022,48(1):75-81. Chen Y, Chen CM, Liu ZY, et al. The methodology function of CiteSpace mapping knowledge domains [J]. Stud Sci Sci,2015,33(2):242-253. Chen C, Song M. Visualizing a field of research: A methodology of systematic scientometric reviews[J]. PLoS One, 2019,14(10): e0223994. Loeza-Uribe MP, Hinojosa-Azaola A, Sánchez-Hernández BE, et, al. VEXAS syndrome: Clinical manifestations, diagnosis, and treatment[J]. Reumatol Clin (Engl Ed), 2024,20(1):47-56. Hu X, Li J, Fu M, et al. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther, 2021,6(1):402. Liu XX, Zhang C, Huang SQ, et al. Bibliometric analysis of current status and development trend of polysaccharidefrom Polygonati Rhizoma[J]. Chin Med Herbal Drugs, 2023,54(21):7130-7141. Ling N, Guo CQ, Tiang HY, et al. Visualized analysis of research status and development trend of Hippophae rhamnoides polysaccharides based on bibliometrics[J]. Chin Med Herbal Drugs,2024,55(20):7074-7061. Poulter JA, Collins JC, Cargo C, et al. Novel somatic mutations in UBA1 as a cause of VEXAS syndrome[J]. Blood,2021,137(26): 3676-3681. Georgin-Lavialle S, Terrier B, Guedon AF, et al. Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients[J]. Br J Dermatol,2022,186(3):564-574. Khoury JD, Solary E, Abla O, et al. The 5th edition of the world health organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms[J]. Leukemia, 2022,36(7):1703–1719. Pierre S, Laetitia L, Yvan J, et al. VEXAS: is it time to reshape the nosology of clonal hematopoiesis? [J]. Expert Rev Hematol,2023,16(7):495-499. Obiorah IE, Patel BA, Groarke EM, et al. Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1[J]. Blood Adv,2021,5(16):3203–3215. Gutierrez-Rodrigues F, Kusne Y, Fernandez J, et al. Spectrum of clonal hematopoiesis in VEXAS syndrome[J]. Blood,2023,142(3): 244-259. Patel BA, Gutierrez-Rodrigues F, Kusne Y, et al. Clonal Hematopoiesis in Vexas Syndrome[J]. Blood, 2022;140(3):5745-5746. Malcovati L. VEXAS: walking on the edge of malignancy[J]. Blood, 2023 Jul 20;142(3):214-215. Lytle A, Bagg A. VEXAS: a vivid new syndrome associated with vacuoles in various hematopoietic cells[J]. Blood, 2021;137(26):3690. Gutierrez-Rodrigues F, Kusne Y, Fernandez J, et al. Spectrum of clonal hematopoiesis in VEXAS syndrome[J]. Blood, 2023,142(3):244–259. Katja Sockel, Katharina Götze, Christina Ganster, et al. VEXAS syndrome: complete molecular remission after hypomethylating therapy[J]. Ann Hematol,2024,103(3):993–997. Fraison JB, Mekinian A, Grignano E, et al. Efficacy of Azacitidine in Autoimmune and Inflammatory disorders associated with myelodysplastic syndromes and Chronic Myelomonocytic Leukemia[J]. Leuk Res, 2016,43:13–17. Tzvika Porges, Elli Rosenberg, Ofir Wolach, et, al. Case report: VEXAS syndrome with excellent response to treatment with azacytidine[J/OL]. Ann Hematol. Raaijmakers MHGP, Hermans M, Aalbers A, et al. Azacytidine Treatment for VEXAS Syndrome. Hemasphere,2021,5(12): e661. Kataoka A, Mizumoto C, Kanda J, et al. Successful azacitidine therapy for myelodysplastic syndrome associated with VEXAS syndrome. Int J Hematol, 2023,117(6):919–924. Cordts I, Hecker JS, Gauck D, et al. Successful treatment with azacitidine in VEXAS syndrome with prominent myofasciitis. Rheumatology, 2022,61(5): e117–e119. Bourbon E, Heiblig M, Gerfaud VM, et al. Therapeutic options in VEXAS syndrome: insights from a retrospective series. Blood,137(26):3682–3684. Poulter JA, Collins JC, Cargo C, et al. Novel somatic mutations in UBA1 as a cause of VEXAS syndrome. Blood, 2021,137(26):3676–3681. Stiburkova B, Pavelcova K, Belickova M, et al. Novel somatic UBA1 variant in a patient with VEXAS syndrome. Arthritis Rheumatol, 2023,75(7):1285–1290. Sakuma M, Blombery P, Meggendorfer M, et al. Novel causative variants of VEXAS in UBA1 detected through whole genome transcriptome sequencing in a large cohort of hematological malignancies. Leukemia, 2023,37(5):1080–1091. Collins JC, Magaziner SJ, English M, et al. Shared and distinct mechanisms of UBA1 inactivation across different diseases. EMBO J. 2024;43(10):1919-1946. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 02 Jul, 2025 Reviews received at journal 02 Jul, 2025 Reviewers agreed at journal 26 Jun, 2025 Reviewers agreed at journal 01 Jun, 2025 Reviews received at journal 25 May, 2025 Reviewers agreed at journal 15 May, 2025 Reviewers agreed at journal 02 May, 2025 Reviewers invited by journal 02 May, 2025 Editor assigned by journal 24 Apr, 2025 Submission checks completed at journal 24 Apr, 2025 First submitted to journal 01 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6353181","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":451309543,"identity":"6e2f0b62-a1e1-402c-9947-8e3cca25015d","order_by":0,"name":"mengke mao","email":"","orcid":"","institution":"Zhejiang Provincial Hospital of TCM","correspondingAuthor":false,"prefix":"","firstName":"mengke","middleName":"","lastName":"mao","suffix":""},{"id":451309544,"identity":"cad328af-17d5-42ab-89a6-8a7f483cbe52","order_by":1,"name":"Yifei Shao","email":"","orcid":"","institution":"Zhejiang Chinese Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yifei","middleName":"","lastName":"Shao","suffix":""},{"id":451309545,"identity":"aac3b431-9748-4ab0-86c2-66a64a25cc8f","order_by":2,"name":"Shan Liu","email":"","orcid":"","institution":"Zhejiang Provincial Hospital of TCM","correspondingAuthor":false,"prefix":"","firstName":"Shan","middleName":"","lastName":"Liu","suffix":""},{"id":451309546,"identity":"c17dc4cf-3b3e-45b5-ac31-857a26fc625e","order_by":3,"name":"Shu Deng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA30lEQVRIiWNgGAWjYDCCA0DM2MAgx8befODAhx8kaDHm4zmWeHBmDwlaEudJ5Bgf5mAjQgff8d7DL3/uOJzYxnPmw2EGHgZ5frED+LVInjmXZs175rBxG3vvhsMFFgyGM2cn4NdicCPHzJix7bBsG8/ZDYdn8DAkGNwmpOX+GzPDn22HGdskch4c5mEjRssNHuMHvG2HFYFaGIjTInkmx4yZty3dmI3nmAEwkCUI+4Xv+Bnjjz/brOXk25sff/jww0aeX5qAFiBgk0DiSOBUhgyYPxClbBSMglEwCkYuAAAxt0zpxlHaCAAAAABJRU5ErkJggg==","orcid":"","institution":"Zhejiang Provincial Hospital of TCM","correspondingAuthor":true,"prefix":"","firstName":"Shu","middleName":"","lastName":"Deng","suffix":""}],"badges":[],"createdAt":"2025-04-01 12:38:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6353181/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6353181/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82308665,"identity":"f8341484-3957-4b7c-871f-6b05e3ceb275","added_by":"auto","created_at":"2025-05-09 01:35:29","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":21850,"visible":true,"origin":"","legend":"\u003cp\u003ePosting Trend Chart\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6353181/v1/6836d04202cb6f0854489be0.png"},{"id":82309427,"identity":"91e55ae1-0326-4436-8324-065fd57eb88f","added_by":"auto","created_at":"2025-05-09 01:43:29","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":168073,"visible":true,"origin":"","legend":"\u003cp\u003eCo-occurrence of Author Collaboration\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6353181/v1/36586f4820614fc5b7ef09a8.png"},{"id":82308668,"identity":"47552d6b-d27a-466b-ac6d-45f7b41baad7","added_by":"auto","created_at":"2025-05-09 01:35:29","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":220942,"visible":true,"origin":"","legend":"\u003cp\u003eCo-occurrence of Institutions(a) and National co-occurrence map (b)\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6353181/v1/c40dd935c22a5897b399e9e6.png"},{"id":82308670,"identity":"005edc84-ef02-434a-aee1-6ce0950ecc03","added_by":"auto","created_at":"2025-05-09 01:35:29","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":168415,"visible":true,"origin":"","legend":"\u003cp\u003eKeyword co-occurrence chart\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6353181/v1/2b2b1c4f8389c025088388e5.png"},{"id":82308676,"identity":"24456559-d8e2-4596-b08e-b3c3a3b670fd","added_by":"auto","created_at":"2025-05-09 01:35:30","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":77583,"visible":true,"origin":"","legend":"\u003cp\u003eKeyword clustering diagram\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-6353181/v1/114ae2f4bd656e48feccbbda.png"},{"id":82308667,"identity":"9559c2ff-1445-4b45-b22f-dda18542e16e","added_by":"auto","created_at":"2025-05-09 01:35:29","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":136700,"visible":true,"origin":"","legend":"\u003cp\u003eKeyword Timeline Chart\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-6353181/v1/bb57f04b5c527d9bed16a233.png"},{"id":82308683,"identity":"2acaf43b-151a-4e7a-885f-9e6fdb803b20","added_by":"auto","created_at":"2025-05-09 01:35:30","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":70150,"visible":true,"origin":"","legend":"\u003cp\u003eKeyword Burstness Chart\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-6353181/v1/36512e6fcb429c6d7f3a6e64.png"},{"id":82310344,"identity":"9c707d47-4122-4168-9ea6-6472cd820fb7","added_by":"auto","created_at":"2025-05-09 01:51:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1311993,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6353181/v1/d2277159-d5af-40f9-a887-aadd2f48c2f6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Visual analysis of the current status and trends of VEXAS syndrome research based on Citespace","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVEXAS syndrome is an adult-onset autoinflammatory syndrome first reported in 2020. The name of the syndrome is derived from the initial letters of its distinct features: Vacuoles, E1 enzyme, X-linked, Autoinflammatory, and Somatic. Its pathogenic mechanism involves mutations in the UBA1 gene in hematopoietic progenitor cells, leading to decreased ubiquitination through p.Met41, resulting in reduced protein degradation, disrupted cellular homeostasis, and increased endoplasmic reticulum stress, ultimately causing a systemic inflammatory response [1-4]. The clinical manifestations are diverse, commonly characterized by fever, progressive cytopenias, myeloid and erythroid vacuolation, myelodysplastic syndrome (MDS), chondritis, and pulmonary infiltration [5]. Most patients with VEXAS syndrome are male, with an onset age typically over 40 years [1]. Currently, due to the limited detection methods for VEXAS syndrome, its incidence and prevalence remain unclear, and there is a lack of standard treatment options in clinical practice, making the diagnosis and treatment of VEXAS syndrome a significant challenge [6-7].\u003c/p\u003e\n\u003cp\u003eCurrently, no visual analysis has been conducted specifically for VEXAS syndrome. CiteSpace is a knowledge mapping software based on co-citation analysis and path network algorithms, capable of performing multifaceted, time-sliced, and dynamic visual analysis through authors, institutions, keywords, cited literature, and more. It helps researchers gain a deeper understanding of the organizational structure, research frontiers, and the interrelationships between different research topics within a specific field, and has broad application prospects in academic research and research management [8]. It has been widely used in many endocrine system diseases and traditional Chinese medicine fields [9-10].\u003c/p\u003e\n\u003cp\u003eThis study conducts an in-depth analysis of the literature on VEXAS syndrome using the visualization software CiteSpace, based on the publications, authors, institutions, countries, keywords, and other dimensions from the Web of Science Core Collection (WOSCC). It creates visual network maps to explore the current status, hotspots, and development trends in VEXAS syndrome research, thereby laying a solid foundation for more effective prevention and treatment strategies for this disease in the future.\u003c/p\u003e"},{"header":"Data and Methods","content":"\u003cp\u003e\u003cstrong\u003eData sources\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRelevant publications were retrieved from WOSCC, including SCI-EXPANDED, SSCI, A\u0026amp;HCI, CPCI-S, CPCI-SSH, BKCI-SSH, ESCI, CCR-EXPANDED, and IC. Search method: all fields=VEXAS syndrome. No time span was set.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion and exclusion criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInclude literature pertaining to VEXAS syndrome. Given the limited availability of Chinese literature on VEXAS syndrome, it was not included in the scope of this search. Exclusion criteria: irrelevance to the topic and duplicate literature.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData processing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDownload the selected studies and export them in plain text format, saving them as \u0026apos;download.txt\u0026apos;, and use CiteSpace (6.3 R1) and Microsoft Excel (2021) for further analysis. Each study includes a complete record and all cited references. CiteSpace conducts a visual analysis of keywords, authors, institutions, countries, disciplines, cited literature, cited authors, and cited journals. The parameters for CiteSpace are: time span (2020 to 2024), duration (1 year), gindex (k=25), with \u0026apos;pathfinder\u0026apos;, \u0026apos;pruning sliced networks\u0026apos;, and \u0026apos;pruning the network\u0026apos; checked, while other parameters remain at their system default values. Use Microsoft Excel to create a line chart showing the trend of published articles by year. The core authors are calculated based on Price\u0026apos;s Law\u0026nbsp;\u003cimg width=\"139\" height=\"30\" src=\"data:image/png;base64,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\" alt=\"image\"\u003e\u0026nbsp;(where Mmax is the publication volume of the highest producing author).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eAnalysis of Publishing Trends and Journals\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 470 articles were retrieved through the initial search. Articles classified as conference abstracts, revisions, and news were excluded, leaving 382 articles for further analysis. Using Excel to statistically analyze the annual publication volume, the publication trend is shown in the line graph (Fig. 1). The first article on VEXAS syndrome was published in 2020, and the annual publication volume has shown a year-on-year growth trend, with the fastest growth occurring between 2021 and 2022, indicating that VEXAS syndrome has gradually become one of the research hotspots among scholars. As of now, the peak publication volume in 2024 has reached 136 articles. Overall, VEXAS syndrome, as a recently discovered autoinflammatory disease, has a relatively low overall publication volume but is showing an upward trend; VEXAS syndrome is slowly entering the public eye and receiving increasing attention.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Collaboration Network Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnalysis reveals that from 2020 to the present, a total of 235 authors have published research on VEXAS syndrome. A node represents an author, the size of the node represents the number of papers published by the author, and the connections between nodes reflect collaborations among authors. There are a total of 782 connections between authors, with a network density of 0.0236, indicating that there is communication and collaboration among authors, but it is relatively dispersed and not very close-knit. Many authors have only published one or two papers each. According to Price\u0026apos;s Law, authors with a publication count of \u0026ge;4 are considered core authors in the field, thus authors with a publication count of \u0026ge;4 are displayed, as seen in Fig. 2. David B. Beck from the United States ranks first with 27 publications, followed by Arsene Mekinian (n = 23) and Olivier Kosmider (n = 21) from France, and Peter C. Grayson (n = 20) and Marcela A. Ferrada (n = 16) from the United States, ranking 4th and 6th respectively. High-output authors from the same country exhibit some collaborative relationships, for instance, the team centered around David B. Beck, Peter C. Grayson, and Marcela A. Ferrada mainly focuses on VEXAS syndrome research, covering mechanisms, clinical manifestations, diagnosis, and treatment, among other topics [1,11-12], with published literature from 2020 to 2024. Overall, there is a stable collaboration among Beck David B, Grayson Peter C, and Ferrada Marcela A, while other authors tend to be \u0026nbsp;relatively independent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnalysis of publishing institutions and national cooperation networks\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results are shown in Fig. 3(a), with a total of 184 nodes and 486 connections, resulting in a network density of 0.0208. This indicates that a total of 184 institutions have published related articles, with limited collaboration between them. Among these, 31 institutions have published 10 or more articles, with the highest number being 53 articles, making it the only institution with more than 50 publications, which is Assistance Publique Hopitaux Paris (APHP).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurthermore, 5 of the 31 institutions are part of APHP, while another 8 institutions that are also part of APHP have published fewer than 10 articles. A relatively stable collaborative relationship has formed among these institutions, with major research directions including pustular psoriasis, endocrinology, and several other fields. The second highest number of publications comes from the National Institutes of Health (NIH) \u0026ndash; USA (n=48), followed by NIH National Human Genome Research Institute (NHGRI) (n=24), NIH National Institute of Arthritis \u0026amp; Musculoskeletal \u0026amp; Skin Diseases (NIAMS) (n=21), and NIH National Heart Lung \u0026amp; Blood Institute (NHLBI).\u003c/p\u003e\n\u003cp\u003e(n=19) all belong to research institutions under the National Institutes of Health (NIH) in the United States. A comprehensive analysis reveals that collaboration among institutions is mainly between affiliated entities. This collaborative model has the advantage of facilitating the allocation and utilization of internal resources, demonstrating significant synergistic effects. However, it lacks the integration of resources across organizations, which may lead to data being singular and lacking breadth and depth.\u003c/p\u003e\n\u003cp\u003eA total of 40 countries have published literature related to VEXAS syndrome, with a connection count of 104 and a network density of 0.1103, as shown in Fig. 3(b). Among these countries, only 9 have published more than 10 articles, accounting for 77.5% of the total publication volume. The country with the highest number of publications is the United States (n=121), followed by France (n=89), Italy (n=30), Japan (n=28), and the United Kingdom (n=24). The country with the highest centrality is the United Kingdom (0.86), followed by Italy (0.81) and the United States (0.57), with these three countries playing a significant role in international cooperation.\u003c/p\u003e\n\u003cp\u003eIn summary, there is little connectivity among authors, and the connections between institutions mainly involve affiliated entities. Transnational communication and cooperation are primarily concentrated between Italy and the United States, which significantly hinders the development of research in this field.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKeyword co-occurrence analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCo-occurrence network analysis\u003c/p\u003e\n\u003cp\u003eAn analysis of the literature keywords reveals a total of 196 nodes and 503 connections, with a network density of 0.0193. Keywords that occur with a frequency of five or more times are labeled, with larger nodes indicating a higher frequency of occurrence [13-14]. The keyword co-occurrence graph is presented in Fig. 4. Among the 196 keywords, 17 have a frequency of occurrence of ten or more times, and the top ten keywords are listed in Table 1. Somatic mutations, autoinflammatory diseases, and the e1 enzyme are among the primary characteristics of VEXAS syndrome, which explains their higher frequency. Furthermore, VEXAS syndrome, an autoimmune disease associated with mutations in the UBA1 gene, most commonly presents with myelodysplastic syndrome in hematology. Meanwhile, manifestations, which are among the most concerning issues, appeared 48 times, while relapsing polychondritis and clonal hematopoiesis may represent significant clinical manifestations aside from the primary characteristics.\u003c/p\u003e\n\u003cp\u003eTable 1 Top Ten Keywords in VEXAS Comprehensive Essay Contest\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eNumber\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003eKeywords\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003eFrequency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eThe earliest year of publication\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003evexas syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003esomatic mutations\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003emyelodysplastic syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003emanifestations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003eautoinflammatory diseases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003erelapsing polychondritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003eautoimmune diseases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003euba1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003eclonal hematopoiesis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003ee1 enzyme\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eCentrality analysis\u003c/p\u003e\n\u003cp\u003eCentrality Betweenness (CB) is an indicator that assesses the significance of a node within a network, with values ranging from 0 to 1. A node with a CB greater than 0.1 can be classified as a core node, where higher values signify greater influence [13]. In the context of VEXAS syndrome, there are 23 keywords with high centrality, the top five being acute myeloid leukemia (0.49), risk (0.38), adult-onset Still\u0026apos;s disease (0.29), familial Mediterranean fever (0.26), and stem cell transplantation (0.26). This indicates that VEXAS syndrome frequently manifests with clinical symptoms or laboratory evidence of AML, adult Still\u0026apos;s disease, or familial Mediterranean fever prior to achieving a definitive diagnosis. Stem cell transplantation is the predominant treatment utilized for VEXAS syndrome, occupying a crucial role, while risk has emerged as one of the primary areas of concern since 2021.\u003c/p\u003e\n\u003cp\u003eCluster analysis\u003c/p\u003e\n\u003cp\u003eCitespace clustering analysis classifies keywords related to similar topics and evaluates clustering effectiveness based on the modularity value (Q) and average silhouette value (S). A Q value exceeding 0.3 indicates significant clustering results, whereas an S value greater than 0.5 suggests reasonable clustering outcomes [15]. Different colored blocks represent distinct clusters, with the size of each cluster being inversely proportional to its number; thus, a larger cluster corresponds to a smaller numerical designation [16]. In VEXAS syndrome, a total of 13 clusters are identified (Fig. 5), with Q = 0.7945 and S = 0.9052, indicating that the clustering results are both reasonable and significant. The number of nodes in each cluster and the top four keywords are presented in\u0026nbsp;Table 2. Cluster 0# encompasses e3 ubiquitin ligase, protein, autophagy, and skp2, suggesting that the mechanisms associated with interstitial lung disease, one of the primary manifestations of VEXAS syndrome, may be linked to these keywords. Cluster 1# includes terms such as germline susceptibility, autoinflammatory diseases, and complexity, indicating that VEXAS syndrome is related to germline susceptibility, with its mechanisms and clinical features being relatively complex. Clusters #2, #3, #4, #5, #7, #8, and #9 primarily consist of keywords related to the clinical manifestations of VEXAS syndrome and various differential diagnoses, suggesting that VEXAS syndrome clinically presents mainly as inflammation and hematological issues, including arteritis, chondritis, renal injury, adult Still\u0026apos;s disease, Sweet\u0026apos;s syndrome, and myelodysplastic syndrome, among others. Cluster 6# mainly includes treatment-related terms such as Jak inhibitors, indicating a high thrombotic risk associated with VEXAS syndrome; studies suggest that approximately 35% to 56% of patients with VEXAS syndrome may experience venous thromboembolism (VTE), primarily manifesting as venous thrombosis rather than arterial thrombosis [17]. The activation of the coagulation system may lead to systemic inflammatory responses. JAK inhibitors are a class of non-receptor tyrosine kinases that alleviate inflammation caused by excessive cytokine production by inhibiting the activity of one or more JAKs, thus blocking the corresponding JAK-STAT signaling pathways, demonstrating promising prospects in inflammatory diseases such as rheumatoid arthritis (RA), atopic dermatitis (AD), and inflammatory bowel disease (IBD) [18]. Clusters 10# and 11# include terms such as somatic mutations, vacuolization, Schnitzler syndrome, Still\u0026apos;s disease, anti-collagen antibodies, inflammation, relapsing polychondritis, VEXAS syndrome, and Schnitzler syndrome, indicating an association between bone marrow and cartilage in VEXAS syndrome, with bone marrow playing an irreplaceable role in diagnosis; systemic inflammatory responses also frequently occur in cartilage. Cluster 12# primarily includes venous thromboembolism, IL-6, VEXAS syndrome, and cerebral sinus vein thrombosis, suggesting that VEXAS syndrome, as a newly identified disease, is primarily documented in case analyses, with a notable lack of large-scale clinical data.\u003c/p\u003e\n\u003cp\u003eTable 2 Keyword Clustering Table of VEXAS Syndrome Literature\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003eCluster number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003eNodes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003eYears\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eCluster labels\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eKeywords\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e#0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003einterstitial lung disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003ee3 ubiquitin ligase; protein; autophagy; skp2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e#1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eassociation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003edisease; germline predisposition; autoinflammatory disorder; complex\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e#2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eacute kidney injury\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003erelapsing polychondritis; nosology; web of science; spinal muscular atrophy (sma)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e#3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003egiant cell arteritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003emyelodysplastic-myeloproliferative diseases; systemic; large vessels vasculitis; neurosensory hearing loss\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e#4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003efamilial mediterranean fever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eschnitzler syndrome; stills disease; adult-onset; pfapa syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e#5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003edifferential diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003efibroinflammatory disease ; primary immunodeficiency disease; connective tissue disease; pan\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e#6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003ecoagulation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003ediagnositc; treatment; janus kinase (jak) inhibitors; monocyte\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e#7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003ehemophagocytic lymphohistiocytosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eventriculitis; daptomycin; proteins; a20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e#8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003esweets syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003esweet syndrome; clonal hematopoiesis; bone marrow failure syndromes; immune regulation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e#9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003edysbiosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eschnitzler; drug reaction with eosinophilia and sys-temic symptoms; multisystem inflammatory syndrome in children; common variable immune defi-ciency\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e#10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003ebone marrow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003esomatic mutations; vacuolization; schnitzler syndrome; stills disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e#11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003ecartilage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eanti-collagen antibodies; inflammation; relapsing polychondritis; vexas syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e#12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003ecase report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003evenous thromboembolism; il-6; veaxs syndrome; cerebral sinus vein thrombosis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTimeline analysis\u003c/p\u003e\n\u003cp\u003eThe timeline chart (Fig. 6) visually illustrates the time span of each cluster and the interconnections among different clusters, thereby effectively demonstrating the evolutionary trajectory of VEXAS syndrome. The keyword timeline chart indicates the initial appearance of each keyword within the selected time frame, as well as the evolving trends of research hotspots over time [19]. Cluster #2, concerning acute kidney injury, has been investigated as early as 2020, while cluster #10, related to bone marrow, gained prominence upon its emergence, attracting considerable attention. Research interest in cluster #1, pertaining to association, cluster #6, focusing on coagulation, and cluster #10, concerning bone marrow, began to decline around 2021. In contrast, clusters #0, addressing interstitial lung disease, #2, concerning acute kidney injury, #3, related to giant cell arteritis, #4, focusing on familial Mediterranean fever, #5, dealing with differential diagnosis, #7, concerning hemophagocytic lymphohistiocytosis, #8, related to Sweet\u0026apos;s syndrome, #9, addressing dysbiosis, #11, focusing on cartilage, and #12, pertaining to case reports, have continued to be the subject of research from their year of emergence to the present. This indicates that these areas have been consistently explored and remain prominent research hotspots.\u003c/p\u003e\n\u003cp\u003eBurstness analysis\u003c/p\u003e\n\u003cp\u003eEmergence refers to the sudden increase in the frequency of keywords over a specified period, which can be utilized to comprehend shifts in research frontiers, focal points, and the latest trends in research hotspots [20]. As illustrated in Fig. 7, the study of VEXAS syndrome has emerged as a hotspot beginning in 2021. In terms of emergence intensity, the highest-ranking keyword is \u0026apos;autoimmune disease\u0026apos; (2.12), which, despite having a duration of only one year, exhibits the greatest intensity, indicating that it was the primary focus of researchers in 2021. Conversely, the lowest-ranking keyword is \u0026apos;classification\u0026apos; (1.38), with a duration spanning from 2020 to 2021. Analyzing the research timeline reveals that the emphasis in 2020 was on defining VEXAS syndrome and its related disease classification. From 2021 to 2022, the research hotspots transitioned to clinical manifestations and associated hematological and immunological diseases, including hematological disorders (myelodysplastic syndromes) and immune system diseases (systemic lupus erythematosus, polyarteritis nodosa), among others. The keywords \u0026apos;prevalence\u0026apos; and \u0026apos;immunodeficiency\u0026apos; have persisted in research since 2023, suggesting that they may evolve into future research hotspots.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVEXAS syndrome and MDS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThrough the analysis of keyword co-occurrence networks, it is evident that MDS is the most frequently occurring keyword (59 occurrences), alongside somatic mutations in VEXAS syndrome. Furthermore, MDS appears in the keywords associated with cluster label #3 and in the keyword burst analysis, indicating that MDS is one of the common clinical manifestations of VEXAS syndrome, demonstrating a strong correlation with MDS in the hematological context and garnering widespread attention.\u003c/p\u003e\n\u003cp\u003ePatients diagnosed with VEXAS syndrome are predisposed to hematological malignancies, including MDS and plasmacytoid malignancies [21]. A prospective multicenter study conducted in France revealed that 49% of 116 patients with VEXAS syndrome were diagnosed with MDS. In this study, the median follow-up period was 3 years, and the mortality rate was recorded at 15.5%, with 3 out of 18 deaths attributed to the progression of MDS [22].\u003c/p\u003e\n\u003cp\u003eMDS is typically defined by three criteria: 1. Clonal hematopoietic stem cell disorder; 2. The presence of dysplastic features; 3. Ineffective hematopoiesis resulting in at least one peripheral blood cytopenia [23]. Ineffective hematopoiesis refers to morphological abnormalities observed in more than 10% of red blood cells, granulocytes, and/or megakaryocyte lineages. The prevalence of hematopoietic clones identified through next-generation sequencing (NGS) blurs the distinction between normal and pathological states, rendering clonality no longer a definitive characteristic of MDS [24]. Bone marrow characteristics in patients with VEXAS syndrome, including myeloid proliferation, vacuolization, and the presence of macrocytic hyperplasia [1,25], suggest that VEXAS is associated with ineffective hematopoiesis, similar to MDS.\u003c/p\u003e\n\u003cp\u003eGutierrez-Rodrigues found that patients with VEXAS syndrome exhibit both UBA1 mutations and other typical myeloid mutations, primarily including DNMT3A and TET2, which are independent of inflammatory and hematological manifestations. Cells harboring UBA1 mutations are the principal contributors to systemic inflammation and bone marrow failure [26-27]. Some patients with VEXAS syndrome exhibit ineffective hematopoiesis and display dysplastic features in the bone marrow lineage, thus fulfilling some of the minimal criteria for MDS. However, there is relatively no increase in blasts or progression to AML, which appears to be a critical unmet criterion for classification within the MDS spectrum at this stage [28]. Approximately 20-50% of MDS patients associated with VEXAS exhibit low-risk features and are diagnosed as MDS-MLD or MDS-SLD, with or without ringed sideroblasts (RS), and their somatic mutation profiles do not align with those typical of MDS, lacking genes associated with poor prognosis in MDS (such as TP53, RUNX1, etc.) [29-30]. This indicates that the MDS associated with UBA1 mutations represents a unique clinical and molecular entity, distinct from classic MDS.\u003c/p\u003e\n\u003cp\u003eMultiple retrospective studies have validated the effectiveness of AZA for MDS-related VEXAS, which can prolong the \u0026apos;time to next treatment\u0026apos;, stabilize or improve cytopenias, and even achieve complete clearance of UBA1 mutation clones along with complete remission of MDS [31-37].\u003c/p\u003e\n\u003cp\u003eNevertheless, the precise relationship between UBA1 mutation clones and the onset of MDS remains undetermined. It is still unclear whether myeloid tumors are primarily driven by UBA1 mutation clones or if a highly inflammatory microenvironment facilitates clonal selection.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe trend of published articles shows that in 2020, research on VEXAS syndrome was in its early stages, with only 2 articles published. Since then, the number of publications has increased year by year, with the largest annual growth occurring between 2021 and 2022. In 2024, the number of publications reached its peak at 136 articles. This indicates that with the development of society, the field of VEXAS syndrome is receiving more and more attention.\u003c/p\u003e\n\u003cp\u003eThe co-occurrence analysis of authors, institutions, and countries found that there are few connections between authors, while high-output authors tend to have collaborative relationships within their country. The institutions with the highest publication output are APHP and the National Institutes of Health in the United States, with the United States (n=121) being the country with the most publications. Collaboration between institutions mainly occurs among affiliated institutions, with a lack of inter-institutional and cross-national flow and cooperation, which greatly hinders the progress of research in this field and provides a reference for future researchers in this area.\u003c/p\u003e\n\u003cp\u003eFrom the analysis of the keyword co-occurrence map, it can be seen that somatic mutations, autoinflammatory diseases, and E1 enzyme are among the main features of VEXAS syndrome. Clinical manifestations are the topics of greatest concern for researchers studying VEXAS syndrome, primarily including autoinflammatory reactions and hematological manifestations. Myelodysplastic syndromes have become one of the most commonly mentioned hematological manifestations of VEXAS syndrome. At the same time, recurrent polychondritis and clonal hematopoiesis may be comparatively important clinical manifestations apart from the main features.\u003c/p\u003e\n\u003cp\u003eThe keyword clustering and keyword timeline chart reflect the hot topics and development trends in VEXAS syndrome research. Since the discovery of VEXAS syndrome in 2020, research has mainly focused on the pathogenesis of the disease (e1 enzyme, immune dysregulation, etc.). After 2021, this disease became a research hotspot, and from 2021 to 2024, the research content mainly revolved around mechanisms and clinical manifestations. The clinical manifestations primarily include inflammatory responses (fever, polyarthritis, vasculitis, thrombosis, etc.) and hematological manifestations (MDS, macrocytic anemia, thrombocytopenia, etc.). There is a high correlation with MDS in hematological aspects. In terms of treatment, azacitidine, interferon gamma inhibitors, IL-1 receptor antagonists, tumor necrosis factor inhibitors, stem cell transplantation, and biological agents have been mentioned successively.\u003c/p\u003e\n\u003cp\u003eOverall, VEXAS syndrome, as a new autoimmune disease, has garnered increasing attention since its discovery in 2020. The main research focus is on the mechanisms and clinical manifestations of the disease. Currently, over 70% of published VEXAS cases have the p.Met41 substitution, loss of exon 3 from the cytoplasmic isoform of UBA1 (UBA1b), and the formation of a subtype enzyme (UBA1c) with reduced catalytic activity, leading to decreased cell ubiquitination, accumulation of misfolded proteins, and endoplasmic reticulum stress. The activation of the unfolded protein response ultimately triggers inflammation. Recent studies have also reported non-classical somatic UBA1 mutations that are neither Met41 nor exon 3 [38-41]. Research into the mechanisms of VEXAS syndrome is still gradually being explored.\u003c/p\u003e\n\u003cp\u003eLimitations of this study: 1. The data used in this article is solely from the WOSCC database, which may exclude some valuable information; 2. The absence of references in the obtained data restricts the visualization analysis to the co-occurrence level and does not allow for citation analysis to explore the intrinsic relationships between authors and topics; 3. There may be some errors due to the involvement of a large number of foreign vocabulary when manually combining synonyms of keywords. 4. The literature visualization analysis is only conducted using CiteSpace software, which has a considerable degree of subjectivity in threshold selection. Future research could combine various visualization methods for in-depth exploration from multiple perspectives and corroborate each other to ensure the objectivity of the research results.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study conducted a visual analysis utilizing Citespace software on all pertinent literature regarding VEXAS syndrome retrieved from the WOSCC database. The analysis revealed that while the publication volume associated with VEXAS syndrome has been increasing annually, the level of attention towards VEXAS syndrome remains relatively low. Furthermore, there is limited collaboration across institutions and nations among various authors and institutions, and currently, no standard treatment protocol exists for VEXAS syndrome.\u003c/p\u003e\n\u003cp\u003eGiven the hematological and immunological manifestations of VEXAS syndrome, it is susceptible to misdiagnosis in clinical practice, which has led to heightened interest in VEXAS. With the advancement of global medical standards, targeted therapies are anticipated to emerge as a new focal point for research. It is expected that in the future, targeted treatments for VEXAS syndrome associated with UBA1 mutations will undergo more comprehensive investigations. We hope that more researchers will accord sufficient attention to this matter and engage in in-depth discussions regarding mechanisms, treatments, and other aspects to provide valuable references for clinical practice. Building on this foundation, large-sample, cross-provincial clinical research should be undertaken for the benefit of humanity.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by The Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project (ZJ-TCM-Major Projects) (Project number: GZY-ZJ-KJ-24013).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data generated in the present study may be requested from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: Mengke Mao, Shao Yifei. Data curation: Shan Liu. Formal analysis: Mengke Mao, Shao Yifei. Methodology: Shan Liu. Software: Mengke Mao. Supervision: Shu Deng. Writing\u0026ndash;original draft: Mengke Mao. All authors read and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOpen Access\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution, and reproduction in any medium or format, provided that appropriate credit is given to the original author(s) and source, a link to the Creative Commons license is provided, and it is indicated whether any modifications were made to the licensed material. Under this license, you do not have the right to share adapted material derived from this article or any parts thereof. Images or other third parties. The materials in this article are covered under the article\u0026apos;s Creative Commons license, unless otherwise indicated in the acknowledgments of the materials. If the materials are not included under the article\u0026apos;s Creative Commons license, and your intended use is not permitted by statutory regulations or exceeds the permitted use, you need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eBeck DB, Ferrada MA, Sikora KA, et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease[J]. N Engl J Med, 2020,383(27):2628-2638.\u003c/li\u003e\n \u003cli\u003eBeck DB, Werner A, Kastner DL, et sl. Disorders of ubiquitylation: unchained inflammation[J]. Nat Rev Rheumatol, 2022,18(8):435-447.\u003c/li\u003e\n \u003cli\u003eLacombe V, Prevost M, Bouvier A, et al. Vacuoles in neutrophil precursors in VEXAS syndrome: diagnostic performances and threshold[J]. Br J Haematol, 2021, 195(2):286-289.\u003c/li\u003e\n \u003cli\u003ePoulter JA, Savic S. Genetics of somatic auto-inflammatory disorders[J]. Semin Hematol, 2021,58(4):212-217.\u003c/li\u003e\n \u003cli\u003eHuang H, Zhang W, Cai W, et al. VEXAS syndrome in myelodysplastic syndrome with autoimmune disorder[J]. Exp Hematol Oncol, 2021,10(1):23.\u003c/li\u003e\n \u003cli\u003eBourbon E, Heiblig M, Gerfaud VM, et al. Therapeutic options in VEXAS syndrome: insights from a retrospective series[J]. Blood, 2021,137 (26) :3682-3684.\u003c/li\u003e\n \u003cli\u003ePadureanu V, Marinas CM, Bobirca A, et al. Clinical manifestations in vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: A narrative review[J]. Cureus, 2024,16(1): e53041.\u003c/li\u003e\n \u003cli\u003eChen CM. CiteSpace II: Detecting and visualizing emerging trends and transient patterns in scientific literature[J]. J Am Soc Inf Sci, 2006,57(3):359-377.\u003c/li\u003e\n \u003cli\u003eJiao YT,\u0026nbsp;Qin XM, Wu XK. Visualization analysis of research status and trend of traditional Chinese medicine in treatment of senile depression based on Citespace [J]. Chin Med Herbal Drugs,2024,55(21):7409-7418.\u003c/li\u003e\n \u003cli\u003eRen YY,\u0026nbsp;Hou Y, Zhe BB. Based on VOSviewer and CiteSpace, visual analysis of research on non-drug intervention of traditional Chinese medicine in diabetes in recent 10 years[J/OL]. J Trad Chin Med.\u003c/li\u003e\n \u003cli\u003eObiorah IE, Patel BA, Groarke EM, et al. Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in\u0026nbsp;UBA1. Blood Adv,2021,5(16):3203-3215.\u003c/li\u003e\n \u003cli\u003eFerrada MA, Sikora KA, Luo YM, et al.\u0026nbsp;Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS[J]. ARTHRITIS RHEUMATOL\u0026zwnj;\u0026zwnj;,2021,73(10):1886-1895.\u003c/li\u003e\n \u003cli\u003eLiang GC.\u0026nbsp;Research hotspots and application patterns of Earthworms based on CiteSpace and data mining analysis[D].\u0026nbsp;Yichun Univ, 2023.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eChen YQ,\u0026nbsp;Xing XF,\u0026nbsp;Cheng DL,\u0026nbsp;et al.\u0026nbsp;Construction of National Agricultural Informatization Knowledge Graph Based on Citespace and Intermediary Centrality Algorithm [J]. J SW Univ Natls (Nat Sci Ed), 2022,48(1):75-81.\u003c/li\u003e\n \u003cli\u003eChen Y, Chen CM, Liu ZY, et al. The methodology function of CiteSpace mapping knowledge domains [J]. Stud Sci Sci,2015,33(2):242-253.\u003c/li\u003e\n \u003cli\u003eChen C, Song M. Visualizing a field of research: A methodology of systematic scientometric reviews[J]. PLoS One, 2019,14(10): e0223994.\u003c/li\u003e\n \u003cli\u003eLoeza-Uribe MP, Hinojosa-Azaola A, S\u0026aacute;nchez-Hern\u0026aacute;ndez BE, et, al. VEXAS syndrome: Clinical manifestations, diagnosis, and treatment[J]. Reumatol Clin (Engl Ed), 2024,20(1):47-56.\u003c/li\u003e\n \u003cli\u003eHu X, Li J, Fu M, et al. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther, 2021,6(1):402.\u003c/li\u003e\n \u003cli\u003eLiu XX, Zhang C, Huang SQ, et al. Bibliometric analysis of current status and development trend of polysaccharidefrom Polygonati Rhizoma[J]. Chin Med Herbal Drugs, 2023,54(21):7130-7141.\u003c/li\u003e\n \u003cli\u003eLing N, Guo CQ, Tiang HY, et al. Visualized analysis of research status and development trend of Hippophae rhamnoides polysaccharides based on bibliometrics[J]. Chin Med Herbal Drugs,2024,55(20):7074-7061.\u003c/li\u003e\n \u003cli\u003ePoulter JA, Collins JC, Cargo C, et al. Novel somatic mutations in UBA1 as a cause of VEXAS syndrome[J]. Blood,2021,137(26): 3676-3681.\u003c/li\u003e\n \u003cli\u003eGeorgin-Lavialle S, Terrier B, Guedon AF, et al. Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients[J]. Br J Dermatol,2022,186(3):564-574.\u003c/li\u003e\n \u003cli\u003eKhoury JD, Solary E, Abla O, et al. The 5th edition of the world health organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms[J]. Leukemia, 2022,36(7):1703\u0026ndash;1719.\u003c/li\u003e\n \u003cli\u003ePierre S, Laetitia L, Yvan J, et al. VEXAS: is it time to reshape the nosology of clonal hematopoiesis? [J]. Expert Rev Hematol,2023,16(7):495-499.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eObiorah IE, Patel BA, Groarke EM, et al. Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1[J]. Blood Adv,2021,5(16):3203\u0026ndash;3215.\u003c/li\u003e\n \u003cli\u003eGutierrez-Rodrigues F, Kusne Y, Fernandez J, et al. Spectrum of clonal hematopoiesis in VEXAS syndrome[J]. Blood,2023,142(3): 244-259.\u003c/li\u003e\n \u003cli\u003ePatel BA, Gutierrez-Rodrigues F, Kusne Y, et al. Clonal Hematopoiesis in Vexas Syndrome[J]. Blood, 2022;140(3):5745-5746.\u003c/li\u003e\n \u003cli\u003eMalcovati L. VEXAS: walking on the edge of malignancy[J]. Blood, 2023 Jul 20;142(3):214-215.\u003c/li\u003e\n \u003cli\u003eLytle A, Bagg A. VEXAS: a vivid new syndrome associated with vacuoles in various hematopoietic cells[J]. Blood, 2021;137(26):3690.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Gutierrez-Rodrigues F, Kusne Y, Fernandez J, et al. Spectrum of clonal hematopoiesis in VEXAS syndrome[J]. Blood, 2023,142(3):244\u0026ndash;259.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKatja Sockel, Katharina G\u0026ouml;tze, Christina Ganster, et al. VEXAS syndrome: complete molecular remission after hypomethylating therapy[J]. Ann Hematol,2024,103(3):993\u0026ndash;997.\u003c/li\u003e\n \u003cli\u003eFraison JB, Mekinian A, Grignano E, et al. Efficacy of Azacitidine in Autoimmune and Inflammatory disorders associated with myelodysplastic syndromes and Chronic Myelomonocytic Leukemia[J]. Leuk Res, 2016,43:13\u0026ndash;17.\u003c/li\u003e\n \u003cli\u003eTzvika Porges, Elli Rosenberg, Ofir Wolach, et, al. Case report: VEXAS syndrome with excellent response to treatment with azacytidine[J/OL]. Ann Hematol.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRaaijmakers MHGP, Hermans M, Aalbers A, et al. Azacytidine Treatment for VEXAS Syndrome. Hemasphere,2021,5(12): e661.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKataoka A, Mizumoto C, Kanda J, et al. Successful azacitidine therapy for myelodysplastic syndrome associated with VEXAS syndrome. Int J Hematol, 2023,117(6):919\u0026ndash;924.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCordts I, Hecker JS, Gauck D, et al. Successful treatment with azacitidine in VEXAS syndrome with prominent myofasciitis. Rheumatology, 2022,61(5): e117\u0026ndash;e119.\u003c/li\u003e\n \u003cli\u003eBourbon E, Heiblig M, Gerfaud VM, et al. Therapeutic options in VEXAS syndrome: insights from a retrospective series. Blood,137(26):3682\u0026ndash;3684.\u003c/li\u003e\n \u003cli\u003ePoulter JA, Collins JC, Cargo C, et al. Novel somatic mutations in UBA1 as a cause of VEXAS syndrome. Blood, 2021,137(26):3676\u0026ndash;3681.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eStiburkova B, Pavelcova K, Belickova M, et al. Novel somatic UBA1 variant in a patient with VEXAS syndrome. Arthritis Rheumatol, 2023,75(7):1285\u0026ndash;1290.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSakuma M, Blombery P, Meggendorfer M,\u0026nbsp;et al. Novel causative variants of VEXAS in UBA1 detected through whole genome transcriptome sequencing in a large cohort of hematological malignancies. Leukemia, 2023,37(5):1080\u0026ndash;1091.\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Collins JC, Magaziner SJ, English M, et al. Shared and distinct mechanisms of UBA1 inactivation across different diseases. EMBO J. 2024;43(10):1919-1946.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"VEXAS syndrome, CiteSpace, visual analysis, Myelodysplastic syndrome","lastPublishedDoi":"10.21203/rs.3.rs-6353181/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6353181/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eUnderstanding the current research status and hotspots of VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Syndrome) syndrome provides reference and guidance for the diagnosis and treatment of VEXAS syndrome.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod: \u003c/strong\u003eUsing the Web of Science Core Collection (WOSCC) literature retrieval platform, we filtered literature related to VEXAS syndrome and conducted a visual analysis of the publication volume, authors, publishing institutions, countries, and keywords of VEXAS syndrome based on CiteSpace 6.3.R1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eA total of 382 articles were obtained through the results filtering. The first article on VEXAS syndrome was published in 2020, and 136 articles were published in 2024. According to the author collaboration network analysis, Beck David B from the United States had the highest number of publications, with 27 articles. Institution and country analysis revealed that APHP and the National Institutes of Health had the highest number of publications, while the United States had the highest publication count (n=121). The top ten keywords ranked by co-occurrence mainly revolve around the definition, mechanism, and clinical manifestations of VEXAS syndrome. Keyword cluster analysis indicates that the main features of VEXAS syndrome are inflammatory and hematological manifestations, with its mechanisms and clinical characteristics being relatively complex. In terms of treatment, azacitidine and interferon-gamma inhibitors, IL-1 receptor antagonists, tumor necrosis factor inhibitors, stem cell transplantation, and biological agents were mentioned in succession. The primary publication format is case analysis reports. The timeline shows the sustained intensity of inflammatory and hematological manifestations from the onset of the disease to the present. Burstness analysis revealed that the research focus in 2020 was on the definition and classification of VEXAS syndrome. From 2021 to 2022, the research hotspots shifted to clinical manifestations, including hematological and immunological diseases such as myelodysplastic syndromes (MDS), chronic monocytic leukemia, systemic lupus erythematosus, and polyarteritis nodosa.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e VEXAS syndrome has gradually attracted the attention of researchers, with an overall upward trend in annual publications, although the total number of publications is relatively low. Collaboration between authors and institutions is relatively dispersed, primarily based on collaboration among their affiliated institutions, lacking cross-border cooperation. Currently, the research focus on VEXAS syndrome lies mainly in genetic mutations, immune regulation, and multi-system pathologic presentations, which show high correlation with MDS in hematology. The lack of guidance for treatment plans and standardized protocols may be related to the short research duration on VEXAS syndrome and the absence of large-scale clinical trials. At present, the main published format is case analyses. In summary, this disease still requires more attention in clinical practice, and the mechanisms, clinical features, and treatment strategies of VEXAS syndrome should be explored in depth to lay a solid foundation for more effective prevention and treatment in the future.\u003c/p\u003e","manuscriptTitle":"Visual analysis of the current status and trends of VEXAS syndrome research based on Citespace","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-09 01:35:24","doi":"10.21203/rs.3.rs-6353181/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-02T11:33:02+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-02T08:47:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"319317779928546361751388754152958353455","date":"2025-06-26T10:37:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"309777146125343703912557695824745529089","date":"2025-06-01T14:27:47+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-25T08:13:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"194351607378382423242885049255801612164","date":"2025-05-15T10:51:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"251314920040160254075117080550376505658","date":"2025-05-03T01:27:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-02T10:29:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-24T14:05:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-24T14:02:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Medicine","date":"2025-04-01T12:26:16+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"154a725b-dcf0-47eb-8b60-767f1116e7b8","owner":[],"postedDate":"May 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-07-26T10:08:28+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-09 01:35:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6353181","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6353181","identity":"rs-6353181","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}