Two Decades of Port-Wine Stain Research (2005-2024): A Bibliometric Mapping of the Shift Toward Molecular Pathogenesis

Two Decades of Port-Wine Stain Research (2005-2024): A Bibliometric Mapping of the Shift Toward Molecular Pathogenesis | 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 Two Decades of Port-Wine Stain Research (2005-2024): A Bibliometric Mapping of the Shift Toward Molecular Pathogenesis Yingjie Zhu, Ye Zhang, Xingyu Zhu, Yubing Nie, Chaonan Wang, Xiaonan Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9137673/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Port-wine stains (PWS) are congenital capillary malformations. Although laser-based therapies have dominated the field for decades, recent research has increasingly focused on molecular pathogenesis and targeted intervention. Objectives To map the global research landscape of PWS from 2005 to 2024 and to identify changes in research priorities following major genetic discoveries. Methods We analyzed 1,742 publications retrieved from the Web of Science Core Collection using a search strategy informed by the ISSVA 2024 classification. Bibliometric analyses and visualizations were performed with CiteSpace, VOSviewer, and the Bibliometrix R package. Results Publication output showed an overall upward trend, with 102 records indexed for 2024. The United States (731) and China (367) were the leading contributors. Research hotspots shifted from laser physics and selective photothermolysis to GNAQ/GNA11-related molecular mechanisms. Keyword burst analysis identified vascular anomalies and somatic mutation as recent frontiers. Conclusions PWS research has shifted from optimizing physical treatments to investigating molecular pathogenesis. This transition, driven largely by the 2013 discovery of the GNAQ mutation, supports the development of targeted therapeutic strategies. Future studies will likely focus on genotype-phenotype correlations and multimodal interventions. Port-Wine Stains Bibliometrics Vascular Anomalies GNAQ Mutation Pulsed Dye Laser Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 1 Introduction Port-wine stains (PWS) are congenital low-flow capillary malformations (CMs) affecting approximately 0.3% of newborns [ 1 – 3 ] . According to the 2024 International Society for the Study of Vascular Anomalies (ISSVA) classification, PWS are characterized by abnormal dilation of dermal capillaries [ 4 , 5 ] . If untreated, these lesions typically darken and thicken over time and may develop nodularity or soft-tissue hypertrophy, resulting in substantial cosmetic and psychosocial burden. PWS may also occur as part of complex syndromes, most notably Sturge-Weber syndrome (SWS), which is associated with neurological and ocular complications [ 1 , 6 – 12 ] . For decades, PWS research centered on clinical description and the optimization of laser therapy. In 2013, the identification of a somatic activating mutation (c.548G > A, p.Arg183Gln) in GNAQ reframed PWS as a disorder with a defined molecular basis [ 13 – 16 ] . Subsequent work on related GNAQ/GNA11 alterations and downstream signaling pathways moved the field toward a molecular era characterized by growing interest in MAPK and PI3K/AKT signaling [ 17 – 21 ] . Bibliometric analysis enables the quantitative evaluation of this research evolution. Although previous reviews have summarized parts of the field, many relied on outdated terminology or did not include the most recent literature. The present study provides an updated overview through 2024, interpreted within the ISSVA 2024 framework, to identify major knowledge domains, emerging hotspots, and research trends [ 22 – 24 ] . 2 Materials and Methods 2.1 Search Strategy Data were retrieved from the Web of Science Core Collection (WoSCC) on January 1, 2025, covering the publication period from 2005 to 2024. To capture the most complete possible record for 2024, the search was conducted after the close of the calendar year. The search strategy incorporated conventional disease terms, related syndromic entities, and recurrent driver genes relevant to the ISSVA 2024 framework: TS = ("port-wine stain*" OR "port wine stain*" OR "nevus flammeus" OR "capillary malformation*") OR TS = ("Sturge-Weber syndrome" OR "Klippel-Trenaunay syndrome" OR "GNAQ" OR "GNA11"). 2.2 Inclusion Criteria Only documents classified as "Article" or "Review" were included. Meeting abstracts, editorial materials, letters, and book chapters were excluded. After deduplication, 1,742 records were retained for the final analysis. Full records and cited references were exported in plain-text format, including titles, authors, institutions, countries, keywords, abstracts, publication years, and cited references. 2.3 Data Analysis Descriptive bibliometric indicators were generated with the Bibliometrix R package. VOSviewer was used to construct collaboration networks among countries, institutions, and authors. CiteSpace was used for reference co-citation analysis and keyword burst detection to identify knowledge bases and emerging research frontiers. 3 Results 3.1 Publication Trends Total annual output showed an overall upward trajectory across the 20-year period (R² = 0.85). Although annual counts fluctuated after 2013, the database contained 102 records for 2024 (Fig. 1 ). Overall, the pattern suggests sustained expansion of the field, with increasing attention to molecular mechanisms and targeted therapeutic strategies. 3.2 Core Journals and Foundational Literature Table 1 lists the major journals in the field. Lasers in Surgery and Medicine (139 papers) and Dermatologic Surgery (71 papers) remained important outlets for clinical and laser-oriented research. Broad-scope dermatology journals such as the Journal of the American Academy of Dermatology and the British Journal of Dermatology more often featured studies on pathogenesis, classification, and clinical management. Table 1 Major journals in PWS research and their relevance Rank Journal Title Publications H-Index Impact Factor (2023) JCR Quartile (2023) Primary Role / Relevance to PWS Research 1 Lasers in Surgery and Medicine 139 42 2.2 Q2 Premier journal in laser medicine; the main platform for PWS physical therapy (PDL, photothermolysis) research. 2 Dermatologic Surgery 71 31 2.5 Q1 Authoritative journal in dermatologic surgery; focuses on clinical treatment techniques and practices for PWS. 3 Journal of the American Academy of Dermatology 46 28 12.8 Q1 Top-tier comprehensive dermatology journal; publishes high-impact clinical and basic research on PWS. 4 Photodiagnosis and Photodynamic Therapy 44 17 3.1 Q2 Specializes in photodynamic diagnosis and therapy; the core journal for PWS photodynamic therapy (PDT) research. 5 British Journal of Dermatology 36 25 11 Q1 A leading, long-standing dermatology journal; publishes important research on PWS pathology, genetics, and treatment. 6 Lasers in Medical Science 65 16 2.1 Q2 Covers laser applications across medical fields; a key supplementary platform for PWS laser technology and mechanism studies. 7 Journal of Biomedical Optics 29 16 3 Q2 Professional journal in biomedical optics; focuses on the optical principles and technological development for PWS diagnosis and treatment. 8 JAMA Dermatology 15 14 11.5 Q1 Leading dermatology journal publishing practice-shaping studies relevant to PWS. 9 Physics in Medicine and Biology 15 13 3.3 Q1 Authoritative journal in medical physics; publishes research on the physical models of laser-tissue interactions in PWS. 10 American Journal of Medical Genetics Part A 17 11 1.7 Q3 A medical genetics journal; an important venue for research on PWS-related syndromes and genetic etiologies. Reference co-citation analysis identified the literature that forms the knowledge base of PWS research. As shown in Table 2 , the most frequently co-cited studies reflect two major intellectual foundations of the field: laser-based therapeutic theory and advances in molecular genetics [ 3 , 13 , 25 – 32 ] . Table 2 Most co-cited foundational articles in PWS research and their core contributions Rank First Author (Year) Source Journal Co-Citations Core Contribution 1 Shirley MD (2013) New England Journal of Medicine 299 [Milestone in Molecular Etiology] First to reveal that a somatic mutation in the GNAQ gene is the underlying cause of PWS and SWS, launching the genomic era of PWS research. 2 Anderson RR (1983) Science 206 First to propose the theory of "Selective Photothermolysis," laying the scientific foundation for pulsed dye laser treatment of vascular skin lesions. 3 Jacobs AH (1976) Pediatrics 182 [Epidemiological Foundation] Conducted an early, large-scale investigation into the incidence of birthmarks in newborns, providing foundational data for PWS epidemiology. 4 Barsky SH (1980) Journal of Investigative Dermatology 119 [Early Pathological Exploration] Used computer-assisted methods to study the pathological evolution of PWS, deepening the understanding of its vascular nature. 5 Thomas-Sohl KA (2004) Pediatric Neurology 115 Provided a comprehensive review of Sturge-Weber Syndrome (SWS), serving as a key reference for this complication. 6 Sujansky E (1995) Journal of Child Neurology 114 Systematically described the natural course of SWS, providing an important basis for its clinical management. 7 Chen JK (2012) Journal of the American Academy of Dermatology 107 Systematically reviewed various clinical and experimental treatment methods for PWS, serving as an authoritative reference in the therapeutic field. 8 Jasim ZF (2007) Journal of the American Academy of Dermatology 91 Focused on treatment strategies for PWS resistant to pulsed dye laser (PDL), providing direction for challenging clinical cases. 9 Yang M (2005) Journal of the American Academy of Dermatology 90 Explored the use of the long-pulsed Nd:YAG laser for PWS treatment, expanding therapeutic options beyond PDL. 10 Renfro L (1993) Archives of Dermatology 89 Analyzed anatomical differences in response to pulsed dye laser treatment, highlighting site-specific variability in therapeutic outcomes. The journal co-citation network (Fig. 2 ) underscores the interdisciplinary structure of the field. Major clusters correspond to laser medicine, pediatric neurology, general dermatology, and photodynamic therapy. Together, these patterns indicate that PWS research has developed at the intersection of lesion-directed treatment and the management of associated syndromic complications. 3.3 Collaboration Network Analysis 3.3.1 Country/Region Collaboration Network Researchers from 62 countries/regions contributed to the field. The United States (731 papers) and China (367 papers) were the most productive contributors (Fig. 3 ). The United States showed broad international collaboration, particularly with European partners, whereas Chinese output was characterized by dense domestic collaboration together with notable bilateral links with the United States. 3.3.2 Institutional Collaboration Network The University of California, Irvine (94 papers) was the most productive institution, followed by Xi'an Jiaotong University and Shanghai Jiao Tong University (Fig. 4 ). Institutional collaboration was organized around several geographic hubs, most prominently a California cluster centered on the Beckman Laser Institute and a Boston cluster associated with Harvard and Boston Children's Hospital. 3.3.3 Author Collaboration Network The author network revealed several major research communities (Fig. 5 ). Anne M. Comi and Csaba Juhasz led the cluster focused on the neurological aspects of Sturge-Weber syndrome. J. Stuart Nelson and Kristen M. Kelly were central figures in the laser-therapy cluster. A distinct Chinese cluster, represented by authors such as Gu Ying and Lin Xiaoxi, focused primarily on photodynamic therapy and clinical optimization. 3.4 Knowledge Structure and Research Frontiers The dual-map overlay in Fig. 6 provides a macroscopic view of knowledge flow in PWS research. Journals in clinical fields such as dermatology, surgery, and general medicine primarily cited work rooted in molecular biology, genetics, and related medical disciplines. This pattern illustrates the translational character of the field, in which basic biological insights increasingly inform clinical investigation and therapeutic development. 3.4.1 Knowledge Evolution Pathways and Research Theme Timeline The keyword timeline (Fig. 7 ) suggests three broad stages of development. Between 2005 and 2012, research concentrated on physical treatment parameters and selective photothermolysis. From 2013 to 2018, genetic themes became more prominent, especially in relation to PWS and SWS. Since 2019, the field has expanded further toward targeted therapy, photodynamic therapy, and ISSVA-oriented vascular-anomaly classification. 3.4.2 Keyword Co-occurrence and Thematic Evolution The keyword co-occurrence network (Fig. 8 ) revealed four major thematic clusters: (1) SWS and its complications, such as epilepsy and glaucoma; (2) light-based technologies, including PDL and Nd:YAG; (3) molecular genetics, including GNAQ and somatic mutation; and (4) photodynamic therapy, especially HMME-related studies. The genetics-related cluster appeared particularly active in recent years and increasingly intersected with diagnostic and classification themes. 3.4.3 Keyword Burst Analysis (Research Frontiers) Keyword bursts (Fig. 9 ) quantify the shift in research attention. Early bursts (2005–2010) included terms such as "wavelength" and "photothermolysis," whereas more recent bursts emphasized "somatic mutation," "vascular anomalies," and "diagnosis." These findings support a transition from empirical vessel-directed treatment toward biologically informed disease characterization. 4 Discussion 4.1 The Shift to Molecular Pathogenesis The identification of a GNAQ mutation in 2013 marked a turning point in PWS research. Bibliometric signals from the timeline, co-occurrence network, and burst analysis indicate that the literature increasingly focused on downstream signaling mechanisms, including the ANGPT2/TIE2 axis and the PI3K/AKT/mTOR pathway. This shift highlights potential therapeutic targets and supports growing interest in combining molecularly informed strategies with conventional laser treatment, especially in refractory disease [ 33 – 44 ] . 4.2 Regional Divergence: Laser Therapy vs Photodynamic Therapy A prominent pattern in the literature is the regional divergence in therapeutic emphasis. Studies from Europe and North America remained centered on pulsed dye laser (PDL), whereas Chinese publications placed greater emphasis on hemoporfin-mediated photodynamic therapy (HMME-PDT). Although some Chinese cohorts reported high clearance rates for PDT, direct international comparisons and head-to-head trials remain limited [ 45 – 48 ] . 4.3 The Gap in Surgical Intervention Our analysis also highlights a clear gap in the literature on surgical management. Despite the clinical relevance of hypertrophic and nodular PWS in older patients, surgical studies remain relatively scarce. Because advanced lesions may respond poorly to non-surgical modalities alone, stronger evidence is needed for multimodal strategies that integrate plastic surgery with laser or medical therapy [ 49 – 54 ] . 4.4 Future Directions and Limitations The recent prominence of the keyword "vascular anomalies" suggests that PWS is increasingly being interpreted within the broader ISSVA molecular taxonomy. Future research will likely prioritize genotype-phenotype correlation, treatment stratification, and the development of multimodal precision-therapy frameworks. This study has several limitations. It relied exclusively on the WoSCC database, and bibliometric patterns may therefore have omitted relevant studies indexed elsewhere. In addition, citation-based indicators are influenced by indexing practices and citation lag, meaning that they reflect knowledge structure and research attention rather than the methodological quality of individual studies. 5 Conclusion PWS research has evolved from optimizing laser parameters to exploring molecular pathogenesis. The United States and China remain the leading contributors, but they emphasize partly different therapeutic approaches. Future progress will depend on translating genetic and mechanistic insights into precision-oriented treatment strategies and on generating internationally comparable clinical evidence. Declarations Funding: This study was financially supported by the National clinical key specialty construction project (No. 23003), the Plastic Medicine Research Fund of Chinese Academy of Medical Sciences (No. 2024-ZX-1-01) and the Special Research Fund for Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (YSZ2024CG007). The funding body played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. Conflicts of interest: The authors declare that they have no competing interests. Consent to participate: Not applicable. Consent for publication: Not applicable. Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Code availability: Not applicable. Clinical trial number: Not applicable. 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Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 07 May, 2026 Reviews received at journal 06 May, 2026 Reviews received at journal 02 May, 2026 Reviewers agreed at journal 23 Apr, 2026 Reviewers agreed at journal 23 Apr, 2026 Reviewers invited by journal 22 Apr, 2026 Editor assigned by journal 04 Apr, 2026 Submission checks completed at journal 29 Mar, 2026 First submitted to journal 16 Mar, 2026 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. 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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-9137673","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":633466615,"identity":"fd17f789-af09-4305-a3c8-601279189905","order_by":0,"name":"Yingjie Zhu","email":"","orcid":"","institution":"Plastic Surgery Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yingjie","middleName":"","lastName":"Zhu","suffix":""},{"id":633466616,"identity":"92c3ae5b-d781-4d23-9871-3b6c016133cc","order_by":1,"name":"Ye Zhang","email":"","orcid":"","institution":"Plastic Surgery Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ye","middleName":"","lastName":"Zhang","suffix":""},{"id":633466617,"identity":"75b037e1-76e5-4977-8ebd-13bba995240a","order_by":2,"name":"Xingyu Zhu","email":"","orcid":"","institution":"Plastic Surgery Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xingyu","middleName":"","lastName":"Zhu","suffix":""},{"id":633466618,"identity":"9f3c84bb-aea1-4459-8a71-4ca4875f32df","order_by":3,"name":"Yubing Nie","email":"","orcid":"","institution":"Plastic Surgery Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yubing","middleName":"","lastName":"Nie","suffix":""},{"id":633466619,"identity":"02adafdb-926c-49b3-8153-29bcf83cf31b","order_by":4,"name":"Chaonan Wang","email":"","orcid":"","institution":"Plastic Surgery Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chaonan","middleName":"","lastName":"Wang","suffix":""},{"id":633466620,"identity":"42111fb6-c43f-4bd3-af5f-d571a98dbceb","order_by":5,"name":"Xiaonan Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsklEQVRIiWNgGAWjYNCCCgYZNhK1nGHgIVELYxsDD/GqDW7kHvxcOM+Oh08ix+wBQ41NNGEtZ84lS8/clszDJpFjbsBwLC23gaCW4z0G0rzbmEFazCQYGw4ToeUwj/Fv3jn1pGg53mMmzdtwmAQtkmfOmFnzHDvOw8bzrEwigRi/8N3IMb7NU1MtJ9+evE3iQ40NYS0KB2AsgQQGhgRCykFAHm4o/wHcqkbBKBgFo2BkAwCBIzV29oUSnAAAAABJRU5ErkJggg==","orcid":"","institution":"Plastic Surgery Hospital","correspondingAuthor":true,"prefix":"","firstName":"Xiaonan","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2026-03-16 12:09:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9137673/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9137673/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108456218,"identity":"c5ebb196-b598-4573-b3e6-f1b536fc9ba6","added_by":"auto","created_at":"2026-05-04 21:46:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1535436,"visible":true,"origin":"","legend":"\u003cp\u003eAnnual number of PWS-related articles and reviews indexed in WoSCC from 2005 to 2024. The fitted regression line (R² = 0.85054) is shown.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9137673/v1/0a6760f353608fc62bceb4ad.png"},{"id":108493562,"identity":"6e15fefd-949a-4247-95c6-5da427e8d79c","added_by":"auto","created_at":"2026-05-05 10:00:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2333305,"visible":true,"origin":"","legend":"\u003cp\u003eJournal co-citation network in PWS research. Node size reflects citation frequency, links indicate co-citation relationships, and colors denote major thematic clusters.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-9137673/v1/fe6034173ba592e1b010cf2a.png"},{"id":108456220,"identity":"e72717ad-6ace-4870-9d2e-d472920e058a","added_by":"auto","created_at":"2026-05-04 21:46:30","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1131978,"visible":true,"origin":"","legend":"\u003cp\u003eCountry/region collaboration network in PWS research. Node size is proportional to publication volume, and link thickness reflects collaboration strength.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-9137673/v1/d4bdc5f6915e34d1b6ae6696.png"},{"id":108494202,"identity":"accc0fe2-4672-4a9f-a6ef-51dc9967e1f6","added_by":"auto","created_at":"2026-05-05 10:03:04","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":2304847,"visible":true,"origin":"","legend":"\u003cp\u003eInstitutional collaboration network in PWS research. Node size indicates publication volume, and links represent co-authorship relationships among institutions.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-9137673/v1/35f7b930e0bc2dddafc586d2.png"},{"id":108493763,"identity":"fbc6fdd5-6fcd-4e83-af8e-765cbb883e0d","added_by":"auto","created_at":"2026-05-05 10:01:36","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1836179,"visible":true,"origin":"","legend":"\u003cp\u003eAuthor collaboration network in PWS research. Node size reflects publication output, links denote co-authorship, and colors identify major collaborative communities.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-9137673/v1/58baddc1765e22fac292ea41.png"},{"id":108456223,"identity":"0a7be451-d251-43e4-94fd-eece67bcbbbe","added_by":"auto","created_at":"2026-05-04 21:46:30","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":3535708,"visible":true,"origin":"","legend":"\u003cp\u003eDual-map overlay of journal citations in PWS research. The left side represents the disciplines of citing journals, the right side represents the disciplines of cited journals, and the citation paths illustrate knowledge flow between them.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-9137673/v1/6b4937f8280847d827426676.png"},{"id":108493841,"identity":"36e0303b-f921-490d-9f98-e0abf7a68a93","added_by":"auto","created_at":"2026-05-05 10:01:57","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":6230767,"visible":true,"origin":"","legend":"\u003cp\u003eTimeline view of keyword clusters in PWS research from 2005 to 2024. Each horizontal line represents a thematic cluster, node size reflects citation frequency, and links indicate the evolution of related research themes over time.\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-9137673/v1/c13aebaac7e9cfd8e8181039.png"},{"id":108493917,"identity":"bf80b5f2-8c96-47d0-a5ad-0f5502878669","added_by":"auto","created_at":"2026-05-05 10:02:14","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":1764751,"visible":true,"origin":"","legend":"\u003cp\u003eKeyword co-occurrence network in PWS research. Node size indicates keyword frequency, links indicate co-occurrence, and colors group related terms into major thematic clusters\u003c/p\u003e","description":"","filename":"floatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-9137673/v1/8e5a2c6d848b09e992ab872c.png"},{"id":108493577,"identity":"eb1e40c4-92ee-4351-b5e3-0aaa1e69800b","added_by":"auto","created_at":"2026-05-05 10:00:59","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":399754,"visible":true,"origin":"","legend":"\u003cp\u003eTop 25 keywords with the strongest citation bursts during 2005-2024. Red bars indicate the time intervals during which individual keywords experienced a marked surge in attention.\u003c/p\u003e","description":"","filename":"floatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-9137673/v1/98846570204cfc25d51bf44e.png"},{"id":108804705,"identity":"de8a0b87-7b8c-4acc-aa3f-21b4d671e65e","added_by":"auto","created_at":"2026-05-08 15:22:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":20580967,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9137673/v1/45286acd-9b2a-4bfd-8245-65d45662db75.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Two Decades of Port-Wine Stain Research (2005-2024): A Bibliometric Mapping of the Shift Toward Molecular Pathogenesis","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003ePort-wine stains (PWS) are congenital low-flow capillary malformations (CMs) affecting approximately 0.3% of newborns \u003csup\u003e[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. According to the 2024 International Society for the Study of Vascular Anomalies (ISSVA) classification, PWS are characterized by abnormal dilation of dermal capillaries \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. If untreated, these lesions typically darken and thicken over time and may develop nodularity or soft-tissue hypertrophy, resulting in substantial cosmetic and psychosocial burden. PWS may also occur as part of complex syndromes, most notably Sturge-Weber syndrome (SWS), which is associated with neurological and ocular complications \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFor decades, PWS research centered on clinical description and the optimization of laser therapy. In 2013, the identification of a somatic activating mutation (c.548G\u0026thinsp;\u0026gt;\u0026thinsp;A, p.Arg183Gln) in GNAQ reframed PWS as a disorder with a defined molecular basis \u003csup\u003e[\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Subsequent work on related GNAQ/GNA11 alterations and downstream signaling pathways moved the field toward a molecular era characterized by growing interest in MAPK and PI3K/AKT signaling\u003csup\u003e[\u003cspan additionalcitationids=\"CR18 CR19 CR20\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eBibliometric analysis enables the quantitative evaluation of this research evolution. Although previous reviews have summarized parts of the field, many relied on outdated terminology or did not include the most recent literature. The present study provides an updated overview through 2024, interpreted within the ISSVA 2024 framework, to identify major knowledge domains, emerging hotspots, and research trends\u003csup\u003e[\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e"},{"header":"2 Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Search Strategy\u003c/h2\u003e \u003cp\u003eData were retrieved from the Web of Science Core Collection (WoSCC) on January 1, 2025, covering the publication period from 2005 to 2024. To capture the most complete possible record for 2024, the search was conducted after the close of the calendar year. The search strategy incorporated conventional disease terms, related syndromic entities, and recurrent driver genes relevant to the ISSVA 2024 framework: TS = (\"port-wine stain*\" OR \"port wine stain*\" OR \"nevus flammeus\" OR \"capillary malformation*\") OR TS = (\"Sturge-Weber syndrome\" OR \"Klippel-Trenaunay syndrome\" OR \"GNAQ\" OR \"GNA11\").\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Inclusion Criteria\u003c/h2\u003e \u003cp\u003eOnly documents classified as \"Article\" or \"Review\" were included. Meeting abstracts, editorial materials, letters, and book chapters were excluded. After deduplication, 1,742 records were retained for the final analysis. Full records and cited references were exported in plain-text format, including titles, authors, institutions, countries, keywords, abstracts, publication years, and cited references.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Data Analysis\u003c/h2\u003e \u003cp\u003eDescriptive bibliometric indicators were generated with the Bibliometrix R package. VOSviewer was used to construct collaboration networks among countries, institutions, and authors. CiteSpace was used for reference co-citation analysis and keyword burst detection to identify knowledge bases and emerging research frontiers.\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Publication Trends\u003c/h2\u003e \u003cp\u003eTotal annual output showed an overall upward trajectory across the 20-year period (R\u0026sup2; = 0.85). Although annual counts fluctuated after 2013, the database contained 102 records for 2024 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Overall, the pattern suggests sustained expansion of the field, with increasing attention to molecular mechanisms and targeted therapeutic strategies.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Core Journals and Foundational Literature\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e lists the major journals in the field. Lasers in Surgery and Medicine (139 papers) and Dermatologic Surgery (71 papers) remained important outlets for clinical and laser-oriented research. Broad-scope dermatology journals such as the Journal of the American Academy of Dermatology and the British Journal of Dermatology more often featured studies on pathogenesis, classification, and clinical management.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMajor journals in PWS research and their relevance\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRank\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJournal Title\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePublications\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eH-Index\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eImpact Factor (2023)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eJCR Quartile (2023)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePrimary Role / Relevance to PWS Research\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eLasers in Surgery and Medicine\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e139\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQ2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePremier journal in laser medicine; the main platform for PWS physical therapy (PDL, photothermolysis) research.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eDermatologic Surgery\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQ1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAuthoritative journal in dermatologic surgery; focuses on clinical treatment techniques and practices for PWS.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eJournal of the American Academy of Dermatology\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQ1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTop-tier comprehensive dermatology journal; publishes high-impact clinical and basic research on PWS.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003ePhotodiagnosis and Photodynamic Therapy\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQ2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSpecializes in photodynamic diagnosis and therapy; the core journal for PWS photodynamic therapy (PDT) research.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eBritish Journal of Dermatology\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQ1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eA leading, long-standing dermatology journal; publishes important research on PWS pathology, genetics, and treatment.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eLasers in Medical Science\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQ2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCovers laser applications across medical fields; a key supplementary platform for PWS laser technology and mechanism studies.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eJournal of Biomedical Optics\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQ2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eProfessional journal in biomedical optics; focuses on the optical principles and technological development for PWS diagnosis and treatment.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eJAMA Dermatology\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQ1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLeading dermatology journal publishing practice-shaping studies relevant to PWS.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003ePhysics in Medicine and Biology\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQ1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAuthoritative journal in medical physics; publishes research on the physical models of laser-tissue interactions in PWS.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eAmerican Journal of Medical Genetics Part A\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQ3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eA medical genetics journal; an important venue for research on PWS-related syndromes and genetic etiologies.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eReference co-citation analysis identified the literature that forms the knowledge base of PWS research. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the most frequently co-cited studies reflect two major intellectual foundations of the field: laser-based therapeutic theory and advances in molecular genetics\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR26 CR27 CR28 CR29 CR30 CR31\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMost co-cited foundational articles in PWS research and their core contributions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRank\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFirst Author (Year)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSource Journal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCo-Citations\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCore Contribution\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eShirley MD (2013)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eNew England Journal of Medicine\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e299\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[Milestone in Molecular Etiology] First to reveal that a somatic mutation in the GNAQ gene is the underlying cause of PWS and SWS, launching the genomic era of PWS research.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnderson RR (1983)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eScience\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFirst to propose the theory of \"Selective Photothermolysis,\" laying the scientific foundation for pulsed dye laser treatment of vascular skin lesions.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJacobs AH (1976)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ePediatrics\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e182\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[Epidemiological Foundation] Conducted an early, large-scale investigation into the incidence of birthmarks in newborns, providing foundational data for PWS epidemiology.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBarsky SH (1980)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eJournal of Investigative Dermatology\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e119\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[Early Pathological Exploration] Used computer-assisted methods to study the pathological evolution of PWS, deepening the understanding of its vascular nature.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThomas-Sohl KA (2004)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ePediatric Neurology\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eProvided a comprehensive review of Sturge-Weber Syndrome (SWS), serving as a key reference for this complication.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSujansky E (1995)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eJournal of Child Neurology\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSystematically described the natural course of SWS, providing an important basis for its clinical management.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChen JK (2012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eJournal of the American Academy of Dermatology\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSystematically reviewed various clinical and experimental treatment methods for PWS, serving as an authoritative reference in the therapeutic field.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJasim ZF (2007)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eJournal of the American Academy of Dermatology\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFocused on treatment strategies for PWS resistant to pulsed dye laser (PDL), providing direction for challenging clinical cases.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYang M (2005)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eJournal of the American Academy of Dermatology\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eExplored the use of the long-pulsed Nd:YAG laser for PWS treatment, expanding therapeutic options beyond PDL.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRenfro L (1993)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eArchives of Dermatology\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAnalyzed anatomical differences in response to pulsed dye laser treatment, highlighting site-specific variability in therapeutic outcomes.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe journal co-citation network (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) underscores the interdisciplinary structure of the field. Major clusters correspond to laser medicine, pediatric neurology, general dermatology, and photodynamic therapy. Together, these patterns indicate that PWS research has developed at the intersection of lesion-directed treatment and the management of associated syndromic complications.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Collaboration Network Analysis\u003c/h2\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e3.3.1 Country/Region Collaboration Network\u003c/h2\u003e \u003cp\u003eResearchers from 62 countries/regions contributed to the field. The United States (731 papers) and China (367 papers) were the most productive contributors (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The United States showed broad international collaboration, particularly with European partners, whereas Chinese output was characterized by dense domestic collaboration together with notable bilateral links with the United States.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section3\"\u003e \u003ch2\u003e3.3.2 Institutional Collaboration Network\u003c/h2\u003e \u003cp\u003eThe University of California, Irvine (94 papers) was the most productive institution, followed by Xi'an Jiaotong University and Shanghai Jiao Tong University (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Institutional collaboration was organized around several geographic hubs, most prominently a California cluster centered on the Beckman Laser Institute and a Boston cluster associated with Harvard and Boston Children's Hospital.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e \u003ch2\u003e3.3.3 Author Collaboration Network\u003c/h2\u003e \u003cp\u003eThe author network revealed several major research communities (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Anne M. Comi and Csaba Juhasz led the cluster focused on the neurological aspects of Sturge-Weber syndrome. J. Stuart Nelson and Kristen M. Kelly were central figures in the laser-therapy cluster. A distinct Chinese cluster, represented by authors such as Gu Ying and Lin Xiaoxi, focused primarily on photodynamic therapy and clinical optimization.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Knowledge Structure and Research Frontiers\u003c/h2\u003e \u003cp\u003eThe dual-map overlay in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e provides a macroscopic view of knowledge flow in PWS research. Journals in clinical fields such as dermatology, surgery, and general medicine primarily cited work rooted in molecular biology, genetics, and related medical disciplines. This pattern illustrates the translational character of the field, in which basic biological insights increasingly inform clinical investigation and therapeutic development.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e \u003ch2\u003e3.4.1 Knowledge Evolution Pathways and Research Theme Timeline\u003c/h2\u003e \u003cp\u003eThe keyword timeline (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e) suggests three broad stages of development. Between 2005 and 2012, research concentrated on physical treatment parameters and selective photothermolysis. From 2013 to 2018, genetic themes became more prominent, especially in relation to PWS and SWS. Since 2019, the field has expanded further toward targeted therapy, photodynamic therapy, and ISSVA-oriented vascular-anomaly classification.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003e3.4.2 Keyword Co-occurrence and Thematic Evolution\u003c/h2\u003e \u003cp\u003eThe keyword co-occurrence network (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e) revealed four major thematic clusters: (1) SWS and its complications, such as epilepsy and glaucoma; (2) light-based technologies, including PDL and Nd:YAG; (3) molecular genetics, including GNAQ and somatic mutation; and (4) photodynamic therapy, especially HMME-related studies. The genetics-related cluster appeared particularly active in recent years and increasingly intersected with diagnostic and classification themes.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003ch2\u003e3.4.3 Keyword Burst Analysis (Research Frontiers)\u003c/h2\u003e \u003cp\u003eKeyword bursts (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e9\u003c/span\u003e) quantify the shift in research attention. Early bursts (2005\u0026ndash;2010) included terms such as \"wavelength\" and \"photothermolysis,\" whereas more recent bursts emphasized \"somatic mutation,\" \"vascular anomalies,\" and \"diagnosis.\" These findings support a transition from empirical vessel-directed treatment toward biologically informed disease characterization.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e4.1 The Shift to Molecular Pathogenesis\u003c/h2\u003e \u003cp\u003eThe identification of a GNAQ mutation in 2013 marked a turning point in PWS research. Bibliometric signals from the timeline, co-occurrence network, and burst analysis indicate that the literature increasingly focused on downstream signaling mechanisms, including the ANGPT2/TIE2 axis and the PI3K/AKT/mTOR pathway. This shift highlights potential therapeutic targets and supports growing interest in combining molecularly informed strategies with conventional laser treatment, especially in refractory disease\u003csup\u003e[\u003cspan additionalcitationids=\"CR34 CR35 CR36 CR37 CR38 CR39 CR40 CR41 CR42 CR43\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e4.2 Regional Divergence: Laser Therapy vs Photodynamic Therapy\u003c/h2\u003e \u003cp\u003eA prominent pattern in the literature is the regional divergence in therapeutic emphasis. Studies from Europe and North America remained centered on pulsed dye laser (PDL), whereas Chinese publications placed greater emphasis on hemoporfin-mediated photodynamic therapy (HMME-PDT). Although some Chinese cohorts reported high clearance rates for PDT, direct international comparisons and head-to-head trials remain limited\u003csup\u003e[\u003cspan additionalcitationids=\"CR46 CR47\" citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003e4.3 The Gap in Surgical Intervention\u003c/h2\u003e \u003cp\u003eOur analysis also highlights a clear gap in the literature on surgical management. Despite the clinical relevance of hypertrophic and nodular PWS in older patients, surgical studies remain relatively scarce. Because advanced lesions may respond poorly to non-surgical modalities alone, stronger evidence is needed for multimodal strategies that integrate plastic surgery with laser or medical therapy\u003csup\u003e[\u003cspan additionalcitationids=\"CR50 CR51 CR52 CR53\" citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003e4.4 Future Directions and Limitations\u003c/h2\u003e \u003cp\u003eThe recent prominence of the keyword \"vascular anomalies\" suggests that PWS is increasingly being interpreted within the broader ISSVA molecular taxonomy. Future research will likely prioritize genotype-phenotype correlation, treatment stratification, and the development of multimodal precision-therapy frameworks.\u003c/p\u003e \u003cp\u003eThis study has several limitations. It relied exclusively on the WoSCC database, and bibliometric patterns may therefore have omitted relevant studies indexed elsewhere. In addition, citation-based indicators are influenced by indexing practices and citation lag, meaning that they reflect knowledge structure and research attention rather than the methodological quality of individual studies.\u003c/p\u003e \u003c/div\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003ePWS research has evolved from optimizing laser parameters to exploring molecular pathogenesis. The United States and China remain the leading contributors, but they emphasize partly different therapeutic approaches. Future progress will depend on translating genetic and mechanistic insights into precision-oriented treatment strategies and on generating internationally comparable clinical evidence.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis study was financially supported by the National clinical key specialty construction project (No. 23003), the Plastic Medicine Research Fund of Chinese Academy of Medical Sciences (No. 2024-ZX-1-01) and the Special Research Fund for Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (YSZ2024CG007). The funding body played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest:\u003c/strong\u003e The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability:\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number:\u003c/strong\u003e Not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWaelchli R, Aylett SE, Robinson K, Chong WK, Martinez AE, Kinsler VA (2014) New vascular classification of port-wine stains: Improving prediction of sturge-weber risk[J]. 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J Am Acad Dermatol 57(4):677\u0026ndash;682\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNoborio R, Kurokawa M, Kobayashi K, Morita A (2009) Evaluation of the clinical and immunohistological efficacy of the 585-nm pulsed dye laser in the treatment of psoriasis[J]. J Eur Acad Dermatol Venereol 23(4):420\u0026ndash;424\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTremaine AM, Armstrong J, Huang YC, Elkeeb L, Ortiz A, Harris R, Choi B (2012) Kelly. Enhanced port-wine stain lightening achieved with combined treatment of selective photothermolysis and imiquimod[J]. J Am Acad Dermatol 66(4):634\u0026ndash;641\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRubin IK, Farinelli WA, Doukas A (2012) Anderson. Optimal wavelengths for vein-selective photothermolysis[J]. 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Actas Dermosifiliogr 99(7):546\u0026ndash;554\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Bortoli M, Queisser A, Pham VC, Dompmartin A, Helaers R, Boutry S, Claus C, De Roo AK, Hammer F, Brouillard P, Abdelilah-Seyfried S, Boon LM, Vikkula M (2024) Somatic loss-of-function pik3r1 and activating non-hotspot pik3ca mutations associated with capillary malformation with dilated veins (cmdv)[J]. J Invest Dermatol 144(9):2066\u0026ndash;2077 e2066\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBichsel CA, Goss J, Alomari M, Alexandrescu S, Robb R, Smith LE, Hochman M, Greene AK (2019) J. Bischoff. Association of somatic gnaq mutation with capillary malformations in a case of choroidal hemangioma[J]. JAMA Ophthalmol, 137(1): 91\u0026ndash;95\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee KT, Park JE, Eom Y, Lim HS, Ki CS, Lim SY (2019) Phenotypic association of presence of a somatic gnaq mutation with port-wine stain distribution in capillary malformation[J]. Head Neck 41(12):4143\u0026ndash;4150\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang L, Bichsel C, Norris AL, Thorpe J, Pevsner J, Alexandrescu S, Pinto A, Zurakowski D, Kleiman RJ, Sahin M, Greene AK (2022) Bischoff. Endothelial gnaq p.R183q increases angpt2 (angiopoietin-2) and drives formation of enlarged blood vessels[J]. Arterioscler Thromb Vasc Biol 42(1):e27\u0026ndash;e43\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKang J, Liu JJ, Fang YH, Lin YY, Gong W, Wang HY, Lin LH (2023) Xiao. Hemoporfin-mediated photodynamic therapy for port-wine stains on extremities[J]. 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Dermatol Surg 48(5):586\u0026ndash;588\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Q, Yong C, Wang M, Cui L, Yuan SM (2022) Individualized surgical management of refractory port-wine stains in the scalp and face: A single-center retrospective study and a discussion of surgical strategies[J]. Clin Cosmet Investig Dermatol 15:1527\u0026ndash;1535\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu X, Jiang C, Lin X, Lu L, Jin Y, Chen D, Ma G (2011) Reconstruction of the cheek after large port-wine stain lesion resection[J]. Aesthetic Plast Surg 35(5):795\u0026ndash;801\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eColletti G, Negrello S, Rozell-Shannon L, Levitin GM, Colletti L, Chiarini L, Anesi A, Di Bartolomeo M, Pellacani A (2023) Nocini. Surgery for port-wine stains: A systematic review[J]. J Pers Med 13(7):1058\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"lasers-in-medical-science","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"lims","sideBox":"Learn more about [Lasers in Medical Science](https://link.springer.com/journal/10103)","snPcode":"10103","submissionUrl":"https://submission.springernature.com/new-submission/10103/3","title":"Lasers in Medical Science","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Port-Wine Stains, Bibliometrics, Vascular Anomalies, GNAQ Mutation, Pulsed Dye Laser","lastPublishedDoi":"10.21203/rs.3.rs-9137673/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9137673/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePort-wine stains (PWS) are congenital capillary malformations. Although laser-based therapies have dominated the field for decades, recent research has increasingly focused on molecular pathogenesis and targeted intervention.\u003c/p\u003e\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eTo map the global research landscape of PWS from 2005 to 2024 and to identify changes in research priorities following major genetic discoveries.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe analyzed 1,742 publications retrieved from the Web of Science Core Collection using a search strategy informed by the ISSVA 2024 classification. Bibliometric analyses and visualizations were performed with CiteSpace, VOSviewer, and the Bibliometrix R package.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePublication output showed an overall upward trend, with 102 records indexed for 2024. The United States (731) and China (367) were the leading contributors. Research hotspots shifted from laser physics and selective photothermolysis to GNAQ/GNA11-related molecular mechanisms. Keyword burst analysis identified vascular anomalies and somatic mutation as recent frontiers.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003ePWS research has shifted from optimizing physical treatments to investigating molecular pathogenesis. This transition, driven largely by the 2013 discovery of the GNAQ mutation, supports the development of targeted therapeutic strategies. Future studies will likely focus on genotype-phenotype correlations and multimodal interventions.\u003c/p\u003e","manuscriptTitle":"Two Decades of Port-Wine Stain Research (2005-2024): A Bibliometric Mapping of the Shift Toward Molecular Pathogenesis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-04 21:46:24","doi":"10.21203/rs.3.rs-9137673/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"315221766351431716954813232676586761774","date":"2026-05-07T04:58:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T18:36:32+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-02T21:02:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"223817199666231932259564506490815338788","date":"2026-04-23T09:49:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"36059906910583298893387889520214100205","date":"2026-04-23T05:53:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-22T21:49:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-05T02:29:22+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-30T03:28:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"Lasers in Medical Science","date":"2026-03-16T11:59:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"lasers-in-medical-science","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"lims","sideBox":"Learn more about [Lasers in Medical Science](https://link.springer.com/journal/10103)","snPcode":"10103","submissionUrl":"https://submission.springernature.com/new-submission/10103/3","title":"Lasers in Medical Science","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"d8b257f8-d300-49c1-b7da-1bfbf2854d54","owner":[],"postedDate":"May 4th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"315221766351431716954813232676586761774","date":"2026-05-07T04:58:21+00:00","index":41,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T18:36:32+00:00","index":37,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-02T21:02:29+00:00","index":22,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T21:46:25+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-04 21:46:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9137673","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9137673","identity":"rs-9137673","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}