Port-Wine Stains’ Orodental Manifestations and Complications: A Systematic Review

Abstract

Background/Objectives: Port-wine stains (PWSs), also known as naevus flammeus or capillary malformations, are congenital cutaneous lesions, typically located in the head/neck area. The manifestations of PWSs include aesthetic and functional impairments due to soft and hard tissue modifications. Sturge–Weber syndrome is characterised by additional neuro-ocular manifestations. This systematic review aimed to identify and overview the orodental manifestations of PWSs. Methods: Several databases (PubMed, Web of Science, Scopus, Embase, Cochrane Library) were searched using keywords for PWSs and oral and dental manifestations. The results were centralised, deduplicated, and selected in a two-step sequence. Data were extracted using pre-defined extraction forms and represented graphically and tabulated. The Newcastle–Ottawa and Joanna Briggs Institute scales were used for quality assessment. Results: Out of 884 results, 43 studies were selected for inclusion. Eleven studies investigated patients diagnosed with PWSs, while thirty-two studies investigated SWS patients. Regarding study designs, eight studies were retrospective, one was cross-sectional, two were case series, and thirty-two were case reports. The most frequently mentioned manifestations were gingival hypertrophy, lip hypertrophy, mucosal or gingival staining, malocclusion, gingivitis or gingival bleeding, and facial asymmetry. Conclusions: Due to the rarity of this pathology, the orodental manifestations of PWSs are not widely known to dentists. Soft tissue hypertrophy, malocclusion, and bony hypertrophy are significant concerns that need to be addressed during treatment.

1. Introduction

Port-wine stains (PWSs), also known as naevus flammeus or capillary malformations, are congenital vascular malformations that affect the skin and mucosae and which appear at birth, persisting and evolving throughout life. PWSs appear in around 0.03% of newborns, (usually lacking familial patterns) and affect approximately 26 million people worldwide [1,2]. PWSs can appear by themselves or as part of vascular syndromes such Sturge–Weber syndrome (SWS), Klippel–Trenaunay syndrome (KTS), phakomatosis pigmentovascularis (PPV), and Proteus syndrome. PWSs are most frequently found in the head and neck area (~90%) and initially appear as irregular flat pink or red macules, later growing and developing into darker, hypertrophic, nodular lesions, which are susceptible to spontaneous bleeding or haemorrhage [3,4,5]. The lesions seem to follow a pattern dictated by trigeminal nerve (V) branch distribution, affecting one or more neural branches. Most frequently, one hemiface is affected, but bilateral involvement can be encountered [6,7,8]. The distribution of the lesions is considered a significant concern, with ophthalmic branch (V1) dermatomal facial PWSs being associated with an increased risk (15–20%) of Sturge–Weber syndrome (SWS) [9,10,11]. SWS is a comparatively rare (1 in 50,000) congenital neurocutaneous disorder, characterised by vascular malformations including facial (PWSs), ocular, and neurological ipsilateral manifestations; ocular manifestations most frequently translate to congenital or acquired glaucoma, while the neurological manifestations are due to leptomeningeal angiomatosis and include seizures, strokes, and delayed intellectual development [7,12,13,14,15]. Both SWS and PWSs are believed to be the result of a somatic activating mutation in the GNAQ (R183Q) gene, which increases cell proliferation and inhibits apoptosis due to increased downstream signalling through the RAS effector pathways [12,15,16,17]. Often, the first indication of SWS is a PWS, with lesions on the forehead and upper eyelid being deemed as higher risk than others that do not extend to the forehead. The wider the extension of a PWS beyond the forehead, the higher the risk of SWS [7,18,19].

PWSs are characterised by progressive vascular ectasia, leading to the hypertrophy of affected soft and hard tissues [20,21,22,23]. Patients with low amounts of hypertrophy in cutaneous lesions are frequently treated with pulsed-dye laser because it allows selective vascular obliteration. Other laser types, such as Nd:YAG lasers, have been used to improve soft tissue hypertrophy. Local complications such as scars and pigmentation are still considered an issue with laser treatments. Surgery is considered a viable option for cases in which the hypertrophy of soft and hard tissues has reached significant levels [23]. Besides obvious aesthetic concerns, functional concerns arise, especially when considering the areas affected by PWSs and SWS. Distribution on the V2 and V3 trigeminal branches implies the involvement of tissues and structures in the orodental area, including the lips, oral mucosa, tongue, larynx, and maxillary and mandibular bones [5,24,25,26,27]. In the oral cavity, this may manifest as gingival hypertrophy, which can complicate dental treatment and oral hygiene [26,28,29]. Another aspect to consider is the bony hypertrophy of the maxilla and the mandible in the areas affected by a PWS, which is associated with facial asymmetry and malocclusion [20,30,31,32,33]. Due to SWS manifesting more extensive vascular malformations, the hypertrophy of the maxillofacial bones seems to be more frequent and more accentuated in these patients, compared with PWSs alone [30,34]. Despite the oral, dental, and cranio-facial involvement of PWSs, no consensus exists regarding optimal oral healthcare for such patients. Most of the available literature consists of case reports, with some mentioning possible complications such as excessive bleeding derived from the hypervascularisation of affected oral structures, while others cite rare or no complications during dental treatments [29,35,36,37,38,39,40]. Typically, oral prophylaxis, periodontal treatment, and gingival reductive surgery are used to manage symptoms [29,40,41,42,43]. In patients with osseous hypertrophy or severe malocclusion, maxillofacial surgery is indicated [23,44,45]. Patients may also undergo cosmetic surgery to manage aesthetic concerns [46].

This subject has rarely been approached from the dental professionals’ point of view, since most of the literature available on PWSs and SWS is focused on the treatment and improvement of the lesions’ appearance, while a significant part is focused on the management of ophthalmological and neurological complications. Therefore, the aim of this systematic review was to identify and assess recent studies which mention various orodental manifestations of PWSs, in patients diagnosed with SWS and PWSs. A second objective was to identify which orodental manifestations are mentioned most frequently, therefore providing an overview of these pathologies from a dental perspective.

2. Materials and Methods

2.1. Registration and Validation of Study Protocol

This review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 reporting guidelines for both the study design and the abstract [47]. A detailed protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO number CRD42024551610).

2.2. Question of Study

This review was designed to answer the following question: “In patients diagnosed with port-wine stains or Sturge–Weber syndrome, what are the oral, dental, or cranio-facial manifestations and particularities that imply complications or require specific management in dental practice, when compared to healthy individuals?”

2.3. Eligibility Criteria

2.3.1. Inclusion Criteria

The inclusion criteria of this systematic review were organised according to the PECOS strategy:

P (population) = patients diagnosed with facial port-wine stains or Sturge–Weber syndrome, who presented for oral, dental, or cranio-facial treatment.

E (exposure) = diagnosis of facial PWS or SWS.

C (control) = (when available) individuals not diagnosed with a PWS or SWS, who presented a state of health and normal states of oral, dental, and cranio-facial soft and hard tissues and structures.

O (types of outcome measures) = discernible differences in physical and biological properties of orodento-facial tissues, identified by clinical or paraclinical investigations.

S (types of studies) = original studies on humans; prospective, retrospective, and cross-sectional studies; observational studies; clinical trials; case series; and case reports.

2.3.2. Exclusion Criteria

Results were restricted to the last 25 years, based on publication date (from 19 October 1999 to 24 October 2024). The following exclusion criteria were applied:

Studies on patients diagnosed with other cranio-facial genetic or congenital conditions, patients diagnosed with systemic pathologies that could interfere with the studied pathology, patients with recent trauma to the head and neck area, oncologic patients, or patients affected by non-cancerous tumours of the head and neck.

Studies which presented missing or incomplete data regarding orodental manifestations of the studied pathology or studies that described other pathologies’ manifestations or treatments in patients with SWS or a PWS.

Animal studies, in vitro study designs, histology studies, and ex vivo studies.

Study designs: literature reviews and/or meta-analyses, correspondence, editorials, and conference abstracts.

Studies not available in full text.

Studies published in languages other than English.

2.4. Search Strategy

An electronic literature search strategy was developed by AC and DC. This strategy included identifying relevant search terminology, keyword-related term branching, exploratory literature searches, and database-controlled vocabulary translation. The electronic literature search was conducted in the PubMed, Scopus, Embase, Cochrane Library, and Web of Science databases by two independent researchers (AC and DC) until 24 October 2024. The process was supervised by OL. The search consisted of keywords (such as Medical Subject Headings or MeSHs) for port-wine stains and oral structures, combined with Boolean operators “AND” and “OR”, as well as keyword searching of the title, abstract, and text words. Date restrictions were applied: from 19 October 1999 to 24 October 2024 (the last 25 years). Restrictions regarding language (English) and species (humans) were applied. The basic search terminology used in PubMed was as follows:

(Port-wine stains OR Sturge-Weber syndrome OR nevus flammeus) AND (oral OR oral OR dental OR orodental OR tooth OR gingiv* OR periodont* OR tongue OR alveola* OR oral hygiene OR occlusion OR oral disease* OR bone OR lip).

This search query was applied to each database, with minor modifications to accommodate searching particularities. The exact search strategy applied to each database is available in Supplementary File S1.

2.5. Study Selection Process and Data Extraction

The results of the electronic literature database searches were exported in bibliography form from each database and were subsequently imported into a reference manager software (Zotero v7.0.6). Duplicates were identified and removed manually using the same software. The remaining articles were screened by title and/or abstract by two independent contributors to this article (AK and DC) and were filtered based on the inclusion and exclusion criteria. Studies considered relevant were obtained in full text and assessed by the same two researchers. The inclusion and exclusion criteria were subsequently applied to select a final number of studies to be included. A third researcher (AC) was available for conflict resolution when necessary. The study selection process was supervised by MN and SB. Inter-research agreeability was calculated using Cohen’s Kappa coefficient.

The following data were extracted from the included studies:

-

General data about the studies (title, main authors, geographical area, DOI, year of publication, study design);

-

Population (number of subjects, age/gender distribution);

-

Exposure and controls (pathology diagnosed, controls—when available);

-

Outcomes (oral, dental, or cranio-facial manifestations reported in studies, complications of treatments).

2.6. Risk of Bias/Quality Assessment

The risk of bias was quantified and assessed by two independent researchers (AC and AK). If any disagreement occurred, a third researcher (OL) was asked to intervene. The tools used were the Newcastle–Ottawa Scale (NOS) and the Joanna Briggs Institute (JBI) Checklist for Case Reports. The results of the assessment were presented in graphic form. For the NOS, studies with scores between 0 and 3 were considered low-quality, studies with scores of 4–6 were considered medium-quality, and studies with scores of 7–9 were considered high-quality [48,49]. For the JBI Checklist, no scoring scale has been proposed by the developers of the tool [50].

3. Results

3.1. Study Selection

The search retrieved a total of 884 results. After duplicate removal, articles were screened by their titles and abstracts, after which 70 were selected for retrieval and read in full-text form. Eleven studies were ultimately included. The level of agreement between researchers was calculated by the Kappa coefficient (value k = 9.2). The study selection process is presented in the following PRISMA 2020 flowchart (Figure 1).

3.2. Description of Included Studies

We identified 11 studies which investigate or assess tissular changes and manifestations in patients diagnosed with port-wine stains and 32 studies which investigate patients diagnosed with Sturge–Weber syndrome. The studies’ characteristics and findings are presented in two separate tables (

Table 1. Main characteristics and findings of studies on patients diagnosed with port-wine stains.

Main Author	Year	Study Type	Geographic Area	Sample Size	Orodental Manifestations	Treatments	Complications
Frigerio et al. [55]	2015	Retrospective study	USA	26–7 with PWSs (port-wine stains)	Gingival hypertrophy, gingival bleeding, gingival staining, and lip hypertrophy	Laser photocoagulation of vascular lesions	Recurrence of PWSs in some cases
Eivazi et al. [56]	2012	Retrospective study	Germany	9	Lip hypertrophy, gingival bleeding, dysphonia, dysphagia parotidean inflammation, tongue hypertrophy, gingival staining, facial asymmetry due to soft tissue involvement, and ulcerations	None	-
Liu et al. [57]	2024	Retrospective study	China	21	Gingival hypertrophy, early tooth eruption, stained gingiva, and malocclusion,	None	Malocclusion
Zhou et al. [44]	2020	Retrospective study	China	2	Buccal hypertrophy, maxillary hypertrophy, malocclusion, occlusal canting, lip hypertrophy, facial asymmetry, gingival staining, excessive gingival display, mandibular hypertrophy, facial asymmetry, and excessive gingival display	Osteotomies and soft tissue reductive surgery	None
Dowling et al. [27]	2012	Cross-sectional study	USA	30	Lip hypertrophy, stained gingiva, gingival bleeding, gingivitis, malocclusion, tooth spacing, maxillary or mandibular hypertrophy, gingival hypertrophy, tongue hypertrophy, prolonged inflammation after dental interventions, and excessive bleeding	None	Rare haemorrhage after dental procedures
Lee et al. [58]	2015	Retrospective study	South Korea	160	Gingival hypertrophy, lip hypertrophy, buccal hypertrophy, maxillary and mandibular hypertrophy, tongue hypertrophy, and facial asymmetry	None	None
De Castro et al. [46]	2017	Retrospective study	USA	18–6 with PWS	Lip hypertrophy and ulcerations	Full-thickness wedge resection for lip size reduction	None
Deore et al. [53]	2014	Case report	India	1	Gingival staining and recurrent pyogenic granuloma	Sclerotherapy with sodium tetradecyl sulfate, scaling, and root planing	None
Mary R et al. [59]	2024	Case series	India	2 (1 with PWS)	Gingival staining	Oral prophylaxis	None
Patil et al. [35]	2015	Case report	India	1	Gingival staining	None	Risk of excessive bleeding on probing
Priya et al. [60]	2023	Case report	India	1	Gingival staining	Excision of gingival growth	Bleeding tendency and discomfort

and

Table 2. Main characteristics and findings of studies on patients diagnosed with PWS and Sturge–Weber syndrome.

Main Author	Year Published	Study Type	Geographic Area	Sample Size	Orodental Manifestations	Treatments	Complications
Greene et al. [34]	2009	Retrospective study	USA	155	Lip hypertrophy, buccal hypertrophy, maxillary and mandibular hypertrophy, and facial asymmetries	Surgical corrections of soft and hard tissues hypertrophy	Persistent facial asymmetry
Kalakonda et al. [61]	2013	Case series	India	3	Gingival hypertrophy, gingival bleeding, gingivitis, lip hypertrophy, and gingival staining	Scaling, root planing, gingivectomy, and laser gingivectomy	None
Kim et al. [62]	2018	Retrospective study	South Korea	10–5 with SWS (Sturge–Weber syndrome)	Malocclusion, occlusal canting, facial asymmetry, maxillary hypertrophy, drooping labial commissure on affected side, lip hypertrophy, and buccal hypertrophy	Osteotomies, soft tissue reductive surgery, and plastic surgery	None
Yamaguchi et al. [33]	2016	Case series	Taiwan	2	Maxillary hypertrophy, malocclusion, lip hypertrophy, buccal hypertrophy, occlusal canting, excessive gingival display, and excessive bleeding after dental interventions	Osteotomies and soft tissue reductive surgery	None
Babaji et al. [45]	2013	Case report	India	1	Gingival hypertrophy, maxillary hypertrophy, gingival staining, and malocclusion	Maxillectomy and dental extractions	None
Arunkumar et al. [54]	2014	Case report	India	1	Pyogenic granuloma, gingival hypertrophy, lip hypertrophy, and gingival staining	Pyogenic granuloma excision	Difficulty in mastication, bleeding, and recurrent swelling
De Oliveira et al. [36]	2015	Case report	Brazil	1	Gingivitis	Endodontic treatment with non-surgical approach	None
De Oliveira et al. [29]	2019	Case report	Brazil	1	Facial asymmetry, lip hypertrophy, and gingival hypertrophy	Scaling, root planing, and laser therapy	None
Kado et al. [63]	2024	Case report	Japan	1	Lip hypertrophy, facial asymmetry, gingival hypertrophy, and lip incompetence	Sagittal split ramus osteotomy and orthodontic treatment	None
Hino et al. [64]	2017	Case report	Japan	1	Gingival hypertrophy, malocclusion, and gingival staining	Tooth extraction with sedation	None
Gill and Bhaskar [65]	2010	Case report	India	1	Gingival hypertrophy, gingival bleeding, and gingival staining	Tooth extraction	None
Dutt et al. [28]	2016	Case report	India	1	Facial asymmetry, gingival staining, malocclusion, gingival hypertrophy, and gingival bleeding	Scaling, root planing, and gingivectomy	None
Manivannan et al. [66]	2012	Case report	India	1	Gingival bleeding, gingival hypertrophy, gingival staining, and malocclusion	Scaling, root planing, and gingivectomy	Gingival bleeding
Kulkarni et al. [67]	2015	Case report	India	1	Gingival staining, maxillary hypertrophy, gingival hypertrophy, and lip hypertrophy	Gingivectomy, extractions, and prophylaxis	None
Pagin et al. [39]	2012	Case report	Brazil	1	Gingival hypertrophy, gingival staining, and gingival bleeding	Scaling, root planing, and chlorhexidine mouthwash	None
Mopagar et al. [51]	2013	Case report	India	1	Pyogenic granuloma, gingival bleeding, malocclusion, facial asymmetry, and gingival staining	Scaling and laser surgery	None
Mohan et al. [68]	2023	Case report	India	1	Gingival staining and tongue hypertrophy	None	None
Nidhi and Anuj [41]	2016	Case report	India	1	Facial asymmetry, lip hypertrophy, gingival hypertrophy, gingival staining, and malocclusion	Scaling and root planing	None
Neerupakam et al. [42]	2017	Case report	India	1	Gingival hypertrophy, pyogenic granuloma, and gingival staining	Surgical excision of pyogenic granuloma, scaling, root planning, and gingivectomy	Recurrence of pyogenic granuloma
Martins et al. [38]	2019	Case report	Brazil	1	Maxillary hypertrophy, malocclusion, gingival staining, lip incompetence, and lip hypertrophy	Minimally invasive restorative treatment	None
Bhansali et al. [69]	2008	Case report	India	1	Gingival hypertrophy, facial asymmetry, lip hypertrophy, lip incompetence, gingival staining, and maxillary hypertrophy	Scaling, root planning, tooth extraction, and gingivectomy	Recurrent gingival hypertrophy
Lin et al. [23]	2006	Case report	USA	1	Lip hypertrophy, maxillary hypertrophy, and malocclusion	Maxillectomy and reconstruction	Difficulty in mastication and breathing issues
Mukhopadhyay [70]	2008	Case report	India	1	Gingival hypertrophy, gingival staining, malocclusion, and gingival bleeding	None	Bleeding and difficulty in speech
Perez et al. [71]	2005	Case report	Brazil	1	Gingival hypertrophy, malocclusion, lip hypertrophy, and lip incompetence	Prophylaxis and orthodontic treatment	None
Pithon et al. [31]	2011	Case report	Brazil	1	Gingival hypertrophy, early tooth eruption, malocclusion, and occlusal canting	None	None
Pontes et al. [24]	2014	Case report	Brazil	1	Bone resorption, lip hypertrophy, and gingival hypertrophy	Flap surgery, gingivectomy, osteotomy, osteoplasty, and extraction of teeth	None
Reddy et al. [72]	2014	Case report	India	1	Gingival hypertrophy, facial asymmetry, lip hypertrophy, lip incompetence, and alveolar bone loss	Scaling, root planning, prophylaxis, and gingivectomy	None
Sherwani et al. [73]	2023	Case report	India	1	Lip hypertrophy, gingival hypertrophy, mucosal staining, and gingival bleeding	Scaling, root planning, and prophylaxis	None
Suprabha and Baliga [74]	2005	Case report	India	1	Gingival hypertrophy, facial asymmetry, lip hypertrophy, malocclusion, and mucosal staining	Oral prophylaxis	None
Tripathi et al. [40]	2015	Case report	India	1	Gingival hypertrophy and alveolar bone loss	Oral prophylaxis	None
Yadav et al. [43]	2017	Case report	India	1	Gingival hypertrophy, mucosal staining, gingival bleeding, and facial asymmetry	Oral prophylaxis	None
De Benedittis [26]	2007	Case report	Italy	1	Soft tissue hypertrophy, gingival hypertrophy, lower lip hypertrophy, macroglossia, and gingivitis	Laser gingivectomy	None

). From the total number of included studies, we identified eight retrospective studies, one cross-sectional study, three case series, and thirty-two case reports. Four case reports described patients with PWSs, and twenty-eight case reports described patients with SWS. Twenty-two studies were conducted in India, seven studies in Brazil, five studies in the USA, two studies in China, two studies in South Korea, two studies in Japan, one study in Italy, one study in Germany, and one in Taiwan. All studies were published between 2005 and 2024. The total number of included patients diagnosed with a PWS was 239, and the total number of included patients diagnosed with SWS was 193. In most studies, no complications were noted regarding dental or cranio-facial surgery interventions for patients suffering from a PWS or SWS. The development of pyogenic granuloma in PWS or SWS patients was mentioned in four studies [51,52,53,54].

The various manifestations of PWSs, including soft and hard tissue hypertrophy, were the subject of two observational studies [27,57], while one study investigated the natural history of soft and hard tissue hypertrophy in untreated capillary malformations [58]. One study investigated a method of treatment for lip hypertrophy in various vascular anomalies, including PWSs [47], while one study investigated the applications of lasers in oral vascular lesions, including PWS intraoral aspects [56]. One study focused on the periodontal management of patients with SWS, and one study investigated tooth maturation in areas affected by a PWS [62], compared to unaffected areas [58]. Facial asymmetry, soft and hard facial and oral tissue hypertrophy, and their surgical management were the main subjects of four studies [33,35,45,62].

The most frequently mentioned manifestations were gingival hypertrophy (62.7% of studies), followed by lip hypertrophy (55.8% of studies) and mucosal or gingival staining (48.8% of studies). Malocclusion was mentioned in 39% of studies, while gingivitis and facial asymmetry were each mentioned in 32.5% of studies. Maxillary hypertrophy was mentioned more frequently than mandibular hypertrophy (20.9% of studies, as opposed to 11.6% of studies). The frequency of occurrence of the identified manifestations is graphically represented in Figure 2.

3.3. Quality Assessment of the Studies

The results of the quality assessment using the NOS are shown in

Table 3. Results of NOS quality assessment.

Study	Selection				Comparability	Exposure			NOS Score
	Case Definition	Representativeness	Controls	Control Definition		Ascertainment	Methods	Non-Response Rate
Frigerio et al. [55]	*	-	*	-	*	*	*	-	5/9
Eivazi et al. [56]	*	*	*	*	*	*	*	-	8/9
Liu et al. [57]	*	*	*	*	**	*	*	-	8/9
Zhou et al. [44]	*	*	-	-	*	*	-	-	4/9
Dowling et al. [27]	*	*	*	*	**	*	*	*	9/9
Lee et al. [58]	*	*	-	-	**	*	-	-	5/9
De Castro et al. [46]	*	-	*	-	*	*	*	*	6/9
Greene et al. [34]	*	*	*	-	**	*	-	*	7/9
Kalakonda et al. [61]	*	*	-	-	-	*	-	-	3/9
Kim et al. [62]	*	*	*	*	**	*	*	-	8/9
Yamaguchi et al. [33]	*	*	-	-	-	*	-	-	3/9

. We identified five studies of high quality [24,35,45,47,52], four studies of medium quality [45,47,56,59], and two studies of low quality [62,64]. The symbol “*” represents the points given to the studies, in accordance to the NOS scale.

The results of the critical appraisal of case reports using the JBI tool are shown in

Table 4. Results of JBI Checklist for Case Reports.

Study	Q1	Q2	Q3	Q4	Q5	Q6	Q7	Q8
	Were Patient’s Demographic Characteristics Clearly Described?	Was the Patient’s History Clearly Described and Presented as a Timeline?	Was the Current Clinical Condition of the Patient on Presentation Clearly Described?	Were Diagnostic Tests or Assessment Methods and the Results Clearly Described?	Was the Intervention(s) or Treatment Procedure(s) Clearly Described?	Was the Post-intervention Clinical Condition Clearly Described?	Were Adverse Events (Harms) or Unanticipated Events Identified and Described?	Does the Case Report Provide Takeaway Lessons?
Deore et al. [53]	No	No	Yes	Yes	Yes	Yes	No	Yes
Mary R et al. [59]	No	No	Yes	Yes	No	No	No	No
Patil et al. [35]	Yes	Yes	Yes	Yes	NA	NA	NA	Unclear
Priya et al. [60]	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes
Babaji et al. [45]	Yes	Yes	Yes	Yes	No	No	No	Yes
Arunkumar et al. [54]	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes
De Oliveira et al. [36]	No	Unclear	Yes	Yes	Yes	No	No	Yes
De Oliveira et al. [29]	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes
Kado et al. [63]	No	No	Yes	Yes	Yes	Yes	No	Yes
Hino et al. [64]	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes
Gill and Bhaskar [65]	Yes	Yes	Yes	Unclear	Yes	Yes	No	Yes
Dutt et al. [28]	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes
Manivannan et al. [66]	Yes	Yes	Yes	No	Yes	Yes	No	Yes
Kulkarni et al. [67]	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes
Pagin et al. [39]	No	Yes	Yes	No	Yes	Yes	No	Unclear
Mopagar et al. [51]	No	No	Yes	No	Yes	Yes	Yes	Yes
Mohan et al. [68]	No	No	Yes	Unclear	NA	NA	NA	No
Nidhi and Anuj [41]	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Neerupakam et al. [42]	Yes	Yes	Yes	Yes	Yes	No	No	Yes
Martins et al. [38]	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Bhansali et al. [69]	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Lin et al. [23]	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes
Mukhopadhyay [70]	Yes	Yes	Yes	Yes	NA	NA	NA	Yes
Perez et al. [71]	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Pithon et al. [31]	Yes	Yes	Yes	Yes	NA	NA	NA	Yes
Pontes et al. [24]	Yes	No	Yes	Yes	Yes	Yes	Yes	Yes
Reddy et al. [72]	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes
Sherwani et al. [73]	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Suprabha and Baliga [74]	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Tripathi et al. [40]	Yes	Unclear	Yes	Yes	No	No	No	Unclear
Yadav et al. [43]	No	Yes	Yes	Yes	Yes	Yes	Yes	Yes
De Benedittis [26]	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes

.

4. Discussion

To our current knowledge, this is the first systematic review conducted on the orodental manifestations of PWSs and SWS, thus providing valuable insights for healthcare professionals.

The presence of a PWS at birth usually requires proper assessment of the risk of SWS and other syndromes which manifest facial capillary malformations. Newborns considered at risk of SWS should be evaluated by a neurologist and ophthalmologist due to the congenital risk of glaucoma and meningeal involvement [18]. Even if the risk of syndromic involvement is considered to be low, PWSs require early treatment to at least partially prevent the development and evolution of the lesions. Untreated, the natural history of PWSs involves a colour shift from pink to red to burgundy, skin and mucosal thickening, and the potential development of pyogenic granuloma-like lesions prone to bleeding [18,51,52,58]. A study by Geronemus and Ashinoff on 415 patients with facial PWSs stated that two-thirds of patients developed hypertrophy and nodules by the fifth decade of life, significantly increasing morbidity [75]. Van Drooge et al. conducted a study on 335 PWS patients and confirmed these findings; in addition, they related the depth of colour of the PWS to hypertrophy, concluding that darker lesions have a higher chance of hypertrophy. The mean age for thickened hypertrophy was 12 years, while for nodular hypertrophy, it was 39 years [20]. Klapman and Yao observed that thickening and nodularity in PWSs often begin in early adulthood and become more pronounced with age, appearing more frequently in males and particularly affecting facial regions innervated by the second and third branches of the trigeminal nerve [76]. The hypertrophic or nodular changes in a lesion involving the periorbital area may inhibit vision, while nasal or peri-oral and oral involvement may cause difficulty in breathing, eating, and speaking [77]. However, treatment in a macular stage may prevent the hypertrophic component. Currently, the gold standard for PWS treatment is considered the pulsed-dye laser (PDL) at a 595 nm wavelength due to its ability to target haemoglobin species contained in the cutaneous blood vessels with minimal damage to surrounding tissues and its safety of usage, including on children [78,79,80]. Between 50 and 90% lesion clearance is achievable. Treatment requires a mean of three to nine sessions. Improved fading was noted in treatments initiated early during life [22,81]. Other treatment approaches include Nd:YAG laser therapy, intense-pulsed-light (IPL) therapy, photodynamic therapy (PDT), other laser types such as CO₂ laser, and medical tattooing [79,82]. Whichever treatment is chosen for PWSs or SWS-associated PWSs, there are some considerations which need to be addressed: diminishing nodularity and potentially tissue hypertrophy, minimising the psychosocial impact, and financial considerations for the family [83].

The social and psychological impact of PWSs is significant, affecting both adult and paediatric patients [83]; furthermore, the quality of life of families is also impacted. A study by Jiang et al. evaluated the impact of port-wine stains on the quality of life (QoL). The presence of PWSs affected both parents, with the mothers’ QoL being significantly more impacted. They concluded that the QoL of children with PWSs was impaired and was more affected as the children got older and the lesions darkened [84]. A systematic review by Wanitphakdeedecha et al. highlighted the vulnerability that PWS patients experience towards psychological disability, with the aggravation of the lesions and ageing significantly impacting social environment integration, especially in children [85]. The correlation of QoL to age is believed to be due to the higher risk of social stigmatisation due to facial marks experienced by school-aged children and teenagers, compared to pre-school children, which manifests through lower psychological well-being [86]. Adult patients with PWSs, whether associated with a syndrome or not, showed decreased QoL in a study by Hagen et al. [87], especially from an emotional perspective, with up to a third of the study population reporting anxiety and depression. Tissue hypertrophy and reduced facial mobility were predictors for a lower QoL. This was consistent with the findings of Wang et al., who concluded that PWSs have a low to moderate impact on QoL, affecting daily activities and self-perception, which can result in social avoidance and distress. Female patients and patients with extended and hypertrophic PWSs were negatively impacted [88]. However, poor emotional status, depression, and anxiety are known to negatively impact oral health, being associated with poor oral hygiene, carious lesions and non-carious lesions, and tooth loss; the vice versa has also been demonstrated [89,90,91,92,93,94]. Considering the lifelong impact of PWSs, their corelation to QoL, and their impact on oral and peri-oral tissues, dental professionals should be aware of both PWSs and SWS and involved in their management, as part of an interdisciplinary team including other medical professionals and psychological healthcare professionals.

The irregular hypertrophy of facial and oral tissues in the regions affected by PWSs seems to be the most impactful manifestation of this disorder. This is consistent with our findings, with several of the orodental manifestations of PWSs being related to soft or hard tissue hypertrophy. Gingival hypertrophy was the most mentioned manifestation. Gingival bleeding and hypertrophy are typically associated with gingivitis, which can be caused by inconsistent oral hygiene and plaque accumulation or external factors such as medication [95]. Several case reports mentioned SWS patients using anticonvulsive medication to treat the neurological manifestations of the syndrome [24,26,28,38,40,69,71]. This type of medications may cause gingival overgrowth [96]. Gingival enlargement may cause discomfort, interfere with speech and mastication, impede proper oral hygiene, and trigger halitosis and periodontal diseases while also being inaesthetic [69]. The periodontal management of PWS and SWS patients was the main subject of some of the included studies [24,28,29,39,60,69]. Scaling and root planning were deemed effective in the treatment of gingival issues [39,51,53,67,72,73]. Gingival mucosal staining can furtherly affect aesthetics, especially when associated with occlusal canting, a gummy smile, or gingival overgrowth. However, it can be corrected through laser treatments [26,97,98].

Lip hypertrophy was the second most frequently mentioned manifestation. Lip hypertrophy may lead to aesthetic concerns and functional issues such as speech issues and salivary or alimentary incontinence. When associated with poor oral hygiene, this can lead to a decrease in general oral health [99,100,101]. Lip incompetence as a consequence of hypertrophy was mentioned in five studies [19,38,64,69,72]. Lip hypertrophy is treated with surgical resection [33,34,44,46]. Furthermore, the hypertrophy of the lips, buccal area, and tongue may negatively impact the neutral zone balance. This can cause dental eruption issues, eventually causing malocclusion due to the low, constant forces exercised by hypertrophic tissues. However, malocclusion may also be derived from the bony hypertrophy that sometimes accompanies these lesions [20,23,75]. Facial asymmetry may be derived from osseous hypertrophy, soft tissue hypertrophy, or both.

Oral prophylaxis and periodontal treatments can greatly improve the oral status of PWS and SWS patients. Combined approaches of maxillofacial osteotomies and plasties, soft tissue reductive surgeries, and plastic surgery techniques might provide patients with increased functionality of orofacial tissues, improved facial aesthetics, and better social acceptability, thus improving mental health [64,89,102,103].

The lack of existing controlled clinical trials available about PWSs or SWS approached from a dental professional’s point of view represented a disadvantage for this study, since the studies included provide lower levels of evidence due to the nature of their designs. Furthermore, the small sample size of most of the included studies may represent a barrier to the wider applicability of our results. In addition, some of the included studies, even though they noted manifestations in the orodental sphere, were not conducted by dental professionals or developed for observing PWSs or SWS from a dentist’s point of view. Therefore, several studies noted only extraoral manifestations, while others noted intraoral manifestations, with little or no detail about the extent of the modifications to the normal state of the affected structures and tissues reported. Most of the studies did not correlate their findings about orodental manifestations to the status of oral soft tissues, occlusion, or dental status, hence providing an incomplete picture. Due to this and the observational nature of the included studies, meta-analysis was not possible.

However, this study fills a significant gap in the available information and existing literature, being the first systematic review to assess the manifestations of port-wine stains from an orodental point of view to the authors’ knowledge. Therefore, our study brings awareness of this pathology to dental professionals while also providing a comprehensive overview of factors to be considered in dental treatments. The systematic approach provided a detailed and streamlined process, while the graphical and tabulated information delivery ensured clarity. Furthermore, the strengths of this study lie in the development and pre-registration of its protocol on PROSPERO, followed by its development and realisation in conjunction with the PRISMA 2020 guidelines, thus ensuring a rigorous and transparent approach.

Further research should focus on the development of clinical studies assessing the modifications and manifestations of these pathologies in hard and soft tissues of the orofacial area, in direct comparison to healthy individuals, hence providing a better overview of the oral, dental, and cranio-facial implications of such a diagnosis. Larger study samples could provide better applicability of the results, while proper dental diagnosis and assessment of study subjects could provide clarity regarding potential treatment plans, additional treatment needs, and considerations for successful treatment. Since PWSs are mostly researched through a symptomatic and aesthetic-treatment-oriented approach, we consider that these further research directions could contribute to the wide picture described by the implications of this pathology.

5. Conclusions

PWSs and SWS are pathologies with orodental manifestations, therefore impacting oral healthcare. The distribution, extent, and evolution of the lesions influence the severity of the manifestations. Frequent modifications include gingival hypertrophy, osseous hypertrophy, labial hypertrophy, mucosal staining, and malocclusion. Gingival hypertrophy and bleeding may be a consequence of both plaque- and non-plaque-induced gingivitis. Poor oral hygiene can be accentuated in patients with SWS due to the associated mental development issues. However, soft tissue hypertrophy is a well-known manifestation of PWSs and SWS. The lips are also frequently affected, leading to lip incompetence, speech deficiencies, and aesthetic impairment. Osseous hypertrophy is usually the cause of malocclusion and facial asymmetry and is more frequently encountered in SWS. Maxillofacial surgery can help ameliorate these issues. Non-surgical periodontal treatment, oral prophylaxis, and gingivectomy surgery are effective in resolving periodontal issues. Few complications resulting from surgical and non-surgical treatments have been described. In most cases, patients with SWS and PWSs can be treated with standard procedures in the dental office. Dental professionals should be aware of the manifestations of these pathologies and the available treatment options. Adequate dental care can increase the quality of life of SWS and PWS patients.