Dataset Information

Pathogenesis of Port-Wine Stains: Directions for Future Therapies.

ABSTRACT: Port-wine stains (PWSs) are congenital vascular malformations that involve the skin and mucosa. To date, the mechanisms underlying the pathogenesis and progression of PWSs are yet to be clearly elucidated. The potential reasons for dilated vessels are as follows: (1) somatic GNAQ (R183Q) mutations that form enlarged capillary malformation-like vessels through angiopoietin-2, (2) decreased perivascular nerve elements, (3) the coexistence of Eph receptor B1 and ephrin B2, and (4) the deficiency of αSMA expression in pericytes. In addition, ERK, c-JNK, P70S6K, AKT, PI3K, and PKC are assumed to be involved in PWS development. Although pulsed-dye laser (PDL) remains the gold standard for treating PWSs, the recurrence rate is high. Topical drugs, including imiquimod, axitinib, and rapamycin, combined with PDL treatments, are expected to alter the recurrence rate and reduce the number of PDL sessions for PWSs. For the deep vascular plexus, photosensitizers or photothermal transduction agents encapsulated by nanocarriers conjugated to surface markers (CD133/CD166/VEGFR-2) possess a promising therapeutic potential in photodynamic therapy or photothermal therapy for PWSs. The pathogenesis, progression, and treatment of PWSs should be extensively investigated.

SUBMITTER: Liu L

PROVIDER: S-EPMC9603382 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Pathogenesis of Port-Wine Stains: Directions for Future Therapies.

Liu Lian L Li Xiaoxue X Zhao Qian Q Yang Lihua L Jiang Xian X

International journal of molecular sciences 20221012 20

Port-wine stains (PWSs) are congenital vascular malformations that involve the skin and mucosa. To date, the mechanisms underlying the pathogenesis and progression of PWSs are yet to be clearly elucidated. The potential reasons for dilated vessels are as follows: (1) somatic <i>GNAQ</i> (R183Q) mutations that form enlarged capillary malformation-like vessels through angiopoietin-2, (2) decreased perivascular nerve elements, (3) the coexistence of Eph receptor B1 and ephrin B2, and (4) the defici ...[more]

PMID: 36292993

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Project description:Background and objectivesPort wine birthmark, also known as port wine stain (PWS) is a skin discoloration characterized by red/purple patches caused by vascular malformation. PWS is typically treated by using lasers to destroy abnormal blood vessels. The laser heating facilitates selective photothermolysis of the vessels and attenuates quickly in the tissue due to high optical scattering. Therefore, residual abnormal capillaries deep in the tissue survive and often lead to the resurgence of PWS. Ultrasound (US) has also been proposed to treat PWS, however, it is nonselective with respect to the vasculature but penetrates deeper into the tissue. We aim to study the feasibility of a hybrid PWS treatment modality combining the advantages of both modalities.Materials and methodsIn this manuscript, we propose a photoacoustic (PA) guided US focusing methodology for PWS treatment which combines the optical contrast-based selectivity with US penetration to focus the US energy onto the vasculature. The PA signals collected by the transducers, when time-reversed, amplified, and transmitted, converge onto the PWS, thus minimally affecting the neighboring tissue. We performed two- and three-dimensional simulations that mimic realistic transducers and medium properties in this proof of concept study.ResultsThe time-reversed PA signals when transmitted from the transducers converged onto the vasculature, as expected, thus reducing the heating of the neighboring tissue. We observed that while the US focus is indeed affected due to experimental factors such as limited-view, large detector separation and finite detection bandwidth, and so forth, the US did focus completely or partially onto the vasculature demonstrating the feasibility of the proposed methodology.ConclusionThe results demonstrate the potential of the proposed methodology for PWS treatment. This treatment method can destroy the deeper capillaries while minimally heating the neighboring tissue, thus reducing the chances of the resurgence of PWS and as well as cosmetic scarring.

Project description:BackgroundThe Sturge-Weber syndrome is a sporadic congenital neurocutaneous disorder characterized by a port-wine stain affecting the skin in the distribution of the ophthalmic branch of the trigeminal nerve, abnormal capillary venous vessels in the leptomeninges of the brain and choroid, glaucoma, seizures, stroke, and intellectual disability. It has been hypothesized that somatic mosaic mutations disrupting vascular development cause both the Sturge-Weber syndrome and port-wine stains, and the severity and extent of presentation are determined by the developmental time point at which the mutations occurred. To date, no such mutation has been identified.MethodsWe performed whole-genome sequencing of DNA from paired samples of visibly affected and normal tissue from 3 persons with the Sturge-Weber syndrome. We tested for the presence of a somatic mosaic mutation in 97 samples from 50 persons with the Sturge-Weber syndrome, a port-wine stain, or neither (controls), using amplicon sequencing and SNaPshot assays, and investigated the effects of the mutation on downstream signaling, using phosphorylation-specific antibodies for relevant effectors and a luciferase reporter assay.ResultsWe identified a nonsynonymous single-nucleotide variant (c.548G→A, p.Arg183Gln) in GNAQ in samples of affected tissue from 88% of the participants (23 of 26) with the Sturge-Weber syndrome and from 92% of the participants (12 of 13) with apparently nonsyndromic port-wine stains, but not in any of the samples of affected tissue from 4 participants with an unrelated cerebrovascular malformation or in any of the samples from the 6 controls. The prevalence of the mutant allele in affected tissues ranged from 1.0 to 18.1%. Extracellular signal-regulated kinase activity was modestly increased during transgenic expression of mutant Gαq.ConclusionsThe Sturge-Weber syndrome and port-wine stains are caused by a somatic activating mutation in GNAQ. This finding confirms a long-standing hypothesis. (Funded by the National Institutes of Health and Hunter's Dream for a Cure Foundation.).

Project description:BackgroundA plethora of outcome measurement instruments (OMIs) are being used in port wine stain (PWS) studies. It is currently unclear how valid, responsive, and reliable these are.ObjectivesThe aim of this systematic review was to appraise the content validity and other measurement properties of OMIs for PWS treatment to identify the most appropriate instruments and future research priorities.MethodsThis study was performed using the updated Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) methodology and adhered to PRISMA guidelines. Comprehensive searches in Medline and Embase were performed. Studies in which an OMI for PWS patients was developed or its measurement properties were evaluated were included. Two investigators independently extracted data and assessed the quality of included studies and instruments to perform qualitative synthesis of the evidence.ResultsIn total, 1,034 articles were screened, and 77 full-text articles were reviewed. A total of 8 studies were included that reported on 6 physician-reported OMIs of clinical improvement and 6 parent- or patient-reported OMIs of life impact, of which 3 for health-related quality of life and 1 for perceived stigmatization. Overall, the quality of OMI development was inadequate (63%) or doubtful (37%). Each instrument has undergone a very limited evaluation in PWS patients. No content validity studies were performed. The quality of evidence for content validity was very low (78%), low (15%), or moderate (7%), with sufficient comprehensibility, mostly sufficient comprehensiveness, and mixed relevance. No studies on responsiveness, minimal important change, and cross-cultural validity were retrieved. There was moderate- to very low-quality evidence for sufficient inter-rater reliability for some clinical PWS OMIs. Internal consistency and measurement error were indeterminate in all studies.ConclusionsThere was insufficient evidence to properly guide outcome selection. Additional assessment of the measurement properties of OMIs is needed, preferentially guided by a core domain set tailored to PWS.

Project description:Background Port wine stains (PWS) often cause cosmetic effects and psychological distress. Pulsed dye lasers (PDL) and photodynamic therapy (PDT) are the most commonly used treatments. PDL is still the “gold standard” of therapy to date. However, its shortcomings have become apparent as clinical applications have increased. PDT has been proven as an alternative to PDL. Patients with PWS still lack enough evidence about PDT to make informed treatment decisions. Objective The purpose of this systematic review and meta-analysis was to assess the safety and effectiveness of PDT for PWS. Methods The online datasets, comprising PubMed, Embase, Web of Science, and the Cochrane Library, were searched for meta-analysis-relevant publications. Two reviewers separately evaluated the risk of bias in each listed study. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the treatment and safety outcomes. Results Our search retrieved 740 hits and only 26 studies were finally included. Among the 26 studies included, 3 were randomized clinical trials, and 23 were prospective or retrospective cohort investigations. Based on a gathered assessment, the percentage of individuals achieving a 60% improvement was estimated to be 51.5% [95% confidence interval (CI): 38.7–64.1; I2 = 83.8%] and a ≥75% improvement was 20.5% (95% CI: 14.5–26.5; I2 = 78.2%) after 1–8.2 treatment sessions (GRADE score: very low). Due to the statistical diversity of the meta-analysis, a subgroup assessment was performed to determine the sources of diversity. The collected findings indicated that the impact of PDT on enhancing the medical effectiveness of PWS was significant in different treatment sessions, different types of ages, different locations of PWS, and different types of PWS. Pain and edema occurred in most patients. Hyperpigmentation was present in 7.9–34.1% of the patients in 17 studies. Photosensitive dermatitis, hypopigmentation, blister, and scar were infrequently reported, with 0–5.8% incidences. Conclusion Photodynamic therapy is recommended as a safe and effective treatment for PWS based on the current evidence. However, our findings are based on poor-quality evidence. Therefore, comparative investigations of a large scale and high quality are necessary to support this conclusion.

Dataset Information

Pathogenesis of Port-Wine Stains: Directions for Future Therapies.

Publications

Pathogenesis of Port-Wine Stains: Directions for Future Therapies.

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