Assessment of Outcomes With Pulsed Dye Laser Treatment of Port-Wine Stains Located Proximally vs Distally on Extremities.
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ABSTRACT:
SUBMITTER: Yu W
PROVIDER: S-EPMC7191473 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPort-wine stains (PWS) are capillary malformations, typically located in the dermis of the head and neck, affecting 0.3% of the population. Current theories suggest that port-wine stains are caused by somatic mutations that disrupt vascular development.ObjectivesUnderstanding PWS genetic determinants could provide insight into new treatments.MethodsOur study used a custom next generation sequencing (NGS) panel and digital polymerase chain reaction to investigate genetic variants in 12 individuals with isolated port-wine stains. Importantly, affected and healthy skin tissue from the same individual were compared. A subtractive correction method was developed to eliminate background noise from NGS data. This allowed the detection of a very low level of mosaicism.ResultsA novel somatic variant GNAQ, c.547C>G, p.Arg183Gly was found in one case with 4% allele frequency. The previously reported GNAQ c.548G>A, p.Arg183Gln was confirmed in 9 of 12 cases with an allele frequency ranging from 1.73 to 7.42%. Digital polymerase chain reaction confirmed novel variants detected by next generation sequencing. Two novel somatic variants were also found in RASA1, although neither was predicted to be deleterious.ConclusionsThis is the second largest study on isolated, non-syndromic PWS. Our data suggest that GNAQ is the main genetic determinant in this condition. Moreover, isolated port-wine stains are distinct from capillary malformations seen in RASA1 disorders, which will be helpful in clinical evaluation.
| S-EPMC4508108 | biostudies-literature
Project description: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.
| S-EPMC9603382 | biostudies-literature
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.
| S-EPMC9892359 | biostudies-literature
Project description:Port wine stains (PWS) are the most common vascular malformation of the skin, occurring in 0.3% to 0.5% of the population. Noninvasive laser irradiation with flashlamp-pumped pulsed dye lasers (selective photothermolysis) currently comprises the gold standard treatment of PWS; however, the majority of PWS fail to clear completely after selective photothermolysis. In this review, the clinically used PWS treatment modalities (pulsed dye lasers, alexandrite lasers, neodymium:yttrium-aluminum-garnet lasers, and intense pulsed light) and techniques (combination approaches, multiple passes, and epidermal cooling) are discussed. Retrospective analysis of clinical studies published between 1990 and 2011 was performed to determine therapeutic efficacies for each clinically used modality/technique. In addition, factors that have resulted in the high degree of therapeutic recalcitrance are identified, and emerging experimental treatment strategies are addressed, including the use of photodynamic therapy, immunomodulators, angiogenesis inhibitors, hypobaric pressure, and site-specific pharmaco-laser therapy.
| S-EPMC4143189 | biostudies-literature
Project description:BackgroundThe prevalence of capillary malformations, also known as port-wine stains (PWS), is 0.3%. Familial segregation can occur. The capillary malformation-arteriovenous malformation (CM-AVM) phenotype is caused by mutations in the RASA1 gene. In PWS familial cases, the inheritance is considered to be autosomal dominant with variable penetrance.ObjectiveInvestigation of the heredity of PWS among patients who attended the vascular anomaly section at the Department of Dermatology in Malmoe, Southern Sweden, between 1993 and 2004 and to study the involvement of the RASA1 gene in patients with a positive family history of PWS.Subjects and methodsA total of 254 patients were examined and given a questionnaire regarding family history of PWS. The first group of 175 patients (109 females and 66 males) reported a negative family history. The other group of 65 patients (46 females and 19 males) reported a positive family history (50% parents or brothers and sisters).ResultsThe heredity of PWS was 27% (65/240). Twenty-one patients with a positive family history and relatives had no CM-AVM phenotype for mutations in the RASA1 gene.ConclusionPWS may have a stronger heredity component than it was reported earlier and inheritance should be considered when counseling a patient. RASA1 mutations do not explain the PWS in our patients.
| S-EPMC4975081 | biostudies-literature
Project description:The 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.We 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.We 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 G?q.The 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.).
| S-EPMC3749068 | biostudies-literature
Project description:BackgroundVascular targeted photodynamic therapy (V-PDT) is a safe and effective therapeutic modality for port-wine stains (PWS) by targetedly damaging the dilated and malformed blood vessels. This study aims to monitor and quantify the changes in oxygen saturation (StO2), blood volume fraction (BVF) and perfusion in PWS lesions before and during V-PDT.MethodsMicrovascular parameters (i.e., StO2 and BVF) and skin perfusion were measured noninvasively by using diffuse reflectance spectroscopy (DRS) and laser Doppler imaging (LDI), respectively. The change in StO2, BVF and perfusion that occurred in the PWS lesions of 26 patients were monitored and investigated before and during V-PDT in vivo with the systematic administration of the porphyrin-based photosensitizer HiPorfin.ResultsThe mean StO2 (P<0.05), BVF (P<0.05), and perfusion (P<0.001) in PWS lesions of all subjects significantly increased by 6%, 34%, and 113%, respectively, 3 min after the initiation of V-PDT. The StO2 increased first and fluctuated during V-PDT. The overall trend of BVF change was consistent with the perfusion change. The BVF and the perfusion of PWS lesions increased after the initiation of V-PDT, and then gradually decreased.ConclusionsV-PDT is an effective therapeutic modality in treating PWS. Results showed that LDI and DRS permitted the noninvasive monitoring of the changes in StO2, BVF, and perfusion in PWS lesions during V-PDT, and these methods can be useful in facilitating our understanding of the basic physiological mechanisms during V-PDT.
| S-EPMC7940906 | biostudies-literature
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.
| S-EPMC8117375 | biostudies-literature
Project description:Port-wine stains (PWSs) are a congenital capillary malformed disorder and are caused by a number of somatic mutations that disrupt vascular development. However, the underlying genetic mutations in the pathogenesis of PWS have not yet been fully elucidated. To understand PWS genetic variations and investigate novel genetic mutations, we extracted genomic DNA from four sporadic PWS patients and then performed whole-genome sequencing (WGS). Using Sorting Intolerant from Tolerant (SIFT), PolyPhen2, Mutation Assessor, MetaSVM to identify candidate genetic mutations and whole-exome sequencing (WES) to confirm the identified variants. We found a previously reported G protein subunit alpha q (GNAQ) mutation c.548G > A, p.Arg183Gln in one case, whereas no such mutation was found in the other three samples. Moreover, six novel somatic mutations in three genes, including KCNJ12, SLC25A5, POTEE, were found in these four samples. Importantly, WES also verified the KCNJ12 (c.433G > A, p.Gly145Ser) and SLC25A5 (c.413G > A, p.Arg138His) mutations in other five sporadic PWS patients, with the frequency of 60% (3 of 5) and 40% (2 of 5), respectively. Thus, we reveal in this study two novel somatic mutations, KCNJ12 and SLC25A5, in the sporadic PWS patients for the first time. These findings highlight the genetic polymorphism of PWS and provide potential clinical prediction targets for this disease.
| S-EPMC9348515 | biostudies-literature
Project description:BACKGROUND:Valid and reliable outcome measures are needed to determine and compare treatment results of port wine stain (PWS) studies. Besides, uniformity in outcome measures is crucial to enable inter-study comparisons and meta-analyses. This study aimed to assess the heterogeneity in reported PWS outcome measures by mapping the (clinical) outcome measures currently used in prospective PWS studies. METHODS:OVID MEDLINE, OVID Embase, and CENTRAL were searched for prospective PWS studies published from 2005 to May 2020. Interventional studies with a clinical efficacy assessment were included. Two reviewers independently evaluated methodological quality using a modified Downs and Black checklist. RESULTS:In total, 85 studies comprising 3,310 patients were included in which 94 clinician/observer-reported clinical efficacy assessments had been performed using 46 different scoring systems. Eighty-one- studies employed a global assessment of PWS appearance/improvement, of which -82% was expressed as percentage improvement and categorized in 26 different scoring systems. A wide variety of other global and multi-item scoring systems was identified. As a result of outcome heterogeneity and insufficient data reporting, only 44% of studies could be directly compared. A minority of studies included patient-reported or objective outcomes. Thirteen studies of good quality were found. CONCLUSION:Clinical PWS outcomes are highly heterogeneous, which hampers study comparisons and meta-analyses. Consensus-based development of a core outcome-set would benefit future research and clinical practice, especially considering the lack of high-quality trials.
| S-EPMC7332045 | biostudies-literature