Acquired port-wine stain: a case report and differential diagnosis.

Port-wine stain (PWS) are vascular malformations characterised by dilated dermal capillaries with normal endothelial cells. Congenital PWS are the most prevalent vascular malformation affecting 0.3-1% of newborns while acquired PWS (APWS), though an uncommon entity, exhibit morphological and histological similarity to congenital PWS. We hereby report a case of APWS along with a comprehensive comparison of clinical, histopathological and dermoscopic findings of other acquired vascular malformations.

Maternal history of angioma is associated with infantile hemangioma and port-wine stain in children: a population-based, cohort study of mother-child pairs from the United Kingdom.

The two most prevalent childhood vascular abnormalities are infantile hemangioma (IH) and port-wine stain (PWS). They become apparent shortly after birth but have distinct pathophysiology and clinical manifestations. The goal of this study was to determine if mother's history of angioma or PWS is associated with these vascular abnormalities. We evaluated an UK anonymized electronic medical records database with medical records that were linked between children and their mothers. Cox proportional hazards models were used to evaluate the association between maternal factors and the time of onset of either IH or PWS in children. Between 2004 and 2021, 639,085 children were linked to their mom's medical data with a total of 4,270,773 person-years of follow up. Children born to mothers with an angioma as compared to a mother without an angioma were more than 60% more likely to have an IH (HR: 1.64 [1.07, 2.52]). Children born to mothers with a PWS as compared to children born to mothers without a PWS were nearly 20 times more likely to have a PWS (18.95 [4.71,76.26]). Mothers with angiomas were not more likely to have children with PWS and mothers with PWS were not more likely to have children with IH. The effect estimates were minimally changed after adjustment. We demonstrated that children born to mothers with angiomas or PWS were at increased risk of IH or PWS, respectively.

Biomarker Landscape in RASopathies.

RASopathies are a group of related genetic disorders caused by mutations in genes within the RAS/MAPK signaling pathway. This pathway is crucial for cell division, growth, and differentiation, and its disruption can lead to a variety of developmental and health issues. RASopathies present diverse clinical features and pose significant diagnostic and therapeutic challenges. Studying the landscape of biomarkers in RASopathies has the potential to improve both clinical practices and the understanding of these disorders. This review provides an overview of recent discoveries in RASopathy molecular profiling, which extend beyond traditional gene mutation analysis. mRNAs, non-coding RNAs, protein expression patterns, and post-translational modifications characteristic of RASopathy patients within pivotal signaling pathways such as the RAS/MAPK, PI3K/AKT/mTOR, and Rho/ROCK/LIMK2/cofilin pathways are summarized. Additionally, the field of metabolomics holds potential for uncovering metabolic signatures associated with specific RASopathies, which are crucial for developing precision medicine. Beyond molecular markers, we also examine the role of histological characteristics and non-invasive physiological assessments in identifying potential biomarkers, as they provide evidence of the disease's effects on various systems. Here, we synthesize key findings and illuminate promising avenues for future research in RASopathy biomarker discovery, underscoring rigorous validation and clinical translation.

Bilateral ocular manifestations of Sturge-Weber syndrome: a rare case report.

The rare neurocutaneous condition known as Sturge-Weber syndrome (SWS) is characterized by leptomeninges, or angiomas affecting the face, eyes, and brain. We report a newly diagnosed case that came to our institute complaining of a diminution of vision BE that had been going on for the past 1 year. Upon examination, the patient exhibited bluish discoloration of the sclera, an increase in the size of the cornea, and the characteristic port wine stain (PWS) on the face. Intraocular pressure BE was 30 mmHg with an applanation tonometer. The cup disc ratio on fundoscopy was 0.9 RE and 0.8 LE with characteristic glaucomatous disc changes BE. The child was treated with antiglaucoma medications. Abbreviations: SWS = Sturge-Weber syndrome, PWS = Port wine stain, CNS = Central nervous system, CT = Computed Tomography, IOP = Intraocular pressure, OCT = Optical coherence tomography, RE = Right eye, LE = Left eye, BE = Both eyes, ASOCT = Anterior segment optical coherence tomography.

A feasible way to explore real blood vessels thermal responses to laser irradiation by combing optical clearing and the reflectance spectra measurements: animal experiment study.

Laser therapy has been widely used to treat port-wine stains (PWS) and other cutaneous vascular lesions via selective photothermolysis. Animal models are a valuable tool for investigating thermal responses beneath the skin. However, in previous animal experiments, such as the dorsal skin chamber model, one side of the skin was removed, resulting in the loss of mechanical support for the target blood vessel. In this study, the optical clearing technique was applied to the dorsal skin, allowing direct observation of real thermal responses within the tissue without removing the covering skin. The target blood vessels were irradiated with a pulsed 1064 nm Nd: YAG laser. The corresponding thermal responses were recorded using a CCD camera. Additionally, variations in skin reflectance spectra were measured before and after laser irradiation. Due to the optical clearing and reflectance spectra measurement, vessel responses such as contraction, reperfusion, and full occlusion were correlated with specific variation patterns in reflectance spectral signals.

Non-invasive efficacy assessment of pulsed dye laser and photodynamic therapy for port-wine stain.

Port wine stain (PWS) is a congenital vascular malformation that commonly occurs on the face and neck. Currently, the main treatments for port wine stain are pulsed dye laser (PDL) and photodynamic therapy (PDT). However, the efficacy evaluation of PWS mostly relies on the subjective judgement of clinicians, and it is difficult to accurately respond to many small changes after treatment. Therefore, some non-invasive and efficient efficacy assessment methods are also needed. With the continuous development of technology, there are currently many visualisation instruments to evaluate PWS, including dermoscopy, VISIA-CR™ system, reflectance confocal microscopy (RCM), high-frequency ultrasound (HFUS), optical coherence tomography (OCT), Photoacoustic imaging (PAI), laser speckle imaging (LSI) and laser Doppler imaging (LDI). Among them, there are simple and low-cost technologies such as dermoscopy and the VISIA-CR™ system, but they may not be able to observe the deeper structures of PWS. At this time, combining techniques such as HFUS and OCT to increase penetration depth is crucial to evaluate PWS. In the future, the combination of these different technologies could help overcome the limitations of a single technology. This article provides a systematic overview of non-invasive methods for evaluating treatment efficacy in port wine stains and summarises their advantages and disadvantages.

Large birth mark and unilateral swelling of the lower extremity in a young teenager.

We describe an early adolescent male who was diagnosed with vascular malformation associated with unilateral limb overgrowth based on the clinical findings of a persistent port-wine stain since birth and gradually progressing right lower limb oedema since early childhood. Clinicians should keep in mind to clinically evaluate such malformations in detail, as well as contemplate genetic testing in patients presenting with a large port-wine stain at birth, particularly if well demarcated and lateral in a lower extremity.

Photodynamic therapy for the treatment of port-wine stains in phakomatosis pigmentovascularis.

BACKGROUND: Phakomatosis pigmentovascularis (PPV) is a rare congenital syndrome. Only a few studies have reported the treatment of PPV, including a case using photodynamic therapy (PDT) to treat PPV-associated port-wine stains (PWS). OBJECTIVE: To investigating the efficacy and adverse effects of hemoporfin-PDT in PPV-associated PWS. METHODS: The efficacy and adverse effects in patients with PPV who underwent two sessions of hemoporfin-PDT from January 2019 to December 2022 were retrospectively analyzed. RESULTS: Twenty patients were included (13 females, 7 males, age range: 2-31 years; mean: 8.20 ± 8.92 years). Two, nine, seven, and two patients had PPV types Ia, IIa, IIb, and IIIa, respectively. After two treatments, the visual evaluation indicated the color of the PWS in 4, 5, 6, and 5 patients showed poor, fair, good, and excellent improvements, respectively. The combined good and excellent improvement rates in patients with PWS and pigmentary nevus overlapping in the same treatment area and in patients with PWS in the treatment areas only were 33.3% versus 87.5%, respectively, and were significantly different (p = 0.02). Minor side effects, such as edema, scabbing, hyperpigmentation, and blistering, were observed in some patients after PDT. CONCLUSION: Hemoporfin-PDT is an effective treatment for PPV-associated PWS. Patients with PWS and pigmentary nevus overlapping in the same treatment area showed poorer efficacy than patients with PWS in the treatment areas only.

532-nm potassium titanyl-phosphate laser versus 595-nm pulsed dye laser for port-wine birthmarks: A prospective, randomized, split-side study.

BACKGROUND: Pulsed dye lasers (PDL) are currently the first-line treatment of port-wine birthmarks (PWB). Due to high maintenance costs and instable technology, alternative methods are needed. OBJECTIVES: To compare clinical outcomes of a variable-sequenced, long-pulsed 532-nm potassium titanyl-phosphate (KTP) laser and PDL on treating PWB. METHODS: A prospective, randomized, split-side study. Patients were treated with a KTP laser and PDL with 1 to 5 sessions at intervals of 6-8 weeks. A follow-up visit was scheduled 6 weeks post-treatment. Efficacy was evaluated through colorimetric analysis, area reduction measurements and clinical evaluations by two blinded investigators based on photo documentation. Subjects provided rating of pain intensity during treatment, post-treatment reactions and satisfaction. Safety was measured by adverse events. Maintenance issues of the laser systems were documented. RESULTS: A total of 35 patients (mean age 42.1 years) were enrolled. 63% were female. Patients received 2.4 (SD 1.4; 1-5) treatment sessions. Colorimetric analysis indicated a comparable clearance effect in PWB of both KTP laser and PDL. Independent investigators rated clinical appearance to be significantly improved compared to baseline. No significant difference was observed between both laser systems. Regarding post-treatment reactions, the KTP laser caused less swelling, purpura and crusts. 96% would recommend both treatment modalities. Patients were satisfied with both laser systems. During the study, PDL systems malfunctioned for 6.6 months in total. For the KTP laser, we did not observe any system failures. CONCLUSION: Our data indicate that the KTP laser of the latest generation with large-spot sizes, subpulse technology and cryogen cooling has a comparable efficacy to the PDL in treating PWB. In addition, KTP laser is associated with greater tolerability, fewer technical failures and lower repair costs. Further prospective studies are required to determine the true effectiveness of the KTP laser in PWB treatment. This study was preregistered in Clinicaltrials.gov (NCT05771298).

Quantitative analysis of lesion images to evaluate the efficiency of vascular-targeted photodynamic therapy for port-wine stains: Four case reports.

SIGNIFICANCE: Vascular-targeted photodynamic therapy (V-PDT) is a clinically approved therapeutic approach for treating vascular-related diseases, such as port-wine stains (PWS). For accurate treatment, varying light irradiance is required for different lesions due to the irregularity of vascular size, shape and degree of disease, which commonly alters during different stages of V-PDT. This makes quantitative analysis of the treatment efficiency urgently needed. APPROACH: Lesion images pre- and post- V-PDT treatment of patients with PWS were used to construct a quantitative method to evaluate the differences among lesions. Image analysis techniques were applied to evaluate the V-PDT efficiency for PWS by determining the Euclidean distances and two-dimensional correlation coefficients. RESULTS: According to the image analysis, V-PDT with good treatment efficiency resulted in a larger Euclidean distance and a smaller correlation coefficient compared with the case having lower V-PDT efficiency. CONCLUSIONS: A new method to quantify the Euclidean distances and correlation coefficients has been proposed, which is promising for the quantitative analysis of V-PDT efficiency for PWS.

Simulating PDT of port-wine stains in the in vivo chicken wattle model using Hemoporfin and radiation at 532 nm: Comparison of a LED and a laser source.

Port-wine stain (PWS) birthmarks are congenital capillary malformations occurring in 0.3 %∼0.5 % of newborns. Hemoporfin-mediated vascular-acting photodynamic therapy (Hemoporfin PDT) is an emerging option for treating PWS. This in vivo study aimed to compare laser and light-emitting diodes (LED) as light source for Hemoporfin PDT. Chicken wattles were used as the animal model. Color and histopathological changes were evaluated after combining Hemoporfin with KTP laser or LED light source of 532 nm at the same doses. Both PDT approaches could induce significant vascular injury and color bleaching. Although the use of the laser resulted in a greater vascular clearance, the LED showed more uniform distribution both in the beam profiles and tissue reaction and exhibited better safety. This in vivo study suggests that the LED is a favorable choice for larger PWS lesion.

Weekly Pulsed Dye Laser Treatments for Port-Wine Birthmarks in Infants.

Importance: Early treatment of port-wine birthmark (PWB) can be life-altering and is often associated with improved outcomes and quality of life. There is growing evidence that shorter treatment intervals may play a role in more rapid PWB clearance; however, the optimal treatment interval has not been established. Objective: To describe the outcomes of once-weekly pulsed dye laser (PDL) treatments for PWB in infants. Design, Setting, and Participants: This case series analyzed the medical records of patients with PWB who received once-weekly PDL treatments between January 1, 2022, and December 31, 2023, at the Laser & Skin Surgery Center of New York. These patients were younger than 6 months. Before-and-after treatment photographs were independently assessed and graded 2 months after initiation of treatment. Intervention: Once-weekly PDL treatments. Main Outcomes and Measures: The primary outcome was the percentage improvement of PWB, which was graded using the following scale: 0% (no improvement), 1% to 25% (mild improvement), 26% to 50% (moderate improvement), 51% to 75% (marked improvement), 76% to 95% (near-total clearance), and 96% to 100% (total clearance). Results: Of the 10 patients (6 males [60%]; median [range] age at first treatment, 4 [<1 to 20] weeks) included, 7 (70%) had experienced either near-total clearance (76%-95%) or total clearance (96%-100%) of their PWB with once-weekly PDL treatments after 2 months. The other 3 patients all saw marked improvement (51%-75%) and subsequently went on to achieve near-total clearance with additional treatments. The median (range) duration of treatment and number of treatments to achieve near-total or total clearance in all patients were 2 (0.2-5.1) months and 8 (2-20) treatments, respectively. No adverse events were noted. Conclusion and Relevance: This case series found that once-weekly PDL treatments for PWB in the first few months of life was associated with near-total or total clearance of PWB with no reported adverse events, suggesting improved outcomes can be achieved with shorter overall treatment duration. Further investigation into this novel decreased treatment interval of 1 week is warranted.

[Rapamycin and HPPH Co-Loaded Nanodrug Delivered via Dissolvable Microneedles to Treat Port-Wine Stains]. / å ±è½½é›·å¸•éœ‰ç´ å’Œå ‰å ‹æ´›çš„çº³ç±³è¯ç‰©å¤åˆå¯æº¶è§£å¾®é’ˆæ²»ç–—é²œçº¢æ–‘ç—£çš„å®žéªŒç ”ç©¶.

Objective: Port-wine stains are a kind of dermatological disease of congenital capillary malformation. Based on the biological characteristics of port-wine stains and the advantages of microneedle transdermal administration, we intend to construct a nanodrug co-loaded with rapamycin (RPM), an anti-angiogenesis drug, and photochlor (HPPH), a photosensitizer, and integrate the nanodrug with dissolvable microneedles (MN) to achieve anti-angiogenesis and photodynamic combination therapy for port-wine stains. Methods: First, RPM and HPPH co-loaded nanoparticles (RPM-HPPH NP) were prepared by the emulsification solvent-volatilization method, and its ability to generate reactive oxygen species (ROS) was investigated under 660 nm laser irradiation. Mouse hemangioendothelioma endothelial cells (EOMA) were used as the subjects of the study. The cellular uptake behaviors were examined by fluorescence microscopy and flow cytometry. The cytotoxicity effects of RPM-HPPH NP with or without 660 nm laser irradiation on EOMA cells were examined by MTT assays (with free RPM serving as the control). Then, hyaluronic acid (HA) dissolvable microneedles loaded with RPM-HPPH NP (RPM-HPPH NP@HA MN) were obtained by compounding the nanodrug with HA dissolvable microneedle system through the molding method. The morphological characteristics and mechanical properties of RPM-HPPH NP@HA MN were investigated by scanning electron microscope and electronic universal testing machine. The penetration ability of RPM-HPPH NP@HA MN on the skin of nude mice was evaluated by trypan blue staining and H&E staining experiment. Results: The RPM-HPPH NP prepared in the study had a particle size of 150 nm and generated large amounts of ROS under laser irradiation. At the cellular level, RPM-HPPH NP was taken up by EOMA cells in a time-dependent manner. The cytotoxicity of RPM-HPPH NP was higher than that of free RPM with or without laser irradiation. Under laser irradiation, RPM-HPPH NP exhibited stronger cytotoxic effects and the difference was statistically significant (P<0.05). The height of the needle tip of RPM-HPPH NP@HA MN was 600 µm and the mechanical property of a single needle was 0.75048 N. Trypan blue staining and HE staining showed that pressing on the microneedles could produce pores on the skin surface and penetration of the stratum corneum. Conclusion: RPM-HPPH NP@HA MN can deliver RPM-HPPH NP percutaneously to the lesion tissue and realize the synergistic treatment of port-wine stains with anti-angiogenic therapy and photodynamic therapy, providing a new strategy for the construction of nanodrug-loaded microneedle delivery system and the clinical treatment of port-wine stains.

Current clinical evidence is insufficient to support HMME-PDT as the first choice of treatment for young children with port wine birthmarks.

BACKGROUND: Port wine birthmark (PWB) is a congenital vascular malformation of the skin. Pulsed dye laser (PDL) is the "gold standard" for the treatment of PWB globally. Hematoporphyrin monomethyl ether (HMME or hemoporfin)-mediated photodynamic therapy (HMME-PDT) has emerged as the first choice for PWB treatment, particularly for young children, in many major hospitals in China during the past several decades. AIM: To evaluate whether HMME-PDT is superior to PDL by comparing the clinical efficacies of both modalities. METHOD: PubMed records were searched for all relevant studies of PWB treatment using PDL (1988-2023) or HMME-PDT (2007-2023). Patient characteristics and clinical efficacies were extracted. Studies with a quartile percentage clearance or similar scale were included. A mean color clearance index (CI) per study was calculated and compared among groups. An overall CI (C0), with data weighted by cohort size, was used to evaluate the final efficacy for each modality. RESULT: A total of 18 HMME-PDT studies with 3910 patients in China were eligible for inclusion in this analysis. Similarly, 40 PDL studies with 5094 patients from nine different countries were eligible for inclusion in this analysis. Over 58% of patients in the HMME-PDT studies were minors (<18 years old). A significant portion (21.3%) were young children (<3 years old). Similarly, 33.2% of patients in the PDL studies were minors. A small proportion (9.3%) was young children. The overall clearance rates for PDL were slightly, but not significantly, higher than those for HMME-PDT in cohorts with patients of all ages (C0, 0.54 vs. 0.48, p = 0.733), subpopulations with only minors (C0, 0.54 vs. 0.46, p = 0.714), and young children (C0, 0.67 vs. 0.50, p = 0.081). Regrettably, there was a lack of long-term data on follow-up evaluations for efficacy and impact of HMME-PDT on young children in general, and central nervous system development in particular, because their blood-brain barriers have a greater permeability as compared to adults. CONCLUSION: PDL shows overall albeit insignificantly higher clearance rates than HMME-PDT in patients of all ages; particularly statistical significance is nearly achieved in young children. Collectively, current evidence is insufficient to support HMME-PDT as the first choice of treatment of PWBs in young children given: (1) overall inferior efficacy as compared to PDL; (2) risk of off-target exposure to meningeal vasculature during the procedure; (3) administration of steriods for mitigation of side effects; -and (4) lack of long-term data on the potential impact of HMME on central nervous system development in young children.

Hematoporphyrin monomethyl ether-mediated photodynamic therapy for acquired port-wine stain at lower extremity: Two case reports.

Two cases of acquired port-wine stain (APWS) at lower extremity were treated with hematoporphyrin monomethyl ether (HMME) and 532 nm LED green light-mediated photodynamic therapy (HMME-PDT). No serious adverse reactions were observed during or post-treatment period. Five-month follow-up showed significant reduction of red patches after a single HMME-PDT treatment in both cases.

Klippel-Trenaunay syndrome or not? An exploration of atypical presentations.

Klippel-Trenaunay syndrome (KTS) is a rare, congenital disorder typically emerging in early infancy or childhood. The classic presentation of KTS is distinguished by a triad of clinical features: a port-wine stain, early-onset varicosities and limb overgrowth. However, a notable variant of KTS has been documented, characterised by limb shortening rather than lengthening, occasionally referred to as 'inverse KTS'. This report details two cases that display this unusual presentation-both patients had classical features of port-wine stain and varicose veins but both experienced shortening of the affected limb. Whether these cases represent a variant of KTS or a new clinical syndrome altogether is uncertain. They however offer valuable insights into the nuances and breadth of clinical manifestations associated with this syndrome.