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.

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.

KTWS (Klippel-Trenaunay-Weber syndrome): A systematic presentation of a rare disease.

BACKGROUND: Klippel-Trenaunay-Weber syndrome (KTWS) is a rare disease with a wide range of manifestations. KTWS is characterized by a clinical triad of varicosities of the extremities, cutaneous vascular malformations, and hypertrophy of soft tissues and long bones. The diagnosis is made clinically supplemented with magnetic resonance imaging and computed tomography. AIM: Hereby we aim to highlight the significance of the possible life-threatening first-time presentations associated with the GI system in previously undiagnosed KTWS patients. PATIENT: We report the case of a 47-year-old male with KTWS, who presented with various symptoms such as rectorrhagia since childhood, digestive problems and abnormal lateral vascular malformations of the left buttock which extended all the way to the leg, vascular malformations of the left fourth and fifth toes as well as soft tissue swelling of the left foot. There was no evidence of other clinical presentations. The patient was hospitalized with severe rectorrhagia and a hemoglobin level of 3/9. Physical examination revealed a blood pressure of 85/55 and pulse rate of 115. Ruptured aneurysm of the superior mesenteric artery was found on angiography and subsequently treated with embolization. Dermatologic evaluation showed pitting edema of the left leg and foot and multiple vascular lesions. Thus a diagnosis of KTWS was established. Pulsed dye laser therapy and compression bandage was performed for the patient. The patient's follow-up was done 3 months after discharge for which the patient was again consulted by a dermatologist and gastroenterologist. Lymphedema of the left leg had improved to a great extend so treatment with compression bandage was continued. Colonoscopy was repeated for the patient to evaluate and control possible active sources of bleeding, due to potential life-threating complications. RESULTS: According to previous findings, there have been few case reports of KTWS presenting with gastrointestinal manifestations, fewer of which have covered acute life-threatening bleedings associated with this system.

Klippel-Trenaunay Syndrome: To Be or Not to Be Afraid.

Klippel-Trenaunay syndrome (KTS) is a rare genetic syndrome comprising an abnormal development of soft tissues and the lymphovascular system with bony overgrowth, venous malformation, and port wine stains. We present an interesting case of a three-year-old child brought to our hospital with a swollen limb and raised skin lesions associated with bleeding from minor trauma. Most of the clinical characteristics of KTS were seen in our patient, including arteriovenous, soft tissue, capillary, and lymphatic abnormalities. The diagnosis of KTS is based on clinical examinations and imaging investigations. He had gross hypertrophy of the left lower limb with measurable lengthening compared to the opposite limb. Ultrasonography of the left limb revealed soft tissue hypertrophy with abnormal venous communication. The management of KTS is mainly symptomatic and should be approached conservatively if the patient has functional limbs without edema, bleeding, ulceration, or pain.

Pulsed dye laser and adjuvant topical therapies for the treatment of port-wine stains: A systematic review.

OBJECTIVES: The current gold standard treatment for port-wine stains (PWS) is pulsed dye laser (PDL). However, multiple treatment sessions may be necessary and complete resolution is often not achieved. Neoangiogenesis can occur soon after treatment and is thought to be a major factor contributing to treatment failure. Adjuvant antiangiogenic topical therapies may therefore improve the efficacy of pulsed dye laser treatment of port-wine stains. MATERIAL AND METHODS: Following PRISMA guidelines, we searched PubMed, Embase, Web of Science, and clinicaltrials.gov using "port-wine stain," "nevus flammeus," "capillary malformation," "sturge weber," and "pulsed dye laser" as keywords and medical subject heading (MeSH) terms. Articles were included if they (1) were a randomized controlled trial (RCT); (2) studied patients with PWS; and (3) investigated topical adjuvant therapies with PDL. Bias was assessed using the Critical Appraisal Skills Programme (CASP) Randomized Controlled Trial Standard Checklist. RESULTS: 1835 studies were identified, with six studies meeting inclusion criteria. The total number of patients studied was 103 (range: 9-23), with 8-36 week follow-up. The average age ranged from 11 to 33.5 years old. Three studies examined adjuvant topical sirolimus (n = 52), two examined timolol (n = 29), and one studied imiquimod (n = 22). Two of three RCTs reported no improvement through colorimetric analysis with topical sirolimus; however, one of these studies did show a significant improvement through Investigator Global Assessment (IGA) score. The last sirolimus study showed significant improvement through digital photographic image scoring (DPIA). Studies examining topical timolol reported no change in PWS appearance compared to placebo. The addition of 5% adjuvant imiquimod cream did lead to significant improvement. A variety of outcome measures were used. Imiquimod and sirolimus led to mild cutaneous adverse events, while timolol caused no side effects. None of the adverse events led to treatment discontinuation. Study quality was moderate in three, high in two, and low in one. CONCLUSION: The efficacy of adjuvant topical therapy was unclear. Limitations included variation in concentration and duration of adjuvant therapies, differences in follow-up time, and inconsistent outcome measure reporting. Given their potential clinical promise, larger prospective studies examining topical adjuvant therapies should be considered.

Efficacy and influential factors of hematoporphyrin monomethyl ether mediated photodynamic therapy in the treatment for port-wine stains.

BACKGROUNDS: Hematoporphyrin monomethyl ether mediated photodynamic therapy (HMME-PDT) has emerged as an alternative approach for port-wine stain (PWS), which was primarily treated with pulsed dye laser (PDL). This study was aimed to evaluate the efficacy and safety of HMME-PDT for PWS and to explore influential factors on the efficacy. METHODS: A total of 254 patients were enrolled. Patients received an intravenous injection of HMME at 5 mg/kg. Lesion areas were irradiated with 532-nm light for 20-25 min. Efficacy was assessed according to fading of lesions and graded as excellent (≥90 %), good (60 %-89 %), fair (20 %-59 %), or poor (<20 %). Adverse events were recorded. Clinical data were analyzed including gender, age, lesion sub-type, lesion location and number of treatments. RESULTS: Overall, 72.4 % of patients achieved an effective response, with 27.6% showing excellent efficacy, 24.8 % showing good efficacy and 20.1 % showing fair efficacy. Only 27.6 % showed poor efficacy. Patients under the age of 18 obtained a better efficacy than adults. Lesions in face showed a better therapeutic outcome than those in neck or trunk and extremities. A more effective response was seen in pink type compared with nodular thickening type. Multiple HMME-PDT treatments could improve the clinical response. Lesion location, lesion sub-type, number of treatments were independent influential factors on efficacy. Adverse events included edema, blister, crust, hypopigmentation, hyperpigmentation, pain, itch and burning sensation. No severe systemic side events were observed. CONCLUSIONS: HMME-PDT was effective for treating PWS and was safe and well-tolerated by patients. It is worth further investigation in efficacy and safety involving more patients from medical institutions in different regions in China. The optimal treatment parameters and treatment protocols are still being explored in the clinical treatment for PWS.

Subcutaneous Cavernous Haemangioma in a Patient with Klippel-Trenaunay Syndrome: A Case Report.

Background: Klippel-Trenaunay syndrome (KTS) is a rare congenital disease that mainly involves blood vessels and is characterized by the presence of capillary malformations (port wine stains), varicose veins, soft tissue and/or bone hypertrophy. Case Presentation: We report a 28-year-old man who was diagnosed 20 years ago with Klippel-Trenaunay syndrome. Approximately 3 years ago, he found enlarged masses on both upper extremities and a new dark red mass that was pathologically diagnosed as cavernous haemangioma appeared on the right index finger. Conclusion: KTS is a rare and potentially multisystem disease requiring multidisciplinary management for which imaging examination is an important auxiliary diagnostic method. Various complications may occur during its development, so regular follow-up is required to prevent serious accidents.

Diffuse choroidal hemangioma in pregnancy: Symptomatic diffuse choroidal hemangioma spontaneously resolving postpartum.

We present the case of a pregnant young woman with symptomatic diffuse choroidal hemangioma (CH), diagnosed with Sturge-Weber syndrome (SWS). Three months postpartum, there was full spontaneous resolution of the subretinal fluid and improvement in the visual acuity (VA). A 29-year-old, 31-week pregnant female with a coagulation disorder and enoxaparin (clexane) treatment, complained of a left visual disturbance of 2 weeks duration. On examination, the right eye was normal; left eye VA was 6/12 (20/40) with a left eyelid port-wine stain and on funduscopic examination there was a serous retinal detachment. On ultrasound, there was diffuse thickening of the choroid with a focus superior and nasal to the disc with active vascularization - a diagnosis of diffuse CH was made. Magnetic resonance imaging (MRI) and MR venography studies of the brain and orbit revealed engorged orbital vasculature, and the diagnosis of SWS was made. Three months after Cesarean section with birth of a healthy baby boy, VA returned to 6/9 with full resorption of subretinal fluid. On fundoscopic exam, there were no retinal or vein occlutions but there were tortuous blood vessels with A-V crossing. This is a rare case of newly diagnosed SWS with symptomatic diffuse CH in pregnancy. Postpartum, there was full resolution of the subretinal fluid. A watchful waiting approach can be considered in such cases.

Complication rates and safety of pulsed dye laser treatment for port-wine stain: a systematic review and meta-analysis.

Pulsed dye laser (PDL) is the most commonly used method for port-wine stain (PWS); however, no studies have reported the safety of PDL. This review aimed to collect and summarize complications reported in relevant literature, assess complication rates in treating PWS with PDL, and explore the relevant influencing factors. A systematic review and meta-analysis were conducted to search for related studies in PubMed, Embase, and the Cochrane Library until August 2022. Two reviewers independently evaluated the risk of bias of included studies. Stata Software version 17.0 was used for the analysis. All complications reported in the literature are divided into acute phase complications and long-term complications. Overall pooled purpura, edema, crusting, blistering, hyperpigmentation, hypopigmentation, and scarring rates were 98.3%, 97.6%, 21.5%, 8.7%, 12.8%, 0.9%, and 0.2%, respectively. Although the acute adverse reactions were found to be common, the long-term permanent complications clearly have a lower frequency, and the occurrence of scarring is much lower than that initially thought. This indicates that effective protective measures after treatment are very important for preventing scar formation. Overall, PDL treatment for PWS shows a high level of safety and low chances of causing long-term complications.

Klippel-Trénaunay Syndrome and Developmental Coxa Vara in the Same Limb: A Case Report with a Review of the Literature.

We present a case of a 14-year-old girl who was first treated when she was 4 years old. She had progressive limping of the left lower limb from the age of 3 years. She was diagnosed to have developmental coxa vara of the left hip and treated by a subtrochanteric valgus osteotomy of the left femur. Later, she developed hypertrophy of the left upper and lower limbs. There were port-wine stains over the left lower limbs with multiple superficial varicosities. Her diagnosis was Klippel-Trénaunay syndrome (KTS). She is asymptomatic at the final follow-up. Both developmental coxa vara and KTS are rare conditions. We present this case to demonstrate the rarest combination of two rare conditions occurring in the same limb.

Efficacy and safety of 595-nm pulsed dye laser treating port wine stains in Vietnamese patients: analysis of 124 cases and optimal treatment regimens.

The purpose of this study is to determine the efficacy and safety of 595-nm pulsed dye laser (PDL) for port wine stains (PWS) treatment in Vietnamese patients. The study also analyzed the association between the response to treatment and the characteristics of patients and treatment regimens. Parallelly, the study contributed to further optimal treatment sessions for different subjects based on the data collected. One hundred twenty-five patients who underwent 595-nm PDL to treat PWS were included in the study, in which data from 124 patients was retrospectively analyzed. Data on demographic characteristics of patients, treatment regimens, and clinical improvement were collected. SPSS version 25 was used to analyze the relationship between associated factors and the response rate. The overall response rate of Vietnamese patients who had Fitzpatrick skin classification type III and IV was 73.4%. Age, gender, treatment sessions, and lesion positions were generally not associated with the response rate. The lesion grade was the sole element that affected the clinical improvement. The lesion grade 1 had the best response (100%) even after a short duration of treatment (six to ten treatments). Lesion grade 4 demanded over 16 treatments to reach > 60% of improvement. The lesion grades 1 and 2 could be blanched with regimen < 10 treatments while regimens exceeding 15 treatments should be carefully considered for lesions at grade 3 after evaluating associated conditions. Lesions at grade 4 demanded ≥ 16 treatments to reach acceptable outcomes. These results could help physicians establish a reasonable treatment strategy for patients.

Capillary malformations in a child caused by a novel HRAS mutation.

A 6-year-old boy with multiple capillary malformations of the port-wine birthmark (PWB) type on the right leg since birth presented with a varicose vein and segmental overgrowth of the affected leg. Genetic testing on affected skin confirmed the presence of a somatic novel pathogenic HRAS 30 bp in-frame duplication/insertion in the switch II domain. This case illustrates the phenotypic overlap of different genotypes and shows that somatic HRAS pathogenic variants, especially in-frame duplications/insertions, must be added to the list of the underlying causes in capillary malformations.

Effect of Hemoporfin-mediated photodynamic therapy in the treatment of facial port-wine stains on intraocular pressure.

BACKGROUND: Photodynamic therapy (PDT) is a potential treatment for port-wine stains (PWS), but its effects on intraocular pressure (IOP) have not been reported. This study evaluated the efficacy of PDT for facial PWS and analyzed the changes in IOP before and after treatment. METHODS: Data from 32 patients with facial PWS who underwent single PDT treatment at our department were collected. The patients were divided into three groups based on the location of the PWS. Group A (15 cases) involved the eyelid of the eye being measured; Group B (10 cases) was located near the eyes but did not involve the measured eyelid; and Group C (7 cases) was situated on the face but not near the eyes. IOP measurements were taken before and after treatment, and the efficacy and changes in IOP were analyzed. RESULTS: The overall efficacy rates of single PDT were 84.37 %, demonstrating superior efficacy for the pink type, age < 6 years, and skin lesions < 10 cm2 (P < 0.05). The higher IOP was observed on the side with eyelid involvement of PWS (P < 0.001). The IOP of the affected side in Group A decreased by 2.13 ± 2.10 mmHg on average after treatment, which was statistically significant compared with the other two groups (P<0.05). CONCLUSIONS: Eyelid involvement in PWS increases the risk of elevated IOP. Hemoporfin-mediated PDT can reduce the IOP in patients with PWS involving the eyelid within a safe range. PDT for facial PWS is considered to be safe and effective.

Dermatology Life Quality Index in Thai Patients with Facial Port-Wine Stains.

INTRODUCTION: Port-wine stains (PWS) are congenital capillary abnormalities caused by immature, venule-like vasculature that progressively dilates due to poor endothelial cell differentiation. PWS affects between 0.3% and 0.9% of newborns, with 90% of cases occurring on the face. Individuals with facial PWS and their parents had a significant negative impairment on their quality of life (QoL) and also suffered from psychological disabilities. METHODS: This was a cross-sectional questionnaire-based survey study in Thailand from July 2021 to April 2022. The questionnaires included demographic data, subjective evaluation (SE), and the Dermatology Life Quality Index (DLQI). The questionnaire was performed with a full scale and adjusted scale of validity and reliability test of DLQI using factor analysis and Cronbach's alpha. The study outcome was a subjective evaluation and DLQI in patients who received pulsed dye laser (PDL) treatment. RESULTS: Of the 54 patients, 35.2% (19) are male, and 64.8% (35) are female. Regarding age groups, 64.8% (35) are below 5 years old, and 35.2% (19) are older than 5 years. SE results showed that males evaluated an improvement of the facial PWS lesion significantly better than females (P < 0.05). The older age group graded the percentage of improvement better than the younger age group (P < 0.01). The result of the DLQI showed no difference in DLQI between gender. Older age result resulted in a significantly different DLQI compared with younger age (P < 0.01). Parent-reported DLQI improvement was less than self-reported DLQI improvement in patients with PWS treated with PDL (P < 0.05). Concerning the instrument of the study, the validity and reliability analysis of the DLQI questionnaire using factor analysis and Cronbach's alpha have been performed. The adjusted scale with the 5-item DLQI questionnaire is more appropriate in terms validity and reliability. CONCLUSION: This study demonstrates that facial PWS reduces the QoL as measured by DLQI. We discovered that the QoL of patients and parents with PWS was significantly impaired. The main influencing factors were older age, the improved perception between gender, and PDL treatments. In addition, we found only five questions that are reliable for PWS. The adjusted five-item DLQI questionnaires are more appropriate regarding validity and reliability. TRIAL REGISTRATION NUMBER: TCTR20230210001, COA no. si 1059/2020.

A retrospective 10 years- experience overview of dye laser treatments for vascular pathologies.

INTRODUCTION: The Flash-lamp pulsed dye laser (FPDL) is nowadays considered the most precise laser currently on the market for treating superficial vascular lesions. In this study, we gathered data from 10 years of experience regarding dye laser treatment of patients presenting vascular malformations such as telangiectasia, rhinophyma, port-wine stain, cherry and spider angioma and vascular tumours. METHODS: Subjects were enrolled from 2013 to 2023 based on the vascular anomalies they presented. They underwent different treatment sessions with the FPDL device. RESULTS: The age-range distribution by vascular anomaly confirmed that haemangiomas are typical in children while rhinophyma is a condition very common in older adults. A difference in sex distribution showed that pathologies such as telangiectasias typically affect women whereas rhinophyma is more frequent in men. Most of the treatments interested the face area but no permanent side effects were registered. CONCLUSIONS: Our 10 years of experience with FPDL demonstrated good results in a wide range of applications for the treatment of different vascular anomalies. The absence of long-term side effects and bearable pain during the treatment makes it a valuable solution for the resolution of benign tumours also in very young patients.

Comparative effectiveness among available treatments in difficult-to-treat port-wine stains (PWS): a Network Meta-Analysis of observational evidence.

BACKGROUND: Although pulsed dye laser (PDL) is the treatment of choice for port-wine stains (PWS), clinical resistance to PDL has been observed in 20-30% of cases. Several alternative treatment modalities have been introduced; however, there is still a lack of definite recommendations regarding the optimal treatment for difficult-to-treat PWS. OBJECTIVE: We aimed to systematically review and analyze the comparative effectiveness among treatments for problematic PWS. METHODS & MATERIALS: We systematically searched for comparative studies assessing treatments for patients with difficult-to-treat PWS through relevant biomedical databases until August 2022. A Network Meta-Analysis (NMA) was conducted to estimate the odds ratio (OR) for all pairwise comparisons. The primary outcome is the improvement of lesions of more than 25%. RESULTS: Of the 2498 studies identified, six treatments from five studies were available for NMA. Compared with 585 nm short-pulsed dye laser (SPDL), intense pulsed light (IPL) was the most effective in clearing lesions (OR 11.81, 95% CI 2.15 to 64.89, very low confidence rating), followed by 585 nm long-pulsed dye laser (LPDL) (OR 9.95, 95% CI 1.75 to 56.62, very low confidence rating). The 1064 nm NdYAG, 532 nm NdYAG, and LPDL >585 nm exhibited potential superiority over SPDL 585 nm, although statistical significance was not observed. CONCLUSIONS: IPL and 585 nm LPDL are likely to be more effective than 585 nm SPDL for treating difficult-to-treat PWS. Well-designed clinical trials are warranted to confirm our findings.

Concurrent Occurrence of Lobular Capillary Haemangioma and Port-Wine Stain: A Case Report and Literature Review.

A port-wine stain is a type of non-neoplastic hamartomatous malformation of capillary blood vessels, resulting from ectatic capillaries present from birth. Lobular capillary hemangioma is a form of capillary hemangioma that occurs from hamartomatous malformation of capillaries. In our report, we discuss the rare case of both port-wine stain and capillary haemangioma on the gingiva in a 22- year-old young male.

Hematoporphyrin Monomethyl Ether Photodynamic Therapy of Port Wine Stain: Narrative Review.

Port wine stain (PWS) is a congenital and progressive capillary malformation characterized by structural abnormalities of intradermal capillaries and postcapillary venules. The visible manifestation is often considered a disfigurement and the accompanying social stigma often causes serious emotional and physical impact. Hematoporphyrin monomethyl ether (HMME) is a newly authorized photosensitizer for treating PWS in China. Hematoporphyrin monomethyl ether photodynamic therapy (HMME-PDT) has successfully treated thousands of Chinese patients with PWS since 2017, and HMME-PDT may be one of the most promising strategies for the treatment of PWS. However, there are few reviews published about the clinical use of HMME-PDT. So in this article, we want to briefly review the mechanism, efficacy evaluation, effectiveness and influencing factors, and the common postoperative reactions and treatment suggestions of HMME-PDT in the treatment of PWS.