[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.

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.

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.

Efficacy of hemoporfin-PDT on port-wine stains: A retrospective analysis of 2952 cases.

OBJECTIVE: To conduct a retrospective analysis of Hemoporfin photodynamic therapy (HMME-PDT) in the treatment of port-wine stains (PWS). METHOD: A retrospective analysis was conducted based on the clinical data from March 2017 to December 2022, so as to summarize the demographic characteristics, clinical efficacy and adverse reactions. The effectiveness of HMME-PDT was examined with respect to treatment times, age, gender, subtype, and location of PWS lesions. RESULT: The age of the 2952 cases ranged from 8 months to 56 years old (median, 2.8 years), with 1419 males (48.07 %), and 1533 females (51.93 %). There were 669 cases of pink type (22.66 %), 2184 cases of purplish red type (73.98 %), and 99 cases of nodular thickening type (3.35 %). The prevalence location was face (88.04 %), neck (14.94 %), limbs and trunk. 1602 cases (54.27 %) had never received treatment, 661 cases (22.39 %) had been treated by pulse dye laser (PDL), 229 cases (7.76 %) had previously been treated by PDT, 296 cases (10.03 %) had received both the modalities. The 2952 cases completed totally 7996 HMME-PDT times. Cure rate and effective rate increased continuously with the number of treatments. The pink type has the highest cure rate and effective rate, followed by the purplish red type and the last was the nodular thickening type. The therapeutic effects are considerably influenced by age, subtype, and treatment site (P < 0.05). However, there was no significant difference in the effectiveness of HMME-PDT between both genders. The local adverse reactions after the first treatment included edema (97.73 %), itching (82.62 %), purpura-like change (79.51 %), crusts (24.59 %), infection (4.07 %), scars (1.08 %), hyperpigmentation (0.61 %), and depigmentation (0.41 %). Nausea and vomiting occurred in 2 juveniles and 1 young adult (5, 6 and 22 years old respectively) immediately after treatment, and did not interfere with the administration of the treatment. Patients aged 21-30 were found to have a 3.4-fold higher likelihood of undergoing HMME-PDT under general anesthesia compared to those aged 15 or younger. There was no distinct systemic adverse reaction, such as allergic responses, cardiovascular effects, neurological symptoms, hematological abnormalities, respiratory symptoms, or musculoskeletal issues. CONCLUSION: HMME-PDT is preferred in treating PWS, with relatively high effective rate and cure rate, mild local reactions and no distinct systemic adverse reaction.

Influential Factors in the Efficacy of Hemoporfin-Mediated Photodynamic Therapy for Port-wine Stains.

Hemoporfin-mediated photodynamic therapy (HMME-PDT) is commonly used in the treatment of port-wine stains (PWS). However, the influential factors for the efficacy of the treatment are not well defined. This study intends to observe the influential factors for the efficacy of HMME-PDT in the treatment of port-wine stains (PWS). A total of 551 patients with PWS of head and neck was enrolled in this retrospective study. Further screening the patients of facial PWS, 484 patients were chosen. Patients were treated with HMME-PDT. All patients received 1~3 sessions of treatment with 2~3-month intervals. We photographed the lesions before each session and 2~3 months after the last session. Ages, sessions, lesion subtypes, and previous treatment history were related to the response of HMME-PDT (P =0.032, P<0.001, P=0.012, P=0.003 respectively). Treatment sessions were the independent factor correlated with efficacy after 3 sessions of treatment. Patients with no treatment history targeting PWS showed higher efficacy than those were treated with laser or other photodynamic treatment (P<0.05). The efficacy was higher by increasing the sessions of treatment. The efficacy was higher for lesion on maxillary prominence area and mandibular prominence area that on frontonasal prominence area and optic vesicle area (P<0.05). HMME-PDT is an effective in the treatment of PWS. Patients received no previous treatment for PWS, total treatment sessions and lesion on maxillary prominence area and mandibular prominence area are positive factors.

Clinical efficacy and safety of two different hematoporphyrin monomethyl ether-mediated photodynamic therapy regimen in Chinese children with port-wine stain.

Hematoporphyrin monomethyl ether-photodynamic therapy (HMME-PDT) has achieved encouraging clinical outcomes in adult port-wine stain (PWS). Optimal treatment option for children with PWS was minimal. To compare whether the clinical effectiveness of HMME-PDT with the 5-min (fast) administration treatment regimen (FATR) was better than the 20-min (slow) administration treatment regimen (SATR) for PWS of children in vivo and in vitro. Thirty-four children with PWS were divided into two groups including FATR and SATR. The two groups received three times HMME-PDT, respectively. Treatment efficacy and safety were evaluated in vivo and in vitro. Erythema index (EI) was used to evaluate the clinical outcomes. Both FATR and SATR were effective and safe in children with PWS after HMME-PDT. There were significance differences between the two groups in reductions of EI after the second treatment (p < 0.001) and the third treatment (p < 0.001) with HMME-PDT. The serum HMME concentration reach the peak level at short time compare with SATR group. A significance increased superoxide levels were observed in FATR group compare to SATR groups in vitro (p < 0.05). Our study suggested that HMME-PDT was effective and safe for children with PWS, the therapy regimen with FATR was better in clinical efficacy than that of the SATR.

Analysis of related factors affecting hemoporfin-mediated photodynamic therapy for port-wine stain: A retrospective study.

BACKGROUND: Hemoporfin-mediated photodynamic therapy (HMME-PDT) is currently considered one of the most promising therapies for port-wine stain (PWS). However, the efficacy of this is very variable and needs further studies. METHODS: A total of 101 patients with PWS in the face, neck, or extremities who received at least 2 HMME-PDT sessions were included in the study, and correlations of efficacy with age, gender, locations, treatment sessions, and PDL treatment history were analyzed. RESULTS: The efficacy of HMME-PDT in patients with different ages, locations, and different numbers of prior PDL treatment showed constantly significant differences after 1/2/last session (p < .05). The number of treatments was associated with efficacy, and patients who received more than two sessions had a better response than those who underwent two sessions only (p < .001). Ordinal logistic regression analysis confirmed the above-mentioned associations. Nevertheless, patients of different sex, subtype, and lesion size showed no significant differences. CONCLUSIONS: Our studies demonstrated that HMME-PDT is effective in the treatment of PWS. The more prior PDL treatments, older age, lips involvement, PWS on limbs were adverse factors for Hemoporfin-PDT, while multiple HMME-PDT sessions can improve effective and response rate. Besides, ambient temperature and lesions temperature should be concerned, local cooling provides some relief from pain but may influence effect.

Hemoporfin-mediated photodynamic therapy for the treatment of port-wine stain: A multicenter, retrospective study.

BACKGROUND: Hemoporfin-mediated photodynamic therapy (Hemoporfin-PDT) has been approved for port-wine stain (PWS) in China in 2017. This study evaluated the efficacy and safety of Hemoporfin-PDT for PWS in a real life setting and investigated factors that influence the efficacy. METHODS: A multicenter retrospective study included patients with PWS who underwent Hemoporfin-PDT in 29 hospitals across China and completed at least two months of follow-up. The efficacy was evaluated based on patien photographs. RESULTS: A total of 1679 patients were included. After the first and second sessions of Hemoporfin-PDT, 63.5 and 75.3% of patients responded, respectively. The response rate of purple-type PWS was significantly lower than that of pink-type PWS (OR: 0.71, 95% CI: 0.54-0.94, P < 0.05), and there was no significant difference between thick- and pink-type (OR: 0.72, 95% CI: 0.42-1.22, P > 0.05). The response rate of PWS on the limbs was significantly lower than that on the mid-face (OR: 0.35, 95% CI: 0.23-0.53, P < 0.0001), while no significant difference was observed between PWS on the peripheral part of the face, neck or other parts of the body and PWS on the mid-face (P > 0.05). The response rate was lower in male patients with an age > 3 years or ≤ 6 years (P < 0.05). Previous treatment history did not affect the efficacy (P > 0.05). Hemoporfin-PDT was well tolerated. CONCLUSION: Patients with PWS have a good response and good tolerance to Hemoporfin-PDT.

General anaesthesia for photodynamic therapy of port-wine stain in children: A retrospective study.

AIMS: This report intended to assess the safety and efficiency of general anaesthesia with preserved spontaneous breathing for pain management in photodynamic therapy (PDT) of port-wine stains (PWS) in paediatric patients. METHODS: This study included 1960 Hemoporfin PDT procedures performed under general anaesthesia on 560 PWS patients. Medical records were retrospectively analysed. All of the procedures performed under general anaesthesia with preserved spontaneous breathing. RESULTS: The patients comprised males (43.93%) and females (56.07%). Ninety percent of cases were ASA class I, and 10% were class II, no case was class III or higher. Adverse events accompanying general anaesthesia included postoperative irritability (8.98%), carbon dioxide pressure (PCO2) >50 mmHg (15.97%), movement during surgery (6.98%), vomiting (0.2%), laryngospasm (0.2%), unplanned endotracheal intubation (0.05%), upper airway obstruction (0.05%), and hypoxia (0.1%). The FLACC score was <4 points in 84% of cases and 4∼6 points in 16% of cases. CONCLUSIONS: General anaesthesia with preserved spontaneous breathing has few complications and appears safe and feasible for PDT in most children with PWS.

Experimental study of combined photodynamic and photothermal therapy in the treatment of port wine stain.

Laser therapy has become the golden standard of port wine stain (PWS), but complete clearance of resistant PWSs is still difficult. The application of photodynamic therapy (PDT) in the treatment of PWS shows potential in clinical practice, especially for large-area and deep lesions. In this work, in vivo animal experimental investigation on the coupling effect of PDT with multi-pulse laser (MPL) irradiation on the treatment of PWS was conducted by using a dorsal skin window chamber model. Through visualization of the thermal response of blood vessels and damage evaluation, it is found that the combination of PDT with MPL results in 96.2% more vascular injury than PDT alone and 90% more than MPL alone, thus reducing side effects such as purpura after treatment. The combined therapy also has the benefit of large treatment area, uniform fading effect, shortened light duration, and reduced photosensitizer admit.

Retrospective analysis of Hemoporfin-mediated photodynamic therapy in the treatment of naïve port-wine stains.

BACKGROUND: Hemoporfin-mediated photodynamic therapy (Hemoporfin-PDT) is a safe and effective treatment modality for port-wine stain (PWS). However, there is still no consensus about the influential factors for the efficacy of the treatment. This study investigated the influential factors associated with the efficacy of Hemoporfin-PDT. METHODS: We retrospectively analyzed 321 PWS patients who underwent Hemoporfin-PDT at our center from August 2017 to July 2021. The correlation between efficacy versus sex, age, location, type of PWS, treatment numbers, and the lesion size were analyzed. RESULTS: The numbers of treatment sessions undertaken were associated with the response to therapy, and compared with patients who received one session, patients who received two or more sessions showed a better response (ORadj=2.46, 95%CI, 1.49-4.07; ORadj=6.01, 95%CI, 3.38-10.70, P<0.001). The effect on central face, peripheral face, and neck was superior to the extremity and trunk, respectively (P<0.001). The lesion size smaller than and equal to 25 cm² showed a better effect than those whose lesion size was larger than 64 cm² (ORadj=1.92, 95%CI, 1.03-3.57, P=0.040). However, other variables, including sex and age, were not associated with the efficacy of the treatment. CONCLUSIONS: Hemoporfin-PDT is an effective and safe treatment for PWS. The number of treatments was a favorable factor for Hemoporfin-PDT, smaller lesion sizes showed a better effect than the larger one, and the location of extremity and trunk was a negative factor.

Treatment Update of Port-Wine Stain.

We read with great interest the recent publication by Fölster-Holst et al1 in the May issue of Journal of Drugs in Dermatology, which offered a brief update on the treatment of port-wine stains.

Histological Characteristics of Port-Wine Stains with Complete Regression After Photodynamic Therapy Treatment: A 7-Year Follow-Up.

Background: Vascular-targeted photodynamic therapy (PDT) is an effective alternative treatment choice for port-wine stains (PWSs). The histological characteristics of PWSs after PDT treatment have not yet been reported. Objective: To investigate the morphological features of PWSs treated by PDT and define the histopathological characteristics of PWS that achieve clinical cure. Methods: Thirteen patients with facial PWSs, who presented with complete regressive PWS lesions after a mean of 4.38 (standard deviation = 4.907) sessions of PDT. Post-treatment biopsy samples were obtained from each patient. The number of blood vessels, vascular diameter, and depth were measured and compared in all samples of PDT-regressive sites, PDT-resistant sites, and normal skin. Results: Within the 7-year follow-up after PDT, there was no recurrence in the regression area of PDT. In the PDT-regressive sites, within 800 µm of the dermal-epidermal junction, the dilated vessels were occluded and remained fissure-like after PDT. Conclusions: When the vascular lesions within 800 µm of the dermal-epidermal junction were closed after PDT, a stable clinical cure (no recurrence) was achieved.

Hematoporphyrin monomethyl ether photodynamic therapy for the treatment of Sturge-Weber syndrome and large segmental facial port-wine stain.

Hematoporphyrin monomethyl ether (HMME) is a newly authorized photosensitizer for the treatment of port-wine stain (PWS) in China. However, no research on its efficacy for treating PWS lesions of Sturge-Weber syndrome (SWS) has been made. To assess the efficacy and safety of HMME-photodynamic therapy (PDT) in the treatment of SWS and simple large segmental facial PWS. Medical records of patients with SWS and large segmental facial PWS were reviewed. Efficacy was evaluated according to color blanching and graded as excellent (≥75%), good (50%-74%), fair (25%-49%), and poor (≤24%). Adverse events were analyzed. Nineteen patients with SWS and 33 patients with large segmental facial PWS were analyzed. 52.6% SWS and 69.7% PWS patients (p > .05) achieved at least 25% improvement. Common adverse events included short-term pain, edema, pruritus, exudation, and scab. No severe adverse event occurred. HMME-PDT was effective and safe for SWS and large segmental facial PWS.

Successful management of an arteriovenous malformation with trametinib in a patient with capillary-malformation arteriovenous malformation syndrome and cardiac compromise.

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is an autosomal dominant condition characterized by multifocal, noncontiguous pink patches on the skin that often have a surrounding pale halo. In some cases, an association with a fast flow, arteriovenous malformation (AVM) can be identified. Here, we describe a case report of a 16-year-old woman with CM-AVM syndrome and significant cardiac compromise successfully treated with trametinib, a mitogen-activated protein kinase (MEK) inhibitor.

Efficacy of hemoporfin photodynamic therapy for pulsed dye laser-resistant facial port-wine stains in 107 children: A retrospective study.

BACKGROUND: Port-wine stains occur in 0.3-0.5% newborns, mainly on the face and neck. Pulsed dye laser is recognized as the gold standard treatment; nevertheless, it is associated with a low cure rate and a high recurrence rate. AIMS: This study aims to evaluate the efficacy of hemoporfin photodynamic therapy for pulsed dye laser-resistant port-wine stains in children. METHODS: We studied 107 children who received hemoporfin photodynamic therapy for port-wine stains on the face and neck that were resistant to pulsed dye laser. After intravenous injection of 5 mg/kg hemoporfin, the local lesion was irradiated with 532 nm LED green light for 20 min with a power density of 80-100 mW/cm2. A total of 65 patients were given a second treatment after eight weeks. The efficacy and therapeutic responses were recorded at four days and eight weeks after each treatment. RESULTS: The efficacy was positively correlated with the number of treatments received; two treatment sessions yielded significantly better results compared to a single treatment with a response rate of 96.9%, a significant response rate of 50.8% and a cure rate of 21.5%, respectively (P < 0.001). After two treatment sessions, the efficacy was negatively correlated with age (P = 0.04). The efficacy for port-wine stains located on the lateral part was better than that of the central face (P = 0.04). The efficacy for the pink type was better than that for the red and purple types (P = 0.03). No allergic or systematic adverse reactions were reported. LIMITATIONS: No objective measurement data were available. CONCLUSION: Hemoporfin photodynamic therapy is effective and safe for pulsed dye laser-resistant facial port-wine stains in children.

Topical metformin suppresses angiogenesis pathways induced by pulsed dye laser irradiation in animal models.

Pulsed dye laser (PDL) is the first-line treatment for port-wine stain (PWS). However, only a small portion of the lesions could be completely cleared by PDL treatment, which might be related to the regeneration and revascularization of the vascular structures after laser irradiation. Recently, it is believed that the suppression of regeneration and revascularization of photocoagulated blood vessels can achieve a better therapeutic outcome. We use rabbit ear and SD rat as the animal models to investigate whether PDL-induced angiogenesis can be suppressed by topical metformin. Our results showed that topical application of metformin can effectively suppress the PDL-induced early stage of angiogenesis via inhibition of the AKT/mTOR/P70S6K pathway in animal models.

Hematoporphyrin monomethyl ether-mediated photodynamic therapy for phakomatosis pigmentovascularis type â ¡: A case report.

Phakomatosis pigmentovascularis (PPV) is a rare congenital syndrome characterized by capillary malformation (mainly port-wine stains, PWS) and pigmentary nevi with or without extracutaneous signs. Efforts are ongoing to develop laser therapy to treat vascular and pigmentation abnormalities in PPV. The status of pulsed-dye lasers in the treatment of PWS has been challenged by vascular-targeted photodynamic therapy (PDT). Hematoporphyrin monomethyl ether-mediated PDT (HMME-PDT) has become a research hotspot for PWS. The long-term efficiency and safety of HMME-PDT for vascular lesions coexisting with pigmented lesions in PPV have not been reported. We report a pediatric case of PPV type Ⅱa presenting with PWS and nevus of Ota efficiently treated through a 3-session HMME-PDT. After treatment, the PWS lesions regressed significantly without noticeable adverse reactions or recurrence. Besides, we share the dermoscopy data of PPV lesions and discuss the clinical manifestations and therapeutic strategies for PPV based on existing related literature.