Novel RASA1 mutations in Japanese pedigrees with capillary malformation-arteriovenous malformation.

Capillary malformation-arteriovenous malformation (CM-AVM, MIM#608354) is a rare autosomal dominant disorder characterized by multiple cutaneous capillary malformations co-occurring with fast-flow vascular anomalies, such as arteriovenous malformation or fistula. Despite the identification of RASA1 as the first causative gene in Western patients with CM-AVM, there have been no literature reports of Japanese patients with this gene mutation. We herein report two Japanese pedigrees harboring multiple affected members with CM-AVM. Whole-exome sequencing in the two probands identified novel heterozygous mutations in RASA1, which were co-segregated with the disease in each family and were not reported in large-scale sequencing databases. One was a frameshift mutation and the other a splice-site mutation causing aberrant splicing, confirmed by a minigene assay. There were no other genes commonly disrupted among these probands. RASA1 was a major causative gene even in Japanese patients with CM-AVM, although obvious locus heterogeneity was known for this disease.

Shorter Treatment Intervals of East Asians with Port-Wine Stain with Pulsed Dye Laser Are Safe and Effective-A Prospective Side-by-Side Comparison.

OBJECTIVE: To compare the safety and efficacy of pulsed dye laser (PDL) at different intervals for the treatment of East Asians with Port-Wine Stain (PWS). BACKGROUND: The population of East Asians around the world is about 1.6 billion, and they are considered to have more melanin in their skin compared with Caucasians. Nevertheless, no studies about the optimal treatment intervals for East Asians with PWS have been carried out. METHODS: We prospectively investigated 39 East Asian patients with untreated PWS. Half of the PWS lesion was randomly allocated to be treated at 3 weeks and the other half at 6 weeks. Both halves of the PWS were treated three times in total. The efficacy outcome 2 months post final treatment was evaluated by visual and chromameter evaluation. RESULTS: The average blanching rate was 40.27% and 44.17% for PDL treatments at the 3- and 6-week interval sites, respectively (p > 0.05). No patient developed scarring or permanent pigmentation change. LIMITATIONS: There was no age criteria involved in the enrollment of patients in this study. Additionally, there is no comparison with long-term treatments at different intervals. CONCLUSIONS: PDL treatment at 3-week interval proved to be safe for East Asians with PWS. This can reduce the total duration of the course of treatments and had no increase in side effects compared with the standard interval treatments.

Successful treatment of two pediatric port wine stains in darker skin types using 595 nm laser.

BACKGROUND AND OBJECTIVE: Port wine stain (PWS) is a congenital vascular malformation of skin involving post-capillary venules, which commonly occurs on the face. While successful treatment has been reported with Caucasian, Hispanic, and Asian skin, physicians have battled treating these progressive lesions in patients of darker skin color, as the targeted chromophore (hemoglobin) shares a similar absorption coefficient as melanin. There are no reports of favorable outcomes in African-American children or adults. Although treatment in darker skin types has been previously discouraged we present a case series of patients of African descent with port wine stains treated using a pulsed-dye laser (Vbeam Perfecta, Candela Laser,Wayland, Mass) with significant improvement and no complications. STUDY DESIGN/MATERIAL AND METHODS: Presentation of two pediatric patients of African descent (skin types 4 and 5) ages 1 month and 4 years old seen and treated in our office using a pulsed-dye laser until resolution. Laser parameters were spot size 10 mm; fluence 7-8.25 J/cm2; wavelength 595 nm; pulse duration 1.5 Millisecond with dynamic cooling. RESULTS: Resolution of the port wine stain without complication. CONCLUSION: This early approach represents a new and safe therapeutic option for treating port wine stains in this patient population. To our knowledge, the successful use of pulsed dye laser for the treatment of port wine stain in patients of African descent without complications has not yet been reported.

Treatment of vascular skin lesions with the variable-pulse 595 nm pulsed dye laser.

BACKGROUND: In the dermatology field, variable-pulse 595 nm pulsed dye lasers (PDLs) are now being widely used to treat vascular skin lesions. However, there is little information available on variable-pulse 595 nm PDL treatment of dark-skinned patients. OBJECTIVE: The objective of this study was to evaluate the outcome of variable-pulse 595 nm PDL treatment on Korean patients. METHOD: Two hundred thirty-nine patients (Fitzpatrick skin phototypes III to V) with vascular skin lesions, such as nevus flammeus, telangiectasia, or hemangioma, were included in this study. All patients were treated with a variable-pulse 595 nm PDL, and the outcomes were assessed by comparing preoperative and postoperative photographs. RESULTS: The average number of treatments per patient was 4.29, and 51.9% of patients showed a good (51-75% clearance) to excellent (76-100% clearance) response. For nevus flammeus, 48.0% of the patients achieved good to excellent results. The gender and age of the patients did not influence the clinical response; however, lesions of the head and neck were found to respond more favorably to treatment. For telangiectasia, 78.0% of patients showed good to excellent results, and, again, the gender and age of the patients did not alter the treatment outcome. For hemangioma, the male to female ratio of patients was 1.0:3.1 and 54.1% of the patients achieved a good to excellent response. Superficial hemangioma showed a better clinical response than deep hemangioma, and the lesions of younger patients responded more favorably than those of older patients. CONCLUSION: The variable-pulse 595 nm PDL was found to be effective for treating several vascular skin lesions in dark-skinned patients. However, there were differences in treatment outcome owing to disease, age, and the location of the lesions.

Prospective study of pulsed dye laser in conjunction with cryogen spray cooling for treatment of port wine stains in Chinese patients.

BACKGROUND: Pulsed dye laser (PDL) in conjunction with cryogen spray cooling (CSC) is effective in improving efficacy and safety for treatment of port wine stains (PWSs) in whites. However, for dark-skinned patients such as Chinese, only retrospective studies have been performed. OBJECTIVES: To compare prospectively clinical efficacy in terms of blanching and acute and long-term adverse effects of PDL alone and PDL-CSC for treatment of PWSs in Chinese patients. METHODS: Thirty-five Chinese patients (13 males and 22 females) were recruited, and 131 treatments were performed. Half of the test area on the PWS was treated with PDL alone, and the contralateral half was treated with PDL-CSC. The degree of PWS blanching was objectively assessed by spectrophotometer. Skin textural changes were detected by cutometer. All measurements were taken at baseline and before each subsequent laser treatment. Patients were interviewed immediately after treatment and again the following week using a visual analog scale questionnaire to assess the degree of pain and swelling. Occurrence of blisters was noted during each follow-up visit. Patients were evaluated for evidence of long-term adverse effects such as dyspigmentation and scarring after three treatments. RESULTS: Statistically significant higher fluences were used on the PDL-CSC-treated group. The percentage change in the spectrophotometer a* value was significantly greater using PDL-CSC, indicating that there was more PWS blanching after treatment. There was no significant difference in the incidence of skin textural changes after three treatments with PDL alone or PDL-CSC. The immediate pain scores were significantly higher for PDL alone than with PDL-CSC. Blisters were significantly more common on the area treated using PDL alone than PDL-CSC. The overall incidence of long-term adverse effects was not significantly different between the PDL alone and PDL-CSC treatments. PDL-CSC was also the preferred treatment modality for most patients. CONCLUSIONS: PDL-CSC was more effective than PDL alone for blanching of PWS in Chinese patients. Moreover, PDL-CSC was better tolerated and resulted in a lower incidence of acute adverse effects such as blistering.

Clinical application of lasers in Asians.

BACKGROUND: Laser surgery for Asians differs from that for Caucasians in several important respects. In Asians, some conditions such as nevus of Ota are frequently seen and certain adverse reactions, especially postinflammatory hyperpigmentation, tend to be more common. OBJECTIVE: This article reviews the use of different types of lasers and intense pulsed light (IPL) sources for the treatment of Asian patients. METHODS: Various cutaneous conditions amenable to laser treatment, including lentigines, nevus of Ota, acquired bilateral nevus of Ota-like macules, port-wine stains, and acne scarring, are discussed. Strategies for the management of postinflammatory hyperpigmentation are offered. RESULTS: Appropriate selection and careful planning of the treatment can lead to excellent clinical outcome. CONCLUSION: Lasers and intense pulsed light sources are important tools for the treatment of a wide range of cutaneous conditions in Asians.

Copper vapour laser treatment of port-wine stains in brown skin.

Forty-seven Korean patients with port-wine stains were treated with a copper vapour laser and clinical responses were assessed at three months after the last treatment by comparing photographs taken before each treatment. The immediate histologic changes within 15 min after laser treatment were also observed by routine H&E and nitroblue tetrazolium chloride staining. When we treated port-wine stains with minimal whitening doses of 6-8 J/cm2, no or slight colour changes were obtained. Thus, all port-wine stain lesions in this study were treated with non-specific energy densities ranging from 10-20 J/cm2. Good to excellent results were obtained in 18 (38.2%) of 47 Korean patients with port-wine stains. Repeated treatment can continue to reduce colour. Darker lesions (purple or red) are more likely to result in a marked colour change. At above threshold dose, there was wedge-shaped diffuse coagulation necrosis and loss of viability of the epidermis and underlying dermis. Even though copper vapour laser treatment of port-wine stains in brown skin is not as selective as in white skin because of epidermal melanin, our clinical data demonstrate the usefulness of the copper vapour laser for the treatment of port-wine stains in brown skin.