Hypothalamic-pituitary dysfunction in Sturge-Weber syndrome: case report and review of the literature.

OBJECTIVES: Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder that is characterized by a segmental dermatomal facial port-wine stain birthmark and is frequently accompanied by ipsilateral brain and eye abnormalities. We present a case of a patient with SWS who exhibited hypogonadotropic hypogonadism, growth hormone (GH) deficiency, and central hypothyroidism at the age of 20 despite the absence of radiographic findings in the pituitary and hypothalamus. CASE PRESENTATION: A 20-year-old male with SWS with epilepsy and Klippel-Trenaunay syndrome presents with delayed pubertal development, short stature, and obesity. Upon further examination, he was found to have biochemical and clinical evidence of hypogonadism, hypothyroidism, and GH deficiency. A pituitary MRI displayed no abnormalities of the pituitary or hypothalamus. Treatment with testosterone cypionate and levothyroxine was initiated. Despite successful pubertal induction, IGF-1 levels have remained low and treatment with recombinant human growth hormone (rhGH) is now being considered for metabolic benefits. CONCLUSIONS: This case emphasizes the importance of endocrine evaluation and treatment of hormonal deficiencies in patients with SWS despite the absence of radiographic findings.

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.

Vascular uses of LP1064 applicator on the harmony XL pro device.

INTRODUCTION: Vascular lesions of the lower extremities and face, such as varicose veins and telangiectasias, are a common dilemma for the dermatologist. In recent years, laser therapy has emerged as a viable treatment option for these vascular anomalies. MATERIALS AND METHODS: Although there are several types of lasers, the 1064-nm Nd:YAG in particular is popularly selected for its safety profile and versatility. The longer 1064 nm wavelength penetrates deeper into the skin while also being less absorbed by hemoglobin and melanin, thus resulting in minimized damage to surrounding structures and less pigmentation changes. The new LP1064 applicator on the Harmony XL Pro Device is one such laser. RESULTS: Numerous publications have corroborated the efficacy of 1064 nm Nd:YAG lasers. These studies cite at least over 75% of patients experiencing significant improvement in common vascular lesions. Efficacy of this laser is also seen for other vascular lesions such as port wine stains, hemangiomas, venous lakes, poikiloderma of Civatte, and angiokeratomas. Overall, the reported studies also show a low incidence of adverse events. CONCLUSION: The 1064 nm Nd:YAG laser, such as the Harmony LP1064 applicator, is a safe and effective tool to treat vein anomalies of the face and leg. Although commonly used for vein ablation, it has demonstrated a robust response in other indications as well.

Largest comparative analysis: Novel large spot size 595 nm, high-energy, pulsed dye laser reduces number of treatments for improvement of adult and pediatric port wine birthmarks.

OBJECTIVE: Port wine birthmarks (PWBs) are vascular malformations affecting 0.3%-0.5% of newborns with the tendency to persist into adulthood without adequate treatment of the heterogenous ectatic vessels. This study compares treatment outcomes and parameters of the prior generation pulsed dye laser (PPDL) and the larger spot novel generation pulsed dye laser (NPDL) to establish whether a larger spot size laser provides greater clearance with fewer treatments. METHODS: One hundred and sixty patients were treated with either the PPDL (80 patients) and NPDL (80 patients) with retrospective review of age, body site, laser treatment parameters, number of treatments, and improvement following laser therapy. RESULTS: Patients treated with PPDL were older on average than patients treated with NPDL (mean 24.8 ± 19.7 vs. mean 17.1± 19.3 years, p < 0.05). The majority of lesions treated with PPDL were located on the face and neck, whereas truncal and extremity sites were more frequently treated with the NPDL. Use of NPDL was associated with a mean maximum spot size of 13.1 mm and mean maximum fluence of 7.3 J/cm2 with pulse durations of 0.45-3 ms, whereas use of the PPDL was associated with a mean spot size of 10.8 mm and mean maximum fluence of 8.8 J/cm2 with pulse durations of 0.45-6 ms. Fifty percent improvement was seen with 8.8 PPDL treatments compared to 4.3 NPDL treatments (p ≤ 0.01) with no significant difference in overall mean improvement between both devices at the chosen parameters. Multiple regression analysis showed that device type, not age or lesion location, was the only statistically significant independent variable to affect the endpoint of at least 50% improvement of the lesion. CONCLUSIONS: Use of the larger spot NPDL is associated with achieving 50% improvement with fewer treatments.

Treating pediatric port-wine stains in aesthetics.

A port-wine stain (PWS) is a vascular birthmark present in 0.3% to 0.5% of newborns. If untreated, this erythematous patch will grow proportionally with the child to thicken and darken with age. PWSs have implications for the child's quality of life for many years, with cosmetic, medical, and psychosocial disability. Controversy exists in many aspects surrounding laser treatment of these birthmarks in the pediatric population. We have reviewed the clinical features as well as the historic and current laser treatment of PWS. We have also examined the current hot topics of debate surrounding the treatment of PWS in the pediatric population. These controversies include the patient age of treatment initiation, the long-term psychologic impact, the use of general anesthesia, the application of eye shields, and alternative treatments for recalcitrant PWS. We have concluded with a discussion on the future directions of management and treatment.

Triple pass laser therapy for recalcitrant facial port wine stains.

Patients with recalcitrant facial port wine stains (rfPWS) can be challenging to manage, often leaving the clinician with difficult decisions for treatment options. 'Triple therapy' consists of using three different laser wavelengths at each treatment setting. The evidence on outcomes is limited as this treatment approach has not been previously reported to the best of our knowledge. Children who received triple therapy at least once for rfPWS, and for whom SIAscopy readings had been taken, were retrospectively identified. SIAscope readings were compared before the first triple therapy treatment and at final the most recent clinical follow-up. The clinical appearance was also assessed using a Visual Analogue Scale comparing clinical photographs taken before triple therapy to those taken at the most recent clinical follow-up. A total of 47 children were identified and included in our review. The SIAscope readings showed an overall significant (p < 0.001) lightening with 39 (83%) showing lightening and 8 (17%) patients showing a darkening. Scores using the VAS also showed improvement with 55% experiencing an improvement in their clinical appearance, 38% showing no visible change and 6% appearing to have worsened. Triple therapy can offer improvement of rfPWS which have failed to respond to single wavelength laser therapy. SIAscopy and VAS scores correlate well in assessing clinical response; however, the added clinical benefit of SIAscopy in vascular laser clinics remains uncertain.

Imaging and Pathological Characteristics of Port-Wine Stain Patients with Tissue Hypertrophy Before Laser Therapy: Retrospective Data.

Background: Port-wine stain (PWS) patients may simultaneously have accompanied soft tissue hypertrophy. The outcome of laser therapy can be poor. Objective: To study the imaging and histopathological characteristics of PWS patients with facial overgrowth. Materials and methods: We retrospectively assessed the effect of therapy on a subset of PWS patients with facial overgrowth. The degree of hypertrophy and the density of enhanced signals on T1-weighted magnetic resonance imaging (MRI) were independently graded by two radiologists using a quartile scale. Biopsies/resection of tissue deep to the facial muscle was reviewed and compared with flat PWS. Results: Thirty-two PWS patients with facial hypertrophy and 15 patients with flat PWS were included. MRI revealed a statistically significant correlation between the degree of hypertrophy and the density of enhanced signals (3.02 ± 0.92 vs. 2.47 ± 0.69; p < 0.01). Histological features of a subset of patients showed that vascular malformations existed in the dermis and also in the subcutaneous fat and muscle with much larger vessel diameters (fat, 0.048 vs. 0.020; muscle, 0.035 vs. 0.017) and thicker vessel walls (fat, 0.014 vs. 0.006; muscle, 0.010 vs. 0.006) (both p < 0.05). Conclusions: The imaging and pathological findings indicate that capillary malformation in subcutaneous tissue might be a major cause of poor therapeutic effect of laser therapy for PWS. Clinical trial registration no.: ChiCTR1800014278.

Combination Therapy of Pulsed Dye Laser With Intense Pulsed Light in Port-Wine Stain Treatment: A Prospective Side-by-Side Comparison.

BACKGROUND: Pulsed dye laser (PDL) treatment currently represents the mainstream choice for port-wine stain (PWS) treatment in accordance with selective photothermolysis. However, most PWS lesions cannot be removed despite several treatments. Intense pulsed light (IPL) is reportedly an effective alternative to PDL for PWS treatment. No studies have thus far been reported on the combination therapy of PDL with IPL in PWS treatment. OBJECTIVE: This study evaluated the efficacy and safety of PDL with IPL for PWS treatment. METHODS: A total of 33 PWS lesions underwent 3 treatment sessions. Each PWS was divided into IPL + PDL, PDL, and untreated sites. Therapeutic outcomes were evaluated by visual assessment and chromametric assessment 3 months after the final treatment. RESULTS: The overall average blanching rates were 36.2% and 32.6% at the sites treated with IPL + PDL and PDL, respectively (p > .05). No permanent side effects were reported. CONCLUSION: In this laser setting, although IPL + PDL is a safe and effective PWS treatment, no significant improvement in the efficacy was observed using IPL + PDL in contrast to PDL alone.

Treatment Update of Port-Wine Stain: A Narrative Review.

BACKGROUND: Port-wine stain (PWS) is a congenital vascular malformation affecting 0.3–0.5% of normal population. These characteristic lesions arise due to the interplay of vascular, neural, and genetic factors. Treatment options include lasers, cosmetic tattooing, electrotherapy, cryosurgery, derma-abrasion, and skin grafting; however, none of these treatment alternatives appears to be satisfactory and is unable to provide consistent, satisfactory responses or even complete cures. Currently, laser is the treatment of choice, as it is comparatively safe and more effective than other procedures. The most commonly used modality is pulsed dye laser (PDL). The literature research includes peer-reviewed articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) to January 2020 and reference lists of respective articles. Only articles published in English language were included. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5005.

Adjuncts to pulsed dye laser for treatment of port wine stains: a literature review.

Noninvasive pulsed dye laser is the current gold standard for the treatment of port wine stains. However, most port wine stains are not completely cleared after pulsed dye laser therapy, owing to insufficient photocoagulation and laser-induced vascular regeneration and reperfusion. Several studies have explored approaches designed to improve treatment efficacy. This integrative literature review summarizes the results of clinical and animal studies published between 2004 and 2021. Pulsed dye laser has been administered in combination with photoelectric devices (the neodymium: yttrium-aluminum-garnet lasers, dual-wavelength 1064-/595-nm laser irradiation, fiberoptic Nd-YAG laser, photodynamic therapy, and radio frequency), and drugs (rapamycin, imiquimod, timolol, axitinib, endothelin receptor antagonist, artificial red blood cells and oxymetazoline). The initial results suggest that combination therapy is a direction worth exploring in the future. Further large prospective, blinded and controlled multicenter clinical trials with longer follow-up period are required to obtain more robust evidence.

Consensus Statement for the Management and Treatment of Port-Wine Birthmarks in Sturge-Weber Syndrome.

Importance: Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome involving the skin, brain, and eyes. Consensus recommendations for management are lacking. Objective: To consolidate the current literature with expert opinion to make recommendations that will guide treatment and referral for patients with port-wine birthmarks (PWBs). Evidence Review: In this consensus statement, 12 nationally peer-recognized experts in dermatology with experience treating patients with SWS were assembled. Key topics and questions were formulated for each group and included risk stratification, optimum treatment strategies, and recommendations regarding light-based therapies. A systematic PubMed search was performed of English-language articles published between December 1, 2008, and December 1, 2018, as well as other pertinent studies identified by the expert panel. Clinical practice guidelines were recommended. Findings: Treatment of PWBs is indicated to minimize the psychosocial impact and diminish nodularity and potentially tissue hypertrophy. Better outcomes may be attained if treatments are started at an earlier age. In the US, pulsed dye laser is the standard for all PWBs regardless of the lesion size, location, or color. When performed by experienced physicians, laser treatment can be safe for patients of all ages. The choice of using general anesthesia in young patients is a complex decision that must be considered on a case-by-case basis. Conclusions and Relevance: These recommendations are intended to help guide clinical practice and decision-making for patients with SWS and those with isolated PWBs and may improve patient outcomes.

Light-based treatment of pediatric port-wine birthmarks.

Port-wine birthmarks (PWBs) are progressive vascular malformations with significant disfigurement and psychosocial morbidity; early light-based treatment has shown improved outcomes in the pediatric population. Somatic mosaic mutations underly the progressive nature of PWBs and explain the significant differences in response and heterogeneity of vessel architecture in the pediatric population when compared to the adult cohort. Here, we summarize a review of pediatric specific literature on the various light-based treatment modalities, including pulsed dye laser, near-infrared lasers, and intense pulsed light, providing the various indications, tips, advantages, and disadvantages for the pediatric dermatologist.

Hematoporphyrin monomethyl ether photodynamic therapy for the treatment of facial port-wine stains resistant to pulsed dye laser.

BACKGROUND: Pulsed dye laser is the first treatment choice for port-wine stains. However, as some facial port-wine stains are resistant to this modality, we evaluated the efficacy and safety of hematoporphyrin monomethyl ether (hemoporfin) photodynamic therapy for the treatment of such resistant port-wine stains. METHODS: Patients were treated with two sessions of hemoporfin photodynamic therapy in our department. Patients received an intravenous injection of hematoporphyrin monomethyl ether (5 mg/kg) followed by 532 nm LED green light therapy. Three physicians graded the improvement in the port-wine stain, using a 4-level scale. Patients' satisfaction, reaction to treatment, and adverse effects were evaluated. RESULTS: Thirty-one patients (mean age, 23.9 ± 11.9 years, range, 3-48 years) were enrolled in this study. Hypertrophic lesions accounted for 48.4% of port-wine stain, with 80.6% of lesions being larger than 40 cm2. With regard to location, 41.9% were located on the central face and 32.3% involved a mix of the central and peripheral face. After one session, a treatment response was identified in 87.1% of cases, with the response deemed 'significant' in 29.0%. After two sessions, these rates increased to 100.0% and 61.3%, respectively. The clinical effect after two sessions was significantly greater than that after one session. Treatment reactions and adverse effects were well tolerated, and included pruritus, burning sensation, pain, edema, purpura-like change, blister, crust, and hyperpigmentation. CONCLUSIONS: Hemoporfin photodynamic therapy is a promising treatment for port-wine stains resistant to pulsed dye laser therapy.

Retrospective study of photodynamic therapy for pulsed dye laser-resistant port-wine stains.

Pulsed dye laser-resistant port-wine stains present a therapeutic challenge. The aim of this study was to evaluate the efficacy and safety of photodynamic therapy for treating these lesions. A total of 67 patients with pulsed dye laser-resistant cervicofacial port-wine stains were retrospectively assessed after undergoing photodynamic therapy mediated with a combination of hemoporfin and 532-nm light. For objective evaluation of photodynamic therapy efficacy, first, the colorimetric changes in the port-wine stain lesions were evaluated according to the L*a*b* color coordinate system, then the values of color changes (ΔE) and blanching rate were calculated. For subjective evaluation of improvement, photographs taken before and after photodynamic therapy were evaluated by three independent assessors blindly. Patient satisfaction was also used as a factor in the subjective evaluation. Adverse events were recorded after treatment. The median ΔE decreased significantly from the pretreatment value of 13.42 to 9.90 at the 2-month follow up (P < 0.001). The median blanching rate of port-wine stains was 28.04% after an average of 1.21 sessions of photodynamic therapy. Based on the overall visual assessment, 46.2% patients showed excellent or good levels of improvement (>50% color blanching). Adverse events were minimal, transient and self-limiting. In conclusion, photodynamic therapy serves as an alternative means to treat pulsed dye laser-resistant port-wine stains.

Good response to pulsed dye laser in patients with capillary malformation-arteriovenous malformation syndrome (CM-AVM).

Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is an autosomal dominant disorder caused by heterozygous mutations in RASA1 and EPHB4. Capillary stains in CM-AVM are compatible with Schöbinger's phase I AVMs. Vascular laser has been classically contraindicated for the treatment of AVMs, as there is a fear of accelerating their progression. In this study, we have treated capillary stains in five CM-AVM patients with pulsed dye laser, with improvement and without worsening or recurrence of the lesions after 1 year of clinical and ultrasound follow-up.

Treatment of port wine stains with 595-nm pulsed dye laser in 27 pediatric patients: A prospective study in the Iranian population.

Port wine stain (PWS) is a congenital vascular malformation, which is visible at the birth as the red patches, mostly on the face and neck. Previous studies have shown good efficacy and safety of 595-nm pulsed dye laser (PDL). Here, we have conducted a prospective study to assess the efficacy and safety profile of pediatrics with PWS, treated with 595-nm PDL. Twenty-seven patients (10 males and 17 females) with the mean age of 5.7 ± 2.8 (range 1-13) years old were included in the study. Following 6.2 (range 4-10) sessions of treatment, 70.74 ± 18.5% of improvement was detected three months after the final session. Fourteen (51.8%) patients achieved a higher than 75% of improvement; nine (33.4%) patients experienced 50%-75% improvement; four (14.8%) patients experienced a less than 50% improvement. V1 involvement and a marked improvement within the first five sessions found to be good prognostic factors. Regarding age, sex, skin type, color and size of the PWS, no significant association with therapeutic response were detected. Blister and crust, atrophic macules, and hyperpigmentation were noted in six (22.2%), one (3.7%), and one (3.7%), respectively. In conclusion, 595-nm PDL looks an effective and relatively safe therapeutic approach in the treatment of Iranian pediatric PWS patients.

Clinical characteristics and treatment of 52 cases of phakomatosis pigmentovascularis.

Phakomatosis pigmentovascularis is a rare syndrome characterized by widespread capillary malformation and pigmented nevus. The objective of this study was to evaluate its characteristics and treatment. Fifty-two patients presenting between 2003 and 2017 were retrospectively reviewed. Type IIa (port-wine stain and dermal melanocytosis with oculocutaneous involvement) was most common. Systemic involvement was observed in 17.3% and it was not significantly correlated to extent of capillary malformation or pigmented nevus. However, systemic involvement was significantly frequent in patients with nevus of Ota and in patients with pigmented nevus located on the head and neck (P = 0.004 and 0.035, respectively). Capillary malformation was almost cleared in 28.6% of patients using pulsed dye laser, whereas pigmented nevus was almost cleared in 23.7% and completely cleared in 42.1% of patients using Q-switched neodymium:yttrium-aluminum-garnet laser. Treatment outcome score showed significant inverse correlation with the extent of port-wine stain or pigmented nevus (P = 0.047, ρ = -0.308 and P = 0.011, ρ = -0.410, respectively). Pigmented nevus demonstrated better treatment response to lasers than did capillary malformation. Smaller lesions tended to show better treatment outcomes for both capillary malformation and pigmented nevus.