Superficial Infantile Hemangiomas Research Articles

Topical timolol for superficial cutaneous infantile hemangiomas in very preterm infants

Introduction. Infantile hemangiomas (IHs) occur 3 to 4 times more frequently in preterm infants than in those born at term. Yet, data about efficacy and safety of topical therapy for IHs in preterm infants, especially in those born with very low gestational age (less than 33 gestational weeks) is very scarce. Case report. We reported five very preterm girls treated with topical timolol maleate 0.5% gel for superficial cutaneous IHs. In four infants topical timolol was applied on a single IH each, and in one infant two IHs were treated. Out of six treated IHs, one was located on the face, four on the trunk and one on the leg. They were regularly monitored for IH involution and potential adverse effects of timolol for 6?13 months of local treatment. Good therapeutic effect was achieved in all the presented infants, with no adverse effects related to topical administration of timolol-maleate. Conclusion. Topical timolol is an effective and safe therapy for superficial cutaneous infantile hemangiomas in very preterm infants. The treatment should be discussed in detail with parents and individualized management plan should be tailored for each infant in order to maximize the chances of a successful outcome, while avoiding adverse effects.

Sequelae After Involution of Superficial Infantile Hemangioma: Early Intervention with 595-nm Pulsed Laser Combined with 755-nm Long-Pulsed Alexandrite Laser versus Wait-and-See.

Background and ObjectiveInfantile haemangioma (IH) is the most common benign tumor in children. At present, pulsed dye laser (PDL) has made great progress in the treatment of superficial IH, showing good safety and effectiveness. But some doctors think that superficial IH should choose to wait-and-see. However, studies have reported that most of the IH after resolution still has residual disease, and thickness seems to be an important factor. Therefore, the purpose of this study is to investigate the relationship between Sequelae and thickness after superficial IH involution. In addition, compare the Sequelae difference between 595-nm pulsed laser combined with 755-nm long-pulse alexandrite laser treatment and wait-and-see.Materials and MethodsThis retrospective observational study included patients with superficial IH evaluated in the past 6 years and divided them into a laser group and an observation group.ResultsThe incidence of sequelae in the laser group was 44.6%, and the incidence of sequelae in the observation group was 69.5%. The incidence of Sequelae of superficial IH in the laser group was significantly lower than that in the observation group (χ2-test, χ2=10.790, P <0.001). In the observation group, the average A scores of the three thickness subgroups (<2mm, 2–5mm, and >5mm) were 4.38, 3.39, and 1.80, and there were significant differences in the A scores between the three groups (Kruskal–Wallis, p<0.05). There is a significant difference in the A score between the laser group and the observation group in the superficial IH with a thickness of 2–5 mm and>5mm (Wilcoxon rank sum test, P<0.05).ConclusionThis retrospective study showed that the degree of Sequelae of superficial IH after involution is related to its thickness. In addition, the early intervention of 595-nm pulsed laser combined with 755-nm long-pulse alexandrite laser can reduce the incidence and extent of sequelae.

Topical timolol versus oral propranolol for the treatment of hemangioma in children

Objective To evaluate the clinical efficacy and adverse effects of oral propranolol in comparison with topical timolol for the treatment of hemangioma. BackgroundPrevious research declares that hemangioma is the most common tumor of infancy and childhood, occurring in 4–10% of white infants.Patients and methodsTo reach the goal of this research, a prospective randomized study was performed by selecting 20 patients with hemangioma attending the Pediatric Surgery Clinic at Menoufia Main University Hospital and Damanhur National Medical Institute. All patients were subjected to detailed history taking, clinical examination, echocardiogram, complete blood picture, liver and kidney functions, and blood glucose level. Determination of the location and dimensions of hemangioma was based on direct measurement and photographic analysis. Doppler ultrasound was used for baseline data regarding site, size, depth, vascularity, and flow.ResultsThere was a statistically significant difference regarding dimensions of the lesion (mm) when comparing propranolol patients before treatment and after treatment (P = 0.010) and also when comparing timolol patients before treatment and after treatment (P = 0.008). There was a statistically significant difference regarding to dimensions of the lesion (mm) by ultrasound when comparing propranolol patients before treatment and after treatment (P = 0.003) and also, when comparing timolol patients before treatment and after treatment (P = 0.008).ConclusionOur study reveals that both systemic and topical beta-blockers can be used effectively for treatment of hemangioma; however, much better improvements were obtained on using systemic propranolol than topical timolol. Topical timolol can be used as a first-line treatment for superficial infantile hemangiomas.

Enhanced skin delivery of propranolol HCl using nonionic surfactant-based vesicles for topical treatment of infantile hemangioma

Infantile hemangiomas (IHs) are frequent neoplasms that consist of proliferating endothelial-like cells. Although oral administration of propranolol hydrochloride (PLH) was proposed for treating IHs, it was associated with several adverse effects. Hence the present study aimed at optimizing the efficacy as well as safety of propranolol niosomes which are topically prepared for treating IHs. Different types of Span and Brij were utilized for preparing niosomes via the use of a thin-film hydration technique. Among the tested types of Span, Span 60 produced the highest EE %, while Brij 52 produced niosomes of higher EE% than Brij 35. Increasing cholesterol levels from 30% to 50% in the prepared niosomes resulted in an insignificant decrease in EE %. Increasing the surfactant concentration from 90 to 180 μM resulted in increasing in EE%. The measured Zeta potential for the selected formulations was found in the range of −16 to −35 mv, which ensured repulsion forces between the prepared vesicles that prevent their aggregations. The diameter of the vesicles is almost uniform and correlated to Z-size analysis. F14 (Brij 52-based niosomes) produced a more sustained release of PLH as compared to F13 (Span 60-based vesicles). Clinical studies concluded that topical application of the prepared niosomes of propranolol is an effective treatment for superficial and deep IH without the side effects seen with the systemic route. Moreover, dermoscopy is a good non-invasive tool that was very helpful in detecting the type of hemangioma as well as for following the patients under treatment.

The Efficacy and Safety of Topical β-Blockers in Treating Infantile Hemangiomas: A Meta-Analysis Including 11 Randomized Controlled Trials

Background: To evaluate the efficacy and safety of topical β-blockers in the treatment of superficial infantile hemangiomas (SIH) and mixed infantile hemangiomas (MIH), respectively, and compare the efficacy and safety of topical β-blockers with other interventions. Methods: The PRISMA guidelines were adhered to. We searched for randomized controlled trials in databases from 2010 to 2018 comparing topical β-blockers with other interventions for infantile hemangiomas. The outcomes evaluated were efficacy and adverse effects. Data analyses were performed using RevMan 5.3. Publication bias was assessed to account for bias in patient selection. Results: Eleven studies, involving 1,235 patients, were subjected to this meta-analysis. Six studies compared topical β-blockers with other interventions (propranolol, placebo, corticosteroids or pulsed dye laser) in treating SIH, and 5 studies evaluated the efficacy and safety of a topical β-blocker when it was combined with another intervention in treating MIH. A topical β-blocker was discovered to be as effective as oral propranolol in treating SIH (risk ratio, RR, 0.96, 95% confidence interval, CI, 0.91–1.02, p = 0.20, I² = 0%), and topical β-blockers were more beneficial than placebo, corticosteroids or pulsed dye laser in treating SIH (RR 2.25, 95% CI 1.66–3.05, p < 0.00001, I² = 0%). Topical β-blockers combined with another intervention gave rise to a better clinical response in the treatment of MIH than intervention alone (RR 1.99, 95% CI 1.10–3.60, p = 0.02, I² = 55%) (standard mean difference 0.80, 95% CI 0.28–1.31, p = 0.002, I² = 0%). Compared with oral propranolol, topical β-blockers were associated with fewer incidences of adverse effects (RR 0.05, 95% CI 0.01–0.39, p = 0.004, I² = 0%). No significant difference in adverse effects was found when a topical β-blocker was combined with another intervention in treating MIH (RR 1.01, 95% CI 0.58–1.74, p = 0.98, I² = 0%). Conclusions: This meta-analysis provided evidence that topical β-blockers may replace oral propranolol as first-line therapy for SIH and that they are of additive value in treating MIH.

The effect of 0.5% topical timolol cream on regression of superficial infantile haemangioma in the involuting phase: a prospective, randomized, self-controlled study.

Infantile haemangiomas are the most common benign tumours affecting infants. Over time, the tumours may involute to some extent. However, sequelae, such as telangiectasia or fibrofatty tissue, often occur following this condition, which may cause disfigurement and influence patients' psychosocial development. This prospective, randomized, self-controlled study aimed to assess the effects of topical timolol (0.5%) on involuting infantile haemangiomas. Each involuting superficial infantile haemangioma (n = 29) was randomly divided into two regions; one region was treated with topical timolol (0.5%) cream, three times daily, and the other region was untreated. The comparative treatments continued for three months. Five independent assessors, blinded to the treatment regimen, judged the treated and untreated regions by comparing photographs before and after treatment. The topical timolol-treated tumour sections showed no difference compared with the untreated sites (p = 0.355) after three months of treatment, and by the end of the treatment, the untreated lesions showed significant differences relative to pre-treatment (p<0.001). Topical timolol was not observed to have any effect on the regression of infantile haemangiomas in the involuting phase.

A new clinical and dermoscopic monitoring of infantile hemangiomas treated with oral propranolol.

Oral propranolol (OP) demonstrated high efficacy and safety profile for treatment of critical infantile hemangiomas (IHs). Our aim was to assess the morphologic changes of IHs with standard and high-resolution video dermoscopy (HRVD) from baseline to 18 months either in presence or absence of OP therapy; to investigate if extended anamnestic perinatal data and clinical-dermoscopic characteristics of the IHs can correlate with therapeutic outcome. We enrolled 94 patients (112 IHs): 58 were treated with OP, 35 (42 IHs) for 6 months (group 1), and 23 (25 IHs) for 12-months (group 2); 36 (45 IHs) were followed-up. Clinical-dermoscopic examinations were performed every 3 months during therapy and follow-up. Among 67 treated IHs, superficial and deep IHs with homogenous clinical-dermoscopic aspect developed after the 2 weeks of life achieved the better outcome, stable at 9-month follow-up, independently form treatment duration. Under HRVD, glomerular vessels were prevalent at baseline; corckscrew, comma, and linear-irregular vessels were the prevalent pattern at 1, 3, and 6 months of therapy, respectively. At 12-month follow-up, adequate healing was achieved by 96% of IHs in group 2 and by 78% in group 1, showing dotted vessels. Persistent IHs displayed a reticulated aspect and linear irregular vessels, while arborizing vessels characterized relapsed IHs. A 12-month OP therapy can be considered for newborns presenting with nonhomogenous mixed IHs >3 cm on the perineal area/lower extremities. In conclusion, HRVD allows a real time monitoring of vascular changes in IHs treated with OP and can support physicians in identifying relapses before they become clinically evident.

Enhanced Percutaneous Delivery of Beta-Blockers Using Thermal Resurfacing Drug Delivery System for Topical Treatment of Infantile Hemangiomas

Background: Infantile hemangiomas (IHs) are the most common vascular tumors in children. In the past few years, topical beta-blockers (bBs) have been reported to be an effective treatment of superficial IHs. Objective: We sought to evaluate the clinical effectiveness and safety profile of enhanced percutaneous delivery of bBs for the treatment of IH. Methods: A retrospective study of all cases of IHs treated with enhanced percutaneous delivery of bBs between 2018 and 2019 was performed. Epidemiologic, clinical, and treatment data, including effectiveness score and safety, were reviewed. Results: The study included 11 patients with a total of 11 IHs. Of the total number of IHs, 7 (63.7%) showed a good response to treatment and 4 (36.3%) had a partial response; thus all patients (100%) had good or partial response to treatment. No systemic or local adverse effects were reported. Limitations: This is an uncontrolled retrospective study. Conclusion: Enhanced percutaneous delivery of bBs is a safe and efficient topical therapy for IH.

Oral B-blockers versus intralesional corticosteroids in treatment of infantile cutaneous hemangiomas

Aim Infantile hemangioma (IH) is one of the most common benign tumors of childhood, with an incidence of between 4 and 10%. Multiple modalities for treatment for IH were proposed, most commonly B-blockers and corticosteroids. Our study objective was to compare between oral B-blockers and intralesional corticosteroids injections in treatment of IHs. Patients and methods This was a prospective study that included 52 patients diagnosed with IH in two pediatric surgery tertiary centers in Egypt. Patients were divided into two groups: group A patients underwent intralesional injection of betamethasone at a dose of 10–40 mg/ml in three to six separate sessions at an interval of 1 month, whereas group B patients were given oral propranolol at a low dose of 0.5–1 mg/kg/day for 3–6 months. Changes in size and color of the hemangioma each month and the occurrence of any complications were recorded for 6 months. Regression of size was classified into excellent (75–100% decrease in size), good (50–75% decrease), poor (25–50% decrease), and no response. Results ‘Good’ response to intralesional corticosteroids was achieved in nine patients, whereas most patients had either ‘poor’ or ‘no response’ (n=14). On the contrary, most patients in the propranolol group exhibited ‘excellent’ or ‘good’ response (n=21) with only four patients not responding to treatment. Ulceration occurred in two patients who underwent intralesional steroid injection, whereas hypotension occurred in one patient with B-blockers. Conclusion Our study confirms the superiority of oral B-blockers in treatment of superficial IH when compared with intralesional injection of steroids.

Infantile Hemangioma: An Updated Review.

Infantile hemangiomas are the most common vascular tumors of infancy, affecting up to 12% of infants by the first year of life. To familiarize physicians with the natural history, clinical manifestations, diagnosis, and management of infantile hemangiomas. A Pubmed search was conducted in November 2019 in Clinical Queries using the key term "infantile hemangioma". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews published within the past 20 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article. The majority of infantile hemangiomas are not present at birth. They often appear in the first few weeks of life as areas of pallor, followed by telangiectatic or faint red patches. Then, they grow rapidly in the first 3 to 6 months of life. Superficial lesions are bright red, protuberant, bosselated, or with a smooth surface, and sharply demarcated. Deep lesions are bluish and dome-shaped. Infantile hemangiomas continue to grow until 9 to 12 months of age, at which time the growth rate slows down to parallel the growth of the child. Involution typically begins by the time the child is a year old. Approximately 50% of infantile hemangiomas will show complete involution by the time a child reaches age 5; 70% will have disappeared by age 7; and 95% will have regressed by 10 to 12 years of age. The majority of infantile hemangiomas require no treatment. Treatment options include oral propranolol, topical timolol, and oral corticosteroids. Indications for active intervention include hemorrhage unresponsive to treatment, impending ulceration in areas where serious complications might ensue, interference with vital structures, life- or function-threatening complications, and significant disfigurement. Treatment should be individualized, depending upon the size, rate of growth, morphology, number, and location of the lesion (s), existing or potential complications, benefits and adverse events associated with the treatment, age of the patient, level of parental concern, and the physician's comfort level with the various treatment options. Currently, oral propranolol is the treatment of choice for high-risk and complicated infantile hemangiomas. Topical timolol may be considered for superficial infantile hemangiomas that need to be treated and for complicated infantile hemangiomas in patients at risk for severe adverse events from oral administration of propranolol.

Safety and Efficacy of Imiquimod in the Treatment of Infantile Hemangioma; a Systematic Review and Meta-Analysis

Objective: To study the safety and efficacy of imiquimod in the treatment of infantile hemangioma (IH).&#x0D; Method: Systematic search was conducted in nine electronic databases for selecting relevant articles reporting the safety and efficacy of imiquimod as a therapeutic agent for treatment of IH. Meta-analysis was used to pool the results.&#x0D; Results: Of total 180 records screened, we included 9 studies for this systematic review and meta-analysis. About one-fifth of the patients (20.9%) have showed clinical resolution with 95% confidence interval (CI) of 11.8% to 34.1%. Regarding IH type, superficial type showed the highest rates of both clinical resolution and excellent response rates with 31.2% (95% CI= 16.6% to 50.8%) and 26.5% (95% CI= 11.6% to 49.6%), respectively. A relatively high prevalence of any side effects with 63.1% (95% CI= 47.6% to 76.3%) has been reported. The highest reported side effect was crustation (44.1%; 95% CI= 27.8% to 61.8%).&#x0D; Conclusion: Imiquimod is effective in the treatment of superficial IH and it is associated with local side effects.

Colorimetric analysis of images in the follow-up of infantile hemangiomas.

Infantile hemangiomas (IH) are common vascular tumors that appear early in life, have a rapid proliferative phase and slowly involute. There are no standardized ways to evaluate the regression of these lesions. We propose a colorimetric analysis of photographs to allow a more precise determination of IH treatment response and involution. Patients 1-10months of age with superficial or mixed IH were included. The lesions were managed with 0.5% topical timolol ophthalmic solution. Patients were followed for 16weeks with 6 evaluations each. Photographic images were taken with a red and green circle placed beside each hemangioma. The photographs were treated as to equalize the size, color, and brightness among them based on the colors of the two circles. A grading scale was established based on the color of the patient skin (0) and the color of the hemangioma at the beginning of treatment (100) by pixel analysis using Adobe Photoshop® software. A total of 17 patients 1 to 10months of age were included, of whom 16 were girls (94%). Fourteen lesions were superficial, and 3 were mixed IH. The median time prior to initiation of treatment was 105days (44-232). All lesions showed some degree of clearing. The mean of lightening of color intensity observed was of 45% (17%-74%) over the period of follow-up. The colorimetric analysis of the digital images allowed an accurate and objective evaluation of IH clearing.

Clinical evaluation of infantile hemangiomas treated with atenolol

Currently, propranolol, is the first line treatment for problematic infantile hemangioma (IH) management. However, serious side effects have been reported. For that reason, atenolol, a hydrophilic selective beta-1 blocker with the potential for fewer side effects, has been explored. A descriptive, observational case series study of 30 patients between the ages one to 5 months with superficial, deep, or mixed IH was conducted between January 2016 and December 2017. Oral atenolol was administered using a single once daily dose of 1mg/kg, which was adjusted for weight gain each month. The IH was assessed using the Hemangioma Activity Score (HAS) at initiation of treatment, four months, and 9 months of age and improvement percentage was calculated at four and nine months of age. A total of 25 patients completed three evaluations. The baseline, four-month, and 9-month HAS were 4.6, 2.39, and 0.65, respectively. Mean improvement percentage at four months of age was 46.76% and at 9 months of age was 85.65%. No side effects were reported. This study suggests atenolol as an effective treatment for IH in almost all cases, especially in patients who initiated treatment before three months of age. It was well tolerated in all our cases.

Periocular infantile hemangiomas: Characteristics, ocular sequelae, and outcomes.

To identify clinical factors associated with complications of periocular infantile hemangioma (IH) and monitor improvement in complication rates post-treatment. Retrospective cohort study. Eighty-nine patients diagnosed with periocular IH at a pediatric dermatology clinic of a tertiary care center between 2001 and 2013 were included with parental approval. Parents were interviewed by telephone between July and September of 2015, then again in January 2018 to inquire about ophthalmologic follow-up. Electronic medical records were reviewed from January 2001 through January 2018. Sixty percent of patients demonstrated ocular sequelae, including astigmatism (33%), visual axis obstruction (29%), nasolacrimal duct obstruction (7%), ptosis (4%), amblyopia (3%), and strabismus (1%). Compared with superficial IH, deep and mixed IH had higher odds, 3.4 (P=0.025) and 3.8 (P=0.034), respectively, of developing ocular sequelae. All patients with astigmatism prior to involution of IH received systemic therapy, with a significant post-treatment decrease in the proportion of patients with astigmatism (40% to 18%, P=0.027). Three-quarters of patients experienced complete IH involution by time of enrollment in kindergarten. Fifty-one (57.3%) patients received formal ophthalmologic evaluation confirmed through chart review or phone interview, with average follow-up duration of 51.2months (range: 1.9, 99.3). Deep and mixed IH were more likely to demonstrate ocular complications than superficial IH. Rate of astigmatism decreased with systemic therapy. Our study suggests that patients with periocular IH have a lower rate of amblyopia now compared with the prepropranolol era and emphasizes the importance of early treatment of periocular IH to prevent permanent visual sequelae.

Clinical and radiological outcomes of infantile hemangioma treated with oral propranolol: A long-term follow-up study.

Infantile hemangiomas (IH) undergo rapid growth during early infancy followed by gradual involution. After involution, a part of IH remain as residual lesions. Since 2008, oral propranolol has been widely used in the treatment of IH. However, long-term outcome of IH treated with propranolol remains unknown. This study aimed to investigate the sequelae of IH treated with propranolol. In this study, propranolol was given at a dose of 2 mg/kg per day at the age of 3.8 ± 2.5 months and follow-up visits were arranged to continue at least through the age of 4 years. Types of sequela were recorded and classified as four degrees ("none", "minimal", "significant" and "severe" at last visit), then subsequent therapy was evaluated with the help of magnetic resonance imaging (MRI). A total of 73 patients with complete follow up were enrolled in the study. The most common types of sequela were telangiectasia, fibrofatty tissue and erythema. Significant and severe sequelae were observed in 72.4% of treated IH; superficial IH led to more but not significantly significant and severe sequelae than mixed IH (P > 0.05). Despite propranolol treatment, surgery was still needed in 37.5% of IH at a mean age of 70.3 months, and for the main reason of surgery, fibrofatty or hemangioma residua, MRI was useful for us to choose an appropriate surgical procedure.

Superficial Genital Infantile Hemangiomas

Abstract Introduction. Superficial infantile hemangiomas (IH) are rarely localized in the genital region. Case Report. We present 8 infants with IHs in the genital region (3 boys and 5 girls). Our patients had only superficial IHs, their internal organs were not affected and there were no associated anomalies. In the boys, IHs were localized on the scrotum and the foreskin in 2 cases and 1 case, respectively. In the girls, IHs were on the labia majora and near the vaginal introitus. None of the IHs showed any IH-related complications. No therapy for IHs was administered in any of the presented infants, either because IHs were small and non-aggressive, or because their parents rejected the proposed therapy. Conclusion. Genital IHs have increased tendency for ulceration, so thorough examination and follow-up are of outmost importance. If therapy is indicated, oral propranolol is the treatment of choice for genital IHs.

Clinical Practice Guideline for the Management of Infantile Hemangiomas.

Infantile hemangiomas (IHs) occur in as many as 5% of infants, making them the most common benign tumor of infancy. Most IHs are small, innocuous, self-resolving, and require no treatment. However, because of their size or location, a significant minority of IHs are potentially problematic. These include IHs that may cause permanent scarring and disfigurement (eg, facial IHs), hepatic or airway IHs, and IHs with the potential for functional impairment (eg, periorbital IHs), ulceration (that may cause pain or scarring), and associated underlying abnormalities (eg, intracranial and aortic arch vascular abnormalities accompanying a large facial IH). This clinical practice guideline for the management of IHs emphasizes several key concepts. It defines those IHs that are potentially higher risk and should prompt concern, and emphasizes increased vigilance, consideration of active treatment and, when appropriate, specialty consultation. It discusses the specific growth characteristics of IHs, that is, that the most rapid and significant growth occurs between 1 and 3 months of age and that growth is completed by 5 months of age in most cases. Because many IHs leave behind permanent skin changes, there is a window of opportunity to treat higher-risk IHs and optimize outcomes. Early intervention and/or referral (ideally by 1 month of age) is recommended for infants who have potentially problematic IHs. When systemic treatment is indicated, propranolol is the drug of choice at a dose of 2 to 3 mg/kg per day. Treatment typically is continued for at least 6 months and often is maintained until 12 months of age (occasionally longer). Topical timolol may be used to treat select small, thin, superficial IHs. Surgery and/or laser treatment are most useful for the treatment of residual skin changes after involution and, less commonly, may be considered earlier to treat some IHs.

Topical Timolol Vs. Oral Propranolol for the Treatment of Superficial Infantile Hemangiomas.

Objective: Infantile hemangiomas (IHs) are the most common vascular tumors of infancy. Oral propranolol has achieved great success in treating IHs since 2008. To minimize the systemic side events caused by oral administration of propranolol, topical timolol started to be applied in the treatment of IHs, especially for superficial lesions.Methods: We treated 724 children with superficial IHs using oral propranolol or topical timolol, and investigated the efficacy and safety of the two treatment patterns.Results: Both oral propranolol and topical timolol achieved a satisfactory therapeutic outcome, with an effective response rate of 97 and 96.4%, respectively. No significant differences in visual analog scale (VAS) improvement between the two groups were observed. Occurrence rate of systemic adverse events for patients treated with oral propranolol (3.9%) was significantly higher than that for patients treated with topical timolol (0%). Clinical response was not associated with gender, duration of treatment, lesion location, lesion size, gestational age, and progesterone use during pregnancy, but closely associated with age at treatment initiation, which indicated that younger age at treatment initiation predicted for a better regression rate.Conclusions: We recommend that topical timolol instead of oral propranolol could be the first-line therapy for superficial IHs because of its good efficacy and improved safety.

595 nm染料激光联合外用0.5%马来酸噻吗洛尔溶液治疗浅表型婴儿血管瘤的疗效评价

Objective To evaluate the clinical efficacy and safety of 595-nm pulsed dye laser with topical timolol maleate 0.5% solution for the treatment of superficial infantile hemangioma (IH) . Methods Complete clinical data were collected from 156 infants with superficial IH, who received treatment with 595-nm pulsed dye laser combined with topical timolol maleate 0.5% solution in the Department of Dermatology of the Second Affiliated Hospital and Yuying Children′s Hospital of Wenzhou Medical University from July 2015 to July 2016, and analyzed retrospectively. Of the 156 patients, 44 were males, and 112 were females, with an average age of 3.8 ± 0.7 months (range, 24 days - 1 year) . These patients were treated with 595-nm pulsed dye laser every 5 weeks and topical application of timolol maleate solution twice a day. Each treatment with timolol maleate solution lasted 30 minutes. When the hemangioma regressed generally, the treatment with laser and timolol maleate solution was stopped. At weeks 5, 10, 15 and 30, the visual analogue scale (VAS) was used to evaluate the efficacy, and adverse reactions were recorded. These patients were followed up till 6 months after the end of treatment. The relationships of area and thickness of hemangioma with treatment duration, treatment sessions and VAS scores were analyzed. Results After 5 - 30 weeks of treatment, hemangiomas regressed to different extents, and the cure rate was 93.59% (146/156) . At weeks 5, 10, 15 and 30, the VAS scores were 3.12 ± 0.23, 4.45 ± 0.52, 5.45 ± 0.71 and 7.59 ± 1.64 respectively. Repeated-measures analysis of variance showed that the VAS scores all significantly increased over time (F = 189.35, P 3 mm) , and significantly differed among the above 3 groups at different time points (F = 215.56, P 3 mm (11.03 ± 0.72 months, P 9 cm2) , and significantly increased over time in these groups; Kruskal-Wallis H test showed that there was a significant difference in the treatment sessions among the above 3 groups (H = 10.45, P < 0.01) , and the group with the initial area of hemangiomas < 3 cm2 showed the least treatment session. The adverse reactions were mild, and no adverse cardiovascular or respiratory events were observed. Conclusion The 595-nm pulsed dye laser combined with topical timolol maleate 0.5% solution is effective and safe for the treatment of superficial IH. Key words: Hemangioma; Infant; Lasers, dye; Timolol; Treatment outcome; 595-nm Pulsed dye laser

Development and Characterization of Nanoemulsion Containing Almond Oil, Biodegradable Polymer and Propranolol as Potential Treatment in Hemangioma

Hemangiomas are benign tumors, which cause an abnormal proliferation of endothelial cells. In recent years, propranolol (POP) has been used for the therapy of infantile hemangiomas (IH). Topical POP has been prescribed instead of systemic steroids to reduce the risk of side effects. In order to increase the effectiveness of the POP, nanoemulsions (NEs) were developed as drug delivery carriers for topical delivery. NEs are stable dispersions consisting of oil, water and surfactants. To develop NEs water‐in‐oil, POP was solubilized in two concentrations, at 0.25 wt% and 0.5 wt% in water. To prepare the external phase, the almond oil, a biocompatible vegetable oil, was chosen due its anti‐inflammatory properties. An optimal proportion of surfactant and co‐surfactant, Tween 80/Span 80, were assessed by pseudo‐ternary phase diagram. NEs were obtained by ultrasonic processor and the mean droplet size was measured by Dynamic Light Scattering (DLS) and it was less than 300 nm. POP was included in the best formulation for stability studies, Nuclear Magnetic Resonance (NMR) studies, by the analysis of proton relaxation time, cell viability studies and occlusivity test. At the end of the work, the stable NEs, containing POP, diluted above 200 fold, did not affect cell viability and it can be considered as a promising formulation for the treatment of superficial infantile hemangioma.