Therapy For Infantile Hemangiomas Research Articles

The Profiles of Infantile Hemangiomas Patients

Background: Infantile hemangiomas (IH) are the most prevalent benign tumors in children, predominantly in girls. Most IH cases do not require treatment due to spontaneous involution, but 10% of cases do require early treatment due to size, location, and complications. Purpose: This study tried to define the profile, clinical aspects, and therapy of IH in Dr. Zainoel Abidin General Hospital, Banda Aceh. Methods: A descriptive approach using a retrospective analysis employing secondary data from the outpatient clinic's patient registration book. This study included all new cases of infantile hemangioma at the outpatient clinic general hospital between 2013 and 2021. Result: A total of 105 patients were involved in this study. The majority of IH patients (59%) were under the age of one year, with 64 female patients (61%) making the most visits to the pediatric clinic in 2017, 2018, and 2019 (77.1%). The most prevalent clinical features of skin lesions were nodules in 69 individuals (65.7%), and the most common site was the facial region (13.3%) in 44 patients. In 20 individuals, a combination of propanolol and oral corticosteroids was used as the most effective treatment strategy (19% ). Conclusion: Infantile hemangiomas is the most frequently reported benign tumor in children. Females are more likely than males to develop IH. The majority of IH is minor and normally resolves on its own without therapy. However, certain rare kinds of IH require clinician attention and systematic treatment.

Shikonin reverses pyruvate kinase isoform M2-mediated propranolol resistance in infantile hemangioma through reactive oxygen species-induced autophagic dysfunction.

Infantile hemangioma (IH) is the most common benign tumor in infancy. Propranolol, a nonselective β-adrenergic receptor blocker, is now the first-line therapy for IH. Recently, low sensitivity to propranolol therapy has become one major reason for the failure of IH treatment. However, the exact underlying mechanisms are yet to be fully elucidated. Here, we reported that pyruvate kinase isoform M2 (PKM2), an essential glycolytic enzyme, played a critical role in regulating the progression of IH and the therapeutic resistance of propranolol treatment. Shikonin reversed the propranolol resistance in hemangioma-derived endothelial cells and in hemangioma animal models. Moreover, shikonin combined with propranolol could induce excessive reactive oxygen species (ROS) accumulation and lead to autophagic dysfunction, which is essential for the enhanced therapeutic sensitivity of propranolol treatment. Taken together, our results indicated that PKM2 has a significant role in hemangiomas progression and therapeutic resistance; it could be a safe and effective therapeutic strategy for those hemangiomas with poor propranolol sensitivity combined with shikonin.

Efficacy and safety of propranolol cream in infantile hemangioma: A prospective pilot study

Infantile hemangioma (IH) is a common tumor in infants that gradually resolves and is often untreated. However, for cosmetic reasons, parents often opt for treatment. Oral propranolol, the first-line therapy for IH, is sometimes associated with several side effects, including hypotension, bradycardia, and hypoglycemia. No clinical studies on topical propranolol have been conducted using standardized procedures. We evaluated the efficacy and safety of topical propranolol in patients with IH. This multicenter, prospective pilot study was conducted from June 2019 to October 2020 and involved eight Japanese infants aged 35–150 days with proliferating IH. Patients were treated with 5% propranolol cream twice daily. We examined the efficacy rate based on central evaluation (complete or near-complete healing of the target hemangioma) at weeks 24 and 12, respectively, compared to baseline values. The efficacy rate at week 24 was 68.8% (95% confidence interval: 44.1–85.9%). The surface area, maximum diameter, and color intensity of the target IH decreased over time. Adverse event and drug-related adverse event rates were 87.5% and 0%, respectively. Propranolol cream may be effective and safe in Japanese patients with IH and may be considered a first-choice treatment for small and superficial IHs in cosmetically problematic areas.

Oral Atenolol versus Propranolol in the Treatment of Infantile Hemangioma: A Systematic Review and Meta-Analysis.

ABSTRACTBackground:Infantile hemangioma (IH) is the most common benign vascular tumor of infancy. Propranolol is considered first-line therapy for IH. However, it is associated with side effects. Therefore, there was a need for alternative therapy. Atenolol, a selective b1-blocker may be free from such side effects. Hence, the present study aims to develop a more accurate estimate of the safety and efficacy of atenolol compared to propranolol in the treatment of IH.Methodology:A search of various literature databases (PubMed, Embase, Ovid, Scopus, Cochrane Central, CINAHL, Web of Science, and Google Scholar) was done to identify studies which compared propranolol versus atenolol in the treatment of IH. The combined odds ratio along with corresponding 95% confidence intervals (CIs) were evaluated using a fixed-effects model.Results:A total of 300 articles were screened of which five studies including 116 patients in atenolol arm and 138 patients in the propranolol arm were analyzed. Atenolol was comparable to propranolol in terms of efficacy as no significant difference was seen between both the treatment arms in terms of hemangioma activity score (mean difference 0.25 [95% CI;‒0.21, 0.71]) and complete response (odds ratio [OR] =0.43; 95% CI; 0.17, 1.11; P = 0.08,). Atenolol therapy was better than propranolol in terms of safety, i.e., serious/potentially serious side effect, (OR = 0.11; 95% CI; 0.02, 0.51; P = 0.005) and wheezing/bronchial hyperreactivity (OR = 0.11; 95% CI; 0.02, 0.51; P = 0.005).Conclusion:The present meta-analysis provides evidence that atenolol has got a comparable efficacy and better safety profile with propranolol

Propranolol for Treatment of Infantile Hemangioma: Efficacy and Effect on Pediatric Growth and Development.

Purpose Propranolol has been successful in treating problematic infantile hemangiomas (IH) but concerns regarding its effect on normal growth and development have been raised. This study examines physical growth, developmental milestones, and human growth hormone (hGH) levels in infants receiving propranolol for problematic IH. Method Monthly heights and weights of children undergoing propranolol therapy for IH were prospectively collected and tabulated. Data analysis and comparison to World Health Organization (WHO) weight-for-age and weight-to-length z-scores was performed. Questionnaires regarding milestones, efficacy, and guardian satisfaction were performed, and a combination of both chart results and phone conducted surveys was tabulated. Serum from a small representative cohort of age-matched children with IH treated and not treated with propranolol was collected. Results A total of 185 children receiving propranolol therapy between 2008 and 2013 for IH were assigned to this study. The children were divided into two cohorts based on the presence of comorbidities or risk factors that may affect growth and development (n = 142 no comorbidities, n = 43 with comorbidities). Neither cohort demonstrated deviation from normal weight in comparison to WHO normative data. There was a significant deviation for BMI-for-age and weight-for-age z-scores in our population, especially in patients on propranolol for more than 7 months. Based on data from participants, via either completed questionnaires or chart results, most children met their developmental milestones at or before target ages, regardless of the presence of comorbidities. Eighty percent of guardians noticed clinical improvement of the IH, with 91% either happy about or neutral to using the medication. hGH levels were higher in patients receiving propranolol therapy, but not significantly different. Conclusion Propranolol therapy is effective and well tolerated in the treatment of infantile hemangiomas. This study suggests that propranolol does not impair growth and has no impact on normal pediatric development.

A survey on the application of oral propranolol and atenolol for the management of infantile hemangiomas in mainland China: Survey on propranolol atenolol hemangiomas.

Since 2008, oral propranolol has evolved as the first-line therapy for infantile hemangiomas (IHs). Meanwhile, oral atenolol gradually shows comparative effectiveness versus oral propranolol with few side effects. Here, we conducted a mobile internal survey among a group of Chinese clinicians about how they choose the dosage, dose regimen, and dose escalation methods of propranolol and atenolol for the treatment of IH.A mobile-ready internal survey on the application of oral propranolol and oral atenolol for IH in mainland China was performed and distributed to 333 potential clinicians from different levels of healthcare institutions in mainland China. Eighty-one doctors responded to the survey. All the respondents had the experience of treating IH with oral propranolol and 32 had the experience with oral atenolol.Most of the doctors from tertiary hospitals chose 2 mg/kg/d twice daily, while most of those with the experience of propranolol from private hospitals chose 1 mg/kg/d once daily. More doctors from tertiary hospitals had the experience of atenolol than those from private hospitals.Oral atenolol has become another medication intervention option for IH in mainland China. This survey is helpful to standardize and develop a guideline of oral atenolol therapy for IH.

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.

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.

A RATING SCALE IN DETERMINING INDICATIONS FOR SYSTEMIC MEDICAMENTOUS TREATMENT OF INFANTILE HEMANGIOMAS WITH BETA-BLOCKERS

Introduction. Infantile hemangioma (IH) is the most common benign vascular tumor of childhood. Currently, the first line of IH therapy are beta-blockers (Propranolol, Atenolol). However, their application may cause some complications, like cardiac, pulmonary and others. Practitioners who are engaged in HI therapy should be well aware of criteria for prescribing such treatment. Up to now, there are no uniform criteria anywhere in the world when to start and to finish the systemic therapy with beta-blockers. Material and methods. We have developed a rating scale for determining indications for IH systemic treatment with beta-blockers which includes the following parameters: IH volumetric component (thickness), child’s age, IH location, IH dimensions, number of IH on the skin and complications. A physician examines a patient, analyzes the abovementioned criteria and summarizes scores. During the period from October 1, 2018 to May 31, 2019, the Center for Vascular Pathology conducted 923 initial consultations for children using an assessment scale (main group). During an 8-month period from February 1, 2018 to September 30, 2018, 879 children consulted without using an assessment scale were included in the comparison group. Results. After analyzing results in two compared groups , one can see a clear decrease in prescription of the medicamentous therapy by 1.5 times: from 43.3% to 27.3%. Conclusions. The discussed rating scale, developed for determining indications of IH systemic treatment with beta-blockers, objectively and reliably evaluates prescription of medicamentous therapy not only due to physician’s experience but also due to summarized indicators. Such an approach can produce a positive effect at the disease course. However, it is worth reminding that the proposed scale is more a proposed direction in choosing a technique for IH treatment.

Propranolol Accelerats Hemangioma Stem Cell Transformation Into Adipocyte

Infantile hemangioma (IH) is the most common childhood benign vascular tumor. Recently, propranolol has been found to be an effective therapy for IH, but its mechanism of action is not yet understood. Hemangioma stem cells (HemSCs) have a mesenchymal morphology, robust proliferation, and multilineage differentiation (into adipocytes). Therefore, we hypothesized that propranolol could accelerate the transdifferentiation of HemSCs and prevent the growth of proliferating IH. In this study, the fibrofatty tissue of IH that received therapy with propranolol appeared much earlier than without the treatment. We isolated HemSCs with CD133-tagged immunomagnetic beads, and then we used flow cytometry technology to analyze the HemSC phenotypes and determine whether propranolol induced HemSC death. The proliferation and adipogenesis abilities of propranolol-treated HemSCs were analyzed by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide assay, Oil red O staining, and Western blotting. We observed that the HemSC morphological traits gradually became spindle shaped, like fibroblasts, and the average extraction yield of HemSCs was about 0.25%. The HemSCs had high rates of expression for CD90 (98.8%) and CD105 (97.8%) but did not significantly express CD31 (0.7%). We also found a 100 μM concentration of propranolol cutoff point. Propranolol did not affect HemSC survival significantly at low concentrations (6.25, 12.5, 25.0, and 50.0 μM). However, propranolol resulted in a sharp and significant variation in cell morphology and survival rates at high concentrations (100, 200, and 400 μM). The results suggest that treatment with propranolol inhibited HemSC proliferation and induced cell death and apoptosis in a concentration-dependent manner. Oil droplets determined by Oil red O staining showed that propranolol increased the transdifferentiation rate of HemSCs into adipocytes. Furthermore, the expressions of phosphorylated AKT and peroxisome proliferator-activated receptor gamma (PPARγ) were increased with a 100 μM concentration of propranolol in HemSC culture. Our study found that propranolol inhibited proliferation, induced apoptosis and necrosis, and promoted differentiation of HemSCs. Propranolol may upregulate PPARγ via PI3K pathways, thereby accelerating lipogenesis and enhancing IH HemSC adipogenesis.

Propranolol-Loaded Mesoporous Silica Nanoparticles for Treatment of Infantile Hemangiomas.

Infantile hemangioma (IH) is one of the most common neoplasm of infancy. Although with the potential to involute slowly after proliferation, IH has several subsets that could develop severe complications and lead to functional impairment or permanent disfigurement. In the present study, a novel propranolol (PRN) delivery system is developed that encapsulated in mesoporous silica nanoparticles (MSN). The primary nanoparticles are further treated with polyvinyl alcohol (PVA) to form PVA-MSN-PRN nanoparticles. The encapsulation efficiency is 58.8% ± 7.2%, and nanoparticles could release PRN in a controlled-release way. It is discovered that PVA-MSN-PRN could significantly suppress hemangioma stem cell (Hemsc) proliferation, promote Hemsc apoptosis in vitro, and inhibit the growth of hemangiomain xenografts in vivo. A conclusion could be made that this novel nanodrug delivery system has high therapeutic efficacy, low cytotoxicity, low administration frequency, and provides an attractive strategy for efficient IH therapy.

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.

Vectra 3D Imaging for Quantitative Volumetric Analysis of the Efficacy of Propranolol in Infantile Hemangioma

Infantile hemangioma (IH) is a common tumor in infants. After the proliferative phase, hemangiomas regress, but sometimes leave scars. Propranolol is now the recommended first-line oral therapy for IH. To evaluate the effectiveness of oral propranolol administration, we measured quantitative changes in an IH by digital camera and Computed Tomography (CT) or Magnetic Resonance Imaging (MRI). Although digital cameras are very simple, changes in color tones occur with time, lesions are evaluated in two dimensions, and changes in the thickness of the hemangioma are difficult to evaluate. Therefore, we investigated the feasibility of 3D photography to quantify volumes in IH during oral propranolol treatment.

Serum concentrations of VEGF and bFGF in the course of propranolol therapy of infantile hemangioma in children: Are we closer to understand the mechanism of action of propranolol on hemangiomas?

Propranolol has become the treatment of choice for infantile hemangiomas (IH). Neither the pathogenesis of IH nor the mechanism of action of propranolol on them are well understood. Possible explanations include the inhibition of angiogenesis by decreasing vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), induction of vascular endothelial cell apoptosis and vasoconstriction. The aim of the study was to assess serum concentrations of VEGF and bFGF in the course of propranolol therapy of IH in children, and to assess their clinical implications. The study included 51 children with IH treated with propranolol. The participants were assessed before, during and after the therapy with Hemangioma Activity Score (HAS), Doppler ultrasound (US) of the lesions, as well as VEGF and bFGF serum concentrations. All children showed clinical improvement measured in the HAS. A complete involution of the IH was reported in 32 (63%) children at the time of decision of the gradual withdrawing of propranolol, and in 28 (61%) patients at the end of the treatment (out of 46 patients present at the follow up after 1.5 months). Doppler US at the follow-up showed a complete disappearance of the blood flow in the lesion in 24 (52%) children and its reduction in 12 (26%) children. There was a significant decrease in VEGF and bFGF during and after treatment compared to pretreatment values. There was a correlation between the outcome of the Doppler US and changes in bFGF during and after treatment. Changes in VEGF during treatment did not correlate with changes in the Doppler US. Serum concentrations of VEGF and bFGF decreased during the propranolol treatment of IH, which may indicate the effect of propranolol on both. However, the statistical analysis showed their low prognostic value as biochemical markers of propranolol treatment. Clinical evaluation combined with Doppler US is the most valuable method of monitoring the therapy.

Pigment epithelium-derived factor/vascular endothelial growth factor ratio plays a crucial role in the spontaneous regression of infant hemangioma and in the therapeutic effect of propranolol.

Infantile hemangioma (IH) is a benign tumor that is formed by aberrant angiogenesis and that undergoes spontaneous regression over time. Propranolol, the first‐line therapy for IH, inhibits angiogenesis by downregulating activation of the vascular endothelial growth factor (VEGF) pathway, which is hyperactivated in IH. However, this treatment is reportedly ineffective for 10% of tumors, and 19% of patients relapse after propranolol treatment. Both pro‐angiogenic and anti‐angiogenic factors regulate angiogenesis, and pigment epithelium‐derived factor (PEDF) is the most effective endogenous anti‐angiogenic factor. PEDF/VEGF ratio controls many angiogenic processes, but its role in IH and the relationship between this ratio and propranolol remain unknown. Results of the present study showed that the PEDF/VEGF ratio increased during the involuting phase of IH compared with the proliferating phase. Similarly, in hemangioma‐derived endothelial cells (HemEC), which were isolated with magnetic beads, increasing the PEDF/VEGF ratio inhibited proliferation, migration, and tube formation and promoted apoptosis. Mechanistically, the VEGF receptors (VEGFR1 and VEGFR2) and PEDF receptor (laminin receptor, LR) were highly expressed in both IH tissues and HemEC, and PEDF inhibited HemEC function by binding to LR. Interestingly, we found that propranolol increased the PEDF/VEGF ratio but did so by lowering VEGF expression rather than by upregulating PEDF as expected. Furthermore, the combination of PEDF and propranolol had a more suppressive effect on HemEC. Consequently, our results suggested that the PEDF/VEGF ratio played a pivotal role in the spontaneous regression of IH and that the combination of PEDF and propranolol might be a promising treatment strategy for propranolol‐resistant IH.

Phace синдром у дітей: поєднання сегментарних гемангіом обличчя і розщеплення груднини

Мета роботи: визначення поширеності PHACE синдрому у дітей з інфантильними гемангіомами (ІГ), оцінка результатів лікування пропранололом та встановлення необхідності проведення додаткових хірургічних втручання.Матеріали і методи. У дослідження включено 27 дітей з ІГ в ділянці голови і шиї, які знаходилися на стаціонарному лікуванні в НДСЛ «ОХМАТДИТ» від грудня 2010 до березня 2017 року. Для встановлення діагнозу використовували УЗД, МРТ, КТ з контрастуванням, ехокардіографію, пацієнтам проводили також офтальмологічне обстеження.Результати та обговорення. Діагноз PHACE синдрому встановлено у 4 (14,81%) пацієнтів серед 27 дітей з ІГ ділянки обличчя і шиї діаметром понад 5 см. PHACE синдром діагностували за наступними критеріями: наявність сегментарних ІГ обличчя (n=4), в тому числі сітчаста гемангіома (n=1), розщеплення груднини (n=3), патологія задньої черепної ямки (n=1), коарктація аорти (n=1), правобічна дуга аорти (n=1), надпупковий шов (n=1). Усі пацієнти були жіночої статі. Поширення ІГ на ділянку дихальних шляхів з порушенням їх прохідності діагностовано у 3 (75%) випадків з PHACE синдромом. Для лікування ІГ використовували консервативну терапію: пропранолол – неселективний бета-блокатор – в дозі 2 мг/кг/добу. Консервативна терапія ІГ у дітей з PHACE синдромом є ефективною та безпечною, однак характеризується відносно більшою тривалістю. Операційне лікування з приводу розщеплення груднини виконано у 3 пацієнтів, у двох застосована первинна рання корекція вади у віці 2 і 4 місяці. В усіх пацієнтів досягнуто доброго функціонального і косметичного результату після хірургічного лікування.

Propranolol Versus corticosteroids for Infantile Hemangiomas: A Randomized Control Trial in a Tertiary care Hospital

Infantile hemangiomas are the most common vascular tumor of infancy and childhood. Sometimes these lesions interfere with normal function & produce serious disfigurement that is unlikely to resolve on its own and then treatment is required. While evidence most supports the use of corticosteroids, there is no well- studied or Federal Drug Administration (FDA) approved systemic therapy for haemangiomas of Infancy. Dramatic improvement of complicated haemangioma by propranolol has recently been reported, but to date, details for initiating therapy, monitoring and potential risks in relation to Corticosteroids were not compared in a large scale. This research was designed to observe the effectiveness of oral propranolol compared to oral corticosteroid aimed at treatment of clinically important groups of infantile hemangiomas that require aggressive treatment. We conducted a randomized control study among the diagnosed case of infantile hemangiomas, age of <10 years. The total sample size was 60 (30 for propranolol group i.e. in group A, and 30 for corticosteroid group i.e. in group B) & grouping was done with the simple random technique. A clinical & photograph based VAS (Visual Analogue Scale) scale with a defined monitoring schedule was used for evaluation of treatment response. Our study result showed, (3.33%) patients of group A, response to color change (red-purple-grey) within 1st month of treatment whereas none of the patient (0.00%) of group B had any response to color by this time. Patients response to propranolol therapy was also continued even up to 5th month (3.33%) but it was absent (0.00%) in corticosteroid therapy even after 4th month & p= 0.025, that was statistically significant. Regarding the mean size (diameter) of the tumor, most of the tumor size reduced and near to stabilize at 4th month in group A, but in group B, the rate was slower and needed longer time (5-6 month), the p value was 0.030. Again 60% of tumor became non-palpable at 3rd week of treatment in group A patients, but in group B, 70% of tumor was still remain palpable on that time & p=0.001, that was statistically significant. Again, in Propranolol therapy group, the rate of complications was (24%) whereas in Corticosteroid therapy group, it was (76%).The p value was 0.020 that was also statistically significant. Hence, the present study results denote that, oral propranolol can be considered as an emerging and effective treatment over oral corticosteroid therapy for infantile hemangiomas.

Molecular and immunohistochemical expression of apoptotic proteins Bax, Bcl-2 and Caspase 3 in infantile hemangioma tissues as an effect of propranolol treatment

BackgroundInfantile hemangiomas (IHs) are the most common benign tumors of childhood. They are characterized by a unique clinical course with two phases, proliferation and involution, which are followed by regression. The therapy of infantile hemangiomas was revolutionized in 2008 by the introduction of propranolol, however, the mechanism of its influence on hemangiomas remains unclear. MethodsThe study included 71 patients with IHs, 27 of whom were treated with propranolol while the remaining 44 were used as a comparative group. The expression of Bcl-2, Bax and Caspase3 was determined with immunohistochemistry and mRNA of Bax, Bcl-2 and Caspase3 were assessed with the use of RT-PCR. ResultsBoth methods revealed a statistically significant decrease in Bcl-2 expression and an increase in Bax in IHs tissues after propranolol treatment. ConclusionsThe results obtained for Bax and Bcl-2 proteins may indicate a link between the effect of propranolol and apoptosis. Higher Bax and lower Bcl-2 expression in the propranolol treated group indicates a strong pro- apoptotic action countering any anti-apoptotic activity; apoptosis was indicted in IH tissue as a potential result of propranolol treatment, with potential clinical impact in other tumors.

Assessment of the effectiveness of topical propranolol 4% gel for infantile hemangiomas

Infantile hemangiomas (IHs) are the most common vascular tumors in children. Because of their benign character and natural involution, the vast majority of IHs do not require any treatment. In the past few years, topical beta blockers have been reported to be an effective treatment of superficial IHs. We sought to evaluate the clinical effectiveness and safety profile of topical propranolol 4% gel for the treatment of IHs. A retrospective study of all cases of IHs treated with topical propranolol 4% gel between 2013 and 2015 was performed. All patients were evaluated in a pediatric dermatology unit of a tertiary medical center. Epidemiologic, clinical, and treatment data, including effectiveness score and safety, were reviewed. The study included 63 patients with a total of 75 IHs. Of the total number of IHs, 43 (57.3%) showed a good response to treatment, 19 (25.3%) a partial response, and 13 (17.33%) poor or no response, thus 62 (82.6%) had good or partial response to treatment. Age at treatment initiation, treatment time, thickness of the superficial component, and size of the lesions were shown to predict response to therapy. Out of the entire examined group, only two patients reported minor local side effects manifested by irritation, redness, and scaling of the treated area. No systemic adverse effects were reported. This is an uncontrolled retrospective study. Propranolol 4% gel is a safe and efficient topical therapy for IH.

Novel Combination Topical Timolol and Pulsed Dye Laser Therapy for Early Effective Safe Treatment of Infantile Hemangiomas

Introduction: Infantile Hemangiomas (IH) are the most common benign pediatric tumors and carry potential cosmetic and functional sequelae. Topical timolol and Pulsed Dye Laser (PDL) are effective IH therapies and previous studies have suggested the superiority of combination timolol-PDL therapy for IH over timolol alone. We present our experience using combination timolol and PDL therapy for IH, postulate a synergistic effect, and analyze the impact of age on outcomes. Method: Sixteen consecutive children with superficial IH were treated with topical 0.5% timolol. Fourteen responded poorly to one month of timolol-alone treatment and were started on concurrent monthly 595 nm PDL treatment. Outcome was scored at 3 months using a Visual Analog Scale (VAS): 4 for excellent (76-100% improvement), 3 for good (51-75%), 2 for moderate (26-50%), 1 for poor (0-25%). Result: Two patients on timolol alone had excellent response. The rest on combination timolol-PDL therapy were aged 9.6 months on average at initiation of treatment, with mean treatment duration of 4.9 months and a mean 14.3 months follow-up. Treatment was effective in all patients; mean VAS was respectively 3.69 and 3.58 for those younger than 7 months and those older at treatment initiation. Those started on combined treatment before 7 months and who achieved complete IH regression did so within an average 4.6 months and before turning one, compared with the average 11 months for patients started older (p=0.042). One had hyperpigmentation after IH regression. There were no other systemic or local complications. Conclusion: Early first-line topical timolol treatment for superficial IH combined with 595 nm PDL when indicated, seems safe, simple, and appears to promote fast complete regression with high patient satisfaction making it a good active non-surgical treatment option as opposed to passive waiting. Treatment should ideally start before 7 months of age.