Treatment Of Infantile Hemangiomas Research Articles

Solid Lipid Nanoparticles Based Topical Hydrogel for Potential Treatment of Infantile Hemangioma

Solid Lipid Nanoparticles Based Topical Hydrogel for Potential Treatment of Infantile Hemangioma

R(+) Propranolol decreases lipid accumulation in hemangioma-derived stem cells.

Infantile hemangioma (IH) is a benign vascular tumor that undergoes an initial rapid growth phase followed by spontaneous involution. A fibrofatty residuum remains in many tumors and often necessitates resection. We recently discovered that R(+) propranolol, the non-β blocker enantiomer, inhibits blood vessel formation of IH patient-derived hemangioma stem cells (HemSC) xenografted in mice. HemSC are multipotent cells with the ability to differentiate into endothelial cells, pericytes, and adipocytes. We investigated how R(+) propranolol affects HemSC adipogenic differentiation and lipid accumulation, in vitro and in a preclinical murine model for IH. We conducted a 10-day adipogenesis assay on 4 IH patient-derived HemSCs. Oil Red O (ORO) staining was used to identify the onset and level of lipid accumulation in HemSC while quantitative real-time polymerase chain reaction was conducted to determine the temporal expression of key factors implicated in adipogenesis. 5-20µM R(+) propranolol treatment was added to HemSC induced to undergo adiogenesis for 4 and 8 days, followed by quantification of lipid-stained areas and transcript levels of key adipogenic factors. We immunostained for lipid droplet-associated protein Perilipin 1 (PLIN1) in HemSC-xenograft sections from mice treated with R(+) propranolol and quantified the area using ImageJ. We found that different patient-derived HemSC exhibit a robust and heterogenous adipogenic capacity when induced for adipogenic differentiation in vitro. Consistently across four IH patient-derived HemSC isolates, R(+) propranolol reduced ORO-stained areas and lipoprotein lipase (LPL) transcript levels in HemSC after 4 and 8 days of adipogenic induction. In contrast, R(+) propranolol had no significant inhibitory effect on transcript levels encoding adipogenic transcription factors. In a pre-clinical HemSC xenograft model, PLIN1-positive area was significantly reduced in xenograft sections from mice treated with R(+) propranolol, signifying reduced lipid accumulation. Our findings suggest a novel regulatory role for the R(+) enantiomer of propranolol in modulating lipid accumulation in HemSC. This highlights a novel role of R(+) propranolol in the involuting phase of IH and a strategy to reduce fibrofatty residua in IH. Propranolol is the mainstay treatment for infantile hemangioma (IH), the most common tumor of infancy, but its use can be associated with concerning β-blocker side effects.R(+) propranolol, the enantiomer largely devoid of β-blocker activity, was recently shown to inhibit endothelial differentiation of hemangioma-derived stem cells (HemSC) in vitro and reduce blood vessel formation in a HemSC-derived xenograft murine model of IH. R(+) propranolol inhibits lipid accumulation in HemSC in vitro.R(+) propranolol does not affect mRNA transcript levels of key adipogenic transcription factors in differentiating HemSC in vitro.R(+) propranolol reduces lipid accumulation in a pre-clinical xenograft murine model of IH. The R(+) enantiomer of propranolol could be advantageous in terms of reduction in β-adrenergic side effects and fibrofatty tissue formation in the involuting phase of IH.Less fibrofatty residua might reduce the need for surgical resection.Disfigurement and associated psychosocial impacts might be improved in this young patient cohort.

Safety of propranolol in neonates with severe infantile hemangiomas: A fourteen-year experience

Background: Infantile hemangiomas (IH) are the most common vascular tumors of infancy. Nearly 4–10% of infants require systemic treatment due to uncontrolled endothelial cell proliferation. Oral propranolol has been approved for the treatment of IH. Herein, we present our experience about the safety and tolerance of this treatment. Materials and Methods: This was a fourteen-year, prospective study conducted between 2008 and 2022 by the dermatology and pediatrics departments of the Hassan II University Hospital Center, located in Fez, Morocco, involving 215 children with infantile hemangioma with an indication for treatment by oral propranolol. Results: After a median follow-up period of fourteen years, the mean age of onset was six months. We encountered a 19% rate of side effects. Therapy was interrupted due to the occurrence of bronchospasm in two cases. Four patients (2.5%) had episodes of bronchiolitis. Other side effects were digestive disorders in 3%, sleep disorders in 6 cases, and coldness of the extremities in 7 cases. Four patients (8.6%) had a volumetric rebound. However, we noted sequelae, such as residual telangiectasias (39% cases), anetodermal skin in 15%, and unsightly scars in 24%. Conclusion: Our data shows that propranolol was generally well tolerated by young infants. We found side effects to be mostly minor, transient, and manageable, except for two cases of bronchospasm, whose treatment was permanently discontinued. This may be explained by the late age of treatment onset, yet we noted sequelae, such as telangiectasias and anetodermal skin. Key words: Propranolol, Infantile hemangioma, Safety

Beta‐blockers for the treatment of infantile haemangiomas in premature infants

AbstractBeta‐blockers have been established as a treatment of infantile haemangiomas (IH) since its serendipitous discovery for use in IH in 2008. However, data on the safety of these beta‐blockers for use in IH in preterm infants are scarce. A retrospective study was performed to review the safety of oral propranolol and topical timolol in the treatment of IH in a cohort of preterm infants treated at our tertiary paediatric hospital. It was observed that there was an increased risk of adverse events amongst the preterm infants with chronic lung disease, retinopathy of prematurity and gastroesophageal reflux, when treated with oral propranolol.

Comparative Outcomes of Propranolol Monotherapy and Combined Therapy with Intralesional Triamcinolone in Infantile Hemangioma

Background: Infantile Hemangiomas (IHs) are the most common vascular tumors of infancy. Oral propranolol has achieved great success in treating IHs since 2008. Recently combined oral propranolol with intralesional injection of Triamcinolone acetonide is the effective method of treatment for infantile Hemangioma with minimal adverse effects. Objectives: To observe the outcome of Propranolol monotherapy and combined therapy with intralesional Triamcinolone in Infantile Hemangioma. Materials and Methods: This prospective study was carried out in the Department of Pediatric Surgery, Sylhet MAG Osmani Medical College Hospital, Sylhet, during the period from January 2018 to December 2019. It included 42 infantile hemangioma patients divided into two groups: Group A (21) treated with oral propranolol, and Group B (21) treated with oral propranolol plus intralesional triamcinolone acetonide. Patients were followed up at regular intervals for 6 months. Results: The data of two groups of patients with IH were compared in the study. The demographic variables, including median age, sex, size, type, and site of IH, were comparable between the two groups. This showed that pre-treatment complications were slightly higher in Group B but not significantly different. Superior size reduction was observed in Group B (71.4% vs. 38.1%), though the difference was not significant statistically. Group B had excellent color regression, which was significantly higher compared to the other group (90.5% vs. 9.5%, p < 0.001). The mean treatment cost was higher in Group B, which was 187.86. taka compared to 124.76. taka in Group A (P value was <0.001). In summary, Group B had better color regression of the pinprick but at a higher cost of treatment as compared to Group A, and other parameters were almost equal in both groups. Conclusion: Combined propranolol and intralesional Triamcinolone is more effective compared to propranolol alone in the treatment of IHs.

Cardiac Evaluation before and after Oral Propranolol Treatment for Infantile Hemangiomas.

Background: Most recent clinical practice guidelines addressing the management of infantile hemangiomas (IHs) recommend oral propranolol, a non-selective beta-adrenergic antagonist, as first-line treatment. However, few reports have provided continuous follow-up data regarding cardiac evaluations. Methods: Sixty-four patients diagnosed with IHs and treated with oral propranolol before 2 years of age at the Department of Pediatrics, Kangbuk Samsung Hospital (Seoul, Republic of Korea), with regular examinations between 2017 and 2021, were included. Cardiac evaluations, including electrocardiography, Holter monitoring, chest X-ray, and echocardiography, were performed. Results: Sixty-four patients with IHs successfully underwent continuous follow-up cardiac evaluations. The median age at diagnosis was 2 weeks (1 day to 34.3 weeks). The median age at treatment initiation was 13.6 weeks (2.4-87.9 weeks), the mean longitudinal diameter of hemangioma at diagnosis was 2.8 ± 2.1 cm (0.3-12.0 cm), and the mean percentage of size decrease after 1 year of oral propranolol treatment was 71.8%. None of the 64 patients experienced severe adverse side effects during propranolol treatment. There was no statistically significant differences in echocardiographic function and electrocardiographic data after treatment. Conclusions: Propranolol treatment ≥6 months was effective and safe without significant cardiac toxicity in the treatment of patients with infantile hemangiomas.

Recent Advances in Targeted Therapies for Infantile Hemangiomas.

Targeted therapy for infantile hemangiomas (IHs) has been extensively studied as they can concentrate drugs, increase therapeutic efficacy and reduce drug dosage. Meanwhile, they can extend drug release times, enhance drug stability, decrease dosing frequency, and improve patient compliance. Moreover, carriers made from biocompatible materials reduced drug immunogenicity, minimizing adverse reactions. However, current targeted formulations still face numerous challenges such as the non-absolute safety of carrier materials; the need to further increase drug loading capacity; the limitation of animal hemangioma models in fully replicating the biological properties of human infantile hemangiomas; the establishment of models for deep-seated hemangiomas with high incidence rates; and the development of more specific targets or markers. In this review, we provided a brief overview of the characteristics of IHs and summarized the past decade's advances, advantages, and targeting strategies of targeted drug delivery systems for IHs and discussed their applications in the treatment of IHs. Furthermore, the goal is to provide a reference for further research and application in this field.

Cryocarboxy Surgery: A New Armamentarium in the Treatment of Infantile Hemangiomas of the Lips

Cryocarboxy Surgery: A New Armamentarium in the Treatment of Infantile Hemangiomas of the Lips

The burden of treatment of propranolol for infantile hemangiomas: A mixed methods study.

The burden of treatment (BOT) related to propranolol treatment for infantile hemangiomas (IH) has never previously been explored. A modified validated questionnaire, the Treatment Burden Questionnaire, and one-on-one semi-structured interviews were used to assess the BOT for propranolol for IH. Out of 80 caregivers, the overall burden score was very low at 1.2 out of 10; thematic analysis of interviews grouped themes into administration, monitoring, financial, and associated anomalies. The BOT of propranolol for IH is very low but could be reduced further by offering age-based risk stratification related to feeding frequency and risk of hypoglycemia, pragmatic advice around timing of doses before sleep, and reducing frequency of vital sign monitoring.

Has Propranolol Eradicated the Need for Surgery in the Management of Infantile Hemangioma?

To assess the impact of propranolol as the first-line treatment of infantile hemangioma (IH) on the need for surgery in the management of IH. Retrospective study of 420 patients, with IH, referred to our multidisciplinary center between January 2005 and August 2014. Clinical data including sex, age at first consultation and at treatment initiation, location, size, number, aspect, and complication of IH, as well as the type of treatment were collected. Statistical analyses were conducted considering each patient and each tumor independently. A total of 625 IH(420 patients (P))were reviewed, 113 patients had more than one IH (26.91%). Median age at first consultation was 7 months old. Overall, 243 patients were treated (57.86%) using either surgery (n=128 P/141 IH), propranolol (n=79 P/89 IH), corticosteroids (n=51 P/56 IH), and/or laser (n=34 P /36 IH). Propranolol was effective in all but 2 infants with IH. Seven patients (n=7/79 P; 8.86%) initially treated with propranolol, still required surgery, in contrast to 18 patients (n=18/51 P; 35.29%) initially treated with corticosteroids, and 103 patients (n=103/290 P; 35.51%) with no medical treatment. Since the availability of propranolol, patients were less likely to undergo surgery (48 P versus 80 P; P-Value < 0.001). This demonstrated that the use of propranolol reduced the need for surgery (P-Value < 0.001 with an OR of 0.177: CI 95% 0.079-0.396). Propranolol has dramatically reduced the need for surgery, regarding indications and number of patients. Surgical correction remains important for sequelae management, non-responders or strawberry-like IH.

Analysis of a Case of Airway Hemangioma in a 1-Month-Old Infant with Dyspnea – A Secondary Publication

Infantile hemangiomas are the most common benign tumors of infancy. However, hemangiomas located in the respiratory tract are rare and could cause life-threatening events due to airway obstruction. To date, the best recommended treatment for infantile hemangioma is oral propranolol as it exhibits faster effects with fewer adverse effects as compared to systemic corticosteroid therapy. In this study, we reported a case of a 1-month-old girl who was presented with respiratory symptoms and hemangioma on the scalp. The hemangioma extended from the right base of the skull to the thoracic inlet, causing inspiratory stridor and dyspnea. Treatment with oral propranolol was initiated and her symptoms regressed. Imaging showed regression of the hemangioma. This was a rare case of skin hemangioma found on the scalp, in which the hemangioma extended from the base of the skull to the subglottis, precipitating respiratory symptoms from airway obstruction. Based on this encounter, the presentation of skin hemangioma on the head, coupled with respiratory symptoms, necessitates the use of imaging studies, such as computed tomography, ultrasound, and magnetic resonance imaging to ascertain the extent of hemangioma.

ASSESSMENT OF THE THERAPEUTIC EFFICACY OF PROPRANOLOL FOR THE TREATMENT OF INFANTILE HEMANGIOMAS

Infantile hemangiomas (IHs) are common vascular tumors affecting pediatric populations, often necessitating medical intervention due to their potential for complications. Propranolol has emerged as a promising therapeutic option for IHs, although optimal dosing regimens and treatment outcomes remain areas of ongoing research. This prospective observational study aimed to evaluate the therapeutic efficacy, safety profile, and clinical characteristics associated with propranolol treatment in pediatric patients with IHs. Eighty infants aged one month to 1 year were included in the study, with IH occurrence and treatment initiation predominantly observed within the first 12 months of life. Propranolol was administered orally at a starting dose of 2 mg/kg/day, titrated up to 3-4 mg/kg/day as tolerated. Assessment of therapeutic response revealed significant reductions in IH size and vascularity, with 31.3% of patients demonstrating an excellent response and 37.5% showing a good response. Adverse effects were minimal, with diarrhea (22.5%) and decreased heart rate (7.5%) being the most commonly reported side effects. Anatomical distribution analysis identified the parotid region as the most common site of lesion occurrence, highlighting the heterogeneous nature of IHs. Overall, our findings support the favorable outcomes of propranolol therapy in pediatric patients with IHs, emphasizing the need for individualized treatment approaches tailored to patient-specific characteristics.

Hemangioma activity score evaluation in infantile hemangioma patients: a retrospective study

Introduction: Infantile hemangioma (IH) is a benign vascular tumor commonly found in children. Generally, no special therapy is required because spontaneous resolutions occur. However, in some cases, therapy is required due to the potential of complications. During therapy, the side effects and effectiveness of therapy must be evaluated. One of the assessment tools is the Hemangioma Activity Score (HAS). HAS is a simple and objective assessment to evaluate the successful treatment of IH by observing swelling, color, and ulceration. The use of HAS in Indonesia is still minimal. This study aims to evaluate HAS before and after therapy in IH patients at Dr. Soetomo General Academic Hospital and Surabaya Skin Centre. Methods: Twenty-seven patient medical records were selected based on the inclusion and exclusion criteria. This study is an analytic cross-sectional retrospective using consecutive sampling. The collected data were tested for suitability using Cohen's Kappa. Pre- and post-tests were carried out using the Shapiro-Wilk and Wilcoxon tests afterward. Results: Among 27 IH cases occurred in females (81.4%), with the youngest age of the patient being 1 month and the oldest being 8 years. The onset of lesions in all patients appeared before 1 year of age. The most frequent location for IH lesions was the facial area (51.8%), with a clinical manifestation being plaque (37%). The most common therapy used in this study was pulse dye laser (PDL) (48.1%). Analysis of the difference in HAS before and after therapy showed p value = 0.00, a statistically significant difference in HAS before and after therapy. Conclusions: The hemangioma activity score is an effective measurement tool for measuring the severity of IH and evaluating the effectiveness of therapy.

Efficacy and Safety of Oral Propranolol or Topical Timolol for the Treatment of Superficial Infantile Hemangiomas.

Infantile hemangiomas (IHs) are the most common benign soft tissue tumors of infancy. Oral propranolol has become a first-line treatment option since the unexpected discovery of its surprising efficacy in the treatment of IHs in 2008. However, oral propranolol causes systemic complications, including hypotension, bradycardia, and hypoglycemia. To minimize systemic adverse effects of oral propranolol, timolol maleate, a nonselective β-blocker similar to propranolol, has been used as a topical agent to treat superficial IHs. The authors evaluated the efficacy and safety of oral propranolol or topical timolol in 60 patients with IHs. Of the 60 patients recruited, 30 patients were treated using orally administrated propranolol and an additional 30 patients received topical timolol. The efficacy rate of the oral propranolol and topical timolol was 96.7% and 93.3%, respectively. There were no significant differences between the two treatment patterns for the efficacy rate. The incidence of systemic adverse effects for patients treated with oral propranolol was significantly higher than that for cases received topically timolol treatment. Topical timolol maleate is effective and well-tolerated in the treatment of IHs. It could be considered as the first-line treatment choice, especially for superficial IHs.

Liposomal propranolol for treatment of infantile hemangioma at compounding pharmacies

Infantile hemangiomas (IH) are common benign soft tissue tumors, frequently affecting infants. While Propranolol Hydrochloride (Pro HCl) has emerged as a promising treatment for IH, its topical application remains challenging due to the need for stable and efficacious carriers. This study investigates the potential of preformulated liposomes as carriers for topical delivery of Pro HCl for the treatment of IH in compounding pharmacies. Liposomes loaded with Pro HCl were prepared using active pharmaceutical ingredient or commercially available propranolol tablets and various dilution media, including Water for Injection (WFI), Dextrose 5%, and NaCl 0.9%. The physicochemical properties of the liposomal formulations (Pro HCl content, encapsulation efficiency, loading capacity, and colloidal stability) were assessed over a 90-day storage at 4 °C. In vitro release kinetics and transdermal permeation of Pro HCl from liposomes were also evaluated. Liposome properties were influenced by the dilution medium. Pro HCl content remained stable in liposomes encapsulating API (Lipo-Pro), regardless of the dilution medium. Lipo-Pro showed sustained drug release over time, suggesting its potential for maintaining therapeutic levels. Pro HCl exhibited enhanced transdermal permeability from Lipo-Pro compared to aqueous solution, indicating its potential for topical IH treatment. Preformulated liposomes offer a stable and effective carrier for Pro HCl, potentially suitable for extemporaneous preparations in compounding pharmacies. Their enhanced transdermal permeability presents a promising alternative for topical IH treatment. This study provides valuable insights into the development of innovative and effective drug delivery strategies for managing IH, with future research focusing on in vivo applications and therapeutic potential.

Historical and contemporary management of infantile hemangiomas: a single-center experience.

Objective: This study explores the 22-year evolution of Infantile Hemangiomas (IHs) treatment strategies at a single-center hospital, aiming to establish an individualized IHs management protocol. Methods: Retrospective review of IHs infants 2000-2022 at the Department of Plastic Surgery, Jiangxi Provincial Children's Hospital. Results: In our study of 27,513 IHs cases, 72.2% were female, with the median age at first hospital visit being 25 days. The majority of cases had localized and superficial lesions primarily on the head, face, and neck (67.5%). Ulceration rates fell from 21.1% to 12.6% with the introduction of propranolol. Management strategies have shifted over time, with the proportion of cases undergoing expectant management dropping from 32.9% to 12.4%. Since 2008, 26.1% of patients were treated with oral propranolol, largely replacing corticosteroids. Topical β-blockers have been used in 12.1% of cases, leading to a reduction in local injection therapy from 20.8% to 13.2%. Laser therapy, introduced in 2016, has been used in 13.8% of cases, while surgical excision has dropped from 25.0% to 8.5% due to alternative treatment options. Combination therapy was used in 8.8% of cases post-2015, indicating a rising trend. Drawing from the evolution of IHs management strategies, an individualized protocol for the management of IHs was successfully established. Conclusion: Treatment for IHs has evolved over recent decades, with less invasive medical interventions increasingly replacing more invasive methods. Furthermore, a personalized treatment protocol established in this study could boost the cure rate of IHs while minimizing potential side effects and complications.

An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma.

Infantile hemangioma (IH) is the most common tumor in children and a paradigm for pathological vasculogenesis, angiogenesis and regression. Propranolol is the mainstay of treatment for IH. It inhibits hemangioma vessel formation via a β-adrenergic receptor independent off-target effect of its R(+) enantiomer on the endothelial specific transcription factor sex-determining region Y (SRY) box transcription factor 18 (SOX18). Transcriptomic profiling of patient-derived hemangioma stem cells uncovered the mevalonate pathway (MVP) as a target of R(+) propranolol. Loss of SOX18 function confirmed R(+) propranolol mode of action on the MVP. Functional validation in preclinical IH models revealed that statins - targeting the MVP - are potent inhibitors of hemangioma vessel formation. We propose a novel SOX18-MVP-axis as a central regulator of IH pathogenesis and suggest statin repurposing to treat IH. Our findings reveal novel pleiotropic effects of beta-blockers and statins acting on the SOX18-MVP axis to disable an endothelial specific program in IH, which may impact other scenarios involving pathological vasculogenesis and angiogenesis.

Scientific validation of clinical visual scales and Antera 3D™ consistency with derived measurements in the assessment of infantile haemangioma after laser therapy

Laser therapy is a treatment for infantile haemangiomas. The efficacy of laser therapy for red lesions is determined by visual evaluation; however, this assessment is inaccurate and lacks objectivity. To scientifically validate the consistency between pre- and post-treatment visual assessment grades for infantile haemangioma treated with pulsed dye laser (PDL) and the values calculated from images obtained with Antera 3D™. This study involved 81 cases of infantile haemangiomas treated with PDL alone from 2012 to 2015 and with Antera 3D™ images of the lesions. Using images obtained before treatment and 4-6 weeks after the last treatment, the lesions were rated using a visual four-step scale. Ratings were categorised as Poor/Fair/Good/Excellent by the degree of improvement in the red colour tone. The red colour ratio was calculated using the haemoglobin distribution in the lesion and surrounding skin, and the improvement difference and improvement rate were then obtained. The correlation between the improvement difference and improvement rate, and visual evaluation was statistically analysed. No serious adverse effects were observed, with an average of 4.3 treatments per patient; 60.1% of the patients achieved Good/Excellent results. There were statistically significant differences in the post-treatment red colour ratio and improvement ratio in each category after visual evaluation classification. The improvement rate and the four visual grades were statistically correlated. This study confirmed the scientific validity of visual evaluation and the evaluation criteria calculated from Antera 3D™. This method could objectively determine treatment effectiveness.

Multicenter Study of Long-Term Outcomes and Quality of Life in PHACE Syndrome after Age 10

To characterize long-term outcomes of PHACE syndrome. Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains. A total of 104/153 (68%) individuals contacted participated in the study at a median of 14years of age (range 10-77years). There were infantile hemangioma (IH) residua in 94.1%. Approximately one-half had received laser treatment for residual IH, and the majority (89.5%) of participants were satisfied or very satisfied with the appearance. Neurocognitive manifestations were common including headaches/migraines (72.1%), participant-reported learning differences (45.1%), and need for individualized education plans (39.4%). Cerebrovascular arteriopathy was present in 91.3%, with progression identified in 20/68 (29.4%) of those with available follow-up imaging reports. Among these, 6/68 (8.8%) developed moyamoya vasculopathy or progressive stenoocclusion, leading to isolated circulation at or above the level of the circle of Willis. Despite the prevalence of cerebrovascular arteriopathy, the proportion of those with ischemic stroke was low (2/104; 1.9%). PROMIS global health scores were lower than population norms by at least 1 SD. PHACE syndrome is associated with long-term, mild to severe morbidities including IH residua, headaches, learning differences, and progressive arteriopathy. Primary and specialty follow-up care is critical for PHACE patients into adulthood.

Retracted: Propranolol Participates in the Treatment of Infantile Hemangioma by Inhibiting HUVECs Proliferation, Migration, Invasion, and Tube Formation.

[This retracts the article DOI: 10.1155/2021/6636891.].