Treatment Of Infantile Hemangiomas Research Articles

Results of Infantile Hemangioma Laser Therapy in Children with Persistent Residual Signs after Systemic Propranolol Therapy: Clinical Cases

Background. Infantile hemangiomas are revealed in 1-3% of newborns and 10-12% of infants. There are only anecdotal reports on the laser therapy efficacy in this pathology management. However, there is no common approach to the use of this method in the complex treatment of infantile hemangioma in infants. Clinical Cases Description. Two clinical cases of infantile hemangioma are presented. Patients underwent complex treatment: systemic propranolol and laser therapy via pulsed dye laser. Laser exposure modes ware selected individually: laser spot sizes were 10 and 12 mm, energy levels were 5-10 J/cm2, burst duration was short (0.45 ms) or long (10-20 ms), procedure duration was from 15 to 40 minutes, number of procedures varied from 1 to 8. Laser therapy has shown its efficacy in treatment of superficial infantile hemangioma. Conclusion. The indication for using laser therapy in management of infants with hemangiomas is especially persistent residual signs such as telangiectasias and erythema after spontaneous or drug involution phase. Laser therapy allows us to avoid aggressive methods and improves the quality of life of our patients according to this article.

Efficacy Evaluation of 755-nm Long-Pulse Alexandrite Laser Combined with 0.5% Timolol Maleate Eye Drops in the Treatment of Thicker Infantile Hemangioma.

PurposeAssessment of the clinical effectiveness and safety of 755-nm long-pulse alexandrite laser combined with 0.5% timolol maleate eye drops in treating thicker infantile hemangioma (IH).Materials and MethodsRetrospective analysis of IH treated with 755-nm long-pulse alexandrite laser and topical timolol in the Second Affiliated Hospital of Wenzhou Medical University from October 2019 to October 2020. Seventy-eight cases were included, with a five-week laser treatment interval. Treatment status was documented during the 35 weeks before each treatment, the effect was assessed at the visual analog scale (VAS), and side effects were recorded. During the 6-month follow-up period, the recurrence and residual skin lesions were monitored. The relationship between IH thickness, treatment duration and VAS was analyzed.ResultsAmong the 78 children with hemangioma, 4 children were treated with a combination of propranolol, fractional laser and cinnamyl alcohol injection due to poor curative effect. Finally, the lesions were effectively alleviated. At the 5th, 15th, 25th, and 35th weeks of treatment, the average VAS of 74 children were 3.56 ± 1.20, 4.61 ± 1.43, 5.63 ± 1.60, and 6.63 ± 1.72, respectively. We analyzed VAS in different thickness groups with Repeated Measures Analysis of Variance(RMANOVA). The results show that the VAS of the thickness 2–3 mm and 3–5mm groups were higher than the 5–7mm and 7–8mm groups (F group = 440.54, P <0.05, F time = 448.31, P <0.05). During the 6-month follow-up period, none of the 74 children relapsed and the residual skin lesions gradually vanished.ConclusionCombined treatment of IHs with a 755-nm long-pulse alexandrite laser and 0.5% timolol maleate eye drops which has apparent clinical efficacy and safety reduce residual skin lesions and decrease the IH recurrence rate.

Timing and Efficacy of 595-nm Pulsed-Dye Laser Combined with 0.5% Timolol Maleate Solution in the Treatment of Superficial Infantile Hemangiomas.

PurposeInfantile hemangioma (IH) is the most common benign tumor in infancy, and superficial IH is the most common type. IH can reportedly resolve spontaneously, but this is associated with complications, such as scars, atrophy, hypopigmentation, telangiectasia, and skin sagging, in 70% of cases. This study explores the safety and feasibility of therapeutic intervention with the 595-nm pulsed-dye laser (PDL) combined with 0.5% timolol maleate solution in superficial IH and compares the difference in efficacy between the early group and the late group.Patients and MethodsThis retrospective study examined 167 patients with superficial IH who underwent combination therapy at the Dermatology Clinic of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University between July 2019 and July 2020. The early and late groups were composed of children aged ≤2 and >2 months, respectively. Treatment was administered for 6 months, and patients were followed up for another 6 months. Two independent, double-blinded physicians reviewed photographs of the skin lesions before and after treatment to evaluate efficacy.ResultsThe early group demonstrated higher treatment efficacy than the late group. The early (n = 45) and late (n = 122) groups had treatment efficacy rates of 95.5% and 86.1%, respectively; the difference was statistically significant (P< 0.05). The early and late groups underwent 3.51 ± 0.50 and 4.73 ± 0.68 months of treatment, respectively; the difference was statistically significant (P< 0.05). Seventeen (44.4%) patients in the early group had immediate adverse reactions but no permanent sequelae, whereas 25 (20.49%) and 13 (10.7%) patients in the late group had immediate and permanent sequelae, respectively. The difference was statistically significant (P<0.05).ConclusionThis retrospective study demonstrated that 595-nm PDL combined with 0.5% timolol maleate solution was a safe and effective local treatment for superficial IH. Early treatment required fewer treatments, had better curative effects, and a lower probability of permanent sequelae.

73 Off-label use and safety of drug use in vascular anomalies

Abstract Primary Subject area Clinical Pharmacology and Toxicology Background Vascular anomalies (VA) represent a heterogeneous group of disorders associated with an abnormal development and proliferation of blood and/or lymphatic vessels displaying variable clinical presentations and severity. Infantile hemangiomas, venous, and lymphatic malformations, for example, are commonly encountered in children. Other, less frequent diagnostics include Klippel-Trenaunay syndrome and PIK-3CA-related overgrowth spectrum (PROS). Severe phenotypes can alter organ function and/or lead to pain and chronic functional impairment, and are associated with significant morbidity and mortality. Management includes surgical, interventional radiology, and pharmacologic modalities. Drugs are administered by systemic (e.g., oral, intravenous) or local (topical, intralesional) routes, or by sclerotherapy (endovascular or percutaneous venous, lymphatic, or arterial injection). Off-label drug use is common in pediatrics and in rare diseases, two characteristics applying to vascular anomalies (VA). Off-label use is associated with an increased risk of adverse drug reactions. Objectives To quantify off-label drug use in VA and assess its safety. Design/Methods A guidelines search was conducted to extract a list of drugs used in VA management. The labelling status and safety of each drug was assessed based on the product monograph, Micromedex, and the FDA data. A drug was considered to have significant safety concerns if a black box warning (the FDA’s most stringent warning dedicated to serious or life-threatening risks) or if a serious adverse drug reaction was reported in at least 1% of the patients (leading to hospitalization, congenital malformation, persistent or significant disability or incapacity, life-threatening condition, or death). Results Among 87 drugs, 13 were unlicensed and 73 off-label. Figure 1 describes the reason for considering the 73 drugs off-label. Among 74 licensed drugs, only the oral solution of propranolol hydrochloride (Hemangeol®) for the treatment of infantile hemangiomas (IH) is approved. 98.9% of the drugs are used off-label or unlicensed. Except infantile hemangioma, all other VA are exclusively treated with off-label drugs. Significant safety issues concerned 73% of the drugs and were more frequent among systemic than locally delivered drugs (Figure 2). Conclusion This first study determining the rate of off-label drug use in vascular anomalies shows that off-label drug use in VA is the rule and not the exception. Significant safety concerns are common. It is needed to carefully weigh risk and benefits for every patient when using systemic and local treatments carrying safety concerns. Patients and families should be openly informed and involved in the decision-making process.

Itraconazole versus propranolol: therapeutic and pharmacologic effect on serum angiopoietin-2 in patients with infantile hemangioma

Background The initial recommendation propranolol usage in managing infantile hemangioma was in 2008 followed by various researches assessing the dosage, efficacy, and other parameters. Itraconazole is a world-wide tolerated antifungal but only a few studies have focused on its assessment in the treatment of infantile hemangiomas (IH). Objective This study aimed to investigate the newly proposed antifungal drug ICZ and characterize different aspects of its usage as an antiangiogenic drug. Methods This was an interventional clinical trial to assess the efficacy of ICZ versus propranolol in the treatment of infantile hemangioma with studying the change in serum angiopoietin 2 (Ang2). A total of 36 pediatric patients were divided into two equal groups: firstly treated with oral itraconazole and secondly treated by oral propranolol. Results Response to treatment was observed using a modified IH score. In itraconazole-treated infants, good response was observed in 44.4% of the patients. This was slightly higher than the propranolol group which showed 22.2% with good response. We observed a decrease in serum ang2 level after usage of ICZ and propranolol and the change in serum Ang2 level before and after treatment in each group was statistically significant (p < .001). Conclusion Oral itraconazole can be an equivalent option for oral propranolol while safer and shorter treatment periods.

Propranolol inhibits the angiogenic capacity of hemangioma endothelia via blocking β-adrenoceptor in mast cell.

Propranolol, a non-selective blocker of the β-adrenoceptor (AR), is a first-line treatment for infantile hemangioma (IH). Mast cells have been implicated in the pathophysiology of propranolol-treated hemangioma. However, the function of mast cells remains unclear. HMC-1s (Human mast cell line) having been treated with propranolol for 24 h were centrifuged, washed with PBS twice, and maintained in cell culture medium for another 24 h. The supernatants with propranolol which were named as propranolol-treated HMC-1s supernatants were obtained. The expression of cytokines and mediators was examined among HMC-1s dealt with propranolol. HemECs (hemangioma endothelial cells) were co-cultured with propranolol-treated HMC-1s supernatants, and their proliferation and apoptosis were investigated. The autophagic-related protein was examined in HemECs using immunoblot. In propranolol-treated HMC-1s, the expressions of ADRB1 (β1-AR) and ADRB2 (β2-AR) were reduced by 70% and 60%, respectively, and that of cytokines and mediators were reduced. The proliferation was decreased, but apoptosis and autophagy were induced in HemECs treated with propranolol-treated HMC-1s supernatants. However, propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s. Propranolol inhibit the proliferation of HemECs and promote their apoptosis and autophagy through acting on both β1 and β2 adrenoceptor in mast cell. Treated with propranolol, β1, and β2 adrenoceptor on human mast cell expression was reduced significantly. After hemangioma endothelial cell treated with the supernatants from propranolol-treated human mast cell, its proliferation was decreased, but apoptosis and autophagy were significantly induced. Propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s. Mast cells may have a role in the action of propranolol in infantile hemangioma through both β1 and β2 adrenoceptors to inhibit the angiogenic capacity of hemangioma endothelial cells.

Transposition Mucosal Flap Combined With Autologous Fat Transplantation to Repair Lip Defects Caused by Sclerotherapy of Hemangioma.

Infantile hemangiomas are the most common benign childhood tumors and can occur on any part of the human body. Sclerosing agents are used in the early stage of treatment of infantile hemangioma. Sometimes a lip defect remains after sclerosing agent treatment. We developed a simple technique to repair lip defects. The authors performed transposition mucosal flap and autologous fat transplantation surgery on patients who had lip defects caused by sclerosing agents. The flap was transposed 90° from the intraoral labial mucosa to the vermilion defect. Autologous fat was transplanted to the white lip defect. If necessary, a secondary fat transplantation may be performed every half year. All patients were followed up to evaluate the effect of the operation. Patients were asked to rate their satisfaction with the surgery between 1 and 10. Digital three-dimensional evaluation was performed. Sixteen patients underwent the surgery successfully, and the flaps were all viable. No complications occurred after surgery (5 males, 11 females; age range, 5-27 years; 12 upper lip, 3 lower lip, and 1 median lip). The patients were satisfied with the aesthetic outcome of surgery (mean score, 9). Seven patients wanted to undergo a second fat transplantation, whereas 9 patients felt it was unnecessary to transplant fat again. Transposition mucosal flap combined with autologous fat transplantation is reliable and minimally invasive. It is an effective method for repairing moderate lip defects mainly involving vermilion caused by a sclerosing agent.

Propranolol in the Treatment of Infantile Hemangiomas.

Propranolol, as the first generation of β-blocker family, was initially introduced in the clinical application for tachycardia and hypertension in the 1960s. However, the occasional discovery of propranolol in the involution of infantile hemangiomas (IHs) brought us a new perspective. IHs are the most common infantile tumor, affecting 4–10% newborns. So far, oral propranolol is the first-line medication for IHs treatment. At the same time, local injection and topical propranolol are developing. Despite the worldwide application, the precise mechanism of propranolol of IHs has not been completely studied. In this article, we reviewed and summarized the current information on pharmacology, mechanism, efficacy, and adverse effects of propranolol. Novel design of biomaterials and bioactive molecules are needed for new treatment and ideal pathway to attain the minimal effective treatment concentration and eliminate the adverse effects.

Utility of the Infantile Hemangioma Referral Score (IHReS) as a decision-making tool for referral to treatment

BackgroundThe general paediatricians and primary care physicians sometimes face immense difficulty in referral judgements regarding which infantile hemangiomas (IHs) require referrals and when is the appropriate time to refer IHs...

Periorbital Mass in a 2-month-old Girl.

Periorbital Mass in a 2-month-old Girl.

Printing of cutaneous patches loaded with propranolol for the treatment of infantile haemangiomas

Topical propranolol has been used in clinics for treating cutaneous infantile haemangiomas, but frequent applications of semi-solid preparations are required to maintain therapeutic drug concentrations in the skin layers over time. This work aims to study the preparation of cutaneous propranolol patches by hot-melt ram extrusion printing, a novel technique suitable for the personalization of the dosage forms. The preparation steps are: i) mixing of a poly-ammonium methacrylate polymer (Eudragit RL) with a suitable amount of plasticizer [acetyl triethyl citrate (ATEC), triacetin or tributyl citrate, TBC] and the drug (propranolol base, or hydrochloride), ii) the melting in the ram extruder, and iii) the printing on the backing layer foil. All formulations released the loaded drug in a reasonable time and exhibited suitable adhesive properties. The determination of permeation profiles of the drug revealed the patch made of Eudragit RL and TBC and containing 1% propranolol hydrochloride as the most promising formulation for ensuring the drug retention on the human epidermis (Qret/J = 1.32) and, therefore, it can be selected when a superficial haemangioma has to be treated. Conversely, the patch made of Eudragit RL and ATEC and 1% propranolol base can be used in the case of deep haemangiomas.

LncRNA-TUG1 promotes the progression of infantile hemangioma by regulating miR-137/IGFBP5 axis

BackgroundPrevious studies indicated that lncRNA taurine upregulated gene 1 (TUG1) played essential roles in human cancers. This study aimed to investigate its function in infantile hemangioma (IH).MethodsA total of 30 pairs of clinical infantile specimens were used in this study. The expression of TUG1 in IH tissues was assessed by quantitative reverse transcriptase PCR (qRT-PCR). Two short hairpin RNA targeting TUG1 (sh-TUG1-1 and sh-TUG1-2) were transfected into hemangioma-derived endothelial cells, HemECs, to block its expression. The effects of TUG1 on HemECs were evaluated by Cell Counting Kit-8 (CCK-8), colony formation assay, wound healing assay, and Transwell assay. The underlying molecular mechanism of TUG1 was investigated by Starbase prediction and luciferase reporter assay and further determined by loss- and gain-of-function approaches. In addition, the role of TUG1 on tumorigenesis of HemECs was confirmed in an in vivo mouse model.ResultsTUG1 was significantly upregulated in infant hemangioma tissues compared with normal adjacent subcutaneous tissues. The loss- and gain-of-function approaches indicated that TUG1 overexpression promoted proliferation, migration, and invasion of HemECs in vitro, and TUG1 knockdown inhibited the tumorigenesis of HemECs in vivo. Specifically, TUG1 could compete with IGFBP5 for miR137 binding. Rescue experiments further confirmed the role of the TUG1/miR137/IGFBP5 axis in HemECs.ConclusionTUG1 was closely associated with the progression of IH by regulating the miR-137/IGFBP5 axis, which might be a potential target for IH treatment.

СТРАТЕГИЯ И ОПЫТ ЛЕЧЕНИЯ ИНФАНТИЛЬНЫХ ГЕМАНГИОМ

Objective. To analyze the treatment results of patients with infantile hemangiomas using various methods. Methods. The study is grounded on the treatment results of children (n=189) with infantile hemangiomas during the period of 2000-2018 years. All patients were divided into the groups: 1) dynamic observation - 23 (12.2%) children; 2) local destruction - 78 (41.3%); 3) surgical treatment - 22 (11.6%); 4) drug therapy - 66 (34.9%) patients. The interstitial coagulation (n=28) and electrocoagulation of hemangioma (n=50) were applied for the local destruction. 18 patients underwent the complete removal of hemangioma and 4 - segmental resection of tumor with the subsequent propranolol treatment. Propranolol was used for the drug treatment and it was combined with the topical application of timolol (n=13). Results. Hemangioma regression was registered in 18 (78.3%) patients of the first group. Among the patients of the second group, involution of hemangioma was observed in 26 (92.6%) patients when the interstitial coagulation was applied and 2 (7.4%) children had hemangioma recurrence. A strongpositiveeffect can be reached by electrocoagulation of superficial hemangiomas (all patients). With primary radical intervention, complete cure was noted in all children, and with segmental resection only one (4.5%) child had a relapse. Keloid scars were formed in 3 (13.6%) children after surgery. Propranolol seemed to be effective in treating hemangiomasinchildrenof all ages, and in 41 (62.1%) patients hemangiomas completely disappeared. Conclusion. Before initiatingtherapy, thechildrenneed to be assessed for the contraindications and the treatment strategy.In case of infantile hemangioma should be individual based on the results of clinical investigation. Systemic propranolol treatment has gained rapid popularity as the treatment of choice for infantile hemangiomas and may be applied not only as the basic treatment, but also in combination with other methods. Surgical removal of hemangioma remains one of the common treatments components for children with infantile hemangiomas. What this paper adds Different variants of infantile hemangioma treatment have been analyzed: ranging from dynamic observation to surgical and systemic treatment. It has been shown, that in case of infantile hemangiomas, Beta-blockers have become the treatment of choice in case of the absence of contraindications; and surgical treatment is indicated in children with the risk of complications development.

Topical beta-blockers in dermatologic therapy.

An increasing use of beta‐blockers in dermatology has been described over the last 10 years, despite the fact that their use in diseases other than infantile hemangiomas is off‐label. This review discusses the emerging role of topical beta‐blockers in the treatment of infantile hemangioma, but also pyogenic granuloma, Kaposi sarcoma, wounds and nail paronychia. Data in literature demonstrate that topical beta‐blockers are a safe and valid therapeutic option in numerous cutaneous diseases. Side effects are mainly restricted to the application site. Further studies and randomized trials may contribute to reinforce the role of topical beta‐blockers in the dermatological armamentarium.

Is prolonged monitoring necessary? An updated approach to infantile hemangioma treatment with oral propranolol.

Infantile hemangiomas (IH) are the most common soft-tissue tumors in childhood, occurring in up to 1 in 10 infants. Oral propranolol has been well established as the first-line treatment of complicated hemangiomas; however, variability in the administration protocol remains. We sought to evaluate our current propranolol treatment protocols to determine if the level of monitoring and follow-up predicts immediate or future adverse events by comparing one in-person visit vs two in-person visits versus teledermatology for treatment initiation and dose escalation. We analyzed retrospective data on 279 patients diagnosed with IH and treated with oral propranolol on an in-person or virtual telemedicine outpatient basis from January 01, 2015 through May 31, 2020. Data were collected via chart review on all aspects of patient demographics, treatment indication, treatment initiation, adverse events, and follow-up visits. Two monitoring visits (Protocol 1) versus one (Protocol 2) was not associated with decreased adverse outcomes (P=.255). The odds of having an adverse event in Protocol 1 compared to Protocol 2 was insignificant (OR: 0.64; CI: 0.30-1.38). The most frequently reported adverse event among patients in both protocols was sleep disturbance. However, it did not vary significantly among the groups (P=.980, OR: 0.98, CI: 0.35-2.69). Prolonged in-office monitoring of propranolol initiation and dose escalation (Protocol 1) may not be necessary for the setting of adequate prescreening as it does not predict immediate or future adverse events.

Propranolol vs. steroids in the treatment of infantile hemangiomas: A meta-analysis.

Infantile hemangioma (IH) is a common disease, and drug therapy is the most common treatment method. Clinically, steroids have long been used as first-line drugs, but in recent years, some doctors have begun to use propranolol to treat infantile hemangiomas (IHs). The present study performed a meta-analysis to evaluate the clinical effects of propranolol in comparison with steroids in the treatment of infantile hemangiomas. A detailed review of the literature on PubMed, Cochrane Library, Embase and Web of Science was performed prior to March 31, 2020. All literatures were compared with the clinical effects of propranolol and steroids in the treatment of infantile hemangiomas. A total of two researchers independently screened the literature according to the selection criteria, extracted data and assessed the risk of bias for the included studies. Review Manager 5.3 was used to meta-analyze all the included studies. According to the selection criteria, nine articles were included in the present study. The meta-analysis revealed that the effective rate of propranolol was greater than that of steroids in treating infantile hemangiomas [odds ratio (OR), 3.96, 95% confidence interval (CI), 2.47-6.37; P<0.00001]. Additionally, propranolol had fewer complications than steroids (OR, 0.21; 95% CI, 0.12-0.36; P<0.00001). The recurrence rate of the two groups was not statistically different (OR, 1.83; 95% CI, 0.59-5.70; P=0.3) and the surgical resection rate of propranolol was lower than steroids (OR, 0.19; 95% CI, 0.08-0.46; P=0.0002). The present study demonstrated that propranolol is more effective than steroids for the treatment of IHs, and provides a theoretical basis for the clinical use of propranolol as an alternative to steroids.

Topical Beta Blockers in Small Infantile Hemangioma: State of the Art?

Infantile hemangiomas (IH) are benign forms of endothelial proliferation in the first 8 weeks of life. Leaute-Labreze et al. published the first spontaneous cases of IH treated with beta blockers in 2008 due to their cardiac disease in the New England Journal of Medicine. This was a revolutionary new understanding of treatment in infantile hemangioma (IH). Not only systemic but also topical beta blockers seem to be an effective treatment option for small infantile hemangioma. Efficacy and safety of topical beta blockers in the treatment of infantile hemangioma (IH) were proved in systematic reviews and meta-analysis.

МЕЖДИСЦИПЛИНАРНЫЙ ПОДХОД К ЛЕЧЕНИЮ МЛАДЕНЧЕСКИХ ГЕМАНГИОМ

The aim of the study is to find the best approaches to the treatment of infantile hemangiomas (IH). Materials and methods of research: the experience of treatment of pediatric patients with IH of various localization is presented, which was carried out according to the protocol elaborated by the authors. Systemic therapy with propranolol, local therapy, laser therapy were used in the complex of treatment. The age of patients at the beginning of therapy ranged from 1 month up to 4,5 years. Results: in all cases, patients with propranolol treatment showed a quick and stable effect. Even at the time of the selection of the dose of the drug, IH patients began to involute, became paler, less tense. The thickness of the soft tissues in the IH area decreased by 65% compared to the baseline, the number of functioning vessels decreased by 86%. The maximum effect was achieved within the first 6 months from the start of therapy. Clinical case report – a 2,5-year-old child with extensive hemangioma of the right buttock. There was a complex treatment with propranolol, local therapy, laser therapy. The general course of treatment with propranolol was 2 years 8 months. The total number of laser interventions was 6 with the overall effect in the form of maximum regression of residual clinical manifestations of IH. A positive clinical and ultrasound picture was noted, indicating a pronounced involution of IH, and a gradual withdrawal of propranolol was started. Conclusion: the effectiveness of a comprehensive interdisciplinary approach to the treatment of extensive complicated IH was demonstrated with the participation of specialists of various disciplines: pediatricians, cardiologists, surgeons, specialists in functional and ultrasound diagnostics, specialists in laser therapy, endocrinologists in a severe premature baby with a large number of somatic problems. The clinical treatment algorithm developed and implemented for patients with IH makes it possible to avoid more aggressive methods of treatment of this pathology and to improve the quality of life of this category of patients. On the basis on the results obtained, indications for laser therapy with a selective pulsed laser were formulated.

Update on infantile hemangioma.

The International Society for the Study of Vascular Anomalies classifies vascular anomalies into vascular tumors and vascular malformations. Vascular tumors are neoplasms of endothelial cells, among which infantile hemangiomas (IHs) are the most common, occurring in 5%–10% of infants. Glucose transporter-1 protein expression in IHs differs from that of other vascular tumors or vascular malformations. IHs are not present at birth but are usually diagnosed at 1 week to 1 month of age, rapidly proliferate between 1 and 3 months of age, mostly complete proliferation by 5 months of age, and then slowly involute to the adipose or fibrous tissue. Approximately 10% of IH cases require early treatment. The 2019 American Academy of Pediatrics clinical practice guideline for the management of IHs recommends that primary care clinicians frequently monitor infants with IHs, educate the parents about the clinical course, and refer infants with high-risk IH to IH specialists ideally at 1 month of age. High-risk IHs include those with life-threatening complications, functional impairment, ulceration, associated structural anomalies, or disfigurement. In Korea, IHs are usually treated by pediatric hematology-oncologists with the cooperation of pediatric cardiologists, radiologists, dermatologists, and plastic surgeons. Oral propranolol, a nonselective beta-adrenergic antagonist, is the first-line treatment for IHs at a dosage of 2–3 mg/kg/day divided into 2 daily doses maintained for at least 6 months and often continuing until 12 months of age. Topical timolol maleate solution, a topical nonselective beta-blocker, may be used for small superficial type IHs at a dosage of 1–2 drops of 0.5% gel-forming ophthalmic solution applied twice daily. Pulse-dye laser therapy or surgery is useful for the treatment of residual skin changes after IH involution.

Modern treatment of infantile hemangioma

Infantile hemangioma (IH) is the most common benign vascular tumor in children of the first year, which is based on abnormal proliferation of endothelial cells under the influence of the main pro-angiogenic factors: vascular endothelial growth factor (VEGF) and fibroblast growth factors (FGF). It develops in the first weeks after birth, forming over 3–9 months with regression in the next 3–7 years. Three-quarters of infantile hemangiomas are nodular and are not accompanied by malformations. At the same time, segmental IH is most often associated with syndromic forms. Despite spontaneous regression (in 90% of cases), some forms and localization of IH can lead to the development of complications, local and endangering vital functions. In most cases, the diagnosis is based on anamnesis, characteristic features of the tumor, and clinical course. Additional studies (ultrasound DG, MRI/CT, biopsy) are necessary in complicated forms and in doubtful clinical cases.