Infantile hemangioma. Part 2: Management

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

Infantile hemangiomas are the most common tumor of childhood and undergo rapid growth during early infancy followed by gradual involution. After involution, residual lesions sometimes remain. Oral propranolol usually induces earlier involution and redness reduction of infantile hemangiomas. However, the optimal treatment duration is unknown and infantile hemangiomas sometimes recur after cessation of treatment. We report three Japanese patients with recurrent infantile hemangiomas on their cheek. These patients were a 1-month-old female baby with a superficial infantile hemangioma, a 3-month-old female baby with a mixed infantile hemangioma and a 4-month-old male baby with a mixed infantile hemangioma. Two of them also received pulsed dye laser treatment. They did not reach complete or nearly complete resolution of infantile hemangiomas at week 25. These patients experienced regrowth of their infantile hemangioma after 20 months of age and took propranolol after the age of 24 months. There were no severe adverse effects. Propranolol may not only be therapeutic but also prophylactic. Patients with infantile hemangiomas who have taken oral propranolol should be followed up at least 6 months after cessation of treatment, especially infantile hemangiomas on the cheek, and those with partial response to propranolol may require close attention in prolonged growth.

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.

Topical imiquimod in the treatment of infantile hemangiomas: A retrospective study

The combination treatment for mix infantile hemangiomas (IHs) using oral propranolol with topical timolol maleate was not well documented in the literature. The aim of this study was to evaluate the therapeutic effects and safety of oral propranolol along with topical timolol maleate or oral propranolol alone for treating mixed IHs in the oral and maxillofacial regions. Between March 2013 and June 2014, a total of 31 patients with mixed IHs in the oral and maxillofacial regions were recruited to the study and randomly divided into experimental and control groups. Fourteen patients in the experimental group (A) were treated with oral proranolol in combination with topical timolol maleate, and 17 patients in the control group (B) underwent orally proranolol treatment alone. The maximal treatment duration was planned for 8 months. Ultrasonography and serial photographs based on Visual Analogue Scale (VAS) were used to assess the effects of treatment before and after treatment, as well as adverse effects after medication were evaluated and managed accordingly. All patients completed treatment. Among the most patients, there was obvious fading of color or decrease in size of the IHs when compared with pretreatment. There was significant reduction of color fading in A (mean VAS score: 8.36 ± 1.39) than that in B (7.18 ± 1.71) (P = 0.043) after the end of treatment, whereas the reduction of sizes in A (8.00 ± 1.75) had no significant difference than that in B (7.59 ± 1.80) (P= .51). The treatment duration of A (5.64 ± 1.45) was shorter than that of B (6.71 ± 1.10) (P= .037). No major collateral effects were observed in both the groups throughout the course of treatment. Oral proranolol combined with topical timolol maleate was well tolerated and effective treatment, mild side effects, and especially gave rise to better clinical response in the treatment of mixed IHs than oral propranolol alone.

Clinical observations on the treatment of infantile hemangiomas with topical imiquimod 5% cream

Introduction. Infantile hemangiomas (IH) are the most common benign vascular tumor of children of the first year and are an interdisciplinary problem of neonatologists, pediatricians, pediatric cardiologists, oncologists, pediatric surgeons, dermatologists. Depending on the age of child, phase of pathological process, size, and localization of the IH, the management tactics of such children can be conservative (pharmaceuticals therapy) or invasive (laser therapy, surgical methods). Laser therapy with a pulsed dye laser has proven itself well to correct and minimize residual phenomena because of spontaneous involution and after the completion of pharmaceuticals treatment.The purpose of the study is to analyze the experience of using Hemangiol® (oral solution) for the treatment of children with IH, obtained in 10 medical hospitals in 6 cities of Russia.Materials and methods. Treatment with Hemangiol® was carried out in 6 cities of Russia on the basis of 10 medical hospitals (Children’s CityClinical Hospital named after Z.A. Bashlyaeva of Moscow City Health Department, Research Institute of Pediatric Oncology and Hematology of N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia (Moscow), Russian Children’s Clinical Hospital of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia (Moscow), Children’s City Clinical Hospital named after N.F. Filatov of Moscow City Health Department, Saint Petersburg Clinical Scientific and Practical Center of Specialized Medical Assistance (Oncological) (S.-Petersburg), Almazov National Medical Research Centre, Ministry of Health of Russia (S.-Petersburg), Rostov Regional Clinical Hospital (Rostov-on-Don), Stavropol Regional Children’s Clinical Hospital (Stavropol), Samara Regional Clinical Hospital named after V.D. Seredavin, Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan (Kazan) in the Departments of Pediatric Cardiology, Surgery, Oncology, Pediatrics from January 2020 to December 2021. Therapy with Hemangiol® was received by 49 children with IH for at least 3 months. Before the start of treatment, the patients’ heart rate and blood pressure were measured, general and biochemical blood tests were performed, electrocardiography and ultrasound IH were performed. According to the indications, ultrasound of the liver and thyroid gland was performed to determine the parameters of the thyroid status. Before the start of therapy and during dynamic observation, photo documentation was performed against the background of treatment. In the absence of contraindications to treatment, Hemangiol® was prescribed. During a six-month course of treatment with Hemangiol®, effectiveness was evaluated based on the results of a clinical examination and based on photographs. The appearance of possible adverse reactions was monitored.Results. In 33 (67.3 %) children with IH, therapy with Hemangiol® was completed within 6 months. The effect of treatment in the form of a pronounced regression of vascular tumor was achieved in 25 (75.8 %) of 33 patients. In 16 (32.7 %) of 49 children, treatment with Hemangiol® was continued for more than 6 months. The first symptoms of improvement were observed from the second to 10 days after the start of Hemangiol® therapy in 45 patients, which was (91.8 %). Rebound syndrome (recurrence of IH) was detected in 2 (6.0 %) of 33 children who completed therapy. Transit adverse reactions (decreased heart rate, increased excitability, lethargy) on therapy of Hemangiol® were observed in 8 (16.3 %) children. The duration of therapy with Hemangiol® depended on the prevalence, the depth of the IH lesion, as well as on the presence of prematurity in a child with IH (r = 0.533, p &lt; 0.05). Successful laser treatment with a pulsed laser on a dye after the completion of systemic Hemangiol® therapy, were on 5 children of Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia.Conclusion. The results of the using of Hemangiol® as a modern means of systemic pharmacotherapy of IH therapy in 10 medical hospitals in 6 cities of Russia have demonstrated its high efficiency and safety.

Pulsed dye laser (PDL) is an important treatment for superficial infantile hemangioma, but few studies report on its cellular mechanism. The aim of this study was to evaluate alterations of serum vascular endothelial growth factor (VEGF) level in infantile hemangioma (IH) patients after laser treatment and effects of PDL irradiation on human umbilical vein endothelial cells (HUVECs) in vitro, as well as to explore the biomolecular mechanisms and ultrastructure changes of the PDL effect. 74 children with infant hemangioma including 45 patients in proliferating phase, 18 patients in involuting phase, 11 patients in involuted phase and 10 healthy children were engaged in this study. The plasma VEGF levels of children were measured with the enzymelinked immunosorbent assay (ELISA). 24 hours after, HUVECs cultured in vitro were irradiated with PDL, cell apoptosis, mRNA levels of VEGF, and changes of ultrastructure were evaluated using flow cytometry, real-time reverse transcriptase polymerase chain reaction (RT-PCR), and transmission electron microscopy, respectively. The serum VEGF concentrations in children with proliferating hemangiomas were significantly higher than in patients with involuting / involved hemangiomas and healthy patients. After receiving 3 laser treatments, the plasma VEGF levels of IH patients in proliferating hemangiomas decreased significantly. PDL irradiation could down-regulate VEGF mRNA expression of HUVECs, and increase cell apoptosis rate. The present study demonstrates that PDL irradiation imparts apoptosis induction effects on HUVECs in vitro. Furthermore, our results suggest that vascular endothelial growth factor may be of particular importance in pathophysiology and PDL treatment of hemangiomas, also serum VEGF levels may be used as an aid in the follow up of IH. This provides valuable evidence of the PDL effect on infantile hemangioma.

Relevance.Infantile hemangiomas are the most prevalent vascular tumors in children. Since the natural progression of infantile hemangiomas is typically benign, over 90 % of cases do not require medical intervention. However, treatment is necessary for infantile hemangiomas that present local complications, functional impairments, or arisk of disfigurement. In this article we presented two children with mixed and deep infantile hemangiomas, with satisfactory therapeutic responses after treatment with topical timolol maleate.Conclusion.Timolol maleate is an effective, well-tolerated, and safe treatment option for various types of infantile hemangiomas.

Objective To investigate whether topical mucopolysaccharide polysulfate (MPS) cream can reduce the incidence of eczema and skin atrophy in patients with moderate- or low-risk infantile hemangioma after the treatment with topical beta-blockers or 595-nm pulsed dye laser (PDL) , and to analyze factors influencing the occurrence of eczema and skin atrophy. Methods A total of 722 patients aged 0- 1 years with moderate- or low-risk infantile hemangioma were enrolled from 5 Children′s Hospitals in China. According to the disease condition and therapy acceptability, these patients were divided into 6 groups to be treated with topical beta-blockers and MPS cream (blocker+ MPS group) , topical beta-blockers (blocker group) , 595-nm PDL and topical MPS cream (PDL+ MPS group) , 595-nm PDL (PDL group) , 595-nm PDL combined with topical beta-blockers and MPS cream (PDL+ blocker+ MPS group) , and 595-nm PDL and topical beta-blockers (PDL+ blocker group) , respectively. All the externally applied agents were applied twice a day, and PDL was performed once every 4 weeks. Efficacy and adverse reactions were evaluated after 3-month treatment. Univariate and multivariate Logistic regression analyses were carried out to analyze factors influencing the incidence of eczema and skin atrophy in patients with infantile hemangioma after treatment, and chi-square test was carried out to compare efficacy among the groups. Results After 3-month treatment, multivariate Logistic regression analysis for comparing the blocker+ MPS group with blocker group showed that the risk factor for eczema on the surface of hemangiomas was no topical treatment with MPS cream (P= 0.007, OR= 3.887, 95% CI: 1.439-10.493) , while no correlations were observed between the occurrence of skin atrophy on the surface of hemangiomas and analyzed factors. Multivariate Logistic regression analysis for comparing the PDL+MPS group with PDL group showed that no topical treatment with MPS cream (P 0.05) . Conclusion During the treatment of moderate- or low-risk infantile hemangioma with topical beta-blockers or 595-nm PDL, the combination with topical MPS cream can reduce the occurrence of eczema and skin atrophy without affecting the therapeutic effect. Key words: Hemangioma; Infant; Eczema; Mucopolysaccharide polysulfate; Skin atrophy; Adverse reaction

The purpose of the study is to describe the experience of a multidisciplinary team in a tertiary hospital regarding the management of Infantile Hemangiomas (IH). The method employed is a retrospective analysis of patients with IH followed in a tertiary pediatric hospital between January 2010 and May 2022. A total of 393 IH were diagnosed (56.7% female), with a median age of 5months (interquartile range (IQR), 3-10). Imaging investigation was necessary for diagnosis and for exclusion of other IH in 9.2% and 14.3%, respectively. Focal (74.0%) and superficial (59.7%) lesions were more frequent as was facial location (35.9%). Pre-treatment ulceration or hemorrhage occurred in 6.6%. At follow-up, 87.4% regressed partially and 12.6% completely; 2.7% relapsed. Propranolol was started in 30.0% of cases for a median period of 9months (IQR, 6-12), mainly due to esthetic concerns (41.9%). Side effects occurred in 8.3% (sleep disturbance in 5.1%). Only 1.7% were refractory and 5.9% had a rebound effect. Eleven patients were treated with topical timolol and 41 underwent surgery. Patients that were treated with propranolol had more risk factors (p = 0.016) and presented deeper lesions (p < 0.001) with a larger diameter (p < 0.001); total IH regression was less frequent (p < 0.001). Since 2020, twice-daily dosage was more frequently prescribed than three times daily (p = 0.007) and inpatient initiation of propranolol decreased (p = 0.750), without significant difference in the incidence of adverse reactions, duration of treatment, and lesion evolution. Conclusions: Our protocol proved to be safe and feasible in an outpatient setting and twice daily administration of propranolol was effective. The majority of IH showed at least partial regression. Early detection of high-risk IH is paramount and a multidisciplinary assessment by a specialized team is essential for adequate management. What is Known: • IH are the most common vascular tumors in childhood. Although the majority evolves favorably, treatment may be warranted in selected cases. • Early detection of high-risk IH is paramount, and a multidisciplinary assessment by a specialized team is essential for adequate management. What is New: • One-third of our sample was treated with propranolol. These patients had more risk factors and presented deeper lesions with a larger diameter, and tumor total regression was less frequent. • Our results reinforce safety and feasibility of propranolol initiation in an outpatient setting, including twice daily dosage.

Infantile hemangiomas (IH) are initially warm due to increased proliferation and perfusion then involute with apoptosis and reduced perfusion. Objective quantitative evaluation of IH treatment response is essential for improving outcomes. We applied a functional imaging method, dynamic infrared (IR) thermography, to investigate IH status versus control skin and over time. A preliminary prospective observational study was conducted among 25 subjects with superficial or mixed IHs (< 19 months) over 59 clinic visits. Infrared images of IHs and control sites, standardized color images, and three-dimensional images were obtained. Tissue responses following application and removal of a cold stress were recorded with video IR thermography. Outcomes included areas under the curve during cooling (AUCcool ) and rewarming (AUCrw ) and thermal intensity distribution maps. AUCcool and AUCrw were significantly higher and cooling rate slower for IHs versus uninvolved tissue indicating greater heat, presumably due to greater perfusion and metabolism for the IH. IR distribution maps showed specific areas of high and low temperature. Significant changes in IH thermal activity were reflected in the difference (AUCcool - AUCrw ), with 6.2 at 2.2 months increasing to 37.6 at 12.8 months. IH cooling rate increased with age, indicating slower recovery, and interpreted as reduced proliferation and/or involution. Dynamic IR thermography was a well-tolerated, quantitative functional imaging modality appropriate for the clinic, particularly when structural changes, i.e., height, volume, color, were not readily observed. It may assist in monitoring progress, individualizing treatment, and evaluating therapies. www.clinicaltrials.gov (Identifier NCT02061735).

This systematic analysis is conducted to evaluate advancements in managing extensive infantile hemangiomas (IH). The focus is on functional and aesthetic outcomes for infantile hemangiomas (IH) infants who undergo most recent treatments. IH benign vascular tumors affecting 4-10% of infants that can disrupt vital functions and present aesthetic concerns. Treatments like propranolol which is a beta-blocker have revolutionized care with 90% effectiveness but limitations persist, particularly in addressing residual scarring and tissue remodeling. Study employs a systematic review methodology under PRISMA guidelines while analyzing global IH data and therapeutic advancements and including beta-blockers, laser therapy and combination treatments. We suggest propranolol is a good option for its role in reducing IH size and severity and laser therapy enhancing results for complex cases. Combination therapies like propranolol with laser or topical agents improve efficacy while minimizing side effects and advanced techniques such as pulsed dye laser and Nd: YAG have been effective but are mostly used for residual scars. Despite improvements there are gaps remain in understanding long-term outcomes or recurrence rates and other gaps are concerning to patient satisfaction. We warrant integrated multidisciplinary approaches to improve care. Regional disparities in IH management are noted with limited access to timely diagnosis in low-income regions while future research should focus on personalized treatment strategies and safety and optimizing therapeutic combinations to enhance both functional and aesthetic outcomes. Regional disparities in IH management are noted, with limited access to timely diagnosis in low-income regions. Future research should focus on personalized treatment strategies, safety, and optimizing therapeutic combinations to enhance both functional and aesthetic outcomes.

Infantile hemangiomas, complications and treatments

To review and evaluate the medical literature on new treatments for periocular infantile (capillary) hemangioma. Recent studies have shown a promising new therapy for infantile hemangioma using nonselective β-blockers, including oral propranolol and topical timolol. Conventional treatments for infantile hemangioma include the use of corticosteroids, laser, surgery, and immunomodulator therapy. Recently, systemic and topical β-blockers have been used to successfully treat infantile hemangioma. The drugs' mechanism of action remains uncertain, but plausible theories include vasoconstriction, modulation of pro-survival signal transduction pathways, and endothelial cell apoptosis. Whereas no life-threatening adverse events from β-blocker treatment have been described, there have been reports of bradycardia, hypotension, bronchospasm, hypoglycemia, and electrolyte disturbances resulting from systemic use of propranolol to treat infantile hemangioma. Sleep and gastrointestinal disturbances have also been frequently reported. Topical timolol application for localized, superficial tumors may confer similar efficacy as oral propranolol while reducing systemic effects. Despite the recent explosion of interest surrounding this novel treatment, current treatment and protocol-monitoring recommendations are based largely on the experience of individual centers. Several randomized controlled studies are currently underway, the results of which will guide future standard-of-care treatment for infantile hemangioma.