Infantile Hemangioma (IH) is the most common benign vascular tumor occurred in infants and young children. The larger hemangiomas or lesions located in specific areas can cause severe complications, such as disfigurement, obstruction, or ulceration, increasing the risk of functional impairment. Propranolol, serving as the first-line drug for IH treatment, still poses various challenges. Certain patients exhibit low sensitivity to propranolol therapy or face recurrence, which become the leading reason for the failure of IH treatment. Additionally, the requirement for frequent daily medication can also complicate adherence for patients. Hence, developing novel IH therapy methods or drug administration routes is significantly important to enhance therapeutic effect and reduce side effects. Accordingly, in this study, we introduced an innovative photothermal, dissolving microneedles (MNs) patch designed specifically for IH therapy. Firstly, a pH responsive self-assembly nanoplatform with photothermal effect is designed by encapsulating propranolol (PRN) into zeolitic imidazolate framework-8 (ZIF-8) NPs and modifying with TA/Fe nanocomplexes. The fabricated PRN@ZIF-8@TA/Fe (PZ@TA/Fe) NPs exhibited good biocompatibility, pH-responsive degradation, photothermal conversion efficiency inside hemangioma endothelial cells (HemECs). Importantly, TA/Fe surface modification led to intracellular iron overload, which subsequently induced the Fenton reaction and triggered ferroptosis process. The combination of photothermal therapy and ferroptosis therapy exhibited a superior synergistic effect in damaging HemECs and vascular structures. The PZ@TA/Fe NPs loaded in MNs patch further ensured targeted delivery to lesion areas and achieved precise and maximal release of the PZ@TA/Fe NPs, while reducing systemic side effects to normal vasculature or tissue. The PZ@TA/Fe@MNs showed remarkable anti-angiogenic effect against IH in mice model. This study first investigates the potential of ferroptosis therapy in IH treatment, and highlights the substantial therapeutic effect of combining photothermal therapy and ferroptosis effects against IH proliferation. This approach can also become a more effective and safer treatment method for other diseases characterized by abnormal angiogenesis.

Infantile hemangiomas (IHs) are the most common vascular tumors in children. While many are uncomplicated, a significant minority can cause cutaneous complications or be associated with multiorgan congenital anomalies. Infants with so-called "segmental" IH (patterned and not round) are at-risk for two related syndromes: PHACE (posterior fossa anomalies, hemangioma of the head or neck, cerebrovascular arterial anomalies, cardiac and eye anomalies) and LUMBAR (IH of the lower body; urogenital anomalies and IH ulceration; spinal cord malformations; bony, anorectal, arterial, and renal anomalies). Prompt recognition of LUMBAR syndrome is crucial, given the potential for IH-associated complications, such as ulceration and permanent disfigurement, and more importantly, associated regional birth anomalies. This article synthesizes current knowledge on LUMBAR syndrome, including recognition, evaluation, diagnosis, risk factors, pathogenesis, and management. [Pediatr Ann. 2025;54(3):e112-e116.].

We observed many preterm infants with unexpectedly thick infantile hemangiomas (IH), a subtype known to be associated with an increased risk of scarring.

To cf the clinical features of localized IH in preterm vs term infants.

A retrospective study was conducted at 3 tertiary referral centers involving 830 consecutive patients with localized IH.

Preterm infants had a significantly higher incidence of superficial IH (75% in <33 weeks, 57% in 33 to <37 weeks, and 50% in term infants, P = .007). Overall, their IH had thicker superficial components (P < .001) and more stepped borders (P < .001). These features correlated with the degree of prematurity. The average chronological age at presentation to the specialist was 5.6 (SD = 6.2) months, with no difference observed in gestational age.

The retrospective design and use of nonstandardized clinical photographs. There may be biases introduced toward more severe IH types because the study sites were tertiary referral centers.

Preterm infants have features of IH that have obvious implications for systemic therapies. Most of these infants were seen beyond the typical proliferative phase when irreversible skin changes may have already occurred.

This bibliometric analysis aimed to analyze global research trends in laser therapy for hemangiomas, a common benign vascular tumor in children from 1977 to 2024. Publications in laser therapy for hemangiomas from 1977 to 2024 were retrieved from the Web of Science Core Collection (WoSCC) database, and only articles published in English were analyzed. Bibliometric and visual analyses were performed using VOSviewer, CiteSpace, and the R package "bibliometrix." A total of 1,028 publications from 66 countries and 4,199 authors were analyzed, showing an annual growth rate of 5.61%. The United States led with 365 articles and 11,713 citations. Major contributors included the University of California System and Harvard Medical School, and key journals were Lasers in Surgery and Medicine and Dermatologic Surgery. Pulsed dye laser (PDL) was the most studied laser type. Research focused on optimizing treatment safety, effectiveness, and management, especially in children. The rise of propranolol as a keyword highlighted its increasing role in hemangioma therapy, and the keyword like "classification" and "vascular anomalies" underlining the importance of accurate diagnosis and classification. This study highlights the growing importance of laser therapies for hemangiomas. Future research should explore combining propranolol with laser treatments and the role of precise diagnosis in improving treatment outcomes.

Infantile hemangiomas (IHs) are characterized by spontaneous regression, and their pathogenesis involves immune cell infiltration and programmed cell death. The molecular pathways and mechanisms involved in pyroptosis in IHs are still unclear. This study aimed to identify genes related to pyroptosis in IH regression by bioinformatics methods and to explore the effects of these pyroptosis-related genes (PRGs) on disease pathology and immune cell infiltration.

The microarray dataset GSE127487 was assessed to identify differentially expressed genes (DEGs) between proliferation-phase IH (PIHs) and involution-phase IH (IIHs). The DEGs that overlapped with PRGs were considered IH-PRGs. The IH-PRGs were validated and subjected to functional enrichment analysis and Genomes pathway analyses. Gene set enrichment analysis (GSEA) was also performed to analyse the biological significance of the DEGs. The NetworkAnalyst database was used to analyse the correlation network of IH-PRGs and miRNAs as well as that of IH-PRGs and transcription factors. The STRING online database and Cytoscape were used to identify the hub-IH-PRGs. Additionally, a single-sample GSEA algorithm was applied to assess immune cell infiltration in IHs, and correlation analysis was performed between the hub-IH-PRGs and infiltrating immune cells.

Fourteen IH-PRGs were identified. IL6, EGFR, IRF1 and IL32 were identified as hub-IH-PRGs and displayed excellent diagnostic performance. Immune cell infiltration analysis revealed notable differences in CD8+ T cells, Tgd cells and Th17 cells between PIHs and IIHs. IL-6 was significantly positively correlated with Th17 cell infiltration and significantly negatively correlated with Tgd cell infiltration; EGFR was negatively correlated with Tgd cell infiltration; and IRF1 and IL32 were significantly negatively correlated with Th17 cell infiltration.

Four PRGs, namely, IL6, EGFR, IRF1 and IL32, may play a significant role in IH regression. This study provides insights into the molecular mechanisms underlying IH pathogenesis, highlighting the importance of pyroptosis and immune cell infiltration.

Numerous studies have shown that topical timolol is effective in treating infantile hemangioma (IH) with minimal adverse events. However, consensus is lacking on optimal timing, dosage, frequency, and safety parameters for this treatment. This study aims to explore the timing and safety of topical timolol treatment for superficial IH. A retrospective analysis included pediatric IH patients who underwent topical timolol treatment at the Department of Pediatric Surgery of Sichuan Provincial People's Hospital between January 2019 and January 2023. Medical records were reviewed for patient information, lesion characteristics, outcomes, and complications. Topical timolol was administered to 666 IH patients. Median follow-up was 10 months. 480 cases had excellent or good outcomes, while 186 had fair or poor outcomes. Patients ≤ 3 months had better outcomes than those > 3 months (Z = 4.713, P < 0.001). Small IH had better outcomes than large IH (Z = 1.991, P = 0.046). Lesion locations did not significantly affect outcomes (H = 10.252, P = 0.114). Respiratory problems occurred in 58 (8.7%) cases, localized skin irritation occurred in 48 (7.2%) cases, sleep disturbance occurred in 30 (4.5%) cases, and residual skin lesions occurred in 26 (3.9%) cases. In 59 (8.8%) cases the IH had relapses.

Topical timolol is safe and effective for IH. Patients who are aged 1 < months ≤ 3 or have small (1.5 cm < max diameter ≤ 5 cm) IH are more likely to experience better outcomes. It also may reduce the incidence of residual skin lesions and relapse. Therefore it may be a useful alternative therapy option for superficial IH.

• β-blockers are now considered to be first-line treatment of infantile hemangioma. • Topical timolol treatment is safe and effective for infantile hemangioma.

• Patients who are aged ≤ 3 months or have a max diameter ≤ 5 cm infantile hemangioma are likely to experience better outcomes by topical timolol treatment. • Topical timolol treatment may reduce the incidence of residual skin lesions and infantile hemangioma relapses.

Hemangiomas are common benign vascular tumors that often present in childhood. The 595 nm pulsed dye laser (PDL) is now being widely used to treat vascular skin lesions. This case series was performed to review the therapeutic efficacy and safety of PDL in the treatment of hemangiomas among Vietnamese patients. A total of 43 Vietnamese patients (79.1% females), mean age was 8.83 years old (2 months - 54 years old), with a clinical diagnosis of hemangioma, were treated with the PDL over 2 years. Treatments were performed every 4 weeks. Hemangioma lesions that occur on the head and the neck are seen in 65.1%, 67.4% of superficial, and 32.6% of mixed hemangioma subtypes. The mean treatment is 5.3 times. Excellent-good results were achieved in 86.1%, average results in 11.6%. No permanent side effects during the treatments were observed. Treatment of hemangiomas using the 595 nm PDL is an effective and safe method in the skin types of Vietnamese patients. The effect does require several treatment sessions.

Infantile hemangioma (IH) is the most common pediatric benign vascular tumor. Its pathogenesis is still poorly understood, and it usually appears during the first few weeks of life and follows a characteristic natural course of proliferation and involution. Most IHs are small, benign, resolve spontaneously, and do not require active treatment but only active observation. A minority of IHs are potentially problematic because they can cause life-threatening complications, permanent disfigurement, and functional impairment. Diagnosis is usually clinical, and propranolol is currently the mainstay of treatment. Other therapeutic modalities may be used alone or in combination, depending on the characteristics of the specific IH. New treatment options are being explored every day, and some are showing promising results. It is undeniable that therapeutic modalities for IHs must be selected based on the child's age, the size and location of the lesion, the presence of complications, the implementation conditions, and the possible outcomes of the treatment. The future of IH management will certainly be reflected in improved advanced imaging modalities, research into the genetic and molecular basis, the development of new pharmacological agents or techniques, and the development of standardized protocols, all to optimize outcomes with minimal side effects.

Infantile hemangioma (IH) is a common benign tumor in infants. While most cases exhibit a self-limiting nature, some require medical treatment to avoid complications. Propranolol is the first-line therapy for IH, it has a high success rate, and is safe to use. Unfortunately, some patients might experience rebound growth after propranolol discontinuation. Currently, it is unclear which factors predict this phenomenon. This study aimed to identify factors affecting the rebound growth of IH after propranolol cessation. We also aimed to identify predictors for an excellent response to oral propranolol.

We performed a retrospective cohort study using clinical data from all patients referred to our clinic with IH and placed on systemic oral propranolol between January 2009 to December 2023 in the dermatology outpatient clinic of Rambam Healthcare Campus.

Out of a total of 552 patients with IH, 301 received oral propranolol for at least 6 months. A relapse phenomenon was observed in 38 (12.6%) patients. We found a significant association between limb involvement and the least likelihood of hemangioma rebound (p < 0.001). An excellent response to oral propranolol was observed in 57.8% of patients. Younger age at initiation of oral propranolol was associated with an excellent response (p = 0.015). Also, IHs located on the limbs (67) showed a higher rate of excellent response to oral propranolol compared to other anatomical sites (p = 0.02). Interestingly, patients who were treated with a dose of 2 mg/kg/day were associated with excellent response to treatment (p = 0.007).

IHs located on the limbs demonstrated less rebound growth and a better treatment response. When oral propranolol was initiated earlier or when the target dose was 2 mg/kg/day, there was a higher rate of excellent response to treatment.

Hemangiomas are superficial tumors characterized by dense vascular structures that often affect the patient's aesthetic appearance due to the obvious red appearance on the skin. Current treatments, especially timolol maleate in the form of eye drops and hydrogels, suffer from low transdermal drug delivery rates, resulting in prolonged treatment time. To address this challenge, our study introduced a soluble microneedle patch with dextran as the main material to form microcatheters for sustained delivery of timolol maleate. In addition, we proposed a vascular embolization strategy to disrupt the blood supply in hemangiomas. Oxidized cellulose (C-cellulose) was selected for its excellent hemostatic properties. We incorporated C-cellulose into dextran microneedles to facilitate thrombosis in the vascular-rich areas of hemangiomas. The innovative microneedle patch we developed can penetrate the skin to a depth of 430 μm and dissolve rapidly within 3 minutes, ensuring direct drug delivery to the subcutaneous layer. Notably, the treated skin area regained its original appearance within two hours after treatment. In addition to excellent skin permeability and rapid dissolution, these patches significantly promoted apoptosis and inhibited cell migration in mouse hemangioendothelioma EOMA cells. Our results demonstrate that this approach not only achieves significant tumor inhibition in a mouse hemangioma model, but also represents a more effective, convenient, and non-invasive treatment option. Therefore, dextran/C-cellulose/timolol maleate microneedle patch (MNs/Timolol) has broad clinical application prospects in the treatment of hemangiomas, minimizing the risk of additional damage and improving treatment efficacy.

Infantile haemangiomas (IHs) affect 3-10% of infants, 10% of whom need topical or systemic beta-blocker therapy. Propranolol is the first choice for IHs with a high risk of complications. Since more than half of IHs leave a permanent mark, to reduce outcomes, it is essential to start oral propranolol (2-3 mg/kg/day in 2 doses/day) within the 5th month of life (i.e., during the proliferative phase) and to complete the therapy cycle for at least 6 months. This review aims to summarise the epidemiology, clinical presentation, diagnosis, and treatment of IHs and to highlight the importance of proper referral to specialised hub centres. Patients with vascular anomalies, particularly those suspected of having IH, should be referred to a specialised centre for accurate diagnosis, management by a multidisciplinary team, and timely treatment. IHs may pose life-threatening, functional, and aesthetic risks or may ulcerate. Segmental infantile haemangioma of the face/neck and the lumbosacral regions can be associated with various malformations. To ensure timely specialist evaluation and treatment to reduce the potential risk of complications, it is essential to identify high-risk IHs rapidly. The Infantile Haemangioma Referral Score (IHReS) scale is an important tool to assist primary care paediatricians and general dermatologists.

Propranolol is the first-line treatment for complicated infantile hemangioma (IH). Rebound growth following propranolol discontinuation is reported in 6-25% of patients. Atenolol is considered an effective alternative to propranolol. We aimed to compare the incidence of IH rebound growth following discontinuation of atenolol and propranolol and to identify associated risk factors.

We reviewed the medical records of all the patients diagnosed with IH and treated with oral propranolol or atenolol during 2009-2019 in our tertiary center. Inclusion criteria were completion of at least 3 months of initial treatment and at least 3 months of follow-up after discontinuation of initial treatment.

Of 445 patients in total, 267 (60%) were treated with propranolol and 178 (40%) with atenolol. The incidence of rebound growth was similar between the groups: 59 (22.1%) and 40 (22.5%), respectively. Patients treated with atenolol required a shorter duration of treatment after rebound growth until growth arrest (9.41 ± 5.61 vs. 14.79 ± 10.02 months, p < 0.001). For the patients who initiated atenolol before the age of 5 months, the adjusted odds ratio (aOR) for regrowth was 0.6 (95% CI: 0.33-1.08). As duration of treatment increased, the risk of rebound growth increased; the aOR was 1.24 (95% CI: 1.10-1.38). No other significant risk factors for rebound growth were identified.

The incidence of rebound growth was similar following treatment with two oral β-receptor blockers. Treatment initiation after the age of 5 months and long duration of treatment may increase the risk for regrowth. These findings should be further investigated as they may impact clinical decisions on treating IH.

Vascular anomalies are changes in vascularization that usually appear in the foetal stage, at birth or in early childhood. They can cause chronic pain, motor impairment, cosmetic changes or coagulopathy and may be fatal in some cases, but in every case they have a negative impact on the quality of life of the child and the family. Up to 150 different subtypes have been described. They can involve arteries, capillaries, veins, lymphatic vessels or a combination thereof. They may be associated with additional malformations and frequently cause musculoskeletal and soft tissue hypertrophy or hypotrophy. They can develop anywhere in the body, invade any tissue and affect the function of various organs. The prevalence of the different subtypes varies greatly, from 1/20 to 1/1 000 000. Subtypes considered rare diseases (incidence <1/2000) continue to affect more than 500 000 people in the European Union. Differentiating between vascular tumours and vascular malformations is critical, especially in paediatric patients. They are completely different diseases, although they are often grouped under the umbrella term of vascular anomalies. The diagnostic algorithm used in the clinical evaluation of vascular anomalies should be based on a thorough history-taking and detailed physical examination. Future knowledge in this field will be based above all on genetic findings and therapeutic innovations. New molecules and their indications are being explored with the aim of reducing the aggressiveness of previous treatments and increasing the life expectancy and quality of life of patients who do not respond to conventional treatments.

A wide range of pathologic conditions can originate in the orbit. While it is common to approach the differential diagnosis based on disease categories, such as neoplastic and inflammatory, segmenting the orbit into anatomic compartments can direct the radiologist toward the most common pathologic conditions for each manifestation and space. The orbit can be divided into intraconal, conal, and extraconal compartments. Additionally, the optic nerve sheath complex and lacrimal apparatus can be partitioned into separate compartments due to their unique functions and pathologic features. By using this anatomic approach, the authors review the most common pathologic conditions affecting the orbit and discuss clinical and imaging findings that can guide the differential diagnosis for lesions with similar appearances. Published under a CC BY 4.0 license. Supplemental material is available for this article.

Klippel-Trénaunay syndrome can present with atypical manifestations such as a bleeding vulvar hemangioma. This case report, the first documented in Uganda, highlights the need for awareness of such presentations and underscores the importance of continuous follow-up in female patients to manage potential complications throughout adolescence and pregnancy.

Klippel-Trénaunay syndrome (KTS) is a rare congenital disorder marked by bone and soft tissue hypertrophy, port-wine stains, and varicosities. Cases involving genital hemangiomas are rare. This report highlights a 5-year-old girl in Uganda with typical KTS features, including hypertrophy and port-wine stains, along with a bleeding vulvar hemangioma, emphasizing its uncommon presentation and potential complications. Treatment involved compression bandaging and timolol 0.2% solution. This case underscores the importance of awareness of atypical manifestations of hemangiomas with KTS and continuous follow-up for female patients, especially through adolescence and pregnancy, due to potential complications such as prepubertal per vaginal bleeding, menorrhagia, and post-partum bleeding.

Infantile Hemangioma (IH) is a prevalent benign vascular tumor affecting approximately 5-10% of infants. Its underlying pathogenesis remains enigmatic, and current therapeutic approaches show limited effectiveness. Our study aimed to discover potential IH-associated therapeutics through a transcriptomic, computational drug repurposing methodology.

Utilizing the IH-specific dataset GSE127487 from the Gene Expression Omnibus, we identified differentially expressed genes (DEGs) and conducted weighted gene coexpression network analysis (WGCNA). Subsequently, a protein-protein interaction (PPI) network was constructed to obtain the top 100 hub genes. Drug candidates were sourced from the Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD).

Our analysis revealed 1203 DEGs and a significant module of 1780 mRNAs strongly correlated with IH. These genes were primarily enriched in the PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling pathway. After creating a PPI network of overlapping genes, we filtered out the top 100 hub genes. Ultimately, 44 non-toxic drugs were identified through the CMap and CTD databases. Twelve molecular-targeting agents (belinostat, chir 99021, dasatinib, entinostat, panobinostat, sirolimus, sorafenib, sunitinib, thalidomide, U 0126, vorinostat, and wortmannin) may be potential candidates for IH therapy. Moreover, in vitro experiments demonstrated that entinostat, sorafenib, dasatinib, and sirolimus restricted the proliferation and migration and initiated apoptosis in HemEC cells, thereby underscoring their potential therapeutic value.

Our investigation revealed that the pathogenic mechanism underlying IH might be closely associated with the PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling pathways. Furthermore, we identified twelve molecular-targeting agents among the predicted drugs that show promise as therapeutic candidates for IH.

Infantile hemangioma (IH) is the most common benign tumor in infants and usually resolves on its own. However, a small portion of IH cases are accompanied by serious complications and other problems, impacting the physical and psychological health of the children affected. The pathogenesis of IH is highly controversial. Studies have shown that abnormal blood vessel formation is an important pathological basis for the development of IH. Compared with that in normal tissues, the equilibrium of blood vessel growth at the tumor site is disrupted, and interactions among other types of cells, such as immune cells, promote the rapid proliferation and migration of vascular tissue cells and the construction of vascular networks. Currently, propranolol is the most common systemic drug used to inhibit the growth of IHs and accelerate their regression. The purpose of this review is to provide the latest research on the mechanisms of angiogenesis in IH. We discuss the possible roles of three major factors, namely, estrogen, hypoxia, and inflammation, in the development of IH. Additionally, we summarize the key roles of tumor cell subpopulations, such as pericytes, in the proliferation and regression of IH considering evidence from the past few years, with an emphasis on the possible mechanisms of propranolol in the treatment of IH. Angiogenesis is an important event during the development of IH, and an in-depth understanding of the molecular mechanisms of angiogenesis will provide new insights into the biology and clinical treatment of IH.

The most frequent infantile tumor is a hemangioma, and its most common complication is ulceration. A quickly progressing ulcer called a hemangioma can also result in secondary infection. The mechanism of ulcer formation is unknown but is thought to develop during the rapid growth phase. Infantile hemangiomas are diagnosed clinically, based on the progression of the lesion's history and a clinical examination. Physical interventions (laser surgery, cryosurgery, excision) and systemic corticosteroids or beta-blockers are the usual course of treatment; all carry the potential for substantial side effects. A two-month young female baby approached us, with a diagnosis of hemangiomatous ulcer. Skin grafting was advised by a plastic surgeon, but the baby's parents approached for Ayurveda treatment. The case was treated with oral medicine bilwadi agada and external treatments vranaprakshalana with triphala kwatha and jatyadi taila local application for 2 months. There was complete healing of the ulcer.

Pediatric tumors of the eye and orbit can be benign or malignant as well as congenital or acquired and are usually distinctively different than those seen in adults. Although most of these neoplasms are benign (eg, dermoid cyst, chalazion, molluscum), their location near and within a vital organ can result in serious dermatologic and ophthalmologic sequelae. Lesions discussed include vascular lesions, retinoblastomas (the most common primary pediatric intraocular malignancy), rhabdomyosarcoma (the most common primary pediatric orbital malignancy), Langerhans cell histiocytosis, and metastatic lesions to the orbit (neuroblastoma, Ewing sarcoma). Although cysts and ocular melanoma can occur within the pediatric population, these conditions are covered in other contributions in this issue of Clinics in Dermatology.

Infantile hemangioma with minimal or arrested growth (IHMAG) is an unusual subset of infantile hemangioma, difficult to recognize because they are often mistaken for capillary malformation or other entities. Dermoscopic features of IHMAG have been described only in small case series so far.

The aim of our study was to evaluate epidemiological, clinical, and dermoscopic features in 79 cases of IHMAG with a specific focus on neonates and toddlers with segmental complicated IHMAG and to provide a remarkable dermoscopic criterion to achieve diagnosis.

This case series collected all the cases of IHMAG recorded in our Clinical Registry from January 2012 to March 2022.

A total of 79 cases of IHMAG were identified in our study; 53 (67.1%) were localized and 26 (32.9 %) were segmental. Patients showed some complications during follow-up such as ulceration and soft tissue anomalies. One PHACE syndrome and two LUMBAR syndromes were included. Our study highlights the main dermoscopic features differentiating IHMAG from infantile hemangiomas and capillary malformations in neonatal patients, highlighting the presence of enlarged unfocused telangiectatic vessels as remarkable clues.

This is a large case series described in the literature about this rare entity. We emphasize that segmental IHMAG may be associated with structural abnormalities and may pose a diagnostic challenge especially in its rare facial segmental localization. The use of dermoscopy allowed us to find typical signs for IHMAG, thus avoiding the execution of invasive methods and ensuring the prompt suspicion of a syndrome in segmental neonatal cases.

Hemangioma of infancy is the most common vascular tumor during infancy and childhood. Despite the proven efficacy of propranolol treatment, certain patients still encounter resistance or face recurrence. The need for frequent daily medication also poses challenges to patient adherence. Bleomycin (BLM) has demonstrated effectiveness against vascular anomalies, yet its use is limited by dose-related complications. Addressing this, this study proposes a novel approach for treating hemangiomas using BLM-loaded hyaluronic acid (HA)-based microneedle (MN) patches. BLM is encapsulated during the synthesis of polylactic acid (PLA) microspheres (MPs). The successful preparation of PLA MPs and MN patches is confirmed through scanning electron microscopy (SEM) images. The HA microneedles dissolve rapidly upon skin insertion, releasing BLM@PLA MPs. These MPs gradually degrade within 28 days, providing a sustained release of BLM. Comprehensive safety assessments, including cell viability, hemolysis ratio, and intradermal reactions in rabbits, validate the safety of MN patches. The BLM@PLA-MNs exhibit an effective inhibitory efficiency against hemangioma formation in a murine hemangioma model. Of significant importance, RNA-seq analysis reveals that BLM@PLA-MNs exert their inhibitory effect on hemangiomas by regulating the P53 pathway. In summary, BLM@PLA-MNs emerge as a promising clinical candidate for the effective treatment of hemangiomas.

Over the past several centuries, the integration of contemporary medical techniques and innovative technologies, like genetic sequencing, have played a pivotal role in enhancing our comprehension of congenital vascular and lymphatic disorders. Nonetheless, the uncommon and complex characteristics of these disorders, especially considering their formation during the intrauterine stage, present significant obstacles in diagnosis and treatment. Here, we review the intricacies of these congenital abnormalities, offering an in-depth examination of key diagnostic approaches, genetic factors, and therapeutic methods.

An infantile hemangioma is a congenital benign tumor formed by the proliferation of vascular cells during the embryonic stage. It is more common in the skin but can also occur in the mucous membranes, liver, brain and muscle. Hepatic hemangioma appears to be a benign tumor; however, it may lead to poor outcomes because of severe complications, such as high-output cardiac failure. The main treatment of hepatic hemangioma in infants is oral drugs, such as propranolol and glucocorticoids, but the clinical response is not always satisfactory. We describe a rare case of a 2-month-old boy who presented with infantile cutaneous and hepatic hemangiomas. By using dermoscopy and observations of the abdominal color Doppler ultrasound, after 9 months of oral treatment with itraconazole solution, the infantile cutaneous hemangioma complicated with hepatic hemangioma was eventually cured. There was no liver or kidney function damage during the whole treatment period. Itraconazole oral solution for the treatment of infantile cutaneous hemangioma complicated with hepatic hemangioma showed good efficacy, compliance, and safety in this case.

This narrative review aims to summarise the classification of vascular anomalies, their clinical presentation, and their radiological features to propose a diagnostic algorithm to approach patients with suspected soft tissue vascular anomalies of the extremities. The management of vascular anomalies necessitates a multidisciplinary approach. Clinical presentation and physical examination are sufficient in most cases to achieve a correct diagnosis. This is especially true for small congenital lesions of the skin and subcutaneous tissue. Imaging is used for accurate characterization of these lesions, especially in cases of atypical or vague clinical presentation, and to assess extension in cases of lesions that are larger and localized in deeper tissues.

Infantile hemangiomas (IH) are common benign vascular tumors in pediatric patients, often found on the scalp. While most IH naturally regress without intervention, surgical excision becomes necessary when severe anatomic or physiological complications arise. This review examines previously published case studies on pediatric scalp IH excisions, focusing on surgical outcomes and complications. A comprehensive search of the US National Library of Medicine National Institutes of Health (PubMed) database identified 19 relevant case studies. Most patients were female, with a wide age range at the time of excision. Various anatomic locations and sizes of the hemangiomas were observed. The reviewed literature demonstrates that surgical excision of scalp IH can be performed with minimal complications, even for sizable tumors. Successful outcomes and low complication rates highlight the effectiveness of surgical intervention in cases of life-threatening IH sequelae. Further research is warranted to explore optimal timing, techniques, and adjunct therapies for surgical management of scalp IH.

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.

We previously published that in patients with infantile hemangioma (IH) at the onset (T0) colony forming unit-fibroblasts (CFU-Fs) are present in in vitro cultures from PB. Herein, we characterize these CFU-Fs and investigate their potential role in IH pathogenesis, before and after propranolol therapy. The CFU-F phenotype (by flow cytometry), their differentiation capacity and ability to support angiogenesis (by in vitro cultures) and their gene expression (by RT-PCR) were evaluated. We found that CFU-Fs are actual circulating MSCs (cMSCs). In patients at T0, cMSCs had reduced adipogenic potential, supported the formation of tube-like structures in vitro and showed either inflammatory (IL1β and ESM1) or angiogenic (F3) gene expression higher than that of cMSCs from CTRLs. In patients receiving one-year propranolol therapy, the cMSC differentiation in adipocytes improved, while their support in in vitro tube-like formation was lost; no difference was found between patient and CTRL cMSC gene expressions. In conclusion, in patients with IH at T0 the cMSC reduced adipogenic potential, their support in angiogenic activity and the inflammatory/angiogenic gene expression may fuel the tumor growth. One-year propranolol therapy modifies this picture, suggesting cMSCs as one of the drug targets.

The authors report long-term results of the oral propranolol treatment protocol for periocular infantile hemangioma regardless of conventional indications.

This is a retrospective study (2008-2018) on children with propranolol treatment protocol for periocular infantile hemangioma and last follow-up (FU) of ≥4 months after treatment and age of >24 months. After systemic evaluation, it was started with 0.5 and increased by 0.5 every 3 days to reach 2 mg/kg/day. If there was no good response, it would be gradually increased up to 3 mg/kg/day. Tapering (0.5 mg/kg/day every 4 weeks) was started when patients were on treatment for ≥6 months and ≥12 months old and there was no change in the infantile hemangioma size for ≥3 months. Rebound growth was based on the parents' report and would be treated by increasing the dose to at least 2 mg/kg/day for 3 months. FU was either in-person or via social media. Change in periocular infantile hemangioma size on the photos was scored by 3 masked observers (visual analog scale) and presented as excellent (≥50% reduction), good (1%-49%), fair (no change), and failure (enlarged).

Forty-three patients were included. Orbital involvement was in 49%, ptosis in 58%, and risk of amblyopia in 63%. Mean treatment, tapering, and FU duration were 37, 13, and 74 months, respectively. Mean age at presentation, start of propranolol treatment protocol, tapering, stop, and last FU were 1.5, 5, 29, 42, and 78 months, respectively. Twenty-seven patients received 2, seven 2.5, and nine 3 mg/kg/day. Mean visual analog scale significantly increased from 43% (FU1) to 92% (last FU) when 97.6% of patients showed an excellent response. The remaining skin lesions were observed in 35%. No side effect was reported.

Long-term results of the propranolol treatment protocol for periocular infantile hemangioma showed an excellent response in 97.6% of patients with no side effects. A residual skin lesion was observed in 1/3 of the patient.

Infantile hemangioma is a common benign vascular tumor in children, but it is very unusual to be found intracranially. Our literature review identified 44 reported cases. Presentation can vary from asymptomatic to a life-threatening presentation that necessitates urgent surgical removal. There is no general consensus on management of these rare lesions and until recently, treatment was limited to surgery or pharmacological management with steroids, propranolol or interferon. We present a case of a four-week-old male infant with history of vomiting and increase in head circumference since birth. MRI of the brain revealed a large complex cyst occupying the right frontoparietal region, with round soft tissue component that is isointense on T1 and hyperintense on T2 weighted images. Complete surgical resection with evacuation of the cyst was achieved. Histopathology of the mass showed infantile hemangioma with positive CD31 on immunohistochemistry. The patient achieved an excellent outcome following surgical resection.

This study aims to add proof to the safety profile of propranolol as first-line choice in treating infantile haemangiomas, in particular related to its cardiac side effects the main hindering reason for parents and physicians to start and comply with treatment.

This is a prospective observational and analytic study with a sample of 476 patients diagnosed with infantile haemangioma and treated with systemic propranolol during the time interval January 2011 to December 2021. We studied clinical propranolol adverse events experienced in hospital or outpatient and measured the impact of propranolol on blood pressure and heart rate.

This study showed that symptomatic adverse events caused by propranolol were mild and severe adverse events were rare. The most common clinical side effects were paleness, sweating, reduced feeding, and agitation. Only in 28 (5.9%) cases these symptoms were severe enough to review treatment, 1.8% had severe respiratory symptoms, 2.7% experienced hypoglycaemia, and 1.2% had heart-related symptoms. Mean blood pressure reduction with treatment was statistically significant only after achieving the maintenance dose 2 mg/kg body weight. Blood pressure under the 5th percentile was registered in 2.9% of cases, but only four patients had symptomatic hypotension. While heart rate reduction was noticed with the first dose, only two experienced symptomatic bradycardia.

We conclude that propranolol is not only an excellent drug in treating infantile haemangioma, but it has also a very safe profile, with mild side effects and very rare severe cardiac adverse events, easily overcome with treatment interruption.

Infantile hemangioma (IH) has received global attention, resulting in a significant volume of literature. However, there is a lack of bibliometric analyses specifically focusing on IH publications. This study aims to fill this gap by conducting a comprehensive analysis of IH publications, investigating their characteristics, contribution distribution, and developmental trends. By enhancing our understanding of IH and identifying potential research topics and collaborators, this study will contribute to the advancement of the field.

A total of 4333 articles and reviews on IH were collected from the Web of Science (WoS) database, spanning the years 2000-2022. The study encompassed a comprehensive analysis of IH publications, evaluating their quantity and quality. Additionally, we profiled publishing groups based on country, institution, author publication records, and collaboration networks. Lastly, we identified and summarized the prominent research topics.

Annual publications on IH have increased over the past 20 years. The United States has the highest number of publications and the highest total number of citations. Pediatric Dermatology was the most influential journal in the IH field. The citation analysis indicated that the articles published by Léauté-Labrèze in 2008 had the highest number of citations. The articles published by North PE in 2000 and Boye E in 2001 laid a certain research foundation for this field. Concerning institutions, most of the cooperative relationships were established in the same country/region. The United States has the largest number of scientific research institutions and IH researchers, leading most of the cross-country collaboration. The University of California, San Francisco, Medical College of Wisconsin, Harvard University, and Shanghai Jiaotong University were the research centers that published the most IH-related research. Frieden IJ, Mulliken JB, and Drolet BA were the top three most influential authors. Frieden IJ, Garzon MC, and Mulliken JB were the top three authors with the most cited frequency. In addition, keywords and keyword co-occurrence networks prompted that the pathological mechanism of IH, clinical analysis, and other vascular anomalies are research hotspots. Analysis of trending topics suggests that research on IH has evolved from treatment-focused studies towards investigations of other vascular diseases and a series of clinical case studies. Currently, clinical case studies receive the most attention in the field.

This comprehensive bibliometric study provides a thorough analysis of post-2000 publications in the field of IH, offering insights into current research trends for the first time. The findings suggest that future investigations will continue to prioritize understanding IH mechanisms, treatment approaches, and treatment evaluation. Furthermore, the exploration of other vascular diseases and the inclusion of clinical case studies are expected to contribute to advancements in IH clinical practice. By identifying potential collaborators, partner institutions, and new research avenues, this study offers valuable guidance for future in-depth research on IH.

Determining the shape of a skin lesion may provide a diagnostic clue in dermatology practice, more commonly for inflammatory diseases but also for skin tumors. The annular formation may develop by diverse mechanisms in skin tumors. Annular lesions may occur from the onset of the tumor as sparing the central area or depression and/or ulceration in the center of the tumor or outward expansion of the primary lesion. Clustering of multiple papulonodular lesions sparing the central area or relatively independent processes acting on the central and peripheral components of the tumor may also result in an annular appearance. We have explored a wide variety of benign and malignant skin tumors and lymphoproliferative diseases forming an annular shape.

Infantile hemangioma (IH) is the most common neoplasm in children, but it may mimic other types of vascular anomalies or nonvascular benign and malignant tumors. In most cases, the clinical appearance, time of onset, and pattern of involution facilitate its diagnosis. Imaging evaluation is not always needed since the IH features at clinical presentation are usually characteristic, but when needed, US and frequently MRI are the imaging modalities of choice. Clinical photography or photographic documentation plays a central role in monitoring these lesions over their clinical course. Photographic documentation can also add confidence and alert the radiologist when interpreting imaging studies. Some vascular anomalies, especially vascular malformations, are a frequent source of confusion, as these may resemble IHs clinically and at imaging. The lack of uniform terminology also hinders an accurate diagnosis. To unify the terminology and minimize confusion, the International Society for the Study of Vascular Anomalies created a helpful classification in 1994. In addition, radiologists need to be aware of and become familiar with other neoplasms in children that may resemble IH to avoid misdiagnosis and unnecessary procedures. Fibrous and lipomatous tumors are examples of benign tumors that can mimic IHs clinically and at imaging, whereas rhabdomyosarcoma, infantile fibrosarcoma, neuroblastoma, and lymphoproliferative disorders are examples of malignant neoplasms. The authors review the features of IH at clinical presentation and imaging evaluation, highlighting its different phases of evolution and stressing the importance of photographic documentation. The authors also review pitfalls of IH with helpful pearls for differentiation. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material. See the invited commentary by Khanna and Briones in this issue.

(1) Background: With an incidence of 4-10%, infantile hemangiomas (IH) are the most encountered benign tumors in infancy. Low birth weight (LBW), prematurity, female sex, multiple gestations, and family history of IH are some of the statistically proven risk factors for developing IH. The aim of our study was to evaluate the prevalence of IH in our clinic and its connection to maternal and perinatal factors. (2) Methods: We conducted a cross-sectional study, over three years (2020-2022), at the Clinical Hospital of Obstetrics and Gynecology, "Prof. Dr. P. Sârbu", in Bucharest, Romania. (3) Results: During this period, 12,206 newborns were born and we identified 14 infants with infantile hemangioma. In our study, the prevalence of infantile hemangioma was 0.11%. The prevalence of IH in pregnancies obtained through in vitro fertilization was 1%, in twin pregnancies it was 2.27%, and in those with placenta previa, it was 4.16%. (4) Conclusions: Our findings provide a solid image of the prevalence of IH in our country and underline that the development of IH is strongly connected to maternal and perinatal variables, such as: preterm newborns, in vitro fertilization, high blood pressure, anemia, hypothyroidism, placenta previa, and twin pregnancy.

Infantile hemangiomas (IHs) are benign vascular tumors commonly observed in children. The pathogenesis of hemangiomas is complex and poorly understood. IH occur most commonly on the head and neck. There are different classification of them according to the depth, number, distribution and locations. A multidisciplinary approach is needed for the diagnosis and treatment of hemangiomas because it is easy to misdiagnose or decide on a wrong treatment in the existing single-treatment system.

In this retrospective study between 2018 and 2022 we provided an overview of the hemangiomas located in the head and neck in 232 patients, and the different treatment approaches used.

Of the 232 patients 60.3 % were females and 38.7% males. The youngest age was 10 weeks old and the oldest age who underwent treatment was 79 years old. The most common lesion sites were the mid-cheek, the upper lip and the upper eyelid. 104 patients (53.4 %) underwent surgical intervention due to the location of the lesion, size and functional reasons. Meanwhile 128 patients (46.6 %) were observed and treated with propranolol and pulsed dye laser.

Hemangiomas are generally benign tumors. Hemangiomas present a number of diagnostic and therapeutic challenges; thus, early diagnosis by a specialist clinic is key in preventing associated morbidity with these vascular tumors.

Parents of infants treated with beta-blockers for infantile haemangioma are often concerned about the long-term aesthetic outcome. This cross-sectional study assessed the influence on the long-term aesthetic outcome of characteristics of the infantile haemangioma, the beta-blocker treatment, and the infant. The study included 103 children aged 6-12 years, treated with beta-blockers (propranolol or atenolol) for infantile haemangioma during infancy (age at treatment initiation ≤1 year) for ≥6 months. Dermatologists and parents scored the Patient Observer Scar Assessment Scale, and the child scored a visual analogue scale. Dermatologists identified whether telangiectasia, fibrofatty tissue, and atrophic scar tissue were present. The long-term aesthetic outcome of infantile haemangioma was judged more negatively by dermatologists and parents in case of a superficial component, ulceration, older age at treatment initiation, higher cumulative dose, and/or shorter follow-up time. According to children, infantile haemangioma located on the head had better aesthetic outcome than infantile haemangioma located elsewhere. Close monitoring, particularly of infantile haemangioma with a superficial component, is essential for early initiation of treatment, and to prevent or treat ulceration. These outcome data can support parental counselling and guide treatment strategy.

Infantile hemangiomas (IH) are common benign tumors of infancy. Most IH either involute spontaneously or respond to treatment with systemic Beta- blockers, but unfortunately not in all cases. In poor responses or in cases of contra indications for pharmacological treatment, laser treatment poses a very good solution.

As a search strategy and study selection we searched the MEDLINE database via PubMed starting 1982 to June 2022 using a key terms related to interventions for IH (e.g., infantile hemangioma, laser, Beta blockers).

In this article, we reviewed the published data regarding the use of energy-based devices in treatment of children with IH, and noted our experience over the course of treating dozens of cases over the years.

There are many laser systems used for the treatment of hemangioma and vascular tumors. These laser systems are of different wavelengths and penetration depths, however, they operate by similar mechanisms and in some cases two or more lasers can be applied during the course of treating these lesions.

Determining the shape of the skin lesion may provide a diagnostic clue in dermatology practice, more commonly for inflammatory diseases but also for skin tumors. The annular formation may develop by diverse mechanisms in skin tumors. Annular lesions may occur from the onset of the tumor as sparing the central area or depression and/or ulceration in the center of the tumor or outward expansion of the primary lesion. Clustering of multiple papulonodular lesions sparing the central area or relatively independent processes acting on the central and peripheral components of the tumor may also result in an annular appearance. We have explored a wide variety of benign and malignant skin tumors and lymphoproliferative diseases forming an annular shape.

This literature review outlines the current pathogenesis, clinical features, and complications of infantile hemangiomas and explores the current treatment modalities, including corticosteroids, surgery, pulsed dye laser, and beta-blockers. Although oftentimes benign, these lesions can potentially lead to physical or cosmetic disfigurement in growing children. The issue of depth and location-dependent treatment for infantile hemangiomas is explored as it reveals which treatments are correlated with better outcomes in specific presentations. For example, beta-blockers were found to be an effective first-line treatment for superficial infantile hemangiomas specifically, whereas the pulsed dye laser procedure was shown to be an effective option for deep hemangiomas, speeding up the involution process when combined with other treatment modalities and reducing scarring in ulcerated hemangiomas. Although the various infantile hemangioma treatment modalities available are appropriately tailored to specific cases of hemangiomas, they are also not without significant, sometimes life-threatening complications. This is why this literature review aims to outline the therapeutic benefits and risks of all treatment modalities to aid in the establishment of optimal case-dependent treatments. [Pediatr Ann. 2023;52(5):192-197.].

Infantile hemangioma (IH) is important to all dentists, particularly dentists providing services to pediatric populations, because significant morbidity and mortality can occur from vascular lesions in children. Specialists of the oral cavity have the responsibility to identify patients with IH, a lesion that could be potentially life threatening. We present a case of IH and will provide a narrative review of the most recent literature. We discuss the diagnosis, risk stratification, treatment, complications, and impact on routine dental procedures. A proper diagnosis is crucial as oral and perioral IH are considered high-risk due to the increased risk of ulceration and feeding impairment. Referral to a hemangioma specialist for comprehensive team treatment is optimal. The natural history of IH consists of a long proliferative phase, which manifests as clinically visible growth. As a result of early encounters with patients, the pediatric dentist may often be considered the primary care provider.

Infantile hemangioma (IH), the most common benign tumor in infancy, is generally sensitive to propranolol treatment. However, the challenge remains because resistance or recurrence could occur in some patients, and the mechanism or target of propranolol remains unknown. Therefore, advancement in the drug development is needed. In this study, we explored whether apelin receptor (APJ) can become a candidate target. We found that APJ is expressed only in endothelial cells of IH (HemECs) but not in other vascular anomalies, and its antagonist, ML221, can negatively regulate cellular viability and functions of HemECs. This inhibitory effect could be replicated in a murine hemangioma model. Importantly, in vitro experiments also indicated that ML221 failed to affect the proliferation or angiogenesis of normal endothelial cells or APJ-knockout HemECs. Through analysis of the phosphoantibody microarray data, ML221 was revealed to have an inhibitory effect on HemECs by suppressing the activation of mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. These results verified the distinctive expression of APJ in IH and specific inhibition of HemEC activity caused by ML221. In addition, APJ was also detected in propranolol-resistant IH. Collectively, we propose that APJ can act as a specific marker and a promising therapeutic target for IH, which will facilitate further drug development.

Background: Periorbital infantile hemangiomas (POIHs) are associated with a high incidence of visual complications. Objective(s): To analyze the sites of predilection of POIHs and to determine whether certain sites require earlier intervention due to their higher rate of visual complications. Methods: A retrospective case series study was conducted on patients from two tertiary care centers for 25 years. The location of POIHs was determined from clinical photographs, medical records, and radiological studies. The presence or absence of anisometropic astigmatism (anisoastigmatism) and amblyopia was recorded. Data were analyzed using a chi-square test. Results: There were 486 patients, of which 302 patients had ophthalmology evaluations and 245 patients had refractive error data. At presentation, 10% of patients already had amblyopia and 44% had anisoastigmatism. Medial eyelid lesions had the highest risk of developing anisoastigmatism (anisoastigmatism correlates with eyelid position, p = 0.0001). Segmental and upper medial lesions had the highest risk of amblyopia at initial evaluation. Conclusion: The site of POIH is an important indicator for developing clinically significant anisoastigmatism and amblyopia, underlining the need for early ophthalmologic assessment and management.

β-adrenoreceptors (ARs) are members of the superfamily of G-protein-coupled receptors (GPCRs), and are activated by catecholamines, such as epinephrine and norepinephrine. Three subtypes of β-ARs (β₁, β₂, and β₃) have been identified with different distributions among ocular tissues. Importantly, β-ARs are an established target in the treatment of glaucoma. Moreover, β-adrenergic signaling has been associated with the development and progression of various tumor types. Hence, β-ARs are a potential therapeutic target for ocular neoplasms, such as ocular hemangioma and uveal melanoma. This review aims to discuss the expression and function of individual β-AR subtypes in ocular structures, as well as their role in the treatment of ocular diseases, including ocular tumors.

PHACE is a rare syndrome that can present with airway hemangiomas. Management for these patients is variable and the utilization of operative endoscopic airway evaluation has not been described. The objectives of this study were to identify the incidence of airway symptoms in patients being evaluated for PHACE syndrome and determine the utility of operative endoscopy.

An IRB-approved retrospective cohort study was conducted on consecutive pediatric patients with head and neck infantile hemangioma (IH) evaluated in a multi-disciplinary vascular anomalies center between 2013 and 2019. Patients were included if they were being worked up for PHACE syndrome and had an otolaryngology evaluation. Demographics, clinical, and surgical variables were collected.

There were 317 patients with head and neck IH. Thirty-six patients met inclusion criteria. The majority of patients were female (31/36; 86.1%) and less than half of the patients (15/36; 41.7%) were eventually diagnosed with PHACE syndrome. Median age at presentation was 2 months (range 0-82 months). A total of 28/36 (77.8%) of patients were managed with propranolol. The majority of the patients presented without aerodigestive symptoms; however, 16/36 (44.4%) of patients presented with symptoms such as stridor, hoarseness, and dysphagia. A total of 20/36 (55.6%) of patients underwent operative endoscopy. A total of 8/20 (40.0%) of patients who underwent operative endoscopy had operative intervention. Of the entire cohort, only 2/15 (13.3%) patients diagnosed with PHACE were found to have a subglottic hemangioma. Both patients presented with stridor.

Operative endoscopy remains useful in the workup of PHACE syndrome to identify subglottic hemangiomas, however there may be relatively low yield in asymptomatic patients. In office flexible laryngoscopy may be a less invasive means to examine the subglottic region. A multi-center prospective study would be necessary to evaluate incidence of subglottic hemangiomas in asymptomatic patients evaluated for PHACE.

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 5 months (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 9 months (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 hemangioma (IH) is the most common vascular tumor among infants and children. However, the understanding of pathogenesis about IH has not been fully elucidated, and the potential diagnostic maker remains further explored. In this study, we aimed to find miRNAs as potential biomarkers of IH through bioinformatic analysis. The microarray datasets GSE69136, GSE100682 were downloaded from the GEO database. The co-expressed differential miRNAs were identified by analyzing these two datasets. The downstream common target genes were predicted by the ENCORI, Mirgene, miRWalk, and Targetscan databases. GO annotation and KEGG pathway enrichment analysis for target genes were performed. The STRING database and Cytoscape software were used to construct the protein-protein interaction network and screen hub genes. Then potential diagnostic markers for IH were further screened and identified by using Receiver operating characteristic curve analysis. A total of thirteen co-expressed up-regulated miRNAs were screened out in the above two datasets, and 778 down-regulated target genes were then predicted. GO annotation and KEGG pathway enrichment analysis indicated that the common target genes strongly correlated with IH. Through the DEM-hub gene network construction, six miRNAs associated with the hub genes were identified. Finally, has-miR-522-3p, has-miR-512-3p, has-miR-520a-5p with high diagnostic values were screened out by receiver operating characteristic analysis. In the study, the potential miRNA-mRNA regulatory network was firstly constructed in IH. And, the three miRNAs might be used as potential biomarkers for IH, which also provided novel strategies for the therapeutic intervention of IH.