Cutaneous Infantile Hemangiomas Research Articles

Clinical features of cutaneous infantile hemangioma combined with asymptomatic infantile hepatic hemangioma and efficacy of propranolol treatment.

Infantile hepatic hemangioma (IHH) is a common liver tumor in infants and shares the same characteristics as cutaneous infantile hemangioma (IH). Propranolol is effective for symptomatic IHH. The clinical features between cutaneous IH and IHH, and treatment efficacy of IHH (smaller than 4 cm) is unclear. To evaluate the correlation of clinical features between cutaneous IH and IHH, as well as efficacy of systemic propranolol in the treatment of cutaneous IH combined with IHH. The clinical data of infants with complicated cutaneous IH combined with IHH treated with systemic propranolol (1.5 ~ 2 mg/(kg d)) from January 2011 to October 2020 were retrospectively analyzed. Forty-five cases with IHH combined with complicated cutaneous IH were reviewed. Single cutaneous IH is more likely to be combined with focal IHH, cutaneous IH greater than 5, more likely to be combined with multiple IHH (Pearson = 0.546, p < 0.01). The mean age of focal and multiple IHH regression was 11.93 ± 14.42 months and 10.20 ± 9.15 months, respectively. The number of cutaneous IH were correlated with the number of IHH. There was no difference in the age of complete remission for focal and multiple IHH.

Update on Treatment of Infantile Hemangiomas: What's New in the Last Five Years?

Among benign vascular tumors of infancy, hemangiomas are the commonest, affecting approximately 5–10% of one-year-old children. They are derived from a benign proliferation of vascular endothelial cells (VECs) in the mesoderm and may arise anywhere on the body around 1–2 weeks after birth. Infantile hemangiomas (IHs) are characterized by an early proliferative phase in the first year followed by a spontaneous progressive regression within the following 5 years or longer. IH prevalence is estimated to be 5%–10% in one-year-old children and commonly affects female, Caucasian and low-birth weight infants. Although most of them spontaneously regress, approximately 10% requires treatment to prevent complications due to the site of occurrence such as bleeding, ulceration, cosmetically disfigurement, functional impairment, or life-threatening complications. For over 30 years, steroids have represented the first-line treatment for IHs, but recently topical or systemic β-blockers are increasingly being used and recognized as effective and safe. A search for “Cutaneous infantile hemangioma” [All Fields] AND “Treatment” [All Fields] was performed by using PubMed and EMBASE databases. Treatment of IHs with labeled drugs, such as oral propranolol, but also with off-label drugs, such as topical β-blockers, including topical timolol and carteolol, steroids, itraconazole or sirolimus, with a focus on formulations types and adverse events were described in our review. We also discussed the benefits of pulsed dye laser and the treatment of IHs with involvement of central nervous system, namely the PHACE and LUMBAR syndrome.

Multifocal Infantile Hemangiomas Treated by Oral Itraconazole: A Case Report

We describe a case of a 2-month-old girl presented with more than 60 papules and nodules of hemangiomas involving the skin of the sclera, endocanthion, lower lip, and labium majus pudenda without visceral hemangiomas and laboratory abnormality. A skin biopsy showed numerous scattered, clearly limited, irregular cellular lobules in the dermis circumvoluted into capillaries comprising incomplete vessel walls, which was consistent with a diagnosis of multifocal cutaneous infantile hemangioma. Oral treatment with itraconazole (5mg/kg/day) for 26 weeks resulted in predominantly involution of the skin hemangiomas. We would like to report a rare case of multifocal cutaneous infantile hemangioma, successfully treated with oral itraconazole.

Uncomplicated Cutaneous Infantile Strawberry Hemangioma: Educational Images and Evidence-Based Recommendation

Uncomplicated Cutaneous Infantile Strawberry Hemangioma: Educational Images and Evidence-Based Recommendation

Spontaneous evolution patterns of focal congenital hepatic hemangiomas: a case series of 25 patients.

Hepatic hemangiomas are the most common benign liver tumors of infancy. They are termed congenital if fully developed at birth or infantile if they appear in the first weeks of life. Previous studies suggested that most focal hepatic hemangiomas are congenital in nature, exhibit no postnatal growth and have an evolution that parallels their cutaneous counterparts. They are subdivided by pattern of involution, whether rapidly involuting (RICH), partially involuting (PICH) or non-involuting (NICH) congenital hemangiomas. In our experience, some focal hepatic hemangiomas show postnatal growth, behaving like infantile forms. To analyze the spontaneous evolution of focal congenital hepatic hemangiomas with quantification of tumor volume changes over time and to identify initial postnatal ultrasound (US) imaging biomarkers predictive of their evolution pattern. A retrospective review of clinical, imaging and pathology data of children diagnosed with focal congenital hepatic hemangioma (prenatal diagnosis or age at diagnosis <7days and/or glucose transporter protein 1 [GLUT1]-negative tumor) diagnosed between 2000 and 2018 was performed with analysis of tumor volume changes over time. Exclusion criteria were treatment inducing a tumor volume change (hepatic artery embolization, propranolol, or corticosteroids), imaging follow-up less than 1month or fewer than two US examinations. Volumetric analysis was based on US and cross-sectional imaging. Lesion volumes were estimated using the standard ellipsoid formula. A 35% margin of error was assumed for tumor volume variation to account for variability in measurements. Imaging studies, including US, computed tomography, and magnetic resonance imaging, were reviewed and initial postnatal US features were correlated with evolution pattern. Twenty-five patients with focal congenital hepatic hemangiomas were included. The median follow-up time was 46.5months (range: 4-144months). Eight (32%) lesions showed postnatal growth before involuting, without signs of intralesional hemorrhage, as do cutaneous infantile hemangiomas. The other 17 (68%) lesions exhibited a strict decrease in volume with age, of which 15 underwent complete involution (8 before age 18months and 7 after age 18months) and 2 underwent partial involution. The different evolution patterns of focal congenital hepatic hemangiomas showed overlapping imaging features and we found no initial US feature to be significantly associated with postnatal growth. However, large vascular spaces with marked vascularity at US were noted in three of the eight rapidly involuting lesions. Focal congenital hepatic hemangiomas are not the equivalent of cutaneous RICH, as some may increase in size and tumor regression may be rapid or slow. The different evolution patterns of focal congenital hepatic hemangiomas show overlapping US features.

Infantile hepatic hemangiomas: looking backwards and forwards.

Infantile hepatic hemangiomas (IHHs) are common benign tumors seen in the liver of infants. IHHs are true infantile hemangiomas (IHs) and have phases of proliferation and involution parallel to those of cutaneous IHs. The definition and classification of IHH are still confusing in the literature. The mechanisms during the pathogenesis of IHH have yet to be discovered. The clinical manifestations of IHH are heterogeneous. Although most IHH lesions are asymptomatic, some lesions can lead to severe complications, such as hypothyroidism, consumptive coagulopathy, and high-output congestive cardiac failure. Consequently, some patients can possibly encounter a fatal clinical condition. The heterogeneity of the lesions and the occurrence of disease-related comorbidities can make the treatment of IHH challenging. Oral propranolol is emerging as an effective systemic approach to IHH with obvious responses in tumor remission and symptom regression. However, the precise clinical characteristics and treatment strategies for patients with severe IHH have not yet been well established. Here, we summarize the epidemiology, pathogenic mechanism, clinical manifestations, diagnosis, and treatment of IHH. Recent updates and future perspectives for IHH will also be elaborated.

Management of Upper Airway Infantile Hemangiomas: Experience of One Italian Multidisciplinary Center.

Airway infantile hemangiomas (IHs) can represent a life-threatening condition since the first months of life. They may be isolated or associated to cutaneous IHs, and/or part of PHACES syndrome. Diagnosis, staging, and indication to treatment are not standardized yet despite the presence in the literature of previous case series and reviews. The diagnosis might be misleading, especially in the absence of cutaneous lesions. Airway endoscopy is the gold standard both for diagnosis and follow-up since it allows evaluation of precise localization and entity of obstruction and/or stricture. Proliferation of IH in the infant airways manifests frequently with stridor and treatment is required as soon as possible to prevent further complications. The first line of therapy is oral propranolol, but duration of treatment is not yet well-defined. All considered, we report the experience of our multidisciplinary center from 2009 to date, on 36 patients affected by airway IHs, and successfully treated with oral propranolol. Thus, the authors propose their experience for the management of airway IHs, specifically early diagnosis, when to perform endoscopy, how to interpret its findings, and when to stop the treatment.

Infantile hemangioma affecting the iris.

An infant girl developed a hemangioma affecting her left iris concurrently with diffuse cutaneous infantile hemangiomas from day 2 of life. Intraocular hemangiomas are rarely reported and are usually associated with neonatal hemangiomatosis, the presence of which indicates a high risk for visceral lesions. This striking case highlights the unusual clinical presentation of iris hemangioma and demonstrates the importance of conducting visceral screening when faced with these lesions. Oral propranolol was commenced and resulted in rapid improvement of all lesions without complication.

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.

Novel Treatment of a Diffuse Infantile Hepatic Hemangioma With a Selective Beta-1 Antagonist

Propranolol has been the new standard-of-care treatment for infantile hepatic hemangioma (IHH) cases necessitating medical treatment based on a case series in 2008 that reported how propranolol resulted in involution of cutaneous infantile hemangioma in 2 patients with heart failure. The mechanism of action of propranolol on cutaneous infantile hemangiomas and IHHs is not well-understood, although new research suggests that hemangiomas and other vascular tumors express high amounts of β1 to β3 receptors, and thus explains why these vascular tumors are susceptible to beta-antagonists. However, there are reports of adverse side effects with the use of propranolol, including hypoglycemia, bronchial hyperreactivity, and sleep disturbances. There has been an interest in utilizing selective beta-antagonists to avoid potential side effects of propranolol in treating vascular tumors. We report the first documented case of a 4-month-old patient with diffuse IHH successfully treated with atenolol.

Use of Propranolol for Infantile Hepatic Hemangioma

Infantile hepatic hemangioma (IHH) is the most common type of benign hepatic vascular tumor that presents in infancy. IHH presents as abdominal mass, cutaneous hemangiomas, and unexplained jaundice. Children with asymptomatic lesions generally undergo spontaneous regression within a year, but it may become symptomatic and be associated with life-threatening complications including congestive heart failure, consumptive coagulopathy and hepatic rupture. Treatment options are divided into medical treatment, interventional therapy including embolization, and surgical resection. The steroid has been considered as first-line medical treatment, but it has a low therapeutic effect and may be associated with significant side effects. Since propranolol has been recently used successfully to treat cutaneous infantile hemangiomas, we decided to use it in a patient who presented with hepatic hemangioma and skin hemangiomatosis. In our case, regression of both skin and hepatic lesions was noted without any adverse effects. We think propranolol can be considered as a potential first-line therapy in patients with symptomatic hepatic hemangioma.

Topical timolol for superficial cutaneous infantile hemangiomas in very preterm infants

Introduction. Infantile hemangiomas (IHs) occur 3 to 4 times more frequently in preterm infants than in those born at term. Yet, data about efficacy and safety of topical therapy for IHs in preterm infants, especially in those born with very low gestational age (less than 33 gestational weeks) is very scarce. Case report. We reported five very preterm girls treated with topical timolol maleate 0.5% gel for superficial cutaneous IHs. In four infants topical timolol was applied on a single IH each, and in one infant two IHs were treated. Out of six treated IHs, one was located on the face, four on the trunk and one on the leg. They were regularly monitored for IH involution and potential adverse effects of timolol for 6?13 months of local treatment. Good therapeutic effect was achieved in all the presented infants, with no adverse effects related to topical administration of timolol-maleate. Conclusion. Topical timolol is an effective and safe therapy for superficial cutaneous infantile hemangiomas in very preterm infants. The treatment should be discussed in detail with parents and individualized management plan should be tailored for each infant in order to maximize the chances of a successful outcome, while avoiding adverse effects.

Screening for infantile hepatic hemangioma in patients with cutaneous infantile hemangioma: A multicenter prospective study

Abdominalultrasonography has been proposed to screen for infantile hepatic hemangioma (IHH) in patients with multiple cutaneous infantile hemangiomas (IHs). The aim of this study was to establish the optimal cutoff point for the number of cutaneous IHs needed to screen for IHH. We performed a prospective, multicenter study to screen for IHH in patients younger than 9months who had multiple cutaneous IHs (n≥3) on ultrasonography. For comparison, a group of patients with 1 or 2 focal cutaneous IHs was also recruited. In total, 676 patients with at least 3 cutaneous IHs and 980 patients with 1 or 2 focal cutaneous IHs were enrolled. Thirty-one patients were found to have IHH. A higher number of cutaneous IHs was associated with an increased risk of IHH (R=0.973; P<.001). Receiver operating characteristic curve analysis showed that 5 cutaneous IHs was the optimal cutoff point to screen for IHH, with an area under the curve of 0.872 (P<.001; 95% confidence interval, 0.789-0.955). This was an uncontrolled study. Screening for IHH is recommended in patients younger than 9months who present with 5 or more cutaneous IHs.

Cutaneous Infantile Haemangiomas with Intracranial and Intraspinal Involvement: A European Multicentre Experience and Review.

Infantile haemangiomas are very common benign tumours in the first months of life. They are mostly cutaneous; however, extracutaneous lesions are possible, and occur in very rare cases in the central nervous system. A European multicentre observational retrospective study was conducted in the last 5 years. Seven patients with intracranial or intraspinal infantile haemangiomas were selected and treated with oral propranolol. Propranolol was interrupted after complete or almost complete resolution of infantile haemangiomas. All patients tolerated the treatment well without side-effects. Central nervous system infantile haemangiomas are probably underestimated due to the frequent absence of symptoms and their spontaneous involution. However, they should be investigated in case of segmental cutaneous infantile haemangiomas, particularly on the head, neck, upper trunk, lumbar or sacral area in order to diagnose intra-central nervous system involvement at an early stage.

Cutaneous mastocytosis and infantile hemangioma. Only a coincidence?

Cutaneous mastocytosis and infantile hemangioma. Only a coincidence?

Infantile hemangiomas: An update on pathogenesis, associations, and management

Infantile hemangiomas (IH) are the most common vascular neoplasm in infants. The typical clinical course of IH follows a pattern of growth (proliferation) followed by spontaneous involution. The majority of IH are isolated to the skin; however, some cutaneous IH can be associated with internal organ involvement or anomalies. IH which are functionally impairing, ulcerated or potentially disfiguring require therapy. Treatment options include systemic or topical beta-blockers, systemic or intralesional corticosteroids, pulsed dye laser therapy, or surgical excision. In this article, we review the updated understanding of IH pathogenesis, clinical presentations and associations, and approaches to management.

Infantile hemangiomas with conjunctival involvement: Anunderreported occurrence.

Infantile hemangiomas (IHs) involving the conjunctiva are only anecdotally reported in the literature and little is known about their clinical course. In a retrospective case series we aimed to better delineate the clinical presentation, complications, and response to treatment of this uncommon subtype of IH. A classification of conjunctival IH is proposed. Medical charts at three academic pediatric dermatology institutions were retrospectively analyzed. Data were collected on the clinical characteristics, ophthalmologic findings, treatments, and outcomes of 22 individuals with conjunctival IH. Growth characteristics of conjunctival IH closely mirrored those of their cutaneous counterparts. Ophthalmologic abnormalities were associated with the IH in six individuals (27%); in three, they were considered severe. Seventeen subjects (77%) required treatment, most commonly because of risk of ocular compromise. All treated individuals responded favorably to topical timolol or systemic propranolol. Conjunctival IH have clinical characteristics similar to those of cutaneous IH and respond readily to beta-blocker treatment. Ocular complications may occur in a minority of individuals receiving treatment.

A case of cutaneous infantile hemangiomas associated with cardiac dextroposition, hemivertebra, and unilateral renal agenesis

A case of cutaneous infantile hemangiomas associated with cardiac dextroposition, hemivertebra, and unilateral renal agenesis

Oral versus topical propranolol for management of superficial infantile hemangiomas

Background/purpose: Oral propranolol has been used successfully for the treatment of infantile hemangiomas (IHs). However, its safety is questioned. Topical therapy with 1% propranolol ointment has been reported to be safe and effective. The objective of this study was to compare the effectiveness and safety of oral versus topical propranolol (1% ointment) as a nonselective b-blocker in the management of cutaneous IH. Patients and methods: Forty-eight patients with IH were randomly divided into two equal groups: group A ( n = 24) was treated with oral propranolol and group B ( n = 24) was treated with propranolol ointment 1%. The patients were followed up for 3 months after treatment was stopped. Results: There was a significant statistical difference between the two groups as regards the effectiveness of the drug ( P = 0.041). In the oral group, 50% ( n = 12) showed an excellent response, 33.33% ( n = 8) showed good response, and 16.67% ( n =4) showed a fair response, whereas in the topical group 16.67% ( n = 4) showed an excellent response, 45.83% ( n = 11) showed good response, and 37.5% ( n = 9) showed a fair response. There was no significant adverse event in any group during the follow-up period. Conclusion: Oral propranolol is an effective, safe, and fastacting drug for treating IH and can be monitored on an outpatient basis. Topical propranolol is an easily prepared drug and seems to be an alternative therapeutic option for superficial cutaneous hemangioma. However, the optimal dosing and duration of treatment are still to be defined. Keywords: infantile hemangiomas, propranolol, propranolol ointment, topical propranolol

Topical Treatment of Infantile Haemangiomas: A Comparative Study on the Selection of a Semi-Solid Vehicle

Background/Aim: Topical β-blockers have recently been proposed as a valid alternative to oral drugs for treating cutaneous infantile haemangiomas, but clinical results in the literature are inconsistent due to the empirical choice of topical preparations. The current investigation aimed to rationalize the selection of a semi-solid vehicle for a locally applied drug product containing 1% w/w propranolol hydrochloride (PR-Cl). Methods: A hydrophobic ointment of PR-Cl, two lipophilic creams, and a hydrophilic cream were prepared. In vitro release and skin permeation studies through human epidermis and full-thickness skin were performed by Franz diffusion cells. Results: The overall results highlighted that PR-Cl was able to permeate the human epidermis, and its penetration pattern was strongly influenced by the composition of the semi-solid vehicle. PR-Cl release and permeation from lipophilic vehicles were extremely limited and influenced by their composition. Best results were obtained by using the hydrophilic cream. Furthermore, the retention study evidenced that epidermis acted as a reservoir, releasing the PR-Cl accumulated after preparation removal. Conclusion: The 1% w/w PR-Cl cream resulted the most suitable formulation for improving drug permeation through the human epidermis. On the contrary, the negligible permeation profile through full-thickness skin pointed out that PR-Cl cannot diffuse significantly to reach the deeper layers of human skin.