Infantile Hemangiomas Research Articles

Infantile hemangiomas: a dermatologist's perspective.

Infantile hemangioma (IH), the most common vascular tumor in pediatrics, is thought to arise from aberrant stem cell responses to stimuli such as hypoxia. This review explores the diverse manifestations, complications, and management strategies for IH, emphasizing the importance of a multidisciplinary approach. The epidemiology and risk factors associated with IH, including connections to prematurity, low birth weight, and family background, are discussed. The intricate pathogenesis involving hemangioma stem cells, KIAA1429, hypoxia, and the renin-angiotensin system is examined. The natural history and clinical features, as well as extracutaneous involvements such as hepatic IH, PHACES syndrome, and LUMBAR syndrome, are detailed. Complications such as ulceration, functional impairment, hypothyroidism, and cosmetic concerns are highlighted. The differential diagnosis and diagnostic modalities, including colorimeters, high-frequency ultrasonography, and imaging techniques, are discussed. Management approaches, including the use of propranolol, atenolol, corticosteroids, alternative systemic treatments, topical therapy, laser therapy, and surgery, are comprehensively reviewed. The evolving landscape of IH management is underscored, with ongoing research exploring alternative treatments and individualized approaches based on IH characteristics.

Parental Assessment of Infantile Hemangioma Cosmetic Clinical Outcomes: Results of the Spanish Hemangioma Nationwide Prospective Cohort

BackgroundFunctional impairment is the main consideration when it comes to choosing therapy for infantile hemangiomas (IH). However, since most hemangiomas are treated for cosmetic reasons, it is important to know the cosmetic outcome assessed by the parents. ObjectiveTo evaluate the aesthetic outcomes of IH, considering the characteristics of the lesions and the treatments used. Patients and methodsThe Spanish Infantile Hemangioma Nationwide Prospective Cohort (2016–2022) recruited all consecutive patients diagnosed with IH in 12 Spanish hospitals. The children included had two photos of the IH lesion (at both baseline and at the end of the study). A panel of parents blindly assessed all available photos using a scale from 0 (worst cosmetic outcomes) to 10 (best cosmetic outcomes). The different scores – both before and after treatment – as well as the outcomes percent considered excellent (>9) were described and compared. We analyzed the effect of receiving different therapies and performed causal model analyses estimating the mean treatment effect of parents’ assessments. ResultsThe median follow-up was 3.1 years. A total of 824 photos were evaluated. Baseline aesthetic impact was higher in the propranolol group vs the topical timolol and observation treatment groups (1.85 vs 3.14 vs 3.66 respectively; p<0.001). After treatment, the aesthetic impact was similar between both treatment groups (7.59 vs 7.93 vs 7.90; p>0.2). The causal model could only be applied to the comparison between topical timolol and observation, revealing no differences whatsoever. ConclusionThis is the first prospective cohort to analyze the aesthetic outcome of IH. The final aesthetic results of the three therapies were similar, with nearly 40% of patients achieving excellent aesthetic outcomes.

A Rare Case of Mature Cystic Teratoma with Infantile Hemangioma and Pericardial Invasion

A Rare Case of Mature Cystic Teratoma with Infantile Hemangioma and Pericardial Invasion

Placental ACE2 Expression: A Possible Pathogenetic Mechanism for Infantile Hemangiomas.

ACE2 is a mono-carboxypeptidase with remarkable vasculo-protective properties, and its expression in the human placenta plays a central role in blood pressure homeostasis and fetal perfusion. Therefore, an alteration in the placental expression of ACE2 could be responsible for reduced placental perfusion and infantile hemangioma (IH) development. Study placentae were collected from patients affected by IHs who were referred to our Dermatology Clinic from 2016 to 2022, while control placentae were randomly collected while matching cases for gestational age. Immunohistochemical investigations were performed with a recombinant anti-ACE2 rabbit monoclonal antibody. A total of 47 placentae were examined, including 20 study placentae and 27 control ones. The mean placental weight was significantly lower in the study group (380.6 g vs. 502.3 g; p = 0.005), while subclinical chorioamnionitis occurred more frequently in the study group (20% vs. 0%, p = 0.03). The mean ACE2 expression was dramatically lower in the study group (χ2 = 42.1 p < 0.001), and the mean placental weight was significantly lower when ACE2 was not expressed compared to the 25-75% and >75% classes of expression (p < 0.05). This study demonstrated that ACE2, as a marker for tissue hypoxia, is dramatically hypo-expressed in placentae belonging to mothers who delivered one or more babies with IH compared to the controls.

Is the identification of multiple infantile cutaneous haemangiomas always a definitive diagnosis? A case report of an infant with multifocal hepatic haemangioma

Multifocal hepatic haemangiomas are the most common benign vascular tumours of the liver that are detected in children with concomitant multiple infantile haemangiomas. Reported lesions are usually undetectable at birth, which presents a diagnostic problem for general practitioners. Ultrasound should be the imaging examination performed in the first instance in search for vascular anomalies in children. In pharmacotherapy, the first-choice treatment is propranolol, administered orally. In the described case, a boy with multiple hepatic and skin haemangiomas, after treatment with propranolol, achieved a significant improvement in the ultrasound image of the liver. Skin lesions were also reduced. The importance of the physical examination should be emphasised in the context of detecting cutaneous haemangiomas, which usually accompany multifocal hepatic haemangiomas and should prompt the physician to regularly observe and repeat abdominal ultrasound examinations of the diagnosed and/or treated child.

Guía mexicana para el diagnóstico y el tratamiento del hemangioma infantil.

Infantile hemangioma is a benign vascular tumor, the most common in childhood, whose natural evolution is the disappearance of the lesion in the pediatric age and which has effective and safe treatments that limit its growth and favor its disappearance at younger ages. Infantile hemangioma continues to be a reason for attention to complications, due to erroneous diagnoses, lack of knowledge of the condition, late referral or fear of the effects of the medications used for its treatment. Furthermore, its presence is normalized without taking into account that it can cause uncertainty, anxiety, feelings of guilt and, as a consequence, a significant impact on the quality of life, mainly in the parents or caregivers of the child. The need for a clinical practice guideline in our country arises from the high presentation of late-remitted complications in infantile hemangioma even with the availability of adequate treatments, the continuous evolution of medicine and the appearance of new evidence. Throughout the guide you will find recommendations regarding the diagnosis, treatment and follow-up of patients with infantile hemangioma, taking into account the paraclinical tests that can be performed, topical or systemic management options, as well as adjuvant therapies. For the first time, objective tools for patient follow-up are included in a guide for the management of infantile hemangioma, as well as to help the first contact doctor in timely referral.

Capillary Haemangioma of Fallopian Tube: Usual Tumor at Unusual Site

Fallopian tube neoplasms are uncommon, accounting to approximately 1-2% of all female genital tract neoplasms. Hemangiomas are the most common soft tissue neoplasms. We present an unusual case of capillary hemangioma of fallopian tube which was incidentally detected in a patient who underwent abdominal hysterectomy with salphingo-oophorectomy.

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

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

A novel hsa_circ_0006903 circular RNA promotes tumor development and dendritic cells activated expression in infantile hemangioma

BackgroundIncreasing reports revealed that circular RNAs (circRNAs) and immune cells infiltration were related with tumor development. However, its role in infantile hemangioma (IH) is unknown. We will explore a novel hsa_circ_0006903-based ceRNA network and investigate the landscape of dendritic cells activated expression in IH. Material and methodsDifferentially expressed circRNAs (DECs) were identified from Gene Expression Omnibus (GEO) database. Regulatory networks and functional enrichment analysis were constructed. CIBERSORT was used to characterize immune cells composition. qRT-PCR was performed to detect the expression of hsa_circ_0006903 in cell lines. Then, the role of hsa_circ_0006903 in IH were validated in vitro using transwell assay. Immunofluorescence was applied to the colocalization of CD11b for dendritic cells activated as a biomarker in IH tissues. ResultsUsing GEO database, a total of 67 DECs were screened out in IH. Hsa_circ_0006903 was the most significant DECs. Then, a novel hsa_circ_0006903 circular RNA-ceRNA network was constructed. Mechanistically, functional enrichment analysis showed that the p53 signaling pathway played the most important roles, and hsa_circ_0006903/miR-6721-5p/CACNA2D2 and hsa_circ_0006903/miR-4786-3p/ATP13A4 axis were identified. CACNA2D2, ATP13A4, and P53 were significantly downregulated in IH cell lines. We validated that dendritic cell activated was significantly overexpressed. Moreover, CD11b as a biomarker of dendritic cells activated were tested in IH tissues. Finally, hsa_circ_0006903 was significantly overexpressed, and hsa_circ_0006903 promoted infantile hemangioma cell proliferation, invasion, and migration in vitro. ConclusionOverall, our study revealed that a novel hsa_circ_0006903 promoted tumor progression, and indicated a potential biomarker CD11b of dendritic cells activated in IH.

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

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

A Systematic Review on Management of Infantile Hemangiomas: How Far We Have Reached in this Past Decade

Infantile hemangioma (IH) is a common condition in children. It may lead to cosmetic disfigurement, functional impairment, and various complications. There are various treatment options available for this condition. This article aims to discuss the various therapeutic options available for the treatment of IH. We searched PubMed, Google Scholar, and Embase (from December 2013 to December 2023) for human studies/case reports/case series assessing the management of IH. We reviewed 198 papers including different therapeutic regimens. β-blockers other than propranolol, such as nadolol, timolol, atenolol, acebutolol, and captopril, have shown comparable results to propranolol. Pulsed dye laser (PDL) and neodymium-doped yttrium aluminum garnet laser have shown promising results. Other therapies observed were sclerotherapy, cryotherapy, and surgical resection. A conventional combination of β-blockers with a laser might be the first-line treatment to arrest the growth of IH. PDL has shown promising results.

Hemangioma Neck: Clinical Overview and Management

Hemangiomas are benign vascular tumors that arise due to the proliferation of blood vessels. They can occur anywhere in the body but rarely occur in the neck. They are broadly classified into capillary and cavernous hemangioma. Here, we present a case of a 53-year-old female who presented to our outpatient department with swelling on the right side of the neck for 3 years with a recent increase in size associated with tingling, numbness, and pain in the right shoulder radiating to the arms and fingers for 6 months. Imaging studies suggested the diagnosis of right cervical hemangioma. After two failed sclerotherapy attempts, surgical excision of the mass was performed. Histopathology was suggestive of venous hemangioma.

Advantages of Early Surgical Management of Periorbital Infantile Hemangiomas

Advantages of Early Surgical Management of Periorbital Infantile Hemangiomas

Development of a New Non-Invasive Approach to Treat of Infantile Hemangioma with Growth-Inhibiting Endogenous Factors (Non-Invasive Approach to Treat of Infantile Hemangioma with Endogenous Factors)

Background: Infant hemangioma is a benign vascular tumor, the main reason for the development of which is genetic disorders occurring in embryogenesis. It should be noted that all methods of treating the disease, both general and local, have potential negative risks and side effects. The identification of endogenous regulatory factors and researching the possibilities of using them for treatment is relevant. There is the thermostable proteins complex (TPC) which has been identified in the cells of phylogenetically distant almost all organisms, which has the ability to decrease the mitotic activity of cells by inhibition of transcription. In the experimental model of hemangioma, it has been established that inhibition of capillary growth can only be achieved by injection. The aim of the work was to develop a new, less invasive method of hemangioma treatment with endogenous factors.

Treatment of telangiectasias with a 595-nm pulsed dye laser following hemangioma involution: a retrospective analysis.

Telangiectasias are the most frequent type of sequelae of infantile hemangiomas after involution. Few studies have reported the treatment of telangiectasias with 595-nm pulsed dye lasers. Therefore, the objective of this study was to assess the efficacy and safety of a 595-nm pulsed dye laser for treating residual telangiectasias following hemangioma involution. This is a retrospective case series that analyzes the medical records and reviews the charts of 22 patients who had undergone 595-nm pulsed dye laser treatment for residual telangiectasias. Pre- and post-treatment digital images were independently assessed, and the changes were scored to ascertain the efficacy of the treatment (0 = no change, 4 = complete improvement). Of the 22 patients, 59.1% experienced complete resolution of telangiectasias following treatment. No serious complications or side effects were reported. The observations indicate that the 595-nm pulsed dye laser is effective and safe for treating residual telangiectasias following hemangioma involution.

Infantile haemangioma treated with Homoeopathy: A case report

Infantile haemangioma treated with Homoeopathy: A case report

Comparison of efficacy and safety between oral propranolol combined with and without intralesional injection of lauromacrogol for infantile hemangioma.

The purpose of this study was to compare efficacy and side effects between oral propranolol combined with and without intralesional injection of lauromacrogol for infantile hemangioma (IH). This was a single center randomized controlled prospective study, all participants were firstly diagnosed with IH between August 2022 and January 2023 in our hospital and without any treatment before. Patients were randomized into two groups. PRO group: oral propranolol (2 mg/kg/day) continued for 6 months; PRO + LAU group: oral propranolol (2 mg/kg/day) for 6 months and intralesional injection of lauromacrogol for 2-4 times within 6 months. The dimensions, color, consistency, photographic documentation were well recorded based on Visual Analogue Scale (VAS) before and after starting treatment. According to the treatment response after 6 months, the results were classified into four levels: Grade 1, complete resolution achieved; Grade 2, with ≥50% reduction in size of IH; Grade 3, with <50% reduction in size of IH; Grade 4, no response or worsening of IH. A total of 67 patients were involved in the study (17 boys, 50 girls; mean age, 3.6 months, range, 1.1-7.2 months) and randomized to receive oral propranolol combined with or without intralesional injection of lauromacrogol (29 in PRO group, 38 in PRO + LAU group). All patients completed treatment. Eleven patients (37.9%) in PRO group were in Grade 1, 14 patients (48.3%) in Grade 2, 4 patients (13.8%) in Grade 3, compared with these in PRO + LAU group, 11 patients (28.9%) in Grade 1, 24 patients (63.2%) in Grade 2, and 3 patients (7.9%) in Grade 3. No patient was in Grade 4, and no severe side effects were observed in both group. In PRO group, it takes an average of 17.1 ± 5.4 weeks from the start of treatment to cure, and in PRO + LAU group, the average time is 13.7 ± 4.9 weeks. Oral propranolol with intralesional injection of lauromacrogol was a safety treatment strategy for IH. But it was not superior to oral propranolol in final cure rates (P = 0.45), moreover, it cannot certainly offer the benefits of shortening the duration of oral drug treatment (P = 0.24).

Microneedle delivery system with rapid dissolution and sustained release of bleomycin for the treatment of hemangiomas

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.Graphical

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

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

Diagnostic approach to hepatic vascular lesions: a paediatric perspective.

The pathological evaluation of hepatic vascular lesions in children requires special consideration. Inconsistent terminology, rarity of pathology specimens and overlapping pathological features between various lesions may pose a serious diagnostic challenge. In this review, we highlight the importance of using the International Society for the Study of Vascular Anomalies (ISSVA) classification scheme to characterise these lesions. Selected entities are discussed, including hepatic vascular tumours exclusively seen in the paediatric age group, hepatic infantile haemangioma and hepatic congenital haemangioma. Vascular malformations, with emphasis on their syndromic associations (venous malformation in blue rubber bleb naevus syndrome) and complications (hepatocellular nodules in Abernethy malformation) are also covered.