Complicated Infantile Hemangiomas Research Articles

Large ulcerated hemangioma treated with topical timolol drops

Infantile hemangiomas (IH) are the most common benign tumors of infancy and undergo spontaneous remission by about four to five years of age. Usually, only superficial and uncomplicated hemangiomas are treated by topical timolol while larger and complicated hemangiomas require oral propranolol or corticosteroids. Uncommonly reported in the literature is that even larger complicated IHs on low-risk sites can be treated with timolol drops locally. Our case is unique, as we treated a large ulcerated IH with oral and topical antibiotics and only topical timolol drops with rapid and complete resolution of symptoms.

Treatment of infantile hemangioma with topical β-blockers in pediatric practice: a review of the literature

The purpose of this review is to acquaint the audience with the benefits of infantile hemangioma (IH) treatment with local β-blockers, which are safe for the child, allow for the complete cure of hemangiomas without surgery, complications, scars, and cosmetic defects, and have practically no systemic side effects. We aimed to analyze the effectiveness and limitations of the use of local β-blockers, to show the possibility and expediency of IH management in pediatric practice, and to demonstrate that the goal of therapy is not the treatment of complications, but the prevention of their occurrence and complete resolution of the hemangioma without surgical intervention. The use of topical β-blockers, such as timolol gel or solution, provides a non-surgical, non-invasive treatment option for IH, minimizing the systemic exposure and possible side effects associated with oral β-blockers. Local treatment is best started before the age of 2 months - at an early stage, when IHs are small in size, potentially preventing the need for more invasive treatment methods. Topical use is associated with a lower risk of systemic side effects, such as hypotension or bradycardia, that can occur with oral β-blockers. Topical treatment can be applied at home, which can be more convenient for parents and caregivers, and also increases the opportunity for treatment and follow-up by pediatricians. In case of natural disasters or military operations, treatment can be done remotely using teledermatology. The effectiveness of local β-blockers mostly depends on the age at which treatment was started: the earlier it was started, the higher the effectiveness. Treatment of complicated IH with deep soft tissue, mucosal, or airway involvement usually requires a combination of systemic propranolol and topical β-blockers or other interventions such as laser therapy. The choice of treatment should be selected individually according to the degree of risk of IH, its size, localization, child's age, weight, and other parameters in each clinical case. β-adrenoblockers are the most modern, effective, non-surgical, and safe method of treating IH, they can be used both for systemic and local application. IH can be successfully treated by pediatricians and dermatologists. No conflict of interests was declared by the authors.

A commentary on 'Indications for surgical resection of complicated infantile hemangiomas in the β-blocker's era: a single-institution experience from a retrospective cohort study'.

A commentary on 'Indications for surgical resection of complicated infantile hemangiomas in the β-blocker's era: a single-institution experience from a retrospective cohort study'.

POSTER ABSTRACTSP01 Our experience with outpatient initiation of propranolol in the treatment of complicated infantile haemangiomas

Abstract During the COVID-19 pandemic, consensus expert opinion published guidelines on the outpatient initiation of propranolol in the treatment of complicated infantile haemangiomas (IH). We performed an audit from 2015 to 2019 which demonstrated that the establishment of a dedicated IH clinic both improved access to and resulted in earlier initiation of propranolol in the Mid-West region. The aims of this re-audit were to evaluate patients referred to our clinic with IH, and to assess our compliance with international guidelines on the use of propranolol for the treatment of IH. All patients commenced on propranolol following referral to our dedicated IH clinic from January 2019 to September 2021 were identified from our dermatology database, and clinical and demographic data were collected from their charts. Data analysis demonstrated a 21-fold increase in outpatient initiation of propranolol, with 57% (n = 16/28) of patients commencing treatment as outpatients. In those patients who received inpatient initiation of propranolol, inpatient initiation was indicated in 88% (n = 8/9). We report treatment of 28 patients over 2 years with IH, 16 of whom were safely initiated in the outpatient setting, consistent with updated international guidelines. The main focus should now be on primary care education about IH in our community to ensure early intervention with propranolol when indicated.

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.

Infantile Hämangiome

With an incidence of approximately 4% infantile hemangiomas are the most common vascular tumors in children and show characteristic growth dynamics. In order to avoid erroneous treatment, they need to be differentiated from other vascular tumors (granuloma pyogenicum and kaposiform hemangioendothelioma) and vascular malformations. Of all infantile hemangiomas 85% are uncomplicated and undergo spontaneous resolution starting towards the end of the first year of life. First-line treatment for complicated infantile hemangiomas (15%), i.e. those with imminent obstruction (eyes and nose), ulceration or permanent disfigurement, is oral propranolol (2 mg/kg BW and day for at least 6months).

Indications for surgical resection of complicated infantile hemangiomas in the β-blocker's era: a single-institution experience from a retrospective cohort study.

This study aims to review how the introduction of propranolol as the primary treatment option for children with infantile hemangiomas (IHs) has affected the use of other treatment options at our institution and to determine the indications for surgical treatment of children with IHs in the propranolol era. The authors conducted a single-center, noncompeting, historical/retrospective cohort study to review all cases referred to the institution for IH evaluation from 2005 to 2020. The authors analyzed the complete charts of patients who received surgery from 2011 to 2020 and evaluated the reasons for each surgical intervention. Detailed descriptive statistics are provided. Logistic regression analysis and Pearson's χ2 -test were applied. During the study period, 592 children received treatment. From 2011, oral propranolol ( n =268; 74%) and surgery ( n =95; 26%) were the only treatments of choice for complicated IH cases. A significant decrease in the frequency of surgical treatment was observed ( P =0.01). The authors identified four main indications for surgical treatment: (1) patients with ulceration and IH size appropriate for surgical resection (15%); (2) patients whose parents preferred surgical treatment (19%); (3) patients who presented late and underwent surgery before the age of three (29%); and (4) patients with sequelae after IH involution and excision after the third year of life (37%). Despite the significant decrease in the need for surgical treatment of children with IHs since the introduction of propranolol, there are still several clear indications for treating IH cases where surgery plays a crucial role.

An unusual deep seated haemangioma successfully treated with propranolol

Infantile hemangiomas (IH) are most common vascular tumors. It usually resolves on its own, treatment becomes necessary if there is disease progression. Oral propranolol is a medical therapeutic option for complicated IH with impressive efficacy and generally good tolerance. We report a case of deep seated IH of the cheek in a 4 month old successfully treated with propranolol.

Medical Management of Infantile Hemangiomas: An Update.

Infantile hemangioma (IH) is the most common benign vascular tumor of infancy, affecting about 5% of infants. It has a characteristic growth pattern of early rapid proliferation followed by progressive involution. Although most IH evolve favorably, complications are observed in 10-15% of cases, justifying treatment. For over 10 years now, propranolol has become the first-line therapy for complicated IH, revolutionizing their management and their prognosis. In this article, we review the clinical features, associations, complications/sequelae and therapeutic approaches for IH, focusing on current medical therapy. Indications for treatment and various treatment options, including propranolol and other oral β-blockers, topical timolol, and corticosteroids are presented. Current controversies regarding oral propranolol such as pre-treatment screening, in- vs out-patient initiation of treatment, early and potential long-term side effects and recommended monitoring are discussed.

МЕЖДИСЦИПЛИНАРНЫЙ ПОДХОД К ЛЕЧЕНИЮ МЛАДЕНЧЕСКИХ ГЕМАНГИОМ

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

Infantile Hemangioma: A Review of Current Pharmacotherapy Treatment and Practice Pearls.

Infantile hemangioma (IH) is the most common vascular tumor of infancy, affecting as many as 5% to 10% of all infants. The exact cause is unclear, but specific risk factors, such as low birth weight, prematurity, female sex, white race, and family history are associated with IH development. Most IHs are benign and self-resolving, but a small subset of patients with IHs are at risk of severe or life-threatening outcomes. Systemic and topical β-blockers are effective and safe for use in pediatric patients and considered first-line treatment for both complicated and uncomplicated IHs. Recently published guidelines provide a thorough review of IH and management. This article focuses on IH pharmacotherapy and provides practice pearls to support health care providers in IH medication management.

Infantile Hemangioma: An Updated Review.

Infantile hemangiomas are the most common vascular tumors of infancy, affecting up to 12% of infants by the first year of life. To familiarize physicians with the natural history, clinical manifestations, diagnosis, and management of infantile hemangiomas. A Pubmed search was conducted in November 2019 in Clinical Queries using the key term "infantile hemangioma". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews published within the past 20 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article. The majority of infantile hemangiomas are not present at birth. They often appear in the first few weeks of life as areas of pallor, followed by telangiectatic or faint red patches. Then, they grow rapidly in the first 3 to 6 months of life. Superficial lesions are bright red, protuberant, bosselated, or with a smooth surface, and sharply demarcated. Deep lesions are bluish and dome-shaped. Infantile hemangiomas continue to grow until 9 to 12 months of age, at which time the growth rate slows down to parallel the growth of the child. Involution typically begins by the time the child is a year old. Approximately 50% of infantile hemangiomas will show complete involution by the time a child reaches age 5; 70% will have disappeared by age 7; and 95% will have regressed by 10 to 12 years of age. The majority of infantile hemangiomas require no treatment. Treatment options include oral propranolol, topical timolol, and oral corticosteroids. Indications for active intervention include hemorrhage unresponsive to treatment, impending ulceration in areas where serious complications might ensue, interference with vital structures, life- or function-threatening complications, and significant disfigurement. Treatment should be individualized, depending upon the size, rate of growth, morphology, number, and location of the lesion (s), existing or potential complications, benefits and adverse events associated with the treatment, age of the patient, level of parental concern, and the physician's comfort level with the various treatment options. Currently, oral propranolol is the treatment of choice for high-risk and complicated infantile hemangiomas. Topical timolol may be considered for superficial infantile hemangiomas that need to be treated and for complicated infantile hemangiomas in patients at risk for severe adverse events from oral administration of propranolol.

Limited utility of repeated vital sign monitoring during initiation of oral propranolol for complicated infantile hemangioma

Initial propranolol recommendations for infantile hemangioma published in 2013 were intended as provisional best practices to be updated as evidence-based data emerged. A retrospective multicenter study was performed to evaluate utility of prolonged monitoring after first propranolol dose and escalation(s). Inclusion criteria included diagnosis of hemangioma requiring propranolol of greater than or equal to 0.3mg/kg per dose, younger than 2years, and heart rate monitoring for greater than or equal to 1hour. Data collected included demographics, dose, vital signs, and adverse events. A total of 783 subjects met inclusion criteria; median age at initiation was 112days. None of the 1148 episodes of prolonged monitoring warranted immediate intervention or drug discontinuation. No symptomatic bradycardia or hypotension occurred during monitoring. Mean heart rate change from baseline to 1hour was -8.19/min (±15.54/min) and baseline to 2hours was -9.24/min (±15.84/min). Three preterm subjects had dose adjustments because of prescriber concerns about asymptomatic vital sign changes. No significant difference existed in pretreatment heart rate or in heart rate change between individuals with later adverse events during treatment and those without. Prolonged monitoring for initiation and escalation of oral propranolol rarely changed management and did not predict future adverse events. Few serious adverse events occurred during therapy; none were cardiovascular.

Assessment of Oral Propranolol Administration for Infantile Hemangioma in Oral and Maxillofacial Region Aided by Ultrasonography

Propranolol has become the first-line therapy for the treatment of complicated infantile hemangioma. However, there are still many queries regarding the hemangioma volume in relation to drug's dose and duration. The aim of this study was to evaluate the therapeutic effect of oral propranolol for treating infantile hemangiomas in the oral and maxillofacial region aided by gray scale ultrasonography (GSU). Twelve patients with infantile hemangioma, age ranged between 2 and 11 months, have been treated with oral propranolol for 6 months' period. They received a dose of 1 mg/kg per body weight per day, increased after 1 week to 2 mg/ kg per body weight per day maintenance for 24 weeks. The changes in tumor sizes were evaluated by ultrasonography (GSU) using 4-points scale system: excellent, good, fair, poor) RESULTS:: All infants less than 6 months of age showed more hemangiomas regression in size in comparison with of those aged >6 months (P value 0.042) as a rapid response. After the 24 week; 5 patients had excellent results, 4 patients had good results, 2 patients had fair results, and only 1 patient had poor results. None of the treated infants showed rebound phenomena after cessation of treatment. Oral propranolol at dose of 2 mg/kg/day in 2 divided doses for 24 weeks aided by GSU is shown to be a safe and effective treatment of infantile hemangioma during the proliferative phase.

Angiomes superficiels : traitements

Beta-blockers are efficient for treating complicated infantile hemangiomas; propranolol is currently the first-line treatment. Superficial vascular malformations have to be managed by multidisciplinary teams. T2 FAT-SAT MRI is the most interesting sequence to explore superficial vascular malformations. Recent advances in molecular biology allow exploring new genetic mutations which could be involved in vascular malformations and be the target of new drugs. Mammalian target of rapamycin (mTOR) inhibitors are promising drugs for slow-flow malformations. Arteriovenous malformations are aggressive lesions with very few treatment options.

Management of infantile haemangioma

Infantile haemangiomas (IH) are common benign vascular neoplasms of infancy. Natural history follows a characteristic pattern - proliferation, stabilisation, and involution. Most IH remain uncomplicated. Watchful expectancy will suffice for this group. Segmental type of IH over face and lower back can be associated with extra cutaneous abnormalities. A small subset of IH gets complicated with risk of functional impairment, cosmetic disfigurement, or ulceration. Systemic treatment is required for this selective group to hasten natural involution and prevent secondary complications. Oral propranolol has revolutionised the management of IH and is now the first line systemic treatment. Topical beta blockers have also been used increasingly in the management of superficial localised lesions. Other systemic options include oral steroids, vincristine, interferon but all of these have a limited role due to adverse side effects. A multidisciplinary approach with the team of paediatricians, paediatric dermatologists and other specialists is essential in management of complicated IH.

Large Infantile Hemangioma on the Face: Let’s ‘PHACE’ It

Background: Infantile hemangiomas (IH) are the most common benign (vascular) tumors in infancy but due to their natural self-limiting course do not necessarily need treatment; in case of ulceration, bleeding or potential deformity, treatment is necessary. Large segmental facial hemangiomas may be associated with PHACE syndrome. Case presentation: We present a case of a boy with a large segmental facial IH. Ulceration, size and location were indications for starting propranolol up to a dose of 3 mg/kg/day in three doses, eleven days after birth. Because of the location and distribution, PHACE syndrome had to be excluded: the patient was checked for possible brain, cardiac and vascular malformations and visual impairment. The IH improved. At the age of nine months, there were no adverse effects or IH progression. Discussion: Propranolol is a beta-blocker effective in treating IH. Its working mechanism has not been completely clarified. We provide a thorough description of our approach to the early propranolol treatment of this large segmental facial IH. Conclusion: Complicated IH like the one described here can be treated safely and effectively with propranolol; very early treatment initiation is recommended to prevent the development of anatomic deformities. Our patient was treated with propranolol 3 mg/kg/day in three doses in order to prevent future disfigurement when it is located in a high-risk area like the face. Further research is needed to create a uniform approach and universal guideline for the treatment of IH with propranolol.

Lower socioeconomic status is associated with delayed access to care for infantile hemangioma: A cohort study

Early specialist evaluation during rapid proliferative growth of complicated infantile hemangiomas (IHs) is crucial. Health disparities and barriers of access to care for children with IHs have not been examined. To investigate whether socioeconomic status (SES) is associated with age at presentation to a subspecialist for IH evaluation. A retrospective cohort study of 804 children presenting to a large academic hospital. The primary outcome was age at initial presentation. Covariates included demographic, socioeconomic, geographic, and clinical characteristics. Medicaid and the Children's Health Insurance Program were proxies for lower SES. Analysis of covariance, chi-square tests, and generalized ordered logistic regressions were performed. Children with lower SES had higher odds of presenting after 3months of age (odds ratio, 2.11; 95% confidence interval, 1.31-3.38). In the subset that qualified for the institutional care management program (ICMP), no risk factors were associated with delayed presentation. Use of insurance and economic distress asproxies for SES; exclusion of uninsured children, which may have resulted in underestimation of racioethnic effects; and examination of a single academic center, which may limit generalizability. Children with IHs and lower SES were more likely to present later to specialists, but those enrolled in an ICMP were not, suggesting that integrated ICMPs may mitigate disparities and delayed access to care for IHs among lower-SES populations.

Surgical resection of infantile hemangiomas following medical treatment with propranolol versus corticosteroids

PurposeThere has been a paradigm shift from corticosteroid to propranolol treatment for infantile hemangiomas (IHs), with surgical resection reserved for complicated or persistent IHs. The purpose of this study was to determine if propranolol treatment was associated with decreased utilization of surgical resection compared to corticosteroids. MethodsA single center retrospective chart review of all corticosteroid or propranolol treated IHs between 2005 and 2014 was performed. Demographic and clinical data were collected. Both univariate and multivariate analyses were performed with the primary outcome of requiring surgical intervention. ResultsOf 652 patients with IH, 52 were treated with oral corticosteroids and 195 with propranolol only. Surgical intervention was required in 14 (27%) of steroid patients vs 18 (9%) of propranolol patients (p < .001). On multivariable analysis patients treated with steroids had 3.3 the odds of requiring surgery when compared to propranolol patients (p = .001). Prematurity (<37 weeks) was also associated with increased odds of surgery (OR = 2.8, p = .003). ConclusionPatients treated with propranolol required significantly fewer surgical interventions than those treated with corticosteroids suggesting a more efficacious treatment paradigm. Prematurity increases the need for surgical intervention regardless of the modality of medical treatment. Level of evidenceLevel III, treatment study.

Propranolol pharmacokinetics in infants treated for Infantile Hemangiomas requiring systemic therapy: Modeling and dosing regimen recommendations.

Propranolol has become the first choice therapy for complicated Infantile Hemangiomas (IH). The pharmacokinetics of propranolol were evaluated after repeated oral administration of a new pediatric solution of propranolol at 3 mg kg−1 day−1 given twice daily (BID) in infants (77‐243 days) with IH. A population model was built to describe the pharmacokinetics of propranolol in infants and to simulate different dosing regimens. One hundred and sixty‐seven plasma concentrations from 22 infants were used in the population analysis. Weight effect was tested on apparent clearance and volume of distribution. Monte‐Carlo simulations were performed for 4 dosing regimens: BID dosing with irregular or strict 12‐hour intervals and 2 different 3 time daily dosing (TID) regimens. The best model was a one‐compartment model with first‐order absorption and elimination rates. The weight affected the clearance but not the volume. Typical oral clearance was estimated at 3.06 L hour−1 kg−1 (95% CI: 1.14‐8.61 L hour−1 kg−1), close to adult clearance data. When regular BID dosing was compared to TID or irregular BID regimens, simulated median Cmin and Cmax were <20% different. To conclude, a model using a weight allometric function on clearance was established and confirmed that the dose in mg/kg should be used without adaptation by range of age in treatment of complicated IH. The simulations support the use of a BID dosing preferably to a TID dosing thanks to close Cmin and Cmax at steady state between both regimen and showed the possibility of irregular BID dosing, allowing early administration in the evening when needed.