Propranolol For Treatment Of Infantile Hemangiomas Research Articles

JAAD Game Changers: “Propranolol treatment of infantile hemangioma (IH) is not associated with developmental risk or growth impairment at age 4 years”

JAAD Game Changers: “Propranolol treatment of infantile hemangioma (IH) is not associated with developmental risk or growth impairment at age 4 years”

Cardiac Evaluation before and after Oral Propranolol Treatment for Infantile Hemangiomas.

Background: Most recent clinical practice guidelines addressing the management of infantile hemangiomas (IHs) recommend oral propranolol, a non-selective beta-adrenergic antagonist, as first-line treatment. However, few reports have provided continuous follow-up data regarding cardiac evaluations. Methods: Sixty-four patients diagnosed with IHs and treated with oral propranolol before 2 years of age at the Department of Pediatrics, Kangbuk Samsung Hospital (Seoul, Republic of Korea), with regular examinations between 2017 and 2021, were included. Cardiac evaluations, including electrocardiography, Holter monitoring, chest X-ray, and echocardiography, were performed. Results: Sixty-four patients with IHs successfully underwent continuous follow-up cardiac evaluations. The median age at diagnosis was 2 weeks (1 day to 34.3 weeks). The median age at treatment initiation was 13.6 weeks (2.4-87.9 weeks), the mean longitudinal diameter of hemangioma at diagnosis was 2.8 ± 2.1 cm (0.3-12.0 cm), and the mean percentage of size decrease after 1 year of oral propranolol treatment was 71.8%. None of the 64 patients experienced severe adverse side effects during propranolol treatment. There was no statistically significant differences in echocardiographic function and electrocardiographic data after treatment. Conclusions: Propranolol treatment ≥6 months was effective and safe without significant cardiac toxicity in the treatment of patients with infantile hemangiomas.

The burden of treatment of propranolol for infantile hemangiomas: A mixed methods study.

The burden of treatment (BOT) related to propranolol treatment for infantile hemangiomas (IH) has never previously been explored. A modified validated questionnaire, the Treatment Burden Questionnaire, and one-on-one semi-structured interviews were used to assess the BOT for propranolol for IH. Out of 80 caregivers, the overall burden score was very low at 1.2 out of 10; thematic analysis of interviews grouped themes into administration, monitoring, financial, and associated anomalies. The BOT of propranolol for IH is very low but could be reduced further by offering age-based risk stratification related to feeding frequency and risk of hypoglycemia, pragmatic advice around timing of doses before sleep, and reducing frequency of vital sign monitoring.

Timing of Propranolol Treatment for Infantile Hemangioma

Timing of Propranolol Treatment for Infantile Hemangioma

Early propranolol treatment of infantile hemangiomas improves outcome

BackgroundInfantile hemangiomas (IH) are the most common soft tissue tumors of childhood. Although most of these tumors are not worrisome, some IH may be life or function-threatening, can lead to permanent disfigurement, or have associated structural congenital anomalies, requiring early recognition and referral to specialists for treatment consideration. Since 2008, oral propranolol has been widely considered to be the first-line treatment for IH. ObjectivesTo evaluate aesthetic and functional outcome in propranolol-treated infantile hemangiomas according to the age of treatment onset. MethodsRetrospective, observational study of infantile hemangioma patients under 4 years of age at the time of diagnosis, treated with oral propranolol. Evaluated parameters included: pre and post-treatment morphologic/aesthetic aspects of the hemangioma, total resolution rate, degree of functional compromise of affected areas and its evolution. Two independent pediatric dermatologists evaluated all cases reviewing clinical data from medical records and comparing clinical photographs taken at initiation and at the end of treatment of each patient. Data were analyzed with STATA 13.0 program. ResultsThe cohort included 138 patients, with a female predominance. The median age at therapy onset was 3 months. The morphological/aesthetic improvement rate was 99% (95% CI 96‒99), the total resolution rate was 48% (95% CI 44‒60) and the functional improvement rate reached 100%. When comparing total resolution outcome versus age when treatment started, the improvement was larger in younger patients (3.5 vs. 4.9 months, p = 0.01). When comparing the total resolution rate in those younger or older than 3 months at treatment initiation, the percentage of total resolution in the younger group was 57% vs. 40% in the older one (p = 0.05). Study limitationsRetrospective design; patients photographs were the sole indicators used to measure regression rates. Visual assessment is subjective. ConclusionThe present results strongly suggest that early (before 3 months of age) initiation of treatment of infantile hemangiomas with propranolol results in significantly higher aesthetic and functional improvement rates and a higher percentage of total resolution.

Monitoring oral propranolol for infantile hemangiomata.

Treating infantile hemangiomas with oral propranolol may be initiated in accordance with various protocols some require hospitalization. However, different adverse events have been reported during treatment, thus it is of special importance to find a protocol which is both safe and feasible. We performed a retrospective cohort study of all cases of infantile hemangiomas treated with oral propranolol at our institute between January 2010 and February 2020. Pretreatment evaluation consisted of pediatric cardiologist evaluation including electrocardiography and echocardiography. The propranolol starting dosage was 0.5mg/kg bid; 2 weeks later the dosage was escalated to 1mg/kg bid. During the initiation and escalation visits, heart rate and blood pressure were measured before and every hour for a total of 3h, and blood glucose level was measured within the first hour of treatment. A total of 131 children were treated during the study period. Scalp, facial and genital region infantile hemangiomas were more prevalent in regard to their relative body surface area. No symptomatic bradycardia, hypotension, hypoglycemia, or any other adverse events were documented; few patients had asymptomatic bradycardia and hypotension, which were more common in infants below 6-months of age. Only one patient had asymptomatic hypoglycemia, not requiring any intervention. Initiation and escalation of propranolol treatment for infantile hemangiomas proved to be safe, and without symptomatic adverse effects. However, considering the young age of the patients and the possible asymptomatic adverse reactions, we recommend the following simple protocol as presented, for pretreatment evaluation and short monitoring during treatment initiation and dose escalation.

The VASCERN-VASCA working group diagnostic and management pathways for severe and/or rare infantile hemangiomas

The European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN), is dedicated to gathering the best expertise in Europe and provide accessible cross-border healthcare to patients with rare vascular diseases. Infantile Hemangiomas (IH) are benign vascular tumors of infancy that rapidly growth in the first weeks of life, followed by stabilization and spontaneous regression. In rare cases the extent, the localization or the number of lesions may cause severe complications that need specific and careful management. Severe IH may be life-threatening due to airway obstruction, liver or cardiac failure or may harbor a risk of functional impairment, severe pain, and/or significant and permanent disfigurement. Rare IHs include syndromic variants associated with extracutaneous abnormalities (PHACE and LUMBAR syndromes), and large segmental hemangiomas. There are publications that focus on evidence-based medicine on propranolol treatment for IH and consensus statements on the management of rare infantile hemangiomas mostly focused on PHACES syndrome. The Vascular Anomalies Working Group (VASCA-WG) decided to develop a diagnostic and management pathway for severe and rare IHs with a Nominal Group Technique (NGT), a well-established, structured, multistep, facilitated group meeting technique used to generate consensus statements. The pathway was drawn following two face-to-face meetings and in multiple web meetings to facilitate discussion, and by mail to avoid the influence of most authoritative members.The VASCA-WG has produced this opinion statement reflecting strategies developed by experts and patient representatives on how to approach patients with severe and rare IH in a practical manner; we present an algorithmic view of the results of our work.

Safety of propranolol for infantile hemangioma in infants less than five weeks corrected age.

Propranolol is used to treat problematic infantile hemangiomas (IHs), but its safety in infants <5weeks corrected age has not been established. The objective of this study was to assess the safety and efficacy of propranolol for treatment of IH in infants <5weeks corrected age, or 45weeks corrected gestational age (CGA). We performed a single institution, retrospective review of patients treated with propranolol prior to the age of 6months between 2017 and 2021. Patient characteristics, location of hemangioma(s), weight at initiation of treatment, dosing information, side effects, response, and duration of treatment were documented. Of 200 patients with IH treated with propranolol, 24 started treatment prior to 45weeks CGA. Mean CGA at initiation of treatment was 42weeks. Sixty-seven percent were female and 75% were white, non-Hispanic. Mean duration of treatment was 255days. Twenty-two patients (92%) had clear benefit from treatment at a dose of 1-3mg/kg/day. The most common side effects were sleep disturbance (21%), irritability (17%), and cool hands/feet (13%). There were no serious adverse events. In this cohort of 24 patients with corrected age <5weeks (CGA <45weeks), propranolol was safe and effective for the treatment of infantile hemangiomas. Larger, prospective studies are indicated to investigate propranolol in this age group.

Ultrasound and MRI findings as predictors of propranolol therapy response in patients with infantile hemangioma.

ObjectivesTo evaluate the prognostic value of ultrasound and MRI findings in patients with infantile hemangioma undergoing propranolol therapy.MethodsThis study was based on retrospective interpretation of prospectively acquired data. Thirty-eight consecutive patients (28 females and 10 males; mean age ± standard deviation, 3.2 ± 2.2 months) who underwent propranolol treatment for infantile hemangioma were included. Pre-treatment ultrasound images were assessed in terms of echogenicity, lesion height and vascularity. Presence of prominent intratumoral fat, non-fat septa, and enhancement pattern on MRI were retrospectively evaluated. Mann-Whitney test, chi-square, and Fisher’s exact tests were used to compare imaging parameters between patients with treatment success and failure.ResultsAll patients underwent ultrasound and 15 patients underwent MRI. A total of 24 patients showed successful treatment. Between patients with treatment success and failure, there were significant differences in increased vascularity on pre-treatment ultrasound (19/24 vs. 6/14, p = 0.025), decreased vascularity on post-treatment ultrasound (21/24 vs. 5/14, p = 0.001), and prominent intratumoral fat on MRI (1/8 vs. 5/7 p = 0.033). There were no significant differences in echogenicity, lesion height on ultrasound, non-fat septa and MR enhancement pattern.ConclusionsIncreased vascularity on pre-treatment ultrasound was significantly associated with successful treatment for propranolol therapy in patients with infantile hemangioma, whereas prominent fat component on MRI was significantly associated with treatment failure.

Propranolol Treatment for Infantile Hemangiomas: Short-Term Adverse Effects and Follow-Up to Age Two.

Objective To analyse the short-term adverse effects (AEs) of propranolol in the treatment of infantile hemangiomas (IHs) and their relevant factors, as well as the relationship between child growth and propranolol. Methods A total of 506 patients with confirmed or suspected IHs were enrolled, and a total of 439 cases were included in the study. Short-term AEs were analysed using single-factor analysis and binary logistic regression. Out of 439 patients, 292 were enrolled to examine the effect of propranolol on 2-year-olds' height and body weight (BW), by comparison with reference range and among groups. Spearman rank correlation analysis was used to determine the relationship between BW, height, and duration of propranolol treatment. Results Among 439 patients, 70 (16.0%) experienced AEs. Among them, 48 had gastrointestinal (GI) symptoms, 23 had central nervous system (CNS) symptoms, 8 had both symptoms above, and 7 had other symptoms. Most of the AEs occurred on the starting day (day 0), and 6 children's AEs were transient. Starting age of no older than 3 months led to more CNS symptoms, and starting age of older than 3 months was a protective factor against CNS symptoms, with an OR value of 0.303 (0.117–0.783). Height and BW of 292 two-year-old children were no less than the reference levels, although those of 3 females and 1 male were less than the average −2 standard deviation (−2SD). The height and BW of the children at the age of two was not related to the length of time of propranolol treatment. Conclusion Oral propranolol has a good tolerance in the treatment of IHs. Oral propranolol exerts more adverse effects on the CNS of lower age children, and it has exhibited no effect on the growth of two-year-old children.

Effectiveness, Indications, and Side Effects of Oral Propranolol Treatment for Infantile Hemangioma in Japanese Patients

Effectiveness, Indications, and Side Effects of Oral Propranolol Treatment for Infantile Hemangioma in Japanese Patients

No Increased Risks Associated with Propranolol Treatment for Infantile Hemangioma in Preterm Infants were Identified at 3 Years of Age.

Concerns have been raised that propranolol treatment of infantile hemangioma (IH) may be associated with increased risks of adverse effects and growth impairment in preterm infants due to their immature development. This study aimed to find out whether treatment of IH with propranolol in preterm infants is associated with higher incidences of long-term adverse effects and growth impairment in comparison with term infants. The clinical data of 55 preterm infants and 180 term infants with IH treated with oral propranolol for 6months were retrospectively collected and analyzed. The preterm and term patients did not differ significantly in terms of the general characteristics and adverse effect incidence (all p > 0.05). Height, weight, and head circumference of the preterm infants at ages 1, 2, and 3years did not differ significantly from the normal references (all p > 0.05). In the term patients, only 1-year-old female weight and head circumference were significantly higher than the normal references (both p < 0.05). Treatment of IH with propranolol for 6months did not increase the risks for adverse effects or growth impairment up to age 3years in preterm versus term patients in our study.

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.

Serum concentrations of VEGF and bFGF in the course of propranolol therapy of infantile hemangioma in children: Are we closer to understand the mechanism of action of propranolol on hemangiomas?

Propranolol has become the treatment of choice for infantile hemangiomas (IH). Neither the pathogenesis of IH nor the mechanism of action of propranolol on them are well understood. Possible explanations include the inhibition of angiogenesis by decreasing vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), induction of vascular endothelial cell apoptosis and vasoconstriction. The aim of the study was to assess serum concentrations of VEGF and bFGF in the course of propranolol therapy of IH in children, and to assess their clinical implications. The study included 51 children with IH treated with propranolol. The participants were assessed before, during and after the therapy with Hemangioma Activity Score (HAS), Doppler ultrasound (US) of the lesions, as well as VEGF and bFGF serum concentrations. All children showed clinical improvement measured in the HAS. A complete involution of the IH was reported in 32 (63%) children at the time of decision of the gradual withdrawing of propranolol, and in 28 (61%) patients at the end of the treatment (out of 46 patients present at the follow up after 1.5 months). Doppler US at the follow-up showed a complete disappearance of the blood flow in the lesion in 24 (52%) children and its reduction in 12 (26%) children. There was a significant decrease in VEGF and bFGF during and after treatment compared to pretreatment values. There was a correlation between the outcome of the Doppler US and changes in bFGF during and after treatment. Changes in VEGF during treatment did not correlate with changes in the Doppler US. Serum concentrations of VEGF and bFGF decreased during the propranolol treatment of IH, which may indicate the effect of propranolol on both. However, the statistical analysis showed their low prognostic value as biochemical markers of propranolol treatment. Clinical evaluation combined with Doppler US is the most valuable method of monitoring the therapy.

Safety and effectiveness of oral propranolol for infantile hemangiomas started before 5\xa0weeks and after 5\xa0months of age: an Italian multicenter experience

BackgroundDespite not being licensed for the treatment of infantile hemangiomas (IH) in infants younger than 5 weeks or older than 5 months, propranolol is often used in these age groups to prevent or to treat potentially severe complications. The objective of the present study was to review the experience of 8 Italian pediatric and dermatologic centers regarding propranolol treatment for IH started before 5 weeks or after 5 months of age.MethodsWe retrospectively reviewed the records of patients followed up for IH, on propranolol treatment started before 5 weeks or after 5 months of age, and collected information on sociodemographic data, treatment indications, IH involution, IH relapse, and treatment side effects.ResultsA total of 343 patients were enrolled; 15 were started on propranolol before 5 weeks (group 1), 328 were started after 5 months of age (group 2). The most frequent indications were permanent aesthetical disfigurement (91.8%) and function threatening complications (42.6%).In most cases, the treatment was effective. The involution was partial in 67.7% of patients. In 11.8% of cases a relapse was observed. No relapse was observed in group 1. Treatment complications were reported in 15.8% of children, most frequently sleep disorders (6.6%), followed by irritability (5.1%) and diarrhea (2.2%). Only a case of mild constipation was observed in group 1.ConclusionThe safety and effectiveness profile of propranolol in infants younger than 5 weeks or older than 5 months may be acceptable. Taking in account propranolol's potential in preventing severe complications, further studies should assess the acceptability of propranolol treatment, especially in the <5-week age group .

Propranolol treatment for infantile hemangioma does not increase risk of childhood wheezing

Propranolol is the treatment of choice for infantile hemangiomas requiring medical intervention. Although contraindicated in asthma, its bronchoconstrictive effect in infants and children has not been extensively studied. We aimed to assess the incidence of wheezing episodes in infants and children treated with propranolol for infantile hemangiomas. A retrospective case-control study. a tertiary pediatric hospital. All Children followed for infantile hemangioma between 2009 and 2014. Children followed conservatively served as control group and were matched 1:1 for gender and month of birth by random matching to children treated with propranolol. All respiratory episodes (asthma, wheezing, stridor, and pneumonia) and respiratory associated hospitalizations were recorded from hospital records, from the primary care physician visits records and pharmacy prescriptions. The main outcome measure was the incidence of respiratory episodes in the treatment and the control groups. A total of 1828 clinic visits were reviewed for 683 children. In addition, primary care physician visits records were available in 80% of them. Two hundred and sixteen children were treated with propranolol. Incidence of respiratory episodes and recurrent respiratory episodes was similar in the propranolol and control groups (8.3% vs 12%, P = 0.265; 3.7% vs 6.5%, P = 0.274, respectively). Time to first episode was similar in the treatment and control groups (5.03 ± 3.32 vs 4.45 ± 3.21 months, respectively, P = 0.09). Respiratory hospital admission rate was similar in both groups. Propranolol treatment does not exacerbate wheezing episodes in infants and children.

When to stop propranolol for infantile hemangioma

There is no definitive conclusion regarding the optimal timing for terminating propranolol treatment for infantile hemangioma (IH). A total of 149 patients who underwent detailed color Doppler ultrasound examination were included in this study. The characteristics and propranolol treatment of all patients were summarized and analyzed. Patients were divided into two groups according to the lesion regression rate. Among the 149 patients, 38 were assigned to the complete regression group, and 111 were assigned to the partial regression group. The age at which propranolol treatment started, duration of follow-up after treatment discontinuation and rate of adverse events were not significantly different between the two groups. The duration of oral propranolol treatment was shorter in the complete regression group. The age at which propranolol was terminated was younger in the complete regression group, and this group had a lower recurrence rate. Propranolol is safe and effective for the treatment of IHs that require intervention, but it should be stopped at an appropriate time, which is determined primarily by the lesion regression rate after propranolol treatment. Ultrasound is helpful in determining when to stop propranolol for IH.

Propranolol treatment of infantile hemangioma is not associated with psychological problems at 7 years of age

Concern has been raised about the potential long-term effects of propranolol treatment for infantile hemangioma (IH). We sought to assess psychologic (social, emotional, behavioral, and executive) functioning in children treated with propranolol for IH. Twenty-seven patients with IH (6.1-7.6years of age) treated with propranolol for ≥6months during infancy, and without other developmental risk factors, were recruited. Parents completed the Behavior Rating Inventory of Executive Function, Social Emotional Questionnaire, Child Behavior Checklist, and Strengths and Difficulties Questionnaire. For each questionnaire, the number of patients with abnormal scores, based on established cutoff points, was calculated. Only 1 child (3.7%) scored outside the normal range. The Hemangioma Severity Scale did not correlate with psychologic problems in these patients. Longer treatment duration was found to correlate with less attention-deficit hyperactivity disorder (ADHD) characteristics (ρ=-0.476; P=.012) and better executive functioning (ρ=-0.466; P=.014). Exclusion of children born at gestational age <36weeks or small for gestational age, no reference group and relatively small study size. We found no increased risk for psychologic problems at age 7 in IH patients treated with propranolol.

Is Routine Electrocardiography Necessary Before Initiation of Propranolol for Treatment of Infantile Hemangiomas?

In recent years propranolol has become the treatment of choice for infantile hemangiomas (IHs). There is broad variation in the approach to propranolol initiation in clinical practice. This retrospective study explored the effectiveness of routine pre-treatment ECG in screening infants being considered for systemic treatment with propranolol. All patients seen in the outpatient pediatric dermatology clinics at Oregon Health and Sciences University (OHSU) and The Mayo Clinic Rochester (MCR), as well as those seen in multidisciplinary vascular anomalies clinics, who had ECGs obtained prior to planned initiation of propranolol for treatment of IH from 2008 to 2013, were identified. A total of 162 patients were included in the study. We found that 43% (69) of routine ECGs were read as abnormal, leading to 28 formal consultation appointments with pediatric cardiologists. After either formal consultation or informal discussion with cardiology, no patients with initially "abnormal" ECGs were ultimately excluded from treatment with propranolol based on routine ECG findings. Additionally no patients in our cohort experienced an adverse effect during treatment that could have been predicted or prevented by ECG prior to initiation of the propranolol. Our findings suggest that routine ECG may not be necessary or helpful in the vast majority of patients treated with propranolol for IHs.

Propranolol treatment for infantile hemangioma: a case series of sixty-two patients.

Infantile hemangiomas (IH) complicated by ulceration, disfigurement, functional impairment or life-threatening conditions need early, safe and effective treatment. This study explores the impact of propranolol on complicated IH. We report our experience of 62 patients treated with oral propranolol for complicated IH. The effect of propranolol was assessed using a score on a visual analogue scale integrated with echo, magnetic resonance or endoscopic findings. The average age at the beginning of the treatment was seven months [standard deviation (SD)±8.9], with a median of four months (range 1-53 months). The average age at the end of the treatment was 15 months (SD±8.4), with a median of 13 months (range 7-59 months). The mean treatment length was eight months (SD±3.2). Oral propranolol was successful in 95.2% of the patients in reducing the volume, the intensity of color and the elevation of IH. Statistically significant improvement of IH volume was observed in the first two months of therapy (P≤0.001), and between the second month and the end of the treatment (P&lt;0.05). No significant bradycardia or hypotension occurred. Severe hypoglycemia occurred in one patient. Mild adverse effects were observed in seven patients. Our study demonstrates that propranolol administered orally at 2 to 3 mg/kg/day has a rapid therapeutic effect leading to remarkable shortening of the natural course of IH and it is safe in the majority of patients.