Large, ulcerated infantile hemangioma of the chest wall complicated by life-threatening hemorrhage: Case report and literature review.

While ulceration is one of the most common infantile hemangioma (IH) complications, severe bleeding is a rare consequence, with a paucity of patients reported. We report a 5-month-old girl with a very large, mixed, partial segmental IH of the upper chest wall who, despite medical intervention, developed severe ulceration and multiple episodes of life-threatening bleeding that ultimately led to hemorrhagic shock. Experience in our patient and a review of six previous reports shows that severe bleeding is a risk when ulceration extends directly into an arterial feeding vessel that is often visible clinically. Other potential predictors for severe bleeding include large to very large IH size with extension of the tumor into underlying structures, segmental or partial segmental patterning, mixed and bulky morphology, and white discoloration as a sign of impending or worsening ulceration.

Factors associated with early relapse of infantile haemangioma in children treated for at least six months with oral propranolol: A case-control study using the 2014-2021 French Ouest DataHub.

BACKGROUND: The factors associated with early relapse of infantile haemangioma (IH) after a first course of treatment with oral propranolol for at least six months (initiated after the marketing authorization had been granted) have not previously been investigated. OBJECTIVES: To identify factors associated with the risk of early relapse in children with IH treated with oral propranolol according to the current prescribing guidelines. METHODS: We performed a multicentre, retrospective, case-control study, using the Ouest Data Hub database. All children treated for at least 6 months with oral propranolol for IH between 31 June 2014 and 31 December 2021, and with a follow-up visit at least three months after treatment discontinuation were included. A case was defined as relapse of IH within three months of treatment discontinuation; each case was matched for age at treatment initiation and for centre, with four (relapse-free) controls. The association between relapse and treatment or IH characteristics was expressed as an odds ratio (OR) from univariate and multivariate conditional logistic regressions. RESULTS: A total of 225 children were included. Of these, 36 (16%) relapsed early. In a multivariate analysis, a deep IH component was a risk factor for early relapse [OR = 8.93; 95%CI: 1.0-78.9, p = 0.05]. A propranolol dosage level of less than 3 mg/kg/day protected against early relapse [OR = 0.11; 95%CI: 0.02-0.7, p = 0.02]. Tapering before propranolol discontinuation was not associated with a lower risk of early relapse. CONCLUSION: The risk factors for late and early relapse are probably different. Investigation of the risk factors for early vs. late IH relapse is now warranted.

Hemangiol in infantile haemangioma: A paediatric post-marketing surveillance drug study.

AIM: Infantile haemangioma (IH) is the most common benign tumour in children. Since 2014, propranolol has become the first-choice therapy and currently Hemangiol is the only approved drug for complicated haemangioma. This post-marketing study reports the use of Hemangiol for IH in paediatric practice. METHOD AND RESULTS: From January 2014 to November 2018, 94 children (median age 4 [0; 21] months; 75% female) treated with Hemangiol for proliferative IH were enrolled in the study. The systematic paediatric cardiology consultation never contraindicated beta-blockers. Two Hemangiol initiation protocols were used: a conventional ambulatory 3-week titration phase protocol (n = 76, 80.9%), and a rapid initiation protocol with a 48-hour dose escalation in conventional hospitalization for severe proliferative or ulcerated IH (n = 18, 19.1%). In both protocols, the haemodynamic tolerance was good. The mean maintenance dose of Hemangiol was 2.7 ± 0.8 mg/kg/day, with a median treatment duration of 7 [1.5; 19] months. Adverse events (AEs) have been found in 25 (26,6%) patients, including 8 (8.5%) patients with serious AEs (uncontrolled bronchial hyperreactivity, n = 5; serious hypoglycaemia, n = 3). Some patients had one or more AEs, a total of 24 nonserious AEs was reported in 19 patients (sleep disturbances, n = 9; respiratory disorders, n = 5; digestive disorders, n = 6). No cardiac adverse event was reported. CONCLUSION: This post-marketing surveillance drug study supports the good tolerance of Hemangiol in children with IH. A rapid initiation protocol is of interest when treatment is urgent. The pretherapeutic paediatric cardiology consultation should not be systematic but only indicated for specific patients. CLINICALTRIALS.GOV: NCT04105517.

Value of Doppler ultrasound scans in deciding whether to treat infantile haemangioma with oral propranolol.

BACKGROUND: Oral propranolol (Pr) must be administered until the end of the proliferation phase of infantile haemangioma (IH). This phase may be difficult to assess, particularly where a deep component is involved. Doppler ultrasound scans (DUS), which identify vascular activity (VA), could assist the clinician in making the correct therapeutic decision (CTD). PATIENTS AND METHODS: All children with IH treated with Pr for at least 3 months and up to the age of 9 months, and who also underwent DUS, were enrolled in this retrospective, single-centre, observational study. The quality of DUS as a binary diagnostic test for IH proliferation was assessed, together with its value in deciding whether to discontinue Pr (at the end of the presumed proliferation phase) or resume this drug (in the case of suspected recurrence). RESULTS: A total of 29 children were enrolled and 45 DUS were performed. Thirty-nine (87%) DUS were of high quality (80% sensitivity, 95% specificity) and made a major, moderate, or minimal contribution to the CTD in respectively 20%, 60% and 7% of cases. DISCUSSION: DUS proved to be a high-value tool. They were essential in some cases of IH, mainly periocular and localised forms, and those involving deep components, in which the question of discontinuing Pr arose (age>1 year) and where clinical examination had not been sufficient to make the CTD. Furthermore, in the vast majority of cases, they provide a helpful examination and complement clinical findings in terms of patient follow-up and reaching a CTD. CONCLUSION: DUS is an effective and complementary tool to clinical investigation.

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 diagnosis intra-central nervous system involvement at an early stage.

Orbital infantile haemangioma: radiological features and treatment - case series and literature review.

AIM: The aim of this study is to report a retrospective case series on orbital infantile haemangiomas (OIH). Radiological features and treatment with oral propranolol (OP) are illustrated along with an updated literature review. METHODS: A retrospective chart review of six children, diagnosed with OIH from November 2015 to October 2016, was carried out. Only children with deep documented orbital involvement were included. All patients underwent magnetic resonance imaging (MRI) under general anaesthesia. OP was administered to the infants according to the Nottingham Children's Hospital guideline. As per the guideline, a preliminary paediatric assessment was performed and a 1 mg/kg test dose was administered, followed by definitive treatment at a dosage of 2 mg/kg in three divided doses. RESULTS: Average age at presentation was within the first 3 weeks of life. T1 hypointensity, T2 hyperintensity, avid enhancement with contrast, and the presence of flow-voids appear a fixed pattern of OIH on MRI. Response to treatment was noticed within 4 weeks in all children, and two of them (33.3%) responded within the first 7 days. In two children (33.3%), the haemangioma became clinically undetectable by the seventh month of treatment, while the other four (66.6%) experienced an almost complete regression of the OIH by the last follow-up. No complications were found. CONCLUSIONS: Our series strengthens the understanding that MRI is the preferred imaging modality in the investigation of OIH, showing vascular features, detailed orbital extension, and possible associated malformations. OP is the treatment of choice for OIH, and our study confirms its safety and effectiveness.

The outcome of combination of low dose oral prednisolone with propranolol for the treatment of infantile haemangioma.

OBJECTIVE: To determine the outcome of combination of low dose oral Prednisolone with oral propranolol for the treatment of infantile hemangioma. METHODS: The patients fulfilling the inclusion criteria were registered through outpatient department. Diagnosis was confirmed clinically and on Color Doppler ultrasonography (CD). All the patients were given oral prednisolone in a dose of 1mg/kg/day and propranolol in a dose of 0.5mg/kg/day twice a day and increased up to 1.5mg/kg/day BID within three days with close monitoring of heart rate, blood pressure and blood glucose as inpatient. Treatment was given for three months then titered down for two weeks before cessation of treatment. The follow-up of patients were performed at 7(th) day, at 1(st) month and finally at 3(rd) month. Treatment compliance was checked during each visit along with outcome parameters i.e. response which was excellent, good, moderate slight improvement and no effect. All the information's were collected. Data was analyzed by using SPSS version 10. RESULTS: Out of total 73 patients, 36.99% (n=27) were one year of age, 32.88% (n=24) were two years of age and 30.13% (n=22) were three years of age, mean± SD: 1.96±0.54 years, 53.42% (n=39) were male and 46.58% (n=34) were females, frequency of response of the treatment was recorded as 56.16% (n=41) had excellent, 23.29% (n=17) had good, 15.07% (n=11) had moderate response, 4.11% (n=3) had slight improvement and 1.37% (n=1) had no effect while frequency of acceptable outcome revealed as acceptable in 79.45% (n=58) while 20.55% (n=15) had not acceptable outcome. CONCLUSION: The frequency of acceptable outcome of combination of low dose oral Prednisolone with oral propranolol for the treatment of infantile hemangioma is higher.

Hematohidrosis: A Rare Case of Bleeding Ears.

Hematohidrosis is a rare disease and should be treated as a diagnosis of exclusion. Its pathogenesis remains unclear, though several theories have been proposed. It is often associated with psychological stress and anxiety, with the most commonly affected areas being the ears, nose, and oral mucosa. There is no specific management modality for hematohidrosis yet, as it is generally self-limiting. Enhanced monitoring and surveillance are required to avoid complications and determine the severity of the condition.

The First Case of Eruptive Pyogenic Granuloma following COVID-19 Vaccination.

Introduction: Pyogenic granuloma presents clinically as a rapidly growing, friable, red papule of skin or mucosa, commonly measuring less than 10 mm with frequent bleeding due to ulceration. Angioproliferative diseases including pyogenic granuloma and cherry angioma have been reported during COVID-19 infection or following COVID-19 vaccination. Case Presentation: Here, we report a 52-year-old female patient who developed diffuse skin eruptions 3 weeks after the second dose of COVID-19 vaccination. Conclusion: As per our knowledge, this is the first case of eruptive PG following COVID-19 vaccination. Oral propranolol and PDL laser therapy were administered after obtaining inconvenient results from electro-cautery, and there was a good response within 6 weeks of starting therapy, defined by the cessation of new lesion formation and a decrease in the size of large lesions.

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

Aims and objectives: 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). Material and methods: 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. Results: 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. Conclusion: 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).

Propranolol for the treatment of infantile hemangiomas: a nine-year monocentric experience from a tertiary hospital.

BACKGROUND: Propranolol is currently considered the first-line therapy for problematic infantile hemangiomas (IH), the most common benign vascular neoplasm of infancy. OBJECTIVES: We present a retrospective observational study aimed at assessing the efficacy of propranolol in 44 IH patients. MATERIALS & METHODS: A nine-year retrospective review considering clinicodemographical and therapy-related variables was performed on medical records of infants treated for IH with oral propranolol. Each lesion was assessed through a numeric severity score based on size and colour both at baseline and after treatment conclusion (p <0.05 was considered statistically significant). RESULTS: Complete remission was achieved in 90.7% cases of IH with a general mean improvement in severity of 94.94%. No severe adverse effects were reported. Preterm patients showed a superior response compared to term infants, even though the difference was not significant (p=0.185). CONCLUSION: Propranolol showed high efficacy in terms of safety profile and cosmetic results. Prematurity and precocious therapy could be linked to a superior response.

Capillary Hemangioma in Joubert Syndrome: A Case Report.

A baby girl who underwent cesarean section delivery and had a complicated postnatal course requiring neonatal intensive care unit (NICU) is followed in the pediatrics clinic for several months. At five months old, the baby girl was referred to an ophthalmology clinic with brain stem and cerebellum malformation consistent with the molar tooth sign (MTS) on magnetic resonance imaging (MRI) of the brain, hypotonia, and developmental delay. She has the classic features of Joubert Syndrome (JS). Other findings not typically associated with the clinical picture of the syndrome were observed in this patient, specifically skin capillary hemangioma of the forehead. Cutaneous capillary hemangioma was an incidental finding in this JS patient and responded favorably to medical treatment with propranolol where a significant reduction in the size of the mass was observed. This incidental finding can be seen as a potential addition to the spectrum of associated findings in JS.

Color Doppler Evaluation of Arterial Resistive Index in Infantile Hemangioma: A Useful Parameter to Monitor the Response to Oral Propranolol?

Infantile hemangioma (IH) is the most common benign vascular tumor in childhood. In more than 85% of all cases, IHs undergo spontaneous involution, but nearly 10-12% of IHs develop complications and require immediate therapy. Oral propranolol is currently the first-line treatment for IHs. Color Doppler ultrasound is the gold standard in the diagnosis of deep IH, and it is used to evaluate the morphological change and the modification of vascularization that occur during its evolution and treatment. To date, only few data in the literature described the changes of intralesional arterial resistive index (RI) during treatment with propranolol; particularly, some authors have shown an increase of intralesional arterial RI in IHs with clinical regression during treatment with propranolol. The objective of this paper is to evaluate the changes of RI of the intralesional arteries of the IHs during the treatment with oral propranolol. We retrospectively analyzed a total of 64 IHs in 60 patients treated with oral propranolol with a good clinical response. Gray-scale ultrasonography and color Doppler imaging were performed before and during the therapy. The intralesional RIs were measured before and during the treatment. For each lesion, we recorded the RI values, and then we calculated the mean RI value for any single lesion. We compared the mean RI value observed at the baseline with the mean RI value of the last detectable sampling at color Doppler. We also compared between them the mean RI values observed during intermediate ultrasound. The RI values were compared in 44 lesions, with at least two significant samplings of RI. In the 44 lesions compared, we did not find statistically significant variations in the mean RI values between the baseline control and the values recorded at the last post-treatment control. The time trend of mean RI values of the intermediate color Doppler analysis performed between the first pre-treatment control and the last measurable control did not show any statistically significant variation in the trend of mean RI values. Contrarily to what has been described by some authors, in our experience, we have not observed an increase of RI in IHs treated with oral propranolol.

To compare intralesional and oral propranolol for treating periorbital and eyelid capillary hemangiomas.

Purpose: A pilot randomized control trial to compare the efficacy and side effects of intralesional and oral propranolol in periorbital and eyelid capillary hemangiomas. Methods: Twenty patients were prospectively randomized to two groups of ten each. Group 1 was initiated on oral propranolol 1 mg/kg/day titrated to final dose of 3 mg/kg/day over 1 week which was continued for 6 months and then tapered over 1 week; Group 2 received 3 doses of direct intralesional propranolol hydrochloride 1 mg/ml; 0.2 ml/cm 4-6 weeks apart. Hemangioma area and corneal astigmatism were measured. Results: Within each group at 6 months there was a significant reduction in area (group 1: 83.48 ± 11.67%,P= 0.0019; group 2: 67.78 ± 21.71%,P= 0.0019) and improvement in astigmatism (pre, post: group 1: 2.98D @ 179.8°, 1.13D @ 179.8°,P= 0.0045; group 2: 1.62D @ 90.16°, 0.75D @ 179.9°,P= 0.0001). There was no difference in area reduction (P = 0.056), change in appearance (P = 0.085), ptosis (P = 0.23) and side effects (lethargy, poor feeding;P= 0.171) between the two groups. Conclusion: Efficacy and side effects with intralesional propranolol are comparable to oral propranolol for periorbital and eyelid lesions.

Central Nervous System Effects of Oral Propranolol for Infantile Hemangioma: A Systematic Review and Meta-Analysis.

Concerns about the effects of propranolol on the central nervous system (CNS) in the infantile hemangioma (IH) population have been raised. We conducted a meta-analysis of the CNS and sleep-related effects of oral propranolol in IH patients. PubMed, Embase, Cochrance, Web of Science, and Clinicaltrials.gov were searched for relevant studies. We included clinical trials that compared oral propranolol with other treatments among IH patients under 6 years old and monitored and reported any adverse events. Study characteristics, types and number of adverse events were abstracted. Cochrane Collaboration Risk of Bias Tool was used to assess risk of bias. Our main outcomes were CNS and sleep-related effects. Random-effects models were used to estimate the pooled risk ratio. We did not observe statistically significant associations between oral propranolol and CNS or sleep-related effects. Oral propranolol appeared to have a safer profile of CNS effects than corticosteroids (RR = 0.27, 95% CI 0.02⁻3.00), but had an increased risk versus non-corticosteroids (for CNS effect, RR = 1.40, 95% CI 0.86⁻2.27; for sleep-related effects, RR = 1.63, 95% CI 0.88⁻3.03). Despite no statistically significant associations, there were suggestive findings of increased CNS effects and sleep-related risk of propranolol versus non-corticosteroids. In practice, CNS and sleep-related events should be monitored more closely among IH patients treated with oral propranolol.

Effect of combined low-dose oral prednisone with beta-adrenergic receptor antagonists for refractory infantile hemangiomas: retrospective cohort study in 76 patients.

BACKGROUND: Beta-adrenergic receptor antagonists have been the first-line treatment for infantile hemangiomas (IHs); however, monotherapy may fail to achieve sufficient efficacy for certain patients, especially for refractory IHs. The aim of this study was to evaluate the efficacy and safety of the combination of prednisone and beta-adrenergic receptor antagonists for refractory IHs. METHODS: We studied 76 patients with refractory IHs. After more than one month of insufficient oral propranolol therapy, forty-four patients received additional treatment of prednisone, while thirty-two patients continued to receive beta-adrenergic receptor antagonists monotherapy. The response to treatment was assessed according to hemangioma score values. RESULTS: The outcomes of patients after combined treatment were significantly better than those with monotherapy of beta-adrenergic receptor antagonists. The age to initiate prednisone was significantly negatively correlated with the improvement in the combination treatment group. The age at initiate treatment showed significant correlation with score variation percentage in both groups. There was no significant difference in the treatment duration observed between the two groups. Multivariable logistic regression analysis for all patients showed prednisone administration was the most important factor to better overall outcomes. CONCLUSIONS: Short-term addition of low-dose oral prednisone is an effective and safe adjunctive treatment for oral propranolol in contributing to refractory IH. Both early administration and long enough duration would be necessary.

Topical Timolol Vs. Oral Propranolol for the Treatment of Superficial Infantile Hemangiomas.

Objective: Infantile hemangiomas (IHs) are the most common vascular tumors of infancy. Oral propranolol has achieved great success in treating IHs since 2008. To minimize the systemic side events caused by oral administration of propranolol, topical timolol started to be applied in the treatment of IHs, especially for superficial lesions. Methods: We treated 724 children with superficial IHs using oral propranolol or topical timolol, and investigated the efficacy and safety of the two treatment patterns. Results: Both oral propranolol and topical timolol achieved a satisfactory therapeutic outcome, with an effective response rate of 97 and 96.4%, respectively. No significant differences in visual analog scale (VAS) improvement between the two groups were observed. Occurrence rate of systemic adverse events for patients treated with oral propranolol (3.9%) was significantly higher than that for patients treated with topical timolol (0%). Clinical response was not associated with gender, duration of treatment, lesion location, lesion size, gestational age, and progesterone use during pregnancy, but closely associated with age at treatment initiation, which indicated that younger age at treatment initiation predicted for a better regression rate. Conclusions: We recommend that topical timolol instead of oral propranolol could be the first-line therapy for superficial IHs because of its good efficacy and improved safety.

Oral propranolol for infantile hemangiomas: a prospective study on the role of 48-hour Holter monitoring in additional safety assessment.

PURPOSE: Oral propranolol has been recently approved for infantile hemangiomas (IHs), but potential side effects stay a challenge. We sought to make an additional assessment on oral propranolol safety for this indication. MATERIALS AND METHODS: Prospective study included 108 infants consecutively treated for IHs at the University Children's Hospital Tirsova, Belgrade from January 2010 to December 2013. Propranolol was administered orally at a daily dose of 0.5 mg/kg and doubled every 48 hours in the absence of side effects until reaching the maximum dose of 2 mg/kg daily. Systolic and diastolic blood pressure and heart rate were measured every 48 hours with clinical observation. Heart rate was monitored by standard electrocardiogram (ECG) and 48-hour Holter ECG. RESULTS: Statistically significant, but asymptomatic decreases in systolic blood pressure and heart rate recorded by Holter ECG were observed during the first doubling of dose and then remained stable. Arrhythmias were not detected. Despite mild sleep disturbance observed in 31% of infants in the hospital milieu, Holter monitoring indicated circadian rhythm maintenance. CONCLUSIONS: Oral propranolol for IHs does not remarkably affect heart rhythm including circadian variations throughout hospital initiation. Therefore, there is no necessity for Holter monitoring in additional safety assessment.

Comparison of the efficacy and safety of topical timolol and oral propranolol for the treatment of Superficial Infantile Haemangiomas

Background: Infantile haemangiomas (IHs) are the most common vascular tumours of infancy. In recenttime oral propranolol has achieved great success in treating IHs. To minimize the systemic side events caused by oral propranolol, topical timolol started to be applied in the treatment of IHs, especially for superficial lesions. Methods: We treated 50 children with superficial IHs using oral propranolol on 25 patients and, topical timolol on 25 patients and investigated the efficacy and safety of the two treatment patterns. Results: Both oral propranolol and topical timolol achieved a satisfactory therapeutic outcome, with an effective response rate of 96 and 95.4%, respectively. No significant differences in visual analogy scale (VAS) improvement between the two groups were observed. Systemic adverse events for patients treated with oral propranolol (3.9%) was significantly higher than that for patients treated with topical timolol. Clinical response was not associated with gender, duration of treatment, lesion location, lesion size, and gestational age but closely associated with age at treatment initiation, which indicated that younger age at treatment initiation predicted for a better regression rate. Conclusion: Topical timolol could be the first-line therapy for superficial IHs because of its good efficacy and improved safety profile.

Propranolol therapy for infantile hemangioma: our experience.

OBJECTIVE: Hemangiomas are the most common benign vascular tumors of infancy. Although most infantile hemangiomas (IHs) have the ability to involute spontaneously after initial proliferation and resolve without consequence, intervention is required in a subset of IHs, which develop complications resulting in ulceration, bleeding, or aesthetic deformity. The primary treatment for this subset of IHs is pharmacological intervention, and propranolol has become the new first-line treatment for complicated hemangiomas. Here, we evaluated the efficacy of propranolol on proliferation IH in a clinical cohort including 578 patients. METHODS: We retrospectively reviewed a total of 578 IH patients who were treated with oral propranolol from January 2010 to December 2012. Responses to the propranolol treatment were graded as: excellent, good, poor, or no response. Based on the response to propranolol treatment (once daily at a dose of 1.0 mg/kg for patients younger than 2 months; twice daily at daily total dose of 2 mg/kg for patients older than 2 months), additional pharmacotherapies or surgery were used for IH patients for satisfactory clinical outcome. RESULTS: Five hundred and sixty (96.9%) of 578 IH patients in our study responded to oral propranolol treatment, and the response rate was significantly different for different ages of patients (P<0.05), with the youngest patients having the highest response rate. The mean time of treatment was 6 months (range, 3-12 months). For example, response rate to propranolol was 98.1% in patients younger than 2 months, compared with 93.3% in patients older than 2 months and younger than 8 months, and 73.7% in patients older than 8 months. One hundred and thirty one patients who exhibited incompletely involuted hemangiomas were further treated with timolol maleate (n=89) or pulsed dye laser (n=42). One hundred and seventeen (89.3%) of 131 patients showed a positive response. There were no instances of life-threatening complications after propranolol. However, minor side effects were observed including 10 (1.73%) cases of sleep disturbance, 7 (1.21%) cases of diarrhea, and 5 (0.86%) cases of bronchospasm. CONCLUSION: IH requires early intervention. During the involution phase, tapering propranolol dosage can be done to minimize side effects before discontinuing treatment. For patients exhibiting telangiectasia and chromatosis after propranolol treatment, administration of a 0.5% solution of timolol maleate or pulse dye laser is an effective therapeutic approach for complete involution.