OBJECTIVE: Propranolol hydrochloride is a safe and effective medication for treating infantile hemangiomas (IHs), with decreases in IH volume, color, and elevation. METHODS: Forty children between the ages of 9 weeks and 5 years with facial IHs or IHs in sites with the potential for disfigurement were randomly assigned to receive propranolol or placebo oral solution 2 mg/kg per day divided 3 times daily for 6 months. Baseline electrocardiogram, echocardiogram, and laboratory evaluations were performed. Monitoring of heart rate, blood pressure, and blood glucose was performed at each visit. Children younger than 6 months were admitted to the hospital for monitoring after their first dose at weeks 1 and 2. Efficacy was assessed by performing blinded volume measurements at weeks 0, 4, 8, 12, 16, 20, and 24 and blinded investigator scoring of photographs at weeks 0, 12, and 24. RESULTS: IH growth stopped by week 4 in the propranolol group. Significant differences in the percent change in volume were seen between groups, with the largest difference at week 12. Significant decrease in IH redness and elevation occurred in the propranolol group at weeks 12 and 24 (P = .01 and .001, respectively). No significant hypoglycemia, hypotension, or bradycardia occurred. One child discontinued the study because of an upper respiratory tract infection. Other adverse events included bronchiolitis, gastroenteritis, streptococcal infection, cool extremities, dental caries, and sleep disturbance. CONCLUSION: Propranolol hydrochloride administered orally at 2 mg/kg per day reduced the volume, color, and elevation of focal and segmental IH in infants younger than 6 months and children up to 5 years of age.

A Randomized Controlled Trial of Propranolol for Infantile Hemangiomas

Port wine stains (PWS) are the most common vascular malformation of the skin, occurring in 0.3% to 0.5% of the population. Noninvasive laser irradiation with flashlamp-pumped pulsed dye lasers (selective photothermolysis) currently comprises the gold standard treatment of PWS; however, the majority of PWS fail to clear completely after selective photothermolysis. In this review, the clinically used PWS treatment modalities (pulsed dye lasers, alexandrite lasers, neodymium:yttrium-aluminum-garnet lasers, and intense pulsed light) and techniques (combination approaches, multiple passes, and epidermal cooling) are discussed. Retrospective analysis of clinical studies published between 1990 and 2011 was performed to determine therapeutic efficacies for each clinically used modality/technique. In addition, factors that have resulted in the high degree of therapeutic recalcitrance are identified, and emerging experimental treatment strategies are addressed, including the use of photodynamic therapy, immunomodulators, angiogenesis inhibitors, hypobaric pressure, and site-specific pharmaco-laser therapy.

https://www.jaad.org/article/S0190-9622(11)02247-X/pdf

An overview of clinical and experimental treatment modalities for port wine stains

Beta-blockers are a highly promising treatment modality for complicated infantile hemangiomas (IH). However, data on propranolol as first-line treatment, objective outcome measures and impact on hemodynamics in young infants is limited. We retrospectively evaluated a homogenous group of infants with proliferating complicated IH treated with propranolol (2 mg/kg/day). Outcome was assessed by blinded evaluation of clinical photographs by visual analogue scale (VAS), ultrasound examination and ophthalmological review (if appropriate). Tolerance and hemodynamic variables were recorded over time, including a 2-day in-patient observation at the initiation of therapy. Twenty-five infants (median age 3.6 (1.5–9.1) months) were included in the study. The median follow-up-time was 14 (9–20) months and 14 patients completed treatment at a median age of 14.3 (11.4–22.1) months, after a duration of 10.5 (7.5–16) months. In all patients, there was significant fading of colour (with a VAS of −9 (−6 to −9) after 7 months) and significant decrease in size of the IH (with a VAS of −8 (−3 to −10) after 7 months). Median thickness of the lesions assessed by ultrasound at baseline and after 1 month was 14 (7–28) mm and 10 (5–23) mm, respectively (p < 0.01). In children with periocular involvement, astigmatism and amblyopia resolved rapidly within 8 weeks. The overall tolerance of propranolol was good, and no relevant hemodynamic changes were noted. Conclusion: Our report supports the excellent effect and good tolerance of this novel therapy, and we propose the use of propranolol as first-line treatment for IH.

/pdf/efficacy-and-safety-of-propranolol-as-first-line-treatment-2hflfrvhvx.pdf

Efficacy and safety of propranolol as first-line treatment for infantile hemangiomas

Infantile haemangioma is the commonest childhood tumour and approximately 10% requires treatment.(1,2) Recent reports have highlighted the impressive efficacy of propranolol in treating rapidly proliferating haemangioma. The aims of our study were to prospectively assess the efficacy of propranolol as a first line treatment for problematic haemangioma, and develop a treatment regime. 31 consecutive patients with rapidly proliferating infantile haemangioma with functional impairment or cosmetic disfigurement were treated with propranolol as a first line treatment. All patients had cardiovascular pre-treatment work-up and commenced on propranolol at 3 mg/kg/day. A rapid halt in haemangioma proliferation was seen in 100% of patients and significant regression in 87% of patients. This treatment is well tolerated and has little side effects. Since this study, our unit has adopted the policy of using propranolol as a first line treatment for all problematic proliferative infantile haemangiomas.

https://www.jprasurg.com/article/S1748-6815(10)00419-5/pdf

Propranolol as first-line treatment for rapidly proliferating Infantile Haemangiomas

Infantile haemangiomas are the most common benign tumour of infancy. However the majority are self-resolving and only a small minority of cases require treatment, with various different medications being used in the past. Over the last few years, propranolol, a non-selective β-blocker, has become a popular and successful treatment for infantile haemangiomas. However, further research on its safety is needed if it is going to be used more frequently. This article summarises the current literature on propranolol for haemangioma treatment with emphasis on its toxicity and adverse event profile.

https://adc.bmj.com/content/archdischild/96/9/890.full.pdf

Propranolol for infantile haemangiomas: a review

Photodynamic therapy of port wine stains-a report of 238 cases.

Objective To evaluate the short-term efficacy and safety of propranolol in the treatment of infantile hemangiomas. Methods Between October 2008 and May 2009, oral propranolol was applied to 58 infants with heamngiomas at a dose of 1.0 - 1.5 mg per kilogram of body weight per day in Linyi, Shandong and Shanghai. There were 19 males and 39 females 1 to 12 months old with a mean age of 4 months. The primary tumor size was 1.5 cm × 1.0 cm to 18.0 cm × 5.0 cm. Twenty-seven were superficial, nine deep-seated and 22 mixed. The tumors were located in head and neck (n=41), trunk and extremities (n = 12), labium vulvae (n = 2),perianal region (n = 1), perineum (n = 1) and scrotum (n = 1). The patients were hospitalized for 7 to 10 days, continued medication at home and revisited every 2 weeks. The changes of tumor size, texture and color were monitored and recorded at a regular interval. The adverse effects after medication were observed and managed accordingly. The short-term results were evaluated using a 4-point scale system. Results At 24 hours post-medication, all the tumors decreased in density, color and size. The changes became conspicuous within 5 to 7 days. Seven patients had medication for 2 months, 22 for 3 months, 21 for 4 months and 8 for 5 months. The follow-up period was 5 to 9 months. The overall response was scale Ⅰ (poor) in 1 patient (1.7%), scale Ⅱ (moderate) in 12 patients (20.7%), scale Ⅲ (good) in 35 patients (60.4%) and scale Ⅳ (excellent) in 10 patients (17.2%). Statistical analysis showed that the treatment response for deep-seated hemangiomas was significantly better than that for superficial hemangiomas (P 0.05). The main adverse effects were bradycardia (100%), diarrhea (63.8%) and sleep change (30.2%), which resolved after expectant treatment without any significant sequel. No serious adverse effect was observed. Conclusions Oral propranolol treatment at a low dose is a safe and effective regimen for infantile proliferating hemangiomas. And it can be used as the first-line therapeutic modality. The short-term efficacy is excellent while the side effects are minimal.

Key words: 
Hemangioma;  Infant;  Propranolol

[Treatment of infantile hemangiomas with low-dose propranolol: evaluation of short-term efficacy and safety].

The aim of this study was to identify RASA1 mutation in Chinese population with sporadic Sturge–Weber syndrome (SWS). Genomic DNA was obtained from peripheral blood of nine patients with sporadic SWS. The 25 exons, promoter regions (−1,000 bp) as well as intron-exon boundaries of RASA1 were amplified by polymerase chain reaction, and products were sequenced directly. A novel synonymous mutation (c.1229 G > A [p.K420K]) of RASA1 was identified in the present series. It implied that RASA1 may be not a virulence gene, but further study is needed to know RASA1 gene mutation in SWS patients.

Detection of RASA1 mutations in patients with sporadic Sturge–Weber syndrome

Objective
To explore the indications of hemangiomas of different types by observing the clinical efficacy of oral propranolol.


Methods
For this retrospective study from October 2009 to June 2013, a total of 1 080 cases were classified into 5 types according to their clinical characteristics. There were 338 males and 742 females. Their types were telangiectasis (n=58), papular (n=424), plump (n=106), deep (n=176) and mixed (n=306). Propranolol was orally administered at a dose of 1.0 or 1.5 mg/kg daily (1.0 mg/kg for infants aged 2.5 months or under; 1.5 mg/kg for those aged 2.5 months or above). Dynamic observations of hemangioma size, texture or color change and adverse events during treatment were performed. Drug withdrawal was usually made after dosing for 1 year or under when there was a total regression of hemandiomas. The efficacy was evaluated on a 4-level scale.


Results
Rank test results showed no significant differences between 5 types during the changes of lesions (χ2=1.738, P>0.05). Changing of lesions occurred 8.0 (3.7, 16.2) hours after dosing in telangiectasis type, whereas 6.5 (4.1, 14.3) hours in papular type, 7.0 (5.5, 12.7) hours in plump type, 7.5 (3.8, 11.3) hours in deep type and 6.5 (4.2, 13.4) hours in mixed type. After a follow-up of 6 months to 2.5 years, there were 378 grade Ⅳ case (35.00%), 574 grade Ⅲ case (53.15%), 120 grade Ⅱcases (11.11%) and 8 gradeⅠcases (0.74%). And there were significant differences between patients of different types (P<0.05). Patients of deep type had the best grade Ⅳ curative effect rate of 59.09% (104/176), then papular type of 51.25% (162/316) and telangiectasis type of 26.41% (112/424).


Conclusion
As a first-line treatment for hemangioma, propranolol shows excellent efficacies for patients of deep, mixed, plaque and papular types.


Key words: 
Hemangioma; Infant; Propranolol; Treatment outcome; Adverse effects

Clinical analysis for treatment of 1 080 cases of infantile hemangiomas with oral propranolol

Objective To evaluate the short-term results and safety of propranolol for the treatment of infantile parotid hemangiomaMethods Oral propranolol was administered to 17 infants with parotid heamngiom at a dose of 10-15 mg per kilogram of body weight per dayThe patients were revisited once a weekThe changes of the tumor size, texture and colour were monitored and recorded at a regular intervalThe adverse effects after medication were observed and managed accordinglyThe short-term results were evaluated using a 4 scales systemResults Among the 17 patients treated, the follow-up time was 5 to 10 monthsThe overall response was scale I in 0 patient, scale Ⅱ in 0 patients, scale Ⅲ in 5 patients, and scale Ⅳ in 12 patientsNo serious adverse effects were encounteredConclusions Oral propranolol at a lower dose is a safe and effective method for the treatment of infantile parotid heamngiomaThe short-term results were excellent and the side effects minimal

Key words: 
Hemangioma; Parotid gland; Propranolol

Zhong-ping Qin

Papers

Photodynamic therapy of port wine stains-a report of 238 cases.

[Treatment of infantile hemangiomas with low-dose propranolol: evaluation of short-term efficacy and safety].

Detection of RASA1 mutations in patients with sporadic Sturge–Weber syndrome

Clinical analysis for treatment of 1 080 cases of infantile hemangiomas with oral propranolol

Treatment of infantile parotid hemangioma with propranolol