About MEAJO | Editorial board | Search | Ahead of print | Current Issue | Archives | Instructions to authors | Online submission | Subscribe | Advertise | Contact | Login 
Middle East African Journal of Ophthalmology Middle East African Journal of Ophthalmology
Users Online: 148   Home Print this page Email this page Small font sizeDefault font sizeIncrease font size


 
  Table of Contents 
ORIGINAL ARTICLE
Year : 2011  |  Volume : 18  |  Issue : 4  |  Page : 298-303  

Oral propranolol for the treatment of periorbital infantile hemangioma: A preliminary report from Oman


1 Department of Ophthalmology, Sultan Qaboos University Hospital, Muscat, Oman
2 Department of Dermatology, Sultan Qaboos University Hospital, Muscat, Oman
3 Department of Cardiology, Sultan Qaboos University Hospital, Muscat, Oman
4 Department of Medical Imaging, Sultan Qaboos University Hospital, Muscat, Oman
5 Department of Child Health, Sultan Qaboos University Hospital, Muscat, Oman

Date of Web Publication23-Nov-2011

Correspondence Address:
Abdullah Al-Mujaini
Department of Ophthalmology, Sultan Qaboos University Hospital
Oman
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-9233.90131

Rights and Permissions
   Abstract 

Purpose : To investigate the efficacy and safety of oral propranolol in the management of periorbital infantile hemangioma in four subjects.
Materials and Methods : Consecutive patients who presented with periorbital capillary hemangioma with vision-threatening lesions were prospectively enrolled in this study between January 2009 and October 2010. All subjects underwent treatment with 2 mg/kg/day oral propranolol. All subjects underwent ocular, systemic, and radiologic evaluations before treatment and at periodic intervals after starting therapy. Side effects from therapy were also evaluated.
Results : Four subjects, between 3 months and 19 months of age, with periorbital hemangioma were enrolled in this study. Two subjects had been previously treated with oral corticosteroids with unsatisfactory response. All subjects had severe ptosis, with the potential for deprivation amblyopia. Three subjects had orbital involvement. After hospital admission, oral propranolol was initiated in all subjects under monitoring by a pediatric cardiologist. Subsequent therapy was performed with periodic out-patient monitoring. All subjects had excellent response to treatment, with regression of periorbital and orbital hemangioma. There were no side effects from therapy.
Conclusions : Oral propranolol for periorbital hemangioma was effective in all the four subjects. Oral propranolol may be appropriate for patients who are nonresponsive to intralesional or systemic steroids. In patients with significant orbital involvement and lesions causing vision-threatening complications, oral propranolol can be the primary therapy.

Keywords: Amblyopia, Infants, Orbital Hemangioma, Propranolol


How to cite this article:
Harikrishna B, Ganesh A, Al-Zuahibi S, Al-Jabri S, Al-Waily A, Al-Riyami A, Al-Azri F, Masoud F, Al-Mujaini A. Oral propranolol for the treatment of periorbital infantile hemangioma: A preliminary report from Oman. Middle East Afr J Ophthalmol 2011;18:298-303

How to cite this URL:
Harikrishna B, Ganesh A, Al-Zuahibi S, Al-Jabri S, Al-Waily A, Al-Riyami A, Al-Azri F, Masoud F, Al-Mujaini A. Oral propranolol for the treatment of periorbital infantile hemangioma: A preliminary report from Oman. Middle East Afr J Ophthalmol [serial online] 2011 [cited 2019 Aug 19];18:298-303. Available from: http://www.meajo.org/text.asp?2011/18/4/298/90131


   Introduction Top


Infantile hemangioma (IH) is a common benign orbital tumor that occurs more frequently in females (female to male ratio 3:1). IH occurs more frequently in premature infants and in the products of multiple gestation. Prenatal associations include older maternal age, placenta previa, and pre-eclampsia. [1] The natural history of the tumor includes a proliferative phase that may last the full first year of life, followed by an involution phase that is completed between 5 years and 8 years of age. The maximum growth occurs during the first 4-6 months of life. Generally, between 1 year and 5 years of age, IH remains quiescent or it may begin to involute. [2],[3] Although most hemangiomas are benign and require no intervention, an IH can cause complications due to the location of the lesion and the association with systemic anomalies. Intervention is warranted for large disfiguring lesions or lesions that impair vital functions [Table 1]. [4]
Table 1: Local and systemic complications of hemangioma with associated anomalies


Click here to view


Various options are available for the treatment of IH. [5],[6] Corticosteroids have been used as the first-line therapy since their discovery in the 1960s. Corticosteroid therapy for IH can result in a varied response, with some authors reporting remarkable improvement in 30%-55% of cases and others reporting unchanged status in 40% of cases and continued proliferation in the remaining cases. [7] Therapy is most effective when initiated during the proliferative phase. Oral prednisolone (2-3 mg/kg/day) over a period of 6 months is a commonly used therapy. However, systemic steroids are associated with side effects including gastrointestinal upset, weight gain, growth retardation, hypertension, adrenal suppression and, rarely, immunosuppression. Intralesional corticosteroid injection was introduced to circumvent the adverse systemic side effects. [8] However, intralesional corticosteroids carry the risks of skin hypopigmentation, fat atrophy, lid necrosis, and central retinal artery occlusion. [9]

Propranolol, a nonselective beta-blocker, is a promising treatment modality for IH and has been shown to be effective and safe. [10] In the current study, we prospectively studied the efficacy and safety of oral propranolol in four children with proliferating and complicated infantile hemangiomas.


   Materials and Methods Top


Consecutive patients with periorbital capillary hemangioma, with vision threatening lesions, who presented to our institution between January 2009 to October 2010 were treated with oral propranolol and followed up prospectively. Prior to commencing treatment, a comprehensive ophthalmic examination was performed, which included assessment of ptosis and globe position, measurement of visual acuity with age-appropriate methods (quality of fixation response in infants), orthoptic assessment, anterior segment evaluation with slit lamp, dilated fundus examination, and cycloplegic refraction. Data were collected on the extent of periorbital hemangioma and complications such as ptosis, proptosis, strabismus, astigmatism, and amblyopia. Magnetic resonance imaging (MRI) of the orbits was performed to establish the diagnosis and determine the extent of orbital involvement. All subjects underwent a pediatric evaluation to exclude systemic anomalies, neuroimaging to rule out intracranial abnormalities, and abdominal ultrasonography to assess visceral involvement. All subjects underwent a complete systemic examination to establish cardiovascular and respiratory fitness, chest x-ray, electrocardiography (EKG), and echocardiography (echo).

Oral propranolol at a dose of 1 mg/kg/day in three divided doses was administered to all subjects. Propranolol syrup was prepared from tablets. While initiating therapy, all children were admitted in order to monitor pulse rate and blood pressure every half an hour for the first 4 hours. If the child tolerated the treatment well, therapy was continued on an out-patient basis and the subjects (subjects' caregivers/parents) were requested to return 1 week after discharge. The dose was increased to 2 mg/kg/day in three divided doses if there were no adverse effects from the initial therapy. The subjects were admitted for cardiac monitoring as described above. The subjects were maintained on oral propranolol thereafter and followed up at monthly intervals. Data were collected at each follow-up visit on the response to treatment (extent and color of the lesions) and the level of ptosis, proptosis, and amblyopia. Additionally, screening for cardiovascular and metabolic side effects of propranolol was performed at each visit by a cardiologist.

This study was approved by the Research Ethics Committee of the College of Medicine at Sultan Qaboos University, Oman. Written informed consent was obtained from the parents of all subjects.


   Results Top
Four subjects (three females; one male) between 3 months and 19 months of age met the inclusion criteria. The patient characteristics are summarized in [Table 2].
Table 2: Demographic data and clinical manifestations of study subjects


Click here to view


Two subjects had passed the proliferative phase and were older than 1 year of age when therapy was initiated. These subjects had undergone treatment with high-dose prednisone for several months with a poor response and had rebound growth of the hemangioma after steroid withdrawal. One child developed a cushingoid appearance due to the therapy.

All subjects had vision-threatening lesions due to ptosis (n=4), astigmatism (n=4), proptosis (n=1), and strabismus (n=1). Deep amblyopia was evident in two subjects. MRI brain and orbit showed deep extension of orbital hemangioma in one subject. Two subjects had orbital involvement. There were no features suggestive of the posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities, sternal clefting (PHACES) syndromein any subject. None of the subjects had visceral lesions on abdominal ultrasonography. Systemic workup revealed no contraindications for systemic beta-blocker therapy in any of the subjects.

Subject 1 was a 19-month-old female who presented with an extensive hemangioma involving the right periorbital region, right cheek, tip of the nose, and upper lip. She had severe ptosis, proptosis, esotropia, myopic astigmatism, and deep amblyopia of the right eye [Figure 1]a. Hypertrophy of underlying tissues, ulceration, and severe disfigurement was noted. MRI showed deep intraorbital extension. She was treated with several injections of intralesional triamcinolone at multiple sites and with oral predisolone twice during the first year of life; however, she had ill-sustained regression and rebound growth of the tumor after steroid cessation. We initiated oral propranolol and, at the time of writing, she has continued therapy for over 12 months [Figure 1]b.
Figure 1: Subject 1 - a) Pretreatment; b) after 8 months of treatment with oral propranolol for infantile hemangioma

Click here to view


Subject 2 was a 12-month-old female who presented with extensive hemangioma of the right periorbital region and forehead, left parotid region, ear and lower lip, airways, right upper limb, and upper chest [Figure 2]a. She had moderate to severe ptosis, myopic astigmatism, and amblyopia. Significant tissue distortion by both the superficial and deep components of the hemangioma, ulceration, and severe disfigurement were noted. She had twice received a course of pulse steroids, with transient improvement of the hemangioma. Oral propranolol was initiated and, at the time of writing, she has continued therapy for 10 months [Figure 2]b.
Figure 2: Subject 2 - a) Pretreatment; b) after 9 months of treatment with oral propranolol for infantile hemangioma

Click here to view


Subject 3 was a four-month-old male, ex-preterm, born at 35 weeks of gestation, who presented with a left upper lid subcutaneous hemangioma, causing complete ptosis and astigmatism [Figure 3]a. He had another small lesion in the chest on the same side. Propranolol was started shortly after presentation. A visible shrinkage of the hemangioma was noted within 24 hours of commencement of therapy. He has continued propranolol for 5 months at the time of writing [Figure 3]b.
Figure 3: Subject 3 - a) Pretreatment; b) after 3 months of treatment with oral propranolol for infantile hemangioma

Click here to view


Subject 4 was a 3-month-old girl who presented with a right upper lid hemangioma that caused complete ptosis, exotropia, and astigmatism of the right eye, with exfoliation of the periorbital skin [Figure 4]a. She had extraconal extension of hemangioma into the right orbit. Oral propranolol therapy was commenced and an accelerated involution of the hemangioma was observed. She has continued propranolol for 3 months at the time of writing [Figure 4]b.
Figure 4: Subject 4 - a) Pretreatment; b) after 3 months of treatment with oral propranolol for infantile hemangioma

Click here to view


All subjects remained systemically stable at the initiation of treatment and during follow-up. Although all subjects showed visible signs of tumor regression, an accelerated involution of the hemangioma was observed in the subjects who were below 6 months of age at the time of initiation of therapy. Notable regression in the deeper orbital components was observed on examination and imaging in all subjects [Figure 5]. No adverse effects were noted. All subjects underwent occlusion therapy for amblyopia and correction of refractive error over the same period. All subjects had remarkable improvement in vision.
Figure 5: Magnetic resonance imaging of the orbit and brain of subject 2 - coronal T1-W fat-suppressed postcontrast enhancement images; a) Pretreatment; b) after 9 months of treatment with oral propranolol for infantile hemangioma (note the generalized reduction in the extent of the lesion)

Click here to view


Two subjects required concomitant therapy with intralesional steroids for poorly regressing lip lesions. All subjects were maintained on propranolol at a dose of 2 mg/kg/day at the time of writing (average duration 6 months). We plan to gradually stop therapy over 3 months, when no more regression is observable (both clinically and by imaging).


   Discussion Top


Although IH is usually innocuous, with spontaneous involution occurring in the first five years of life, 10%-20% of infants with IH require intervention during the proliferative phase to prevent or reduce complications, which include disfigurement, interference with breathing, life-threatening pressure over the internal organs, and local complications such as hemorrhage, ulceration, and necrosis. [11] Periorbital lesions pose a risk to vision through occlusion of the pupil, compression of the globe, and expansion in the retrobulbar space, leading to amblyopia, strabismus, astigmatism, and optic nerve atrophy. [12],[13]

Direct intervention such as local corticosteroid injection, laser therapy, and surgical excision are not suitable for IH with deep orbital components due to poor access and risk of injury to the optic nerve and extraocular muscles. [5] Conventional pharmacological treatment with systemic corticosteroids may be efficacious within 2-3 weeks of initiating treatment, but can cause significant systemic effects such as cushingoid facies, stunted growth, gastrointestinal symptoms, hypertension, and hypertrophic obstructive cardiomyopathy. [14] In the treatment of hemangiomas steroids likely have multiple modes of action, including an anti-anabolic effect, a vasoconstrictive effect, possible pharmacologic inhibition of angiogenesis, and inhibition of fibrinolysis activators in the vessel walls; all of these can increase the effect of propranolo. [15]

Other agents are less predictable and have more serious side effects. Use of interferon-a[16] is associated with the risk of hematologic and hepatic toxicity, hypothyroidism, depression, and neurotoxicity (spastic diplegia). [17] The use of vincristine [18] may lead to peripheral neuropathy, hematologic toxicity, and the syndrome of inappropriate secretion of anti-diuretic hormone (SIADH). Propranolol is a nonselective beta-blocker that has been used for several decades in cardiac, neurologic, endocrine, and other disorders. It is emerging as a promising treatment for IH. [10] The effect of propranolol in IH was serendipitously discovered when two infants with hemangioma were treated with propranolol for cardiac complications while on corticosteroid treatment. Twenty-four hours after propranolol was initiated, the hemangioma appeared smaller and lighter in both children and was completely flat in one child by the age of 14 months. [10] No rebound growth was noted on cessation of treatment in both children. [10] After this initial report, [10] many authors have reported the efficacy of propranolol for the treatment of IH. [5],[19],[20],[21],[22],[23],[24] Propranolol has been used successfully in two cases of subglottic hemangioma associated with cutaneous hemangiomas that were resistant to standard treatments. [25] Deep-seated lesions also respond to propranolol therapy. Fay et al.[5] and Taban et al. [26] reported the efficacy of treatment in patients with extensive orbital disease.

All four subjects in the current study showed a quick and intense response to therapy. One child showed a dramatic response within 24 hours. The lesion softened, changed color, and decreased in size, with improvement in ptosis. The youngest child was 3 months and the oldest 19 months at the time of initiating propranolol therapy. It is of interest to note that two of the four subjects had begun the proliferative phase for IH. These subjects had undergone unsuccessful steroid therapy previously. Three subjects had extensive periorbital lesions with orbital extension. After initiation of propranolol, there was a reduction in the size and extent of the lesions, and imaging studies confirmed the regression of the deeper lesions in all subjects.

The proposed mechanism of action of propranolol on IH includes vasoconstriction, apoptosis of capillary endothelial cells, [27] and decreased production of vascular endothelial growth factor (VEGF) and fibroblastic growth factor (FGF). The latter is believed to occur through the down regulation of the RAF-mitogen-activated protein kinase pathway. [28]

Propranolol has been prescribed for decades in infants and is reported to be safe and well tolerated. [29] However, in rare instances, the drug can cause deleterious adverse effects such as hypoglycemia, bradycardia, hypotension, and bronchospasm. [30] High-output cardiac failure can occur in infants with very large hemangiomas, and PHACES syndrome. Ophthalmologists who are not familiar with use of propranolol need to be aware of these risks. Although some authors advise outpatient administration of therapy, [19] in order to avoid the few complications likely to occur with systemic propranolol, a strict pretherapy protocol is advisable. [31] Our patients underwent comprehensive pediatric pretreatment examination and were admitted for 48 hours. Topical beta-blockers provide a safe and effective alternative to systemic therapy and are being investigated for use in the treatment of IH. [32]

Response to treatment can usually be determined by clinical examination (supplemented with photographs). However some lesions require imaging studies for accurate assessment. The earlier the onset of therapy during the proliferative phase, the more dramatic the response. Treatment is recommended until 1 year of age; the lesions rarely proliferate after this age. Gradual withdrawal through a tapering dose is recommended to avoid hyperadrenergic effects. However, we noted that even later initiation of therapy can have a beneficial effect. In such cases, therapy may be continued until no further regression is noted. At the time of writing, all subjects were still undergoing treatment and responding well.

In conclusion, we recommend the use of propranolol in all vision-threatening periorbital hemangiomas, provided there are no contraindications to its use. Although propranolol was safely used in the four subjects in this study, it is debatable if propranolol should be the first line of therapy for focal periorbital lesions, which are usually amenable to more standard protocols. Further studies with larger sample sizes are recommended to fully evaluate the safety, efficacy, and limitations of propranolol in the management of periocular IH.


   Acknowledgment Top


We acknowledge with gratitude the contributions of all staff involved with patient care. We thank the families for their willing participation in the study.

 
   References Top

1.Hemangioma Investigator Group; Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, et al. Prospective study of infantile hemangiomas: Demographic, prenatal, and perinatal characteristics. J Pediatr 2007;150:291-4.  Back to cited text no. 1
    
2.Haik BG, Karcioglu ZA, Gordon RA, Pechous BP. Capillary hemangioma (infantile periocular hemangioma). Surv Ophthalmol 1994;38:399-426.  Back to cited text no. 2
    
3.Waner M, Suen JY. The natural history of hemangiomas. In: Warner M, Suen JY, editors. Hemangiomas and vascular malformations of the head and neck. New York: Wiley-Leiss; 1999. p. 13-46.  Back to cited text no. 3
    
4.Shields JA, Shields CL. Eyelid, conjunctival, and orbital tumors: An atlas and textbook. 2 nd ed. Philadelphia, PA: Lippincott, Williams and Wilkins; 2008. p. 132-41.  Back to cited text no. 4
    
5.Fay A, Nguyen J, Jakobiec FA, Meyer-Junghaenel L, Waner M. Propranolol for isolated orbital hemangioma. Arch Ophthalmol 2010;128:256-8.   Back to cited text no. 5
    
6.Maguiness SM, Frieden IJ. Current management of infantile hemangiomas. Semin Cutan Med Surg 2010;29:106-14.  Back to cited text no. 6
    
7.Sadan N, Wolach B. Treatment of hemangiomas of infants with high doses of prednisone. J Pediatr 1996;128:141-6.  Back to cited text no. 7
    
8.Kushner BJ. Intralesional corticosteroid injection for infantile adnexal hemangioma. Am J Ophthalmol 1982;93:496-506.  Back to cited text no. 8
    
9.Ranchod TM, Frieden IJ, Fredrick DR. Corticosteroid treatment of periorbital haemangioma of infancy: A review of the evidence. Br J Ophthalmol 2005;89:1134-8.  Back to cited text no. 9
    
10.Léauté-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taïeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008;358:2649-51.  Back to cited text no. 10
    
11.Frieden IJ, Haggstrom A, Drolet BA, Mancini AJ, Friedlander SF, Boon L, et al. Infantile hemangiomas: Current knowledge, future directions: Proceedings of a research workshop on infantile hemangiomas. Pediatr Dermatol 2005;22:383-406.   Back to cited text no. 11
    
12.Thomson HG, Ward CM, Crawford JS, Stigmar G. Hemangiomas of the eyelid: visual complications and prophylactic concepts. Plast Reconstr Surg 1979;63:641-7.   Back to cited text no. 12
    
13.Goldberg NS, Rosanova MA. Periorbital hemangiomas. Dermatol Clin 1979;10:653-61.  Back to cited text no. 13
    
14.Rössler J, Wehl G, Niemeyer CM. Evaluating systemic prednisone therapy for proliferating haemangioma in infancy. Eur J Pediatr 2008;167:813-5.  Back to cited text no. 14
    
15.Bang GM, Setabutr P. Periocular capillary hemangioma: Indications and options for treatment. Middle East Afr J Ophthalmol 2010;17:121-8.  Back to cited text no. 15
[PUBMED]  Medknow Journal  
16.Ezekowitz RA, Mulliken JB, Folkman J. Interferon alfa-2a therapy for life-threatening hemangiomas of infancy. N Engl J Med 1992;326:1456-63.  Back to cited text no. 16
    
17.Dubois J, Hershon L, Carmant L, Bélanger S, Leclerc JM, David M. Toxicity profile of interferon alfa-2b in children: A prospective evaluation. J Pediatr 1999;135:782-5.   Back to cited text no. 17
    
18.Enjolras O, Breviere GM, Roger G, Tovi M, Pellegrino B, Varotti E, et al. Vincristine treatment for function- and life-threatening infantile hemangioma. Arch Pediatr 2004;11:99-107.  Back to cited text no. 18
    
19.Haider KM, Plager DA, Neely DE, Eikenberry J, Haggstrom A. Outpatient treatment of periocular infantile hemangiomas with oral propranolol. J AAPOS 2010;14:251-6.  Back to cited text no. 19
    
20.Kathleen L. Oral beta blocker reduces periocular infantile hemangiomas in most cases. J AAPOS 2010;14:251-6.  Back to cited text no. 20
    
21.Buckmiller LM, Munson PD, Dyamenahalli U, Dai Y, Richter GT. Propranolol for infantile hemangiomas: Early experience at a tertiary vascular anomalies center. Laryngoscope 2010;120:676-81.  Back to cited text no. 21
    
22.Holmes WJ, Mishra A, Gorst C, Liew SH. Propranolol as first-line treatment for infantile hemangiomas: Plast Reconstr Surg 2010;125:420-1.  Back to cited text no. 22
    
23.Denoyelle F, Leboulanger N, Enjolras O, Harris R, Roger G, Garabedian EN. Role of propranolol in the therapeutic strategy of infantile laryngotracheal hemangioma. Int J Pediatr Otorhinolaryngol 2009;73:1168-73.  Back to cited text no. 23
    
24.Sans V, de la Roque ED, Berge J, Grenier N, Boralevi F, Mazereeuw-Hautier J, et al. Propranolol for severe infantile hemangiomas: Follow-up report. Pediatrics 2009;124:423-31.   Back to cited text no. 24
    
25.Theletsane T, Redfern A, Raynham O, Harris T, Prose NS, Khumalo NP. Life-threatening infantile haemangioma: A dramatic response to propranolol. J Eur Acad Dermatol Venereol 2009;23:1465-6.  Back to cited text no. 25
    
26.Taban M, Goldberg RA. Propranolol for orbital hemangioma. Ophthalmology 2010;117:195-5 e4.  Back to cited text no. 26
    
27.Sommers Smith SK, Smith DM. Beta blockade induces apoptosis in cultured capillary endothelial cells. In vitro Cell Dev Biol Anim 2002;38:298-304.   Back to cited text no. 27
    
28.D'Angelo G, Lee H, Weiner RI. cAMP-dependent protein kinase inhibits the mitogenic action of vascular endothelial growth factor and fibroblast growth factor in capillary endothelial cells by blocking Raf activation. J Cell Biochem 1997;67:353-66.  Back to cited text no. 28
    
29.Gillette P, Garson A Jr, Eterovic E, Neches W, Mullins C, McNamara DG. Oral propranolol treatment in infants and children. J Pediatr 1978;92:141-4.  Back to cited text no. 29
    
30.Siegfried EC, Keenan WJ, Al-Jureidini S. More on propranolol for hemangiomas of infancy. N Engl J Med 2008;359:2846.  Back to cited text no. 30
    
31.Procedings of the 2 nd International Symposium on Hemangiomas and Vascular Malformations. Little Rock, Arkansas; Oct 2009.  Back to cited text no. 31
    
32.Guo S, Ni N. Topical treatment for capillary hemangioma of the eyelid using beta-blocker solution. Arch Ophthalmol 2010;128:255-6.  Back to cited text no. 32
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]


This article has been cited by
1 Propranolol represses infantile hemangioma cell growth through the 2-adrenergic receptor in a HIF-1a-dependent manner
Peng Li,Zhengtuan Guo,Ya Gao,Weikang Pan
Oncology Reports. 2015;
[Pubmed] | [DOI]
2 The effectiveness of propranolol in treating infantile haemangiomas: a meta-analysis including 35 studies
Yin Lou,Wen-jia Peng,Yi Cao,Dong-sheng Cao,Juan Xie,Hong-hong Li
British Journal of Clinical Pharmacology. 2014; 78(1): 44
[Pubmed] | [DOI]
3 Efficacy of topical brimonidine-timolol for haemangioma of infancy and perils of off-label prescribing
Chu, M.B. and Searcy, G. and Siegfried, E.
BMJ Case Reports. 2013;
[Pubmed]



 

Top
  
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Acknowledgment
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed4346    
    Printed137    
    Emailed2    
    PDF Downloaded201    
    Comments [Add]    
    Cited by others 3    

Recommend this journal