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 Table of Contents  
Year : 2014  |  Volume : 4  |  Issue : 4  |  Page : 191-193

Low-dose propranolol for the treatment of deep infantile hemangioma with orbital involvement

1 Division of Orbital and Oculoplastic Surgery, Department of Ophthalmology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
2 Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
3 Division of Neonatology, Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan

Date of Web Publication1-Oct-2014

Correspondence Address:
Yueh-Ju Tsai
Division of Orbital and Oculoplastic Surgery, Department of Ophthalmology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, 5 Fu-Hsing Street, Kwei-Shan, Taoyuan 333
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Source of Support: None, Conflict of Interest: None

DOI: 10.1016/j.tjo.2013.12.004

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Capillary hemangiomas are the second most common childhood tumor of the orbit and may cause proptosis and amblyopia if untreated. Oral propranolol has recently been reported to be an effective and safe alternative. Herein, we describe a 2-month-old boy presented with a deep capillary hemangioma of his left eye. It continued to enlarge rapidly and magnetic resonance imaging of the orbit demonstrated hemangioma infiltration over the left superonasal orbit. The patient was treated with oral propranolol starting at 0.5 mg/kg/day with an incremental increase of 0.5 mg/kg/day every 2 days, up to a maximum of 1.5 mg/kg/day. The patient continued 1.5 mg/kg/day of oral propranolol for 5 months as an outpatient without any complications. The volume of the hemangioma has decreased on the following magnetic resonance imaging and the swollen eyelid dramatically improved after treatment. Oral propranolol at 1.5 mg/kg/day may reduce the volume of deep infantile hemangioma in the proliferative stage. Relatively long duration and slow tapering are recommended to prevent relapse.

Keywords: hemangioma, infancy, orbit, propranolol

How to cite this article:
Wu SY, Chen CC, Chiang MC, Tsai YJ. Low-dose propranolol for the treatment of deep infantile hemangioma with orbital involvement. Taiwan J Ophthalmol 2014;4:191-3

How to cite this URL:
Wu SY, Chen CC, Chiang MC, Tsai YJ. Low-dose propranolol for the treatment of deep infantile hemangioma with orbital involvement. Taiwan J Ophthalmol [serial online] 2014 [cited 2020 May 25];4:191-3. Available from: http://www.e-tjo.org/text.asp?2014/4/4/191/204139

  1. Introduction Top

Infantile capillary hemangiomas are the most common benign vascular tumors of the periorbital region and demonstrate a typical clinical course characterized by a rapid proliferative phase during early infancy followed by gradual involution.[1] Corticosteroids are considered first-line therapy for problematic infantile capillary hemangiomas. A dose of 2–3 mg/kg/day of oral steroid frequently reduce the volume of lesions in the first 2 weeks. Rebound in the lesion size with attempted discontinuation or inadequate reduction in the hemangioma results in continuation of the oral steroids with an increasing chance of adrenal suppression, Cushing syndrome, and developmental delays.[2] These complications encourage alternative treatments of which intralesional injection of corticosteroids remain the most popular management for periocular hemangi-omas.[3] However, intralesional steroid injections for capillary hemangiomas with orbital involvement have risks associated with retroseptal or retrobulbar injection.[4] In 2008, Leaute-Labreze et al[5] described the use of oral propranolol for infantile hemangiomas. Here, we report the efficacy of oral propranolol in the treatment of capillary hemangioma with orbital involvement in a 2-month-old infant.

  2. Case report Top

A 2-month-old boy was referred to us for a swollen and droopy left-sided eyelid. A mass had been present since age 10 days and had been increasing in size with resultant occlusion of the left eye and proptosis [Figure 1]A. Given the patient’s age, ptosis of his eye, and the rapid growth of the lesion, he was felt to be at high risk for developing amblyopia. He was admitted on the day of consultation to the newborn intensive care unit and underwent magnetic resonance imaging (MRI) of the orbit, as well as electrocardiogram. The T2-weighted MRI revealed a heterogeneous tumor mass in the superonasal orbital region with a signal intensity higher than that of the extraocular muscles [Figure 2]A and [Figure 2]C. The electrocardiogram was normal. On the 2nd day of hospitalization, oral propranolol was started at 0.5 mg/kg/day divided over three doses. Heart rate and blood pressure were monitored every 4 hours and compared with age-related reference ranges. With good tolerance, the dose was increased incrementally by 0.5 mg/kg/day every 2 days, reaching 1.5 mg/kg/day. The lesion notably improved on oral propranolol. On the 7th day of hospitalization, the boy was discharged home and his parents were informed of the possible adverse effects and to discontinue immediately if poor feeding, cool and clammy skin, breathing difficulty, or lethargy occurred. Follow-up after discharge was conducted monthly, and monitoring of heart rate and blood pressure was performed by the pediatrician at each visit. He was treated with propranolol at a maintenance dose of 1.5 mg/kg/day titrated to his increasing body weight. Five months later, a follow-up MRI showed the lesion to be reduced in size from 6.38 cm3 to 2.92 cm3 by computation of volumetric data on image workstation [Figure 2]B and [Figure 2]D. His eyelid position was nearly symmetric. At that point, his propranolol was tapered by 0.5 mg/kg per month [Table 1]. The propranolol was discontinued at age 9 months. Cycloplegic refraction showed −0.5/−0.50 × 162 OS at that time. There was no evidence of recurrence of the hemangioma 6 months after discontinuing propranolol [Figure 1]. Then the capillary hemangiomas were supposed to be in involution stage.
Table 1: Protocol for the administration and discontinuation of oral propranolol.

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Figure 1: Infant aged 2 months with deep hemangioma. (A) Before oral propranolol treatment. (B) One month after the start of oral propranolol. (C) Five months after the start of oral propranolol—note symmetrical eyelid position. (D) Six months after stopping oral propranolol.

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Figure 2: (A) Infantile hemangioma on the superonasal side of the left orbit. Magnetic resonance imaging of the orbit demonstrated lobulated high signal intensity tumor on the transaxial T2-weighted sequence with central low signal intensity dots and tubules, representing high flow vessels without hemorrhage, phleboliths or venous lakes; scale = 1 cm. (B) The tumor size was markedly reduced after propranolol treatment. (C) The tumor manifested intense contrast enhancement on the T1-weighted image with mass effect on the left eye globe causing downward displacement. (D) Owing to tumor shrinkage after propranolol treatment, the displaced eye returned to a neutral position.

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  3. Discussion Top

Depending on the depth of tumor infiltration, capillary hemangiomas are classified into superficial, deep, and combined hemangiomas. Deep infantile hemangiomas are posterior to the orbital septum and usually lie in the deep tissue of the lid and anterior orbit. The clinical characteristics include ptosis, proptosis, and displacement of the globe, which are strongly associated with occlusion of the visual axis, astigmatism, and strabismus resulting in amblyopia. A group in Texas compared growth characteristics of superficial and deep hemangiomas and noted that deep hemangi-omas are more likely to have a longer proliferative stage,[6] and indicate an increased risk of potential complications and the need to be treated aggressively during the early stage.

There is no standard treatment for capillary hemangiomas. In general, intralesional steroid injections have been given for peri-orbital lesions,[3] but retroseptal or retrobulbar injections for deeper lesions may cause retrobulbar hemorrhage, bilateral arterial embolization,[7] and central retinal artery occlusion,[8] leading some authors to advise against treating deep hemangiomas by direct injection of corticosteroids.[9]

Propranolol is a nonselective β-adrenergic antagonist that has been used for many years in neonates to treat cardiovascular disorders, including certain forms of tachycardia. Due to the dramatic results reported by Leaute-Labreze et al,[5] propranolol is currently advocated in the treatment of infantile hemangioma and fast becoming a first-line treatment.[10] However, there are some case reports of discontinuing propranolol treatment because of side effects (symptomatic hypotension, bradycardia, bronchospasm, and hypoglycemia) and tumor lysis syndrome.[11],[12]

Currently, a standard protocol for treatment of infantile hem-angioma with oral propranolol has not been established. An effective therapeutic dose of 2 mg/kg/day is usually recommended for focal and segmental infantile hemangiomas in infants younger than 6 months.[10] Although Tan et al[13] reported to use the dosage of 1.5 mg/kg/day in 13 patients could achieve good response, none of these 13 patients had lesions in the orbit. Cornish and Reddy[14] reviewed the use of propranolol in the management of periocular capillary hemangiomas. All of 11 patients with orbital extension were treated with oral propranolol at a dose of 2 mg/kg/day. Besides, Chik et al[15] revealed that hemangiomas may recur after relatively shorter courses of treatment and after relatively more rapid tapering of therapy. In our case, low-dose propranolol was administered at 1.5 mg/kg/day for 5 months and tapered off slowly over 2 months until the patient was 9 months old. Six months after discontinuing the medication, there was involution of the heman-gioma without relapse. Mostly, infantile hemangiomas had accelerated growth before the age of 8 weeks[16] and cessation of growth after the age of 9 months.[6] Some reports have been advocated that oral propranolol is continued until the proliferative phase has ended (age 6–12 months) or until stabilization of the involution.[10],[14] Depending on the clinical response, we would suggest keeping the maintaining dose of oral propranolol beyond at least 6 months of age and tapering should be gradual over months.

In conclusion, deep hemangiomas of the orbit should be treated during the early stage; a low dose (1.5 mg/kg/day) of oral pro-pranolol can effectively reduce the size without any complications. However, a larger multicenter randomized clinical control trial is needed to confirm the safety profile and efficacy of propranolol for use in the management of periocular infantile hemangioma in Taiwan.

Conflicts of interest: All contributing authors declare no conflicts of interest.

  References Top

Frieden IJ, Eichenfield LF, Esterly NB, Geronemus R, Mallory SB. Guidelines of care for hemangiomas of infancy. J Am Acad Dermatol 1997;37:631–7.  Back to cited text no. 1
Boon LM, MacDonald DM, Mulliken JB. Complications of systemic corticosteroid therapy for problematic hemangioma. Plast Reconstr Surg 1999;104:1616–23.  Back to cited text no. 2
Wasserman BN, Medow NB, Homa-Palladino M, Hoehn ME. Treatment of periocular capillary hemangiomas. J AAPOS 2004;8:175–81.  Back to cited text no. 3
Neumann D, Isenberg SJ, Rosenbaum AL, Goldberg RA, Jotterand VH. Ultra-sonographically guided injection of corticosteroids for the treatment of retro-septal capillary hemangiomas in infants. J AAPOS 1997;1:34–40.  Back to cited text no. 4
Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Tai’eb A. Propranolol for severe hemangiomas of infancy. New Engl J Med 2008;358:2650–1.  Back to cited text no. 5
Chang LC, Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, et al. Growth characteristics of infantile hemangiomas: implications for management. Pediatrics 2008;122:360–7.  Back to cited text no. 6
Ruttum MS, Abrams GW, Harris GJ, Ellis MK. Bilateral retinal embolization associated with intralesional corticosteroid injection for capillary hemangioma of infancy. J Pediatr Ophthalmol Strabismus 1993;30:4–7.  Back to cited text no. 7
Shorr N, Seiff SR. Central retinal artery occlusion associated with periocular corticosteroid injection for juvenile hemangioma. Ophthalmic Surg 1986;17: 229–31.  Back to cited text no. 8
Kushner BJ. Intralesional corticosteroid injection for infantile adnexal heman-gioma. Am J Ophthalmol 1982;93:496–506.  Back to cited text no. 9
Hogeling M, Adams S, Wargon O. A randomized controlled trial of propranolol for infantile hemangiomas. Pediatrics 2011;128:e259–66.  Back to cited text no. 10
Al Dhaybi R, Superstein R, Milet A, Powell J, Dubois J, McCuaig C, et al. Treatment of periocular infantile hemangioma with propranolol cases series of 18 children. Ophthalmology 2011;118:1184–8.  Back to cited text no. 11
Cavalli R, Buffon RB, Souza MD, Colli AM, Gelmetti C. Tumor lysis syndrome after propranolol therapy in ulcerative infantile hemangioma: rare complication or incidental finding? Dermatology 2012;224:106–9.  Back to cited text no. 12
Tan ST, Itinteang T, Leadbitter P. Low-dose propranolol for infantile heman-gioma. J Plast Reconst Aesth Surg 2011;64:292–9.  Back to cited text no. 13
Cornish KS, Reddy AR. The use of propranolol in the management of periocular capillary haemangioma–a systematic review. Eye 2011;25:1277–83.  Back to cited text no. 14
Chik KK, Luk CK, Chan HB, Tan HY. Use of propranolol in infantile hemangioma among Chinese children. Hong Kong Med J 2010;16:341–6.  Back to cited text no. 15
Tollefson MM, Frieden IJ. Early growth of infantile hemangiomas: what parent’s photographs tell us. Pediatrics 2012;130:e314–20.  Back to cited text no. 16


  [Figure 1], [Figure 2]

  [Table 1]


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2. Case report
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