The Impact of Combined Steroid-propranolol Therapy on the Involution of Infantile Hemangioma
American Journal of Pediatrics
Volume 6, Issue 4, December 2020, Pages: 397-407
Received: Sep. 17, 2020; Accepted: Oct. 7, 2020; Published: Oct. 17, 2020
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Authors
Mosaad Abdel Hameed Soliman, Department of Vascular Surgery, Mansoura University, Mansoura, Egypt
Khalid Abdel Aziz Mowafy, Department of Vascular Surgery, Mansoura University, Mansoura, Egypt
Mohamed Adel Abdel Maksoud, Department of Vascular Surgery, Mansoura University, Mansoura, Egypt
Amr Mostafa Elshafey, Department of Vascular Surgery, Mansoura University, Mansoura, Egypt
Nashaat Abdrabo Elsaadany, Department of Vascular Surgery, Mansoura University, Mansoura, Egypt
Reem Mosaad Soliman, Department of Vascular Surgery, Mansoura University, Mansoura, Egypt
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Abstract
Infantile hemangioma (IH) is the most common benign vascular neoplasm of infancy, occurring in 1.0–2.5% of white infants, especially girls. Steroids and propranolol are the most widely used drugs as a primary treatment for IH. Although their mechanism of action is not well understood, their beneficial effect is documented. Our purpose was to compare the clinical efficacy of propranolol alone and propranolol combined with steroids on the outcome of IH. A total of 450 children (median age: 9 months; range: 7 days to 3 years) were included in this randomized controlled study, being treated with combined steroid and propranolol (Group A: 230 children) compared to those treated with propranolol plus placebo (Group B: 220 children). The steroid was given as a loading dose of 2–3 mg/kg/day and then gradually tapered over 6 months, whereas propranolol was given as an incremental dose starting at 0.16 mg/kg/day and reaching a maximum of 2 mg/kg/day maintained for 18 months (duration of therapy). Frequent monitoring of the blood sugar level was mandatory in the first 2 months: electro- and echocardiograms were recorded initially but not repeated. A more rapid involution rate, recognized by color fading and flattening of the lesions, was noted in Group A compared to Group B, with the peak response reached after 10 months of therapy followed by a slower but steady rate of further improvement. No major adverse effects were observed in Group A with regard to hypoglycemia or hypotension. On the other hand, ten cases of vomiting and diarrhea, one case of fungal infection and twelve cases of somnolence and fatigue were observed in Group B. Steroid induction seems to cover the gap at initiation of therapy where propranolol cannot be given as a full dose, especially in neonates. Steroid combination minimizes the adverse effects of propranolol, namely, hypoglycemia, hypotension and bradycardia. Children treated with a combined regimen showed more effective clearing of lesions, were less likely to require surgery for residual lesions and had minimal adverse effects compared to the single-drug group. In both groups there was a faster clearing rate for the head and neck lesions than elsewhere in the body, which can be explained by the higher blood flow to this region, magnifying the level of medication to these lesions and achieving a better response.
Keywords
Infantile Hemangioma, Propranolol, Steroid, Involution
To cite this article
Mosaad Abdel Hameed Soliman, Khalid Abdel Aziz Mowafy, Mohamed Adel Abdel Maksoud, Amr Mostafa Elshafey, Nashaat Abdrabo Elsaadany, Reem Mosaad Soliman, The Impact of Combined Steroid-propranolol Therapy on the Involution of Infantile Hemangioma, American Journal of Pediatrics. Vol. 6, No. 4, 2020, pp. 397-407. doi: 10.11648/j.ajp.20200604.13
Copyright
Copyright © 2020 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
References
[1]
Hoornweg MJ, Smeulders MJ and Van der Horst CM. Prevalence and characteristics of haemangiomas in young children. Ned. Tijdschr. Geneeskd. 2005; 149 (44): 2455-8.
[2]
Dickison P, Christou E and Wargon O. A prospective study of infantile hemangiomas with a focus on incidence and risk factors. Pediatr. Dermatol. 2011; 28 (6): 663-9.
[3]
Hoeger PH, Harper JI, Baselga E, Bonnet D, Boon LM, Ciofi Degli Atti M, et al. Treatment of infantile haemangiomas: Recommendations of a European expert group. Eur. J. Pediatr. 2015; 174 (7): 855-65.
[4]
Luu M and Frieden IJ. Haemangioma: Clinical course, complications and management. Br. J. Dermatol. 2013; 169 (1): 20-30.
[5]
Ranchod TM, Frieden IJ and Fredrick DR. Corticosteroid treatment of periorbital haemangioma of infancy: A review of the evidence. Br. J. Ophthalmol. 2005; 89: 1134-8.
[6]
Chamlin SL, Haggstrom AN, Drolet BA, Baselga E, Frieden IJ, Garzon MC, et al. Multicenter prospective study of ulcerated hemangiomas. J. Pediatr. 2007; 151 (6): 684-9.
[7]
Izadpanah A, Izadpanah A, Kanevsky J, Belzile E and Schwarz K. Propranolol versus corticosteroids in the treatment of infantile hemangioma: A systematic review and meta-analysis. Plast. Reconstr. Surg. K 2013; 131: 601-13.
[8]
Boon LM, MacDonald DM and Mulliken JB. Complications of systemic corticosteroid therapy for problematic hemangioma. Plast. Reconstr. Surg. 2010; 104: 1616-23.
[9]
Drolet BA, Frommelt PC, Chamlin SL, Haggstrom A, Bauman NM, Chiu YE, et al. Initiation and use of propranolol for infantile hemangioma: Report of a consensus conference. Pediatrics 2013; 131 (1): 128-40.
[10]
El Hachem M, Gesualdo F, Diociaiuti A, Berti I, Vercellino N, Boccaletti V, et al. Safety and effectiveness of oral propranolol for infantile hemangiomas started before 5 weeks and after 5 months of age: An Italian multicenter experience. Ital. J. Pediatr. 2017; 43: 40-46.
[11]
Leaute-Labreze C, Hoeger P, Mazereeuw-Hautier J, Guibaud L, Baselga E, Posiunas G, et al. A randomized, controlled trial of oral propranolol in infantile hemangioma. New Engl. J. Med. 2015; 372 (8): 735-46.
[12]
Novoa M, Baselga E, Giraldo L, Shahbaz A, Pardo-Hernandez H and Arevalo-Rodriguez I. Interventions for infantile haemangiomas of the skin: Abridged Cochrane systematic review and GRADE assessments. Br. J. Dermatol. 2019; 180: 527-33.
[13]
Berk DR, Berk EJ and Bruckner AL. A novel method for calculating the volume of hemangiomas. Pediatr. Dermatol. 2011; 28 (4): 478-82.
[14]
Pandey A, Gangopadhyay AN, Gopal SC, Kumar V, Sharma SP, Gupta DK, et al. Twenty years’ experience of steroids in infantile hemangioma: A developing country’s perspective. J. Pediatr. Surg. 2009; 44: 688-94.
[15]
Lèautè-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo J and Taieb A. Propranolol for severe hemangiomas of infancy. New Engl. J. Med. 2008; 358 (24): 2649-51.
[16]
Léauté-Labrèze C, Prey S and Ezzedine K. Infantile haemangioma: Part I. Pathophysiology, epidemiology, clinical features, life cycle and associated structural abnormalities. J. Eur. Acad. Dermatol. Venereol. 2011; 25: 1245-53.
[17]
Bingham MM, Saltzman B, Vo NJ and Perkins JA. Propranolol reduces infantile hemangioma volume and vessel density. Otolaryngol. Head Neck Surg. 2012; 147: 338-44.
[18]
Greenberger S and Bischoff J. Infantile hemangioma: Mechanism (s) of drug action on a vascular tumor. Cold Spring Harb. Perspect. Med. 2011; 1: a006460.
[19]
Egert S, Nguyen N and Schwaiger M. Contribution of alpha adrenergic and beta adrenergic stimulation to ischemia-induced glucose transporter (GLUT) 4 and GLUT1 translocation in the isolated perfused rat heart. Circ. Res. 1999; 84: 1407-15.
[20]
Pope E, Krafchik BR, Macarthur C, et al. Oral versus high-dose pulse corticosteroids for problematic infantile hemangiomas: A randomized, controlled trial. Pediatrics 2007; 119: e12391247.
[21]
Rössler J, Schill T, Bähr A, Truckenmüller W, Noellke P and Niemeyer CM. Propranolol for proliferating infantile haemangioma is superior to corticosteroid therapy: A retrospective, single centre study. J. Eur. Acad. Dermatol. Venereol. 2012; 26: 1173-5.
[22]
Bertrand J, McCuaig C, Dubois J, Hatami A, Ondrejchak S and Powell J. Propranolol versus prednisone in the treatment of infantile hemangiomas: A retrospective comparative study. Pediatr. Dermatol. 2011; 28: 649-54.
[23]
Awadein A and Fakhry MA. Evaluation of intralesional propranolol for periocular capillary hemangioma. Clin. Ophthalmol. 2011; 5: 1135-40.
[24]
Schupp CJ, Kleber J-B, Gunther P and Holland-Cunz S. Propranolol therapy in 55 infants with infantile hemangioma: Dosage, duration, adverse effects, and outcome. Pediatr. Dermatol. 2011; 28: 640-44.
[25]
Martinez Roca C, Rodríguez Ruíz M, Vilaboa Pedrosa C, Perez Morales ME and Sanchez Palacio JL. Oral propranolol in the treatment of infantile hemangioma: A case series of 50 infants. Eur. J. Pediatr. Dermatol. 2014; 24: 86-90, 2014.
[26]
Castaneda S, Garcia E, De la Cruz H, Sanchez-palacio J, Ramirez O and Melendez S. Therapeutic effect of propranolol in Mexican patients with infantile hemangioma. Drugs - Real World Outcomes 2016; 3: 25-31.
[27]
Andersen I, Rechnitzer C and Charabi B. Effectiveness of propranolol for treatment of infantile haemangioma. Dan. Med. J. 2014; 61 (2): A4776.
[28]
Malik MA, Menon P, Rao KL and Samujh R. Effect of propranolol vs. prednisolone vs. propranolol with prednisolone in the management of infantile hemangioma: A randomized controlled study. J. Pediatr. Surg. 2013; 48 (12): 2453-9.
[29]
Ma X, Zhao T, Xiao Y, Yu J, Chen H, Huang Y, et al. Preliminary experience on treatment of infantile hemangioma with low-dose propranolol in China. Eur. J. Pediatr. 2013; 172 (5): 653-9.
[30]
Koay AC, Choo MM, Nathan AM, Omar A and Lim CT. Combined low-dose oral propranolol and oral prednisolone as first-line treatment in periocular infantile hemangiomas. J. Ocul. Pharmacol. Ther. 2011; 27: 309-11.
[31]
Rosbe KW, Suh KY, Meyer AK, Maguiness SM and Frieden IJ. Propranolol in the management of airway infantile hemangiomas. Arch. Otolaryngol. Head Neck Surg. 2010; 136: 65865.
[32]
Hogeling M, Adams S and Wargon O. A randomized controlled trial of propranolol for infantile hemangiomas. Pediatrics 2011; 128: e259-66.
[33]
Holland KE, Frieden IJ, Frommelt PC, Mancini AJ, Wyatt D and Drolet BA. Hypoglycemia in children taking propranolol for the treatment of infantile hemangioma. Arch. Dermatol. 2010; 146: 775-8.
[34]
Morrell DS, Buck S, Zdanski C, Gold S, Stavas J, Blatt J et al. Beta-blockers for infantile hemangiomas: A single institution experience. Clin. Pediatr. (Phila.) 2011; 50: 757-63.
[35]
Fulkerson DH, Agim NG, Al-Shamy G, Metry DW, Izaddoost SA and Jea A. Emergent medical and surgical management of mediastinal infantile hemangioma with symptomatic spinal cord compression: Case report and literature review. Child. Nerv. Syst. 2010; 26: 1799-805.
[36]
Bagazgoitia L, Hernandez-Martin A and Torrelo A. Recurrence of infantile hemangiomas treated with propranolol. Pediatr. Dermatol. 2011; 28 (6): 658-62.
[37]
Tan ST, Itinteang T and Leadbitter P. Low-dose propranolol for infantile hemangioma. J. Plast. Reconstr. Aesthet. Surg. 2011; 64 (3): 292-9.
[38]
Rubin L, Levin M, Ljungman P, Davies E, Avery R, Tomblyn M, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin. Infect. Dis. 2014; 58 (3): e44-100.
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