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Current Pediatric Reviews


ISSN (Print): 1573-3963
ISSN (Online): 1875-6336

Review Article

Infantile Hemangioma: An Updated Review

Author(s): Alexander K.C. Leung*, Joseph M. Lam, Kin F. Leong and Kam L. Hon

Volume 17, Issue 1, 2021

Published on: 08 May, 2020

Page: [55 - 69] Pages: 15

DOI: 10.2174/1573396316666200508100038

Price: $65


Background: Infantile hemangiomas are the most common vascular tumors of infancy, affecting up to 12% of infants by the first year of life.

Objective: To familiarize physicians with the natural history, clinical manifestations, diagnosis, and management of infantile hemangiomas.

Methods: A Pubmed search was conducted in November 2019 in Clinical Queries using the key term "infantile hemangioma". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews published within the past 20 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article.

Results: The majority of infantile hemangiomas are not present at birth. They often appear in the first few weeks of life as areas of pallor, followed by telangiectatic or faint red patches. Then, they grow rapidly in the first 3 to 6 months of life. Superficial lesions are bright red, protuberant, bosselated, or with a smooth surface, and sharply demarcated. Deep lesions are bluish and dome-shaped. Infantile hemangiomas continue to grow until 9 to 12 months of age, at which time the growth rate slows down to parallel the growth of the child. Involution typically begins by the time the child is a year old. Approximately 50% of infantile hemangiomas will show complete involution by the time a child reaches age 5; 70% will have disappeared by age 7; and 95% will have regressed by 10 to 12 years of age. The majority of infantile hemangiomas require no treatment. Treatment options include oral propranolol, topical timolol, and oral corticosteroids. Indications for active intervention include hemorrhage unresponsive to treatment, impending ulceration in areas where serious complications might ensue, interference with vital structures, life- or function-threatening complications, and significant disfigurement.

Conclusion: Treatment should be individualized, depending upon the size, rate of growth, morphology, number, and location of the lesion (s), existing or potential complications, benefits and adverse events associated with the treatment, age of the patient, level of parental concern, and the physician's comfort level with the various treatment options. Currently, oral propranolol is the treatment of choice for high-risk and complicated infantile hemangiomas. Topical timolol may be considered for superficial infantile hemangiomas that need to be treated and for complicated infantile hemangiomas in patients at risk for severe adverse events from oral administration of propranolol.

Keywords: Involution, propranolol, corticosteroids, laser, surgical resection, timolol.

Graphical Abstract
Bota M, Popa G, Blag C, Tataru A. Infantile hemangioma: A brief review. Clujul Med 2015; 88(1): 23-7.
[PMID: 26528043]
Hon KL, Shen PC, Li JJ, Chow CM, Luk DC. Pediatric vascular anomalies: an overview of management. Clin Med Insights: Dermatology 2014; 7: 1-7.
Chen CC, Chen CK. Capillary hemangioma of the external auditory canal. Ear Nose Throat J 2020; 99(2): NP21-2.
[] [PMID: 32162552]
Mendiratta V, Jabeen M. Infantile hemangioma: an update. Indian J Dermatol Venereol Leprol 2010; 76(5): 469-75.
[] [PMID: 20826985]
Leung AK. Capillary hemangiomaThe Encyclopedia of Molecular Mechanisms of Disease. Berlin: Springer-Verlag 2009; pp. 790-1.
Leung AK, Barankin B, Hon KL. Infantile hemangioma. Pediatr Neonatal Nurs Open J 2014; 1(1): 1-6.
Lo K, Mihm M, Fay A. Current theories on the pathogenesis of infantile hemangioma. Semin Ophthalmol 2009; 24(3): 172-7.
[] [PMID: 19437354]
Roberts N. Infantile haemangioma: harmless ‘strawberry’ or life-threatening vascular anomaly? Clin Med (Lond) 2009; 9(4): 385-9.
[] [PMID: 19728520]
Leung AK. Infantile hemangiomaCommon Problems in Ambulatory Pediatrics: Specific Clinical Problems. New York: Nova Science Publishers, Inc. 2011; Vol. 2: pp. 137-41.
Soliman YS, Khachemoune A. Infantile hemangiomas: our current understanding and treatment options. Dermatol Online J 2018; 24(9)
Kanada KN, Merin MR, Munden A, Friedlander SF. A prospective study of cutaneous findings in newborns in the United States: correlation with race, ethnicity, and gestational status using updated classification and nomenclature. J Pediatr 2012; 161(2): 240-5.
[] [PMID: 22497908]
Stier MF, Glick SA, Hirsch RJ. Laser treatment of pediatric vascular lesions: Port wine stains and hemangiomas. J Am Acad Dermatol 2008; 58(2): 261-85.
[] [PMID: 18068263]
Enjolras O, Gelbert F. Superficial hemangiomas: associations and management. Pediatr Dermatol 1997; 14(3): 173-9.
[] [PMID: 9192407]
Anderson KR, Schoch JJ, Lohse CM, Hand JL, Davis DM, Tollefson MM. Increasing incidence of infantile hemangiomas (IH) over the past 35 years: Correlation with decreasing gestational age at birth and birth weight. J Am Acad Dermatol 2016; 74(1): 120-6.
[] [PMID: 26494585]
Chen XD, Ma G, Chen H, Ye XX, Jin YB, Lin XX. Maternal and perinatal risk factors for infantile hemangioma: a case-control study. Pediatr Dermatol 2013; 30(4): 457-61.
[] [PMID: 23278441]
Darrow DH, Greene AK, Mancini AJ, Nopper AJ. section on dermatology, section on otolaryngology–head and neck surgery, and section on plastic surgery. Diagnosis and management of infantile hemangioma. Pediatrics 2015; 136(4): e1060-104.
[] [PMID: 26416931]
Darrow DH, Greene AK, Mancini AJ, Nopper AJ. Section on dermatology, section on otolaryngology-head & neck surgery, and section on plastic surgery. Diagnosis and management of infantile hemangioma: Executive summary. Pediatrics 2015; 136(4): 786-91.
[] [PMID: 26416928]
Harter N, Mancini AJ. Diagnosis and management of infantile hemangiomas in the neonate. Pediatr Clin North Am 2019; 66(2): 437-59.
[] [PMID: 30819347]
Itinteang T, Withers AH, Davis PF, Tan ST. Biology of infantile hemangioma. Front Surg 2014; 1: 38.
[] [PMID: 25593962]
Kawaguchi A, Kunimoto K, Inaba Y, et al. Distribution analysis of infantile hemangioma or capillary malformation on the head and face in Japanese patients. J Dermatol 2019; 46(10): 849-52.
[] [PMID: 31418467]
Liang MG, Frieden IJ. Infantile and congenital hemangiomas. Semin Pediatr Surg 2014; 23(4): 162-7.
[] [PMID: 25241092]
Metry DW. Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications.UpToDate Waltham.
Blei F, Walter J, Orlow SJ, Marchuk DA. Familial segregation of hemangiomas and vascular malformations as an autosomal dominant trait. Arch Dermatol 1998; 134(6): 718-22.
[] [PMID: 9645641]
Castrén E, Salminen P, Vikkula M, Pitkäranta A, Klockars T. Inheritance patterns of infantile hemangioma. Pediatrics 2016; 138(5)e20161623
[] [PMID: 27940781]
Couto RA, Hassanein AH, Maclellan RA, Greene AK. Infantile hemangioma in four siblings. Pediatr Dermatol 2013; 30(3): e14-5.
[] [PMID: 22784313]
Grimmer JF, Williams MS, Pimentel R, et al. Familial clustering of hemangiomas. Arch Otolaryngol Head Neck Surg 2011; 137(8): 757-60.
[] [PMID: 21844408]
Satterfield KR, Chambers CB. Current treatment and management of infantile hemangiomas. Surv Ophthalmol 2019; 64(5): 608-18.
[] [PMID: 30772366]
Walter JW, Blei F, Anderson JL, Orlow SJ, Speer MC, Marchuk DA. Genetic mapping of a novel familial form of infantile hemangioma. Am J Med Genet 1999; 82(1): 77-83.
[<77:AID-AJMG15>3.0.CO;2-A] [PMID: 9916848]
de Jong S, Itinteang T, Withers AH, Davis PF, Tan ST. Does hypoxia play a role in infantile hemangioma? Arch Dermatol Res 2016; 308(4): 219-27.
[] [PMID: 26940670]
Hunjan MK, Schoch JJ, Anderson KR, et al. Prenatal risk factors for infantile hemangioma development. J Invest Dermatol 2017; 137(4): 954-7.
[] [PMID: 27940221]
Huoh KC, Rosbe KW. Infantile hemangiomas of the head and neck. Pediatr Clin North Am 2013; 60(4): 937-49.
[] [PMID: 23905829]
Ames JA, Sykes JM. Current trends in medical management of infantile hemangioma. Curr Opin Otolaryngol Head Neck Surg 2015; 23(4): 286-91.
[] [PMID: 26101875]
Hochman M. Infantile hemangiomas: current management. Facial Plast Surg Clin North Am 2014; 22(4): 509-21.
[] [PMID: 25444725]
Tang YJ, Zhang ZZ, Chen SQ, et al. Effect of topical propranolol gel on plasma renin, angiotensin II and vascular endothelial growth factor in superficial infantile hemangiomas. J Huazhong Univ Sci Technolog Med Sci 2015; 35(5): 759-62.
[] [PMID: 26489635]
Tanyildiz HG, Unal EC, Gokce H, et al. Serum basic fibroblastic growth factor levels in children with infantile hemangioma. Indian J Pediatr 2016; 83(9): 937-40.
[] [PMID: 26816137]
Munabi NC, Tan QK, Garzon MC, Behr GG, Shawber CJ, Wu JK. Growth hormone induces recurrence of infantile hemangiomas after apparent involution: Evidence of growth hormone receptors in infantile hemangioma. Pediatr Dermatol 2015; 32(4): 539-43.
[] [PMID: 25690955]
Adams DM, Ricci KW. Infantile hemangiomas in the head and neck region. Otolaryngol Clin North Am 2018; 51(1): 77-87.
[] [PMID: 29217069]
Bilodi AK, Singh S, Ebenezer DA, Suman PMR. Capillary haemangioma of the right elbow and forearm in new born child. J Clin Diagn Res 2013; 7(12): 2941-2.
[] [PMID: 24551681]
Chisti M, Banka N, Alfadley A. Pallor sign: an indicator of hemangioma in evolution. J Cutan Med Surg 2012; 16(6): 451-2.
[] [PMID: 23149206]
Leung AK, Kao CP. Pediatric vascular lesions. Consultant Pediatrician 2004; 3: 278-83.
Beck DO, Gosain AK. The presentation and management of hemangiomas. Plast Reconstr Surg 2009; 123(6): 181e-91e.
[] [PMID: 19483535]
Püttgen KB. Diagnosis and management of infantile hemangiomas. Pediatr Clin North Am 2014; 61(2): 383-402.
[] [PMID: 24636652]
Holland KE, Drolet BA. Approach to the patient with an infantile hemangioma. Dermatol Clin 2013; 31(2): 289-301.
[] [PMID: 23557656]
O’Brien KF, Shah SD, Pope E, et al. Late growth of infantile hemangiomas in children >3 years of age: A retrospective study. J Am Acad Dermatol 2019; 80(2): 493-9.
[] [PMID: 30293898]
Grzesik P, Wu JK. Current perspectives on the optimal management of infantile hemangioma. Pediatric Health Med Ther 2017; 8: 107-16.
[] [PMID: 29388636]
Frieden IJ, Rogers M, Garzon MC. Conditions masquerading as infantile haemangioma: Part 1. Australas J Dermatol 2009; 50(2): 77-97.
[] [PMID: 19397559]
Hon KL, Burd A, Chu WC, Lee V, Li CK. Propranolol for infantile hemangiomas: strawberry matters? Indian J Pediatr 2012; 79(1): 130-1.
[] [PMID: 21779825]
Atherton DJ. Infantile haemangiomas. Early Hum Dev 2006; 82(12): 789-95.
[] [PMID: 17059871]
Sethuraman G, Yenamandra VK, Gupta V. Management of infantile hemangiomas: current trends. J Cutan Aesthet Surg 2014; 7(2): 75-85.
[] [PMID: 25136206]
Holland KE, Drolet BA. Infantile hemangioma. Pediatr Clin North Am 2010; 57(5): 1069-83.
[] [PMID: 20888458]
George A, Mani V, Noufal A. Update on the classification of hemangioma. J Oral Maxillofac Pathol 2014; 18(Suppl. 1): S117-20.
[] [PMID: 25364160]
Léauté-Labrèze C, Prey S, Ezzedine K. Infantile haemangioma: part I. Pathophysiology, epidemiology, clinical features, life cycle and associated structural abnormalities. J Eur Acad Dermatol Venereol 2011; 25(11): 1245-53.
[] [PMID: 21569112]
Higuera S, Gordley K, Metry DW, Stal S. Management of hemangiomas and pediatric vascular malformations. J Craniofac Surg 2006; 17(4): 783-9.
[] [PMID: 16877935]
Dauge C, Fenouil T, Petit T, Jeanne-Pasquier C, Collardeau-Frachon S. Pulmonary infantile hemangioma mimicking a congenital cystic adenomatoid malformation. Pediatr Dev Pathol 2019; 22(5): 480-5.
[] [PMID: 30913983]
Lockman JL, Schwartz AJ. Infantile hemangioma in the airway. Anesthesiology 2015; 123(6): 1449.
[] [PMID: 26039327]
Shabbir Z, Javaid A. Islah Ud Din. Infantile Hepatic Hemangioma. J Pak Med Assoc 2018; 68(12): 1846-7.
[PMID: 30504955]
Steinberger J, Nistal DA, Ghatan S. T3 infantile hemangioma: first case of a tumor involving epidural, intradural extramedullary, and intradural intramedullary spaces. J Neurosurg Pediatr 2019; 1-5.
[] [PMID: 30849748]
Hoover L. Infantile hemangioma: AAP releases guideline for management. Am Fam Physician 2019; 100(3): 186-7.
[PMID: 31361095]
Nip SY, Hon KL, Leung WK, Leung AK, Choi PC. Neonatal abdominal hemangiomatosis: Propranolol beyond infantile hemangioma. Case Rep Pediatr 2016; 20169803975
[] [PMID: 27110421]
Uda K, Okubo Y, Matsushima T, Sadahira C, Kono T, Hataya H. Multifocal infantile hemangioma. J Pediatr 2019; 210: 238-238.e1.
[] [PMID: 30955789]
Leung AK, Rafaat M. Benign neonatal hemangiomatosis. Pediatr Dermatol 2003; 20(2): 161-3.
[] [PMID: 12657017]
Bellaud G, Puzenat E, Billon-Grand NC, Humbert P, Aubin F. PHACE syndrome, a series of six patients: clinical and morphological manifestations, propranolol efficacy, and safety. Int J Dermatol 2015; 54(1): 102-7.
[] [PMID: 24962639]
Chamli A, Litaiem N. PHACE Syndrome StatPearls. Treasure Island, FL: StatPearls Publishing 2019.
Sekioka A, Fukumoto K, Horikoshi Y, Nii M, Urushihara N. PHACE syndrome with unnoticeable skin lesion and rare anomaly of coronary artery. Pediatr Int (Roma) 2019; 61(5): 524-6.
[] [PMID: 31090165]
Siegel DH. PHACE syndrome: Infantile hemangiomas associated with multiple congenital anomalies: Clues to the cause. Am J Med Genet C Semin Med Genet 2018; 178(4): 407-13.
[] [PMID: 30580483]
O TM, Alexander RE, Lando T, et al.. Segmental hemangiomas of the upper airway. Laryngoscope 2009; 119(11): 2242-7.
[] [PMID: 19806648]
Suh KY, Frieden IJ. Infantile hemangiomas with minimal or arrested growth: a retrospective case series. Arch Dermatol 2010; 146(9): 971-6.
[] [PMID: 20855695]
Oiso N, Kawada A. The dermoscopic features in infantile hemangioma. Pediatr Dermatol 2011; 28(5): 591-3.
[] [PMID: 21854412]
Metry DW. Infantile hemangiomas: Evaluation and diagnosis.UpToDate Waltham.
Haggstrom AN, Drolet BA, Baselga E, et al. Prospective study of infantile hemangiomas: clinical characteristics predicting complications and treatment. Pediatrics 2006; 118(3): 882-7.
[] [PMID: 16950977]
Horii KA, Drolet BA, Baselga E, et al. Hemangioma Investigator Group. Risk of hepatic hemangiomas in infants with large hemangiomas. Arch Dermatol 2010; 146(2): 201-3.
[] [PMID: 20157038]
Wildgruber M, Sadick M, Müller-Wille R, Wohlgemuth WA. Vascular tumors in infants and adolescents. Insights Imaging 2019; 10(1): 30.
[] [PMID: 30868300]
Callahan AB, Yoon MK. Infantile hemangiomas: A review. Saudi J Ophthalmol 2012; 26(3): 283-91.
[] [PMID: 23961007]
Ding A, Gong X, Li J, Xiong P. Role of ultrasound in diagnosis and differential diagnosis of deep infantile hemangioma and venous malformation. J Vasc Surg Venous Lymphat Disord 2019; 7(5): 715-23.
[] [PMID: 31421839]
Rodríguez Bandera AI, Sebaratnam DF, Feito Rodríguez M, de Lucas Laguna R. Cutaneous ultrasound and its utility in pediatric dermatology: Part II-Developmental anomalies and vascular lesions. Pediatr Dermatol 2020; 37(1): 40-51.019.
[] [PMID: 31742750]
Hoornweg MJ, Theunissen CI, Hage JJ, van der Horst CM. Malignant differential diagnosis in children referred for infantile hemangioma. Ann Plast Surg 2015; 74(1): 43-6.
[] [PMID: 23903077]
Kwon EK, Seefeldt M, Drolet BA. Infantile hemangiomas: an update. Am J Clin Dermatol 2013; 14(2): 111-23.
[] [PMID: 23338947]
Hochman M. The role of surgery in the management of infantile hemangiomas: What is the best timing? Otolaryngol Clin North Am 2018; 51(1): 119-23.
[] [PMID: 29217056]
van Vugt LJ, van der Vleuten CJM, Flucke U, Blokx WAM. The utility of GLUT1 as a diagnostic marker in cutaneous vascular anomalies: A review of literature and recommendations for daily practice. Pathol Res Pract 2017; 213(6): 591-7.
[] [PMID: 28552538]
Leung AKC, Leong KF, Barankin B. A male infant born with an ulcerated vascular mass. Paediatr Child Health 2019; 24(1): 7-9.
[] [PMID: 30792591]
Ayturk UM, Couto JA, Hann S, et al. Somatic activating mutations in GNAQ and GNA11 are associated with congenital hemangioma. Am J Hum Genet 2016; 98(6): 1271.
[] [PMID: 27259057]
Boull C, Maguiness SM. Congenital hemangiomas. Semin Cutan Med Surg 2016; 35(3): 124-7.
[] [PMID: 27607320]
Garcia-Monaco RD, Giachetti A. Infantile hemangioma or kaposiform hemangioendothelioma? J Vasc Interv Radiol 2014; 25(5): 810.
[] [PMID: 24745913]
Tribolet S, Hoyoux C, Boon LM, et al. A not so harmless mass: Kaposiform hemangioendothelioma complicated by a Kasabach-Merritt phenomenon. Arch Pediatr 2019; 26(6): 365-9.
[] [PMID: 31353149]
Rambhia KD, Khopkar US. Tufted angioma. Indian Dermatol Online J 2016; 7(1): 62-3.
[] [PMID: 26955593]
Sethia R, Cerne JW, Jatana KR, Elmaraghy CA. Pediatric facial kaposiform hemangioendothelioma: a case report and review of the literature. J Surg Case Rep 2019; 2019(4)rjz113
[] [PMID: 31044058]
Leung AK. Port-wine stain associated with maternal use of lithium carbonate. J Natl Med Assoc 1987; 79(8): 877-8.
[PMID: 3149678]
Leung AK, Telmesani AM. Salmon patches in Caucasian children. Pediatr Dermatol 1989; 6(3): 185-7.
[] [PMID: 2798254]
Leung AK. The nature of naevus flammeus. Eur J Pediatr 2003; 162(11): 816.
[] [PMID: 12937975]
Leung AK, Barankin B, Hon KL. Persistent salmon patch on the forehead and glabellum in a chinese adult. Case Rep Med 2014; 2014139174
[] [PMID: 24963301]
Leung AKC, Lam JM, Leong KF. Childhood Langerhans cell histiocytosis: a disease with many faces. World J Pediatr 2019; 15(6): 536-45.
[] [PMID: 31456157]
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): 684-9.689.e1.
Mauskar MM, Pichard DC, Norton SA. Ulcers on an Infant’s Sacrum. Ulcerated segmental infantile hemangioma (IH). JAMA Pediatr 2015; 169(9): 873-4.
[] [PMID: 26348856]
Castrén E, Salminen P, Gissler M, Stefanovic V, Pitkäranta A, Klockars T. Risk factors and morbidity of infantile haemangioma: preterm birth promotes ulceration. Acta Paediatr 2016; 105(8): 940-5.
[] [PMID: 27146410]
Leung AKC, Leong KF, Lam JM. An ulcerated giant segmental hemangioma resulting in contracture of the left elbow. Paediatr Child Health 2020.
Boscolo E, Bischoff J. Vasculogenesis in infantile hemangioma. Angiogenesis 2009; 12(2): 197-207.
[] [PMID: 19430954]
Huang SA, Tu HM, Harney JW, et al. Severe hypothyroidism caused by type 3 iodothyronine deiodinase in infantile hemangiomas. N Engl J Med 2000; 343(3): 185-9.
[] [PMID: 10900278]
Léauté-Labrèze C, Prey S, Ezzedine K. Infantile haemangioma: part II. Risks, complications and treatment. J Eur Acad Dermatol Venereol 2011; 25(11): 1254-60.
[] [PMID: 21569113]
Metry DW, Haggstrom AN, Drolet BA, et al. A prospective study of PHACE syndrome in infantile hemangiomas: demographic features, clinical findings, and complications. Am J Med Genet A 2006; 140(9): 975-86.
[] [PMID: 16575892]
Rais R, González I, Saito JM, Dehner LP. Infantile hemangioma presenting as colocolic intussusception in an infant case report with review of pathologic lead points. Case Rep Pediatr 2018.20186494075
[] [PMID: 30034903]
Ramtohul P, Beylerian M, Dambricourt L, Matonti F, Denis D. Secondary Congenital glaucoma associated with retro-orbital infantile hemangioma: A masquerade syndrome. J Glaucoma 2019; 28(6): e103-6.
[] [PMID: 30839414]
Soukoulis IW, Liang MG, Fox VL, Mulliken JB, Alomari AI, Fishman SJ. Gastrointestinal infantile hemangioma: Presentation and management. J Pediatr Gastroenterol Nutr 2015; 61(4): 415-20.
[] [PMID: 25859824]
Theiler M, Hoffman WY, Frieden IJ. Breast hypoplasia as a complication of an untreated infantile hemangioma. Pediatr Dermatol 2016; 33(2): e129-30.
[] [PMID: 26763884]
Akcay A, Karakas Z, Saribeyoglu ET, et al. Infantile hemangiomas, complications and follow-up. Indian Pediatr 2012; 49(10): 805-9.
[] [PMID: 22791668]
Schwager K, Waner M, Höhmann D. Hemangioma: differential diagnosis and necessary early laser treatment. Adv Otorhinolaryngol 1995; 49: 70-4.
[] [PMID: 7653390]
Tollefson MM, Frieden IJ. Early growth of infantile hemangiomas: what parents’ photographs tell us. Pediatrics 2012; 130(2): e314-20.
[] [PMID: 22826568]
Jeng MR, Fuh B, Blatt J, et al. Malignant transformation of infantile hemangioma to angiosarcoma: response to chemotherapy with bevacizumab. Pediatr Blood Cancer 2014; 61(11): 2115-7.
[] [PMID: 24740626]
Yu Z, Cai R, Chang L, et al. Clinical and radiological outcomes of infantile hemangioma treated with oral propranolol: A long-term follow-up study. J Dermatol 2019; 46(5): 376-82.
[] [PMID: 30916822]
Moyakine AV, Spillekom-van Koulil S, Küpers EM, van der Vleuten CJM. Influence of infantile hemangioma severity and activity on QoL of patients and their parents: A cross-sectional study. Pediatr Dermatol 2018; 35(5): 628-34.
[] [PMID: 30015356]
Tanner JL, Dechert MP, Frieden IJ. Growing up with a facial hemangioma: parent and child coping and adaptation. Pediatrics 1998; 101(3 Pt 1): 446-52.
[] [PMID: 9481012]
de Wild SR, Moyakine AV, van der Vleuten CJM. Does treatment with propranolol affect quality of life in infantile hemangioma patients and their parents? Pediatr Dermatol 2019; 36(6): 958-60.
[] [PMID: 31566792]
Cazeau C, Blei F, Gonzáles Hermosa MDRF, et al. Burden of infantile hemangioma on family: An international observational cross-sectional study. Pediatr Dermatol 2017; 34(3): 295-302.
[] [PMID: 28382698]
Chokoeva A, Sokolova R, Lotti T, et al. Congenital progressive mutilating hemangioma. Open Access Maced J Med Sci 2017; 5(3): 395-6.
[PMID: 28698762]
Cheirif-Wolosky O, Novelo-Soto AD, Orozco-Covarrubias L, Sáez-de-Ocariz M. Infantile hemangioma: an update in the topical and systemic treatments. Bol Méd Hosp Infant México 2019; 76(4): 167-75.
[PMID: 31303649]
Pauly NG, Kurian N, Kashyap RR, Kini R, Rao PK, Thomas A. The star-crossed curse of childhood: A case of infantile hemangioma. J Indian Soc Pedod Prev Dent 2019; 37(2): 209-13.
[] [PMID: 31249188]
Al-Haddad C, El Salloukh NA, El Moussawi Z. β-blockers in the treatment of periocular infantile hemangioma. Curr Opin Ophthalmol 2019; 30(5): 319-25.
[] [PMID: 31394556]
Kim J, Hong JW, Roh TS, Lee WJ. Oral propranolol therapy in 23 infants with infantile hemangioma. Arch Plast Surg 2018; 45(6): 517-24.
[] [PMID: 30466231]
Raphael MF, Breur JM, Vlasveld FA, et al. Treatment of infantile hemangiomas: therapeutic options in regard to side effects and adverse events - a review of the literature. Expert Opin Drug Saf 2016; 15(2): 199-214.
[] [PMID: 26646657]
Sirachainan N, Lekanan W, Thammagasorn Y, Wanitkun S, Kadegasem P, Chunharas A. Response to propranolol in infantile hemangioma. Pediatr Int (Roma) 2016; 58(7): 662-5.
[] [PMID: 27460401]
Baselga E, Dembowska-Baginska B, Przewratil P, et al. Efficacy of propranolol between 6 and 12 months of age in high-risk infantile hemangioma. Pediatrics 2018; 142(3)e20173866
[] [PMID: 30082451]
Wu C, Guo L, Wang L, Li J, Wang C, Song D. Associations between short-term efficacy and clinical characteristics of infantile hemangioma treated by propranolol. Medicine (Baltimore) 2019; 98(6)e14346
[] [PMID: 30732164]
Wu W, Wang H, Hao J, Gao Z, Li F, Chen Y. Therapeutic efficacy of propranolol for infantile hemangiomas. Oral Surg Oral Med Oral Pathol Oral Radiol 2019; 128(2): 132-138. [B].
[] [PMID: 31133517]
Yun YJ, Gyon YH, Yang S, Lee YK, Park J, Park M. A prospective study to assess the efficacy and safety of oral propranolol as first-line treatment for infantile superficial hemangioma. Korean J Pediatr 2015; 58(12): 484-90.
[] [PMID: 26770224]
Léauté-Labrèze C, Hoeger P, Mazereeuw-Hautier J, et al. A randomized, controlled trial of oral propranolol in infantile hemangioma. N Engl J Med 2015; 372(8): 735-46.
[] [PMID: 25693013]
Lou H, Xu G, Huo R. Curative effect and safety of propranolol combined with prednisone in the treatment of infantile hemangiomas. Exp Ther Med 2018; 15(6): 4677-82.
[] [PMID: 29805486]
Chinnadurai S, Fonnesbeck C, Snyder KM, et al. Pharmacologic interventions for infantile hemangioma: A meta-analysis. Pediatrics 2016; 137(2)e20153896
[] [PMID: 26772662]
Novoa M, Baselga E, Beltran S, et al. Interventions for infantile haemangiomas of the skin. Cochrane Database Syst Rev 2018; 4CD006545
[] [PMID: 29667726]
Léaute-Labrèze C, Boccara O, Degrugillier-Chopinet C, et al. Safety of oral propranolol for the treatment of infantile hemangioma: A systematic review. Pediatrics 2016; 138(4)e20160353
[] [PMID: 27688361]
Marqueling AL, Oza V, Frieden IJ, Puttgen KB. Propranolol and infantile hemangiomas four years later: a systematic review. Pediatr Dermatol 2013; 30(2): 182-91.
[] [PMID: 23405852]
Wong A, Hardy KL, Kitajewski AM, Shawber CJ, Kitajewski JK, Wu JK. Propranolol accelerates adipogenesis in hemangioma stem cells and causes apoptosis of hemangioma endothelial cells. Plast Reconstr Surg 2012; 130(5): 1012-21.
[] [PMID: 23096601]
Albuquerque JC, Magalhães RA, Félix JA, et al. Treatment of children and adolescents with hemangioma using propranolol: preliminary results from a retrospective study. Sao Paulo Med J 2014; 132(1): 48-54.
[] [PMID: 24474080]
Kagami S, Katori T. Oral propranolol for infantile hemangiomas beyond the proliferative phase. J Dermatol 2018; 45(10): 1199-202.
[] [PMID: 30051930]
Vivas-Colmenares GV, Bernabeu-Wittel J, Alonso-Arroyo V, Matute de Cardenas JA, Fernandez-Pineda I. Effectiveness of propranolol in the treatment of infantile hemangioma beyond the proliferation phase. Pediatr Dermatol 2015; 32(3): 348-52.
[] [PMID: 25721095]
Zvulunov A, McCuaig C, Frieden IJ, et al. Oral propranolol therapy for infantile hemangiomas beyond the proliferation phase: a multicenter retrospective study. Pediatr Dermatol 2011; 28(2): 94-8.
[] [PMID: 21362031]
Metry DW. S Infantile hemangiomas: In: Management Corona R, ed. Waltham, MA: UpToDate Inc. Available from:
Prasad A, Sinha AK, Kumar B, Prasad A, Kumari M. Individualized dosing of oral propranolol for treatment of infantile hemangioma: a prospective study. Pan Afr Med J 2019; 32: 155.
[PMID: 31303926]
Shehata N, Powell J, Dubois J, et al. Late rebound of infantile hemangioma after cessation of oral propranolol. Pediatr Dermatol 2013; 30(5): 587-91.
[] [PMID: 24016283]
Bakalli I, Kola E, Lluka R, et al. Deep coma in a child treated with propranolol for infantile hemangioma. BMC Pediatr 2019; 19(1): 216.
[] [PMID: 31266444]
Breur JM, de Graaf M, Breugem CC, Pasmans SG. Hypoglycemia as a result of propranolol during treatment of infantile hemangioma: a case report. Pediatr Dermatol 2011; 28(2): 169-71.
[] [PMID: 20738795]
MacIsaac ZM, Nayar HS, Gehris R, Mehta D, Geisler S, Grunwaldt LJ. Treatment for infantile hemangiomas: Selection criteria, safety, and outcomes using oral propranolol during the early phase of propranolol use for hemangiomas. J Craniofac Surg 2016; 27(1): 159-62.
[] [PMID: 26674892]
Droitcourt C, Kerbrat S, Rault C, et al. Safety of oral propranolol for infantile hemangioma. Pediatrics 2018; 141(6)e20173783
[] [PMID: 29844139]
Ji Y, Chen S, Wang Q, et al. Intolerable side effects during propranolol therapy for infantile hemangioma: frequency, risk factors and management. Sci Rep 2018; 8(1): 4264.
[] [PMID: 29523832]
Li L, Wei L, Xu ZG, Ma L. No increased risks associated with propranolol treatment for infantile hemangioma in preterm infants were identified at 3 years of age. Am J Clin Dermatol 2019; 20(2): 289-93.
[] [PMID: 30618026]
Mei-Zahav M, Blau H, Hoshen M, et al. Propranolol treatment for infantile hemangioma does not increase risk of childhood wheezing. Pediatr Pulmonol 2017; 52(8): 1071-5.
[] [PMID: 28267266]
Moyakine AV, Kerstjens JM, Spillekom-van Koulil S, van der Vleuten CJ. Propranolol treatment of infantile hemangioma (IH) is not associated with developmental risk or growth impairment at age 4 years. J Am Acad Dermatol 2016; 75(1): 59-63.e1.
[] [PMID: 27021240]
Moyakine AV, Spillekom-van Koulil S, van der Vleuten CJM. Propranolol treatment of infantile hemangioma is not associated with psychological problems at 7 years of age. J Am Acad Dermatol 2017; 77(1): 105-8.
[] [PMID: 28190620]
Thai T, Wang CY, Chang CY, Brown JD. Central nervous system effects of oral propranolol for infantile hemangioma: A systematic review and meta-analysis. J Clin Med 2019; 8(2)E268
[] [PMID: 30813242]
Prey S, Voisard JJ, Delarue A, et al. Safety of propranolol therapy for severe infantile hemangioma. JAMA 2016; 315(4): 413-5.
[] [PMID: 26813215]
Yang H, Hu DL, Shu Q, Guo XD. Efficacy and adverse effects of oral propranolol in infantile hemangioma: a meta-analysis of comparative studies. World J Pediatr 2019; 15(6): 546-58.
[] [PMID: 31342465]
Ahogo CK, Ezzedine K, Prey S, et al. Factors associated with the relapse of infantile haemangiomas in children treated with oral propranolol. Br J Dermatol 2013; 169(6): 1252-6.
[] [PMID: 23662995]
Chang L, Ma G, Jin Y, et al. Recurrence of infantile hemangioma after termination of propranolol treatment. Ann Plast Surg 2014; 72(2): 173-5.
[] [PMID: 24406852]
Shah SD, Baselga E, McCuaig C, et al. Rebound growth of infantile hemangiomas after propranolol therapy. Pediatrics 2016; 137(4)e20151754
[] [PMID: 26952504]
Wedgeworth E, Glover M, Irvine AD, et al. Propranolol in the treatment of infantile haemangiomas: lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce survey. Br J Dermatol 2016; 174(3): 594-601.
[] [PMID: 26473312]
Ábarzúa-Araya A, Navarrete-Dechent CP, Heusser F, Retamal J, Zegpi-Trueba MS. Atenolol versus propranolol for the treatment of infantile hemangiomas: a randomized controlled study. J Am Acad Dermatol 2014; 70(6): 1045-9.
[] [PMID: 24656727]
Blanchet C, Nicollas R, Bigorre M, Amedro P, Mondain M. Management of infantile subglottic hemangioma: acebutolol or propranolol? Int J Pediatr Otorhinolaryngol 2010; 74(8): 959-61.
[] [PMID: 20557953]
Fernandez-Pineda I, Williams R, Ortega-Laureano L, Jones R. Cardiovascular drugs in the treatment of infantile hemangioma. World J Cardiol 2016; 8(1): 74-80.
[] [PMID: 26839658]
Ji Y, Wang Q, Chen S, et al. Oral atenolol therapy for proliferating infantile hemangioma: A prospective study. Medicine (Baltimore) 2016; 95(24)e3908
[] [PMID: 27310994]
Pope E, Chakkittakandiyil A, Lara-Corrales I, Maki E, Weinstein M. Expanding the therapeutic repertoire of infantile haemangiomas: cohort-blinded study of oral nadolol compared with propranolol. Br J Dermatol 2013; 168(1): 222-4.
[] [PMID: 22762503]
Ruitenberg G, Young-Afat DA, de Graaf M, Pasmans SG, Breugem CC. Ulcerated infantile haemangiomas: the effect of the selective beta-blocker atenolol on wound healing. Br J Dermatol 2016; 175(6): 1357-60.
[] [PMID: 27105937]
Tasani M, Glover M, Martinez AE, Shaw L. Atenolol treatment for infantile haemangioma. Br J Dermatol 2017; 176(5): 1400-2.
[] [PMID: 28112790]
Villalba-Moreno AM, Cotrina-Luque J, Del Vayo-Benito CA, Flores-Moreno S, Bautista-Paloma FJ. Nadolol for the treatment of infantile hemangioma. Am J Health Syst Pharm 2015; 72(1): 44-6.
[] [PMID: 25511837]
Wang Q, Xiang B, Chen S, Ji Y. Efficacy and safety of oral atenolol for the treatment of infantile haemangioma: A systematic review. Australas J Dermatol 2019; 60(3): 181-5.
[] [PMID: 30515761]
Ovadia SA, Landy DC, Cohen ER, Yang EY, Thaller SR. Local administration of β-blockers for infantile hemangiomas: a systematic review and meta-analysis. Ann Plast Surg 2015; 74(2): 256-62.
[] [PMID: 25590249]
Painter SL, Hildebrand GD. Review of topical beta blockers as treatment for infantile hemangiomas. Surv Ophthalmol 2016; 61(1): 51-8.
[] [PMID: 26408055]
Püttgen K, Lucky A, Adams D, et al. Hemangioma Investigator Group. Topical timolol maleate treatment of infantile hemangiomas. Pediatrics 2016; 138(3)e20160355
[] [PMID: 27527799]
Wu HW, Liu C, Wang X, et al. Topical application of 0.5% timolol maleate hydrogel for the treatment of superficial infantile hemangioma. Front Oncol 2017; 7: 137.
[] [PMID: 28702374]
Wu HW, Wang X, Zhang L, Zheng JW, Liu C, Wang YA. Topical timolol vs. oral propranolol for the treatment of superficial infantile hemangiomas. Front Oncol 2018; 8: 605.
[] [PMID: 30619747]
Yu L, Li S, Su B, et al. Treatment of superficial infantile hemangiomas with timolol: Evaluation of short-term efficacy and safety in infants. Exp Ther Med 2013; 6(2): 388-90.
[] [PMID: 24137194]
Frommelt P, Juern A, Siegel D, et al. Adverse events in young and preterm infants receiving topical timolol for infantile hemangioma. Pediatr Dermatol 2016; 33(4): 405-14.
[] [PMID: 27246751]
Paul SP, Davis RF. Infantile haemangioma: topical timolol gel may be safer in premature babies. Br J Hosp Med (Lond) 2019; 80(8): i.
[] [PMID: 31437034]
Danarti R, Ariwibowo L, Radiono S, Budiyanto A. Topical timolol maleate 0.5% for infantile hemangioma: Its effectiveness compared to ultrapotent topical corticosteroids - A single-center experience of 278 Cases. Dermatology (Basel) 2016; 232(5): 566-71.
[] [PMID: 27592104]
Park KH, Jang YH, Chung HY, Lee WJ, Kim DW, Lee SJ. Topical timolol maleate 0.5% for infantile hemangioma; it’s effectiveness and/or adjunctive pulsed dye laser - single center experience of 102 cases in Korea. J Dermatolog Treat 2015; 26(4): 389-91.
[] [PMID: 25424048]
Tawfik AA, Alsharnoubi J. Topical timolol solution versus laser in treatment of infantile hemangioma: a comparative study. Pediatr Dermatol 2015; 32(3): 369-76.
[] [PMID: 25740672]
Zheng L, Li Y. Effect of topical timolol on response rate and adverse events in infantile hemangioma: a meta-analysis. Arch Dermatol Res 2018; 310(4): 261-9.
[] [PMID: 29362868]
Zaher H, Rasheed H, El-Komy MM, et al. Propranolol versus captopril in the treatment of infantile hemangioma (IH): A randomized controlled trial. J Am Acad Dermatol 2016; 74(3): 499-505.
[] [PMID: 26685718]
Mannschreck DB, Huang AH, Lie E, Psoter K, Puttgen K. Topical timolol as adjunct therapy to shorten oral propranolol therapy for infantile hemangiomas. Pediatr Dermatol 2019; 36(3): 283-9.
[] [PMID: 30968438]
Boos MD, Castelo-Soccio L. Experience with topical timolol maleate for the treatment of ulcerated infantile hemangiomas (IH). J Am Acad Dermatol 2016; 74(3): 567-70.
[] [PMID: 26892656]
Almebayadh M. Successful treatment of ulcerated infantile hemangioma with brimonidine-timolol cream: 2 cases report and review of the literature. J Dermatolog Treat 2019; 1-2.
[] [PMID: 30973791]
Beal BT, Chu MB, Siegfried EC. Ulcerated infantile hemangioma: novel treatment with topical brimonidine-timolol. Pediatr Dermatol 2014; 31(6): 754-6.
[] [PMID: 25424217]
Nieuwenhuis K, de Laat PC, Janmohamed SR, Madern GC, Oranje AP. Infantile hemangioma: treatment with short course systemic corticosteroid therapy as an alternative for propranolol. Pediatr Dermatol 2013; 30(1): 64-70.
[] [PMID: 22958179]
Bennett ML, Fleischer AB Jr, Chamlin SL, Frieden IJ. Oral corticosteroid use is effective for cutaneous hemangiomas: an evidence-based evaluation. Arch Dermatol 2001; 137(9): 1208-13.
[] [PMID: 11559219]
Izadpanah A, Izadpanah A, Kanevsky J, Belzile E, Schwarz K. Propranolol versus corticosteroids in the treatment of infantile hemangioma: a systematic review and meta-analysis. Plast Reconstr Surg 2013; 131(3): 601-13.
[] [PMID: 23142941]
Polites SF, Rodrigue BB, Chute C, Hammill A, Dasgupta R. Propranolol versus steroids for the treatment of ulcerated infantile hemangiomas. Pediatr Blood Cancer 2018; 65(10)e27280
[] [PMID: 29932302]
Xu SQ, Jia RB, Zhang W, Zhu H, Ge SF, Fan XQ. Beta-blockers versus corticosteroids in the treatment of infantile hemangioma: an evidence-based systematic review. World J Pediatr 2013; 9(3): 221-9.
[] [PMID: 23929254]
Leung AK, Hon KL, Robson WL. Atopic dermatitis. Adv Pediatr 2007; 54: 241-73.
[] [PMID: 17918474]
Sawa K, Yazdani A, Rieder MJ, Filler G. Propranolol therapy for infantile hemangioma is less toxic but longer in duration than corticosteroid therapy. Plast Surg (Oakv) 2014; 22(4): 233-6.
[] [PMID: 25535459]
Aly MM, Hamza AF, Abdel Kader HM, Saafan HA, Ghazy MS, Ragab IA. Therapeutic superiority of combined propranolol with short steroids course over propranolol monotherapy in infantile hemangioma. Eur J Pediatr 2015; 174(11): 1503-9.
[] [PMID: 25982338]
Lou Y, Peng WJ, Cao Y, Cao DS, Xie J, Li HH. The effectiveness of propranolol in treating infantile haemangiomas: a meta-analysis including 35 studies. Br J Clin Pharmacol 2014; 78(1): 44-57.
[] [PMID: 24033819]
Couto JA, Greene AK. Management of problematic infantile hemangioma using intralesional triamcinolone: efficacy and safety in 100 infants. J Plast Reconstr Aesthet Surg 2014; 67(11): 1469-74.
[] [PMID: 25104131]
Kwon SH, Choi JW, Byun SY, et al. Effect of early long-pulse pulsed dye laser treatment in infantile hemangiomas. Dermatol Surg 2014; 40(4): 405-11.
[] [PMID: 24460784]
Zhang W, Li F, Yang Y, Xue L, Cao M, Wang L. Hemangioma treatment with pulsed dye laser-distinct parameters used between neonatal and non-neonatal patients. J Cosmet Laser Ther 2016; 18(7): 389-92.
[] [PMID: 27331875]
Asilian A, Mokhtari F, Kamali AS, Abtahi-Naeini B, Nilforoushzadeh MA, Mostafaie S. Pulsed dye laser and topical timolol gel versus pulse dye laser in treatment of infantile hemangioma: A double-blind randomized controlled trial. Adv Biomed Res 2015; 4: 257.
[] [PMID: 26918239]
Furuta S, Sato H, Tsuji S, Murakami F, Kitagawa H. Effective treatment for infantile hemangioma with long-pulsed dye laser with oral propranolol medication: a preliminary report. Pediatr Surg Int 2016; 32(9): 857-62.
[] [PMID: 27461431]
Reddy KK, Blei F, Brauer JA, et al. Retrospective study of the treatment of infantile hemangiomas using a combination of propranolol and pulsed dye laser. Dermatol Surg 2013; 39(6): 923-33.
[] [PMID: 23458381]
Sun X, Liu X, Lu N, Yao S, Xu X, Niu L. Short-term curative effect and safety of propranolol combined with laser in the treatment of infantile hemangiomas. Oncol Lett 2018; 16(5): 6561-5.
[] [PMID: 30405795]
Su WT, Xue JX, Ke YH. Noteworthy effects of a long-pulse Alexandrite laser for treatment of high-risk infantile hemangioma: A case report and literature review. World J Clin Cases 2019; 7(14): 1876-83.
[] [PMID: 31417934]
Cheng J, Liu B, Lee HJ. Outcomes of surgical treatment for hemangiomas. Pediatr Dermatol 2019; 36(2): 207-12.
[] [PMID: 30793785]
Polites SF, Watanabe M, Crafton T, et al. Surgical resection of infantile hemangiomas following medical treatment with propranolol versus corticosteroids. J Pediatr Surg 2019; 54(4): 740-3.
[] [PMID: 30249358]
Woody MM, Levy ML, Weinfeld AB. Propranolol for preoperative management of a large infantile hemangioma. Pediatr Dermatol 2016; 33(3): e198-200.
[] [PMID: 27071982]
Metz BJ, Rubenstein MC, Levy ML, Metry DW. Response of ulcerated perineal hemangiomas of infancy to becaplermin gel, a recombinant human platelet-derived growth factor. Arch Dermatol 2004; 140(7): 867-70.
[] [PMID: 15262700]
Sugarman JL, Mauro TM, Frieden IJ. Treatment of an ulcerated hemangioma with recombinant platelet-derived growth factor. Arch Dermatol 2002; 138(3): 314-6.
[] [PMID: 11902979]
Enjolras O, Brevière GM, Roger G, et al. Vincristine treatment for function- and life-threatening infantile hemangioma. Arch Pediatr 2004; 11(2): 99-107.
[] [PMID: 14761730]
McCuaig CC, Dubois J, Powell J, et al. A phase II, open-label study of the efficacy and safety of imiquimod in the treatment of superficial and mixed infantile hemangioma. Pediatr Dermatol 2009; 26(2): 203-12.
[] [PMID: 19419474]
Bessar H, Kandil AH, Nasr NM, Khattab F. Itraconazole versus propranolol: Therapeutic and pharmacologic effect on serum angiopoietin-2 in patients with infantile hemangioma. J Dermatolog Treat 2019; 1-25.
[] [PMID: 31668109]
Chen S, Zhuang K, Sun K, et al. Itraconazole induces regression of infantile hemangioma via downregulation of the platelet-derived growth factor-D/PI3K/Akt/mTOR pathway. J Invest Dermatol 2019; 139(7): 1574-82.
[] [PMID: 30690033]
Zaher H, Rasheed H, Esmat S, et al. Propranolol and infantile hemangiomas: different routes of administration, a randomized clinical trial. Eur J Dermatol 2013; 23(5): 646-52.
[] [PMID: 24135427]
Düzenli Kar Y, Özdemir ZC, Acu B, Bör Ö. Infantile hemangioma: Efficacy of low-dose propranolol and of intralesional bleomycin injection for propranolol non-response. Pediatr Int (Roma) 2019; 61(5): 459-64.
[] [PMID: 30861274]
Sabry HH, Sorour NE, Akl EM. Intralesional injection of bevacizumab versus triamcinolone acetonide in infantile hemangioma. J Dermatolog Treat 2019; 1-6. Epub ahead of print
[] [PMID: 30835573]
Yuan SM, Zhang M, Guo Y, Cui L, Hong ZJ, Jiang HQ. Intralesional injection of diprospan is effective for infantile hemangioma. J Craniofac Surg . 2015; 26(2): 422-4.
[] [PMID: 25643331]

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