- Infantile hemangioma
Infantile hemangioma
	Paediatric surgery.Ukraine.2020.3(68):49-57; doi 10.15574/PS.2020.68.49
	Pereyaslov A. A.1, Rybalchenko V. F.2, Losev О. О.3
	1Danylo Halytsky Lviv national medical university, Ukraine
	2Shupyk national academy of postgraduate education, Kyiv, Ukraine
	3Odessa national medical university, Ukraine
	For citation: Pereyaslov AA, Rybalchenko VF, Losev ОО. (2020). Infantile hemangioma. Paediatric Surgery.Ukraine. 3(68):49-57. doi 10.15574/PS.2020.68.49
	Article received: Jun 15, 2020. Accepted for publication: Sep 09, 2020.
	Infantile hemangioma is one of the most common benign vascular malformations in children. Besides that, some questions about classification, diagnostic, and choice of method of treatment remains the questionable. The modern data about classification, clinical course, diagnostic, and main principles of treatment of infantile hemangioma are presented in this work. In most cases, the uncomplicated clinical course of infantile hemangioma was observed. However, in some patients the complications may arise. Ulceration, obstruction, functional impairment, and disfigurement are the most often complications of infantile hemangioma. Although, most infantile hemangiomas tend to regress spontaneously, some of them required the treatment. Applying of the β-blockers (systemic or topical), laser therapy, and surgery are the main methods that used for the treatment of infantile hemangiomas. Patients with infantile hemangiomas, despite the simplicity of diagnostic, should be treated on specialized centers. Early detection of at-risk infantile haemangioma is a major point, requiring an increased awareness by paediatricians, with the aim to prevent the complications development. However, it was proven the efficacy of propranolol treatment for the all types of infantile hemangiomas, the long-term follow-up studies are needed to assess its safety with regard to neurodevelopment.
	No conflict of interest was declared by the authors.
	Key words: infantile hemangioma, diagnostic, treatment.
REFERENCES
1. Ábarzúa-Araya A, Navarrete-Dechent CP, Heusser F et al. (2014). Atenolol versus propranolol for the treatment of infantile hemangiomas: a randomized controlled study. J Am Acad Dermatol. 70 (6): 1045-1049. https://doi.org/10.1016/j.jaad.2014.01.905; PMid:24656727
2. Ahogo CK, Ezzedine K, Prey S et al. (2013). Factors associated with the relapse of infantile haemangiomas in children treated with oral propranolol. Br J Dermatol. 169 (6): 1252-1256. https://doi.org/10.1111/bjd.12432; PMid:23662995
3. Bauland CG, Lüning TH, Smit JM et al. (2011). Untreated hemangiomas: growth pattern and residual lesions. Plast Reconstr Surg. 127 (4): 1643-1648. https://doi.org/10.1097/PRS.0b013e318208d2ac; PMid:21460670
4. Bernabeu-Wittel J, Narváez-Moreno B, de la Torre-Garciá JM et al. (2015). Oral nadolol for children with infantile hemangiomas and sleep disturbances with oral propranolol. Pediatr Dermatol. 32 (6): 853-857. https://doi.org/10.1111/pde.12686; PMid:26447831
5. Bitar MA, Moukarbel RV, Zalzal GH. (2005). Management of congenital subglottic hemangioma: trends and success over the past 17 years. Otolaryngol Head Neck Surg. 132 (2): 226-231 https://doi.org/10.1016/j.otohns.2004.09.136; PMid:15692531
6. Brandling-Bennett HA, Metry DW, Baselga E et al. (2008). Infantile hemangiomas with unusually prolonged growth phase: a case series. Arch Dermatol. 144 (12): 1632-1637. https://doi.org/10.1001/archderm.144.12.1632; PMid:19075148
7. Castren E, Salminen P, Gissler M et al. (2016). Risk factors and morbidity of infantile haemangioma: preterm birth promotes ulceration. Acta Paediatr. 105 (8): 940-9455. https://doi.org/10.1111/apa.13460; PMid:27146410
8. Cazeau C, Blei F, Gonzáles Hermosa MDRF et al. (2017). Burden of infantile hemangioma on family: an international observational cross-sectional study. Pediatr Dermatol. 34 (3): 295-302. https://doi.org/10.1111/pde.13133; PMid:28382698
9. Chamlin SL, Haggstrom AN, Drolet BA et al. (2007). Multicenter prospective study of ulcerated hemangiomas. J Pediatr. 151 (6): 684-689. https://doi.org/10.1016/j.jpeds.2007.04.055; PMid:18035154
10. Chang L, Chen H, Yang X et al. (2018). Intralesional bleomycin injection for propranolol-resistant hemangiomas. J Craniofac Surg. 29 (2): e128-130. https://doi.org/10.1097/SCS.0000000000004152; PMid:29381619
11. Chang L, Ye X, Qiu Y et al. (2016). Is propranolol safe and effective for outpatient use for infantile hemangioma? A prospective study of 679 cases from one center in China. Ann Plast Surg. 76(5): 559-563. https://doi.org/10.1097/SAP.0000000000000506; PMid:26101993
12. Chen XD, Ma G, Chen H et al. (2013). Maternal and perinatal risk factors for infantile hemangioma: a case-control study. Pediatr Dermatol. 30 (4): 457-461. https://doi.org/10.1111/pde.12042; PMid:23278441
13. Chen ZY, Wang QN, Zhu YH et al. (2019). Progress in the treatment of infantile hemangioma. Ann Transl Med. 7 (22): 692. https://doi.org/10.21037/atm.2019.10.47; PMid:31930093 PMCid:PMC6944559
14. Cheng CE, Friedlander SF. (2016). Infantile hemangiomas, complications and treatments. Semin Cutan Med Surg. 35 (3):108-116. https://doi.org/10.12788/j.sder.2016.050; PMid:27607318
15. Chinnadurai S, Snyder K, Sathe N et al. (2016). Diagnosis and management of infantile hemangioma. Rockville (MD): Agency for Healthcare Research and Quality (US). Report No: 16-EHC002-EF.
16. Cho YK, Ryu DW, Chung HY et al. (2015). Surgical management of scalp infantile hemangiomas. J Craniofac Surg. 26 (4): 1169-1172. https://doi.org/10.1097/SCS.0000000000001561; PMid:26080151
17. Couto JA, Greene AK. (2014). Management of problematic infantile hemangioma using intralesional triamcinolone: efficacy and safety in 100 infants. J Plast Reconstr Aesthet Surg. 67 (11): 1469-1474. https://doi.org/10.1016/j.bjps.2014.07.009; PMid:25104131
18. Dai Y, Hou F, Buckmiller L et al. (2012). Decreased eNOS protein expression in involuting and propranolol-treated hemangiomas. Arch Otolaryngol Head Neck Surg. 138 (2): 177-182. https://doi.org/10.1001/archoto.2011.1096; PMid:22351865
19. Darrow DH, Greene AK, Mancini AJ, Nopper AJ, Section on Dermatology, Section on Otolaryngology-Head and Neck Surgery, and Section on Plastic Surgery. (2015). Diagnosis and management of infantile hemangioma. Pediatrics. 136 (4): e1060-1104. https://doi.org/10.1542/peds.2015-2485; PMid:26416931
20. Darrow DH, Greene AK, Mancini AJ, Nopper AJ, Section on Dermatology, Section on Otolaryngology-Head and Neck Surgery, and Section on Plastic Surgery. (2015). Diagnosis and management of infantile hemangioma: executive summary. Pediatrics. 136 (4): 786-791. https://doi.org/10.1542/peds.2015-2482; PMid:26416928
21. Ding Y, Zhang JZ, Yu SR et al. (2020). Risk factors for infantile hemangioma: a meta-analysis. World J Pediatr. 16 (4): 377-384. https://doi.org/10.1007/s12519-019-00327-2; PMid:31853885
22. Drolet BA, Esterly NB, Frieden IJ. (1999). Hemangiomas in children. Engl J Med. 341 (3): 173-181. https://doi.org/10.1056/NEJM199907153410307; PMid:10403856
23. Drolet BA, Frommelt PC, Chamlin SL et al. (2013). Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics. 131 (1): 128-140. https://doi.org/10.1542/peds.2012-1691; PMid:23266923 PMCid:PMC3529954
24. Düzenli Kar Y, Ozdemir ZC, Acu B, Bor O. (2019). Infantile hemangioma: efficacy of low-dose propranolol and of intralesional bleomycin injection for propranolol non-response. Pediatr Int. 61 (5): 459-464. https://doi.org/10.1111/ped.13830; PMid:30861274
25. FDA. (2014). HEMANGEOLTM (propranolol hydrochloride oral solution). Cited 2019 Sep 25. URL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205410s000lbl.pdf.
26. Fuchsmann C, Quintal MC, Giguere C et al. (2011). Propranolol as first-line treatment of head and neck hemangiomas. Arch Otolaryngol Head Neck Surg. 137 (5): 471-478. https://doi.org/10.1001/archoto.2011.55; PMid:21576558
27. Gorincour G, Kokta V, Rypens F et al. (2005). Imaging characteristics of two subtypes of congenital hemangiomas: rapidly involuting congenital hemangiomas and non-involuting congenital hemangiomas. Pediatr Radiol. 35 (12): 1178-1185. https://doi.org/10.1007/s00247-005-1557-9; PMid:16078073
28. Haggstrom AN, Drolet BA, Baselga E et al. (2006). Prospective study of infantile hemangomas: clinical characteristics predicting complications and treatment. Pediatrics. 118 (3): 882-887. https://doi.org/10.1542/peds.2006-0413; PMid:16950977
29. Haggstrom AN, Drolet BA, Baselga E, Hemangioma Investigator Group et al. (2007). Prospective study of infantile hemangiomas: demographic, prenatal, and perinatal characteristics. J Pediatr. 150 (3): 291-294. https://doi.org/10.1016/j.jpeds.2006.12.003; PMid:17307549
30. Harter N, Mancini AJ. (2019). Diagnosis and management of infantile hemangiomas in the neonate. Pediatr Clin North Am. 66 (2): 437-459. https://doi.org/10.1016/j.pcl.2018.12.011; PMid:30819347
31. Hermans DJ, Boezeman JB, Van de Kerkhof PC et al. (2009). Differences between ulcerated and non-ulcerated hemangiomas, a retrospective study of 465 cases. Eur J Dermatol. 19 (2): 152-156. https://doi.org/10.1684/ejd.2008.0576; PMid:19106042
32. Hoeger PH, Harper JI, Baselga E et al. (2015). Treatment of infantile haemangiomas: recommendations of a European expert group. Eur J Pediatr. 174 (7): 855-865. https://doi.org/10.1007/s00431-015-2570-0; PMid:26021855
33. Hunjan MK, Schoch JJ, Anderson KR et al. (2017). Prenatal risk factors for infantile hemangioma development. J Invest Dermatol. 137 (4): 954-957. https://doi.org/10.1016/j.jid.2016.10.047; PMid:27940221 PMCid:PMC6309253
34. International Society for the Study of Vascular Anomalies. (2014). ISSVA classification of vascular anomalies. Accessed: April 2015. URL: issva.org/classification.
35. Itinteang T, Withers AH, Davis PF, Tan ST. (2014). Biology of infantile hemangioma. Front Surg. 1: 38. https://doi.org/10.3389/fsurg.2014.00038; PMid:25593962 PMCid:PMC4286974
36. Ji Y, Chen S, Xu C, Li L, Xiang B. (2015). The use of propranolol in the treatment of infantile haemangiomas: an update on potential mechanisms of action. Br J Dermatol. 172 (1): 24-32. https://doi.org/10.1111/bjd.13388; PMid:25196392
37. Kessels JP, Hamers ET, Ostertag JU. (2013). Superficial hemangioma: pulsed dye laser versus wait-and-see. Dermatol Surg. 39 3 Pt 1): 414-421. https://doi.org/10.1111/dsu.12081; PMid:23279058
38. Krowchuk DP, Frieden IJ, Mancini AJ et al. (2019). Clinical practice guideline for the management of infantile hemangiomas. Pediatrics. 143 (1): e20183475. https://doi.org/10.1542/peds.2018-3475; PMid:30584062
39. Léauté-Labrèze C, Dumas de la Roque E, Hubiche T et al. (2008). Propranolol for severe hemangiomas of infancy. N Engl J Med. 358 (24): 2649-2651. https://doi.org/10.1056/NEJMc0708819; PMid:18550886
40. Léauté-Labrèze C, Harper JI, Hoeger PH. (2017). Infantile haemangioma. Lancet. 390 (10089): 85-94. https://doi.org/10.1016/S0140-6736(16)00645-0
41. Léauté-Labrèze C, Hoeger PH, Mazereeuw-Hautier J et al. (2015). A randomized controlled trial of oral propranolol in infantile hemangioma. N Engl J Med. 372 (8): 735-746. https://doi.org/10.1056/NEJMoa1404710; PMid:25693013
42. Léauté-Labrèze C, Torres EB, Weibel L et al. (2020). The infantile hemangioma referral score: a validated tool for physicians. Pediatrics. 145 (4): e20191628. https://doi.org/10.1542/peds.2019-1628; PMid:32161112
43. Li H, Lou Y, Zhang R et al. (2019). Propranolol accelerats hemangioma stem cell transformation into adipocyte. Ann Plast Surg. 83 (5): e5-e13. https://doi.org/10.1097/SAP.0000000000002104; PMid:31609806
44. Liang MG, Frieden IJ. (2014). Infantile and congenital hemangiomas. Semin Pediatr Surg. 23 (4): 162-167. https://doi.org/10.1053/j.sempedsurg.2014.06.017; PMid:25241092
45. Lister W. (1938). The natural history of strawberry naevi. Lancet. 231 (5991): 1429-1434. https://doi.org/10.1016/S0140-6736(00)70042-0
46. Marqueling AL, Oza V, Frieden IJ, Puttgen KB. (2013). Propranolol and infantile hemangiomas four years later: a systematic review. Pediatr Dermatol. 30 (2): 182-191. https://doi.org/10.1111/pde.12089; PMid:23405852
47. Mawn LA. (2013). Infantile hemangioma: treatment with surgery or steroids. Am Orthopt J. 63: 6-13. https://doi.org/10.3368/aoj.63.1.6; PMid:24260801
48. Mulliken JB, Glowacki J. (1982). Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg. 69 (3): 412-422. https://doi.org/10.1097/00006534-198203000-00002; PMid:7063565
49. Orlow SJ, Isakoff MS, Blei F. (1997). Increased risk of symptomatic hemangiomas of the airway in association with cutaneous hemangiomas in a «beard» distribution. J Pediatr. 131 (4): 643-646. https://doi.org/10.1016/S0022-3476(97)70079-9
50. Pan WK, Li P, Guo ZT, Huang Q, Gao Y. (2015). Propranolol induces regression of hemangioma cells via the down-regulation of the PI3K/Akt/eNOS/ VEGF pathway. Pediatr Blood Cancer. 62 (8): 1414-1420. https://doi.org/10.1002/pbc.25453; PMid:25728347
51. Pandey A, Gangopadhyay AN, Sharma SP et al. (2010). Evaluation of topical steroids in the treatment of superficial hemangioma. Skinmed. 8 (1): 9-11.
52. Patterson A. (1894). Spontaneous cure of a naevus maternus – large vascular tumor occupying side of neck. South Med Rec. 24: 477.
53. Püttgen K, Lucky A, Adams D, Hemangioma Investigator Group et al. (2016). Topical timolol maleate treatment of infantile hemangiomas. Pediatrics. 138 (3): e20160355. https://doi.org/10.1542/peds.2016-0355; PMid:27527799
54. Raphael MF, Breugem CC, Vlasveld FA et al. (2015). Is cardiovascular evaluation necessary prior to and during beta-blocker therapy for infantile hemangiomas? a cohort study. J Am Acad Dermatol. 72 (3): 465-472. https://doi.org/10.1016/j.jaad.2014.12.019; PMid:25592625
55. Reem RE, Golden RP. (2014). Periocular hemangiomas and lymphangiomas. Pediatr Clin North Am. 61 (3): 541-553. https://doi.org/10.1016/j.pcl.2014.03.007; PMid:24852151
56. Schwartz SR, Blei F, Ceisler E et al. (2006). Risk factors for amblyopia in children with capillary hemangiomas of the eyelids and orbit. J AAPOS. 10 (3): 262-2688. https://doi.org/10.1016/j.jaapos.2006.01.210; PMid:16814181
57. Shah SD, Baselga E, McCuaig C et al. (2016). Rebound growth of infantile hemangiomas after propranolol therapy. Pediatrics. 137(4): e20151754. https://doi.org/10.1542/peds.2015-1754; PMid:26952504
58. Sherrington CA, Sim DK, Freezer NJ, Robertson CF. (1997). Subglottic haemangioma. Arch Dis Child. 76 (5): 458-459. https://doi.org/10.1136/adc.76.5.458; PMid:9196368 PMCid:PMC1717188
59. Smith CJF, Friedlander SF, Guma M et al. (2017). Infantile hemangiomas: an updated review on risk factors, pathogenesis, and treatment. Birth Defects Res. 109 (11): 809-815. https://doi.org/10.1002/bdr2.1023; PMid:28402073 PMCid:PMC5839165
60. Soliman YS, Khachemoune A. (2018). Infantile hemangiomas: our current understanding and treatment options. Dermatol Online J. 24 (9): 13030/qt5jt8q9km.
61. Tan OT, Murray S, Kurban AK. (1989). Action spectrum of vascular specific injury using pulsed irradiation. J Invest Dermatol. 92 (6): 868-871. https://doi.org/10.1111/1523-1747.ep12696885; PMid:2723451
62. Tang LY, Hing JW, Tang JY et al. (2016). Predicting complications with pretreatment testing in infantile haemangioma treated with oral propranolol. Br J Ophthalmol. 100 (7): 902-906. https://doi.org/10.1136/bjophthalmol-2015-307284; PMid:26504177
63. Uthurriague C, Boccara O, Catteau B et al. (2016). Skin patterns associated with upper airway infantile haemangiomas: a retrospective multicentre study. Acta Derm Venereol. 96 (7): 963-966. https://doi.org/10.2340/00015555-2357; PMid:26832659
64. Wassef M, Blei F, Adams D et al. (2015). Vascular anomalies classification: recommendations from the International Society for the Study of Vascular Anomalies. Pediatrics. 136 (1): e203-e214. https://doi.org/10.1542/peds.2014-3673; PMid:26055853
65. Weber FC, Greene AK, Adams DM et al. (2017). Role of imaging in the diagnosis of parotid infantile hemangiomas. Int J Pediatr Otorhinolaryngol. 102: 61-66. https://doi.org/10.1016/j.ijporl.2017.08.035; PMid:29106877
66. Wedgeworth E, Glover M, Irvine AD et al. (2016). Propranolol in the treatment of infantile haemangiomas: lessons from the European propranolol in the treatment of complicated haemangiomas (PITCH) taskforce survey. Br J Dermatol. 174 (3): 594-601. https://doi.org/10.1111/bjd.14233; PMid:26473312
67. Witman PM, Wagner AM, Scherer K et al. (2006). Complications following pulsed dye laser treatment of superficial hemangiomas. Lasers Surg Med. 38 (2):116-123. https://doi.org/10.1002/lsm.20294; PMid:16493677
68. Wu HW, Wang X, Zhang L et al. (2018). Topical timolol vs oral propranolol for the treatment of superficial infantile hemangiomas. Front Oncol. 8: 605. https://doi.org/10.3389/fonc.2018.00605; PMid:30619747 PMCid:PMC6305365
 
       
  
  
  
  
  
 