J Korean Med Assoc.  2016 Sep;59(9):698-704. 10.5124/jkma.2016.59.9.698.

Update on recent research into infantile hemangioma

Affiliations
  • 1Department of Pediatrics, Chungbuk National University College of Medicine, Cheongju, Korea. ming2a@hanmail.net

Abstract

Infantile hemangioma (IH) is the most common type of benign tumor during infancy. Due to their propensity to spontaneously involute, most IHs can be left untreated. However, IHs located in particular anatomic areas and those with complications need rapid and active treatment. It is often challenging for clinicians to predict which IHs are in need of systemic treatment. Data from various studies have revealed further insights into IH. The treatment options include propranolol, steroids, interferon-α, vincristine, surgical excision, and laser therapy. More infants are now treated with propranolol than were previously treated with oral corticosteroids, and the full implications of this shift in practice are not yet clear. This paper summarizes the pathogenesis, clinical course and current recommendations for management of IHs.

Keyword

Infantile hemangioma; Propranolol; Clinical course; Management

MeSH Terms

Adrenal Cortex Hormones
Hemangioma*
Humans
Infant
Laser Therapy
Propranolol
Steroids
Vincristine
Adrenal Cortex Hormones
Propranolol
Steroids
Vincristine

Figure

  • Figure 1 (A) Superficial, (B) mixed, and (C) deep hemangioma.

  • Figure 2 Hemangioma complicated with ulceration (A) pretreament, (B) after 1 month of propranolol treatment, and (C) after 12 month of propranolol treatment.


Cited by  1 articles

Recent advances in pediatric hemato-oncologic disease
Hoi Soo Yoon
J Korean Med Assoc. 2016;59(9):676-677.    doi: 10.5124/jkma.2016.59.9.676.


Reference

1. Dickison P, Christou E, Wargon O. A prospective study of infantile hemangiomas with a focus on incidence and risk factors. Pediatr Dermatol. 2011; 28:663–669.
Article
2. Luu M, Frieden IJ. Haemangioma: clinical course, complications and management. Br J Dermatol. 2013; 169:20–30.
Article
3. Munden A, Butschek R, Tom WL, Marshall JS, Poeltler DM, Krohne SE, Alio AB, Ritter M, Friedlander DF, Catanzarite V, Mendoza A, Smith L, Friedlander M, Friedlander SF. Prospective study of infantile haemangiomas: incidence, clinical characteristics and association with placental anomalies. Br J Dermatol. 2014; 170:907–913.
Article
4. Drolet BA, Swanson EA, Frieden IJ. Hemangioma Investigator Group. Infantile hemangiomas: an emerging health issue linked to an increased rate of low birth weight infants. J Pediatr. 2008; 153:712–715.
Article
5. Hemangioma Investigator Group. Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, Horii KA, Lucky AW, Mancini AJ, Metry DW, Newell B, Nopper AJ, Frieden IJ. Prospective study of infantile hemangiomas: demographic, prenatal, and perinatal characteristics. J Pediatr. 2007; 150:291–294.
Article
6. Tan ST, Itinteang T, Leadbitter P. Low-dose propranolol for infantile haemangioma. J Plast Reconstr Aesthet Surg. 2011; 64:292–299.
Article
7. Puttgen KB. Diagnosis and management of infantile hemangiomas. Pediatr Clin North Am. 2014; 61:383–402.
Article
8. North PE, Waner M, Mizeracki A, Mihm MC Jr. GLUT1: a newly discovered immunohistochemical marker for juvenile hemangiomas. Hum Pathol. 2000; 31:11–22.
Article
9. Barnes CM, Huang S, Kaipainen A, Sanoudou D, Chen EJ, Eichler GS, Guo Y, Yu Y, Ingber DE, Mulliken JB, Beggs AH, Folkman J, Fishman SJ. Evidence by molecular profiling for a placental origin of infantile hemangioma. Proc Natl Acad Sci U S A. 2005; 102:19097–19102.
Article
10. Kleinman ME, Greives MR, Churgin SS, Blechman KM, Chang EI, Ceradini DJ, Tepper OM, Gurtner GC. Hypoxia-induced mediators of stem/progenitor cell trafficking are increased in children with hemangioma. Arterioscler Thromb Vasc Biol. 2007; 27:2664–2670.
Article
11. Dadras SS, North PE, Bertoncini J, Mihm MC, Detmar M. Infantile hemangiomas are arrested in an early developmental vascular differentiation state. Mod Pathol. 2004; 17:1068–1079.
Article
12. Yu Y, Flint AF, Mulliken JB, Wu JK, Bischoff J. Endothelial progenitor cells in infantile hemangioma. Blood. 2004; 103:1373–1375.
Article
13. Drolet BA, Frieden IJ. Characteristics of infantile hemangiomas as clues to pathogenesis: does hypoxia connect the dots? Arch Dermatol. 2010; 146:1295–1299.
14. 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; 82:77–83.
Article
15. Grimmer JF, Williams MS, Pimentel R, Mineau G, Wood GM, Bayrak-Toydemir P, Stevenson DA. Familial clustering of hemangiomas. Arch Otolaryngol Head Neck Surg. 2011; 137:757–760.
Article
16. Itinteang T, Brasch HD, Tan ST, Day DJ. Expression of components of the renin-angiotensin system in proliferating infantile haemangioma may account for the propranololinduced accelerated involution. J Plast Reconstr Aesthet Surg. 2011; 64:759–765.
Article
17. Youmbissi TJ, Tedong F, Fairbank ST, Blackett-Ngu K, Mbede J. Plasma renin activity studies in a group of African neonates and children. J Trop Pediatr. 1990; 36:128–130.
Article
18. Tollefson MM, Frieden IJ. Early growth of infantile hemangiomas: what parentsXMLLink_XYZ photographs tell us. Pediatrics. 2012; 130:e314–e320.
19. Chang LC, Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, Horii KA, Lucky AW, Mancini AJ, Metry DW, Nopper AJ, Frieden IJ;. Growth characteristics of infantile hemangiomas: implications for management. Pediatrics. 2008; 122:360–367.
Article
20. Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, Horii KA, Lucky AW, Mancini AJ, Metry DW, Newell B, Nopper AJ, Frieden IJ. Prospective study of infantile hemangiomas: clinical characteristics predicting complications and treatment. Pediatrics. 2006; 118:882–887.
Article
21. Chamlin SL, Haggstrom AN, Drolet BA, Baselga E, Frieden IJ, Garzon MC, Horii KA, Lucky AW, Metry DW, Newell B, Nopper AJ, Mancini AJ. Multicenter prospective study of ulcerated hemangiomas. J Pediatr. 2007; 151:684–689.
Article
22. Maguiness SM, Hoffman WY, McCalmont TH, Frieden IJ. Early white discoloration of infantile hemangioma: a sign of impending ulceration. Arch Dermatol. 2010; 146:1235–1239.
23. Lopriore E, Markhorst DG. Diffuse neonatal haemangiomatosis: new views on diagnostic criteria and prognosis. Acta Paediatr. 1999; 88:93–97.
Article
24. Boon LM, Burrows PE, Paltiel HJ, Lund DP, Ezekowitz RA, Folkman J, Mulliken JB. Hepatic vascular anomalies in infancy: a twenty-seven-year experience. J Pediatr. 1996; 129:346–354.
Article
25. Horii KA, Drolet BA, Baselga E, Frieden IJ, Metry DW, Morel KD, Newell BD, Nopper AJ, Garzon MC;. Risk of hepatic hemangiomas in infants with large hemangiomas. Arch Dermatol. 2010; 146:201–203.
Article
26. Frieden IJ, Reese V, Cohen D. PHACE syndrome. The association of posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities. Arch Dermatol. 1996; 132:307–311.
Article
27. Drolet BA, Chamlin SL, Garzon MC, Adams D, Baselga E, Haggstrom AN, Holland KE, Horii KA, Juern A, Lucky AW, Mancini AJ, McCuaig C, Metry DW, Morel KD, Newell BD, Nopper AJ, Powell J, Frieden IJ. Prospective study of spinal anomalies in children with infantile hemangiomas of the lumbosacral skin. J Pediatr. 2010; 157:789–794.
Article
28. Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taieb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008; 358:2649–2651.
Article
29. Chung SH, Park DH, Jung HL, Shim JW, Kim DS, Shim JY, Park MS, Koo HH. Successful and safe treatment of hemangioma with oral propranolol in a single institution. Korean J Pediatr. 2012; 55:164–170.
Article
30. 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; 58:484–490.
Article
31. Nguyen J, Fay A. Pharmacologic therapy for periocular infantile hemangiomas: a review of the literature. Semin Ophthalmol. 2009; 24:178–184.
Article
32. Leaute-Labreze C, Taieb A. Efficacy of beta-blockers in infantile capillary haemangiomas: the physiopathological significance and therapeutic consequences. Ann Dermatol Venereol. 2008; 135:860–862.
33. Annabi B, Lachambre MP, Plouffe K, Moumdjian R, Beliveau R. Propranolol adrenergic blockade inhibits human brain endothelial cells tubulogenesis and matrix metalloproteinase-9 secretion. Pharmacol Res. 2009; 60:438–445.
Article
34. Bagazgoitia L, Hernandez-Martin A, Torrelo A. Recurrence of infantile hemangiomas treated with propranolol. Pediatr Dermatol. 2011; 28:658–662.
Article
35. Guo S, Ni N. Topical treatment for capillary hemangioma of the eyelid using beta-blocker solution. Arch Ophthalmol. 2010; 128:255–256.
Article
36. Ni N, Langer P, Wagner R, Guo S. Topical timolol for periocular hemangioma: report of further study. Arch Ophthalmol. 2011; 129:377–379.
Article
37. Chakkittakandiyil A, Phillips R, Frieden IJ, Siegfried E, Lara-Corrales I, Lam J, Bergmann J, Bekhor P, Poorsattar S, Pope E. Timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas: a retrospective, multicenter, cohort study. Pediatr Dermatol. 2012; 29:28–31.
Article
38. Zarem HA, Edgerton MT. Induced resolution of cavernous hemangiomas following prednisolone therapy. Plast Reconstr Surg. 1967; 39:76–83.
Article
39. Khan ZA, Boscolo E, Picard A, Psutka S, Melero-Martin JM, Bartch TC, Mulliken JB, Bischoff J. Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice. J Clin Invest. 2008; 118:2592–2599.
Article
40. Greenberger S, Boscolo E, Adini I, Mulliken JB, Bischoff J. Corticosteroid suppression of VEGF-A in infantile hemangioma-derived stem cells. N Engl J Med. 2010; 362:1005–1013.
Article
41. Enjolras O, Riche MC, Merland JJ, Escande JP. Management of alarming hemangiomas in infancy: a review of 25 cases. Pediatrics. 1990; 85:491–498.
Article
42. Dinehart SM, Kincannon J, Geronemus R. Hemangiomas: evaluation and treatment. Dermatol Surg. 2001; 27:475–485.
Article
43. Boon LM, MacDonald DM, Mulliken JB. Complications of systemic corticosteroid therapy for problematic hemangioma. Plast Reconstr Surg. 1999; 104:1616–1623.
Article
44. Lomenick JP, Backeljauw PF, Lucky AW. Growth, bone mineral accretion, and adrenal function in glucocorticoid-treated infants with hemangiomas: a retrospective study. Pediatr Dermatol. 2006; 23:169–174.
Article
45. Chowdri NA, Darzi MA, Fazili Z, Iqbal S. Intralesional corticosteroid therapy for childhood cutaneous hemangiomas. Ann Plast Surg. 1994; 33:46–51.
Article
46. Sutula FC, Glover AT. Eyelid necrosis following intralesional corticosteroid injection for capillary hemangioma. Ophthalmic Surg. 1987; 18:103–105.
Article
47. Kwon EK, Seefeldt M, Drolet BA. Infantile hemangiomas: an update. Am J Clin Dermatol. 2013; 14:111–123.
48. Schirner M, Hoffmann J, Menrad A, Schneider MR. Antiangiogenic chemotherapeutic agents: characterization in comparison to their tumor growth inhibition in human renal cell carcinoma models. Clin Cancer Res. 1998; 4:1331–1336.
49. Kung AL, Zetterberg A, Sherwood SW, Schimke RT. Cytotoxic effects of cell cycle phase specific agents: result of cell cycle perturbation. Cancer Res. 1990; 50:7307–7317.
50. Barlow CF, Priebe CJ, Mulliken JB, Barnes PD, Mac Donald D, Folkman J, Ezekowitz RA. Spastic diplegia as a complication of interferon Alfa-2a treatment of hemangiomas of infancy. J Pediatr. 1998; 132:527–530.
Article
51. Jimenez-Hernandez E, Duenas-Gonzalez MT, Quintero-Curiel JL, Velasquez-Ortega J, Magana-Perez JA, Berges-Garcia A, Arellano-Galindo J. Treatment with interferon-alpha-2b in children with life-threatening hemangiomas. Dermatol Surg. 2008; 34:640–647.
Article
52. Heyns AD, Eldor A, Vlodavsky I, Kaiser N, Fridman R, Panet A. The antiproliferative effect of interferon and the mitogenic activity of growth factors are independent cell cycle events. Studies with vascular smooth muscle cells and endothelial cells. Exp Cell Res. 1985; 161:297–306.
Article
53. Stier MF, Glick SA, Hirsch RJ. Laser treatment of pediatric vascular lesions: port wine stains and hemangiomas. J Am Acad Dermatol. 2008; 58:261–285.
Article
54. David LR, Malek MM, Argenta LC. Efficacy of pulse dye laser therapy for the treatment of ulcerated haemangiomas: a review of 78 patients. Br J Plast Surg. 2003; 56:317–327.
Article
55. Witman PM, Wagner AM, Scherer K, Waner M, Frieden IJ. Complications following pulsed dye laser treatment of superficial hemangiomas. Lasers Surg Med. 2006; 38:116–123.
Article
56. McHeik JN, Renauld V, Duport G, Vergnes P, Levard G. Surgical treatment of haemangioma in infants. Br J Plast Surg. 2005; 58:1067–1072.
Article
Full Text Links
  • JKMA
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr