Infantile Hemangioma Questions & Answers

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2. Bowers RE, Graham EA, Tomlinson KM. The natural history of the strawberry nevus. Arch Dermatol. 1960. 82:667.

3. Jacobs AH. Strawberry hemangiomas; the natural history of the untreated lesion. Calif Med. 1957 Jan. 86(1):8-10. [QxMD MEDLINE Link].

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5. Zhang L, Lin X, Wang W, et al. Circulating level of vascular endothelial growth factor in differentiating hemangioma from vascular malformation patients. Plast Reconstr Surg. 2005 Jul. 116(1):200-4. [QxMD MEDLINE Link].

6. Zhang L, Lin XX, Qi ZL, et al. [Role of urinary basic fibroblast growth factor in differentiating hemangiomas from vascular malformation]. Zhonghua Wai Ke Za Zhi. 2006 Feb 1. 44(3):186-8. [QxMD MEDLINE Link].

7. Dubois J, Patriquin HB, Garel L, et al. Soft-tissue hemangiomas in infants and children: diagnosis using Doppler sonography. AJR Am J Roentgenol. 1998 Jul. 171(1):247-52. [QxMD MEDLINE Link].

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10. Brooks M. For Propranolol in Infantile Hemangioma, Only 'Provisional' Guidelines Available. Medscape Medical News. Dec 24, 2012. Available at http://www.medscape.com/viewarticle/776692. Accessed: January 8, 2013.

11. Drolet BA, Frommelt PC, Chamlin SL, Haggstrom A, et al. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics. 2013 Jan. 131(1):128-40. [QxMD MEDLINE Link].

12. Kim HJ, Colombo M, Frieden IJ. Ulcerated hemangiomas: clinical characteristics and response to therapy. J Am Acad Dermatol. 2001 Jun. 44(6):962-72. [QxMD MEDLINE Link].

13. Garden JM, Bakus AD, Paller AS. Treatment of cutaneous hemangiomas by the flashlamp-pumped pulsed dye laser: prospective analysis. J Pediatr. 1992 Apr. 120(4 Pt 1):555-60. [QxMD MEDLINE Link].

14. Achauer BM, Chang CJ, Vander Kam VM. Management of hemangioma of infancy: review of 245 patients. Plast Reconstr Surg. 1997 Apr. 99(5):1301-8. [QxMD MEDLINE Link].

15. Ritter MR, Reinisch J, Friedlander SF, Friedlander M. Myeloid cells in infantile hemangioma. Am J Pathol. 2006 Feb. 168(2):621-8. [QxMD MEDLINE Link].

16. Bischoff J. Progenitor cells in infantile hemangioma. J Craniofac Surg. 2009 Mar. 20 Suppl 1:695-7. [QxMD MEDLINE Link].

17. Banks RE, Forbes MA, Searles J, et al. Evidence for the existence of a novel pregnancy-associated soluble variant of the vascular endothelial growth factor receptor, Flt-1. Mol Hum Reprod. 1998 Apr. 4(4):377-86. [QxMD MEDLINE Link].

18. Hornig C, Barleon B, Ahmad S, Vuorela P, Ahmed A, Weich HA. Release and complex formation of soluble VEGFR-1 from endothelial cells and biological fluids. Lab Invest. 2000 Apr. 80(4):443-54. [QxMD MEDLINE Link].

19. Bree AF, Siegfried E, Sotelo-Avila C, Nahass G. Infantile hemangiomas: speculation on placental trophoblastic origin. Arch Dermatol. 2001 May. 137(5):573-7. [QxMD MEDLINE Link].

20. Burton BK, Schulz CJ, Angle B, Burd LI. An increased incidence of haemangiomas in infants born following chorionic villus sampling (CVS). Prenat Diagn. 1995 Mar. 15(3):209-14. [QxMD MEDLINE Link].

21. Itinteang T, Chudakova DA, Dunne JC, Davis PF, Tan ST. Expression of Cathepsins B, D, and G in Infantile Hemangioma. Front Surg. 2015 Jun 17. 2:26. [QxMD MEDLINE Link].

22. de Jong S, Itinteang T, Withers AH, Davis PF, Tan ST. Does hypoxia play a role in infantile hemangioma?. Arch Dermatol Res. 2016 May. 308 (4):219-27. [QxMD MEDLINE Link].

23. Kleinman ME, Greives MR, Churgin SS, et al. Hypoxia-induced mediators of stem/progenitor cell trafficking are increased in children with hemangioma. Arterioscler Thromb Vasc Biol. 2007 Dec. 27(12):2664-70. [QxMD MEDLINE Link].

24. Jinnin M, Medici D, Park L, et al. Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma. Nat Med. 2008 Nov. 14(11):1236-46. [QxMD MEDLINE Link]. [Full Text].

25. Khan ZA, Boscolo E, Picard A, et al. Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice. J Clin Invest. 2008 Jul. 118(7):2592-9. [QxMD MEDLINE Link]. [Full Text].

26. Yu Y, Flint AF, Mulliken JB, Wu JK, Bischoff J. Endothelial progenitor cells in infantile hemangioma. Blood. 2004 Feb 15. 103(4):1373-5. [QxMD MEDLINE Link].

27. Amaya CN, Bryan BA. Enrichment of the embryonic stem cell reprogramming factors Oct4, Nanog, Myc, and Sox2 in benign and malignant vascular tumors. BMC Clin Pathol. 2015 Sep 26. 15:18. [QxMD MEDLINE Link].

28. Mulliken JB. Update on vascular anomalies. In: Proceedings of the international workshop on vascular anomalies. June 21-24, 2008.

29. Yu Y, Fuhr J, Boye E, et al. Mesenchymal stem cells and adipogenesis in hemangioma involution. Stem Cells. 2006 Jun. 24(6):1605-12. [QxMD MEDLINE Link].

30. Blei F, Walter J, Orlow SJ, Marchuk DA. Familial segregation of hemangiomas and vascular malformations as an autosomal dominant trait. Arch Dermatol. 1998 Jun. 134(6):718-22. [QxMD MEDLINE Link].

31. Hidano A, Nakajima S. Earliest features of the strawberry mark in the newborn. Br J Dermatol. 1972 Aug. 87(2):138-44. [QxMD MEDLINE Link].

32. Amrock SM, Weitzman M. Diverging racial trends in neonatal infantile hemangioma diagnoses, 1979-2006. Pediatr Dermatol. 2013 Jul-Aug. 30 (4):493-4. [QxMD MEDLINE Link].

33. Amir J, Metzker A, Krikler R, Reisner SH. Strawberry hemangioma in preterm infants. Pediatr Dermatol. 1986 Sep. 3(4):331-2. [QxMD MEDLINE Link].

34. Haggstrom AN, Drolet BA, Baselga E, et al. Prospective study of infantile hemangiomas: demographic, prenatal, and perinatal characteristics. J Pediatr. 2007 Mar. 150(3):291-4. [QxMD MEDLINE Link].

35. Enjolras O, Wassef M, Mazoyer E, et al. Infants with Kasabach-Merritt syndrome do not have "true" hemangiomas. J Pediatr. 1997 Apr. 130(4):631-40. [QxMD MEDLINE Link].

36. Sarkar M, Mulliken JB, Kozakewich HP, Robertson RL, Burrows PE. Thrombocytopenic coagulopathy (Kasabach-Merritt phenomenon) is associated with Kaposiform hemangioendothelioma and not with common infantile hemangioma. Plast Reconstr Surg. 1997 Nov. 100(6):1377-86. [QxMD MEDLINE Link].

37. Thomson HG, Lanigan M. The Cyrano nose: a clinical review of hemangiomas of the nasal tip. Plast Reconstr Surg. 1979 Feb. 63(2):155-60. [QxMD MEDLINE Link].

38. 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 Mar. 132(3):307-11. [QxMD MEDLINE Link].

39. Girard C, Bigorre M, Guillot B, Bessis D. PELVIS Syndrome. Arch Dermatol. 2006 Jul. 142(7):884-8. [QxMD MEDLINE Link].

40. [Guideline] Metry D, Heyer G, Hess C, Garzon M, Haggstrom A, Frommelt P, et al. Consensus Statement on Diagnostic Criteria for PHACE Syndrome. Pediatrics. 2009 Nov. 124(5):1447-56. [QxMD MEDLINE Link].

41. Tanner JL, Dechert MP, Frieden IJ. Growing up with a facial hemangioma: parent and child coping and adaptation. Pediatrics. 1998 Mar. 101(3 Pt 1):446-52. [QxMD MEDLINE Link].

42. Liu LS, Sowa A, Antaya RJ. Educating caregivers about the natural history of infantile hemangiomas. Acta Paediatr. 2015 Jan. 104 (1):9-11. [QxMD MEDLINE Link].

43. Waner M, Suen JY. The natural history of hemangiomas. Hemangiomas and Vascular Malformations of the Head and Neck. 1999. 13-45.

44. Boon LM, Enjolras O, Mulliken JB. Congenital hemangioma: evidence of accelerated involution. J Pediatr. 1996 Mar. 128(3):329-35. [QxMD MEDLINE Link].

45. Finn MC, Glowacki J, Mulliken JB. Congenital vascular lesions: clinical application of a new classification. J Pediatr Surg. 1983 Dec. 18(6):894-900. [QxMD MEDLINE Link].

46. Mulliken JB, Marler JJ, Burrows PE, Kozakewich HP. Reticular infantile hemangioma of the limb can be associated with ventral-caudal anomalies, refractory ulceration, and cardiac overload. Pediatr Dermatol. 2007 Jul-Aug. 24(4):356-62. [QxMD MEDLINE Link].

47. Suh KY, Frieden IJ. Infantile hemangiomas with minimal or arrested growth: a retrospective case series. Arch Dermatol. 2010 Sep. 146(9):971-6. [QxMD MEDLINE Link].

48. Maguiness SM, Hoffman WY, McCalmont TH, Frieden IJ. Early white discoloration of infantile hemangioma: a sign of impending ulceration. Arch Dermatol. 2010 Nov. 146(11):1235-9. [QxMD MEDLINE Link].

49. Connelly EA, Viera M, Price C, Waner M. Segmental hemangioma of infancy complicated by life-threatening arterial bleed. Pediatr Dermatol. 2009 Jul-Aug. 26(4):469-72. [QxMD MEDLINE Link].

50. 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 Jul. 140(7):867-70. [QxMD MEDLINE Link].

51. Kaplan M, Paller AS. Clinical pearl: use of self-adhesive, compressive wraps in the treatment of limb hemangiomas. J Am Acad Dermatol. 1995 Jan. 32(1):117-8. [QxMD MEDLINE Link].

52. Morelli JG, Tan OT, Yohn JJ, Weston WL. Treatment of ulcerated hemangiomas infancy. Arch Pediatr Adolesc Med. 1994 Oct. 148(10):1104-5. [QxMD MEDLINE Link].

53. Orlow SJ, Isakoff MS, Blei F. Increased risk of symptomatic hemangiomas of the airway in association with cutaneous hemangiomas in a "beard" distribution. J Pediatr. 1997 Oct. 131(4):643-6. [QxMD MEDLINE Link].

54. Ceisler EJ, Santos L, Blei F. Periocular hemangiomas: what every physician should know. Pediatr Dermatol. 2004 Jan-Feb. 21(1):1-9. [QxMD MEDLINE Link].

55. Esterly NB. Kasabach-Merritt syndrome in infants. J Am Acad Dermatol. 1983 Apr. 8(4):504-13. [QxMD MEDLINE Link].

56. Ersoy S, Mancini AJ. Hemifacial infantile hemangioma with intracranial extension: a rare entity. Pediatr Dermatol. 2005 Jul-Aug. 22(4):309-13. [QxMD MEDLINE Link].

57. Huang SA, Tu HM, Harney JW, et al. Severe hypothyroidism caused by type 3 iodothyronine deiodinase in infantile hemangiomas. N Engl J Med. 2000 Jul 20. 343(3):185-9. [QxMD MEDLINE Link].

58. Konrad D, Ellis G, Perlman K. Spontaneous regression of severe acquired infantile hypothyroidism associated with multiple liver hemangiomas. Pediatrics. 2003 Dec. 112(6 Pt 1):1424-6. [QxMD MEDLINE Link].

59. Ho J, Kendrick V, Dewey D, Pacaud D. New insight into the pathophysiology of severe hypothyroidism in an infant with multiple hepatic hemangiomas. J Pediatr Endocrinol Metab. 2005 May. 18(5):511-4. [QxMD MEDLINE Link].

60. North PE, Waner M, Mizeracki A, et al. A unique microvascular phenotype shared by juvenile hemangiomas and human placenta. Arch Dermatol. 2001 May. 137(5):559-70. [QxMD MEDLINE Link].

61. Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg. 1982 Mar. 69(3):412-22. [QxMD MEDLINE Link].

62. Nakayama H. Clinical and histological studies of the classification and the natural course of the strawberry mark. J Dermatol. 1981 Aug. 8(4):277-91. [QxMD MEDLINE Link].

63. Frieden IJ, Eichenfield LF, Esterly NB, Geronemus R, Mallory SB. Guidelines of care for hemangiomas of infancy. American Academy of Dermatology Guidelines/Outcomes Committee. J Am Acad Dermatol. 1997 Oct. 37(4):631-7. [QxMD MEDLINE Link].

64. Price CJ, Lattouf C, Baum B, McLeod M, Schachner LA, Duarte AM, et al. Propranolol vs Corticosteroids for Infantile Hemangiomas: A Multicenter Retrospective Analysis. Arch Dermatol. 2011 Dec. 147(12):1371-6. [QxMD MEDLINE Link].

65. 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 Jun 12. 358(24):2649-51. [QxMD MEDLINE Link].

66. Siegfried EC, Keenan WJ, Al-Jureidini S. More on propranolol for hemangiomas of infancy. N Engl J Med. 2008 Dec 25. 359(26):2846; author reply 2846-7. [QxMD MEDLINE Link].

67. Saint-Jean M, Leaute-Labreze C, Mazereeuw-Hautier J, et al. Propranolol for treatment of ulcerated infantile hemangiomas. J Am Acad Dermatol. 2011 May. 64(5):827-32. [QxMD MEDLINE Link].

68. Hermans DJ, van Beynum IM, Schultze Kool LJ, van de Kerkhof PC, Wijnen MH, van der Vleuten CJ. Propranolol, a very promising treatment for ulceration in infantile hemangiomas: A study of 20 cases with matched historical controls. J Am Acad Dermatol. 2011 May. 64(5):833-8. [QxMD MEDLINE Link].

69. Léauté-Labrèze C, Voisard JJ, Moore N. Oral Propranolol for Infantile Hemangioma. N Engl J Med. 2015 Jul 16. 373 (3):284-5. [QxMD MEDLINE Link].

70. Poetke M, Philipp C, Berlien HP. Flashlamp-pumped pulsed dye laser for hemangiomas in infancy: treatment of superficial vs mixed hemangiomas. Arch Dermatol. 2000 May. 136(5):628-32. [QxMD MEDLINE Link].

71. 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 Jun. 56(4):317-27. [QxMD MEDLINE Link].

72. Chinnadurai S, Sathe NA, Surawicz T. Laser treatment of infantile hemangioma: A systematic review. Lasers Surg Med. 2016 Mar. 48 (3):221-33. [QxMD MEDLINE Link].

73. Sie KC, McGill T, Healy GB. Subglottic hemangioma: ten years' experience with the carbon dioxide laser. Ann Otol Rhinol Laryngol. 1994 Mar. 103(3):167-72. [QxMD MEDLINE Link].

74. Burstein FD, Simms C, Cohen SR, Williams JK, Paschal M. Intralesional laser therapy of extensive hemangiomas in 100 consecutive pediatric patients. Ann Plast Surg. 2000 Feb. 44(2):188-94. [QxMD MEDLINE Link].

75. Laubach HJ, Anderson RR, Luger T, Manstein D. Fractional photothermolysis for involuted infantile hemangioma. Arch Dermatol. 2009 Jul. 145(7):748-50. [QxMD MEDLINE Link].

76. Coulie J, Coyette M, Moniotte S, Bataille AC, Boon LM. Has Propranolol Eradicated the Need for Surgery in the Management of Infantile Hemangioma?. Plast Reconstr Surg. 2015 Oct. 136 (4 Suppl):154. [QxMD MEDLINE Link].

77. [Guideline] Krowchuk DP, Frieden IJ, Mancini AJ, Darrow DH, Blei F, Greene AK, et al. Clinical Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics. 2019 Jan. 143 (1):[QxMD MEDLINE Link].

78. Phillips D. AAP Guideline Urges Prompt Care for Infantile Hemangiomas. Medscape Medical News. Available at https://www.medscape.com/viewarticle/906955. December 24, 2018; Accessed: February 6, 2019.

79. Hemangeol [package insert]. Parsippany, NJ.: Pierre Fabre Pharmaceuticals, Inc. 2014.

80. Pope E, Chakkittakandiyil A. Topical timolol gel for infantile hemangiomas: a pilot study. Arch Dermatol. 2010 May. 146(5):564-5. [QxMD MEDLINE Link].

81. Khunger N, Pahwa M. Dramatic response to topical timolol lotion of a large hemifacial infantile haemangioma associated with PHACE syndrome. Br J Dermatol. 2011 Apr. 164(4):886-8. [QxMD MEDLINE Link].

82. Bigorre M, Van Kien AK, Valette H. Beta-blocking agent for treatment of infantile hemangioma. Plast Reconstr Surg. 2009 Jun. 123(6):195e-6e. [QxMD MEDLINE Link].

83. Truong MT, Chang KW, Berk DR, Heerema-McKenney A, Bruckner AL. Propranolol for the treatment of a life-threatening subglottic and mediastinal infantile hemangioma. J Pediatr. 2010 Feb. 156(2):335-8. [QxMD MEDLINE Link].

84. Perkins JA, Chen BS, Saltzman B, Manning SC, Parikh SR. Propranolol Therapy for Reducing the Number of Nasal Infantile Hemangioma Invasive Procedures. JAMA Otolaryngol Head Neck Surg. 2014 Feb 20. [QxMD MEDLINE Link].

85. Harding A. Propranolol Associated With Reduced Need for Invasive Hemangioma Treatment. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/821133. Accessed: March 3, 2014.

86. Sommers Smith SK, Smith DM. Beta blockade induces apoptosis in cultured capillary endothelial cells. In Vitro Cell Dev Biol Anim. 2002 May. 38(5):298-304. [QxMD MEDLINE Link].

87. 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. 2016 Sep 3. [QxMD MEDLINE Link].

88. 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 Mar 18. 362(11):1005-13. [QxMD MEDLINE Link].

89. Sadan N, Wolach B. Treatment of hemangiomas of infants with high doses of prednisone. J Pediatr. 1996 Jan. 128(1):141-6. [QxMD MEDLINE Link].

90. Tamayo L, Ortiz DM, Orozco-Covarrubias L, et al. Therapeutic efficacy of interferon alfa-2b in infants with life-threatening giant hemangiomas. Arch Dermatol. 1997 Dec. 133(12):1567-71. [QxMD MEDLINE Link].

91. Ricketts RR, Hatley RM, Corden BJ, Sabio H, Howell CG. Interferon-alpha-2a for the treatment of complex hemangiomas of infancy and childhood. Ann Surg. 1994 Jun. 219(6):605-12; discussion 612-4. [QxMD MEDLINE Link].

92. Barlow CF, Priebe CJ, Mulliken JB, et al. Spastic diplegia as a complication of interferon Alfa-2a treatment of hemangiomas of infancy. J Pediatr. 1998 Mar. 132(3 Pt 1):527-30. [QxMD MEDLINE Link].

93. Dubois J, Hershon L, Carmant L, Belanger S, Leclerc JM, David M. Toxicity profile of interferon alfa-2b in children: A prospective evaluation. J Pediatr. 1999 Dec. 135(6):782-5. [QxMD MEDLINE Link].

94. Michaud AP, Bauman NM, Burke DK, Manaligod JM, Smith RJ. Spastic diplegia and other motor disturbances in infants receiving interferon-alpha. Laryngoscope. 2004 Jul. 114(7):1231-6. [QxMD MEDLINE Link].

95. Welsh O, Olazaran Z, Gomez M, Salas J, Berman B. Treatment of infantile hemangiomas with short-term application of imiquimod 5% cream. J Am Acad Dermatol. 2004 Oct. 51(4):639-42. [QxMD MEDLINE Link].

96. Hazen PG, Carney JF, Engstrom CW, Turgeon KL, Reep MD, Tanphaichitr A. Proliferating hemangioma of infancy: successful treatment with topical 5% imiquimod cream. Pediatr Dermatol. 2005 May-Jun. 22(3):254-6. [QxMD MEDLINE Link].

97. McCuaig CC, Dubois J, Powell J, Belleville C, David M, Rousseau E. 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 Mar-Apr. 26(2):203-12. [QxMD MEDLINE Link].

Richard J Antaya, MD Director of Pediatric Dermatology, Professor, Departments of Dermatology and Pediatrics, Yale University School of Medicine

Richard J Antaya, MD is a member of the following medical societies: American Academy of Dermatology, American Academy of Pediatrics, Society for Pediatric Dermatology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Pierre-Fabre Pharmaceuticals.

Michael J Wells, MD, FAAD Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Van Perry, MD Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Jean Paul Ortonne, MD Chair, Department of Dermatology, Professor, Hospital L'Archet, Nice University, France

Jean Paul Ortonne, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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