Infantile Hemangioma Guidelines: Guidelines Summary

Sections

Guidelines

Guidelines Summary

Guidelines on the management of infantile hemangioma were released in December 2018 by the American Academy of Pediatrics.^{[77, 78]}

Five indications for early treatment of problematic infantile hemangiomas include the following:

Life-threatening lesions, such as those that obstruct the airway, those that are associated with high-output congestive heart failure, or those that are ulcerative and profusely bleed
Infantile hemangiomas associated with functional impairment, such as a disturbance in vision or feeding interference
Infantile hemangioma ulceration
Infantile hemangioma–associated congenital anomalies such as PHACE (posterior fossa abnormalities, hemangioma, arterial lesions, cardiac abnormalities/aortic coarctation, and eye abnormalities) syndrome
Risk of permanent scarring

Consult with a hemangioma specialist by age 1 month for infants that are high risk.

Infantile hemangioma growth occurs most rapidly from age 1-3 months.

Imaging is not necessary unless the diagnosis is uncertain, there are five or more cutaneous infantile hemangiomas present, or there is suspicion of anatomic abnormalities.

Oral propranolol (2-3 mg/kg/dose) is the recommended first-line treatment for cases requiring systemic therapy.

Counsel about the adverse events of propranolol, such as sleep disturbances, bronchial irritation, and clinically symptomatic bradycardia and hypotension.

Use oral prednisolone or prednisone if there are contraindications or if the propranolol response is inadequate.

Intralesional injection of triamcinolone and/or betamethasone can be recommended to treat focal or bulky infantile hemangiomas in certain critical locations (eg, the lip) or during proliferation.

Topical timolol maleate may be prescribed for thin or superficial infantile hemangiomas.

Surgery and laser therapy may be recommended for certain situations such as ulcerated lesions or lesions that obstruct vital structures.

Caregivers should be educated about infantile hemangioma, the natural history of tumors, and the potential for complications or scarring.

Medication

Lister WA. The natural history of strawberry naevi. Lancet. 1938. 1:1429.
Bowers RE, Graham EA, Tomlinson KM. The natural history of the strawberry nevus. Arch Dermatol. 1960. 82:667.
Jacobs AH. Strawberry hemangiomas; the natural history of the untreated lesion. Calif Med. 1957 Jan. 86(1):8-10. [Medline].
Pratt AG. Birthmarks in infants. AMA Arch Derm Syphilol. 1953 Mar. 67(3):302-5. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
Margileth AM, Museles M. Cutaneous hemangiomas in children. Diagnosis and conservative management. JAMA. 1965 Nov 1. 194(5):523-6. [Medline].
Takahashi K, Mulliken JB, Kozakewich HP, Rogers RA, Folkman J, Ezekowitz RA. Cellular markers that distinguish the phases of hemangioma during infancy and childhood. J Clin Invest. 1994 Jun. 93(6):2357-64. [Medline]. [Full Text].
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.
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. [Medline].
Kim HJ, Colombo M, Frieden IJ. Ulcerated hemangiomas: clinical characteristics and response to therapy. J Am Acad Dermatol. 2001 Jun. 44(6):962-72. [Medline].
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. [Medline].
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. [Medline].
Ritter MR, Reinisch J, Friedlander SF, Friedlander M. Myeloid cells in infantile hemangioma. Am J Pathol. 2006 Feb. 168(2):621-8. [Medline].
Bischoff J. Progenitor cells in infantile hemangioma. J Craniofac Surg. 2009 Mar. 20 Suppl 1:695-7. [Medline].
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. [Medline].
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. [Medline].
Bree AF, Siegfried E, Sotelo-Avila C, Nahass G. Infantile hemangiomas: speculation on placental trophoblastic origin. Arch Dermatol. 2001 May. 137(5):573-7. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline]. [Full Text].
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. [Medline]. [Full Text].
Yu Y, Flint AF, Mulliken JB, Wu JK, Bischoff J. Endothelial progenitor cells in infantile hemangioma. Blood. 2004 Feb 15. 103(4):1373-5. [Medline].
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. [Medline].
Mulliken JB. Update on vascular anomalies. In: Proceedings of the international workshop on vascular anomalies. June 21-24, 2008.
Yu Y, Fuhr J, Boye E, et al. Mesenchymal stem cells and adipogenesis in hemangioma involution. Stem Cells. 2006 Jun. 24(6):1605-12. [Medline].
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. [Medline].
Hidano A, Nakajima S. Earliest features of the strawberry mark in the newborn. Br J Dermatol. 1972 Aug. 87(2):138-44. [Medline].
Amrock SM, Weitzman M. Diverging racial trends in neonatal infantile hemangioma diagnoses, 1979-2006. Pediatr Dermatol. 2013 Jul-Aug. 30 (4):493-4. [Medline].
Amir J, Metzker A, Krikler R, Reisner SH. Strawberry hemangioma in preterm infants. Pediatr Dermatol. 1986 Sep. 3(4):331-2. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
Girard C, Bigorre M, Guillot B, Bessis D. PELVIS Syndrome. Arch Dermatol. 2006 Jul. 142(7):884-8. [Medline].
[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. [Medline].
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. [Medline].
Liu LS, Sowa A, Antaya RJ. Educating caregivers about the natural history of infantile hemangiomas. Acta Paediatr. 2015 Jan. 104 (1):9-11. [Medline].
Waner M, Suen JY. The natural history of hemangiomas. Hemangiomas and Vascular Malformations of the Head and Neck. 1999. 13-45.
Boon LM, Enjolras O, Mulliken JB. Congenital hemangioma: evidence of accelerated involution. J Pediatr. 1996 Mar. 128(3):329-35. [Medline].
Finn MC, Glowacki J, Mulliken JB. Congenital vascular lesions: clinical application of a new classification. J Pediatr Surg. 1983 Dec. 18(6):894-900. [Medline].
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. [Medline].
Suh KY, Frieden IJ. Infantile hemangiomas with minimal or arrested growth: a retrospective case series. Arch Dermatol. 2010 Sep. 146(9):971-6. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
Morelli JG, Tan OT, Yohn JJ, Weston WL. Treatment of ulcerated hemangiomas infancy. Arch Pediatr Adolesc Med. 1994 Oct. 148(10):1104-5. [Medline].
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. [Medline].
Ceisler EJ, Santos L, Blei F. Periocular hemangiomas: what every physician should know. Pediatr Dermatol. 2004 Jan-Feb. 21(1):1-9. [Medline].
Esterly NB. Kasabach-Merritt syndrome in infants. J Am Acad Dermatol. 1983 Apr. 8(4):504-13. [Medline].
Ersoy S, Mancini AJ. Hemifacial infantile hemangioma with intracranial extension: a rare entity. Pediatr Dermatol. 2005 Jul-Aug. 22(4):309-13. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
Léauté-Labrèze C, Voisard JJ, Moore N. Oral Propranolol for Infantile Hemangioma. N Engl J Med. 2015 Jul 16. 373 (3):284-5. [Medline].
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. [Medline].
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. [Medline].
Chinnadurai S, Sathe NA, Surawicz T. Laser treatment of infantile hemangioma: A systematic review. Lasers Surg Med. 2016 Mar. 48 (3):221-33. [Medline].
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. [Medline].
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. [Medline].
Laubach HJ, Anderson RR, Luger T, Manstein D. Fractional photothermolysis for involuted infantile hemangioma. Arch Dermatol. 2009 Jul. 145(7):748-50. [Medline].
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. [Medline].
[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):[Medline].
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.
Hemangeol [package insert]. Parsippany, NJ.: Pierre Fabre Pharmaceuticals, Inc. 2014.
Pope E, Chakkittakandiyil A. Topical timolol gel for infantile hemangiomas: a pilot study. Arch Dermatol. 2010 May. 146(5):564-5. [Medline].
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. [Medline].
Bigorre M, Van Kien AK, Valette H. Beta-blocking agent for treatment of infantile hemangioma. Plast Reconstr Surg. 2009 Jun. 123(6):195e-6e. [Medline].
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. [Medline].
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. [Medline].
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.
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. [Medline].
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. [Medline].
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. [Medline].
Sadan N, Wolach B. Treatment of hemangiomas of infants with high doses of prednisone. J Pediatr. 1996 Jan. 128(1):141-6. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].

Media Gallery

Histopathology of a proliferating infantile hemangioma with plump endothelial cells in the dermis.
This proliferating superficial infantile hemangioma on the trunk required no therapy.
Exquisitely painful ulcerated mixed hemangioma (superficial and deep) of the left deltoid in a 6-month-old female infant. This lesion was treated successfully with pulsed dye laser.
This superficial and deep infantile hemangioma resulted in astigmatism of the left eye, requiring spectacles to correct the refractive error and to prevent amblyopia. Further growth of this hemangioma necessitated a course of oral prednisolone. The hemangioma shrunk rapidly, and the patient's astigmatism decreased such that the spectacles were unnecessary 1 month after beginning steroids.
Segmental infantile hemangioma in a female infant with PHACE syndrome involving the posterior neck and right forehead associated with an absent right vertebral artery and a laryngeal hemangioma.
Segmental infantile hemangioma with minimal or arrested growth of the bilateral buttocks and posterior thigh in this male infant with PELVIS syndrome (complicated by cutaneous ulceration, hypospadias, anal stenosis, intraspinal lipoma with tethered cord). The white material is a barrier diaper cream.
Superficial proliferating infantile hemangioma on the lower extremity

of 7

Infantile Hemangioma Guidelines

Guidelines Summary

About

Membership

Apps

WebMD Network

Editions

What to Read Next on Medscape

Infantile Hemangioma Guidelines

Guidelines Summary

References

Tables

Contributor Information and Disclosures

What would you like to print?

Find Us On

About

Membership

Apps

WebMD Network

Editions

What to Read Next on Medscape

Related Conditions and Diseases

Medscape Consult

News & Perspective

Tools

Slideshow

Most Popular Articles

Recommended