Infantile hemangiomas: An update on pathogenesis and therapy

Pediatrics

Volumn 131, Issue 1, 2013, Pages 99-108

  Chen, Tina S ^a   Eichenfield, Lawrence F ^a   Friedlander, Sheila Fallon ^a  

^a RADY CHILDREN'S HOSPITAL   (United States)

Author keywords

Hemangioma

Indexed keywords

BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CORTICOSTEROID; GLUCOSE TRANSPORTER 1; INTERFERON; PREDNISONE; PROPRANOLOL; RAPAMYCIN; TIMOLOL; VASCULOTROPIN A; VASCULOTROPIN C; VINCRISTINE;

BRONCHUS HYPERREACTIVITY; CAPILLARY HEMANGIOMA; CARDIOMYOPATHY; CAUSAL ATTRIBUTION; CELL PROLIFERATION; CEREBRAL PALSY; COLD EXTREMITY; COLD INJURY; CONSTIPATION; DEEP TENDON REFLEX LOSS; DISEASE CLASSIFICATION; DISEASE MARKER; DRUG EFFICACY; DRUG INDUCED DISEASE; DRUG MECHANISM; ENDOTHELIAL PROGENITOR CELL; FLU LIKE SYNDROME; GROWTH INHIBITION; HEMATOLOGIC DISEASE; HISTOCHEMISTRY; HUMAN; HYPERTENSION; HYPOGLYCEMIA; HYPOTENSION; HYPOXIA; INCREASED APPETITE; LOW LEVEL LASER THERAPY; NEUROTOXICITY; NEUTROPENIA; PATHOGENESIS; PRIORITY JOURNAL; REFLEX DISORDER; RESTLESSNESS; REVIEW; SEIZURE; SIDE EFFECT; SKIN ATROPHY; SKIN MANIFESTATION; SLEEP DISORDER; SOMATIC MUTATION; STOMACH IRRITATION; TELANGIECTASIA; TRANSAMMONITIS; TREATMENT DURATION; TREATMENT INDICATION; TREATMENT RESPONSE;

DISEASE MANAGEMENT; HEMANGIOMA; HUMANS; INFANT; INFANT, NEWBORN; VASCULAR NEOPLASMS;

EID: 84872834278     PISSN: 00314005     EISSN: 10984275     Source Type: Journal    
DOI: 10.1542/peds.2012-1128     Document Type: Review

References (70)

1. Kilcline C, Frieden IJ. Infantile hemangiomas: How common are they? A systematic review of the medical literature. Pediatr Dermatol. 2008;25(2):168-173
2. Dickison P, Christou E, Wargon O. A prospective study of infantile hemangiomas with a focus on incidence and risk factors. Pediatr Dermatol. 2011;28(6):663-669
3. 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):240-245
4. North PE, Waner M, Mizeracki A, Mihm MC Jr. GLUT1: A newly discovered immunohistochemical marker for juvenile hemangiomas. Hum Pathol. 2000;31(1):11-22
5. Mihm MC Jr, Nelson JS. Hypothesis: The metastatic niche theory can elucidate infantile hemangioma development. J Cutan Pathol. 2010;37(suppl 1):83-87
6. Walter JW, North PE, Waner M, et al. Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma. Genes Chromosomes Cancer. 2002;33(3):295-303
7. Kleinman ME, Tepper OM, Capla JM, et al. Increased circulating AC133+ CD34+ endothelial progenitor cells in children with hemangioma. Lymphat Res Biol. 2003;1(4): 301-307
8. Yu Y, Flint AF, Mulliken JB, Wu JK, Bischoff J. Endothelial progenitor cells in infantile hemangioma. Blood. 2004;103(4):1373-1375
9. 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;27(12):2664-2670
10. Khan ZA, Boscolo E, Picard A, et al. Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice. J Clin Invest. 2008;118(7):2592-2599
11. Drolet BA, Frieden IJ. Characteristics of infantile hemangiomas as clues to pathogenesis: Does hypoxia connect the dots? Arch Dermatol. 2010;146(11):1295-1299
12. Barnés CM, Huang S, Kaipainen A, et al. Evidence by molecular profiling for a placental origin of infantile hemangioma. Proc Natl Acad Sci U S A. 2005;102(52):19097-19102
13. Waner M, North PE, Scherer KA, Frieden IJ, Waner A, Mihm MC Jr. The nonrandom distribution of facial hemangiomas. Arch Dermatol. 2003;139(7):869-875
14. Pittman KM, Losken HW, Kleinman ME, et al. No evidence for maternal-fetal microchimerism in infantile hemangioma: A molecular genetic investigation. J Invest Dermatol. 2006;126(11):2533-2538
15. 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;93(6):2357-2364
16. Boye E, Yu Y, Paranya G, Mulliken JB, Olsen BR, Bischoff J. Clonality and altered behavior of endothelial cells from hemangiomas. J Clin Invest. 2001;107(6):745-752
17. Praveen V, Vidavalur R, Rosenkrantz TS, Hussain N. Infantile hemangiomas and retinopathy of prematurity: Possible association. Pediatrics. 2009;123(3). Available at: Www.pediatrics.org/cgi/content/full/123/3/e484
18. Mobasheri A, Richardson S, Mobasheri R, Shakibaei M, Hoyland JA. Hypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3: Putative molecular components of the oxygen and glucose sensing apparatus in articular chondrocytes. Histol Histopathol. 2005;20(4):1327-1338
19. Jinnin M, Medici D, Park L, et al. Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma. Nat Med. 2008;14 (11):1236-1246
20. 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(11): 1005-1013
21. Ritter MR, Dorrell MI, Edmonds J, Friedlander SF, Friedlander M. Insulin-like growth factor 2 and potential regulators of hemangioma growth and involution identified by large-scale expression analysis. Proc Natl Acad Sci USA. 2002;99(11):7455-7460
22. Peichev M, Naiyer AJ, Pereira D, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood. 2000;95(3):952-958
23. Haggstrom AN, Drolet BA, Baselga E, et al Hemangioma Investigator Group. Prospective study of infantile hemangiomas: Demographic, prenatal, and perinatal characteristics. J Pediatr. 2007;150(3):291-294
24. Enjolras O, Mulliken JB, Boon LM, Wassef M, Kozakewich HP, Burrows PE. Noninvoluting congenital hemangioma: A rare cutaneous vascular anomaly. Plast Reconstr Surg. 2001;107(7):1647-1654
25. Haggstrom AN, Drolet BA, Baselga E, et al. Prospective study of infantile hemangiomas: Clinical characteristics predicting complications and treatment. Pediatrics. 2006;118(3):882-887
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(3):307-311
27. Haggstrom AN, Garzon MC, Baselga E, et al. Risk for PHACE syndrome in infants with large facial hemangiomas. Pediatrics. 2010; 126(2). Available at: Www.pediatrics.org/cgi/content/full/126/2/e418
28. 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):975-986
29. Metry DW, Heyer G, Hess C, et al; PHACE Syndrome Research Conference. Consensus statement on diagnostic criteria for PHACe syndrome. Pediatrics. 2009;124(5): 1447-1456
30. Metry DW, Garzon MC, Drolet BA, et al. PHACE syndrome: Current knowledge, future directions. Pediatr Dermatol. 2009;26 (4):381-398
31. Chan YC, Eichenfield LF, Malchiodi J, Friedlander SF. Small facial haemangioma and supraumbilical raphe-a forme fruste of PHACES syndrome? Br J Dermatol. 2005;153 (5):1053-1057
32. Torer B, Gulcan H, Kilicdag H, Derbent M. PHACES syndrome with small, late-onset hemangiomas. Eur J Pediatr. 2007;166(12): 1293-1295
33. Haggstrom AN, Lammer EJ, Schneider RA, Marcucio R, Frieden IJ. Patterns of infantile hemangiomas: New clues to hemangioma pathogenesis and embryonic facial development. Pediatrics. 2006;117(3):698-703
34. Metry DW, Dowd CF, Barkovich AJ, Frieden IJ. The many faces of PHACE syndrome. J Pediatr. 2001;139(1):117-123
35. Drolet BA, Dohil M, Golomb MR, et al. Early stroke and cerebral vasculopathy in children with facial hemangiomas and PHACE association. Pediatrics. 2006;117(3):959-964
36. Cartwright MS, Hickling WH, Roach ES. Ischemic stroke in an adolescent with arterial tortuosity syndrome. Neurology. 2006; 67(2):360-361
37. Layde PM, Dooley K, Erickson JD, Edmonds LD. Is there an epidemic of ventricular septal defects in the U.S.A.? Lancet. 1980;1 (8165):407-408
38. Girard C, Bigorre M, Guillot B, Bessis D. PELVIS syndrome. Arch Dermatol. 2006;142 (7):884-888
39. Iacobas I, Burrows PE, Frieden IJ, et al. LUMBAR: Association between cutaneous infantile hemangiomas of the lower body and regional congenital anomalies. J Pediatr. 2010;157(5):795-801, e1-e7
40. Drolet B, Garzon M. SACRAL syndrome. Dermatology. 2007;215(4):360-, author reply 360-361
41. Glick ZR, Frieden IJ, Garzon MC, Mully TW, Drolet BA. Diffuse neonatal hemangiomatosis: An evidence-based review of case reports in the literature. J Am Acad Dermatol. 2012; [epub ahead of print]
42. Horii KA, Drolet BA, Frieden IJ, et al; Hemangioma Investigator Group. Prospective study of the frequency of hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. Pediatr Dermatol. 2011;28(3):245-253
43. 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):185-189
44. Leonardi-Bee J, Batta K, O'Brien C, Bath-Hextall FJ. Interventions for infantile haemangiomas (strawberry birthmarks) of the skin. Cochrane Database Syst Rev. 2011; (5):CD006545
45. 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):1208-1213
46. Rössler J, Wehl G, Niemeyer CM. Evaluating systemic prednisone therapy for proliferating haemangioma in infancy. Eur J Pediatr. 2008;167(7):813-815
47. Ezekowitz RA, Mulliken JB, Folkman J. Interferon alfa-2a therapy for life-threatening hemangiomas of infancy. N Engl J Med. 1992;326(22):1456-1463
48. Dubois J, Hershon L, Carmant L, Bélanger S, Leclerc JM, David M. Toxicity profile of interferon alfa-2b in children: A prospective evaluation. J Pediatr. 1999;135(6):782-785
49. Pérez-Valle S, Peinador M, Herraiz P, Saénz P, Montoliu G, Vento M. Vincristine, an efficacious alternative for diffuse neonatal haemangiomatosis. Acta Paediatr. 2010;99 (2):311-315
50. Léauté-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taïeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008;358(24):2649-2651
51. Sans V, de la Roque ED, Berge J, et al. Propranolol for severe infantile hemangiomas: Follow-up report. Pediatrics. 2009;124 (3). Available at: Www.pediatrics.org/cgi/content/full/124/3/e423
52. Buckmiller L, Dyamenahalli U, Richter GT. Propranolol for airway hemangiomas: Case report of novel treatment. Laryngoscope. 2009;119(10):2051- 2054
53. Marsciani A, Pericoli R, Alaggio R, Brisigotti M, Vergine G. Massive response of severe infantile hepatic hemangioma to propanolol. Pediatr Blood Cancer. 2010;54(1): 176
54. Hogeling M, Adams S, Wargon O. A randomized controlled trial of propranolol for infantile hemangiomas. Pediatrics. 2011; 128(2). Available at: Www.pediatrics.org/cgi/content/full/128/2/e259
55. Price CJ, Lattouf C, Baum B, et al. Propranolol vs corticosteroids for infantile hemangiomas: A multicenter retrospective analysis. Arch Dermatol. 2011;147(12): 1371-1376
56. Marqueling AL, Oza V, Frieden IJ, Puttgen KB. Propranolol for infantile hemangiomas: A meta analysis. Poster at The Society for Pediatric Dermatology annual meeting; July 2012; Monterey, CA 57. A randomized, controlled, multidose, multicentre, adaptive phase II/III study in infants with proliferating infantile hemangiomas requiring systemic therapy to compare four regimens of propranolol (1 or 3 mg/kg/day for 3 or 6 months) to placebo (double blind). Ongoing (active) but not recruiting. Clinical trials.gov identifier: NCT01056341. Available at: Http://clinicaltrials.gov/show/NCT01056341. Accessed November 7, 2012
57. Manunza F, Syed S, Laguda B, et al. Propranolol for complicated infantile haemangiomas: A case series of 30 infants. Br J Dermatol. 2010;162(2):466-468
58. Lawley LP, Siegfried E, Todd JL. Propranolol treatment for hemangioma of infancy: Risks and recommendations. Pediatr Dermatol. 2009;26(5):610-614
59. Itinteang T, Brasch HD, Tan ST, Day DJ. Expression of components of the reninangiotensin system in proliferating infantile haemangioma may account for the propranolol-induced accelerated involution. J Plast Reconstr Aesthet Surg. 2011;64(6): 759-765
60. Coppens G, Stalmans I, Zeyen T, Casteels I. The safety and efficacy of glaucoma medication in the pediatric population. J Pediatr Ophthalmol Strabismus. 2009;46(1):12-18
61. McMahon P, Oza V, Frieden IJ. Topical timolol for infantile hemangiomas: Putting a note of caution in "cautiously optimistic." Pediatr Dermatol. 2012;29(1):127-130
62. Ni N, Guo S, Langer P. Current concepts in the management of periocular infantile (capillary) hemangioma. Curr Opin Ophthalmol. 2011;22(5):419-425
63. Khunger N, Pahwa M. Dramatic response to topical timolol lotion of a large hemifacial infantile haemangioma associated with PHACE syndrome. Br J Dermatol. 2011;164 (4):886-888
64. Pope E, Chakkittakandiyil A. Topical timolol gel for infantile hemangiomas: A pilot study. Arch Dermatol. 2010;146(5):564-565
65. Guo S, Ni N. Topical treatment for capillary hemangioma of the eyelid using betablocker solution. Arch Ophthalmol. 2010; 128(2):255-258
66. Chakkittakandiyil A, Phillips R, Frieden IJ, et al. Timolol maleate 0.5% or 0.1% gelforming solution for infantile hemangiomas: A retrospective, multicenter, cohort study. Pediatr Dermatol. 2012;29(1):28-31
67. Greenberger S, Yuan S, Walsh LA, et al. Rapamycin suppresses self-renewal and vasculogenic potential of stem cells isolated from infantile hemangioma. J Invest Dermatol. 2011;131(12):2467-2476
68. Batta K, Goodyear HM, Moss C, Williams HC, Hiller L, Waters R. Randomised controlled study of early pulsed dye laser treatment of uncomplicated childhood haemangiomas: Results of a 1-year analysis. Lancet. 2002;360(9332):521-527
69. Admani S, Krakowski AC, Nelson JS, Eichenfield LF, Friedlander SF. Beneficial effects of early pulsed dye laser therapy in patients with infantile hemangiomas. Dermatol Surg. 2012;38(10):1739-1740
70. Frieden IJ. Infantile hemangioma research: Looking backward and forward. J Invest Dermatol. 2011;131(12):2345-2348