Medical Management of Vascular Anomalies

Francine Blei

doi:10.1055/s-0032-1329932

Facial Plastic Surgery, Inhaltsverzeichnis

Facial Plast Surg 2012; 28(06): 575-583
DOI: 10.1055/s-0032-1329932

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Medical Management of Vascular Anomalies

Francine Blei

¹Vascular Birthmark Institute of New York, New York, New York

› Institutsangaben

Abstract

The term “vascular anomalies” embraces a spectrum of medical conditions characterized by abnormal growth or development of blood and/or lymphatic vessels. Patient management is frequently provided in a multidisciplinary team approach, as there are many facets to evaluation and treatment. Clinical and basic research during the past decade has enhanced our knowledge, providing insight into possible etiologies, associated genetic mutations, cellular mechanisms modulating the development, and natural history of these disorders. Concomitantly, new therapeutic agents have been identified, which has transformed patient management. In this review, a brief overview of the field including an update in basic research is presented, followed by a discussion of current therapies and their purported mechanism of action.

Keywords

vascular anomalies - hemangioma - vascular malformation

Volltext

Referenzen

References
1 Shirazi F, Cohen C, Fried L, Arbiser JL. Mammalian target of rapamycin (mTOR) is activated in cutaneous vascular malformations in vivo. Lymphat Res Biol 2007; 5: 233-236
2 Adepoju O, Wong A, Kitajewski A , et al. Expression of HES and HEY genes in infantile hemangiomas. Vasc Cell 2011; 3: 19
3 Boscolo E, Bischoff J. Vasculogenesis in infantile hemangioma. Angiogenesis 2009; 12: 197-207
4 Boscolo E, Mulliken JB, Bischoff J. VEGFR-1 mediates endothelial differentiation and formation of blood vessels in a murine model of infantile hemangioma. Am J Pathol 2011; 179: 2266-2277
5 Greenberger S, Adini I, Boscolo E, Mulliken JB, Bischoff J. Targeting NF-κB in infantile hemangioma-derived stem cells reduces VEGF-A expression. Angiogenesis 2010; 13: 327-335
6 Greenberger S, Bischoff J. Infantile hemangioma-mechanism(s) of drug action on a vascular tumor. Cold Spring Harb Perspect Med 2011; 1: a006460
7 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: 2467-2476
8 Boye E, Olsen BR. Signaling mechanisms in infantile hemangioma. Curr Opin Hematol 2009; 16: 202-208
9 Jinnin M, Ishihara T, Boye E, Olsen BR. Recent progress in studies of infantile hemangioma. J Dermatol 2010; 37: 283-298
10 Ostergaard P, Simpson MA, Mendola A , et al. Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy. Am J Hum Genet 2012; 90: 356-362
11 Pansuriya TC, van Eijk R, d'Adamo P , et al. Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nat Genet 2011; 43: 1256-1261
12 Thiex R, Mulliken JB, Revencu N , et al. A novel association between RASA1 mutations and spinal arteriovenous anomalies. AJNR Am J Neuroradiol 2010; 31: 775-779
13 Boon LM, Ballieux F, Vikkula M. Pathogenesis of vascular anomalies. Clin Plast Surg 2011; 38: 7-19
14 Wooderchak-Donahue W, Stevenson DA, McDonald J , et al. Rasa1 analysis: Clinical and molecular findings in a series of consecutive cases. Eur J Med Genet 2011; (Dec) 8
15 Alomari AI. Diversion venography—a modified technique in Klippel-Trenaunay syndrome: initial experience. J Vasc Interv Radiol 2010; 21: 685-689
16 Hernandez-Martin S, Lopez-Gutierrez JC, Lopez-Fernandez S , et al. Brain perfusion SPECT in patients with PHACES syndrome under propranolol treatment. Eur J Pediatr Surg [et al] = . Z Kinderchir 2011; (Nov) 3
17 Lohrmann C, Foeldi E, Langer M. Assessment of the lymphatic system in patients with diffuse lymphangiomatosis by magnetic resonance imaging. Eur J Radiol 2011; 80: 576-581
18 Maus EA, Tan IC, Rasmussen JC , et al. Near-infrared fluorescence imaging of lymphatics in head and neck lymphedema. Head Neck 2012; 34: 448-453
19 Léauté-Labrèze C, Prey S, Ezzedine K. Infantile haemangioma: part I. Pathophysiology, epidemiology, clinical features, life cycle and associated structural abnormalities. J Eur Acad Dermatol Venereol 2011; 25: 1245-1253
20 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 , 715, e1
21 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: 2649-2651
22 Hammill AM, Wentzel M, Gupta A , et al. Sirolimus for the treatment of complicated vascular anomalies in children. Pediatr Blood Cancer 2011; 57: 1018-1024
23 McCuaig CC, Dubois J, Powell J , et al. 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; 26: 203-212
24 Pope E, Chakkittakandiyil A. Topical timolol gel for infantile hemangiomas: a pilot study. Arch Dermatol 2010; 146: 564-565
25 Swetman GL, Berk DR, Vasanawala SS, Feinstein JA, Lane AT, Bruckner AL. Sildenafil for severe lymphatic malformations. N Engl J Med 2012; 366: 384-386
26 Grunewald TG, Damke L, Maschan M , et al. First report of effective and feasible treatment of multifocal lymphangiomatosis (Gorham-Stout) with bevacizumab in a child. Ann Oncol 2010; 21: 1733-1734
27 Baselga E, Cordisco MR, Garzon M, Lee MT, Alomar A, Blei F. Rapidly involuting congenital haemangioma associated with transient thrombocytopenia and coagulopathy: a case series. Br J Dermatol 2008; 158: 1363-1370
28 North PE, Waner M, Mizeracki A , et al. A unique microvascular phenotype shared by juvenile hemangiomas and human placenta. Arch Dermatol 2001; 137: 559-570
29 Metry D, Heyer G, Hess C , et al; PHACE Syndrome Research Conference. Consensus statement on diagnostic criteria for phace syndrome. Pediatrics 2009; 124: 1447-1456
30 Stockman A, Boralevi F, Taïeb A, Léauté-Labrèze C. SACRAL syndrome: spinal dysraphism, anogenital, cutaneous, renal and urologic anomalies, associated with an angioma of lumbosacral localization. Dermatology 2007; 214: 40-45
31 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: 795-801 , e1–e7
32 Alomari AI. CLOVE(S) syndrome: expanding the acronym. Am J Med Genet A 2009; 149A: 294 ; author reply 295
33 Faughnan ME, Palda VA, Garcia-Tsao G , et al; HHT Foundation International - Guidelines Working Group. International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. J Med Genet 2011; 48: 73-87
34 Radhakrishnan K, Rockson SG. Gorham's disease: an osseous disease of lymphangiogenesis?. Ann N Y Acad Sci 2008; 1131: 203-205
35 Tan WH, Baris HN, Burrows PE , et al. The spectrum of vascular anomalies in patients with PTEN mutations: implications for diagnosis and management. J Med Genet 2007; 44: 594-602
36 Kasabach H, Merritt K. Capillary hemangioma with extensive purpura. Am J Dis Child 1940; 59: 1063
37 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; 100: 1377-1386
38 Enjolras O, Wassef M, Mazoyer E , et al. Infants with Kasabach-Merritt syndrome do not have “true” hemangiomas. J Pediatr 1997; 130: 631-640
39 Gruman A, Liang MG, Mulliken JB , et al. Kaposiform hemangioendothelioma without Kasabach-Merritt phenomenon. J Am Acad Dermatol 2005; 52: 616-622
40 Kauvar AN, Wang RS. Laser treatment of cutaneous vascular anomalies. Lymphat Res Biol 2004; 2: 38-50
41 Sun ZY, Yang L, Yi CG , et al. Possibilities and potential roles of estrogen in the pathogenesis of proliferation hemangiomas formation. Med Hypotheses 2008; 71: 286-292
42 Chang EI, Chang EI, Thangarajah H, Hamou C, Gurtner GC. Hypoxia, hormones, and endothelial progenitor cells in hemangioma. Lymphat Res Biol 2007; 5: 237-243
43 Xiao X, Liu J, Sheng M. Synergistic effect of estrogen and VEGF on the proliferation of hemangioma vascular endothelial cells. J Pediatr Surg 2004; 39: 1107-1110
44 Sasaki GH, Pang CY, Wittliff JL. Pathogenesis and treatment of infant skin strawberry hemangiomas: clinical and in vitro studies of hormonal effects. Plast Reconstr Surg 1984; 73: 359-370
45 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: 745-752
46 Yu Y, Flint AF, Mulliken JB, Wu JK, Bischoff J. Endothelial progenitor cells in infantile hemangioma. Blood 2004; 103: 1373-1375
47 Yu Y, Fuhr J, Boye E , et al. Mesenchymal stem cells and adipogenesis in hemangioma involution. Stem Cells 2006; 24: 1605-1612
48 Dosanjh A, Chang J, Bresnick S , et al. In vitro characteristics of neonatal hemangioma endothelial cells: similarities and differences between normal neonatal and fetal endothelial cells. J Cutan Pathol 2000; 27: 441-450
49 Hansen SL, Dosanjh A, Young DM, Boudreau N, Hoffman WY. Hemangiomas and homeobox gene expression. J Craniofac Surg 2006; 17: 767-771
50 Kageyama R, Ohtsuka T, Kobayashi T. The Hes gene family: repressors and oscillators that orchestrate embryogenesis. Development 2007; 134: 1243-1251
51 Itinteang T, Brasch HD, Tan ST, Day DJ. Expression of components of the renin-angiotensin system in proliferating infantile haemangioma may account for the propranolol-induced accelerated involution. J Plast Reconstr Aesthet Surg 2011; 64: 759-765
52 Yaniv E, Preis M, Hadar T, Shvero J, Haddad M. Antiestrogen therapy for hereditary hemorrhagic telangiectasia: a double-blind placebo-controlled clinical trial. Laryngoscope 2009; 119: 284-288
53 Pau H, Carney AS, Walker R, Murty GE. Is oestrogen therapy justified in the treatment of hereditary haemorrhagic telangiectasia: a biochemical evaluation. Clin Otolaryngol Allied Sci 2000; 25: 547-550
54 Dresse MF, David M, Hume H , et al. Successful treatment of Kasabach-Merritt syndrome with prednisone and epsilon-aminocaproic acid. Pediatr Hematol Oncol 1991; 8: 329-334
55 Ortel TL, Onorato JJ, Bedrosian CL, Kaufman RE. Antifibrinolytic therapy in the management of the Kasabach Merritt syndrome. Am J Hematol 1988; 29: 44-48
56 Fernandez-Pineda I, Lopez-Gutierrez JC, Ramirez G, Marquez C. Vincristine-ticlopidine-aspirin: an effective therapy in children with Kasabach-Merritt phenomenon associated with vascular tumors. Pediatr Hematol Oncol 2010; 27: 641-645
57 Zimmermann AP, Wiegand S, Werner JA, Eivazi B. Propranolol therapy for infantile haemangiomas: review of the literature. Int J Pediatr Otorhinolaryngol 2010; 74: 338-342
58 Storch CH, Hoeger PH. Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action. Br J Dermatol 2010; 163: 269-274
59 Trautmann K, Bethke A, Ehninger G, Folprecht G. Bevacizumab for recurrent hemangioendothelioma. Acta Oncol 2011; 50: 153-154
60 Fleagle JM, Bobba RK, Kardinal CG, Freter CE. Iron deficiency anemia related to hereditary hemorrhagic telangiectasia: response to treatment with bevacizumab. Am J Med Sci 2012; 343: 249-251
61 Kline RM, Buck LM. Bevacizumab treatment in multifocal lymphangioendotheliomatosis with thrombocytopenia. Pediatr Blood Cancer 2009; 52: 534-536
62 Héritier S, Le Merrer M, Jaubert F , et al. Retrospective French nationwide survey of childhood aggressive vascular anomalies of bone, 1988–2009. Orphanet J Rare Dis 2010; 5: 3
63 Klement G, Cervi D, Orbach D , et al. Pten associated lesions regress in response to the antiangiogenic therapy with thalidomide/celebrex. Presented at: 17th International Workshop of ISSVA; June 20–24, 2008; Boston, MA
64 Perry BN, Govindarajan B, Bhandarkar SS , et al. Pharmacologic blockade of angiopoietin-2 is efficacious against model hemangiomas in mice. J Invest Dermatol 2006; 126: 2316-2322
65 Ho NT, Lansang P, Pope E. Topical imiquimod in the treatment of infantile hemangiomas: a retrospective study. J Am Acad Dermatol 2007; 56: 63-68
66 Jiang C, Hu X, Ma G , et al. A prospective self-controlled phase II study of imiquimod 5% cream in the treatment of infantile hemangioma. Pediatr Dermatol 2011; 28: 259-266
67 Tremaine AM, Armstrong J, Huang YC , et al. Enhanced port-wine stain lightening achieved with combined treatment of selective photothermolysis and imiquimod. J Am Acad Dermatol 2012; (Jan) 13
68 White CW, Sondheimer HM, Crouch EC, Wilson H, Fan LL. Treatment of pulmonary hemangiomatosis with recombinant interferon alfa-2a. N Engl J Med 1989; 320: 1197-1200
69 Gonzalez D, Elizondo BJ, Haslag S , et al. Chronic subcutaneous octreotide decreases gastrointestinal blood loss in blue rubber-bleb nevus syndrome. J Pediatr Gastroenterol Nutr 2001; 33: 183-188
70 Nardone G, Rocco A, Balzano T, Budillon G. The efficacy of octreotide therapy in chronic bleeding due to vascular abnormalities of the gastrointestinal tract. Aliment Pharmacol Ther 1999; 13: 1429-1436
71 Suver DW, Perkins JA, Manning SC. Somatostatin treatment of massive lymphorrhea following excision of a lymphatic malformation. Int J Pediatr Otorhinolaryngol 2004; 68: 845-850
72 Albiñana V, Bernabeu-Herrero ME, Zarrabeitia R, Bernabéu C, Botella LM. Estrogen therapy for hereditary haemorrhagic telangiectasia (HHT): effects of raloxifene, on Endoglin and ALK1 expression in endothelial cells. Thromb Haemost 2010; 103: 525-534
73 Blei F, Wilson EL, Mignatti P, Rifkin DB. Mechanism of action of angiostatic steroids: suppression of plasminogen activator activity via stimulation of plasminogen activator inhibitor synthesis. J Cell Physiol 1993; 155: 568-578
74 Tan HH, Ge ZZ, Gao YJ , et al. The role of HIF-1, angiopoietin-2, Dll4 and Notch1 in bleeding gastrointestinal vascular malformations and thalidomide-associated actions: a pilot in vivo study. J Dig Dis 2011; 12: 349-356
75 Bauditz J, Lochs H. Angiogenesis and vascular malformations: antiangiogenic drugs for treatment of gastrointestinal bleeding. World J Gastroenterol 2007; 13: 5979-5984
76 Lebrin F, Srun S, Raymond K , et al. Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia. Nat Med 2010; 16: 420-428
77 Thomson K, Pinnock R, Teague L, Johnson R, Manikkam N, Drake R. Vincristine for the treatment of Kasabach-Merritt syndrome: recent New Zealand case experience. N Z Med J 2007; 120: U2418
78 Haisley-Royster C, Enjolras O, Frieden IJ , et al. Kasabach-Merritt phenomenon: a retrospective study of treatment with vincristine. J Pediatr Hematol Oncol 2002; 24: 459-462
79 Hochman M, Adams DM, Reeves TD. Current knowledge and management of vascular anomalies: I. Hemangiomas. Arch Facial Plast Surg 2011; 13: 145-151
80 Maguiness SM, Frieden IJ. Current management of infantile hemangiomas. Semin Cutan Med Surg 2010; 29: 106-114
81 Buckmiller LM, Richter GT, Suen JY. Diagnosis and management of hemangiomas and vascular malformations of the head and neck. Oral Dis 2010; 16: 405-418
82 Elsas FJ, Lewis AR. Topical treatment of periocular capillary hemangioma. J Pediatr Ophthalmol Strabismus 1994; 31: 153-156
83 Garzon MC, Lucky AW, Hawrot A, Frieden IJ. Ultrapotent topical corticosteroid treatment of hemangiomas of infancy. J Am Acad Dermatol 2005; 52: 281-286
84 Buckmiller LM, Francis CL, Glade RS. Intralesional steroid injection for proliferative parotid hemangiomas. Int J Pediatr Otorhinolaryngol 2008; 72: 81-87
85 Pope E, Krafchik BR, Macarthur C , et al. Oral versus high-dose pulse corticosteroids for problematic infantile hemangiomas: a randomized, controlled trial. Pediatrics 2007; 119: e1239-e1247
86 Greene AK. Corticosteroid treatment for problematic infantile hemangioma: evidence does not support an increased risk for cerebral palsy. Pediatrics 2008; 121: 1251-1252
87 Greene AK. Systemic corticosteroid is effective and safe treatment for problematic infantile hemangioma. Pediatr Dermatol 2010; 27: 322-323
88 Chianese J, Blei F. Corticosteroid toxicity in infants treated for endangering hemangiomas: Experience and guidelines for monitoring. Int Pediatr 1999; 14: 146-153
89 Ray WZ, Lee A, Blackburn SL, Lueder GT, Leonard JR. Pseudotumor cerebri following tapered corticosteroid treatment in an 8-month-old infant. J Neurosurg Pediatr 2008; 1: 88-90
90 Maronn ML, Corden T, Drolet BA. Pneumocystis carinii pneumonia in infant treated with oral steroids for hemangioma. Arch Dermatol 2007; 143: 1224-1225
91 Aviles R, Boyce TG, Thompson DM. Pneumocystis carinii pneumonia in a 3-month-old infant receiving high-dose corticosteroid therapy for airway hemangiomas. Mayo Clin Proc 2004; 79: 243-245
92 Al-Mahdi H. Iris depigmentation: an unusual complication of intralesional corticosteroid injection for capillary hemangioma. Middle East Afr J Ophthalmol 2010; 17: 100-102
93 Deboer MD, Boston BA. Failure-to-thrive in an infant following injection of capillary hemangioma with triamcinolone acetonide. Clin Pediatr (Phila) 2008; 47: 296-299
94 Goyal R, Watts P, Lane CM, Beck L, Gregory JW. Adrenal suppression and failure to thrive after steroid injections for periocular hemangioma. Ophthalmology 2004; 111: 389-395
95 Kushner BJ, Lemke BN. Bilateral retinal embolization associated with intralesional corticosteroid injection for capillary hemangioma of infancy. J Pediatr Ophthalmol Strabismus 1993; 30: 397-399
96 Ang LP, Lee MW, Seah LL, Cheong P, Rootman J. Orbital cellulitis following intralesional corticosteroid injection for periocular capillary haemangioma. Eye (Lond) 2007; 21: 999-1001
97 Hogeling M, Adams S, Wargon O. A randomized controlled trial of propranolol for infantile hemangiomas. Pediatrics 2011; 128: e259-e266
98 Menezes MD, McCarter R, Greene EA, Bauman NM. Status of propranolol for treatment of infantile hemangioma and description of a randomized clinical trial. Ann Otol Rhinol Laryngol 2011; 120: 686-695
99 Truong MT, Perkins JA, Messner AH, Chang KW. Propranolol for the treatment of airway hemangiomas: a case series and treatment algorithm. Int J Pediatr Otorhinolaryngol 2010; 74: 1043-1048
100 Leboulanger N, Fayoux P, Teissier N , et al. Propranolol in the therapeutic strategy of infantile laryngotracheal hemangioma: a preliminary retrospective study of French experience. Int J Pediatr Otorhinolaryngol 2010; 74: 1254-1257
101 Haider KM, Plager DA, Neely DE, Eikenberry J, Haggstrom A. Outpatient treatment of periocular infantile hemangiomas with oral propranolol. J AAPOS 2010; 14: 251-256
102 Rosbe KW, Suh KY, Meyer AK, Maguiness SM, Frieden IJ. Propranolol in the management of airway infantile hemangiomas. Arch Otolaryngol Head Neck Surg 2010; 136: 658-665
103 Tan ST, Itinteang T, Leadbitter P. Low-dose propranolol for infantile haemangioma. J Plast Reconstr Aesthet Surg 2010; (Jul) 6
104 Mazereeuw-Hautier J, Hoeger PH, Benlahrech S , et al. Efficacy of propranolol in hepatic infantile hemangiomas with diffuse neonatal hemangiomatosis. J Pediatr 2010; 157: 340-342
105 Guo S, Ni N. Topical treatment for capillary hemangioma of the eyelid using beta-blocker solution. Arch Ophthalmol 2010; 128: 255-256
106 Cante V, Pham-Ledard A, Imbert E, Ezzedine K, Léauté-Labrèze C. First report of topical timolol treatment in primarily ulcerated perineal haemangioma. Arch Dis Child Fetal Neonatal Ed 2012; 97: F155-F156
107 Chakkittakandiyil A, Phillips R, Frieden IJ , et al. Timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas: a retrospective, multicenter, cohort study. Pediatr Dermatol 2012; 29: 28-31
108 Oranje AP, Janmohamed SR, Madern GC, de Laat PC. Treatment of small superficial haemangioma with timolol 0.5% ophthalmic solution: a series of 20 cases. Dermatology 2011; (Dec) 16
109 Bonifazi E, Acquafredda A, Milano A, Montagna O, Laforgia N. Severe hypoglycemia during successful treatment of diffuse hemangiomatosis with propranolol. Pediatr Dermatol 2010; 27: 195-196
110 Breur JM, de Graaf M, Breugem CC, Pasmans SG. Hypoglycemia as a result of propranolol during treatment of infantile hemangioma: a case report. Pediatr Dermatol 2011; 28: 169-171
111 Holland KE, Frieden IJ, Frommelt PC, Mancini AJ, Wyatt D, Drolet BA. Hypoglycemia in children taking propranolol for the treatment of infantile hemangioma. Arch Dermatol 2010; 146: 775-778
112 Allford MA, Brown JL. Case report: intraoperative hypoglycaemia in a child treated with propranolol following a short preoperative fast. Eur J Anaesthesiol 2011; 28: 71-72
113 Naouri M, Schill T, Maruani A, Bross F, Lorette G, Rossler J. Successful treatment of ulcerated haemangioma with propranolol. J Eur Acad Dermatol Venereol 2010; 24: 1109-1112
114 Tan ST, Itinteang T, Leadbitter P. Low-dose propranolol for multiple hepatic and cutaneous hemangiomas with deranged liver function. Pediatrics 2011; 127: e772-e776
115 Thomas J, Kumar P, Kumar DD. Ulcerated infantile haemangioma of leg successfully treated with propranolol. J Cutan Aesthet Surg 2011; 4: 211-213
116 Missoi TG, Lueder GT, Gilbertson K, Bayliss SJ. Oral propranolol for treatment of periocular infantile hemangiomas. Arch Ophthalmol 2011; 129: 899-903
117 Sciveres M, Marrone G, Pipitone S , et al. Successful first-line treatment with propranolol of multifocal infantile hepatic hemangioma with high-flow cardiac overload. J Pediatr Gastroenterol Nutr 2011; 53: 693-695
118 Chamlin SL, Haggstrom AN, Drolet BA , et al. Multicenter prospective study of ulcerated hemangiomas. J Pediatr 2007; 151: 684-689 , 689, e1
119 Naouri M, Schill T, Maruani A, Bross F, Lorette G, Rossler J. Successful treatment of ulcerated haemangioma with propranolol. J Eur Acad Dermatol Venereol 2010; 24: 1109-1112
120 Saint-Jean M, Léauté-Labrèze C, Mazereeuw-Hautier J , et al; Groupe de Recherche Clinique en Dermatologie Pédiatrique. Propranolol for treatment of ulcerated infantile hemangiomas. J Am Acad Dermatol 2011; 64: 827-832
121 Kim LH, Hogeling M, Wargon O, Jiwane A, Adams S. Propranolol: useful therapeutic agent for the treatment of ulcerated infantile hemangiomas. J Pediatr Surg 2011; 46: 759-763
122 Sugarman JL, Mauro TM, Frieden IJ. Treatment of an ulcerated hemangioma with recombinant platelet-derived growth factor. Arch Dermatol 2002; 138: 314-316
123 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; 140: 867-870
124 Lapidoth M, Ben-Amitai D, Bhandarkar S, Fried L, Arbiser JL. Efficacy of topical application of eosin for ulcerated hemangiomas. J Am Acad Dermatol 2009; 60: 350-351
125 Sans V, de la Roque ED, Berge J , et al. Propranolol for severe infantile hemangiomas: follow-up report. Pediatrics 2009; 124: e423-e431
126 Storch CH, Hoeger PH. Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action. Br J Dermatol 2010; 163: 269-274
127 Lamy S, Lachambre MP, Lord-Dufour S, Béliveau R. Propranolol suppresses angiogenesis in vitro: inhibition of proliferation, migration, and differentiation of endothelial cells. Vascul Pharmacol 2010; 53: 200-208
128 Dai Y, Hou F, Buckmiller L , et al. Decreased eNOS protein expression in involuting and propranolol-treated hemangiomas. Arch Otolaryngol Head Neck Surg 2012; 138: 177-182
129 Lai ML, Wang SL, Lai MD, Lin ET, Tse M, Huang JD. Propranolol disposition in Chinese subjects of different CYP2D6 genotypes. Clin Pharmacol Ther 1995; 58: 264-268
130 Sander T, Noll L, Zembles T , et al. Detection of cyp2c19 single nucleotide polymorphisms in patients with infantile hemangioma that predict reduced metabolism of propranolol. Presented at: 18th Congress of the International Society for the Study of Vascular Anomalies; April 21–24, 2010; Brussels, Belgium
131 Blanchet C, Nicollas R, Bigorre M, Amedro P, Mondain M. Management of infantile subglottic hemangioma: acebutolol or propranolol?. Int J Pediatr Otorhinolaryngol 2010; 74: 959-961
132 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; 132 (3 Pt 1) 527-530
133 Michaud AP, Bauman NM, Burke DK, Manaligod JM, Smith RJ. Spastic diplegia and other motor disturbances in infants receiving interferon-alpha. Laryngoscope 2004; 114: 1231-1236
134 Chao YH, Liang DC, Chen SH, Wang LY, Yeh TC, Liu HC. Interferon-alpha for alarming hemangiomas in infants: experience of a single institution. Pediatr Int 2009; 51: 469-473
135 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: 311-315
136 Blatt J, Stavas J, Moats-Staats B, Woosley J, Morrell DS. Treatment of childhood kaposiform hemangioendothelioma with sirolimus. Pediatr Blood Cancer 2010; 55: 1396-1398
137 Burrows PE, Mulliken JB, Fishman SJ, Klement GL, Folkman J. Pharmacological treatment of a diffuse arteriovenous malformation of the upper extremity in a child. J Craniofac Surg 2009; 20 (Suppl. 01) 597-602
138 Iacobas I, Burrows PE, Adams DM, Sutton VR, Hollier LH, Chintagumpala MM. Oral rapamycin in the treatment of patients with hamartoma syndromes and PTEN mutation. Pediatr Blood Cancer 2011; 57: 321-323
139 Trenor III CC. Sirolimus for refractory vascular anomalies. Pediatr Blood Cancer 2011; 57: 904-905
140 Perry B, Banyard J, McLaughlin ER , et al. AKT1 overexpression in endothelial cells leads to the development of cutaneous vascular malformations in vivo. Arch Dermatol 2007; 143: 504-506
141 Frieden IJ. Infantile hemangioma research: looking backward and forward. J Invest Dermatol 2011; 131: 2345-2348