Skip to main content

Advertisement

SpringerLink
Log in

Treatment of infantile haemangiomas: recommendations of a European expert group

  • Review
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

With a prevalence of 2.6–4.5 %, infantile haemangiomas (IH) represent the most common tumour of infancy. While the majority of IH does not require therapy and regresses spontaneously, about 10 % of IH exhibit complications such as obstruction, ulceration or disfigurement. With the advent of oral propranolol, many conventional treatment options have become obsolete. This paper summarizes current recommendations for management of complicated IH. These recommendations have been written by an expert group after a consensus process including bibliographic review, several drafts of synthesis, meetings with quantitative voting system and redaction of an approved final manuscript.

Conclusion: Oral propranolol is the first-line agent for the treatment of complicated IH.

What is Known:

• Infantile haemangiomas (IH) are the most common tumours of infancy. Within a very short period after its discovery and long before the publication of randomized controlled trials, propranolol has become the number one agent for the treatment of complicated IH.

What is New:

• We report IH treatment recommendations of an international, interdisciplinary team of experts, based on an up-to-date review of the literature.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

EMA:

European Medicines Agency

EPC:

Endothelial progenitor cells

FDA:

Food and Drug Administration (USA)

GLUT1:

Glucose transporter 1

HemSC:

Haemangioma stem cells

HIF-1:

Hypoxia-inducible factor

IH:

Infantile haemangioma

Nd:YAG:

Neodym-dotted Yttrium-aluminum-granate laser

PHACE:

Posterior fossa-haemangioma-arterial-cardiac-eye anomaly

RCT:

Randomized controlled trial

VEGF(R):

Vascular endothelial growth factor (receptor)

References

  1. Ábarzúa-Araya A, Navarrete-Dechent CP, Heusser F, Retamal J, Zegpi-Trueba MS (2014) Atenolol versus propranolol for the treatment of infantile hemangiomas: a randomized controlled study. J Am Acad Dermatol 70:1045–9

    Article  PubMed  Google Scholar 

  2. Ahogo C, Ezzedine K, Prey S, Colona V, Diallo A, Boralevi F, Taïeb A, Léauté-Labrèze C (2013) Factors associated with the relapse of infantile haemangiomas in children treated with propranolol. Brit J Dermatol 169:1252–1256

    Article  CAS  Google Scholar 

  3. Bagazgoitia L, Hernández-Martín A, Torrelo A (2011) Recurrence of infantile hemangiomas treated with propranolol. Pediatr Dermatol 28:658–662

    Article  PubMed  Google Scholar 

  4. Bajaj Y, Kapoor K, Ifeacho S, Jephson CG, Albert DM, Harper JI, Hartley BE (2013) Great Ormond Street Hospital treatment guidelines for use of propranolol in infantile isolated subglottic haemangioma. J Laryngol Otol 127:295–298

    Article  CAS  PubMed  Google Scholar 

  5. Bauland CG, Luning TH, Smit JM, Zeebregts CJ, Spauwen PH (2011) Untreated hemangiomas: growth pattern and residual lesions. Plastic Reconstr Surg 127:1643–1648

    Article  CAS  Google Scholar 

  6. Bauman NM, Shin JJ, Oh AK, Preciado DA, He J, Greene EA, Puttgen KB (2014) Propranolol vs prednisolone for symptomatic proliferating infantile hemangiomas: a randomized clinical trial. JAMA Otolaryngol, Head and Neck Surg 140:323–30

    Article  Google Scholar 

  7. Blei F, McElhinney DB, Guarini A, Presti S (2014) Cardiac screening in infants with infantile hemangiomas before propranolol treatment. Pediatr Dermatol 31:465–467

    Article  PubMed  Google Scholar 

  8. Brandling-Bennett HA, Metry DW, Baselga E, Lucky AW, Adams DM, Cordisco MR, Frieden IJ (2008) Infantile hemangiomas with unusually prolonged growth phase: a case series. Arch Dermatol 144:1632–1637

    Article  PubMed  Google Scholar 

  9. Breur JM, de Graaf M, Breugem CC, Pasmans SG (2011) Hypoglycemia as a result of propranolol during treatment of infantile hemangioma: a case report. Pediatr Dermatol 28:169–171

    Article  PubMed  Google Scholar 

  10. Chamlin SL, Haggstrom AN, Drolet BA, Baselga E, Frieden IJ, Garzon MC, Horii KA, Lucky AW, Metry DW, Newell B, Nopper AJ, Mancini AJ (2007) Multicenter prospective study of ulcerated hemangiomas. J Pediatr 151:684–689

    Article  PubMed  Google Scholar 

  11. Chan H, McKay C, Adams S, Wargon O (2013) RCT of timolol maleate gel for superficial infantile hemangiomas in 5–24 week-olds. Pediatrics 131:e1739–1747

    Article  PubMed  Google Scholar 

  12. Chen TS, Eichenfield LF, Friedlander SF (2013) Infantile hemangiomas: an update on pathogenesis and therapy. Pediatrics 131:99–108

    Article  PubMed  Google Scholar 

  13. Colmenero I, Hoeger PH (2014) Vascular tumours in infants. Part II: vascular tumours of intermediate dignity and malignant tumours. Brit J Dermatol 171:474–484

    Article  CAS  Google Scholar 

  14. Del Frari L. Delarue A (2013) Data on file (Pierre Fabre). Presented at World Congress of Paediatric Dermatology, Madrid, 2013

  15. Dickison P, Christou E, Wargon O (2011) A prospective study of infantile hemangiomas with a focus on incidence and risk factors. Pediatr Dermatol 28:663–669

    Article  PubMed  Google Scholar 

  16. Drolet BA, Swanson EA, Frieden IJ, Hemangioma Investigator Group (2008) Infantile hemangiomas: an emerging health issue linked to an increased rate of low birth weight infants. J Pediatr 153:712–5

    Article  PubMed  Google Scholar 

  17. Drolet BA, Frieden IJ (2010) Characteristics of infantile hemangiomas as clue to pathogenesis: does hypoxia connect the dots? Arch Dermatol 146:1295–1299

    Article  PubMed  Google Scholar 

  18. Drolet BA, Frommelt PC, Chamlin SI, Haggstrom A, Bauman NM, Chiu YE, Chun RH, Garzon MC, Holland KE, Liberman L, MacLellan-Tobert S, Mancini AJ, Metry D, Puttgen KB, Seefeldt M, Sidbury R, Ward KM, Blei F, Baselga E, Cassidy L, Darrow DH, Joachim S, Kwon EK, Martin K, Perkins J, Siegel DH, Boucek RJ, Frieden IJ (2013) Initiation and use of propranolol for infantile haemangioma: report of a consensus conference. Pediatrics 131:128–140

    Article  PubMed Central  PubMed  Google Scholar 

  19. Filippi L, Cavallaro G, Bagnoli P, Dal Monte M, Fiorini P, Donzelli G, Tinelli F, Araimo G, Cristofori G, la Marca G, Della Bona ML, La Torre A, Fortunato P, Furlanetto S, Osnaghi S, Mosca F (2013) Oral propranolol for retinopathy of prematurity: risks, safety concerns, and perspectives. J Pediatr 163:1570–1577

    Article  CAS  PubMed  Google Scholar 

  20. Garin EH, Araya CE (2009) Treatment of systemic hypertension in children and adolescents. Curr Opin Pediatr 21:600–604

    Article  PubMed  Google Scholar 

  21. Giachetti A, Garcia-Monaco R, Sojo M, Scacchi MF, Cernadas C, Guerchicoff Lemcke M, Dovasio F (2014) Long-term treatment with oral propranolol reduces relapses of infantile hemangiomas. Pediatr Dermatol 31:14–20

    Article  PubMed  Google Scholar 

  22. Gnarra M, Solman L, Harper JI, Syed SB (2015) Propranolol and prednisolone combination for the treatment of segmental haemangioma in PHACES syndrome. Br J Dermatol. doi:10.1111/bjd.13588, Epub ahead of print

    PubMed  Google Scholar 

  23. Greenberger S, Bischoff J (2013) Pathogenesis of infantile haemangioma. Brit J Dermatol 169:12–19

    Article  CAS  Google Scholar 

  24. Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, Horii KA, Lucky AW, Mancini AJ, Metry DW, Newell B, Nopper AJ, Frieden IJ (2006) Prospective study of infantile hemangiomas: clinical characteristics predicting complications and treatment. Pediatrics 118:882–887

    Article  PubMed  Google Scholar 

  25. 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 (2007) Prospective study of infantile hemangiomas: demographic, prenatal, and perinatal characteristics. J Pediatr 150:291–294

    Article  Google Scholar 

  26. Hengst M, Oelert M, Hoeger PH (2015) Blood pressure monitoring during the induction and maintenance period of propranolol therapy for complicated infantile haemangiomas. A prospective study of 109 infants. Pediatr Dermatol 2015, in press

  27. Hermans DJ, Boezeman JB, Van de Kerkhof PC, Rieu PN, Van der Vleuten CJ (2009) Differences between ulcerated and non-ulcerated hemangiomas, a retrospective study of 465 cases. Eur J Dermatol 19:152–156

    PubMed  Google Scholar 

  28. Hermans DJ, Bauland CG, Zweegers J, van Beynum IM, van der Vleuten CJ (2013) Propranolol in a case series of 174 patients with complicated infantile haemangioma: indications, safety and future directions. Brit J Dermatol 168:837–843

    Article  CAS  Google Scholar 

  29. Hoeger PH, Maerker JM, Kienast AK, Syed SB, Harper JI (2009) Neonatal haemangiomatosis associated with placental chorangiomas: report of three cases and review of the literature. Clin Exp Dermatol 34:e78–80

    Article  CAS  PubMed  Google Scholar 

  30. Hoeger PH, Colmenero I (2014) Vascular tumours in infants. Part I: benign vascular tumours other than haemangioma. Brit J Dermatol 171:466–473

    Article  CAS  Google Scholar 

  31. Hoeger PH (2015) Propranolol for infantile haemangiomas: certain chances, potential risks. Br J Dermatol 172:3–4

    Article  CAS  PubMed  Google Scholar 

  32. Hogeling M, Adas S, Wargon O (2011) A randomized controlled trial of propranolol for infantile hemangiomas. Pediatrics 128:e259–e266

    Article  PubMed  Google Scholar 

  33. Holland KE, Frieden IJ, Frommelt PC, Mancini AJ, Wyatt D, Drolet BA (2010) Hypoglycemia in children taking propranolol for the treatment of infantile hemangioma. Arch Dermatol 146:775–777

    Article  CAS  PubMed  Google Scholar 

  34. Horii KA, Drolet BA, Frieden IJ, Baselga E, Chamlin SL, Haggstrom AN, Holland KE, Mancini AJ, McCuaig CC, Metry DW, Morel KD, Newell BD, Nopper AJ, Powell J, Garzon MC (2011) Hemangioma Investigator Group. Prospective study of the frequency of hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. Pediatr Dermatol 28:245–253

    Article  PubMed  Google Scholar 

  35. Janmohamed SR, Madern GC, de Laat PCJ, Oranje AP (2015) Educational paper: pathogenesis of infantile haemangioma, an update 2014 (part I). Eur J Pediatr 174:97–103

    Article  PubMed  Google Scholar 

  36. Jinnin M, Medici D, Park L, Liu Y, Boscolo EB, Bischoff J, Boye E, Olsen BR (2008) Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma. Nat Med 14:1236–1246

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Kagami S, Kuwano Y, Shibata S, Uwajima Y, Yamada D, Miyamoto A, Miyagawa T, Araki M, Takahashi K, Isomura S, Aozasa N, Masui Y, Yamamoto M, Inuzuka R, Katori T, Sato S (2013) Propranolol is more effective than pulsed dye laser and cryosurgery for infantile hemangiomas. Eur J Pediatr 172:1521–1526

    Article  CAS  PubMed  Google Scholar 

  38. Kaylani S, Theos AJ, Pressey JG (2013) Treatment of infantile hemangiomas with sirolimus in a patient with PHACE syndrome. Pediatr Dermatol 30:194–7

    Article  Google Scholar 

  39. Langley A, Pope B (2015) Propranolol and central nervous system function: potential implications for pediatric patients with infantile hemangiomas. Br J Dermatol 172:13–23

    Article  CAS  PubMed  Google Scholar 

  40. Léauté-Labrèze C, Hoeger P, Mazereeuw-Hautier J, Guibaud L, Baselga E, Posiunas G, Phillips RJ, Caceres H, Lopez Gutierrez JC, Ballona R, Friedlander SF, Powell J, Perek D, Metz B, Barbarot S, Maruani A, Szalai ZZ, Krol A, Boccara O, Foelster-Holst R, Febrer Bosch MI, Su J, Buckova H, Torrelo A, Cambazard F, Grantzow R, Wargon O, Wyrzykowski D, Roessler J, Bernabeu-Wittel J, Valencia AM, Przewratil P, Glick S, Pope E, Birchall N, Benjamin L, Mancini AJ, Vabres P, Souteyrand P, Frieden IJ, Berul CI, Mehta CR, Prey S, Boralevi F, Morgan CC, Heritier S, Delarue A, Voisard JJ (2015) A randomized controlled trial of oral propranolol in infantile hemangioma. N Engl J Med 372:735–46

    Article  PubMed  Google Scholar 

  41. Liu LS, Sokoloff D, Antaya RJ (2013) Twenty-four-hour hospitalization for patients initiating systemic propranololtherapy for infantile hemangiomas—is it indicated? Pediatr Dermatol 30:554–560

    Article  PubMed  Google Scholar 

  42. Luu M, Frieden IJ (2013) Haemangioma: clinical course, complications and management. Brit J Dermatol 169:20–30

    Article  CAS  Google Scholar 

  43. Malik MA, Menon P, Rao KL, Samujh R (2013) Effect of propranolol vs prednisolone vs propranolol with prednisolone in the management of infantile hemangioma: a randomized controlled study. J Pediatr Surg 48:2453–2459

    Article  PubMed  Google Scholar 

  44. Marqueling AL, Oza V, Frieden IJ, Puttgen KB (2013) Propranolol and infantile hemangiomas four years later: a systematic review. Pediatr Dermatol 30:182–191

    Article  PubMed  Google Scholar 

  45. McAinsh J, Cruickshank JM (1990) Beta-blockers and central nervous system side effects. Pharmacol Ther 46:163–97

    Article  CAS  PubMed  Google Scholar 

  46. McMahon P, Oza V, Frieden IJ (2012) Topical timolol for infantile hemangiomas: putting a note of caution in “cautiously optimistic”. Pediatr Dermatol 29:127–130

    Article  PubMed  Google Scholar 

  47. Metry D, Frieden IJ, Hess C, Siegel D, Maheshwari M, Baselga E, Chamlin S, Garzon M, Mancini AJ, Powell J, Drolet BA (2013) Propranolol use in PHACE syndrome with cervical and intracranial arterial anomalies: collective experience in 32 infants. Pediatr Dermatol 30:71–89

    Article  PubMed  Google Scholar 

  48. Mihm MC, Nelson JS (2010) Hypothesis: the metastatic niche theory can elucidate infantile hemangioma development. J Cutan Pathol 37(suppl 1):83–87

    Article  PubMed Central  PubMed  Google Scholar 

  49. Munden A, Butschek R, Tom WL, Marshall JS, Poeltler DM, Krohne SE, Alió AB, Ritter M, Friedlander DF, Catanzarite V, Mendoza A, Smith L, Friedlander M, Friedlander SF (2014) Prospective study of infantile haemangiomas: incidence, clinical characteristics and association with placental anomalies. Brit J Dermatol 170:907–913

    Article  CAS  Google Scholar 

  50. Parikh S, Darrow DH, Grimmer JF, Manning SC (2013) Propranolol use for infantile hemangiomas. American Society of Pediatric Otolaryngology Vascular Anomalies Task Force Practice Patterns. JAMA Otolaryngol Head Neck Surg 139:153–156

    Article  PubMed  Google Scholar 

  51. Pope E, Chakkittakandiyil A, Lara-Corrales I, Maki E, Weinstein M (2013) Br J Dermatol 168:222–4

    Article  CAS  PubMed  Google Scholar 

  52. Price CJ, Lattouf C, Baum B, McLeod MB, Schachner LA, Duarte AM, Connelly EA (2011) Propranolol vs. corticosteroids for infantile hemangiomas: a multicenter retrospective analysis. Arch Dermatol 147:1371–1376

    Article  CAS  PubMed  Google Scholar 

  53. Puttgen KB (2012) Multifocal infantile hepatic hemangiomas—imaging strategy and response to treatment after propranolol and steroids including review of the literature. Eur J Pediatr 171:1023–8

    Article  PubMed  Google Scholar 

  54. Puttgen KB, Summerer B, Schneider J, Cohen BA, Boss EF, Bauman NM (2013) Cardiovascular and blood glucose parameters in infants during propranolol initiation for treatment of symptomatic infantile hemangiomas. Ann Otol Rhinol Laryngol 122:550–554

    Article  PubMed  Google Scholar 

  55. Saidi W, Zaouali A, Saihi N, Mokni S, Denguezli M, Nouira R (2014) Arrêt cardiorespiratoire au décours d’une bronchiolite chez un nourisson traité par propranolol pour un hémangiome. Ann Dermatol Venereol 141:528–530

    Article  CAS  PubMed  Google Scholar 

  56. Solman L, Murabit A, Gnarra M, Harper JI, Syed SB, Glover M (2014) Propranolol for infantile haemangiomas; single centre experience of 250 cases and proposed therapeutic protocol. Arch Dis Child 99:1132–1136

    Article  PubMed  Google Scholar 

  57. Tollefson MM, Frieden IJ (2012) Early growth of infantile hemangiomas: what parents’ photographs tell us. Pediatrics 130:e314–20

    Article  PubMed  Google Scholar 

  58. Vergine G, Marsciani A, Pedini A, Brocchi S, Marsciani M, Desiderio E, Bertelli S, Vecchi V (2012) Efficacy of propranolol treatment in thyroid dysfunction associated with severe infantile hepatichaemangioma. Horm Res Paediatr 78:256–60

    Article  CAS  PubMed  Google Scholar 

  59. Vredenborg AD, Janmohamed SR, de Laat PCJ, Madern GC, Oranje AP (2013) Multiple cutaneous infantile haemangiomas and the risk of internal haemangioma. Brit J Dermatol 169:188–191

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank Laboratoires Pierre Fabre Dermatologie, Inc., for sponsoring the meeting in Castres and for the technical support of the consensus process. Drs. Etienne André and Alain Delarue kindly acted as moderators of the discussion process.

Compliance with ethical standards

The manuscript complies to the ethical rules applicable to the European Journal of Pediatrics.

Conflict of interest

Pierre Fabre Inc., France, hosted the initial meeting of the Expert Group in Castres/France.

Author’s contributions

All coauthors attended the initial meeting and participated in the discussion of topics and in the design of the consensus paper. PHH wrote the initial draft of the manuscript which was then circulated to all coauthors. Comments and annotations of all coauthors were included in subsequent drafts. The final version of the manuscript was approved by all coauthors.

Author information

Authors and Affiliations

  1. Department of Paediatrics and Paediatric Dermatology, Catholic Children’s Hospital Wilhelmstift, Liliencronstr. 130, Hamburg, 22149, Germany

    Peter H. Hoeger

  2. Department Paediatric Dermatology, Great Ormond Street Hospital for Children, London, UK

    John I. Harper

  3. Department Paediatric Dermatology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain

    Eulalia Baselga

  4. M3C-Department Paediatric Cardiology, Université Paris Descartes, Hôpital Universitaire Necker-Enfants Malades, Paris, France

    Damien Bonnet

  5. Division Plastic Surgery, Ctr. Vascular Anomalies, Cliniques Universitaires St Luc, Brussels, Belgium

    Laurence M. Boon

  6. Clinical Epidemiology Unit, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy

    Marta Ciofi Degli Atti

  7. Dermatology Unit, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy

    Maya El Hachem

  8. Department of Dermatology, Maasstad Hospital, Rotterdam, Netherlands

    Arnold P. Oranje

  9. Centre for Laser and Vascular Anomalies, Department of Dermatology, Skane University Hospital, Malmö, Sweden

    Agneta Troilius Rubin

  10. Department of Dermatology, University Hospital and University Children’s Hospital, Zürich, Switzerland

    Lisa Weibel

  11. Department Paediatric Dermatology, CHU de Bordeaux, HôpitalPellegrin-Enfants, Bordeaux, France

    Christine Léauté-Labrèze

Authors
  1. Peter H. Hoeger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John I. Harper
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eulalia Baselga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Damien Bonnet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Laurence M. Boon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marta Ciofi Degli Atti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maya El Hachem
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Arnold P. Oranje
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Agneta Troilius Rubin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lisa Weibel
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Christine Léauté-Labrèze
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter H. Hoeger.

Additional information

Communicated by Beat Steinmann

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 357 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hoeger, P.H., Harper, J.I., Baselga, E. et al. Treatment of infantile haemangiomas: recommendations of a European expert group. Eur J Pediatr 174, 855–865 (2015). https://doi.org/10.1007/s00431-015-2570-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-015-2570-0

Keywords

Search

Navigation