World Journal of Pediatrics

, Volume 9, Issue 3, pp 221–229 | Cite as

Beta-blockers versus corticosteroids in the treatment of infantile hemangioma: an evidence-based systematic review

  • Shi-Qiong Xu
  • Ren-Bing Jia
  • Wei Zhang
  • Huang Zhu
  • Sheng-Fang Ge
  • Xian-Qun Fan
Systematic Review

Abstract

Background

The efficacy and safety of beta-blockers versus corticosteroids in the treatment of infantile hemangiomas (IHs) is controversial. This study aimed to summarize evidence described in the literature and to assess the quality of studies involving beta-blockers and corticosteroids for the treatment of cutaneous IHs.

Methods

Comparative studies were collected from 15 online electronic databases, including OVID Medline, PubMed, ISI Web of Science, CENTRAL, CNKI, ChiCTR, JPCTR, CTRIndia, IranCTR, SLCTR, ISRCTRN, NLCTR, GCTR, ANCTR, ClinicalTrial. gov, and associated references. Studies without a control group were excluded, and the remaining studies were assessed by two reviewers independently using the Downs & Black scale for reported quality. The main areas assessed in the included studies were volume changes, overall improvement in appearance, eye function, and adverse events.

Results

Ten comparative studies were included with a total of 419 children. A meta-analysis was not performed due to the considerable heterogeneity across studies. Some evidence showed that beta-blockers are superior to steroids in reducing volume and improving the overall appearance of IHs, such as lightening of the color and flattening of the surface. Conclusions regarding improved eye function and adverse events were divided, and no consensus has been reached on the superiority of one treatment over another. No episodes of severe-onset asthma, hypotension, or bradycardia occurred in the beta-blocker treatment due to the rigorous exclusion of patients with contraindications.

Conclusions

Available studies indicate that beta-blockers are an alternative option to corticosteroids for IH treatment with respect to volume shrinkage and improvement in appearance. No evidence has shown a significant difference in improved eye function and adverse events between beta-blockers and corticosteroids in the treatment of IH; indeed, there is a lack of well-designed, high-quality randomized control trials.

Key words

adverse events beta-blockers eye functions infantile hemangioma steroids 

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References

  1. 1.
    Kilcline C, Frieden IJ. Infantile hemangiomas: how common are they? A systematic review of the medical literature. Pediatr Dermatol 2008;25:168–173.PubMedCrossRefGoogle Scholar
  2. 2.
    Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, Horii KA, et al. Prospective study of infantile hemangiomas: demographic, prenatal, and perinatal characteristics. J Pediatr 2007;150:291–294.PubMedCrossRefGoogle Scholar
  3. 3.
    Corapcioğlu F, Büyükkapu-Bay S, Binnetoğlu K, Babaoğlu A, Anik Y, Tugay M. Preliminary results of propranolol treatment for patients with infantile hemangioma. Turk J Pediatr 2011;53:137–141.PubMedGoogle Scholar
  4. 4.
    Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in metaanalyses. Eur J Epidemiol 2010;25:603–605.PubMedCrossRefGoogle Scholar
  5. 5.
    Spiteri Cornish K, Reddy AR. The use of propranolol in the management of periocular capillary haemangioma—a systematic review. Eye (Lond) 2011;25:1277–1283.CrossRefGoogle Scholar
  6. 6.
    Ranchod TM, Frieden IJ, Fredrick DR. Corticosteroid treatment of periorbital haemangioma of infancy: a review of the evidence. Br J Ophthalmol 2005;89:1134–1138.PubMedCrossRefGoogle Scholar
  7. 7.
    Wasserman BN, Medow NB, Homa-Palladino M, Hoehn ME. Treatment of periocular capillary hemangiomas. J AAPOS 2004;8:175–181.PubMedCrossRefGoogle Scholar
  8. 8.
    Saint-Jean M, Léauté-Labrèze C, Mazereeuw-Hautier J, Bodak N, Hamel-Teillac D, Kupfer-Bessaguet I, et al. Propranolol for treatment of ulcerated infantile hemangiomas. J Am Acad Dermatol 2011;64:827–832.PubMedCrossRefGoogle Scholar
  9. 9.
    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;360:521–527.PubMedCrossRefGoogle Scholar
  10. 10.
    Jiang C, Hu X, Ma G, Chen D, Jin Y, Chen H, 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.PubMedCrossRefGoogle Scholar
  11. 11.
    Pope E, Krafchik BR, Macarthur C, Stempak D, Stephens D, Weinstein M, et al. Oral versus high-dose pulse corticosteroids for problematic infantile hemangiomas: a randomized, controlled trial. Pediatrics 2007;119:e1239–1247.PubMedCrossRefGoogle Scholar
  12. 12.
    Pandey A, Gangopadhyay AN, Sharma SP, Kumar V, Gupta DK, Gopal SC. Evaluation of topical steroids in the treatment of superficial hemangioma. Skinmed 2010;8:9–11.PubMedGoogle Scholar
  13. 13.
    Grover C, Kedar A, Arora P, Lal B. Efficacy of oral prednisolone use in the treatment of infantile hemangiomas in Indian children. Pediatr Dermatol 2011;28:502–506.PubMedCrossRefGoogle Scholar
  14. 14.
    Blei F. Oral prednisolone for infantile hemangioma: efficacy and safety using a standardized treatment protocol. Plast Reconstr Surg 2012;129:840e–841e; author reply 841e.PubMedCrossRefGoogle Scholar
  15. 15.
    Nieuwenhuis K, de Laat PC, Janmohamed SR, Madern GC, Oranje AP. Infantile hemangioma: treatment with short course systemic corticosteroid therapy as an alternative for propranolol. Pediatr Dermatol 2013;30:64–70.PubMedCrossRefGoogle Scholar
  16. 16.
    Frieden IJ, Haggstrom AN, Drolet BA, Mancini AJ, Friedlander SF, Boon L, et al. Infantile hemangiomas: current knowledge, future directions. Proceedings of a research workshop on infantile hemangiomas, April 7–9, 2005, Bethesda, Maryland, USA. Pediatr Dermatol 2005;22:383–406.PubMedCrossRefGoogle Scholar
  17. 17.
    Bennett ML, Fleischer AB Jr, Chamlin SL, Frieden IJ. Oral corticosteroid use is effective for cutaneous hemangiomas: an evidence-based evaluation. Arch Dermatol 2001;137:1208–1213.PubMedCrossRefGoogle Scholar
  18. 18.
    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.PubMedCrossRefGoogle Scholar
  19. 19.
    Storch CH, Hoeger PH. Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action. Br J Dermatol 2010;163:269–274.PubMedCrossRefGoogle Scholar
  20. 20.
    Semkova K, Kazandjieva J. Topical timolol maleate for treatment of infantile haemangiomas: preliminary results of a prospective study. Clin Exp Dermatol 2013;38:143–146.PubMedCrossRefGoogle Scholar
  21. 21.
    Betlloch-Mas I, Martinez-Miravete MT, Lucas-Costa A, Martin de Lara AI, Selva-Otalaurruchi J. Outpatient treatment of infantile hemangiomas with propranolol: a prospective study. Actas Dermosifiliogr 2012;103:806–815.PubMedCrossRefGoogle Scholar
  22. 22.
    Xu G, Lv R, Zhao Z, Huo R. Topical propranolol for treatment of superficial infantile hemangiomas. J Am Acad Dermatol 2012;67:1210–1213.PubMedCrossRefGoogle Scholar
  23. 23.
    Hsu TC, Wang JD, Chen CH, Chang TK, Wang TM, Chou CM, et al. Treatment with propranolol for infantile hemangioma in 13 Taiwanese newborns and young infants. Pediatr Neonatol 2012;53:125–132.PubMedCrossRefGoogle Scholar
  24. 24.
    Talaat AA, Elbasiouny MS, Elgendy DS, Elwakil TF. Propranolol treatment of infantile hemangioma: clinical and radiologic evaluations. J Pediatr Surg 2012;47:707–714.PubMedCrossRefGoogle Scholar
  25. 25.
    Georgountzou A, Karavitakis E, Klimentopoulou A, Xaidara A, Kakourou T. Propranolol treatment for severe infantile hemangiomas: a single-centre 3-year experience. Acta Paediatr 2012;101:e469–474.PubMedCrossRefGoogle Scholar
  26. 26.
    Zegpi-Trueba MS, Abarzúa-Araya A, Silva-Valenzuela S, Navarrete-Dechent C, Uribe-González P, Nicklas-Díaz C. Oral propranolol for treating infantile hemangiomas: a case series of 57 patients. Actas Dermosifiliogr 2012;103:708–717.PubMedCrossRefGoogle Scholar
  27. 27.
    Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health 1998;52:377–384.PubMedCrossRefGoogle Scholar
  28. 28.
    Pope E, Chakkittakandiyil A, Lara-Corrales I, Maki E, Weinstein M. Expanding the therapeutic repertoire of infantile haemangiomas: cohort-blinded study of oral nadolol compared with propranolol. Br J Dermatol 2013;168:222–224.PubMedCrossRefGoogle Scholar
  29. 29.
    Hogeling M, Adams S, Wargon O. A randomized controlled trial of propranolol for infantile hemangiomas. Pediatrics 2011;128:e259–266.PubMedCrossRefGoogle Scholar
  30. 30.
    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;64:833–838.PubMedCrossRefGoogle Scholar
  31. 31.
    Rössler J, Schill T, Bähr A, Truckenmüller W, Noellke P, Niemeyer CM. Propranolol for proliferating infantile haemangioma is superior to corticosteroid therapy—a retrospective, single centre study. J Eur Acad Dermatol Venereol 2012;26:1173–1175.PubMedCrossRefGoogle Scholar
  32. 32.
    Chakkittakandiyil A, Phillips R, Frieden IJ, Siegfried E, Lara-Corrales I, Lam J, 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.PubMedCrossRefGoogle Scholar
  33. 33.
    Bertrand J, McCuaig C, Dubois J, Hatami A, Ondrejchak S, Powell J. Propranolol versus prednisone in the treatment of infantile hemangiomas: a retrospective comparative study. Pediatr Dermatol 2011;28:649–654.PubMedCrossRefGoogle Scholar
  34. 34.
    Awadein A, Fakhry MA. Evaluation of intralesional propranolol for periocular capillary hemangioma. Clin Ophthalmol 2011;5:1135–1140.PubMedCrossRefGoogle Scholar
  35. 35.
    Chambers CB, Katowitz WR, Katowitz JA, Binenbaum G. A controlled study of topical 0.25% timolol maleate gel for the treatment of cutaneous infantile capillary hemangiomas. Ophthal Plast Reconstr Surg 2012;28:103–106.PubMedCrossRefGoogle Scholar
  36. 36.
    Lawley LP, Siegfried E, Todd JL. Propranolol treatment for hemangioma of infancy: risks and recommendations. Pediatr Dermatol 2009;26:610–614.PubMedCrossRefGoogle Scholar
  37. 37.
    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.PubMedCrossRefGoogle Scholar
  38. 38.
    Schiestl C, Neuhaus K, Zoller S, Subotic U, Forster-Kuebler I, Michels R, et al. Efficacy and safety of propranolol as first-line treatment for infantile hemangiomas. Eur J Pediatr 2011;170:493–501.PubMedCrossRefGoogle Scholar
  39. 39.
    Jacobs AH. Strawberry hemangiomas; the natural history of the untreated lesion. Calif Med 1957;86:8–10.PubMedGoogle Scholar
  40. 40.
    Sans V, de la Roque ED, Berge J, Grenier N, Boralevi F, Mazereeuw-Hautier J, et al. Propranolol for severe infantile hemangiomas: follow-up report. Pediatrics 2009;124:e423–431.PubMedCrossRefGoogle Scholar
  41. 41.
    Phillips RJ, Penington AJ, Bekhor PS, Crock CM. Use of propranolol for treatment of infantile haemangiomas in an outpatient setting. J Paediatr Child Health 2012;48:902–906.PubMedCrossRefGoogle Scholar
  42. 42.
    Vassallo P, Forte R, Di Mezza A, Magli A. Treatment of infantile capillary hemangioma of the eyelid with systemic propranolol. Am J Ophthalmol 2013;155:165–170. e2.PubMedCrossRefGoogle Scholar
  43. 43.
    Weissenstein A, Straeter A, Villalon G, Bittmann S. Topical timolol for small infantile hemangioma: a new therapy option. Turk J Pediatr 2012;54:156–158.PubMedGoogle Scholar
  44. 44.
    Weiss AH, Kelly JP. Reappraisal of astigmatism induced by periocular capillary hemangioma and treatment with intralesional corticosteroid injection. Ophthalmology 2008;115:390–397. e1.PubMedCrossRefGoogle Scholar
  45. 45.
    Samimi DB, Alabiad CR, Tse DT. An anatomically based approach to intralesional corticosteroid injection for eyelid capillary hemangiomas. Ophthalmic Surg Lasers Imaging 2012;43:190–195.PubMedCrossRefGoogle Scholar

Copyright information

© Children's Hospital, Zhejiang University School of Medicine and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Shi-Qiong Xu
    • 1
  • Ren-Bing Jia
    • 1
  • Wei Zhang
    • 2
  • Huang Zhu
    • 3
  • Sheng-Fang Ge
    • 1
  • Xian-Qun Fan
    • 1
    • 4
  1. 1.Department of Ophthalmology, Ninth People’s Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
  2. 2.Department of Emergency, Changzheng Hospitalthe Second Military Medical UniversityShanghaiChina
  3. 3.Department of Ophthalmology, Xinhua Hospital Affiliated to School of MedicineShanghai Jiao Tong UniversityShanghaiChina
  4. 4.Department of Ophthalmology, Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

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