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A prospective study to assess the efficacy and safety of oral propranolol as first-line treatment for infantile superficial hemangioma

  • Yun, Yeong Ju (Department of Pediatrics, Chungbuk National University College of Medicine) ;
  • Gyon, Yun Hee (Department of Pediatrics, Chungbuk National University College of Medicine) ;
  • Yang, Sohyoung (Department of Pediatrics, Chungbuk National University College of Medicine) ;
  • Lee, Youn Kyung (Department of Pediatrics, Chungbuk National University College of Medicine) ;
  • Park, Joohyun (Department of Pediatrics, Chungbuk National University College of Medicine) ;
  • Park, Meerim (Department of Pediatrics, Chungbuk National University College of Medicine)
  • 투고 : 2015.02.25
  • 심사 : 2015.05.21
  • 발행 : 2015.12.10

초록

Purpose: To determine the efficacy and safety of oral propranolol as a first-line treatment for superficially located infantile hemangioma (IH) and propose an assessment tool to measure treatment response. Methods: Patients with superficial IH under 1 year of age were prospectively recruited between May 2012 and December 2013 at the Department of Pediatrics of Chungbuk National University Hospital. Propranolol was administered to 12 infants (median age, 3.8 months) while monitoring cardiovascular and adverse metabolic effects. If a patient showed no adverse events, the dosage was gradually increased up to 3 mg/kg/day and maintained for 1 year. We used our own scoring system to assess treatment response using parameters like change in color, and longest diameter, and thickness of the IH. Results: Eleven out of 12 patients completed the protocol with consistent improvement of hemangiomas during therapy. Patients on propranolol showed a more than 50% involution in the first 3 months, with additional steady involution until 1 year. Patients with the highest scores at 1 month maintained their score and showed better responses until treatment termination. The patient with the lowest score at 1 month did not show any further regression and stopped propranolol treatment 4 months after initiation. In two children with recurrences after successful therapeutic regression, propranolol was effective after being reintroduced. Propranolol treatment was not interrupted in any patient due to adverse events. Conclusion: Oral propranolol at 3 mg/kg/day showed a consistent, rapid, and therapeutic effect on superficial IHs without significant adverse events.

키워드

참고문헌

  1. Leaute-Labreze C, Prey S, Ezzedine K. Infantile haemangioma: part II. Risks, complications and treatment. J Eur Acad Dermatol Venereol 2011;25:1254-60. https://doi.org/10.1111/j.1468-3083.2011.04105.x
  2. 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;358:2649-51. https://doi.org/10.1056/NEJMc0708819
  3. Drolet BA, Esterly NB, Frieden IJ. Hemangiomas in children. N Engl J Med 1999;341:173-81. https://doi.org/10.1056/NEJM199907153410307
  4. Tan ST, Velickovic M, Ruger BM, Davis PF. Cellular and extracellular markers of hemangioma. Plast Reconstr Surg 2000;106:529-38. https://doi.org/10.1097/00006534-200009010-00001
  5. Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg 1982;69:412-22. https://doi.org/10.1097/00006534-198203000-00002
  6. Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, Horii KA, et al. Prospective study of infantile hemangiomas: clinical characteristics predicting complications and treatment. Pediatrics 2006;118:882-7. https://doi.org/10.1542/peds.2006-0413
  7. Beck DO, Gosain AK. The presentation and management of hemangiomas. Plast Reconstr Surg 2009;123:181e-91e. https://doi.org/10.1097/PRS.0b013e3181a65c59
  8. Greinwald JH Jr, Burke DK, Bonthius DJ, Bauman NM, Smith RJ. An update on the treatment of hemangiomas in children with interferon alfa-2a. Arch Otolaryngol Head Neck Surg 1999;125: 21-7. https://doi.org/10.1001/archotol.125.1.21
  9. Barlow CF, Priebe CJ, Mulliken JB, Barnes PD, Mac Donald D, Folkman J, et al. Spastic diplegia as a complication of interferon Alfa-2a treatment of hemangiomas of infancy. J Pediatr 1998;132 (3 Pt 1):527-30. https://doi.org/10.1016/S0022-3476(98)70034-4
  10. Fawcett SL, Grant I, Hall PN, Kelsall AW, Nicholson JC. Vincristine as a treatment for a large haemangioma threatening vital functions. Br J Plast Surg 2004;57:168-71. https://doi.org/10.1016/j.bjps.2003.11.003
  11. Wharton S, Soucid A, Nishikawa H, Sridhar AV. Endangering cutaneous infantile hemangioma treated with vincristine: a case report. Eur J Plast Surg 2009;32:157-61. https://doi.org/10.1007/s00238-008-0295-2
  12. Sondhi V, Patnaik SK. Propranolol for infantile hemangioma (PINCH): an open-label trial to assess the efficacy of propranolol for treating infantile hemangiomas and for determining the decline in heart rate to predict response to propranolol. J Pediatr Hematol Oncol 2013;35:493-9. https://doi.org/10.1097/MPH.0b013e3182a11658
  13. 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:e423-31. https://doi.org/10.1542/peds.2008-3458
  14. Love JN, Sikka N. Are 1-2 tablets dangerous? Beta-blocker exposure in toddlers. J Emerg Med 2004;26:309-14. https://doi.org/10.1016/j.jemermed.2003.11.015
  15. Denoyelle F, Leboulanger N, Enjolras O, Harris R, Roger G, Garabedian EN. Role of propranolol in the therapeutic strategy of infantile laryngotracheal hemangioma. Int J Pediatr Otorhinolaryngol 2009;73:1168-72. https://doi.org/10.1016/j.ijporl.2009.04.025
  16. Fuchsmann C, Quintal MC, Giguere C, Ayari-Khalfallah S, Guibaud L, Powell J, et al. Propranolol as first-line treatment of head and neck hemangiomas. Arch Otolaryngol Head Neck Surg 2011;137: 471-8. https://doi.org/10.1001/archoto.2011.55
  17. Chik KK, Luk CK, Chan HB, Tan HY. Use of propranolol in infantile haemangioma among Chinese children. Hong Kong Med J 2010; 16:341-6.
  18. Siegfried EC, Keenan WJ, Al-Jureidini S. More on propranolol for hemangiomas of infancy. N Engl J Med 2008;359:2846; author reply 2846-7. https://doi.org/10.1056/NEJMc086443
  19. Haggstrom AN, Beaumont JL, Lai JS, Adams DM, Drolet BA, Frieden IJ, et al. Measuring the severity of infantile hemangiomas: instrument development and reliability. Arch Dermatol 2012;148: 197-202. https://doi.org/10.1001/archdermatol.2011.926
  20. 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. https://doi.org/10.1111/j.1525-1470.2011.01664.x
  21. Xiao Q, Li Q, Zhang B, Yu W. Propranolol therapy of infantile hemangiomas: efficacy, adverse effects, and recurrence. Pediatr Surg Int 2013;29:575-81. https://doi.org/10.1007/s00383-013-3283-y
  22. 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. https://doi.org/10.1007/s00431-010-1324-2

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