USE OF PROPRANOL FOR TREATING COMPLICATED HEMANGIOMAS IN CHILDREN

Infantile hemangiomas (IHs) are the most common tumors detectable in infants, including 5–10% of the neonates. Despite the spontaneous involution characteristic of the uncomplicated course of the disease, IHs require therapy in order to prevent disfigurement, functional disorders and cankering. Effective experience of treating IHs with non-selective-blocker propranol was described in 2008. More than 200 articles on effectiveness and safety of -blockers for IH treatment and assessment of potential side effects have been published since then. The article presents published data on the assessment of effectiveness of treating difficult to access hemangiomas with propranol on the basis of the applicable standards of medical care rendering. Special attention is given to the side effects induced by administration of this drug. According to the results of the published scientific works, -blockers appear to be rather effective for IH treatment and feature a high safety profile. However, it is necessary to continue clinical research and establish a sufficient evidence basis in order to definitively confirm this hypothesis.

1. Kimmer M., Bettex M., Genton N., Stockmann M. Haut und Weichteile, Hamangiome, in Kinderchirurgie Diagnostik, Indikation, Therapie, Prognose, Begr undet von M. Grob. Georg Thieme. New York, NY, USA. 1982; ch. 9.4–9.7.

2. Finn M.C., Glowacki J., Mulliken B. Congenital vascular lesions: clinical application of a new classification. Journal of Pediatric Surgery. 1983; 18 (6): 894–900.

3. Schaarschmidt K., Willital H., Lehmann R.R. Tumorchirurgie, Hamangiome, in Chirurgie im Kindesalter, Spitta, Balingen, Germany. 2000. Р. 956–965.

4. Puri P., Nemeth L., Prem P. Hemangiomas and vascular malformations, in Newborn Surgery, ch. 71. Arnold Publisher, London, UK. 2nd ed. 2003.

5. Poetke M., Berlien H.P. Laser treatment in hemangiomas and vascularmalformations. Medical Laser Application. 2005; 20 (2): 95–102.

6. Hochman M., Adams D.M., Reeves T.D. Current knowledge and management of vascular anomalies I: Hemangiomas. Facial Plastic Surgery. JAMA. 2011; 13 (3): 145–151.

7. Dieterich-Miller C.A., Safford P.L. Psychosocial development of children with hemangiomas: home, school, health care collaboration. Children’s Health Care. 1992; 21 (2): 84–89.

8. Achauer B.M., Chang C.J., Vander Kam V.M. Management of hemangioma of infancy: review of 245 patients. Plastic and Reconstructive Surgery. 1997; 99 (5): 1301–1308.

9. Zide B.M., Glat P.M., Stile F.L., Longaker M.T. Vascular lip enlargement, part I: hemangiomas — tenets of therapy. Plastic and Reconstructive Surgery. 1997; 100 (7): 1664−1673.

10. Tanner J.L., Dechert M.P., Frieden I.J. Growing up with a facial hemangioma: Parent and child coping and adaptation. Pediatrics. 1998; 101 (3): 446–452.

11. Restrepo R., Palani R., Cervantes L.F., Duarte A.M., Amjad I., Altman N.R. Hemangiomas revisited: the useful, the unusual and the new; part 2: Endangering hemangiomas and treatment. Pediatric Radiology. 2011; 41 (7): 905–915.

12. Grosfeld J.L., O’Neill J.A., Fonkalsrud J.E.W., Coran A.G. Pediatric surgery. In 2 v. Ed. by Jay L. Grossfeld. 6th ed. Philadelphia: Mosby Elsevier. 2006; 2: 1141−2146.

13. Holcomb G.W. Ashkraft’s Pediatric Surgery. George Whitfield Holcomb III, J. Patrick Murphy. 5th ed. Philadelphia: Saunders Elsevier. 2010. 1101 р.

14. O’Neill J.A., Grosfeld J.L., Fonkalsrud J.E.W., Coran A.G. Pediatric surgery. Philadelphia: Mosby Elsevier. 2006; 2.

15. Schweiger-Kabesch A., Deml M., Kurnik K., Kammer B., Schmidt H., Hamangiome. Glukokortikoid und Interferontherapie. Monatssch Kinderheilk. 2004; 152: 29–37.

16. Ulrich H., Baumler W., Hohenleutner U., Landthaler M. Neodymium-YAG laser for hemangiomas and vascular malformations — long term results. Journal of the German Society of Dermatology. 2005; 3 (6): 436–440.

17. Roganovic J. An update on the treatment of high-risk haemangiomas in infants. European Journal of Pediatric Surgery. 2007; 17 (2): 147.

18. Enjolras O., Riche M.C., Merland J.J., Escande J.P. Management of alarming hemangiomas in infancy: A review of 25 cases. Pediatrics. 1990; 85 (4): 491–498.

19. Leaute-Labreze C., Prey S., Ezzedine K. Infantile hemangioma: part II: Risks, complications and treatment. Journal of the European Academy of Dermatology and Venerology. 2011; 25: 1254–1260.

20. Cremer H., Djawari D. Zur Fruhtherapie der planen und planotuberosen Hamangiome mittels Kontaktkryochirurgie. Monatsschrift Kinderheilkunde. 1995; 143: 365–368.

21. Bause H. Kryotherapie lokalisierter klassischer Hamangiome. Monatsschrift Kinderheilkunde. 2004; 152: 16–22.

22. Grantzow R. Chirurgische Therapie von Hamangiomen. Monatsschrift Kinderheilkunde. 2004; 152: 23–28.

23. Longacre J.J., Benton C., Unterthiner R.A. Treatment of facial hemangioma by intravascular embolization with silicone spheres. Case report. Plastic and Reconstructive Surgery. 1972; 50 (6): 618–621.

24. Wolff K.D., Holzle F., Eufinger H. Indikationen zur primaren operativen Therapie von Gef¨aßanomalien im Sauglingsalter. Mund-, Kiefer- und Gesichtschirurgie. 2002; 6 (5): 303–308.

25. Brown S.H., Neerhout R.C., Fonkalsrud E.W. Prednisone therapy in the management of large hemangiomas in infants and children. Surgery. 1972; 71 (2): 168–173.

26. Apfelberg D.B., Maser M.R., White D.N., Lash H. A preliminary study of the combined effect of neodymium: YAG laser photocoagulation and direct steroid instillation in thetreatment of capillary/cavernous hemangiomas of infancy. Annals of Plastic Surgery. 1989; 22 (2): 94–104.

27. Sadan N., Wolach B. Treatment of hemangiomas of infants with high doses of prednisone. Journal of Pediatrics. 1996; 128 (1): 141–146.

28. Weibel L. Propranolol — eine neue Therapie fur infantile Hamangiome. Paediatrica. 2009; 20 (2): 27–29.

29. Bertrand J., McCuaig C., Dubois J., Hatami A., Ondreichak S., Powell J., Propranolol versus prednisone in the treatment of infantile hemangiomas: A retrospective comparative study. Pediatric Dermatology. 2011; 28 (6): 649–654.

30. Leaute-Labreze C., Dumas de la Roque E., Hubiche T. et al. Propranolol for Severe Hemangiomas of Infancy. New England Journal of Medicine. 2008; 358 (24): 2649–2651.

31. Leaute-Labreze C., Dumas de la Roque E., Taieb A. More on propranolol for hemangiomas of infancy. New England Journal of Medicine. 2008; 359: 2846–2847.

32. Sans V., de la Roque E.D., Berge J. et al. Propranolol for severe infantile hemangiomas: Follow-up report. Pediatrics. 2009; 124 (3): 423–431.

33. Lawley L.P., Siegfried E., Todd J.L. Propranolol treatment for hemangioma of infancy: Risks and recommendations. Pediatric Dermatology. 2009; 26 (5): 610–614.

34. Siegfried E.C., Keenan W.J., Al-Jureidini S. More on propranolol for hemangiomas of infancy. New England Journal of Medicine. 2008; 359 (26): 2846.

35. Buckmiller L.M., Munson P.D., Dyamenahalli U., Dai Y., Richter G.T. Propranolol for infantile hemangiomas: Early experience at a tertiary vascular anomalies center. Laryngoscope. 2010; 120 (4): 676–681.

36. Holland K.E., Frieden I.J., Frommelt P.C., Mancini A.J., Wyatt D.B., Drolet A. Hypoglycemia in children taking propranolol for the treatment of infantile hemangioma. Archives of Dermatology. 2010; 146 (7): 775–778.

37. Manunza F., Syed S., Laguda B. et al. Propranolol for complicated infantile haemangiomas: A case series of 30 infants. British Journal of Dermatology. 2010; 162 (2): 466–468.

38. Naouri M., Schill T., Maruani A., Bross F., Lorette G., Rossler J. Successful treatment of ulcerated haemangioma with propranolol. Journal of the European Academy of Dermatology and Venereology. 2010; 24 (9): 1109–1112.

39. Pavlakovic H., Kietz S., Lauerer P., Zutt M., Lakomek M. Hyperkalemia complicating propranolol treatment of an infantile hemangioma. Pediatrics. 2010; 126 (6): 1589–1593.

40. C.H. Storch and P. H. Hoeger, “Propranolol for infantile haemangiomas: insights into themolecular mechanisms of action,” British Journal of Dermatology. 2010; vol. 163, no. 2: 269–274.

41. Zimmermann A.P., Wiegand S., Werner J.A., Eivazi B. Propranolol therapy for infantile hemangiomas: Review of the literature. International Journal of Pediatric Otorhinolaryngology. 2010; 74 (4): 338–342.

42. Bagazgoitia L., Torrelo A., Lopez Gutierrez J.C. et al. Propranolol for infantile hemangiomas. Pediatric Dermatology. 2011; 28 (2): 108–114.

43. Leaute-Labreze C., Prey S., Ezzedine K. Infantile haemangioma: part I: Pathophysiology, epidemiology, clinical features, life cycle and associated structural abnormalities. Journal of the European Academy of Dermatology and Venerology. 2011; 25: 1245–1253.

44. de Graaf M., Breu J.M.P. Jr., Raphael M.F., Vos M., Breugem C.C., Pasmans S.G.M.A. Adverse effects of propranolol when used in the treatment of hemangiomas: A case series of 28 infants. Journal of the American Academy of Dermatology. 2011; 65 (2): 320–327.

45. Eivazi B., Cremer H.J., Mangold C., Teymoortash A., Wiegand S., Werner J.A. Hemangiomas of the nasal tip: an approach to a therapeutic challenge. International Journal of Pediatric Otorhinolaryngology. 2011; 75 (3): 368–375.

46. Fuchsmann C., Quintal M.C., Giguere C. et al. Propranolol as first-line treatment of head and neck hemangiomas. Archives of Otolaryngology. Head & Neck Surgery. 2011; 137 (5): 471–478.

47. Love J.N., Sikka N. Are 1−2 tablets dangerous? Beta-blocker exposure in toddlers. Journal of Emergency Medicine. 2004; 26 (3): 309–314.

48. Janmohamed S.R., Madern G.C., de Laat P.C.J., Oranje A.P. Haemangioma of infancy: Two case reports with an overdose of propranolol. Case Reports in Dermatology. 2011; 3 (1): 18–21.

49. Kim L.H.C., Hogeling M., Wargon O., Jiwane A., Adams S. Propranolol: useful therapeutic agent for the treatment of ulcerated infantile hemangiomas. Journal of Pediatric Surgery. 2011; 46 (4): 759–763.

50. Missoi T.G., Lueder G.T., Gilbertson K., Bayliss S.J. Oral propranolol for treatment of periocular infantile hemangiomas. Archives of Ophthalmology. 2011; 129 (7): 899–903.

51. Ni N., Guo S., Langer P. Current concepts in the management of periocular infantile (capillary) hemangioma. Current Opinion in Ophthalmology. 2011; 22: 419–425.

52. Peridis S., Pilgrim G., Athanasopoulos I., Parpounas K. A meta-analysis on the effectiveness of propranolol for the treatment of infantile airway haemangiomas. International Journal of Pediatric Otorhinolaryngology. 2011; 75 (4): 455–460.

53. Shayan Y.R., Prendiville J.S., Goldman R.D. Use of propranolol in treating hemangiomas. Canadian Family Physician. 2011; 57 (3): 302–303.

54. Schupp C.J., Kleber J.B., Gunther P., Holland-Cunz S. Propranolol therapy in 55 infants with infantile hemangioma: dosage, duration, adverse effects, and outcome. Pediatric Dermatology. 2011; 28 (6): 640–644.

55. Tan S.T., Itinteanga T., Leadbitter P. Low-dose propranolol for infantile haemangioma. Journal of Plastic, Reconstructive & Aesthetic Surgery. 2011; 64 (3): 292–299.

56. Zaher H., Rasheed H., Hegazy R.A., Abdelhalim D.M., Gawdat H.I. Oral propranolol: An effective, safe treatment for infantile hemangiomas. European Journal of Dermatology. 2011; 21 (4): 558–563.

57. Zvulunov A., McCuaig C., Frieden I.J. et al. Oral propranolol therapy for infantile hemangiomas beyond the proliferation phase: A multicenter retrospective study. Pediatric Dermatology. 2011; 28 (2): 94–98.

58. AWMF online: Leitlinien Register: 006/100, Entwicklungsstufe S 2 k aktueller Stand, Hamangiome im Sauglings und Kleinkindesalter, Leitlinie der Deutschen Gesellschaft f¨ur Kinderchirurgie, der Deutschen Gesellschaft fur Kinder- und Jugendmedizin, der Deutschen Dermatologischen Gesellschaft, der Arbeitsgemeinschaft Padiatrische Dermatologie, und der Deutschen Gesellschaft fur Mund, Kiefer, Gesichtschirurgie. 2012.

59. Bettloch-Mas I., Martinez-Miravete M.T., Lucas-Costa A., de Lara A.M., Selva-Otalaurruchi J. Outpatient treatment of infantile hemangiomas with propranolol: A prospective study. Actas Dermo-Sifiliograficas. 2012; 103: 806–815.

60. Georgountzou A., Karavitakis E., Klimentopoulou A., Xaidara A., Kakourou T. Propranolol treatment for severe infantile hemangiomas: A single centre 3-year experience. Acta Paediatrica. 2012; 101 (10): 469–474.

61. Hsu T.C., Wang J.D., Chen C.H. et al. Treatment with propranolol for infantile hemangioma in 13 Taiwanese newborns and young infants. Pediatrics and Neonatology. 2012; 53: 125–132.

62. Pierre Fabre Dermatology: Randomized controlled multidose multicentre adaptive phase II/III study in infants. Clinical trials gov. identifier: NCTO 01056341. 2012.

63. Vlastarakos P.V., Papacharalampous G.X., Chrysostomou M. et al. Review article: Propranolol is an effective treatment for airway hemangiomas: A critical analysis and meta-analysis of published interventional studies. Acta Otorhinolaryngologica Italica. 2012; 32: 213–221.

64. Chen T.S., Eichenfield L.F., Friedlander S.F. Infantile hemangiomas: An update on pathogenesis and therapy. Pediatrics. 2013; 131: 99–108.

65. Drolet B.A., Frommelt P.C., Chamlin S.L. et al. Initiation and use of propranolol for infantile hemangioma: Report of a consensus conference. Pediatrics. 2013; 131 (1): 128–140.

66. Hesse B., Pedersen J.T. Hypoglycaemia after propranolol in children. Acta Med Scand. 1973; 193: 551−2.

67. Eibs H.G., Oberdisse U., Brambach U. Intoxication by beta-blockers in children and adolescents (authors transl). Monatschr Kinderheilkd. 1982; 130 (5): 292−5.

68. Lane A.S., Woodward A.C., Goldman M.R. Massive propranolol overdose poorly responsive to pharmacologic therapy: use of the intra-aortic balloon pump. Ann Emerg Med. 1987; 16 (12): 1381−3.

69. Polyaev Yu.A., Postnikov S.S., Myl'nikov A.A., Garbuzov R.V., Narbutov A.G., Shimanovskii N.L. New possibilities in the treatment of infantile hemangiomas using propranolol. Mezhdunarodnyi meditsinskii zhurnal – International medical journal. 2012; 2: 94−103.

70. Kucherov Yu.I., Zhirkova Yu.V., Getman A.N., Ivleva S.A., Rekhviashvili M.G. Clinical case propranolol treatment of hemangiomas of the liver in the newborn. Vestnik Rossiiskoi akademii meditsinskikh nauk – Annals of the Russian Academy of Medical Sciences. 2014; 5−6: 81−85.