ORAL TOPICAL TIMOLOL MALEAT OR ORAL PROPRANOLOL TREATMENT FOR INFANTILE HEMANGIOMAS: CLINICAL ANALYSIS OF 403 PATIENTS
Objective: Infantile hemangiomas (IH) are the most common benign vascular tumors of infancy. Propranolol (P), a nonselective beta-blocker, has been successfully used in managing IHs. Ongoing studies investigate the efficacy of the topical β-antagonist timolol maleate (TM) in IHs. The aim of this study is to assess the effects of interventions for managing infantile hemangiomas in children.
Material and Methods: We retrospectively reviewed a total of 403 IH patients from March 2021 to March 2022. The patients were stratified into three groups. Patients in Group 1 were given TM at a dose of one drop topically twice a day, 0.5%. Patients in Group 2 were given P at a dose of 1 mg/kg twice a day. The patients in Group 3 did not receive any treatment, and observation was conducted solely by contacting the controls.
Results: The median age of diagnosis was 5 months (range 0-60), with 57.1% of the cases being male. While TM treatment was applied to 32% of the children and P treatment was applied to 46.9% of the children, no treatment was administered in 21.1%. The most common location of hemangiomas was the face, accounting for 39.2%. Hemangiomas were observed in more than one location in 48 (12%) children. The median follow-up period for the patients was 4 months (range 0-28). Hemangiomas remained unchanged in 28.3% of all cases, shrank in 60.3%, and continued to grow in 11.4%. The primary indication for initiating TM was superficial hemangiomas and infants younger than 6 months. The leading reason for starting P significantly higher than in the other groups (p:0.001). No statistically significant differences were observed between the groups regarding bleeding and ulceration rates (p>0.05).
Conclusion: The efficacy of propranolol in treating IH was higher than that of TM.
1. Léauté-Labréze C, Roque E, Hubiche T, Boralevi F, Thambo JB, Taïeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008;358(24):2649-51. doi: 10.1056/NEJMc0708819.
2. Ji Y, Chen S, Xu C, Li L, Xiang B. The use of propranolol in the treatment of infantile haemangiomas: An update on potential mechanisms of action. Br J Dermatol. 2015;172(1):24-32. doi: 10.1111/bjd.13388.
3. Rodríguez Bandera AI, Sebaratnam DF, Wargon O, Wong LF. Infantile hemangioma. Part 1: Epidemiology, pathogenesis, clinical presentation and assessment. J Am Acad Dermatol. 2021;85(6):1379-92. doi: 10.1016/j.jaad.2021.08.019.
4. Elajmi A, Clapuyt P, Hammer F, Bataille AC, Lengele B, Boon LM. Prise en charge des anomalies vasculaires chez l’enfant [Management of vascular anomalies in children]. Ann Chir Plast Esthet. 2016;61(5):480-97. French. doi: 10.1016/j.anplas.2016.06.015.
5. Chen TS, Eichenfield LF, Friedlander SF. Infantile hemangiomas: an update on pathogenesis and therapy. Pediatrics. 2013;131(1): 99-108. doi: 10.1542/peds.2012-1128.
6. North PE, Waner M, Mizeracki A, Mrak RE, Nicholas R, Kincannon J, et al. A unique microvascular phenotype shared by juvenile hemangiomas and human placenta. Arch Dermatol. 2001;137(5):559-70.
7. Holland KE, Drolet BA. Approach to the patient with an Infantile Hemangioma. Dermatol Clin. 2013;31(2):289-301. doi: 10.1016/j.det.2012.12.006.
8. Ding Y, Zhang JZ, Yu SR, Xiang F, Kang XJ. Risk factors for infantile hemangioma: a meta-analysis. World J Pediatr. 2020;16(4):377-84. doi: 10.1007/s12519-019-00327-2.
9. Chang LC, Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, et al. Growth characteristics of infantile hemangiomas: implications for management. Pediatrics. 2008;122(2):360-7. doi: 10.1542/peds.2007-2767.
10. Luu M, Frieden IJ. Hemangioma: clinical course, complications and management. Br J Dermatol. 2013;169(1):20-30. doi: 10.1111/bjd.12436.
11. Esterly NB. Cutaneous hemangiomas, vascular stains and malformations, and associated syndromes. Curr Probl Pediatr. 1996;26(1):3-39. doi: 10.1016/s0045-9380(96)80023-5.
12. Saka B, Téclessou J, Akakpo S, Mahamadou G, Mouhari-Toure A, Soga Gottara W, et al. Traitement des hémangiomes infantiles au Togo [Treatment of infantile hemangioma in Togo]. Ann Dermatol Venereol. 2018;145(12):790-2. French. doi: 10.1016/j.annder.2018.07.016.
13. Dávila-Osorio VL, Iznardo H, Roé E, Puig L, Baselga E. Propranolol-resistant infantile hemangioma successfully treated with sirolimus. Pediatr Dermatol. 2020;37(4):684-6. doi: 10.1111/pde.14163.
14. Hadžić D, Selimović A, Husarić E, Ćosićkić A, Zulić E. Pediatric emergency of unexpected cause: infantile fibromatosis -case Report. Sanamed. Online First, July 2023. doi:10.5937/sanamed0-44771.
15. Krowchuk DP, Frieden IJ, Mancini AJ, Darrow DH, Blei F, Greene AK, et al. Clinical Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics. 2019;143(1):e20183475. doi: 10.1542/peds.2018-3475.
16. Colmant C, Powell J. Medical management of infantile hemangiomas: An update. Pediatr Drugs. 2022;24(1):29-43. doi: 10.1007/s40272-021-00477-9.
17. Schrenk S, Boscolo E. A transcription factor is the target of propranolol treatment in infantile hemangioma. J Clin Invest. 2022;132(3):e156863. doi: 10.1172/JCI156863.
18. Leung AKC, Lam JM, Leong KF, Hon KL. Infantile hemangioma: an updated review. Curr Pediatr Rev. 2021;17(1):55-69. doi: 10.2174/1573396316666200508100038.
19. Dilek M, Bekdas D, Bilir SG, Demircioglu F, Karatas Z, Erkocoglu M, et al. Infantile hemangioma and oral propranolol therapy. S.E.H.T.B. 2015; 49(2),148-51. doi:10.5350/SEMB.20150106055537.
20. Muñoz-Garza FZ, Ríos M, Roé-Crespo E, Bernabeu-Wittel J, Montserrat-García MT, Puig L, et al. Efficacy and safety of topical timolol for the treatment of infantile hemangioma in the early proliferative stage: a randomized clinical trial. JAMA Dermatol. 2021;157(5):583-7. doi: 10.1001/jamadermatol.2021.0596.
21. Sebaratnam DF, Rodríguez Bandera AL, Wong LF, Wargon O. Infantile hemangioma. Part 2: Management. J Am Acad Dermatol. 2021;85(6):1395-404. doi: 10.1016/j.jaad.2021.08.020.
22. Frommelt P, Juern A, Siegel D, Holland K, Seefeldt M, Yu J, et al. Adverse events in young and preterm infants receiving topical timolol for infantile hemangioma. Pediatr Dermatol. 2016;33(4):405-14. doi: 10.1111/pde.12869.
23. Solman L, Glover M, Beattie PE, Buckley H, Clark S, Gach JE, et al. Oral propranolol in the treatment of proliferating infantile haemangiomas: British Society for Paediatric Dermatology consensus guidelines. Br J Dermatol. 2018;179(3):582-9. doi: 10.1111/bjd.16779.
24. Yu Z, Cai R, Chang L, Qiu Y, Chen X, Chen Q, et al. Clinical and radiological outcomes of infantile hemangioma treated with oral propranolol: A long-term follow-up study. J Dermatol. 2019;46(5):376-82. doi: 10.1111/1346-8138.14853.
25. Yang H, Hu DL, Shu Q, Guo XD. Efficacy and adverse effects of oral propranolol in infantile hemangioma: a meta-analysis of comparative studies. World J Pediatr. 2019;15(6):546-58. doi: 10.1007/s12519-019-00285-9.
26. Ainipully AM, Narayanan SK, Vazhiyodan AP, Somnath P. Oral propranolol in infantile hemangiomas: Analysis of factors that affect the outcome. J Indian Assoc Pediatr Surg. 2019;24(3):170-5. doi: 10.4103/jiaps.JIAPS_12_18.
29. Anwar F, Mahmood E, Sharif S, Shah R, Jamgochian M, Ouellette S, et al. Topical application of 0.5% timolol maleate hydrogel for the treatment of superficial infantile hemangiomas. J Drugs Dermatol. 2023;22(6):594-8. doi: 10.36849/JDD.7054.
30. Sun L, Wang C, Cao Y, Lv X, Tian L, Liu D, et al. Fractional 2940-nm Er: YAG laser-assisted drug delivery of timolol maleate for the treatment of deep infantile hemangioma. J Dermatolog Treat. 2021;32(8):1053-9. doi: 10.1080/09546634.2020.1729330.
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