Evaluation of the efficacy and safety of topical timolol maleate combined with oral propranolol treatment for parotid mixed infantile hemangiomas

Tong,Shuang; Xu,Da‑Peng; Liu,Zi‑Mei; Du,Yang; Wang,Xu‑Kai

doi:10.3892/ol.2016.4818

Evaluation of the efficacy and safety of topical timolol maleate combined with oral propranolol treatment for parotid mixed infantile hemangiomas

Authors:
- Shuang Tong
- Da‑Peng Xu
- Zi‑Mei Liu
- Yang Du
- Xu‑Kai Wang
View Affiliations

Affiliations: Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Liaoning Institute of Dental Research, Shenyang, Liaoning 110002, P.R. China
Published online on: July 7, 2016 https://doi.org/10.3892/ol.2016.4818
Pages: 1806-1810
Copyright: © Tong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to assess the efficacy and safety of topical timolol maleate combined with oral propranolol for parotid infantile hemangiomas. Between October 2012 and April 2014, propranolol was administered orally at a dose of 1.0-1.5 mg/kg/day to 22 infants with proliferating hemangiomas in the Department of Oral and Maxillofacial Surgery (Hospital of Stomatology, China Medical University, Shenyang, Liaoning, China). A small amount of 0.5% timolol maleate eye drop solution was topically applied with medical cotton swabs to the area of the lesion twice a day, every 12 h. The study group consisted of 9 males and 13 females, aged 2‑9 months, with a median age of 4.7 months. The lesions were all located in the parotid region, and measured between 3.5x4x0.5 and 7x8x3 cm in volume. The planned duration of therapy was 6‑8 months, or the two drugs were stopped when complete regression of the lesions was obtained. The therapeutic outcomes and safety were assessed by the change in the size and color of the tumor, and the presence of adverse effects throughout the course of treatment. The mean duration of therapy was 21.1 weeks and ranged from 3 to 8 months. Of the 22 patients, 16 demonstrated an excellent response, 6 showed a good response and 2 displayed a moderate response. No major collateral effects were observed. Overall, oral propranolol combined with topical timolol maleate may be used as the first‑line therapeutic choice in the treatment of infantile parotid mixed hemangioma.

View Figures

View References

1	Phung TL, Hochman M and Mihm MC: Current knowledge of the pathogenesis of infantile hemangiomas. Arch Facial Plast Surg. 7:319–321. 2005. View Article : Google Scholar : PubMed/NCBI
2	Yuan WL, Jin ZL, Wei JJ, Liu ZY, Xue L and Wang XK: Propranolol given orally for proliferating infantile haemangiomas: Analysis of efficacy and serological changes in vascular endothelial growth factor and endothelial nitric oxide synthase in 35 patients. Br J Oral Maxillofac Surg. 51:656–661. 2013. View Article : Google Scholar : PubMed/NCBI
3	Mulliken JB and Glowacki J: Hemangiomas and vascular malformations in infants and children: A classification based on endothelial characteristics. Plast Reconstr Surg. 69:412–422. 1982. View Article : Google Scholar : PubMed/NCBI
4	Buckmiller LM, Richter GT and Suen JY: Diagnosis and management of hemangiomas and vascular malformations of the head and neck. Oral Dis. 16:405–418. 2010. View Article : Google Scholar : PubMed/NCBI
5	Enjolras O and Gelbert F: Superficial hemangiomas: Associations and management. Pediatr Dermatol. 14:173–179. 1997. View Article : Google Scholar : PubMed/NCBI
6	Liu X, Tai M, Qin Z, Li K and Ge C: Clinical analysis for treatment of 1,080 cases of infantile hemangiomas with oral propranolol. Zhonghua Yi Xue Za Zhi. 94:1878–1881. 2014.(In Chinese). PubMed/NCBI
7	Waner M and Suen JY: Management of congenital vascular lesions of the head and neck. Oncology (Williston Park). 9:989–994, 997; discussion 998 passim. 1995.PubMed/NCBI
8	Malik MA, Menon P, Rao KL and Samujh R: 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. 2013. View Article : Google Scholar : PubMed/NCBI
9	Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, Horii KA, Lucky AW, Mancini AJ, Metry DW, Newell B, et al: Prospective study of infantile hemangiomas: Clinical characteristics predicting complications and treatment. Pediatrics. 118:882–887. 2006. View Article : Google Scholar : PubMed/NCBI
10	Achauer BM, Chang CJ and Vander Kam VM: Management of hemangioma of infancy: Review of 245 patients. Plast Reconstr Surg. 99:1301–1308. 1997. View Article : Google Scholar : PubMed/NCBI
11	Mantadakis E, Tsouvala E, Deftereos S, Danielides V and Chatzimichael A: Involution of a large parotid hemangioma with oral propranolol: An illustrative report and review of the literature. Case Rep Pediatr. 2012:3538122012.PubMed/NCBI
12	Zheng JW: Infantile hemangiomas: Seldom wait and see. China Journal of Oral and Maxillofacial Surgery. 10:163–164. 2012.(In Chinese).
13	Bennett ML, Fleischer AB Jr, Chamlin SL and Frieden IJ: Oral corticosteroid use is effective for cutaneous hemangiomas: An evidence-based evaluation. Arch Dermatol. 137:1208–1213. 2001. View Article : Google Scholar : PubMed/NCBI
14	Gangopadhyay AN, Sharma SP, Gopal SC, Gupta DK, Panjawani K and Sinha JK: Local steroid therapy in cutaneous hemangiomas. Indian Pediatr. 33:31–33. 1996.PubMed/NCBI
15	Muir T, Kirsten M, Fourie P, Dippenaar N and Ionescu GO: Intralesional bleomycin injection (IBI) treatment for haemangiomas and congenital vascular malformations. Pediatr Surg Int. 19:766–773. 2004. View Article : Google Scholar : PubMed/NCBI
16	Omidvari S, Nezakatgoo N, Ahmadloo N, Mohammadianpanah M and Mosalaei A: Role of intralesional bleomycin in the treatment of complicated hemangiomas: Prospective clinical study. Dermatol Surg. 31:499–501. 2005. View Article : Google Scholar : PubMed/NCBI
17	Enjolras O, Brevière GM, Roger G, Tovi M, Pellegrino B, Varotti E, Soupre V, Picard A and Leverger G: Vincristine treatment for function- and life-threatening infantile hemangioma. Arch Pediatr. 11:99–107. 2004.(In French). View Article : Google Scholar : PubMed/NCBI
18	Ezekowitz RA, Mulliken JB and Folkman J: Interferon alfa-2a therapy for life-threatening hemangiomas of infancy. N Engl J Med. 326:1456–1463. 1992. View Article : Google Scholar : PubMed/NCBI
19	Hochman A and Mascareno A: Management of nasal hemangiomas. Arch Facial Plast Surg. 7:295–300. 2005. View Article : Google Scholar : PubMed/NCBI
20	Hamou C, Diner PA, Dalmonte P, Vercellino N, Soupre V, Enjolras O, Vazquez MP and Picard A: Nasal tip haemangiomas: Guidelines for an early surgical approach. J Plast Reconstr Aesthet Surg. 63:934–939. 2010. View Article : Google Scholar : PubMed/NCBI
21	Zheng JW, Zhou GY, Wang YA and Zhang ZY: Management of head and neck hemangiomas in China. Chin Med J (Engl). 121:1037–1042. 2008.PubMed/NCBI
22	Léauté-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB and Taïeb A: Propranolol for severe hemangiomas of infancy. N Engl J Med. 358:2649–2651. 2008. View Article : Google Scholar : PubMed/NCBI
23	Price CJ, Lattouf C, Baum B, McLeod M, Schachner LA, Duarte AM and Connelly EA: Propranlol vs corticosteroids for infantile hemangiomas: A multicenter retrospective analysis. Arch Dermatol. 147:1371–1376. 2011. View Article : Google Scholar : PubMed/NCBI
24	Storch CH and Hoeger PH: Propranolol for infantile haemangiomas: Insights into the molecular mechanisms of action. Br J Dermatol. 163:269–274. 2010. View Article : Google Scholar : PubMed/NCBI
25	Ribatti D: The crucial role of vascular permeability factor/vascular endothelial factor in angiogenesis: A historical review. Br J Haematol. 128:303–309. 2005. View Article : Google Scholar : PubMed/NCBI
26	Ye XX, Jin YB, Lin XX, Ma G, Chen XD, Qiu YJ, Chen H and Hu XJ: Topical timolol in the treatment of periocular superficial infantile hemangiomas: A prospective study. Zhonghua Zheng Xing Wai Ke Za Zhi. 28:161–164. 2012.(In Chinese). PubMed/NCBI
27	Coppens G, Stalmans I, Zeyen T and Casteels I: The safety andefficacy of glaucoma medication in the pediatric population. J Pediatr Ophthalmol Strabismus. 46:12–18. 2009. View Article : Google Scholar : PubMed/NCBI
28	Guo S and Ni N: Topical treatment for capillary hemangioma of the eyelid using beta-blocker solution. Arch Ophthalmol. 128:255–256. 2010. View Article : Google Scholar : PubMed/NCBI
29	Prey S, Voisard JJ, Delarue A, Lebbe G, Taïeb A, Leaute-Labreze C and Ezzedine K: Safety of propranolol therapy for severe infantile hemangioma. JAMA. 315:413–415. 2016. View Article : Google Scholar : PubMed/NCBI
30	Pope E and Chakkittakandiyil A: Topical timolol gel for infantile hemangiomas: A pilot study. Arch Dermatol. 146:564–565. 2010. View Article : Google Scholar : PubMed/NCBI
31	Xu Y, Xue L, Wei J, Lei B, Liu Z and Wang X: Oral propranolol treatment for infants with proliferating hemangiomas: Clinical analysis of 35 cases. Zhongguo Kouqiang He Mian Waike Zazhi. 10:159–162. 2012.(In Chinese).
32	Zheng JW, Zhou Q, Yang XJ, Wang YA, Fan XD, Zhou GY, Zhang ZY and Suen JY: Treatment guideline for hemangiomas and vascular malformations of the head and neck. Head Neck. 32:1088–1098. 2010. View Article : Google Scholar : PubMed/NCBI
33	Zheng JW: Comment on efficacy and safety of propranolol in the treatment of parotid hemangioma. Cutan Ocul Toxicol. 30:333–334. 2011. View Article : Google Scholar : PubMed/NCBI
34	Xu DP, Cao RY and Tong S: Topical timolol maleate for superficial infantile hemangiomas: an observational study. J Oral Maxillofac Surg. 73:1089–1094. 2015. View Article : Google Scholar : PubMed/NCBI
35	Chan H, Mckay C, Adam S and Wargon O: RCT of timolol maleate gel for superficial infantile hemangiomas in 5-to 24-week-olds. Pediatrics. 131:e1739–e1747. 2013. View Article : Google Scholar : PubMed/NCBI
36	Li G, Xu DP, Tong S, Xue L, Sun NN and Wang XK: Oral Propranolol With Topical Timolol Maleate Therapy for Mixed Infantile Hemangiomas in Oral and Maxillofacial Regions. J Craniofac Surg. 27:56–60. 2016. View Article : Google Scholar : PubMed/NCBI
37	Storch CH and Hoeger PH: Propranolol for infantile hemangiomas: Insights into the molecular mechanisms of action. Br J Dermatol. 163:269–274. 2010. View Article : Google Scholar : PubMed/NCBI
38	Itinteang T, Brasch HD, Tan ST and Day DJ: Expression of components of the renin-angiotensin system in proliferating infantile hemangioma may account for the propranolol-induced accelerated involution. J Plast Reconstr Aesthet. 64:759–765. 2010. View Article : Google Scholar