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Figure 1.
Regression of infantile hemangiomas over time in 2 patients. A, Four-month-old patient with a left forehead hemangioma. B, A 14-month-old patient with a philtrum hemangioma.

Regression of infantile hemangiomas over time in 2 patients. A, Four-month-old patient with a left forehead hemangioma. B, A 14-month-old patient with a philtrum hemangioma.

Figure 2.
Change in mean combined visual analog scale score (VAS) (range, 0-100 mm) over the course of treatment with timolol maleate, 0.5%, gel.

Change in mean combined visual analog scale score (VAS) (range, 0-100 mm) over the course of treatment with timolol maleate, 0.5%, gel.

Table. 
Summary of Patient Characteristics and Treatment Outcomes
Summary of Patient Characteristics and Treatment Outcomes
1.
Drolet  BAEsterly  NBFrieden  IJ Hemangiomas in children. N Engl J Med 1999;341 (3) 173- 181
PubMedArticle
2.
Metry  DWHebert  AA Benign cutaneous vascular tumors of infancy: when to worry, what to do. Arch Dermatol 2000;136 (7) 905- 914
PubMedArticle
3.
Kilcline  CFrieden  IJ Infantile hemangiomas: how common are they? a systematic review of the medical literature. Pediatr Dermatol 2008;25 (2) 168- 173
PubMedArticle
4.
Léauté-Labrèze  CDumas de la Roque  EHubiche  TBoralevi  FThambo  JBTaïeb  A Propranolol for severe hemangiomas of infancy. N Engl J Med 2008;358 (24) 2649- 2651
PubMedArticle
5.
D’Angelo  GLee  HWeiner  RI cAMP-dependent protein kinase inhibits the mitogenic action of vascular endothelial growth factor and fibroblast growth factor in capillary endothelial cells by blocking Raf activation. J Cell Biochem 1997;67 (3) 353- 366
PubMedArticle
Research Letter
May 2010

Topical Timolol Gel for Infantile Hemangiomas: A Pilot Study

Author Affiliations

Author Affiliations: Section of Dermatology (Dr Pope), Hospital for Sick Children (Dr Chakkittakandiyil), Toronto, Ontario, Canada.

Arch Dermatol. 2010;146(5):564-565. doi:10.1001/archdermatol.2010.67

Infantile hemangiomas (IHs) affect approximately 5% to 10% of white children.13 Most IHs undergo spontaneous involution, with only a small proportion requiring systemic intervention. For these, propranolol, a nonselective β-blocker, has emerged as an alternative systemic treatment to corticosteroids. The proposed therapeutic effects of propranolol on IHs are vasoconstriction; decreased expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) genes through downregulation of the RAF/mitogen–activated protein kinase pathway4,5; and apoptosis of capillary endothelial cells.4

Superficial IHs, particularly facial IHs, are associated with substantial parental distress, and we currently have a limited therapeutic repertoire. Timolol, a nonselective β-blocker similar to propranolol, is available in a topical gel formulation for treatment of glaucoma. We describe herein a series of 6 patients with superficial head and neck IHs treated with timolol maleate, 0.5%, gel.

Methods

A retrospective medical chart review analysis was performed of 6 patients with uncomplicated IHs in the head and neck area who were treated with timolol maleate, 0.5%, gel after informed consent. Timolol maleate, 0.5%, gel was applied topically twice daily to the IHs. Two investigators independently analyzed the response to treatment by comparing digital photographs at baseline vs at 4 weeks, 8 weeks, and final visits using a global score (−4 to +4) representing the difference in the size and/or extent and color of IHs (−2 [much worse], −1 [worse], 0 [same], +1 [better], and +2 [much better]) and a visual analog scale (VAS) (a 100-mm scale where −100 indicates that the hemangioma is twice as big; 0, no change; and +100, complete shrinkage). Descriptive statistics and the observer intraclass correlation were performed.

Results

The Table lists patient characteristics and response data. Clinically, 3 patients had IHs still in the proliferative phase; 2 had IHs that were stable; and 1 had IHs in regression. The difference in appearance of IHs at the various stages of treatment is shown in Figure 1. The mean change in VAS over time is presented in Figure 2. None of the patients experienced any local or systemic adverse events.

Comment

This proof of concept study shows that timolol maleate, 0.5%, gel, a nonselective β-blocker in topical formulation, is effective and safe for the treatment of IHs. Patients with superficial IHs and those treated for longer periods showed better response to timolol. Early intervention during the rapid proliferative phase (age 1-6 months) may result in better and faster resolution of IHs. This preliminary work suggests that topical timolol maleate, 0.5%, gel is an alternative to systemic propranolol for treatment of superficial IHs. Further prospective studies are required to substantiate the safety and efficacy of timolol maleate, 0.5%, gel in the treatment of IHs.

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Article Information

Correspondence: Dr Pope, Section of Dermatology, 555 University Ave, Toronto, ON M5G 1X8, Canada (elena.pope@sickkids.ca).

Accepted for Publication: November 15, 2009.

Author Contributions: Both authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Pope. Acquisition of data: Pope and Chakkittakandiyil. Analysis and interpretation of data: Pope and Chakkittakandiyil. Drafting of the manuscript: Pope and Chakkittakandiyil. Critical revision of the manuscript for important intellectual content: Pope. Statistical analysis: Pope. Administrative, technical, or material support: Chakkittakandiyil. Study supervision: Pope.

Financial Disclosure: None reported.

References
1.
Drolet  BAEsterly  NBFrieden  IJ Hemangiomas in children. N Engl J Med 1999;341 (3) 173- 181
PubMedArticle
2.
Metry  DWHebert  AA Benign cutaneous vascular tumors of infancy: when to worry, what to do. Arch Dermatol 2000;136 (7) 905- 914
PubMedArticle
3.
Kilcline  CFrieden  IJ Infantile hemangiomas: how common are they? a systematic review of the medical literature. Pediatr Dermatol 2008;25 (2) 168- 173
PubMedArticle
4.
Léauté-Labrèze  CDumas de la Roque  EHubiche  TBoralevi  FThambo  JBTaïeb  A Propranolol for severe hemangiomas of infancy. N Engl J Med 2008;358 (24) 2649- 2651
PubMedArticle
5.
D’Angelo  GLee  HWeiner  RI cAMP-dependent protein kinase inhibits the mitogenic action of vascular endothelial growth factor and fibroblast growth factor in capillary endothelial cells by blocking Raf activation. J Cell Biochem 1997;67 (3) 353- 366
PubMedArticle
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