November/December 2015
ORIGINAL CONTRIBUTION
Table. Site of Lesion, Response, and Side Effect of Timolol Maleate Case
Location of Hemangioma
Response to Treatment
Side Effect
1
Face
Good
None
2
Face
Excellent
None
3
Face
Good
Erythematous dermatitis
4
Face
Good
None
5
Nose
Excellent
None
6
Neck
Good
None
7
Upper extremity
Poor
None
8
Trunk
Good
None
9
Genitalia
Partial
None
blood glucose level, and complications, if any, were evaluated and managed accordingly. Photographic evaluation was performed at a subsequent follow-up visit. The response to treatment was evaluated based on criteria established by Garzon and colleagues5: (1) regression or cessation of growth, (2) shrinkage or flattening of the lesion, and (3) lightening of the surface color. Lesions demonstrating responses of two of the three criteria were judged to have good response, one criterion as partial response, and no improvement as no response. The success in reducing the size of the lesion after IH treatment in our case was confirmed clinically and supported by local ultrasonography and clinical photographs. Results The nine patients in our study were younger than 1 year, with a mean age of 5 months, and had a male to female ratio of 4:5. The size of the IHs ranged from 0.62 cm2 to 402 cm2. The anatomic locations of the superficial IHs were as follows: six (66.6%) in the head and neck region, one (11.1%) on the extremities, one (11.1%) in the genital region, and one (11.1%) on the trunk. The mean duration of treatment was 16 weeks (range, 8–13 weeks). Of nine patients, two (22.2%) showed excellent response, five (55.5%) showed good response, one (11.1%) showed partial response, and one (11.1%) showed poor response. One patient had erythematous scaly dermatitis during the treatment, but when inquired about the total number of applications, the patient’s parents revealed application of timolol maleate more than twice a day. The patient’s parents were counseled and timolol was stopped for a week, with administration of syrup prednisolone 1 mg/kg for a week that was gradually tapered and stopped. There was improvement in the erythema after which the patient was again put on timolol with significant reduction in the leSKINmed. 2015;13:429–431
sion color and size after appropriate application. The response to treatment is summarized in the Table. Discussion This study shows the efficacy of timolol in IHs associated with a side effect that occurred during the treatment period for which oral prednisolone was used and managed accordingly. This study is the first to report such a side effect with photographic documentation. The response to propranolol had been previously reported.6 Investigators serendipitously discovered that propranolol effectively treated hemangiomas in two infants, who had received the drug for cardiac complications while on corticosteroid therapy. Topical timolol has been used in IH.7 Long-term and widespread use of timolol and other topical β-blockers has yielded several case reports of drug-related wheezing, bradycardia, and respiratory depression, especially in infants and children treated with ocular timolol solution.8 Use of β-blockers causes vasoconstriction, change in color, and decreased expression of vascular endothelial growth factor and basic fibroblast growth factor genes through downregulation of the RAF/mitogen-activated protein kinase pathway.9 Although ophthalmic timolol solution resembles intravenous timolol in terms of systemic bioavailability, plasma kinetics, and cardiopulmonary effects,10 ophthalmic timolol gel has been shown to have less or insignificant systemic bioavailability than timolol ophthalmic solution. In adults, peak plasma concentrations after ocular administration of timolol 0.5% gel averaged <0.3 ng ⁄mL (lower limit of quantification of the assay), which suggests that there is minimal or no systemic bioavailability of timolol maleate gel.11 A study in 2002 demonstrated that approximately 80% of each drop (0.05 mL) of timolol 0.5% solution administered to an adult sample was systemically absorbed through the ocular and nasopharyngeal mucosa.10 Dif-
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Topical Timolol