Infantile hemangioma (IH) is one of the most common benign tumors of infancy, with occurrence rates of 8.7 to 12.7%, and up to 60% of the tumors presenting in the head and neck region (1). The tumor has a unique life cycle that is divided into three phases: proliferative, involuting and involuted. Although IHs usually regress spontaneously and only a limited number of cases require treatment, the prognostic factors have not yet been elucidated. Therefore, intervention may be necessary during the early proliferative phase to avoid complications, such as hemorrhage, ulceration, disfigurement and associated dysfunctions, depending on the location and size of the IH. In addition, early intervention may relieve the mental burden of the parents and avoid casting an unpredictable psychological shadow on the child. Guo and Ni (2) first revealed successful outcomes following the use of timolol solution in the treatment of a 4-month-old infant with superficial capillary hemangioma of the eyelid in 2010. Moreover, timolol has been demonstrated to be efficacious in the topical treatment of superficial IH in numerous countries, in addition to China. The present study evaluates the efficacy and safety of the use of topical 0.5% timolol maleate drops in the treatment of cutaneous superficial IH in Chinese infants.

A total of 124 patients with superficial IH from March to November, 2012, were included in this prospective study (Table I). Of these, 101 received treatment with topical timolol, and 23 underwent observation only. At one week subsequent to the initiation of timolol treatment, a number of tumors in the treatment group became softer and lighter in color, and at four months following the initiation of treatment (Figs. 1 and 2), the overall response was class 1 in eight patients (7.9%), class 2 in 36 patients (35.6%) and class 3 in 57 patients (56.4%; Table II).

Complete regression was observed in 12 patients, who stopped receiving the drug and showed no relapse during a 3–5-month follow-up period. There was no significant difference in efficacy rates between 1- to 6-month-old patients and 7- to 12-month-old patients (P>0.05); however, the regression rate in the 1- to 6-month-old patients was significantly higher than that in the 7- to 12-month-old patients (P<0.05). No adverse effects were reported. In the observation group, there were 15 class 1 patients (65.2%), seven class 2 patients (30.4%) and one class 3 patient (4.3%). The regression and efficacy rates of the treated group were significantly improved compared with those in the observation group (P<0.05).

Guo and Ni (2) were the first to reveal successful outcomes following the use of timolol solution in the treatment of a 4-month-old infant with superficial capillary hemangioma of the eyelid in 2010, and this success was subsequently reinforced by a series of other studies (4–7). However, to date, there have been relatively few studies on timolol treatment for IH, and the majority of these are case reports. Semkova and Kazandjieva (8) described the initial phase of a prospective study, which evaluated the efficacy and safety of topical 0.1% timolol gel for patients with IH. The patients were evaluated at 4-week intervals using the physician’s Global Assessment Score (GAS), and the mean result was an 85% improvement from baseline. Chambers et al (9) performed a retrospective, consecutive, nonrandomized, comparative single-masked cohort study, in which a good response (61.5%) was observed in the treatment group. By contrast, 0% of the observation group demonstrated a successful response. To date, the study by Chambers et al has been one of few to be undertaken in this field of research in the USA. Ye et al (10) investigated the efficacy and adverse effects of topical timolol maleate in the treatment of 12 periocular hemangiomas in a prospective study and observed that the control and regression rates were 83.3 and 50.0%, respectively. Following three months of treatment, 92.1% efficacy and 56.4% regression rates were observed. These rates were higher than those in the observation group. In the present study, erythromycin ointment was applied to prevent timolol leakage around the lesions and this may have increased the duration of drug action and improved the drug efficacy. The regression rate for the 1- to 6-month-old patients was significantly higher than that for the 7- to 12-month-olds; however, there was no significant difference in the efficacy rate. A further study with a large sample and a long follow-up period is required to confirm the efficacy of the treatment.

Timolol is a nonselective topical β-adrenergic antagonist that has been used in ophthalmology for >30 years. The predominant adverse effects include hypotension, hypoglycemia, bronchospasm and local pruritus. In the present study, the drug was topically applied to the skin of patients and, therefore, there was likely to be minimal absorption of the drug into the bloodstream. As expected, no systemic adverse reactions were observed during the treatment period of the study. Furthermore, no adverse effects have been reported in previous studies (2,7,8), with the exception of mild pruritus over the lesion following four weeks of treatment in a case where timolol application was used to treat an 18-month-old female with ulcerated hemangiomas associated with PHACE syndrome (5). In the experience of the authors, patients with bronchial asthma have not experienced attacks during treatment, and it is therefore proposed that timolol may be safely considered for use in the treatment of IH with bronchial asthma, sinus bradycardia and second- and third-degree atrioventricular block; however, there is a requirement for these patients to be observed closely during treatment. At present, there is a lack of relevant pharmacokinetic studies. Furthermore, the optimal drug dose and duration of treatment remain unclear.

Topical timolol treatment in superficial IH presents numerous advantages, and appears particularly useful as an effective, safe and relatively convenient treatment for this subtype of IH in patients up to 6 months of age.