Topical timolol: a safer alternative for complicated and un-complicated infantile hemangiomas.

Sir,

Infantile hemangiomas are the most common childhood tumors.[1] More than 50% of them occur in the head and neck region.[1] As spontaneous regression occurs over years, active intervention is needed only for large complicated hemangiomas. But, even small uncomplicated hemangiomas in visibly prominent area like face can be emotionally disturbing to parents. Even after reassurance of spontaneous regression, often parents are not ready to wait for years to see the beautiful smile on their child's face.

A 3-month-old boy presented with hemangiomas of left mandibular area and chin and extending to lower lip with ulceration of lip, which was non-healing since 1 month. Recurrent bleeding from ulcer was causing difficulty in feeding [Figure 1]. A detailed examination was done, and patient was investigated.

Figure 1

Infantile hemangioma of chin with ulceration of lip

Ultrasound scan of the lesion was done to know the depth of the lesion. Ultrasound scan of abdomen, echocardiogram, and MRI of brain was done to rule out PHACES (posterior fossa defects, hemangioma, arterial anomalies, cardiac defects, co-arctation of aorta, eye anomalies, sterna clefting, and supra-umbilical raphae). Laryngeal examination ruled out laryngeal involvement. Blood investigations including platelet count were within normal limits.

Treatment was started with topical timolol 0.5% eye drops, 6 drops applied twice daily with gloved index finger over hemangioma. Ulcer was treated topically with plermin (platelet-derived growth factor, PDGF). Heart rate, respiratory rate was recorded every 6 hours, and blood glucose was monitored twice daily for 1 week. No abnormalities were detected. Ulcer healed completely by 1 week with 40% reduction in hemangioma [Figure 2], 90% improvement was observed by 12 weeks [Figure 3].

Figure 2

After 1 week of topical timolol and topical plermin treatment

Figure 3

Near complete resolution, after 12 weeks of treatment

First-line treatment of large complicated hemangiomas is systemic steroids.[2] Knowing the side-effects of steroids,[3] many educated parents are reluctant to start their children on steroids. 40% hemangiomas treated with steroids show rebound after stopping steroids.[2] Systemic propranolol gives excellent results but needs vigilant monitoring.[4] Interferon and laser are costlier alternatives, but results are not better. Intralesional steroids are given for smaller hemangiomas,[5] but its use is limited by side-effects like secondary infection and embolization. Imiquimoid has been found useful. It can cause crusting and erythema. Surgical excision of the hemangioma can be done, but scar may be worse than that of spontaneous regression.

Topical timolol is safer alternative. It can be safely given for both complicated and uncomplicated hemangiomas in proliferative stage, as side effects are minimal and response is excellent. It has been in use for eye-lid hemangiomas.[6] In one study, timolol was used for hemangioma with PHACES; the only side-effect reported was pruritus.[7] Another pilot study showed an average regression in 3.3 months with topical timolol.[8] Topical application of plermin (PDGF) helps in healing of the ulcer by increasing the mitogenesis of fibroblasts and endothelium. It has been found useful in ulcerated hemangiomas of diaper area.[9]

Initial and immediate effect of non-selective Beta-blocker is by vasoconstriction, which can be noticed on 3rd day onwards. It inhibits the growth factor responsible for proliferative phase. Later, it aids in apoptosis, which leads to involution of hemangiomas. Systemically propranalol is found to be very effective during proliferative stage, but complications like respiratory distress, hypo-glycemea, bradycardia needs vigilant monitoring.[4] Topical timolol gives similar response and can be safely used in both complicated and uncomplicated hemangioma. Side-effects like asthma exacerbation, chynestokes breathing have been reported with use of timolol for pediatric glaucoma.[6] So, caution is needed in treating very large lesions and in infants with cardio-respiratory disorders.