Beta-blockers expand treatment options for infantile hemangiomas

VANCOUVER, B.C. – Propranolol may have revolutionized the treatment of infantile hemangiomas over the past decade, but other beta-blockers are making inroads in the treatment of these and other pediatric dermatologic disorders.

One such beta-blocker is atenolol, a hydrophilic cardioselective agent that acts principally on beta₁-adrenergic receptors, “and theoretically has less chance of hypoglycemia and bronchoconstriction,” Dr. Joseph M. Lam said at the annual meeting of the Pacific Dermatologic Association. Atenolol does not cross the blood-brain barrier and features once-daily dosing, he noted.

A recent noninferiority trial in 23 patients with infantile hemangiomas compared atenolol 1 mg/kg/day with propranolol 2 mg/kg/day, and followed the patients for 6 months (J. Am. Acad. Dermatol. 2014;70:1045-9). Patients in both groups achieved a similar rate of complete response (54% in the atenolol group, compared with 60% in the propranolol group) and there were no significant adverse effects in either group. “There was rebound growth in 26% of patients once the medication was withdrawn,” said Dr. Lam of the department of pediatrics at British Columbia Children’s Hospital, Vancouver, who was not affiliated with the study. “Initially there was more rebound growth in the propranolol group versus the atenolol group (four vs. two cases, respectively), but that was not significant.”

Another study compared oral nadolol with propranolol in patients aged 1-12 months: 10 on nadolol and 9 matched controls on propranolol (Br. J. Dermatol; 2013:168:222-4). After 24 weeks of treatment patients in the nadolol group had statistically superior lesion shrinkage, compared with those in the propranolol group (P less than .0001). Dr. Lam described nadolol as a nonselective beta-blocker that “has no intrinsic sympathomimetic activity, little myocardial depressant activity, and does not cross the blood-brain barrier. So theoretically, you have less sleep disturbance than with propranolol. Practically, it’s easier dosing than propranolol. It’s 2 mg/kg per day and you divide that b.i.d. The solution is 10 mg/mL.”

Researchers also are studying topical application of beta-blockers for hemangiomas and other skin conditions, Dr. Lam noted. A pilot study of six patients with infantile hemangiomas on the face and neck demonstrated that twice-daily topical administration of timolol maleate 0.5% was safe and effective (Arch. Dermatol. 2010;146:564-5). Dr. Lam characterized timolol as “a hydrophilic molecule that permeates poorly across intact skin, but doesn’t work great for deep hemangiomas. It’s a good choice for superficial hemangiomas, and anyone can use this.”

A larger, retrospective, multicenter cohort study of timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas also demonstrated positive results (Pediatr. Dermatol. 2012; 29:28-31). In that study, 72 of 73 treated patients improved, with better response seen in those who received the 0.5% solution.

In another pilot study, Chinese researchers assessed the efficacy of fractional carbon dioxide laser–assisted drug delivery of topical timolol solution for the treatment of deep infantile hemangioma (Pediatr. Dermatol. 2014;31:286-91). The regimen consisted of one pass without overlap delivered from a 10,600-nm fractional CO₂ laser to a .12-mm spot size with a single pulse of 25-30 mJ. The researchers rated the results as “excellent” in 44% of patients. “good” in 44%, and “moderate” in 11%. Plasma timolol levels were detectable in all patients.

Additional data from an unrelated case series found that use of topical timolol successfully treated pediatric pyogenic granulomas (Pediatric Dermatol. 2014; 31:203-7). The agent “doesn’t work as fast as with hemangiomas, but it works as well, which is great because most pyogenic granulomas in young children are on the face or neck area,” Dr. Lam noted. “Some took up to 6 months to respond, but all patients in this series had no further bleeding. That’s usually the main concern for families.”

Current evidence suggests that timolol does not work well for port wine stains and other vascular malformations. To date, it has shown mixed results for other vascular tumors such as kaposiform hemangioendothelioma, tufted angioma, and Kasabach-Merritt phenomenon.

Dr. Lam disclosed that he is a member of the scientific advisory board for Johnson & Johnson, and is a speaker for the company. He also is a member of the Eczema Society of Canada’s Board of Directors.

[email protected]

VANCOUVER, B.C. – Propranolol may have revolutionized the treatment of infantile hemangiomas over the past decade, but other beta-blockers are making inroads in the treatment of these and other pediatric dermatologic disorders.

One such beta-blocker is atenolol, a hydrophilic cardioselective agent that acts principally on beta₁-adrenergic receptors, “and theoretically has less chance of hypoglycemia and bronchoconstriction,” Dr. Joseph M. Lam said at the annual meeting of the Pacific Dermatologic Association. Atenolol does not cross the blood-brain barrier and features once-daily dosing, he noted.

A recent noninferiority trial in 23 patients with infantile hemangiomas compared atenolol 1 mg/kg/day with propranolol 2 mg/kg/day, and followed the patients for 6 months (J. Am. Acad. Dermatol. 2014;70:1045-9). Patients in both groups achieved a similar rate of complete response (54% in the atenolol group, compared with 60% in the propranolol group) and there were no significant adverse effects in either group. “There was rebound growth in 26% of patients once the medication was withdrawn,” said Dr. Lam of the department of pediatrics at British Columbia Children’s Hospital, Vancouver, who was not affiliated with the study. “Initially there was more rebound growth in the propranolol group versus the atenolol group (four vs. two cases, respectively), but that was not significant.”

Another study compared oral nadolol with propranolol in patients aged 1-12 months: 10 on nadolol and 9 matched controls on propranolol (Br. J. Dermatol; 2013:168:222-4). After 24 weeks of treatment patients in the nadolol group had statistically superior lesion shrinkage, compared with those in the propranolol group (P less than .0001). Dr. Lam described nadolol as a nonselective beta-blocker that “has no intrinsic sympathomimetic activity, little myocardial depressant activity, and does not cross the blood-brain barrier. So theoretically, you have less sleep disturbance than with propranolol. Practically, it’s easier dosing than propranolol. It’s 2 mg/kg per day and you divide that b.i.d. The solution is 10 mg/mL.”

Researchers also are studying topical application of beta-blockers for hemangiomas and other skin conditions, Dr. Lam noted. A pilot study of six patients with infantile hemangiomas on the face and neck demonstrated that twice-daily topical administration of timolol maleate 0.5% was safe and effective (Arch. Dermatol. 2010;146:564-5). Dr. Lam characterized timolol as “a hydrophilic molecule that permeates poorly across intact skin, but doesn’t work great for deep hemangiomas. It’s a good choice for superficial hemangiomas, and anyone can use this.”

A larger, retrospective, multicenter cohort study of timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas also demonstrated positive results (Pediatr. Dermatol. 2012; 29:28-31). In that study, 72 of 73 treated patients improved, with better response seen in those who received the 0.5% solution.

In another pilot study, Chinese researchers assessed the efficacy of fractional carbon dioxide laser–assisted drug delivery of topical timolol solution for the treatment of deep infantile hemangioma (Pediatr. Dermatol. 2014;31:286-91). The regimen consisted of one pass without overlap delivered from a 10,600-nm fractional CO₂ laser to a .12-mm spot size with a single pulse of 25-30 mJ. The researchers rated the results as “excellent” in 44% of patients. “good” in 44%, and “moderate” in 11%. Plasma timolol levels were detectable in all patients.

Additional data from an unrelated case series found that use of topical timolol successfully treated pediatric pyogenic granulomas (Pediatric Dermatol. 2014; 31:203-7). The agent “doesn’t work as fast as with hemangiomas, but it works as well, which is great because most pyogenic granulomas in young children are on the face or neck area,” Dr. Lam noted. “Some took up to 6 months to respond, but all patients in this series had no further bleeding. That’s usually the main concern for families.”

Current evidence suggests that timolol does not work well for port wine stains and other vascular malformations. To date, it has shown mixed results for other vascular tumors such as kaposiform hemangioendothelioma, tufted angioma, and Kasabach-Merritt phenomenon.

Dr. Lam disclosed that he is a member of the scientific advisory board for Johnson & Johnson, and is a speaker for the company. He also is a member of the Eczema Society of Canada’s Board of Directors.

[email protected]

VANCOUVER, B.C. – Propranolol may have revolutionized the treatment of infantile hemangiomas over the past decade, but other beta-blockers are making inroads in the treatment of these and other pediatric dermatologic disorders.

One such beta-blocker is atenolol, a hydrophilic cardioselective agent that acts principally on beta₁-adrenergic receptors, “and theoretically has less chance of hypoglycemia and bronchoconstriction,” Dr. Joseph M. Lam said at the annual meeting of the Pacific Dermatologic Association. Atenolol does not cross the blood-brain barrier and features once-daily dosing, he noted.

A recent noninferiority trial in 23 patients with infantile hemangiomas compared atenolol 1 mg/kg/day with propranolol 2 mg/kg/day, and followed the patients for 6 months (J. Am. Acad. Dermatol. 2014;70:1045-9). Patients in both groups achieved a similar rate of complete response (54% in the atenolol group, compared with 60% in the propranolol group) and there were no significant adverse effects in either group. “There was rebound growth in 26% of patients once the medication was withdrawn,” said Dr. Lam of the department of pediatrics at British Columbia Children’s Hospital, Vancouver, who was not affiliated with the study. “Initially there was more rebound growth in the propranolol group versus the atenolol group (four vs. two cases, respectively), but that was not significant.”

Another study compared oral nadolol with propranolol in patients aged 1-12 months: 10 on nadolol and 9 matched controls on propranolol (Br. J. Dermatol; 2013:168:222-4). After 24 weeks of treatment patients in the nadolol group had statistically superior lesion shrinkage, compared with those in the propranolol group (P less than .0001). Dr. Lam described nadolol as a nonselective beta-blocker that “has no intrinsic sympathomimetic activity, little myocardial depressant activity, and does not cross the blood-brain barrier. So theoretically, you have less sleep disturbance than with propranolol. Practically, it’s easier dosing than propranolol. It’s 2 mg/kg per day and you divide that b.i.d. The solution is 10 mg/mL.”

Researchers also are studying topical application of beta-blockers for hemangiomas and other skin conditions, Dr. Lam noted. A pilot study of six patients with infantile hemangiomas on the face and neck demonstrated that twice-daily topical administration of timolol maleate 0.5% was safe and effective (Arch. Dermatol. 2010;146:564-5). Dr. Lam characterized timolol as “a hydrophilic molecule that permeates poorly across intact skin, but doesn’t work great for deep hemangiomas. It’s a good choice for superficial hemangiomas, and anyone can use this.”

A larger, retrospective, multicenter cohort study of timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas also demonstrated positive results (Pediatr. Dermatol. 2012; 29:28-31). In that study, 72 of 73 treated patients improved, with better response seen in those who received the 0.5% solution.

In another pilot study, Chinese researchers assessed the efficacy of fractional carbon dioxide laser–assisted drug delivery of topical timolol solution for the treatment of deep infantile hemangioma (Pediatr. Dermatol. 2014;31:286-91). The regimen consisted of one pass without overlap delivered from a 10,600-nm fractional CO₂ laser to a .12-mm spot size with a single pulse of 25-30 mJ. The researchers rated the results as “excellent” in 44% of patients. “good” in 44%, and “moderate” in 11%. Plasma timolol levels were detectable in all patients.

Additional data from an unrelated case series found that use of topical timolol successfully treated pediatric pyogenic granulomas (Pediatric Dermatol. 2014; 31:203-7). The agent “doesn’t work as fast as with hemangiomas, but it works as well, which is great because most pyogenic granulomas in young children are on the face or neck area,” Dr. Lam noted. “Some took up to 6 months to respond, but all patients in this series had no further bleeding. That’s usually the main concern for families.”

Current evidence suggests that timolol does not work well for port wine stains and other vascular malformations. To date, it has shown mixed results for other vascular tumors such as kaposiform hemangioendothelioma, tufted angioma, and Kasabach-Merritt phenomenon.

Dr. Lam disclosed that he is a member of the scientific advisory board for Johnson & Johnson, and is a speaker for the company. He also is a member of the Eczema Society of Canada’s Board of Directors.

[email protected]