Therapies for infantile hemangiomas need more clinical studies

Key Points

National report - Despite recent advances, topical and systemic treatments for infantile hemangiomas need more randomized, controlled trials to help guide treatment decisions.

Topical medications generally work best for localized, superficial hemangiomas, says Maria Garzon, M.D., professor of clinical dermatology and clinical pediatrics, Columbia University, New York.

"The beta blocker that has been reported most commonly is topical timolol maleate (Timoptic, Aton Pharma). It's a nonselective beta blocker, like propranolol," approved for treatment of glaucoma, Dr. Garzon says. In one case series, topical timolol 0.5 percent gel applied twice daily for an average of 3.33 months demonstrated safety and increasing efficacy with longer treatment periods. (Pope E, Chakkittakandiyil A. Arch Dermatol. 2010;146(5):564-565).

Dr. Garzon says that ultra-potent topical corticosteroids achieve moderate success on selected small superficial hemangiomas. In a review of hemangiomas treated with topical steroids by Dr. Garzon and two co-authors, about one-third of patients achieved good responses, which could include color improvement, growth containment or lesion shrinkage (Garzon MC, Lucky AW, Hawrot A, Frieden IJ. J Am Acad Dermatol. 2005;52(2):281-286). Additionally, 38 percent achieved partial response; 27 percent did not respond.

Study authors concluded that topical steroids potentially work for small, thin, focal lesions and lesions on the face or other areas that provoke parental anxiety. Dr. Garzon says patients with periocular lesions should be followed by ophthalmologists to ensure they don't need systemic treatments. "This is true for all periocular lesions treated with any topical therapy," she says.

Several case reports and series have reported on use of imiquimod for hemangiomas.

"Some reports show effectiveness, again for superficial lesions," Dr. Garzon says, but based on these reports, patients can experience local irritation, as well as crusting and erosion of the hemangioma's surface. "That's one of the reasons I have avoided this therapy."

On a broader scale, "Most of the information we have on topical therapy is based on case series and reports. Most of this therapy is employed during the proliferative phase," Dr. Garzon says.

Systemic therapies

Dermatologists typically choose topical treatments for superficial lesions largely because these therapies reduce systemic drug exposure, Dr. Garzon says, but "what you see on the surface of the skin may only be the superficial portion of a deeper lesion. This is particularly true for periocular hemangiomas."

Moreover, "Systemic absorption of topical medications can occur with large lesions. Neonates and infants are at increased risk for systemic absorption. This is particularly true in preterm infants, because in addition to an increased skin surface area to volume ratio, they also have an immature skin barrier," she says.

Ulceration also increases systemic absorption, Dr. Garzon says. "Most often, ulceration occurs within the first four months of life." Risk factors include anogenital location, segmental morphology and mixed subtype. Treating ulcerations requires localized wound care, topical or systemic antiicrobials and treatments that alter the hemangioma proliferation, such as systemic therapy.

The goal of systemic therapy is to slow the rapid proliferative phase, thereby improving ulceration, Dr. Garzon says. Many physicians don't recognize the importance of pain management for patients with ulcerative hemangiomas, she adds.

With pharmacologic and laser therapies for ulcerated hemangiomas, she says, "The big question is, can we make matters worse by halting the proliferation too quickly? Many of us believe you can." Therefore, she recommends starting at the lower range of treatment doses and increasing gradually as needed.

When considering topical therapies, Dr. Garzon says dermatologists must keep keep in mind what would happen if the lesion was left without any treatment. "At time zero and as you're treating these patients, keep reassessing, 'What's the indication for therapy?' The answer may change your therapy as the hemangioma progresses through its growth phase. Consider lesion size, location, morphology and growth stage."