By Abby Van Voorhees, MD, September 01, 2011
In this month’s Acta Eruditorum column, Physician Editor Abby S. Van Voorhees, MD, talks with Christine Leaute-Laberze, MD, about her recent Journal of the American Academy of Dermatology article, “Propranolol for treatment of ulcerated infantile hemangiomas.”
Dr. Van Voorhees: What was the purpose of this study? What population was studied? What was the study design? How many children were treated? What was the dose of propranolol utilized?
Dr. Leaute-Labreze: This study was intended to evaluate the efficacy and tolerance of propranolol in the management of ulcerated infantile hemangiomas. All of the infants in the study were older than one month and were treated with propranolol for an ulcerated infantile hemangioma with follow-up; our follow-up period was at least one month. We treated 33 infants with a dosage of propranolol of 2-3 mg/kg/d.
Dr. Van Voorhees: How was propranolol’s potential for use in the care of hemangiomas identified? What types of hemangiomas were initially treated this way?
Dr. Leaute-Labreze: Our discovery was made while using propranolol in the treatment of severe hemangiomas with functional complications, such as those that affected the airways, and orbital hemangiomas. When we found, serendipitously, that it worked for these hemangiomas, we wanted to study its potential for treatment of other infantile hemangiomas as well.
Dr. Van Voorhees: What are the problems seen associated with ulcerated hemangiomas of childhood? How do these vary from non-ulcerated hemangiomas? What other treatments can be utilized for the management of these lesions? How effective are they? What are their potential risks? How quickly do they work?
Dr. Leaute-Labreze: Problems associated with ulcerated hemangiomas of childhood include pain, bleeding, and in rare cases superinfection; of course the presence of an unsightly scar as a sequel is also a concern. Dressing can be used as an alternative treatment — but with poor results in most cases. It is impossible to say how quickly dressing works, because there is no controlled study.
Non-ulcerating hemangiomas are painless and indolent tumors, but when an ulceration occurs, the child can be quite distressed. In addition, after spontaneous regression, non-ulcerating hemangiomas can result in minor sequelae such as telangiectasia, but ulcerating hemangiomas can induce scars — sometimes retractile or unsightly scars.[pagebreak]
Dr. Van Voorhees: What was the average time for healing of the ulcers in those treated with propranolol? Was there a difference in response time that depended on lesion location? What is the believed mechanism of action?
Dr. Leaute-Labreze: Average time for healing of ulcers with propranolol was four weeks; healing was faster for head and neck locations than the trunk and diaper areas. The mechanism of action is unknown, but we suspect that propranolol is active against hypoxic stress via the HIF (Hypoxic Inducible Factor) pathway.
Dr. Van Voorhees: What was the mean time to pain control? How is propranolol believed to be working to allow for the cessation of pain?
Dr. Leaute-Labreze: Mean time to pain control was 14 days, with a variation from one to 60 days. No clinical factors were identified as predictive of pain control. However, this effect depended on the rapidity of the healing. The larger the hemangioma is, the higher the risk of ulceration and the longer the time to heal.
Propranolol is effective in controlling an infantile hemangioma’s growth and acts on pain via beta2 receptors; it has a direct analgesic effect.
Dr. Van Voorhees: What were the side effects seen in treated patients? What were the parents’ perceptions of the effectiveness of treatment?
Dr. Leaute-Labreze: Side effects were minor: nightmares (five cases), esophageal reflux (one case), and cool hands and feet (one case). In 27 cases out of 33, the parents considered the treatment to be very effective.
Dr. Van Voorhees: Should propranolol be avoided in any types of hemangiomas of infancy?
Dr. Leaute-Labreze: Contraindications of propranolol are related to the child’s health and not the infantile hemangioma itself. Theoretically all hemangiomas could be treated with propranolol. However, oral propranolol should be reserved for complicated infantile hemangiomas; propranolol is a drug with some side effects, and the ratio of benefits versus risks should be evaluated. Eighty percent of infantile hemangiomas are benign and regress spontaneously.
Dr. Van Voorhees: How should one tell hemangiomas that will ulcerate from those that won’t?
Dr. Leaute-Labreze: The larger the hemangioma is, the higher the risk of ulceration; friction and maceration are also involved. That’s why we see many ulcerations in large segmental hemangiomas and in periorificial locations, for example, the diaper area, lips, etc.
Dr. Van Voorhees: How do you currently treat smaller lesions?
Dr. Leaute-Labreze: For small and localized infantile hemangiomas a local treatment is currently being studied. Beta blockers could be applied locally, such as timolol (an off-label use) and probably, soon, propranolol; a clinical study is planned for autumn 2011.
Dr. Leaute-Labreze is a member of the department of pediatric dermatology at the Bordeaux Children’s Hospital and the National Center for Rare Skin Disorders, both in Bordeaux, France. Her article, co-written with Melanie Saint-Jean, MD, Sebastien Barbarot, MD, and the members of the Research Group of the French Society for Pediatric Dermatology, was published in the Journal of the American Academy of Dermatology, 64(5), 827-832 (May 2011) after being published online Feb. 28, 2011. doi:10.1016/j.jaad.2010.12.040.