Origin and development

San Francisco

- As researchers learn more about the origin of infantile hemangiomas, a particularly promising new treatment is emerging in the form of propranolol, an expert says.

"No one really knows where hemangiomas come from, although they’ve been described for a very long time," says Joseph Lam, M.D., assistant clinical professor, department of pediatrics, division of general pediatrics, and associate member, department of dermatology and skin sciences, University of British Columbia, Vancouver.

In recent years, though, researchers have noted several uncanny connections between hemangiomas and placental tissue, he says.For instance, "Hemangiomas tend to occur more in premature infants, a population characterized by placental anomalies, trauma and disease."

Markers

Regarding immunohistochemical markers, he adds, staining assays have shown that markers including GLUT1, FcgRII (FcgammaRII), Lewis Y antigen and merison stain positive in placental tissue and hemangiomas, but negative for any similar tissues (North PE et al. Hum Pathol. 2000;31:11-22; North PE et al. Arch Dermatol. 2001;137:559-70).

However, other researchers looked for trophoblasts, the building blocks of placental tissue, in hemangiomas and found none, he says. Likewise, Dr. Lam says hemangioma tissue lacks the villous organization of placental tissue.

Accordingly, he says, "We have evidence of uncanny similarities between hemangiomas tissue and placental tissue, but we can't fully establish the connection."

Similarly, he says the search for an appropriate animal model frustrated researchers - until recently.

Historically, Dr. Lam says, researchers could create lesions that looked like hemangiomas in mice, but the lesions didn't follow the normal growth-involution lifecycle of typical hemangiomas. Such lesions frequently proved fatal to the mice, he notes.

"However, researchers in China performed a somewhat crude experiment where they chopped up human hemangioma tissue and implanted it into nude mice.

"They found that the tissue behaved like hemangiomas. This may be the first true animal model for hemangiomas (Tang Y et al. Plast Reconstr Surg. 2007; 120(4):869-78.)," Dr. Lam says.

Stem cells

More recently, other researchers injected cultured pluripotent stem cells from human hemangioma tissue into mice.

"Amazingly, these cells that were injected were able to form (human) blood vessels within seven days. And within about two months, they involuted, as hemangiomas do in humans (Khan ZA et al. J Clin Invest. 2008 Jul;118(7):2592-9)."

The success of this experiment suggests that "Hemangiomas may come from a much earlier form of cell than we previously thought."

For treating problematic hemangiomas, Dr. Lam adds, the beta blocker propranolol shows promise.

Clinical study

In a French study involving two children with cardiac problems and hemangiomas, "These hemangiomas showed a dramatic response to the heart medication (Leaute-Labreze C et al. N Engl J Med 358(24):2649-2651, 2008)."

In appropriate therapeutic doses, he adds, propranolol appears safe for pediatric use. For example, according to American Association of Poison Control Centers data, since 1983, "there have been no deaths from propranolol use in children under age 6."

Nevertheless, he says patients on propranolol face a small but real risk of developing hypoglycemia.

Dr. Lam says he expects preliminary data from the first prospective, placebo-controlled trial of propranolol in infantile hemangiomas to be available in early 2010. DT

Disclosure: Dr. Lam reports no relevant financial interests.

For more information:

www.aad.org

http://clinicaltrials.gov/show/NCT00744185