Pharmacologic therapies for infantile hemangioma: is there a rational basis?

BACKGROUND Infantile hemangioma is the most common tumor of infancy. The majority of cases are managed conservatively, but intervention is necessary in approximately 10 percent of cases because of the threat to life or function or because of tissue distortion or destruction. The mainstay treatment for these problematic proliferating infantile hemangiomas is pharmacologic therapy, mostly discovered serendipitously. METHODS This review examines the rational basis of the hitherto empirical pharmacologic therapies for the enigmatic infantile hemangioma, in light of new knowledge regarding its biology, including the critical roles of stem cells and the renin-angiotensin system. RESULTS Steroids have remained the first-line therapy for problematic infantile hemangioma for over 40 years despite their known side effects and failure rates. Vincristine has emerged as an alternative to interferon for steroid-resistant cases because of interferon's adverse effects, especially neurotoxicity. β-Blockers are now the preferred first-line therapy for problematic cases. There is increasing evidence that infantile hemangioma is a disorder of aberrant proliferation and differentiation of primitive mesoderm-derived neural crest phenotypic cells. This primitive phenotype that gives rise to a hemogenic endothelium intermediate has the ability to undergo primitive erythropoiesis and terminal mesenchymal differentiation. CONCLUSIONS The recent discovery of the crucial role of stem cells and the inferred role of the renin-angiotensin system in the biology of infantile hemangioma underscores the possibility of even more targeted therapies, by using modulators of the renin-angiotensin system, on infantile hemangioma. The observation of the potential role of these traditional antihypertensive agents in stem cell biology may lead to better understanding of developmental biology and tumor stem cell growth.