A novel approach to port-wine stains

ORIGINAL ARTICLE, p 669 Port‐wine stains (PWSs) are capillary vascular malformations that occur in 3 per 1000 live births. Selective photothermolysis of PWS blood vessels with the pulsed‐dye laser (PDL) is considered the gold standard of treatment. PDL is very effective at PWS clearance, with a low incidence of side‐effects.1 However, multiple treatments are required in part due to the body's normal wound healing response, which results in revascularization and regeneration of PWS blood vessels following laser exposure.2 PDL‐induced angiogenesis makes it very difficult to achieve complete clearance of PWSs. This has prompted investigation into combination therapy with antiangiogenic agents after laser irradiation to modulate the neovascularization skin response to laser damage and enhance the effects of laser therapy. Rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), was initially investigated as a potential adjuvant therapy after laser irradiation. Rapamycin is thought to have antiangiogenic properties through downregulation of hypoxia‐inducible factor (HIF)‐1α, which leads to a decrease in vascular endothelial growth factor (VEGF) production and reduction in the stimulation of VEGF by vascular endothelial cells.3 4 Both systemic and topical formulations of rapamycin have shown promising inhibition of neovascularization in the skin after laser treatment.5 6 Topical formulations are preferable in order to obviate systemic side‐effects, assuming that an appropriate depth of penetration is achievable. Initial studies with rapamycin have led to the investigation of other antiangiogenic agents such as imiquimod, which activates toll‐like receptor 7 leading to activation of antiangiogenic cytokines and reduction of angiogenic stimulators.7