To the Editor: Ulceration is the most common complication of infantile hemangiomas.1Chamlin S.L. Haggstrom A.N. Drolet B.A. Baselga E. Frieden I.J. Garzon M.C. et al.Multicenter prospective study of ulcerated hemangiomas.J Pediatr. 2007; 151: 684-689Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar Recent studies suggest that ulceration may arise because of an imbalance between angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF), because Ang-2 promotes angiogenesis in the presence of VEGF but causes endothelial cell death in the absence of VEGF.2Reiss Y. Scharpfenecker M. Grunow V. Koidl S. Thurston G. Gale N.W. et al.Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation.Nat Med. 2006; 12: 235-239Crossref PubMed Scopus (713) Google Scholar Agents that decrease the production of Ang-2 might promote ulcer healing. Recently, we showed that triphenylmethane dyes including gentian violet and brilliant green are potent inhibitors of nicotinamide adenine dinucleotide phosphate oxidases, which are highly expressed in endothelial cells and downregulate Ang-2 production.3Perry B.N. Govindarajan B. Bhandarkar S.S. Knaus U.G. Valo M. Sturk C. et al.Pharmacologic blockade of angiopoietin-2 is efficacious against model hemangiomas in mice.J Invest Dermatol. 2006; 126: 2316-2322Crossref PubMed Scopus (106) Google Scholar Eosin, which is also a triphenylmethane dye, is used in many countries for the treatment of diaper dermatitis and as a topical antibiotic.4Arad A. Mimouni D. Ben-Amitai D. Zeharia A. Mimouni M. Efficacy of topical application of eosin compared with zinc oxide paste and corticosteroid cream for diaper dermatitis.Dermatology. 1999; 199: 319-322Crossref PubMed Scopus (30) Google Scholar We tested whether eosin is efficacious in the treatment of ulcerated hemangiomas of infancy. Approval was obtained from the Institutional Review Board of the Schneider Children's Medical Center. Eosin 2% solution was applied three times a day unoccluded for superficial ulcers and once a day under hydrocolloid wound dressings for deep ulcers. Eighteen patients who had 21 well-documented photos of their hemangiomas were included in the study. The mean duration of treatment was 7 weeks (range, 3-14 weeks). Four ulcerated hemangiomas needed adjuvant therapy for complete reepithelialization (pulsed dye laser treatment in two cases and hydrocolloid dressings, with or without topical antibiotics, in four cases). One hemangioma required surgical excision. Complete ulcer healing was achieved in 16 hemangiomas after 4 weeks of treatment (Fig 1). There was no recurrence in any case. In order to determine whether eosin has the same mechanism of activity as gentian violet and brilliant green, we treated bend3 endothelial cells in tissue culture with eosin and demonstrated that eosin causes a significant suppression of Ang-2 mRNA in bend3 cells3Perry B.N. Govindarajan B. Bhandarkar S.S. Knaus U.G. Valo M. Sturk C. et al.Pharmacologic blockade of angiopoietin-2 is efficacious against model hemangiomas in mice.J Invest Dermatol. 2006; 126: 2316-2322Crossref PubMed Scopus (106) Google Scholar (Fig 2). In this study, we show that eosin inhibits production of Ang-2 in endothelial cells and may be efficacious in accelerating the healing of ulcerated hemangiomas of infancy. While eosin has also been shown to have photodynamic properties, it is unlikely that a photodynamic effect played a role, because the sites were not exposed to therapeutic light sources and were often occluded. Eosin offers several advantages in terms of treatment of infantile hemangiomas. First, it has a long record of human safety, including in infants.4Arad A. Mimouni D. Ben-Amitai D. Zeharia A. Mimouni M. Efficacy of topical application of eosin compared with zinc oxide paste and corticosteroid cream for diaper dermatitis.Dermatology. 1999; 199: 319-322Crossref PubMed Scopus (30) Google Scholar Second, in addition to being antiangiogenic, it has antibacterial properties. Third, it is less expensive than many other therapies, and is therefore amenable for use in the developing and the developed world. We believe that our pilot study demonstrates the efficacy of eosin in a pilot study of human hemangiomas of infancy, and provides a rationale for larger scale clinical trials of eosin in the treatment of hemangiomas of infancy and other angiogenic disorders.