PHACE Syndrome—before and after Propranolol Therapy

Abstract

A 5-week-old girl presented to our neuropediatric department to rule out Sturge-Weber syndrome. Eventually, our investigations led to a suspicion of posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities (PHACE) syndrome, a different phacomatosis. We then successfully initiated treatment with propranolol for an extensive facial hemangioma. Postnatally, the mother noted a reddish shimmer on the girl's face, growing rapidly (Figure, A). Initially, the facial lesion was considered to be an atypical port wine-stain, unresponsive to beta-blockers. Within weeks, the facial lesion grew into a massive hemangioma (Figure, B). A magnetic resonance angiography of the head and neck showed severe hypoplasia of the left internal carotid artery with good collateralization, but no leptomeningeal angiomatosis was noted. An ophthalmologic examination revealed no sign of glaucoma. The combination of a large segmental facial hemangioma (>5 cm in diameter) and severe hypoplasia of a large cerebral artery permitted the diagnosis of definite PHACE syndrome.1Metry D. Heyer G. Hess C. Garzon M. Haggstrom A. Frommelt P. et al.Consensus statement on diagnostic criteria for PHACE syndrome.Pediatrics. 2009; 124: 1447-1456Crossref PubMed Scopus (285) Google Scholar, 2Frieden I. Reese V. Cohen D. PHACE Syndrome. The association of posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities.Arch Dermatol. 1996; 132: 307-311Crossref PubMed Google Scholar This phacomatosis includes large facial hemangiomas and variable neurologic, cardiac, vascular, and ophthalmologic involvement. Respiratory compromise or stridor should prompt the clinician to suspect airway hemangioma.3Haggstrom A. Skillman S. Garzon M. Drolet B. Holland K. Matt B. et al.Clinical spectrum and risk of PHACE syndrome in cutaneous and airway hemangiomas.Arch Otolaryngol Head Neck Surg. 2011; 137: 680-687Crossref PubMed Scopus (23) Google Scholar, 4Durr M. Meyer A. Huoh K. Frieden I. Rosbe K. Airway hemangiomas in PHACE syndrome.Laryngoscope. 2012; 122: 2323-2329Crossref PubMed Scopus (35) Google Scholar These are potentially life-threatening hemangiomas that may require intubation and assisted ventilation, and possibly tracheostomy.5Smith D. Lee K. Milczuk K. Otolaryngologic manifestations of PHACE syndrome.Int J Pediatr Laryngol. 2004; 68: 1445-1450Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar Patients with PHACE syndrome and mandibular distribution of the facial hemangiomas are at particular risk of airway hemangioma.3Haggstrom A. Skillman S. Garzon M. Drolet B. Holland K. Matt B. et al.Clinical spectrum and risk of PHACE syndrome in cutaneous and airway hemangiomas.Arch Otolaryngol Head Neck Surg. 2011; 137: 680-687Crossref PubMed Scopus (23) Google Scholar In the absence of severe arteriopathy, early treatment of facial hemangioma with propranolol is a promising option.6Garzon M.C. Epstein L.G. Heyer G.L. Frommelt P.C. Orbach D.B. Baylis A.L. et al.PHACE syndrome: consensus-derived diagnosis and care recommendations.J Pediatr. 2016; 178 (e2): 24-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar Potential serious side effects (ie, bleeding/ulceration from hemangiomas) require close clinical monitoring.7Drolet B. Frommelt P. Chamlin S. Haggstrom A. Bauman N. Chiu Y. et al.Initiation and use of propranolol for infantile hemangioma: report of a consensus conference.Pediatrics. 2013; 131: 128-140Crossref PubMed Scopus (405) Google Scholar In our patient, propranolol therapy was pursued without complications over 3 years with striking success (Figure, C).