A healthy 5-week-old girl presents for evaluation of rapidly growing, flat-topped red papules on the left side of her face.
A healthy 5-week-old girl presents for evaluation of rapidly growing, flat-topped red papules on the left side of her face (Figure 1).
Diagnosis: Large segmental hemangioma with risk of PHACE
PHACE syndrome consists of posterior fossa brain malformation, hemangiomas of the face, arterial anomalies, cardiac anomalies, and eye abnormalities.1 It is primarily a cutaneous condition with many congenital anomalies. The term PHACE(s) is sometimes used when there are additional ventral developmental defects such as sternal cleft and/or subraumbilical raphe, neither of which was present in this patient.
A complete and thorough physical exam should be performed at initial patient presentation to evaluate for developmental anomalies, eye anomalies, and midline defects. Initial workup also includes a head and neck magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) and echocardiogram. If cardiac abnormalities are identified, a cardiac MRI/MRA is recommended to characterize the arch and brachiocephalic anatomy.1,2
A large segmental facial infantile hemangioma (IH) should raise concern for the possibility of PHACE syndrome. Infantile hemangiomas must be distinguished from port wine stains: IH are faintly present or absent at birth, and then grow quickly in the first 2 months of life; in contrast, port wine stains typically are readily apparent at birth and do not grow quickly. Infantile hemangiomas may begin as more of a purplish bruise-like lesion or telangiectasias with surrounding pallor and then develop their characteristic cherry-red color in the first weeks of life. Port wine stains may begin as a pink-red patch and develop a deeper red hue with time.2
The segmental IH of PHACE comprises 1 or more of 4 segments: frontotemporal, maxillary, mandibular, and/or frontonasal. Patients with PHACE may have subglottic airway hemangiomas and are at risk for airway obstruction.3 For this reason, MRA of the neck should be performed in addition to brain imaging.
Anomalies of the medium-sized vessels of the head and neck occur in approximately 40% of patients. Intracranial arterial anomalies localize to the same side as the facial IH. The presence of hypoplastic or progressively narrowing cerebral blood vessels increases the risk of arterial ischemic stroke, typically manifesting as hemiplegia and/or seizures.4 The most common structural brain anomaly in PHACE is unilateral cerebellar hypoplasia, but various cystic malformations of the posterior fossa, such as Dandy-Walker malformation, can be associated.
Cardiac, aortic arch, and brachiocephalic anomalies also are fairly common in PHACE. The prevalence of congenital heart disease can range from 41% to 67%.5 Aberrant subclavian arteries are common in PHACE syndrome. Therefore, when evaluating for coarctation of the aorta, the 4-extremity blood pressure assessment for a gradient between the upper and lower extremities may not be accurate.
Congenital anomalies of the eye may involve the posterior or anterior segment. Posterior segment anomalies are part of the major diagnostic criteria and include persistent fetal vessels, “morning glory” disc, peripapillary staphyloma, and optic nerve hypoplasia. Anterior segment anomalies are minor diagnostic criteria, including coloboma, iris hypoplasia, cataracts, sclerocornea, and iris hypoplasia.5
Propranolol is now first-line therapy for complicated IH but should be used cautiously in PHACE syndrome. If possible, imaging studies of the head and neck should be performed prior to initiation of oral propranolol to evaluate the severity of cervical and cerebral arteriopathy and cardiac anomalies. Blood pressure fluctuations may increase the risk for ischemic stroke. Therefore, starting at the lowest effective dose and titrating the dose slowly is recommended. In high-risk patients, initiation of propranolol may be performed in the inpatient setting. Pediatric dermatologists or other specialists in cutaneous vascular anomalies typically lead propranolol titration.6
Patients with mid- to high-risk arterial anomalies require daily aspirin for ischemic stroke prophylaxis.7 Pediatric neurology can guide prophylaxis recommendations and provide close neurologic follow-up.
Parents of this particular patient reported normal development and denied seizures, cyanosis, or feeding concerns. An MRI of the head and neck confirmed temporal and intraorbital hemangioma with hypoplasia of the left optic nerve (Figure 2). Additionally, hypoplasia of the left cerebellum was noted as well as several dysplastic and hypoplastic intracranial arteries on the affected Dermatology, Ophthalmology, and Neurology were consulted to provide insight and guidance.
The patient was determined to have intermediate risk for stroke and was initiated on low-dose aspirin. She also started propranolol at approximately 6 weeks of life, with marked improvement of her IH (Figure 4). She continues to meet all developmental milestones and follows with the consulting pediatric specialists.
1. Garzon MC, Epstein LG, Heyer GL, et al. PHACE syndrome: consensus-derived diagnosis and care recommendations. J Pediatr. 2016;178:24.e2-33.e2.
2. Darrow DH, Greene AK, Mancini AJ, Nopper AJ; Section on Dermatology; Section on Otolaryngology-Head and Neck Surgery; Section on Plastic Surgery. Diagnosis and management of infantile hemangioma. Pediatrics. 2015;136(4):e1060-e1104.
3. Haggstrom AN, Lammer EJ, Schneider RA, Marcucio R. Frieden IJ. Patterns of infantile hemangiomas: new clues to hemangioma pathogenesis and embryonic facial development. Pediatrics. 2006;117(3):698-703.
4. Haggstrom A, Garzon MC, Baselga E, et al. Risk for PHACE syndrome in infants with large facial hemangiomas. Pediatrics. 2010;126(2):e418-e426.
5. Bayer ML, Frommelt PC, Bleji F, et al.. Congenital cardiac, aortic arch, and vascular bed anomalies in PHACE syndrome (from the International PHACE Syndrome Registry). Am J Cardiol. 2013;112(12):1948-1952.
6. Drolet BA, Frommelt PC, Chamlin SL, et al. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics. 2013;131(1):128-140.
7. Siegel DH, Tefft KA, Kelly T, et al. Stroke in children with posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects and eye abnormalities (PHACE) syndrome: a systematic review of the literature. Stroke. 2012;43(6):1672-1674.