Conference Coverage

New analysis improves understanding of PHACE syndrome



Children with large facial hemangiomas who have S1 involvement, a lesion area greater than 25 cm2, or bilateral location should be prioritized for PHACE syndrome work-up.

In addition, children with isolated S2 or parotid hemangiomas should be recognized as having lower risk for PHACE, and specifics of evaluation should be discussed with parents on a case-by-case basis.

Dr. Colleen Cotton, University of Arizona, Tucson, chief dermatology resident

Dr. Colleen Cotton

Those are key findings from a retrospective cohort study presented by Colleen Cotton, MD, at the annual meeting of the Society for Pediatric Dermatology.

An association between large facial hemangiomas and multiple abnormalities was described as early as 1978, but it wasn’t until 1996 that researchers first proposed the term PHACE to describe the association (Arch Dermatol. 1996;132[3]:307-11). As the National Institutes of Health explain, “PHACE is an acronym for a neurocutaneous syndrome encompassing the following features: posterior fossa brain malformations, hemangiomas of the face, arterial anomalies, cardiac anomalies, and eye abnormalities.” Official diagnostic criteria for PHACE were not established until 2009 (Pediatrics. 2009;124[5]:1447-56) and were updated in 2016 (J Pediatr. 2016;178:24-33.e2).

“A multicenter, prospective, cohort study published in 2010 estimated the incidence of PHACE to be 31% in patients with large facial hemangiomas, while a retrospective study published in 2017 estimated the incidence to be as high as 58%,” Dr. Cotton, chief dermatology resident at the University of Arizona, Tucson, said in an interview in advance of the meeting. “With the current understanding of risk for PHACE, any child with a facial hemangioma of greater than or equal to 5 cm in diameter receives a full work-up for the syndrome. However, there has been anecdotal evidence that patients with certain subtypes of hemangiomas (such as parotid hemangiomas) may not carry this same risk.”

In what is believed to be the largest study of its kind, Dr. Cotton and her associates retrospectively analyzed data from 244 patients from 13 pediatric dermatology centers who were fully evaluated for PHACE between August 2009 and December 2014. The investigators also performed subgroup analyses on different hemangioma characteristics, including parotid hemangiomas and specific facial segments of involvement. All patients underwent magnetic resonance imaging/magnetic resonance angiography of the head and neck, and the researchers collected data on age at diagnosis; gender; patterns of hemangioma presentation, including location, size, and depth; diagnostic procedures and results; and type and number of associated anomalies. An expert reviewed photographs or diagrams to confirm facial segment locations.

Of the 244 patients, 34.7% met criteria for PHACE syndrome. On multivariate analysis, the following factors were found to be independently and significantly associated with a risk for PHACE: bilateral location (positive predictive value, 54.9%), S1 involvement (PPV, 49.5%), S3 involvement (PPV, 39.5%), and area greater than 25cm2 (PPV, 44.8%), with a P value less than .05 for all associations.

Risk of PHACE also increased with the number of locations involved, with a sharp increase observed at three or more locations (PPV, 65.5%; P less than .001). In patients with one unilateral segment involved, S2 and S3 carried a significantly lower risk (P less than .03). Parotid hemangiomas had a negative predictive value of 80.4% (P = .035).

“While we found that patients with parotid hemangiomas had a lower risk of PHACE, 10 patients with parotid hemangiomas did have PHACE, and 90% of those patients had cerebral arterial anomalies,” Dr. Cotton said. “However, only one of these patients had an isolated unilateral parotid hemangioma without other facial segment involvement. Additionally, two patients with isolated involvement of the midcheek below the eye [the S2 location, which was another low risk segment] also had PHACE, both of whom would have been missed without MRI/MRA [magnetic resonance angiography].”

She acknowledged certain limitations of the study, including its retrospective design. “Additionally, many of the very large hemangiomas were not measured in size, and so, estimated sizes needed to be used in calculating relationship of hemangioma size with risk of PHACE,” she said.

The study was funded in part by a grant from the Pediatric Dermatology Research Alliance.* Dr. Cotton reported having no relevant financial disclosures.

Correction, 7/20/18: An earlier version of this article misstated the name of the Pediatric Dermatology Research Alliance.

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