CHICAGO - Infants with large segmental facial hemangiomas should always undergo a detailed workup for PHACE syndrome.
"When we see patients with a large facial hemangioma, we have a different burden of evaluation and diagnosis than we did even a year ago," Dr. Lawrence F. Eichenfield said at the summer meeting of the American Academy of Dermatology. "A new consensus statement describing the diagnostic criteria was published last October and outlines very clearly what we should be looking for in these children."
Because the developmental syndrome can affect several systems, a diagnostic workup should include magnetic resonance imaging of the brain, an echocardiogram, ultrasound and MRI of the great vessels, and a detailed ophthalmologic exam.
"This is the standard evaluation we have now for every child who has a hemangioma of 5 cm2 or larger on the face, head or neck," said Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego.
Hemangiomas are a fairly common finding, occurring in 4%-10% of newborns. They are more likely to appear in girls, premature or low-birthweight infants, in multiples, or in the children of older mothers.
"All of these factors can be associated with intrauterine hypoxic insult or placental insufficiency," Dr. Eichenfield said. This supports a theory that hemangiomas form from capillaries positive for the glucose transport protein type 1 (GLUT1). "It was recently found that GLUT1 is an important responder to hypoxia."
While localized, nonsegmented hemangiomas are generally of only cosmetic concern, unless they interfere with function, the larger segmented type can be dangerous, Dr. Eichenfield noted. "They are more likely to erode and become infected, interfere with vital functions, and are strongly correlated with PHACE syndrome."
The PHACE acronym refers to the abnormalities often found in the disorder: posterior fossa anomalies, hemangioma, arterial lesions, cardiac abnormalities/aortic coarctation, and abnormalities of the eye. According to the recently published Consensus Statement on Diagnostic Criteria for PHACE Syndrome, definite PHACE requires the presence of a characteristic segmental hemangioma at least 5 cm in diameter on the face or scalp plus one major or two minor structural anomalies. Possible PHACE requires the presence of a hemangioma at least 5 cm on the face or scalp plus one minor structural anomaly (Pediatrics 2009;124:1447-56).
“We now understand that the major abnormalities in PHACE are usually the cerebrovascular arteries, including the great vessels of the brain and heart,” Dr. Eichenfield said. "There may be dysplasia, stenoses, occlusions, or even a complete absence of some of these vessels. Among children with these anomalies, cerebrovascular accidents and strokes are not uncommon."
Other major abnormalities associated with PHACE are malformation of the posterior fossa and coarctation of the aorta. "In fact, coarctation of the aorta is as common in PHACE as it is in Turner syndrome," Dr. Eichenfield said.
A recent prospective study of 108 infants with large facial hemangiomas helped define the association between the lesions and the syndrome, he said. Thirty-three (31%) of the infants qualified as having PHACE. Of those, 30 had more than one extracutaneous finding. "The risk for PHACE syndrome was higher in infants with larger hemangiomas and in those with hemangiomas that encompassed more than one facial segment," wrote lead author Anita Haggstrom of Indiana University, Indianapolis. "The most common extracutaneous anomalies were of the arteries of the cerebrovasculature (91%) and cardiac anomalies (67%). Upper face (frontotemporal and frontonasal) hemangiomas were commonly observed in infants with PHACE; isolated maxillary hemangiomas were rarely associated" (Pediatrics 2010;126:e418-26).
Another recent study examined the prevalence of cervical and intracranial arterial anomalies in 70 infants with PHACE syndrome (Am. J. Neuroradiol. 2010 Aug. 12 [epub ahead of print]).
More than half (57%) had more than one arteriopathy. "Dysgenesis was the most common abnormality (56%), followed by anomalous course and/or origin (47%), narrowing (39%), and nonvisualization (20%)," wrote lead author Dr. Christopher Hess of the University of California, San Francisco.
The study also found a link between the site of the hemangioma and arterial anomalies. "Hemangiomas were ipsilateral to arteriopathy in all but one case. The frontotemporal and/or mandibular facial segments were involved in 97% of cases, but no other specific associations between arteriopathy location and hemangioma sites were detected. All cases with posterior fossa anomalies had either internal carotid anomalies or persistent embryonic carotid-basilar connections," he said.
The diagnostic consensus statement also made some observations about hemangioma location and the most likely type of associated anomaly.
"Previous reports noted that [the frontotemporal segment] is probably most predictive of cerebrovascular and ocular anomalies, whereas [the mandibular segment] seems to predict ventral developmental defects and cardiovascular abnormalities," wrote the team headed by Dr. Denise Metry of the Baylor College of Medicine, Houston. "Although the observations may offer insight into pathogenesis, they should not influence anything less than a thorough PHACE evaluation for at-risk infants, which includes MRI and magnetic resonance arteriogram brain imaging, imaging of the cardiovasculature, and an ophthalmologic examination."