Clinical Focus: Pediatrics

New Developments in the Management of Hemangiomas Recent findings in two distinct areas offer a glimpse into the future of hemangioma treatment and evolving the standard of care of evaluation and management. By Lawrence F. Eichenfield, MD

ew research on two fronts may bring signifi- with ophthalmologic and central nervous system dis- cant changes to how physicians approach and ease, even though SWS has been better studied and manage hemangiomas in pediatric patients. characterized. The paper discusses the findings of NEach represents an important advancement retrospective studies and expert experience with the in hemangioma clinical research, but with different hemangiomas and systemic associations. kinds of impact. This article explores the extent to The paper presents the most complete set of data which research may affect the trajectory of the on the findings that may be seen with the syn- standard of care for hemangiomas. drome and is a useful reference to give to other spe- cialists to assist them with “what they should be About PHACE looking for” in evaluating a patient with possible PHACE Syndrome was initially described in 1996, PHACE syndrome. The authors conclude that defining a set of findings in some children with infants with large facial hemangiomas should hemangiomas of infancy that were found to have undergo magnetic resonance imaging/magnetic reso- associated structural anomalies. PHACE is an nance angiograms (MRI/MRAs) of the and acronym for Posterior fossa anomalies, Hemangioma, great vessels, echocardiograms, and ophthalmologic Arterial Lesions, Cardiac Abnormalities/aortic coarc- evaluations. Given the number of abnormalities and tation and Eye abormalities. It had been suggested conditions associated with PHACE syndrome, the that infants with large facial or scalp hemangiomas authors recommend ongoing research into the be considered for the syndrome, but there had been genes/pathways that may underlie the disorder. no organized study of specific diagnostic criteria and They argue that this may lead to a greater under- limited study of associated problems. Two recent standing of broader embryologic developmental publications help to elucidate more details about the pathways. syndrome, greatly strengthening our ability to appro- The second article, “Consensus Statement on priately diagnose and manage these infants. Diagnostic Criteria for PHACE syndrome,” delin- The first is a summary of the collective knowledge eates the diagnostic criteria for PHACE syndrome.2 about PHACE syndrome with the consideration of Based on the multidisciplinary expertise of diverse future directions.1 Metry, et al. organized a multidis- specialists, diagnostic criteria are broadly inclusive, ciplinary, collaborate research group, reporting find- with the definition of a facial hemangioma plus one ings and summarizing state of the art knowledge of or more extracutaneous feature defining either the the syndrome, including cerebral, vascular, and car- PHACE syndrome diagnosis, or “Possible PHACE diac abnormalities. While PHACE syndrome is syndrome” label. A facial hemangioma greater than uncommon, it appears that it is probably much more 5cm should prompt consideration of the syndrome. common than Sturge-Weber syndrome, which is the This plus one major criteria (a subset of cerebrovas- association of port-wine stains (not hemangomas) cular, structural brain, cardiovascular, ocular, or

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ventral/midline anomaies) is considered diagnostic. One safety concern is that propanolol can lower Facial hemangiomas >5cm and one minor criteria, blood pressure and have cardiac effects, such as or neck or upper torso hemangiomas plus one hypotension and lethargy. Hypoglycemia has also major criteria or two minor criteria, or no heman- been observed, as have seizures (perhaps secondary gioma plus two major criteria are proposed to be to hypoglycemia). Some cases have required emer- “possible PHACE syndrome.” gency room care and resuscitation. As formal The list of criteria also includes a vast number of prospective studies have not been performed on associated abnormalities, including anomalies of hemangioma patients, the side effect profile in major cerebral arteries, posterior fossa brain anom- infants is unknown, and it is hard to counsel families alies, aortic arch anomalies, specific eye findings, about specific rates of adverse events. Although these and sternal cleft malformations, as well as instances are rare, they should be taken very serious- endocrinologic anomalies. These criteria help to ly as researchers and clinicians begin to incorporate establish a standard of care that will likely continue propanolol into the repertoire of treatment. to evolve in coming months and years as more data Importantly, there is a multi-center trial currently on more specific elements become available. underway for propanolol to examine and hopefully Recommendations for evaluation are as listed establish efficacy, dosing, and a more defined side above, though the authors have also left open the effects profile. This work may play a significant role possibility of the need for endocrinologic evaluation in determining the role of propanolol in hemangioma of a subset of patients. While the standard of care is . In the interim, I recommended that physi- evolving, these papers are both a resource for cians who are considering using propanolol in their healthcare professionals and a blueprint for appro- practices use a standardized protocol and have a pedi- priate evaluation and management. atrician or pediatric specialist share in patient care. Experts in management of hemangiomas in chil- A New Approach to Treatment? dren often consider propanolol as first-line therapy The other substantial development in hemangioma for functionally significant or deforming heman- research and care concerns the treatment of heman- giomas and may use it in “multi-modal therapy,” giomas of infancy with propanolol and perhaps including systemic or intralesional corticosteroids, other beta blockers. The first documented use of laser therapy, and other treatment modalities. propanolol for infantile hemangioma patients was published in June 2008.3 Initially using propranolol Ongoing Evolution for cardiac and blood pressure changes secondary This is an exciting time in the evolution of the to systemic corticosteroids, the remarkable response knowledge of hemangiomas, with new information in some patients to propanolol appeared much bet- that is very important in the diagnosis and manage- ter than that to the corticosteroids. Some patients ment of a great number of children. As more data were treated with propanolol without prior gluco- become available, there is no doubt that our collec- corticoid treatment, also showing excellent clinical tive understanding of hemangiomas will continue to response. improve as the standard of care evolves. ■

Since then, pediatric dermatologists have been 1. Metry DM, et al. PHACE Syndrome: Current Knowledge, Future Directions. Pediatric abuzz about the possibility of this treatment in Dermatology, 2009. 26; 381-398. more severe cases of hemangiomas. Within the past 2. Metry DM, et al. Consensus Statement on Diagnostic Criteria for PHACE Syndrome. Pediatrics, 2009. 124; 1447-1456. year, clinical experience from around the world has 3. Léauté-Labrèze C, et al. Propanolol for Severe Hemangiomas of Infancy. New England indicated that patients have shown seemingly excel- Journal of Medicine. 2008. 258; 24. 2649-51. lent response to the treatment.4-5 However, there 4. Frieden IJ, et al. Propanolol for Infantile Hemangiomas: Promise, Peril, Pathogenesis. Pediatric Dermatology. 2009. 26; 622-624. have been some concerns about safety, and some 5. Lawley LP, et al. Propanolol treatment for Hemangiomas of Infancy: Risks and significant adverse events have been observed. Recommendations. Pediatric Dermatology. 2009. 26; 610-614.

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