Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jun 16;157(8):1-8.
doi: 10.1001/jamadermatol.2021.1901. Online ahead of print.

Association of Demographic Factors and Infantile Hemangioma Characteristics With Risk of PHACE Syndrome

Colleen H Cotton  1   2 , Jusleen Ahluwalia  3 , Daniel M Balkin  4 , Ilona J Frieden  5 , Anita N Haggstrom  6 , Leslie A Castelo-Soccio  7 , Carmen Liy-Wong  8 , Elena Pope  8 , Jack E Steiner  9 , Dawn H Siegel  9 , Esteban Fernandez-Faith  10 , Kimberly D Morel  11   12 , Christine T Lauren  11   12 , Maria C Garzon  11   12 , Anthony J Mancini  13 , Sarah L Chamlin  13 , Megha M Tollefson  14   15 , Marilyn G Liang  16 , Sophia Delano  16 , Sharon A Glick  17 , Marcia Hogeling  18 , Victoria R Barrio  19 ; PHACE Retrospective Study Group
Affiliations

Association of Demographic Factors and Infantile Hemangioma Characteristics With Risk of PHACE Syndrome

Colleen H Cotton et al. JAMA Dermatol. .

Erratum in

  • Incorrect Author Name.
    [No authors listed] [No authors listed] JAMA Dermatol. 2021 Aug 1;157(8):1008. doi: 10.1001/jamadermatol.2021.2991. JAMA Dermatol. 2021. PMID: 34406345 Free PMC article. No abstract available.

Abstract

Importance: A 2010 prospective study of 108 infants estimated the incidence of PHACE (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, eye anomalies) syndrome to be 31% in children with facial infantile hemangiomas (IHs) of at least 22 cm2. There is little evidence regarding the associations among IH characteristics, demographic characteristics, and risk of PHACE syndrome.

Objectives: To evaluate demographic characteristics and comorbidities in a large cohort of patients at risk for PHACE syndrome and assess the clinical features of large head and neck IH that may be associated with a greater risk of a diagnosis of PHACE syndrome.

Design, setting, and participants: This multicenter, retrospective cohort study assessed all patients with a facial, head, and/or neck IH who were evaluated for PHACE syndrome from August 1, 2009, to December 31, 2014, at 13 pediatric dermatology referral centers across North America. Data analysis was performed from June 15, 2017, to February 29, 2020.

Main outcomes and measures: The main outcome was presence or absence of PHACE syndrome. Data included age at diagnosis, sex, patterns of IH presentation (including size, segment location, and depth), diagnostic procedures and results, and type and number of associated anomalies.

Results: A total of 238 patients (mean [SD] age, 2.96 [4.71] months; 184 [77.3%] female) were included in the analysis; 106 (44.5%) met the criteria for definite (n = 98) or possible (n = 8) PHACE syndrome. A stepwise linear regression model found that a surface area of 25 cm2 or greater (odds ratio [OR] 2.99; 95% CI, 1.49-6.02) and involvement of 3 or more locations (OR, 17.96; 95% CI, 6.10-52.85) to be statistically significant risk factors for PHACE syndrome. Involvement of the parotid gland (OR, 0.39; 95% CI, 0.18-0.85) and segment S2 (OR, 0.38; 95% CI, 0.16-0.91) was associated with a lower risk. Race and ethnicity may also be associated with PHACE syndrome risk, although more studies are needed.

Conclusions and relevance: This cohort study further described factors associated with both a higher and lower risk of PHACE syndrome. The presence of multiple anatomical sites and large surface area were associated with greater risk, whereas S2 or parotid IHs were associated with lower, but still potential, risk. These findings can help in counseling families and decision-making regarding evaluation of infants with large head and neck IHs.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Cotton reported receiving grants from Pediatric Dermatology Research Alliance (PeDRA) during the conduct of the study and other support from Pierre Fabre Food and Beverage outside the submitted work. Dr Frieden reported receiving consulting fees from Venthera Biobridge, serving on the Novartis Advisory Board, receiving consulting fees from Pfizer, serving on the Data Safety Monitoring Board outside the submitted work, and serving as a physician adviser for the PHACE syndrome community and as president of PeDRA. Dr Pope reported receiving consulting fees from Novartis, Boehringer Ingelheim, and Sanofi outside the submitted work. Dr Siegel reported receiving grants from SID-SUN, consulting fees from Merck, and honoraria from UpToDate outside the submitted work. Dr Garzon reported serving as an investigator for the Pediatric Trials Network Topical Timolol Study 2017-2020 during the conduct of the study. Dr Mancini reported serving on the advisory boards of Verrica, ParaPRO, Cassiopea, and Novartis and receiving speaker fees from Sanofi Regeneron outside the submitted work. Dr Glick reported participating in a conference on hemangioma sponsored by Pierre Fabre Pharmaceuticals, which paid expenses outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Isolated Segmental Infantile Hemangioma of the Maxillary (S2) Segment in a Patient With Definite PHACE (Posterior Fossa Malformations, Hemangioma, Arterial Anomalies, Cardiac Defects, Eye Anomalies) Syndrome
This S2 hemangioma spares the preauricular cheek.
Figure 2.
Figure 2.. Infantile Hemangioma Facial Segment (S1-S4) Boundaries With Modifications From the Original Map of Haggstrom et al
See this image and copyright information in PMC

References

    1. Frieden IJ, 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(3):307-311. doi:10.1001/archderm.1996.03890270083012 - DOI - PubMed
    1. Steiner JE, McCoy GN, Hess CP, et al. . Structural malformations of the brain, eye, and pituitary gland in PHACE syndrome. Am J Med Genet A. 2018;176(1):48-55. doi:10.1002/ajmg.a.38523 - DOI - PMC - PubMed
    1. Brosig CL, Siegel DH, Haggstrom AN, Frieden IJ, Drolet BA. Neurodevelopmental outcomes in children with PHACE syndrome. Pediatr Dermatol. 2016;33(4):415-423. doi:10.1111/pde.12870 - DOI - PubMed
    1. Haggstrom AN, Garzon MC, Baselga E, et al. . Risk for PHACE syndrome in infants with large facial hemangiomas. Pediatrics. 2010;126(2):e418-e426. doi:10.1542/peds.2009-3166 - DOI - PubMed
    1. 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. doi:10.1542/peds.2005-1092 - DOI - PubMed