PHACES

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PHACE without Face? Infantile Hemangiomasof the Upper Body Region with Minimal orAbsent Facial Hemangiomas and Associated

Structural Malformations

Adam S. Nabatian, B.A.,* Sandy S. Milgraum, M.D., Christopher P. Hess, M.D., Ph.D.,àAnthony J. Mancini, M.D.,§ Alfons Krol, M.D., F.R.C.P.C.,– and

Ilona J. Frieden, M.D.**

*University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, New Brunswick, New

Jersey, Department of Dermatology, University of Medicine and Dentistry of New Jersey Robert Wood Johnson

Medical School, New Brunswick, New Jersey, àDepartments of Radiology and Biomedical Imaging, University of

California San Francisco School of Medicine, San Francisco, California, §Departments of Dermatology and

Pediatrics, Northwestern University’s Feinberg School of Medicine, Chicago, Illinois, –Departments of

Dermatology and Pediatrics, Oregon Health and Science University, Portland, Oregon, **Departments of

Dermatology and Pediatrics, University of California San Francisco School of Medicine, San Francisco, California

Abstract: Infantile hemangiomas can be associated with congenital

anomalies such as PHACE syndrome with facial hemangiomas and genito-

urinary and spinal anomalies in the setting of lower body hemangiomas.

We describe five infants in whom segmental hemangiomas involving the

upper torso and extremities with absent or small facial hemangiomas were

associated with structural anomalies similar to those reported with PHACE

syndrome, including three with structural arterial anomalies of the sub-

clavian arteries, three with aortic arch anomalies (right sided or narrowed

arch), two with congenital heart disease (atrial septal defect and ventricular

septal defect; tetralogy of Fallot), one with a retinal scar, and one with a

sternal defect (scar). Two of five had small facial hemangiomas of the lower

lip, but none had large segmental hemangiomas of the face. Three of five

would have met diagnostic criteria for PHACE but lacked a facial hemangi-

oma of 5 cm in diameter or greater. Patients with segmental arm and thorax

hemangiomas may have associated structural abnormalities with overlap-

ping features of PHACE, suggesting that a similar syndrome can occur in

this clinical setting.

Address correspondence to Adam S. Nabatian, B.A., 81Brunswick Woods Drive, East Brunswick, NJ 08816, USA, ore-mail: [email protected]. Anthony J. Mancini serves as a principal investigator for PierreFabre.Dr. Ilona J. Frieden serves as a consultant for Pierre FabreDermatology.

DOI: 10.1111/j.1525-1470.2011.01407.x

Ó 2011 Wiley Periodicals, Inc. 235

Pediatric Dermatology Vol. 28 No. 3 235–241, 2011

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Infantile hemangiomas (IH) are the most common

benign tumors of infancy. Most are isolated and with-

out associated complications, but a small subset has

extracutaneous anomalies. The association between IH

and associated structural malformations has received

increased attention in recent years. PHACE is an

acronym referring to the associations of Posterior

fossa brain defects; facial Hemangioma; and Arterial,

Cardiac, and Eye anomalies. Recently, consensus

criteria for PHACE and possible PHACE syndrome

have been proposed (1,2).

The association between lower body IH and spinal

and genitourinary hemangiomas has been reported with

at least three different acronyms: Perineal hemangioma,

External genitalia malformations, Lipomyelomeningo-

cele, Vesicorenal abnormalities, Imperforate anus, and

Skin tag (PELVIS); Spinal dysraphism and Anogenital,

Cutaneous, Renal, and urologic anomalies associated

with an Angioma of Lumbosacral location (SACRAL);and most recently, Lower body hemangioma and other

cutaneous defects, Urogenital anomalies, Ulceration,

Myelopathy, Bony deformities, Anorectal malforma-

tions, Arterial anomalies and Renal anomalies (LUM-

BAR syndrome) (3–6).

We now report five patients in whom segmental

hemangiomas involving the upper torso with minimal to

absent facial involvement were associated with structural

anomalies similar to those reported with PHACE

syndrome and discuss the implications of these findings.

REPORT OF CASES

Case 1

A 6-year-old girl who had last been seen at the age of

15 months presented to the pediatric dermatology clinic

at Children’s Memorial Hospital, Chicago, IL, for a

follow-up visit. She had been followed in the past for a

combined segmental IH of her right clavicular and upper

chest areas. Extrinsic tracheal compression with feeding

and respiratory symptoms had complicated her course,

and she was treated during infancy with high-dose oral

corticosteroids. Magnetic resonance imaging (MRI) in

the past had revealed a large hemangioma with extensioninto the mediastinum, axilla, and anterior chest wall,

causing displacement of the trachea toward the left. It

also revealed a right-sided aortic arch and an aberrant

origin of the left subclavian artery suggestive of a vas-

cular ring. She wastapered off of oral steroids completely

by the age of 17 months.

At 6 years of age, she began to complain of severe

daily headaches. Brain magnetic resonance angiography

(MRA) revealed tortuosity of her right-sided carotid

and basilar artery systems. Skin examination revealed

telangiectatic stains of her right clavicular chest, shoul-

der, and posterior auricular region without a palpable

deeper component, thrill, or bruit. Cardiologic, oph-

thalmologic, and neurologic evaluations were normal,

and despite the arterial abnormalities observed on MRI,

her headaches were felt to more likely be tension-related

than due to arterial disease. Serial MRI studies of the

brain and neck over the subsequent 18 months revealed

stable but severe tortuosity of the basilar artery, a

prominent right posterior communicating artery, and

tortuosity of the right internal carotid artery that ap-

peared progressively less ectatic on serial examinations.

A 9-mm pineal cyst was felt to be incidental and did not

change with time. The patient has done well with

continued but less frequent headaches relieved by

ibuprofen and rest.

Case 2

A 2-month-old girl was referred to the hospital of the

University of California at San Francisco for evaluation

of an extensive vascular birthmark. She was a full-term

female infant weighing 4.3 kg at birth born to a 22-year-

old mother. Her parents were reportedly ‘‘distant

cousins’’; there was no family history of birthmarks. An

extensive vascular stain of the right arm and right upper

torso was noted at birth, with rapid onset of growth of

the affected area beginning at 2 weeks of age, with the

greatest growth occurring on the torso.

Examination at the time of referral demonstratedwidespread vascular stains involving the right neck,

chest, back, and entire right arm, extending slightly onto

the left hemithorax, with bulky hemangioma growth

most evident on the chest, neck, and axilla. Prominent

dilated veins were noted on the affected dorsal and pal-

mar aspects of the hand and distal forearm. The

remainder of her physical examination was remarkable

only forthree accessory tragi on the left preauricular skin

and one on the right preauricular area. Ulceration of the

neck folds and right axilla beginning at 10 weeks of age

complicated her course. Because of rapid and bulky

hemangioma growth and ulceration, she was started on

3 mg ⁄ kg per day of oral prednisolone, which slowedhemangioma growth. Tapering of steroids to every-

other-day dosing was achieved at 6 months of age, but

because of reboundgrowth, steroids were continued until

15 months of age, although at lower dosages.

At 10 months of age, the patient was noted to have

absent pulses of the right arm, but she had no limb length

discrepancy and had normal arm function. She was

referred to vascular surgery. Doppler sonography

demonstrated diminished flow velocity within the right

236 Pediatric Dermatology Vol. 28 No. 3 May ⁄ June 2011

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radial artery and absent flow within the ulnar artery.

Cardiology evaluation was normal except for a small

patent foramen ovale. At age 1 year, a neurological

evaluation was performed that showed normal develop-

ment without deficits, although physical therapy was

recommended because of an awkward crawl. She was

evaluated with a head and neck MRI and MRA that

demonstrateda largehemangiomamostprominent in the

right neck extending to the right anterior chest wall, right

axilla, and subcutaneous fatof the right back and into the

thorax along the right posterior paraspinal region and

superiorly in the neck to the level of the parotid gland.

The right subclavian artery deep to the hemangioma

appeared dysplastic. Brain MRIand MRAwere normal.

At age 2.5 years, extensive residual telangiectasias of

the affected skin and an unusually prominent vein of the

ventral forearm were noted (Fig. 1A–C). Her right hand

was slightly puffy, with nonpitting edema, but was

functionally normal. Her growth and development werenormal. At age 7, she was noted to have normal strength

in both arms and persistent though fading telangiectasias

in the areas of the involuted hemangioma. The pulses in

her right arm were poor, and the arm felt cooler than her

left arm.

She was referred to cardiology for further evaluation

of her vascular anomalies. An electrocardiogram and

heart examination were both normal. A chest MRI and

MRA demonstrated a long segment of narrowing of the

right subclavian artery extending from the origin of the

right vertebral artery to the origin of the long thoracic

artery (Fig. 2) with interval complete regression of herhemangiomas. She is asymptomatic and is being fol-

lowed periodically without specific intervention.

Case 3

A 6-week-old full-term male infant was seen at the

University of California at San Francisco dermatology

clinic for a growing vascular birthmark. His past medical

history wasremarkable for congenital heart disease, with

atrial and ventricular septal defects (ASD and VSD)

diagnosed in early infancy, requiring oral furosemide.

Family history was negative for IH. On physical exami-

nation, he was noted to have a 2.5- · 1.8-cm vascularplaque on his right upper arm, macular erythema and

dilated vessels over the left dorsal aspect of the hand and

wrist, and multiple bright red erythematous papules

coalescing into a plaque on the left anterior aspect of the

chest. A small congenital scar measuring 1 · 0.8 cm was

located on the central chest, just below the xiphoid.

Examination 2 months later at 3.5 months of age

showed only a minimal degree of further proliferation.

He was subsequently lost to follow-up.

A

B C

Figure 1. (A–C) At age 2.5 years, widespread hemangiomaresidua (mainlytelangiectasias) werenoted involving the right

neck, chest, back, and arm, extending slightly onto the lefthemithorax. A prominent dilated vein of the ventral forearm isevident.

Figure 2. Axial fat-suppressed, gadolinium-enhanced T1-weighted image at the level of the thyroid gland showsa massive hemangioma in the right neck. Enlarged arteriesand veins (arrows) are observed within the lesion. The rightsubclavian artery is small (arrowhead).

Nabatian et al: PHACE without Face? 237

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Case 4

A 6-year-old girl was born at full-term without any pre-

natal complications to a G3 P2 (Gravida 3 Para 2)

mother. Birth weight was 3,654 g. At approximately

2 weeks of age, she was noted to have vascular staining

and spots on her left wrist, left anterior aspect of thechest, and left side of lower lip and neck. She developed

progressive stridor and was referred to pediatric otolar-

yngology at 5 weeks of age after presenting in the

emergency department. There was no family history of

vascular birthmarks. Flexible bronchoscopy at 6 weeks

of age showed a left subglottic hemangioma. She was

started on oral prednisolone at a dose of 4 mg ⁄ kgper day

and referred to the vascular anomalies clinic at Oregon

Health and Science University.

Examination at that time showed a well-nourished

infant with inspiratory stridor and suprasternal retrac-

tions. She had a large segmental hemangioma of the leftchest wall, left upper shoulder region, and left side of the

anterior and lateral neck extending to the posterior

hairline (Fig. 3). She had minimal involvement of the left

lower lip and buccal mucosa. There were superficial

vascular papules over the left wrist. At 8 weeks of age,

because of progressive stridor, she underwent surgical

resection of her subglottic hemangioma, noted to

obstruct 50% of her airway, with laryngotracheal

reconstruction with thyroid alar graft. She did well

postoperatively, and steroids were gradually tapered and

discontinued over the next 6 months. Consultation with

pediatric cardiology revealed an outflow tract murmur,

and transthoracic echocardiogram showed accentuatedforward diastolic flow in the left subclavian artery, a

small patent ductus arteriosus, and normal intracardiac

anatomy.

MRI of the chest, neck, and head was performed at

3 months of age. Her brain was normal, with normal

vessel anatomy and no cyst or cerebellar anomalies.

Chest MRI showed a large hemangioma involving the

left anterior chest wall, left superior mediastinum, and

left neck. The chest MRI also showed a small-caliber left

mainstem bronchus, encased by the mass; aberrant ori-

gin of the left subclavian artery (from a left-sided aortic

arch); diminutive but patent left common carotid, left

internal carotid, and left vertebral arteries, which were

encased by the hemangioma; moderate atelectasis of the

left lower lobe; and mild atelectasis of the lingula and

right lower lobe. Mild narrowing of the distal transverse

aortic arch measuring 5 mm in maximum diameter was

noted. A ophthalmologic examination at 2 years of age

revealed dense amblyopia of the left eye due to a retinal

scar involving the retinal macula that was felt might

represent a regression of vascular anomaly or old

inflammatory change.

Case 5

A 6-month-old Hispanic girl was referred to the Uni-

versity of Medicine and Dentistry of New Jersey Robert

Wood Johnson dermatology clinic for multiple heman-

giomas. She was a full-term female infant weighing

3.9 kg born to a 31-year-old mother and was the third

child of healthy parents and siblings. Polyhydramnios

complicated the pregnancy. At birth she was found to

have tetralogy of Fallot (ToF). Corrective surgery for the

ToF was performed at the age of 35 days using atransannular patch with VSD and partial ASD closure.

She had a small IH on her lower lip, and approximately a

week after cardiac surgery, segmental hemangiomas

began to develop on the right upper chest, arm, and

hand. There was no family history of IH, but there was a

history of heart disease on the paternal side.

Examination was notable for multiple vascular pap-

ules on the right anteriorchest, arm, and dorsal hand and

web spaces and a 1-cm-diameter hemangioma of the

lower lip (Fig. 4A,B). Soft-tissue fullness of the right

anterior chest was noted, as was a midline sternal scar

that was present from her ToF surgical repair. There

were no signs of respiratory distress, abdominal disten-tion, or hepatosplenomegaly. Further evaluations

included MRI and MRA of the head and neck, MRI of

the chest, abdominal ultrasound, and eye examination.

The head MRI showed multiple punctuate foci of mag-

netic susceptibility consistent with previous microhem-

orrhages, which were interpreted as likely being due to

effects of cardiac bypass surgery. Brain MRA was

normal. Chest MRI demonstrated a large right anterior

chest and right-sided neck IH, as well as a right-sided

Figure 3. Large segmental hemangioma of the left chestwall, left upper shoulder region, and left side of the anteriorandlateral neck with superficial vascular papules over the leftwrist. She also had a smaller, discontinuous hemangiomainvolving the left side of her chin and lower lip.


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aortic arch and a large IH within the right upper mid

chest wall (Fig. 5). Abdominal ultrasound was normal,

as was eye examination.

DISCUSSION

IH are benign vascular proliferations. Although most are

small, self-limited, innocuous vascular tumors, a subset

can have associated morbidities, including associated

structural anomalies. Some of these associated structural

malformations have been well characterized, includingthose encompassed in PHACE syndrome and those of

the lower body in association with genitourinary and

spinal defects (variously known by the acronyms PEL-

VIS, SACRAL, and LUMBAR syndrome). We now

report five patients with segmental hemangiomas

involving the arms and thorax in association with car-

diovascular and thoracic structural anomalies, an asso-

ciation that has not heretofore been well recognized. Our

cases also add weight to the concept that segmental IH of

specific regions can have regionally associated anomalies

(3–8).

Although our patients did not meet consensus criteria

for PHACE, there was considerable overlap in their

features. In four of the five patients presented, the

structural malformations included those that are major

or minor criteria for the diagnosis of PHACE syndrome.

Three of the five patients (patients 1, 3, and 4) had con-

sensus criteria for possible PHACE syndrome, and def-

inite PHACE could have been diagnosed if a facial

hemangioma of 5 cm or larger had been present. Cases 4

and 5 had small hemangiomas of the lower lip that wereconsiderably smaller than the 5 cm diameter needed for

PHACE diagnosis. In allfive cases,theextent and bulk of

the hemangiomasprimarily involved the upper torso and

upper extremity. Patient 1 had an aberrant left sub-

clavian artery (a major criterion), central nervous system

arterial anomalies (a major criterion), and a right-sided

aortic arch (a minor criterion). Patient 2 had neither

major nor minor consensus criteria but had marked

narrowing of the ipsilateral subclavian artery. Patient 3

had a sternal defect (a major criterion) and a ventricular

septal defect (a minor criterion). Patient 4 had aberrant

inferior origin of the left subclavian artery (a major cri-terion). Patient 5 had a right-sided aortic arch (a minor

criterion) and ToF (Table 1). Although ToF is not a

major or minor criterion, it has been reported in associ-

ation with PHACE in the past (1). Conversely, scrutiny

of many of the patients reported to have PHACE shows

that, in addition to large facial IH, some have also had

hemangiomas of the torso or upper extremities, empha-

sizing the overlapping features of these clinical settings

(2,9–11).

Some have hypothesized that PHACE syndrome is

probably the result of a developmental field defect.

Developmental fields, as Opitz and Gilbert defined, ‘‘are

those units of the embryo in which the developmentof the complex structure appropriate to it is determined

and controlled in a spatially coordinated, temporally

synchronous, and epimorphically hierarchical manner’’

(12). An event occurring at a critical time in gestation and

anatomic site in the developing embryo could, as a result,

cause a constellationof findings.The anatomicproximity

of the congenital anomalies with predominant involve-

ment of the upper torso lends support to this hypothesis.

On the other hand, case 1 had tortuous carotid and

A B

Figure 4. (A, B) Multiple vascular papules on the rightanterior chest, arm, and dorsal hand and web spaces and1-cm hemangioma of the lower lip. Soft-tissue fullness of theright anterior chest corresponding to the presence of deeper

hemangioma was noted, as was a midline sternal scar fromtetralogy of Fallot repair.

Figure 5. Axial fat-suppressed T2-weighted image at thelevel of the main pulmonary artery, with hemangioma(asterisks) in the right chest wall, and an additional lesion inthe right paravertebral region (arrowhead) that may representan additional hemangioma. A right-sided aortic arch (singlearrows), in addition to enlarged right pulmonary artery (doublearrow), the latter the result of repair for tetralogy of Fallot.


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basilar arteries, sites that were not in direct proximity to

the cutaneous hemangiomas of the torso. This finding

has been noted in some previously reported cases as well

(6,13).

All of our patients had arterial or cardiac anomalies.They could not be diagnosed using current consensus

criteria, butthey had many overlapping features,making

it likely that their abnormalities lie along a continuum

with those patients with definite PHACE. Their findings

support the growing body of evidence demonstrating

that segmental cutaneous IH have a developmental vul-

nerability to congenital anomalies being present in the

same region (7,8). This echoes the findings of Iacobas

et al, who systematically studied the structural malfor-

mations of the lower body associated with IH. They

noted that, although there was considerable overlap in

structural anomalies of these patients, some anatomic

sites increased the risk of associated anomalies (e.g.,hemangioma of the lumbosacral area associated with

myelopathy and that involving the buttocks and peri-

neum increased the risk of urogenital, anorectal, and

renal anomalies).

Finally, although this small case series does not con-

stitute compelling evidence for evaluating all patients

with segmental IH of the torso and arms for structural

anomalies, such evaluations should be considered, based

on the clinical setting and whether other relevant signs

and symptoms are present. Echocardiogram and eye

examination are completely noninvasive and reasonable

to perform in all cases. MRI and MRA are expensive

tests and in young infants typically require general

anesthesia. These studies should be performed if echo-cardiography or abnormal ocular findings are detected

or if any signs or symptoms suggesting neurological

problems or arterial anomalies (such as diminished pul-

ses) are present. In addition to finding structural

abnormalities, MRI can also demonstrate, as it did in

four of five of our cases, that the size and anatomic extent

of IH may be considerably greater than initially appre-

ciated with physical examination, which in turn may

affect management. The patients reported herein add to

the growing appreciation of structural abnormalities in

association with segmental IH and suggest that there

may be an upper torso equivalent to PHACE syndrome.

REFERENCES

1. Metry D, Heyer G, Hess C et al. Consensus statementon diagnostic criteria for PHACE syndrome. J Pediatr2009;124:1447–1456.

2. Metry DW,Dowd CF,BarkovichAJ et al.The many facesof PHACE syndrome. J Pediatr 2001;139:117–123.

3. Goldberg NS, Hebert AA, Esterly NB. Sacral hemangio-mas and multiple congenitalabnormalities. ArchDermatol1986;122:684–687.

TABLE 1. Summary of Patients With Torso and Upper Extremity Hemangiomas and Associated Malformations

Case: Sex Location of cutaneous IH Location of internal IH Associated malformations

1: Female Segmental IH of the right clavicle,upper chest, axilla, andpostauricular skin

Mediastinum Right-sided aortic archAberrant left subclavian artery

suggestive of a vascular ring

Tortuosity of right internal carotidand basilar arteries

2: Female Segmental IH of right neck, chest,back, axilla, arm andleft hemithorax

Large IH with dominant mass-likecomponent in right inferior anteriorneck, extending to right chest, axilla, andsubcutaneous fat of back and into thoraxand extending superiorly in the neckabutting the right carotid space andextending to the parotid gland

Patent foramen ovaleLong-segment narrowing of the right

subclavian artery

3: Male Segmental IH of the right arm,left anterior chest, left dorsal handand wrist

Atrial septal defectVentricular septal defecSternal scar

4: Female Segmental IH of the left chest wall,left upper shoulder, left-sidedanterior and lateral neck, left wrist,left lower lip, and buccal mucosa

Left superior mediastinum, subglotticsurrounding left mainstem bronchus,surrounding the left common carotid,left internal carotid, and left vertebralarteries

Patent ductus arteriosusLeft macular scarring resulting in

amblyopiaAberrant inferior origin of left

subclavian artery

Narrowing of distal transverseaortic arch

5: Female Segmental IH of the right anterioraspect of the chest, right arm anddorsal aspect of the hand andweb spaces; lower lip

IH in right chest wall and deep soft tissueof right neck

Tetralogy of FallotRight-sided aortic arch

IH, infantile hemangioma.


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4. Girard C, Bigorre M, Guillot B et al. PELVIS syndrome.Arch Dermatol 2006;142:884–888.

5. Stockman A, Boralevi F, Taieb A et al. SACRALsyndrome: spinal dysraphism, anogenital, cutaneous,renal and urologic anomalies, associated with an angi-oma of lumbosacral localization. Dermatology 2007;214:40–45.

6. Iacobas I, Burrows PE, Frieden IJ et al. LUMBAR:association between cutaneous infantile hemangiomas of the lower body and regional congenital anomalies.J Pediatr 2010; 157: 795–801.

7. Pascual-Castroviejo I, Lopez-Gutierrez JC, Pascual-Pascual SI et al. Cutaneous hemangiomas, vascularmalformations and associated disorders. A new neurocu-taneous syndrome. An Pediatr (Barc) 2003;58:339–349.

8. Phan TA, Adams S, Wargon O. Segmental haemangiomasof infancy: a review of 14 cases. Australas J Dermatol2006;47:242–247.

9. Roganovic J, Adams D. PHACES syndrome – case reportand literature review. Coll Antropol 2009;33:311–314.

10. Durusoy C, Mihci E, Tacoy S et al. PHACESsyndrome presenting as hemangiomas, sternal cleftingand congenital ulcerations on the helices. J Dermatol2006;33:219–222.

11. Thebault N, Le Guern H, Le Fiblec B et al. Prenataldiagnosis of a complete sternal cleft in a child withPHACES syndrome—a case report. Prenat Diagn2009;29:179–181.

12. Opitz JM, Gilbert EF. CNS anomalies and the midline asa ‘‘Developmental Field.’’ Am J Med Genet 1982;12:443–455.

13. Frieden IJ, Reese V, Cohen D. PHACE syndrome. Theassociation of posterior fossa brain malformations,hemangiomas, arterial anomalies, coarctation of the aortaand cardiac defects, and eye abnormalities. Arch Dermatol1996;132:307–311.


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