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Complications of infantile hemangiomas

Bernardo Gontijo, MD, PhD

Department of Dermatology, Federal University of Minas Gerais School of Medicine, Rua Domingos Viera, 300 Suite
505,30150-240 Belo Horizonte, MG, Brazil
Abstract Most infantile hemangiomas have a spontaneous and uneventful involution and, hence, may be
treated expectantly. Others, however, will present some complication along their evolution that may
require prompt therapeutic interventions. Ulceration is the most common complication, and amblyopia
is frequently associated with periocular tumors. Airways hemangiomas may be life-threatening, and
disfigurement can heavily impact the patients quality of life.
2014 Elsevier Inc. All rights reserved.
Introduction
Infantile hemangioma (IH) is the most common benign
vascular tumor of infancy. With a unique and dynamic
natural history, IH is typically absent or present only as a
precursor lesion at birth. Virtually all hemangiomas are
detectable at the end of the first month of life. A rapid
proliferation phase ensues and, by the age of 3 months,
80% of tumor growth has been achieved,
1
and after the first
year of life, an involution phase takes place over several
months or years, resulting in varying degrees of resolution.
A small but significant subset of IHs present with
complications at some point in their evolution. In a large
prospective study of 1058 children with IH, ulceration was
the most frequent complication, observed in 23.2% of the
patients followed by visual impairment (6.9%), airway
obstruction (1.8%), auditory canal obstruction (1.1%), and
cardiac compromise (0.4%). Size, location, and morphology
(segmental) were the most important predictor factors of
complication.
2
Recognition or prediction of such complica-
tions is crucial to establish the need for treatment or further
investigation and intervention Table 1.
Ulceration
The pathogenesis of ulceration is still unclear but is
thought to be the result of (1) ischemia and necrosis
stemming from trauma and friction, and/or (2) rapid tumor
growth exceeding its oxygenated blood supply. Large size,
segmental distribution with a superficial component and
location (lips, diaper area, and neck) (Figure 1) are associated
with a greater risk of ulceration.
3,4
Resulting pain can be
severe enough to cause sleep disturbance, feeding difficulties
(when occurring on the lip), and pain with urination or
defecation (genital location).
Surface breakage (erosion or ulceration) of lesions facilitates
secondary bacterial infection and often coincides with the
late proliferative phase (median age 4 months).
3
Of note, it has
been shown that early white discoloration (average age of 2.6
months) of IH along with softening of the tumor, is highly
predictive of impending ulceration (early white hemangioma
sign).
5
This whitening (Figure 2) is to be differentiated fromthe
typically centrifugal discoloration that heralds spontaneous or
treatment-induced involution of IH (Figure 3) and usually
begins after the completion of tumor growth (between the ages
of 5 and 10 months).
Minor ulcers may require only local wound care with
petrolatum gauze, topical antibiotics, biocclusives (Figure 4),
barrier creams, and recombinant growth factor (becaplermin).

Corresponding author. Tel.: +55 31 9972 4020.


E-mail address: bernardofgontijo@gmail.com.
http://dx.doi.org/10.1016/j.clindermatol.2014.02.002
0738-081X/ 2014 Elsevier Inc. All rights reserved.
Clinics in Dermatology (2014) 32, 471476
Topical preparations of benzocaine, lidocaine or lidocaine/
prilocaine eutectic mixture should be applied sparingly due to
potential toxicity. Methemoglobinemia can develop due to
benzocaine and prilocaine, and this risk may be increased
when acetaminophen, a methemoglobin reductase inhibitor, is
simultaneously administered. Some patients may require oral
opiate derivatives (codeine, morphine).
6,7
Recent reports have highlighted the role of propranolol in
expediting the healing of IHulcerations (Figure 5), which may
be partially explained by the rapid reduction of tumor size.
810
Interestingly, this blocker is also able to induce faster pain
relief, most likely due to its vasoconstriction properties
8
;
therefore, early administration of propranolol may be helpful
in preventing ulceration by halting tumor growth.
In a series of 78 patients treated with pulsed dye laser
alone, there was a 91% success rate in healing ulceration
after a mean number of 2.0 treatments carried out at 3- to 4
week intervals.
11
Bleeding, even when minimal, is often worrisome for the
parents. In most cases hemorrhage can be controlled with
direct pressure. Life-threatening bleeding is fortunately
unusual and may represent a surgical emergency.
12
In a
prospective study of 173 ulcerated IH patients, bleeding
occurred in 41% of the lesions, but only two cases required
blood transfusion.
3
Visual impairment
Periocular IH is notably feared due to its risk of visual
impairment. The most common complication is amblyopia
(lazy eye), defined as a visual disturbance, without a
detectable organic lesion of the eye, arising from inadequate
bilateral stimulation of the visual cortex of the brain.
Table 1 Management of complications
Complication Signs Risk factor Workup Treatment
Ulceration Softening, early blanching Size, segmental distribution,
location (lip, neck, diaper area)
Bacterial culture Local wound care, oral
propranolol, oral
corticosteroids, laser,
surgery
Visual
impairment
Strabismus, exophthalmos,
incomplete closing or opening
of the eyes
Size, location Regular ophthalmologic
evaluations, US, MRI
Oral propranolol
intralesional corticosteroid,
topical timolol, laser
Airway
obstruction
Hoarse cry biphasic
stridor, noisy breathing
Location (beard area) Laryngoscopy Oral propranolol, oral
corticosteroid, laser
Disfigurement Size, location (nasal tip,
breast)
MRI may be used to assess
breast bud involvement
Oral propranolol, oral
corticosteroid, laser,
surgery
Hypothyroidism May be oligo or asymptomatic.
In severe cases, sleepiness, dull
look, puffy face, muscle atony
and thick tongue
Large visceral hemangioma Thyroid US, TSH, fT4, US
for visceral hemangioma
Cardiac failure Tachycardia, tachypnea,
shortness of breath, cyanosis
Liver hemangioma, large
segmental hemangioma
Chest X ray, echocardiography,
US for visceral hemangioma
Fig. 1 Ulcerated IH of the lip. Fig. 2 Whitening and ulceration in a 4-month-old child.
472 B. Gontijo
Refractive errors (astigmatism, myopia), strabismus, or
occlusion of the visual axis, by reducing or suppressing the
proper image transmission to the brain, are the leading causes
of amblyopia and can all be hemangioma-induced.
13
The
incidence of amblyopia in patients with periocular heman-
gioma has been reported to be as high as 73%; however, a
recent population-based study has estimated this rate to
be 19%.
14
Concerning the location, periocular hemangioma can be
palpebral, extraconal, and/or intraconal. Extraocular muscles
(superior, inferior, lateral, and medial rectus) appear in a
cone-shaped arrangement in the retrobulbar space (Figure 6).
Lesions are considered extraconal or intraconal when located
behind the bonny orbit, and outside or inside the muscle
cone, respectively. There seems to be a strong association
between extraconal and extraconal plus intraconal location
and the risk of amblyopia and astigmatism. Palpebral lesions
are also able to promote amblyopia and astigmatism in about
30% of patients.
15
Diagnosis is straightforward and can generally be made
on clinical grounds. In some cases, however, visible lesions
can be clinically deceiving, and apparently innocent
presentations do not always correlate with the amount of
retrobulbar involvement. The child pictured in Figure 7 was
referred for consultation because her parents had noticed
some prominent veins and a small lump on her upper eyelid,
along with difficulty in fully opening her left eye. CT
imaging revealed a significant extraconal and intraconal
extension of the vascular tumor.
Conventional systemic treatment with corticosteroids and
propranolol are the first therapeutic options. Intralesional
steroid injection is a particularly popular procedure among
ophthalmologists, but serious side effects (central retinal
artery occlusion, increased intraocular pressure) must be
weighed. A 0.5% or 0.1% timolol maleate gel-forming
solution may represent an interesting choice for superficial
lesions that are too small to cause ocular impairment but are
too large from the parents viewpoint.
16
Surgical removal, or
debulking is recommended in cases of IH that prove
unresponsive to medical treatment, that present circum-
scribed subcutaneous lesions, or that cause massive orbital
deformity.
17
Although small lesions, especially those on the
lower eyelid, rarely induce visual dysfunctions, the potential
to threaten or permanently compromise vision warrants
close and regular opththalmological monitoring of virtually
Fig. 4 A, Ulceration. B, After 3 weeks of treatment with
biocclusive dressing.
Fig. 3 Treatment-induced atrophy and discoloration. Blanching
progresses radially and centrifugally.
A B
Fig. 5 A, Large ulcerated IH of the parotid region. B, After 4 weeks of treatment with oral propranolol (3mg/kg/day).
473 Complications of infantile hemangiomas
all IH of the orbit and eyelids. Doppler US, a commonly
available and noninvasive exam, is usually the first choice of
imaging for diagnosis. MRI allows more precise determi-
nation of tumor size, extent and relationship to neighboring
structures but requires sedation. CT scan provides a superior
bony imaging but, due to its ionizing radiation and necessity
of sedation, is currently less employed.
Airway obstruction
Based on the systematic analysis of photographic
evidence, four anatomic patterns (segments S1 to S4 have
been proposed) for segmental facial hemangiomas. The
frontotemporal S1 segment comprises the lateral forehead,
anterior temporal scalp, and lateral frontal scalp. S2 and S3
segments correspond to the maxillary and mandibular
prominences, respectively, while the S4 segment encom-
passes the medial frontal scalp, nasal bridge, nasal tip, ala,
and philtrum.
18
The recognition that IH involving the so
called beard area (S3 segment: preauricular area,
mandible, chin, lower lip, and anterior neck) is a marker
for high risk of airway hemangioma is well-established in
the literature. Bilateral presentation and involvement of
multiple regions of the beard area (Figure 8) increase this
risk
19
; however, it should be kept in mind that airway
hemangiomas have been shown in association with
extrafacial IH,
20
with facial IH outside the S3 segment,
21
and even in the absence of cutaneous IH.
Hoarse cry, biphasic (inspiration and expiration) stridor,
and noisy breathing are classic signs of subglottic heman-
giomas. Because many of these lesions are, in practice,
Fig. 6 Schematic representation of the extraocular muscles.
A
B
Fig. 7 A, Visible vessels, discrete elevation of the upper eyelid and false ptosis. B, Contrast CT shows significant retrobulbar involvement.
Fig. 8 Bilateral IH overlying all regions of the beard area. This
child, however, did not develop airway hemangioma.
Fig. 9 Drooping of the nasal tip secondary to cartilage
impairment.
474 B. Gontijo
accidentally diagnosed during bronchoscopy, respiratory
symptoms should prompt otolaryngologic evaluation regard-
less of the presence of cutaneous IH.
21,22
Disfigurement
The dogma of the noninterventional approach to IH,
which reigned over many decades in the past, was
undoubtedly responsible for numerous cases of severe
and permanent disfigurement, coupled with an enormous
impact in these patients quality of life. Knowledge
gathered in recent years, together with the availability of
novel therapeutic modalities, allow for the proper manage-
ment of IH with reduced, or even suppressed, unpleasant
aesthetic results. Along with ulceration, prevention of
disfigurement is the most common reason for active
treatment.
18
Some anatomic areas are more prone to disfigurement.
Ulceration on the lip may result in permanent distortion and
lesions on the nasal tip may cause either the splaying or the
collapse of the alar cartilage (Figure 9). Even small-sized
IH, if sessile or pedunculated, can heal with significant
fibrofatty tissue residuum (Figure 10).
4
The breast area in
girls is another site of concern. If the breast bud is included
or very close to the IH, or the tumor is removed by
aggressive surgical intervention, permanent breast atrophy
may take place.
Other complications
There is the report of a case of severe hypothyroidism in
a three-month-old infant with massive hepatic hemangi-
omas and high levels of type 3 iodothyronine deiododinase
(D3) activity in the hemangioma tissue. This enzyme
catalyzes the conversion of thyroxine to reverse tri-
iodothyronine, as well as the conversion of tri-iodothyr-
onine to 3,3-diiodothyronine, both of which are biologi-
cally inactive.
23
The authors postulated that the degradation
of the thyroid hormone generated by the intense enzymatic
activity of the tumor exceeds the infants gland capacity to
synthesize it.
Few cases of IH-induced hypothyroidism have been
published since then. Characteristically, these are associated
with large visceral hemangiomas (liver, parotid).
24
High
output cardiac failure is a life-threatening complication
generally related to high flow tumors, such as hepatic
hemangiomas. Because patients with neonatal hemangioma-
tosis, particularly those with more than five cutaneous IH,
and large segmental hemangiomas present a higher risk of
visceral hemangiomas, screening imaging with Doppler US
should be considered under these circumstances.
Obstruction of the external auditory canal may lead to
otitis and decreased auditory conduction with speech delay.
25
Structural anomalies associated with IH (PHACE,
PELVIS, and LUMBAR syndromes) are discussed in the
paper by Blei and Guarini.
Conclusions
Complications of IH vary widely in severity, ranging from
pain of ulceration to functional impairment and to life-
threatening airway obstruction. Size, location, and morphol-
ogy are important factors in predicting complications, as well
as early clinical signs, such as whitening of the hemangioma,
heralding ulceration, and a hoarse cry and biphasic stridor
indicative of airway tumors. Recognition or prediction of
complications is fundamental to prompt adequate treatment
and investigation.
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