vascular skin lesions in children
TRANSCRIPT
REVIEW ARTICLES
Vascular Skin Lesions in Children: A Review of LaserSurgical and Medical Treatments
LAUREN M. CRAIG, BA, AND TINA S. ALSTER, MD*
Vascular anomalies are a common finding in children. Although most of these lesions are benign, they can be asevere cosmetic problemand cause structural and functional damage tonearby tissues. Asa result, physicians aretasked with developing effective treatment options with superior safety profiles. Vascular anomalies may bedivided into tumors andmalformations. Vascular tumors, such as infantile hemangiomas, typically appear a fewmonths after birth, whereas themajority of vascular malformations, such as port-wine stains, are present at birth.Although these lesions vary in appearance, etiology, and disease course, many are treated in a similar fashion. Inthis review,wefocuson treatmentmodalities for someof themore-prevalentchildhoodvascular lesions, includingport-wine stains, primary telangiectasias, infantile hemangiomas, pyogenic granulomas, and angiomas.
The authors have indicated no significant interest with commercial supporters.
Vascular anomalies are a common finding in
children. Although most of these lesions are
benign, they can be of severe cosmetic concern and
can cause structural and functional damage to nearby
tissues. As a result, physicians are tasked with
developing effective treatment options with superior
safety profiles. Vascular anomalies may be divided
into tumors and malformations. Vascular tumors,
such as infantile hemangiomas, typically appear a few
weeks after birth, whereas the majority of vascular
malformations, such as port-wine stains, are present
at birth. Although these lesions vary in appearance,
etiology, and disease course, many are treated in a
similar fashion. In this review, we focus on treatment
modalities for some of the more-prevalent childhood
vascular lesions, including port-wine stains (PWS),
primary telangiectasias, infantile hemangiomas,
pyogenic granulomas (PGs), and angiomas.
Vascular Malformations
Port-Wine Stains
Characteristics
PWS, also known as nevus flammeus, are the most
common childhood vascular malformation,
occurring in 0.3% of newborns.1 A PWS is a slow-
flowing capillary malformation, described as a
cluster of pink to purple, sharply demarcated
patches. They are typically located in a unilateral
distribution on the head and neck and may involve
the mucous membranes. Like most vascular mal-
formations, PWS are present at birth and do not
involute spontaneously. Over time, these lesions
darken, with 11% thickening and 24% developing
nodules.2 PWS can be isolated malformations, or
they may be associated with conditions that have
systemic involvement. When PWS are located in a
trigeminal distribution, Sturge-Weber syndrome,
characterized by glaucoma, leptomeningeal venous
angiomas, seizures, hemiparesis contralateral to the
facial lesion, and intracranial calcifications, must be
considered. PWS may also be associated with other
syndromes such as Proteus (with an overgrowth of
the skeleton; skin, adipose, and central nervous
system tissue; severe disfigurement; tumors; pulmo-
nary complications; deep vein thrombosis; and
pulmonary embolism), Beckwith–Wiedemann (with
exomphalos, macroglossia, and gigantism), and
Bonnet–Dechume–Blanc (with unilateral arteriove-
nous malformations involving the retinas, brain,
and skin of the face).3–6 For this reason, children
*Both authors are affiliated with Washington Institute of Dermatologic Laser Surgery, Washington, District of Columbia
© 2013 by the American Society for Dermatologic Surgery, Inc. � Published by Wiley Periodicals, Inc. �ISSN: 1076-0512 � Dermatol Surg 2013;39:1137–1146 � DOI: 10.1111/dsu.12129
1137
born with PWS should receive a complete
diagnostic evaluation.
Treatment
Treatment is usually recommended for PWS even
when they are not associated with an underlying
systemic condition. These lesions can cause signifi-
cant morbidity, bleeding, and psychological and
cosmetic concerns. The most effective treatment is
vascular-specific laser therapy, most notably pulsed
dye laser (PDL).7 Despite significant technologic
advances, many PWS cannot be completely elimi-
nated with PDL treatment alone. As a result,
physicians have become interested in combining
existing therapies to maximize results.
Laser
PDLs emit wavelengths that specifically target
oxyhemoglobin, treating the vascular abnormality
with minimal damage to the surrounding tissue.
Effective treatment protocols include wavelengths of
585 to 600 nm, fluences of 6 to 12 J/cm2, and pulse
durations of 0.45 to 10 ms with concomitant
epidermal cooling. Sequential treatment sessions
every 4 to 8 weeks are recommended.8 Common
side effects include transient erythema, edema,
and mild purpura that spontaneously resolve in a
few days. Progressive lesional fading is seen after
each treatment, with multiple (� 9) treatments
typically necessary to achieve >75%
improvement (Figure 1A,B).9
Studies have suggested that laser treatment is most
effective when initiated in the first year of life, in
part because infant skin is thinner, thus enhancing
laser penetration.10,11 As mentioned above, PWS
become thick and nodular with advancing age, so
treating early allows the malformation to be treated
at its smallest.
In addition to determining optimal laser parameters
and appropriate patient treatment age, varying laser
techniques have been investigated. A double-pass
technique using a PDL produces better blanching
than the typical single pass technique.12 Treated
areas are generally lighter, without evidence of
scarring after a series of laser treatments, but
residual PWS can darken over time because of
progressive vessel ectasia.13 Longer wavelengths and
pulse durations (along with more epidermal cooling
to prevent excess tissue damage) can be applied to
lesions that initially respond to PDL treatment but
reach a treatment plateau.14 The long-pulse alexan-
drite (755 nm),15 long-pulse 1,064-nm neodymium-
doped yttrium aluminum garnet (Nd:YAG),16 and
dual 595-nm PDL and 1,064-nm Nd:YAG17 lasers
have proven useful in these latter cases, particularly
when lesions have developed nodularity, because of
the ability of these systems to achieve deeper
dermal penetration.18
(A)
(B)
Figure 1. Port-wine stain before (A) and after (B) 12 lasertreatments (six pulsed-dye laser (PDL) followed by sixcombination PDL and neodymium-doped yttrium aluminumgarnet laser). Topical imiquimod may be helpful in furtherlesional lightening.
PEDIATRIC VASCULAR LESION TREATMENT REVIEW
DERMATOLOGIC SURGERY1138
Laser and Topical Therapy
Although lasers continue to be used as the primary
treatment for PWS, preliminary studies have evalu-
ated the use of adjunctive anti-angiogenic therapy.
Daily or three times weekly application of topical
imiquimod 5% between laser treatment sessions has
been shown to reduce PWS color reductionmore than
PDL treatment alone.19 Side effects of imiquimod
treatment include minor skin irritation in a minority
of patients.20 Other investigators have demonstrated
in rodents that PDL treatment followed by a 14 day
course of rapamycin prevented reformation and
reperfusion of blood vessels more than PDL alone.21
Other
Intense pulsed light (IPL) has also been advocated
for PWS treatment. Although vascular-specific lasers
remain a more-effective treatment option, IPL
should be considered in PDL-resistant patients.22 A
randomized side-by-side study showed that PDL was
generally more effective in inducing clearance, but in
PDL-resistant lesions, six of 15 patients had more
than 75% clearance with IPL.23
Primary Telangiectasias
Characteristics
Telangiectasias appear as dilated blood vessels on
the skin and mucus membranes. Primary (or essen-
tial) telangiectasias have no causative or coexisting
cutaneous or systemic diseases. Although primary
telangiectasias are usually a sporadic finding, a
benign hereditary form has also been described. This
condition, known as generalized essential telangiec-
tasia, consists of patchy reticular telangiectasias that
may progress to involve large body surface areas.
Generalized essential telangiectasia can present at
any age and has no known etiology, although
familial cases have been described with an autoso-
mal-dominant inheritance pattern.3 Children with
telangiectasias should be fully evaluated to exclude
causes of secondary telangiectasias such as connec-
tive tissue diseases, xeroderma pigmentosum,
poikiloderma, and ataxia-telangiectasia.3
Treatment 3
As with PWS, PDL is the most commonly applied
treatment for primary telangiectasias. Complete
resolution of linear and spider facial telangiectasias
is typically achieved after two to three sequential
595-nm PDL treatments using a 7- to 10-mm spot
and fluences from 6 to 10 J/cm2.7,24 Post-treatment
purpura can be avoided using longer pulse durations
(>6 ms), but lack of purpura after treatment gener-
ally yields less-favorable clinical results.25 Pulse
stacking and use of multiple sequential passes have
also been cited as techniques that may yield better
clinical responses.26,27 Lasers with longer wave-
lengths, such as the long-pulse alexandrite (755 nm)
and long-pulse Nd:YAG (1,064 nm) systems may be
used for deeper lesions but may increase the risk of
scarring and ulceration.
Vascular Tumors
Infantile Hemangiomas
Characteristics
Hemangiomas are the most common tumor in
infancy (1–2% incidence of all live births and
� 10% at 1 year of age), with a greater incidence in
premature infants. These vascular tumors charac-
teristically increase in size, stabilize, and then
spontaneously involute over several months.28
Frieden and colleagues29 recently discovered that the
most rapid hemangioma growth occurs before
8 weeks of age, especially between 5.5 and
7.5 weeks. In addition to prematurity, other risk
factors include Caucasian race, female sex, chorionic
villous sampling, and multiple-gestation pregnancy.1
Hemangiomas are typically classified as superficial,
deep, or mixed.7 Superficial hemangiomas are the
most common (50–60% of cases), appearing bright
red and sometimes protuberant. In contrast, deep
hemangiomas are rare (15% of cases), less well
defined, firm, cystic, or compressible and may
exhibit a bluish hue underneath normal-appearing
skin. Mixed hemangiomas combine characteristics
of superficial and deep lesions and account for 25%
to 30% of cases.28 Hemangiomas can also be
CRAIG AND ALSTER
39 :8 :AUGUST 2013 1139
classified as focal or segmental. Focal hemangiomas
tend to grow in a tumor-like fashion, whereas
segmental hemangiomas are larger and plaque-like.
Segmental hemangiomas are more aggressive, with
greater ulceration and local destruction.30 Left
untreated, 60% of infantile hemangiomas will
involute by 5 years, and 90% to 95% will maxi-
mally involute by 9 years. It was established in 2000
that glucose transporter-1 stains positive in heman-
giomas, making this marker useful in distinguishing
hemangiomas from other vascular tumors.31 Loca-
tion does not appear to affect resolution in most
situations, although lip lesions are the most persis-
tent. Size does not appear to affect involution.1
Treatment 3
The majority of hemangiomas are treated with
simple observation, because 70% resolve spontane-
ously without severe complications. The other 30%
of hemangiomas may result in hemorrhage, ulcera-
tion, and disfigurement of the underlying tissue.1
Depending on location, a hemangioma may cause
airway or orbital obstruction, hearing loss, or spinal
abnormalities. Early treatment is advised for
hemangiomas that interfere with the function of a
vital organ, involve large portions of the face or
inguinal area, risk ulceration, or cause psychological
suffering.32 Hemangiomas requiring treatment are
most effectively managed early to affect the
proliferation phase directly.33 A variety of treat-
ments are available, including topical, intralesional,
oral, and laser therapies.
Oral 2
Oral corticosteroids have been the first-line treat-
ment for hemangiomas since the 1960s. A course of
prednisone is generally effective in decreasing the
size and severity of hemangiomas but can cause
numerous side effects, including impaired immunity,
hypertension, and hyperglycemia.34–36 An effective
dosing regimen consists of 1.5 to 2 mg/kg per day of
prednisone for 4 to 8 weeks.32 One meta-analysis
showed that 3 mg/kg might be a more effective dose,
stabilizing growth in 90% of patients.34 Although
corticosteroids may still be prescribed, other thera-
pies are currently advocated because of the risk of
side effects associated with corticosteroid use.
Recent studies favor the use of propranolol, a
nonselective beta-adrenergic blocker, as first-line
treatment for infantile hemangiomas. Leaute-Labreze
and colleagues37 first discussed its use at a dose of
2 mg/kg per day. Other beta-blockers, such as
acebutolol, have also been found to be effective, but
propranolol use is generally favored.38 Price and
colleagues39 found that propranolol therapy was
more cost effective and had fewer surgical complica-
tions than oral steroids. Koay and colleagues40
reported that propranolol and oral steroids could be
combined at lower doses, reducing the adverse side
effects of both drugs. Young infants are commonly
started on a course of propranolol while hospitalized
to monitor for any adverse reactions, most commonly
hypotension. Older children often start treatment as
outpatients, with appropriate counseling and moni-
toring. Hypoglycemia has been cited as a rare and
dangerous side effect of propranolol.41 Diarrhea and
hyperkalemia have also been described.42,43 The
appropriate course of propranolol has not been
standardized, but physicians should be aware
that hemangiomas can have rebound growth
if treatment is not continued through the growth
phase—generally 1 year.
Recombinant interferon-alpha (3 million U/m2 per
day) and vincristine, a vinca alkaloid chemotherapy
agent (0.05 mg/kg per day), have been used
successfully to treat proliferative hemangiomas.1
These treatments are reserved as third-line therapy
because of the risk of immunosuppressive side effects
with vincristine and irreversible spastic diplegia with
interferon-alpha.44
Intralesional and Topical Agents 2
Ophthalmologists first used intralesional and topical
steroids to treat periorbital hemangiomas.45 Because
of concerns regarding ocular damage, intralesional
therapies are more commonly applied on the lip and
PEDIATRIC VASCULAR LESION TREATMENT REVIEW
DERMATOLOGIC SURGERY1140
nose. Triamcinolone acetonide (10 mg/mL) injections
are administered every 4 weeks at doses not exceed-
ing 3 to 5 mg/kg per treatment.28 Class 1 topical
corticosteroids are applied twice daily with monitor-
ing every 2 weeks.46,47 Topical beta-blockers,
specifically timolol maleate 0.5% gel, have also been
shown to be effective in treating superficial
hemangiomas.48 Lastly, the use of 5% imiquimod,
an immune modulator and upregulator of inter-
feron-alpha, has been used as successful therapy
alone or in combination with laser.49
Laser
Vascular-specific PDL therapy is particularly useful in
treating ulcerated hemangiomas, superficial
hemangiomas, and postinvolution hemangiomas
(Figure 2A,B). Laser treatment parameters are less
aggressive (4–7 J/cm2, 0.45–1.5-ms pulse duration)
than those used for other vascular abnormalities to
reduce such side effects as ulceration, scarring, and
hypopigmentation in these delicate lesions.50–52
Multiple treatments are needed at 4- to 6-week
intervals during the proliferative phase.53 PDL
is less effective in the treatment of mixed and deep
hemangiomas than in ulcerated, superficial or post-
involution lesions because it has limited dermal
penetration. A recent study by Admani and col-
leagues54 found that early PDL treatment is a safe and
effective option for selected patients with infantile
hemangiomas alone or in combination with systemic
therapy. In addition, involuted hemangiomas that
display a variable array of cosmetic defects can be
treated later with PDL, fractional laser skin resurfac-
ing.55 or plastic surgery. Brightman and colleagues56
reported five cases inwhich patients experienced 50%
to 75% improvement in residual hemangioma tex-
tural skin irregularities with minimal side effects after
ablative fractional laser skin resurfacing.
Other
Hemangiomas can be surgically excised, but the risk
of postoperative scarring is high. Scarring is of
particular concern when treating young children
with lesions located in cosmetically sensitive areas
such as the face and neck. Embolization is another
treatment option for high-output lesions when there
is the potential for cardiac failure.1
Pyogenic Granulomas
Characteristics
PGs, also referred to as lobular capillary heman-
giomas, occur at any age but are more common in
children and pregnant women. In children, these
lesions typically present between the ages of 6 to
10 years and appear most commonly on the face and
upper extremities.57 Congenital PGs exist but are
rare. These small, red, “glistening” papules grow
rapidly and bleed easily with trauma. Glucose
transporter (GLUT)-1 staining can be used to
(A)
(B)
Figure 2. Infantile hemangioma before (A) and after (B) fivepulsed-dye laser (PDL) treatments. Concomitant use of oralpropanol would have been anticipated to result in earlierlesional resolution.
CRAIG AND ALSTER
39 :8 :AUGUST 2013 1141
distinguish them from infantile hemangiomas; PGs
stain negative for GLUT-1, and infantile hemangio-
mas stain positive.58 PGs are thought to arise
because of an unregulated angiogenic stimulus, but
the exact pathogenesis is unknown. Trauma is
commonly elicited as an inciting event, but other
causes are being shown to contribute, including the
use of certain systemic and topical drugs such as
retinoids, 5-fluoracil, granulocyte colony-stimulat-
ing factor, and some human immunodeficiency virus
protease inhibitors.59 PGs may also occur within a
vascular malformation, such as a PWS, spontane-
ously or after laser treatment.60,61 If left untreated,
these lesions will most likely persist and continue to
cause bothersome bleeding.
Treatment
PGs, although benign, are often treated because they
bleed easily and cause cosmetic concerns. They may
mimic basal cell carcinomas and nodular melanoma,
so it is essential to obtain biopsies for pathologic
examination if malignancy is suspected. In children,
skin cancer is a rare occurrence, so the prescribed
treatment depends primarily on location, risk of
scarring, and likelihood of recurrence.
Surgical
Surgical excision is the most common treatment
prescribed because of the high recurrence rate of
PGs. Full-thickness excision, shave excision, and
curettage with or without cautery can effectively
remove these lesions, but scarring, infection, and
blood loss can occur. Full-thickness excision has
been shown to result in a lower recurrence rate
(2.9%) than other surgical methods such as
curettage and electrocautery (7–15%).62
Laser
Treatment with PDL or carbon dioxide (CO2) lasers
is advocated in children with small PGs in cosmet-
ically sensitive areas because of the low risk of
scarring with lasers.57 Lee and colleagues62 reported
recurrence rates of 0.43% after PDL treatment of
PGs and 0.49% after CO2 laser vaporization.
Multiple (2–6) sequential PDL treatments are
typically required for clearance, compared with a
single CO2 laser vaporization procedure, but PDL
treatments are easier for children to undergo
because they are painless and have nominal
postoperative recovery.63
Cryotherapy
Although cryotherapy is an effective treatment with
an acceptable side-effect profile and minimal scar-
ring and dyspigmentation risk, it is not first-line
therapy for PGs because of its high lesional recur-
rence rates and number of treatments necessary. Lee
and colleagues62 found a recurrence rate of 1.6%
after cryotherapy, including patients treated multi-
ple times. In a study by Mirshams and colleagues,64
18% of patients experienced resolution after one to
four cryotherapy sessions.
Topical
Topical therapies are associated with high recur-
rence rates and are thus typically reserved for
patients who refuse surgical and laser options. Silver
nitrate cauterization can be used, but burning of
unaffected skin is a common hazard.65 Use of topical
phenol has also been reported, particularly in the
treatment of periungual PGs, but multiple applica-
tions of a 98% solution are usually needed for
clearance.66 A study reporting the use of imiquimod
5% cream demonstrated varied responses, including
no lesional recurrence in some of the cases.67
Intralesional
Sclerotherapy using intralesional injections of
ethanolamine oleate, sodium tetradecyl sulfate, or
polidocanolcan lead toresolutionofPGsbutcancause
cutaneous necrosis of the surrounding tissue.68–70
Spider Angiomas
Characteristics
Spider angiomas, or nevus araneus, are commonly
associated with high levels of estrogen, but they also
appear in 15% of healthy preschool-aged children
PEDIATRIC VASCULAR LESION TREATMENT REVIEW
DERMATOLOGIC SURGERY1142
and 45% of school-aged children.3 Lesions are often
seen on the dorsum of the hands, forearms, face, and
ears, appearing as bright red papules or dilated
vessels radiating from a central artery. Spider
angiomas vary in size and often have surrounding
erythema that can be blanched upon compression.
Treatment
Although spider angiomas are benign, they can be of
cosmetic concern if they are present in a prominent
location or are unusually large or numerous. Treat-
ment with a PDL is the criterion standard, with only
one or two laser sessions typically needed to remove
them.71 (Figure 3A,B)
Other Vascular Lesions
Venous Malformations
Characteristics
Venous malformations are present at birth and,
instead of regressing over time, often become more
noticeable. They appear clinically as soft blue
nodules containing a mass of venules or as large,
widespread abnormalities. Venous malformations
may be superficial, resembling varicose veins, or
deep.3 Blue rubber bleb nevus syndrome is a rare
condition in which a person will have numerous
venous malformations, most commonly involving
the skin and the gastrointestinal (GI) tract. Although
cutaneous venous malformations pose a cosmetic
concern, GI venous malformations can lead to death
due to GI hemorrhage.72
Treatment
Venous malformations have traditionally been
treated using surgical resection, sclerotherapy, and
compression, but Nd:YAG laser treatment is now
commonly used. Multiple laser sessions at 8- to
12-week intervals have been shown to reduce
lesional color and bulk while improving dermal
contour with minimal side effects. Small lesions are
typically eradicated, whereas large venous
malformations are reduced in size after multiple
treatments.73 In addition to laser therapy, larger
malformations can be treated using percutaneous
sclerotherapy with polidocanol microfoam and color
Doppler ultrasonographic guidance.24 In blue rub-
ber bleb nevus syndrome, cutaneous and mucocu-
taneous venous malformations have been similarly
treated using Nd:YAG lasers.74 Yuksekkaya and
colleagues75 successfully used sirolimus to shrink
venous malformations in patients with multiple,
potentially life-threatening lesions.
Angiokeratomas
Characteristics
Angiokeratomas are characterized histologically by
dilations of superficial dermal vessels and hyperker-
atosis of the overlying epidermis.3 Angiokeratoma
circumscriptum is a rare disorder, often presenting at
(A)
(B)
Figure 3. Angioma before (A) and after (B) one neodymium-doped yttrium aluminum garnet laser treatment.
CRAIG AND ALSTER
39 :8 :AUGUST 2013 1143
birth, consisting of solitary or multiple angiokera-
tomas, usually occurring unilaterally on the lower
extremities.76 Angiokeratoma corporis diffusum, or
Fabry disease, is an X-linked inherited disorder
caused by a deficiency of the lysosomal enzyme
alpha-galactosidase. This disease is characterized by
angiokeratomas; irregularities in sweating; edema;
scant body hair; painful sensations; and cardiovas-
cular, gastrointestinal, renal, ophthalmologic,
phlebologic, and respiratory involvement.77
Treatment
Isolated angiokeratomas can be surgically excised,
but this option may not be practical for conditions
resulting in numerous lesions, such as angiokera-
toma circumscriptum and Fabry disease. In these
situations, laser therapy is commonly used. A variety
of vascular-specific lasers have been used, including
532-nm Nd:YAG, 578-nm copper vapor, and 595-
nm PDL.77
Conclusion
Physicians who evaluate and treat childhood vascu-
lar lesions should be familiar with the risks and
benefits associated with all available therapies.
Treatment should be individualized for each patient
based on known lesional response rates and avail-
able treatment options. The management of child-
hood vascular anomalies has advanced with the use
of combination medical and surgical treatments,
leading to greater clearance and minimal side effects.
Additional studies are necessary to further enhance
clinical outcomes.
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Address correspondence and reprint requests to: Tina S.Alster, MD, Washington Institute of Dermatologic LaserSurgery, 1430 K Street, NW Suite 200, Washington, DC20005, or e-mail: [email protected]
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